OBSTETRIC

1. Physiology of pregnancy 7. Systemic Diseases in Pregnancy

Maternal physiology Cardiovascular
Fetal physiology Heart disease
Anaemia
2. Normal labour VTE
1st stage of labour Hypertensive Disorders in Pregnancy (HDP)
2nd stage of labour Gestational hypertension
3rd stage of labour Pre eclampsia
Episiotomy Eclampsia
Partogram Chronic hypertension
Chronic hypertension superimposed on pre
3. Abnormal labour eclampsia
Failure to progress in labour Respiratory
Malpresentation Bronchial asthma
Instrumental deliveries CF
Caesarian section TB
PROM & PPROM Endocrine
IOL DM & GDM
Augmentation of labour Thyroid diseases
Antennal steroid therapy Jaundice
IRDS Renal failure
Meconium stained placenta Autoimmune
Retained placenta SLE
Abnormal placenta APS
Abnormalities of the cord Seizure

4. Obstetric emergencies 8. Infections in Pregnancies

Shoulder dystocia UTI
Cord prolapse HIV
Uterine inversion VDRL
Uterine rupture Hep B
APH & PPH GBS
Eclampsia Maternal Pyrexia

5. Antenatal problems & complications 9. Rhesus incompatibility

High-risk pregnancies
Multiple pregnancies 10. Puerperium
VBAC
Post dates 11. Maternal mortality
Reduced fetal movement
IUGR
IUD
Unstable lie
Uterus larger & smaller than date

6. Obstetric Haemorrhage
Early pregnancy bleeding
Miscarriage
Ectopic pregnancy
Antepartum haemorrhage
Placenta praevia
Abruptio placenta
Vasa Praevia
Postpartum haemorrhage
 GYNAECOLOGY
1. Female Reproductive System
Anatomy, Embryology & Physiology

2. History Taking

3. Physical Examination

4. Premenstrual Syndrome

5. Disorders of Menstrual Bleeding

Amenorrhea
Dysmenorrhea
Menorrhagia

6. Infertility
Male Infertility
Female Infertility
Assisted Reproductive Techniques

7. Adenomyosis

8. Endometriosis

9. Fibroids

10. Pelvic Organ Prolapse

11. Urinary Stress Incontinence

12. Contraception

13. Termination of Pregnancy & Abortion

14. Ectopic Pregnancy

15. Miscarriage

16. Hyperemesis Gravidarum

17. PCOS

18. Gynaecological Infection

Vulvovaginitis
Sexually-Transmitted Infections
Pelvic Inflammatory Disease

19. Gestational Trophoblastic Disease

20. Gynaecological Neoplasm

Vulva
Vagina
Cervix
Ovarian
Uterus

21. Sexual Abuse / Assaults

22. Menopause

23. Common Medication in O&G

24. Common Procedures & Investigations in O&G

 PREMENSTRUAL SYNDROME (PMS)
Also known as ovarian cycle syndrome / menstrual molimina

Etiology
1. Multifactorial – not completely understood
2. CNS-mediated neurotransmitter interactions with sex hormones (progesterone, oestrogen)
3. Serotonic dysregulation

Diagnostic Criteria

At least 1 affective & 1 somatic (physical) symptom during 5 days before menses in each of 3 prior menstrual cycles

Clinical Presentation
Affective Symptoms Somatic Symptoms
• Depression • Breast tenderness
• Angry outburst • Abdominal bloating
• Irritability • Headache
• Anxiety • Swelling of the extremities
• Confusion
• Social withdrawal
Both affective & somatic symptoms must be
• Relieved within 4 days from onset of menses
• Present in absence of any pharmacological therapy, drugs or alcohol use
• Occur reproducibly during 2 previous consecutive cycles

Treatment
Treatment Goal = Symptomatic relief
Treatment Option = All conservative treatments

1. Lifestyle Changes – Diet

• Avoid salts, simple sugars, caffeine & alcohol
• Take more Ca2+, Mg2+, Vitamin E & B6
2. Psychological Therapy
• Cognitive Behavioural Therapy (CBT)
• Relaxation
• Light Therapy Biofeedback
• Guided imaginery
3. Pharmacological Treatment
• NSAIDs for pain relief
• OCP – especially for somatic symptoms
• SSRIs – used during luteal phase for 14 days or continuously
• Spironolactone – if fluid retention present
• GnRH agonist – if PMS is severe & unresponsive to other treatments
4. Herbal remedies – variable evidences
• Evening primrose oil
• Black cohosh
• St John’s wort
• Kava
• Ginkgo
• Agnus Castus fruit extract

PREMENSTRUAL DYSPHORIC DISORDERS

• More severe type of PMS but with specific diagnostic criteria (DSM-5)
• Treatment
1. SSRI – 1st line
2. Yaz® OCP – highly effective
 DISORDERS OF MENSTRUAL BLEEDING
Disorders of Menstrual Bleeding

Amenorrhea Dysmenorrhea Menorrhagia

BACKGROUND PHYSIOLOGY
Menstrual Cycle

Clinical Significance
1. Mittelschimerz — Lower abdominal / suprapubic pain felt at mid cycle due to ovulation
2. Follicular phase varies in length but luteal phase is always fixed to 14 days in duration
AMENORRHEA
Definition = No menses / menstruation

Classification
1° Amenorrhea 2° Amenorrhea
Absence of menses by age 14 in absence of 2° sexual Absence of menses for 3 normal menstrual cycles or 6 months
characteristic in patient who has not previously menstruated in a woman who has previously menstruated
OR
Absence of menses by age 16 in presence of 2° sexual
characteristic in patient who has not previously menstruated

Causes of 1° Amenorrhea
Hypothalamus (Functional hypothalamic amenorrhea / hypothalamic hypogonadism)
1. Stress
Hypothalamus
2. Excessive exercise
(GnRH) 3. Extreme weight loss (anorexia nervosa)

Anterior Pituitary Gland (Hypogonadotrophic hypogonadism)

Anterior Pituitary Gland
(FSH, LH)
Ovaries
(Progesterone, Oestrogen)
1. Constitutional delay – usually a diagnosis of exclusion
2. Congenital
• Isolated GnRH deficiency
• Pituitary adenoma (esp macroprolactinoma)
• Kallman’s syndrome
3. Acquired
• Pituitary tumour (which causes hyperprolactinaemia)
• Drug-induced hyperprolactinaemia
• Hypothyroidism

Endometrium Ovaries (Hypergonadotrophic hypogonadism)

1. Ovarian agenesis / dysgenesis
• Premature ovarian failure (46, XX)
• Turner’s syndrome (45, X0)
Outflow Tract 2. Others (rare):
• Gonadal failure
• Resistant ovary syndrome
• Abnormal folliculogenesis
• PCOS
• Abnormal / Absent germ cells

Outflow Tract (Mechanical obstruction)

Uterus present / normal Uterus absent / abnormal
• Imperforate hymen • Mullerian agenesis
• Transverse vaginal septum • Androgen Insensitivity Syndrome
• Cervical agenesis (AIS)

Also consider systemic disorders:

• IBD
• JRA
• Chronic infection
• T1DM
Kallmann’s Syndrome — characterized by anosmia & hypogonadotrophic hypogonadism
• Definition: Mutation of short arm of X chromosome leading to defect in GnRH synthesis
• Clinical Presentatation:
− 1° amenorrhea
− Anosmia / Hyposmia
− Hallmark: Delay in pubertal development
− Facial asymmetrochidism
− Cryptochidism
− Renal anomalies
• Hormone evaluation reveals low in testosterone, LH & FSH
• Virilization & fertility can be achieved by giving FSH & LH to stimulate testis function

Mullerian Agenesis

• Also known as Meyer-Rokitansky-Kutser-Hauser syndrome / vaginal agenesis

• Definition: Congenital malformation characterized by failure of Mullerian duct to develop resulting in absent uterus &
vaginal (complete or partial)
• Clinical Presentation:
− Normal pubic hair, breast & external genitalia but presented with amenorrhea & dyspareunia
− Urinary tract symptoms
− Skeletal / spine abnormalities
• Diagnosis:
PE → Shorten vagina
TVUS → Blind vaginal pouch (Diagnostic)
Karyotyping → 46,XX
• Treatment
− Frank vaginal dilatation
− Surgery (Vecchietti procedure) if vaginal dilatation fails

Androgen Insensitivity Syndrome (AIS)

• Testicular feminization syndrome caused by mutation in the gene for androgen receptor
• X-linked recessive disorder
• Patients are phenotypically female but with 46,XY karyotype

Turner’s Syndrome (TS) — A form of gonadal agenesis

• Definition: TS is a condition in the female where there is partly or completely missing X
chromosome (45,X0 or 45,X)
• Clinical Presentation: 1° amenorrhea associated with features of Turner’s syndrome CLOWNS
C = Cardiac abnormality — COARCTATION
L= Lymphedema due to poor lymphatics
O = Ovarian failure / underdeveloped
W = Webbed neck
N = Nipples widely spaced
S = Short stature
Causes of 2° Amenorrhea
PREGNANCY is the most common cause for 2° amenorrhea
Pregnancy must be excluded in all cases of 2° amenorrhea is women of child-bearing age
Hypothalamus (Functional hypothalamic amenorrhea / hypothalamic hypogonadism)
Hypothalamus 1. Stress
2. Excessive exercise
(GnRH) 3. Extreme weight loss (anorexia nervosa)

Anterior Pituitary Gland (Hypogonadotrophic hypogonadism)

Anterior Pituitary Gland Mechanism: Increase production of prolactin causing hyperprolactinaemia
1. Pituitary tumour
(FSH, LH)
Mechanism: Due to any pituitary compression or obstruction, which causes pituitary failure
1. Mass occupying effect
Ovaries • Pituitary adenoma
(Progesterone, Oestrogen) • Craniopharyngioma
• Germinoma
• Dermoid cyst
• Lymphocytic hypophysis
Endometrium 2. Infiltration: Sarcoidosis or TB
3. Trauma: Head injuries, irradiation (treatment of pituitary tumour)

Ovaries (Hypergonadotrophic hypogonadism)

1. PCOS
Outflow Tract
2. Premature ovarian failure
• Chemotherapy / Radiotherapy
• Autoimmune disease following infection
• Following surgery e.g for endometriosis
3. Androgen-secreting ovarian tumour

Endometrium
1. Pregnancy – MOST COMMON
2. Anatomical causes – usually due to previous surgery
• Asherman’s syndrome (formation of adhesion in uterine cavity)
• Endometrial ablation
• Hysterectomy
• Cervical stenosis following cone biopsy

Outflow Tract (Mechanical obstruction is less likely in 2° amenorrhea)

Also consider systemic disorders:

1. Endocrine causes
• Thyroid diseases
• Cushing’s disease
These endocrine diseases interfere with normal functioning of hypothalamic-pituitary-
ovarian axis
E.g. ↑[Thyroxine] can inhibit FSH release

2. Drug-induced hyperprolactinaemia
• Phenothiazine
• Methyldopa
• Cimetidine
• Butyrophenones
• Antihistamines

n.b Hyperprolactinaemia
• ↑ [Prolactin] can inhibit GnRH release from hypothalamus
• Causes of hyperprolactinaemia
1. Pituitary tumour – secretes prolactin which inhibit GnRH
2. Drug-induced hyperprolactinaemia
ASSESMENT OF PATIENT WITH AMENORRHEA
History Taking
History Taking Physical Examination
• Obtain patient information Investigation
• Identify 1° or 2° amenorrhea
− Menstrual cycle
− At what age did menarche start?
− If she has menstruated before, how long has she not menstruated (last LMP)?
− Is the previous 3 cycles regular (21-35 days) or irregular (<21 or >35 days)?
− Present of 2° sexual characteristics, ask about breast development, presence of pubic / axillary hair etc?
• Ask detail signs & symptoms that raise a suspicion against a certain cause:
1° amenorrhea

2° amenorrhea

• Rule out pregnancy

− If sexually active, did you perform UPT recently?
− Ask about history of previous pregnancy & childbirth? Is there excessive haemorrhage (PPH)? → Sheehan’s syndrome
Physical Examination
General Examination Calculate BMI → Anorexia nervosa
BP → Elevated in Cushing’s & PCOS
Hirsutism features → PCOS
Virilization features → Ovarian tumour
Secondary 2° characteristics → Absent / Present
Turner’s Syndrome features (CLOWNS)
Stigmata of thyroid disease → Hyper/Hypothyroidism

Abdominal Examination Abdominal mass

Lymphadenopathy (neck or groin nodes) → Malignancy

Pelvic Examination Inspection of genitalia → Imperforated hymen, cervical stenosis

Vaginal examination → Blind vaginal pouch, vaginal atresia, absent or uterus

Investigation
1° Amenorrhea

Work up for 1° amenorrhea:

1. History & PE
2. R/O pregnancy in women of childbearing age
3. Evaluate 2° sexual characteristics
If present → perform USG uterus
If absent → measure FSH / LH
4. USG uterus
If uterus normal / present → R/O outflow obstruction
If uterus abnormal / absent → perform karyotyping TRO AIS or Mullerian agenesis
5. FSH / LH levels
If high FSH → Hypergonadotrophic hypogonadism (gonadal failure) → perform karyotyping
If low FSH → Hypogonadotrophic hypogonadism (pituitary failure or developmental delay) → perform MRI brain
2° Amonerrhea

Work up for 2° amenorrhea:

1. History & PE
2. R/O pregnancy in women of childbearing age → UPT, βhCG
3. R/O thyroid disorders → serum TSH
4. R/O hyperprolactinaemia → serum PRL
If high PRL level → perform MRI brain TRO prolactinoma
If normal PRL level → perform progestin challenge
5. Progestin challenge:
WB → Normogonadotrophic hypogonadism
No WB → perform Estrogen/Progesterone challenge test
6. Estrogen/Progesterone challenge test
No WB → R/O outflow obstruction
WB → measure FSH / LH
If high FSH → Hypergonadotrophic hypogonadism (gonadal failure) → perform karyotyping
If low FSH → Hypogonadotrophic hypogonadism (pituitary failure or developmental delay) → perform MRI
brain
If normal FSH → Functional hypothalamic amenorrhea
Treatment for Amenorrhea — specific depending on underlying cause

Treatment Goals
1. Treat underlying cause of amenorrhea
2. To initiate and maintain secondary sexual characteristics
3. Maintenance of bone mass
4. Ovulation induction for patients desiring pregnancy

Method
1. Medical or surgical therapy
2. Hormone replacement

Treatment for Amenorrhea without 2° sexual characteristics

• Constitutional delay → Reassurance that the anticipated development will occur eventually
• All forms of gonadal failure (hypergonadotropic hypogonadism) → Cyclic estrogen & progestin therapy
To initiate, mature, & maintain 2° sexual characteristics
To prevent osteoporosis (additional benefit of estrogen)
• Mosacism & gonadal streak → HRT (Oestrogen)
• Karyotypes contain a Y cell line → Surgical removal of gonads (Gonadectomy)
− Examples: 45,X/46, XY mosaicism, or pure gonadal dysgenesis 46, XY
− Predisposed to gonadal ridge tumor, such as gonadoblastomas, dysgerminomas, yolk sac tumors
− Removal of gonads are to prevent malignant transformation
• 17α –hydroxylase deficiency → Corticosteroid & estrogen replacement, if uterus present gives progestin supply
• Hypothalamic / Pituitary Causes
1. Kallmann syndrome → HRT
2. Craniopharyngiomas → Resected with a transphenoidal approach or during craniotomy depending on tumor size
3. Germinomas → Radiosensitive (surgery rare)
4. Prolactinomas & hyperprolactinemia → Dopamine agonists (bromocriptine or cabergoline)
5. Functional hypothalamic → specific therapies
(Amenorrhea Malnutrition, malabsorption, weight loss, anorexia nervosa, exercise amenorrhea & chronic disease)
6. Hypogonadotropic hypogonadism
− Treated with long-term administration of pulsaile GnRH indwelling catheter & a portable pump
− Cyclic estrogen and progestin therapy at least until sexual maturity is achieved
− HRT to treat hypoestrogenic symptom
− Nonestrogenic regimens eg. Bisphosphomates (for maintenance of bone mass and prevention of osteoporosis)

Treatment for Amenorrhea with 2° sexual characteristics

• Anatomical abnormalities
1. Imperforate hymen → Making a cruciate incision to open vaginal orifice
2. Transverse vaginal septum → Surgical removal of septum
3. Cervix hypoplasia or absence in presence of a functioning uterus → Hysterctomy required, surgical repair not successful
4. Vagina (absent or short) → Progressive dilation is usually successful in making it functional
5. Complete AIS → Testes removal after complete pubertal development to prevent malignant degeneration
6. Asherman syndrome
− Removed using hysteroscopic resection with scissors or electrocautery
− Paediatric Foley catheter is placed in uterine cavity for 7~10days postop
− A 2-month course of high dose estrogen therapy with monthly progesterone withdrawal is used to prevent
reformation of adhesions
• Hypothalamic / Pituitary cases – refer above
• Gonadal failure (Chronic anovulation or PCOS) → Cyclic estrogen & progestin therapy / Ovulation induction
• Hirsutism
• Systemic disorders
1. Thyroid abnormalities → Thyroid hormone, radioactive • Aim of treatment: Decreasing coarse hair growth
iodine, antithyroid drugs • Treatment Options:
2. Hyperprolactinemia → Dopamine agonists (bromocriptine or 1. OCP (decreases ovarian androgen productions)
2. Antiandrogens = Spironolactone (decreases
cabergoline)
andorgen production, competes with androgen
3. Cushing’s syndrome → Glucocorticoid administration (ie. production), Cyproterone acetate (strong
Dexamethasone 0.5mg at bedtime) progestin)
3. GnRH agonists
4. 5α- reductase inhibitors
5. Eflornithine hydrochloride (topical cream)
 
n.b. Ovulation Induction Therapy: Clomiphene citrate (1st choice)
• MOA: Selective estrogen receptor modulator (SERM), used mainly in female infertility due to anovulation
• Relative safe & effective
• Route of administration is PO
• Relatively low cost
• Indications:
− Adequate levels of estrogen & normal FSH and prolactin
− Inappropriate gonadotropin release (an increased LH-to-FSH ratio ie. PCOS)
• Pregnancy rate: 40%
• Rate of expected ovulation: 80%
• Contraindications: pregnancy, liver disease, pre-existing ovarian cysts
• Side effects: hot flashes(>11% of pts), poorly understood visual symptoms
• Regimen
− 50mg daily for 5days
− Beginning on the 3rd~5th day of menstrual or withdrawal bleeding
DYSMENORRHEA
Definition = Painful period / Menstrual cramps / Pain during menstruation

Classification
1° Dysmenorrhea → Painful menstruation without any pelvic disease (Idiopathic)
2° Dysmenorrhea → Painful menstruation with presence of pelvic pathology

Pathophysiology
During menstruation, there is an increase level of prostaglandin
⇩
High level of prostaglandin stimulates uterine smooth muscle contraction
⇩
Vasoconstriction of uterine arteries
⇩
Uterus hypoxia
⇩
Dysmenorrhea
n.b Highest level of prostaglandin is secreted during 1st 2 days of menstruation hence pain is felt worst during 1st 2 days

Causes
1° Dysmenorrhea 2° Dysmenorrhea
Idiopathic Fibroids
Adenomyosis
Endometriosis
PID
Endometrial polyps
Adhesions
Cervical stenosis
Presence of IUCD

Clinical Presentation
Pelvic pain associated with
• N&V
• Diarrhea
• Headache
• Fatigue
• Dizziness
• Fever
• ± Signs & symptoms of underlying cause

Assessment of Patient with Dysmenorrhea

History Taking
• Pelvic Pain
Site = Suprapubic / Lowe abdominal region
Onset = Within 2 years of menarche if 1° dysmenorrhea, chronic onset in 2° dysmenorrhea
Character = Crampy, cyclic pelvic pain
Radiation = Radiates to lower back & legs
Associated symptoms = Mentioned above
Timing = Associated with menstrual cycle
Exacerbating & Alleviating factors = Depending on individuals
Severity = Varies
• Gynaecological History
Past gynaecological surgeries → adhesion formation, PID, STDs
History of menorrhagia → Adenomyosis, polyps, fibroids
Little or response to steroids
• Obstetrics History = Traumatic childbirth, PPH etc
• Detailed sexual history = Infertility, dyspareunia → Endometriosis
• Systematic review = Constitutional symptoms → Malignancy

Physical Examination = General + Abdominal + Pelvic examinations

Investigations for Dysmenorrhea
1. History + PE
2. If normal PE → Proceed with medical treatments, most probably 1° dysmenorrhea
3. Diagnostic Investigations:
• Pelvic / Transvaginal ultrasound → TRO any pelvic pathology
• Diagnostic laparoscopy
− May be both diagnostic & therapeutic particularly in the management of endometriosis & where the pain is of
uncertain origin
− Failed medical therapy for 2° dysmenorrhea warrants a diagnostic laparoscopy
• Hysteroscopy → Define intrauterine pathology & provide endometrial tissue sample for histology
4. Investigations for complications of diseases
• FBC → anaemia related to chronic menorrhagia & PID
• ESR, CRP → Inflammatory markers
• UFEME → TRO UTIs
• UPT → TRO pregnancy in women of childbearing age (βhCG)
• Cervical C+S → TRO STIs

Treatment for Dysmenorrhea

Treatment Principle:
1° Dysmenorrhea → Medical Treatment
2° Dysmenorrhea → Symptomatic treatment + Treat underlying cause

1. Reassurance
2. Lifestyle changes
• Healthy lifestyle
• Regular exercise
• Reduce salts intake
• Weight reduction
• Smoking cessation
3. Pharmacological Treatment
• NSAIDs – 1st line, e.g: Mefenamic acid & Ibuprofen
• OCP- 2nd line if NSAIDs don’t work or contraindicated, e.g. COCP, Depot progesterone, Mirena IUCD (Levonorgestrel)
MENORRHAGIA
Definition
“A complaint of heavy clinical menstrual blood loss over several consecutive menstrual cycles in woman of reproductive years or
more objectively a total of menstrual blood loss >80ml per menstruation” (MOH, 2004)

“Menorrhagia is excessive menstrual blood loss over several consecutive cycles which interferes with woman’s physical,
emotional, social & maternal quality of life” (NICE, 2007)

Clinical Definition
Menorrhagia is heavy menstrual bleeding of >80ml & when the menstrual loss interferes with woman’s daily lifestyles

Other Important Terminology

• Metorrhagia = Menstrual flow at irregular interval
• Menometorrhagia = Heavy menstrual flow >80ml at irregular interval
• Polymenorrhea = Bleeding interval at <21 days
• Postcoital bleeding = Non-menstrual bleeding that occurs spontaneously after sexual intercourse

Classification
1° Menorrhagia → Idiopathic (Dysfunction Uterine Bleeding / DUB)
2° Menorrhagia → Menorrhagia secondary to other pathologies e.g. uterine or ovarian pathologies, systemic disorders or
iatrogenic causes
Dysfunction Uterine Bleeding (DUB)
Causes • Abnormal bleeding in absence of any structural or
Common Cause of Menorrhagia anatomical abnormalities
1. Dysfunction uterine bleeding (DUB)
• Most common cause of menorrhagia
2. Uterine & ovarian pathologies
• Usually a diagnosis of exclusion
• Fibroids
• Most common at extremes of reproductive age
• Polyps
• Endometrial hyperplasia
• PCOS
Endometrial carcinoma
Less Common Causes of Menorrhagia • Usually in patient >40 years old with postmenopausal or
1. Uterine & ovarian pathologies excessive postcoital & intermenstrual bleeding
• Endometriosis • Commonly associated with pelvic pain
• Adenomyosis • RFs
• PID (Endometritis) 1. Age > 40 years old
• Endometrial carcinoma 2. Obese
2. Systemic disease 3. Nulliparous
4. HRT
• Coagulation disease
5. DM
• Hypothyroidism
6. FHx of malignancy
• Liver / Renal diseases
• Clinical Presentation
3. Iatrogenic
− Pelvic ± abdominal mass
• Anticoagulant medications = Warfarin, Aspirin etc
− Signs of metastasis = Malignant ascites,
• Chemotherapy – disrupt normal menstrual cycle
hepatosplenomegaly, cervical involvement,
• Copper IUCD lymphadenopathy & other constitutional symptoms
• OCP – especially if inadequate dosage or non-compliance − Stigmata of chronic anovulation = Hirsutism, acne,
acanthosis & obesity > 90kg

Systemic Diseases
1. Hypothyroidism → Look for S/Sx of hypothyroidism
2. Liver & renal diseases → Dysfunction of either organ
can interfere with coagulation factors and/or metabolism
hormones, which lead to menorrhagia
• Coagulation disorders → R/O Von Willebrand
disorder, Idiopathic Thrombocytopenic Purpura
(ITP) or coagulation factors deficiency (FII, V, VII
& IX)
• Clinical Presentation = Menorrhagia since
menarche often with FHx of bleeding disorders
• Routine screening of coagulation defects should be
reserved for young patient with menorrhagia at
menarche
Clinical Presentation of Menorrhagia
1. Soaking through one or more sanitary pads or tampons every hour for several consecutive hours
2. Needing to use double sanitary protection to control your menstrual flow
3. Needing to wake up to change sanitary protection during the night
4. Bleeding for longer than a week
5. Passing blood clots with menstrual flow for more than one day
6. Restricting daily activities due to heavy menstrual flow
7. Symptoms of anemia, such as tiredness, fatigue or shortness of breath
8. Complications of menorrhagia:
• Fe deficiency anemia →Menorrhagia may decrease iron levels enough to increase the risk of iron deficiency anemia
• Severe pain → With heavy menstrual bleeding, you might have painful menstrual cramps (dysmenorrhea)

Assessment of Patient with Menorrhagia

History Taking
• Ask when menorrhagia starts
• Ask re the timing of menorrhagia, is it cyclicala & associated with menstrual cycle
• Quantify amount of menstrual loss → How many pads / tampon used? How frequent she changes pads / tampon? Fully
soaked?
• How long menses last? → Usually > 1 week
• Did she pass any blood clot?
• Is there any intermenstrual or postcoital bleeding?
• Ask re any associated symptoms?
1. Dysmenorrhea
2. Dyspareunia
3. Pelvic pain → Endometriosis
4. Vaginal discharge
5. Pelvic mass → Fibroids, malignancy
6. Fever, chills & rigors → PID
• Is there any FHx of bleeding disorders or pelvic malignancy?
• Past gynae & obst history
• Contraception
• PMHx
• Systemic review → Constitutional symptoms?

Physical Examination → General + Abdominal + Pelvic Examination

Investigation
Biochemical Test • FBC → R/O anaemia & bleeding disorders
• Coagulation factors → R/O bleeding disorders
• TFT → R/O hypothyroidism
• RFT → R/O any underlying renal pathology leading to coagulopathy
• LFT → R/O any underlying liver pathology leading to coagulopathy
• Tumour marker → R/O endometrial malignancy
• UPT → R/O pregnancy if suspected
• Serum androgens → R/O PCOS

Imaging Test • Transvaginal Ultrasound (TVUS) → R/O Uterine & ovarian pathologies
n.b.Virgin → Transabdominal US instead of TVUS
• ± CT Abdo/Pelvic/Thorax & MRI → R/O metastasis if malignancy

Other Test • Endometrial biopsy → Histological evaluation of endometrial tissue sample if indicated
• Pap smear → Histological evaluation of cervical tissue sample if indicated
• Hysteroscopy → Inspection of uterine cavity
• Sonohysterogram → During this test, a fluid is injected through a tube into uterus by way of vagina
and cervix using ultrasound to look for problems in the lining of uterus
Treatment

Treatment Overview
1. Medical Treatment
• Non-hormonal medication
• Hormonal medication
2. Surgical Treatment
• Endometrial resection or ablation – Transcervical resection of endometrium (TCRE) or balloon ablation
• Hysterectomy
• Myomectomy – removal of fibroids
• Polypeptomy – removal of polyps
3. Other: Uterine artery embolization

Non-Hormonal Medication
1. Prostaglandin synthetase inhibitors
Mefenamic acid (Ponstan) 500mg TDS → taken during Day 1-5 of menstrual cycle
2. Antifibrinolytic agent
Tranexamic acid (Cyclokapron) 1000mg TDS → taken during Day 1-5 of menstrual cycle
Antifibrinolytics
Reduce menstrual loss
Sometimes both medications are used or as an adjunct to hormonal medication

Hormonal Medication
1. OCP
− If it is not contraindicated
− May take 2 or 3 packets ‘back to back’ i.e. without the usual 7 days break
2. Progestogen
− Norethisterone 5mg TDS x 21/28 days
− Useful if woman has irregular cycle
3. Mirena IUCD
− Contains 52mg Levonorgestrel
− Releases 20mcg Levonorgestrel per day over 5 years
− Advice of possibility of irregular bleeding initially for up to 6 months followed by amenorrhea or very light periods
− Frequently used as 1st line for treatment for menorrhagia especially in perimenopausal women & reduced flow volume in
80% of women
− Can often help with symptoms of dysmenorrhea
4. Danazol – rarely used
− Useful if there is endometriosis
− SEs = Androgenic SEs inc irreversible deepening of voice
5. GnRH analogues
− Short term treatment (max for 6 months) for endometriosis or to shrink fibroids before surgery
− Not licenced for use > 6 months in reproductive age
− Long term use leads to reduction bone density
− SEs = Hypoestrogenic SEs (hot flushes, night sweats, vaginal atrophy), which can be minimized with add back therapy
with low dose oestrogen pill

Surgical Treatment
• Surgical treatment is reserved for patient in whom medical treatment has failed
• Occasionally surgical treatment is required in acute situation to reduce haemorrhage
• Approximately 20-30% of patients with dysfunctional uterine bleeding will ultimately require some form of surgical
intervention
• Common methods used in surgical treatment:
1. Endometrial Resection or Ablation
2. Myomectomy – if patient has fibroids
3. Hysterectomy
4. Uterine Artery Embolization
Endometrial Resection or Ablation
• Involves resection or ablation of the endometrium so that layer of fibrous tissues replaces it
• Minimally invasive – a day case procedure
• Endometrial histology should always be done either prior to or at time of surgery to exclude possibility of atypical
endometrial hyperplasia or carcinoma
• 80% satisfaction rate
• Common techniques used:
1. Laser
2. Diathermy
3. Microwave
4. Thermal balloon ablation (82° C) – MOST COMMONLY USED
• Usually causes oligomenorrhea rather than amenorrhea
• Only suitable if no future pregnancy plan because patient must use contraception (usually Mirena IUCD) afterwards

Myomectomy
• Consider if woman wishes to retain her fertility otherwise hysterectomy is a better option
• Pre-treat with GnRH analogue to shrink & de-vascularise fibroids immediately after surgery
• Some advocates only using GnRH pre-surgery when clinically fibroids are palapable above umbilicus as it may cause fibroids
& obscure surgical planes when fibroids are smaller making procedure more challenging
• Techniques uses: Laparoscopic or open procedure depending on location of fibroids
• SE = Severe risk of haemorrhage
− May necessitate hysterectomy
− Foley catheter wrapped around the lower uterine segment at the time of surgery sometimes used to reduce blood loss
− Patients may need hysterectomy later if fibroids recur

Hysterectomy
• Techniques: Abdominal, Vaginal or Laparoscopic
• Vaginal & laparoscopic routes associated with less post-op pain & shortened hospital admission
Abdominal − Total or subtotal
n.b. Cervix is not removed in subtotal hysterectomy therefore patient must be advised to continue
having Pap smear as cervical ca prevention
− Transverse or midline incision
− ± Bilateral salphingo-oophorectomy
Laparoscopic − LAVH = Laparoscopic Assisted Vaginal Hysterectomy
− TLH = Total Laparoscopic Hysterectomy
Vaginal − Not suitable if large uterus due to fibroids or other insufficient descent / prolapse
− BSO difficult to perform

Uterine Artery Embolization (UAE)

• May be used to treat single or small number of fibroids
• An alternative treatment of myomectomy
• Done by radiologists via catheter in femoral vein
• MOA = UAE causes avascular necrosis of fibroids
• SEs = Pain due to devascularisation of fibroids
 ADENOMYOSIS

Definition
• Adenomyosis is defined by presence of endometrial tissue (endometrial glands & stroma) within myometrium
• Some also define adenomyosis as presence of endometrial glands & stroma to depth of at least 1/3rd of uterine wall thickness
• Used to be called endometriosis interna
• Adenomyoma describes a focus of adenomyosis within a leiomyoma (fibroid). Both conditions are common so it is not
surprising that this overlap condition may occur

Grading of Adenomyosis
Molitors Criteria: According to depth of penetration
Grade I — Inner 1/3rd of myometrium
Grade II — Middle 1/3rd of myometrium
Grade III — Outer 1/3rd of myometrium

Grading of Bird et al: According to number of glands

Mild — 1-3 glands / LPF
Moderate — 4-9 glands / LPF
Severe — >9 glands / LPF

Risk Factor
1. Increasing parity
2. Early menarche
3. Short menstrual cycle
4. History of endomyometrial trauma: C section, endometria D&C
5. Antidepressant drug use (2° to hyperprolactinaemia)
6. Tamoxifen (due to action of oestrogen to the endometrium)

Causes
1. Hereditary
2. Trauma
3. Hyperoestrogenaemia
4. Viral transmission

Clinical Classification
1. Diffuse adenomyosis → Involving large portion of myometrium
2. Focal adenomyosis → Adenomyoma or cystic adenomyosis
• Adenomyoma: Restricted area of myometrium with clear border
• Cystic adenomyosis (Juvenile cystic adenomyosis)
− Age < 30 years old, cystic lesion < 1cm, severe dysmenorrhea
3. Polypoid adenomyosis
4. Endocervical adenomyosis
5. Retroperitoneal adenomyosis
Pathophysiology — can be demonstrated by several theories
Von Recklinghausen theory Adenomyosis originates from Mullerian duct
(1896)
Thomas S. Cullen theory (1896) Adenomyosis results from direct invasion or extension of basal endometrium into
myometrium
Most accepted theory
• Uterine manipulations plays a crucial role in invasion of endometrial cell into
myometrium
• Endomyometrial trauma
1. Normal delivery
2. C Section
It has been suggested that trauma of childbirth leads to breakdown of normal endo-
myometrial border, subsequent reactive hyperplasia of basalis endometrium leads to
an invasion of the myometrium & subsequent endometrium.
3. Myomectomy
4. Dilatation & Curettage (D&C)
5. Endometrial ablation
Ivanoff theory (1898) Adenomyosis occurs due to penetration of myometrium from serous coat after metaplasia

Arterioles angiogenesis theory Alteration of spiral arterioles angiogenesis

The hypothesis postulates that ovulatory menstrual cycles during early reproductive life have
an angiogenic priming effect that will permit successful deep penetration

Pathology
Macroscopic Finding
• Uterus is uniformly enlarged; asymetrically if focal adenomyosis
• External surface: smooth, regular
• On palpation: uterus diffusely boggy or it may have nodular consistency
• Serosa may have patchy pink colour suggesting hyperemia or congestion
Cross-Section
• Myometrium shows diffuse hyperplasia
• Posterior wall may be involved more
• Trabecular or granular appearance on cut section
• Small, dark cystic areas containing fluid or old blood (burnt match stick appearance)

Cross-section through the wall of hysterectomy specimen of a

30-year-old woman who reported chronic pelvic pain & AUB.
The endometrial surface is at the top of image & serosa is at the
bottom

The image above shows myometrial hypertrophy &

endometrial hypertrophy

Burnt match stick appearance

Microscopic Finding
• Novak & Woodruff criteria: Presence of endometrial stroma and glands within myometrium, at least one high power field
below basal endometrium
• Bensen & Sneedens criteria: Presence of endometrial stroma and glands within myometrium, at least two low power field
below basal endometrium

Clinical Feature
Classic presentation → Cyclic, cramping pelvic pain beginning later associated with prolonged heavy menstrual bleeding (HMB)
Pathophysiology of dysmenorrhea in adenomyosis:
Gland tissue grows during menstrual cycle and then at menses tries to slough. However tissue and blood in ectopic glands cannot
escape, as there is no drainage. This trapping of the blood and tissue causes uterine pain in the form of monthly menstrual cramps

Symptoms Signs
• Most cases are asymptomatic • Abdo exam: Enlarged uterus, usually <14w in size
• Pelvic pain • Pelvic exam:
• Dysmenorrhea − Uniform uterine enlargement with no restriction of
• Menorrhagia unresponsive to hormonal therapy or uterine mobility
curettage − Uterus soft, boggy & tender (Halbans sign)
• Dyspareunia
• Dyschezia
• Subfertility
• AUB due to congestion
• Premenstrual spotting
• Subfertility
• Miscarriage

Causes of subfertility
1. Impaired sperm transport: due to altered uterine peristaltic activity
2. Impaired implantation
3. Impaired endometrial receptivity: abnormal vascular proliferation
4. Changes in endometrium: adverse molecular factors like VEGF
5. Changes in myometrium
6. Gene dysregulation

Uterine peristaltic activity

• Originates exclusively from the JZ, while the outer myometrium remains quiescent
• During the follicular and periovulatory phases, contraction waves have a cervico-fundal orientation and their amplitude and
frequency increase significantly towards the time of ovulation
• Role of peristalitic waves: endometrial differentiation, menstruation, sperm transport, implantation
• In humans, interstitial & intravascular trophoblast invasion goes beyond endometrium & involves the JZ, but not the outer
• These physiological phenomena are altered in adenomyosis, & therefore it seems logical to assume that the condition may
cause hypo- or infertility in affected women

Differential Diagnosis
1. Uterine polyps
2. Endometriosis
3. Endometrial carcinoma
4. Uterine fibroid
5. Preagnancy / Ectopic pregnancy

Diagnosis
Diagnosis can only be proven by pathologist
Gynecologist may suspect adenomyosis based on the clinical factors, but the final diagnosis usually has to wait until hysterectomy
is performed

Investigation
1. USG (TVUS)
2. Hysterosalpingogram (HSG)
3. Sonoalpingography (SSG)
4. Endometrial sampling
5. CA-125
6. MRI – highly accurate in diagnosis of adenomyosis
TVUS
Normal Uterus on TVUS
The normal myometrium (M) is moderately echogenic & has a
homogenous echotexture. Note the arcuate veins in the outer
myometrium dorsally. The patient is midcycle & has a trilaminar
endometrium (E)

TVUS Findings Suggestive Of Adenomyosis

Asymmetrical
uterine enlargement
(globular appearing
uterus)

   

   
Heterogenous
echogenicity
 • Hyperechoic: islands of endometrial glands
• Hypoechoic: associated muscle hypertrophy
• "Venetian blind" appearance may be seen due to subendometrial echogenic linear striations and
acoustic shadowing where endometrial tissues cause a hyperplastic reaction

Subendometrial The presence of dilated cystic glands or haemorrhagic foci within heterotopic endometrial tissue results in
cyst (small the presence of small myometrial cyst (usually <5 mm in d)
myometrial cyst)

Subendometrial
echogenic linear
striation

Subendometrial
stripes
HSG
• Characteristic findings are multiple spicules 1-4mm extending from endometrium into myometrium & ending in small sacs
• Honeycomb appearance in myometrium due to communication between endometrium & myometrium
• Non-specific as they can occur due to lymphatic & vascular extravasation also

HSG shows multiple diverticular-like projection of contrast

into myometrium (intramural diverticuli) typical of
adenomyosis.This condition can be confused with intravasation

Sonosalpingography (SSG)
• SSG is done by USG, and HSG is done by an X-ray; either is to check normal shaped uterus, and open tubes
• SSG is the 'newer' updated version, and is more accurate than simply putting the dye in then taking a serious of X-rays

n.b. Role of Color Doppler — To differentiate Leiomyomas & Adenomyosis

• Leiomyoma: Peripheral scattered feeding vessels or outer feeding vessels were noted
• Adenomyosis: vessels traverse the hypertrophic myometrium between cystic spaces.

MRI
• Accurate & superior to USG
• MRI findings suggestive of adenomyosis: widening of JZ & bright foci (seen on T1 or T2-weighted images)
• Normal width of JZ is up to 8mm
• Widening of JZ from 8 up to 12mm is suggestive of focal adenomyosis
• Widening of JZ >12 is suggestive of diffuse adenomyosis
• Homogenous JZ thickness > 12mm with haemorrhagic high signal myometrial spots is highly predictive

Classification for adenomyosis based on MRI uterine JZ:

1. Simple JZ hyperplasia (zone thickness 8 mm but <12 mm on T2-weighted images, in women aged 35 years or less)
2. Partial or diffuse adenomyosis (thickness 12 mm; high-signal-intensity myometrial foci; involvement of the outer
myometrium: <1/3, <2/3, >2/3)
3. Adenomyoma (myometrial mass with indistinct margins of primarily low-signal intensit on all MRI sequences).

CA 125 — raised but not specific

Endometrial Sampling — TRO other pathologies

OVERVIEW: Investigation for Adenomyosis

1. Baseline blood investigation: FBC, ESR, CRP, bhCG (TRO pregnancy)
2. Clinical diagnosis
3. Imaging test: TVUS or MRI (raised a suspicion of adenomyosis but doesn’t confirm dx; also done TRO
other pathologies)
4. Endometrial sampling & HPE – only this can confirm diagnosis
5. Serum CA-125 tumour marker (TRO endometrial ca)
Treatment
Non-surgical Treatment Conservative Treatment For young symptomtomatic patient: Observation & NSAIDS
Pharmacological Treatment 1. Fe supplement as indicated
2. Analgesia (NSAIDS) to relieve pain
3. Progestin
4. OCP esp if a/w menorrhagia & dysmenorrhea
5. GnRH agonist (Leuprolide)
6. Mirena
7. Low dose Danazol
Surgical Treatment 1. Hysterectomy
2. Uterine sparing procedures
1. Total adenomyomectomy
• Preferably used in cases of localized adenomyosis (adenomyoma)
• Selected cases of diffuse adenomyosis with reconstruction of the uterine wall
• This includes the complete removal of all clinically recognizable non-microscopic
lesions
• The integrity of uterine wall is maintained
2. Partial adenomyomectomy
• Done in diffuse adenomyosis
• Partial removal of clinically recognizable non-microscopic lesions because complete
removal of the lesion would lead to the concomitant excision of critical amount of
healthy myometrium, which could lead to “functional” hysterectomy
3. Cystectomy: Used in cases of cystic focal adenomyosis inc entire removal of adenomyotic
cyst
4. Uterine Artery Embolization (UAE)
• Minimally invasive angiographic interventional procedure which delivers embolic
materials into both uterine arteries & leads to ischemia & necrosis of adenomyotic tissue
• PVA pellets of 500-710 um or triacryl gelatin microspheres are used.
• Procedure is done by interventional radiologist
• Under digital flouroscopic control
• Via femoral artery, a percutaneous catheter is passed to IIA & then passed to UA
• Embolic materials are then injected
• Procedure is repeated on other side
• Duration: 45-60 m

Pregnancy & Adenomyosis

Intervention to conception time: At least 3 months after conception

Implications to ART methods:

• ART increased pregnancy rates after operative intervention when compared to natural cycles
• Single embryo transfer
 ENDOMETRIOSIS
Definition
Endometriosis = Benign condition in which endometrial tissue (glands & stroma) is present outside of the uterine cavity
Endometrioma = Endometriotic cyst on surface of ovary (chocolate cyst)

Epidemiology
• Incidence: 15-30% of pre-menopausal women
• Mean age at presentation: 25-30 yr
• Regresses after menopause

Risk Factors
• Family history (7-10x increased risk if affected 1st degree relative)
• Obstructive anomalies of the genital tract (earlier onset) – resolve with treatment of anomaly
• Nulliparity
• Age >25 yr
• Laparotomy scars — especially after C-section or myomectomy where endometrial cavity is entered; probably due to seeding
of endometrial tissue in the surgical incision
• Short menstrual cycle <27 days All of these associated with higher
• Long duration of menstrual flow >7 days risk of retrograde menstruation
• HMB  

Pathophysiology
• Not fully understood, combination likely involved
• Proposed mechanisms
Retrograde menstruation Seeding of endometrial cells by transtubal regurgitation during menstruation
(Sampson’s theory) Endometrial cells most often found in dependent sites of the pelvis
Immunologic theory Altered immunity may limit clearance of transplanted endometrial cells from pelvic cavity
(may be due to decreased NK cell activity)
Mullerian metaplasia Proposes that metaplastic transformation of the peritoneal mesotheium into endothelium occurs
theory (Meyer) under the influence of certain generally unidentified stimuli
Lymphatic spread theory Proposes that endometrial tissues can be taken by lymphatic draining the uterus &
(Halban) subsequently transported to various pelvic & extra-pelvic sites

Sites
• Pelvic: Uterine & extra-uterine
Uterine
Extra-uterine: Ovaries, broad ligament, vesicoperitoneal fold, peritoneal surface of the cul-de-sac, uterosacral ligament,
rectosigmoid colon & appendix
• Extra-pelvic (rare): Lungs & pleura, umbilicus or lap scars

OVARY IS THE MOST COMMON SITE

• Endometriotic implants initially on the mesothelial surface of the ovary
• Subsequently invaginates into stroma of ovary facilitated cyclical bleeding
• Ovarian lesions may trap menstruating blood, which form endometriotic cyst (chocolate cyst) or endometrioma
• Degenerated blood over time turns think & brown giving them the name chocolate cyst
Clinical Feature

Classic Triad of Endometriosis

1. Dysmenorrhea
2. Dyspareunia
3. Dyschezia

Common symptoms:
• May be asymptomatic
• Infertility
• Pain
Pelvic pain: cyclic pain due to growth & bleeding of ectopic endometrium, usually precede menses (24-48h) & continue
throughout & after flow
Dysmenorrhea (Crescendo = Progressive)
Dyspareunia — deep;
Dysuria
Dyschezia — occurs when there is involvement of rectovaginal septum

Less common symptoms:

• Urinary symptoms: WISE, FUN, haematuria
• Bowel symptoms: Cyclic diarrhea/constipation, hematochezia, dyschezia (suggestive of deeply infiltrating disease)
• Haemoptysis — if formation of endometriosis at distant site e.g lungs

Signs:
• Tender pelvic nodules
− Uterosacral nodules
− Pouch of Douglas nodules
− Tender nodule / mulberry-like spot may be seen in the posterior fornix of the vagina
• Firm & fixed adnexal mass (endometrioma)
• Fixed retroverted uterus (blood in the peritoneum is an irritant that promotes adhesion formation leading to fixed retroverted
uterus)
• Nodules along the uterosacral ligament

Differential Diagnoses
• Chronic PID
• Leiomyoma
• Recurrent acute salpingitis
• Hemorrhagic corpus luteum cyst
• Benign/malignant ovarian neoplasm
• Ectopic pregnancy
• Irritable bowel syndrome (IBS)
Investigation
Endometriosis is generally presumptively diagnosed on clinical grounds with a history & physical examination findings
suggestive of it; any investigation performed is limited for its confirmation but should be done to rule out important differentials

Baseline Investigation
1. FBC
2. ESR, CRP
3. UPT or bHCG

Investigation to confirm diagnosis

1. Laparoscopy
• Gold standard
• Direct visualization of lesions typical of endometriosis at laparoscopy
• Can be both diagnostic & therapeutic
• Laparoscopic findings suggestive of endometriosis
1. Mulberry spots: dark blue or brownish-black implants on uterosacral ligaments, cul-de-sac, or anywhere in pelvis
2. Endometrioma: “chocolate” cysts on ovaries
3. “Powder-burn” lesions on peritoneal surface (nodule / small cyst containing old haemorrhae surrounded by fibrosis)
4. White lesions (fibromuscular scarring)
5. Brown lesion (Haemosiderin deposit)
6. Peritoneal “pockets”
7. Adhesion

2. Biopsy & HPE (≥2 endometrial epithelium, glands, stroma, hemosiderin-laden macrophages)
3. Ultrasound (TVUS)
• Only diagnostic if on the ovary (endometrioma / chocolate cyst)
• Useful to rule out other pathologies e.g ectopic pregnancy, tubo-ovarian abscess in chronic PID, haemorrhagic corpus
luteum cyst or neoplastic cyst BUT IT CANNOT CONFIRM DIAGNOSIS
• Classical appearance: Homogenous, hypoechoic mass with in ovary
• Other imaging modalities: TRUS (detect rectal involvement), MRI, CT scan, IVU, Barium enema

Investigation TRO other pathologies

1. UPT — TRO ectopic pregnancy
2. CA-125
• Usually raised in endometriosis typically in range of 50-100 U/ml
• Useful for monitoring treatment
Classification
Stage of Endometriosis (ASRM)
• Stages are depending on size, location & extend of endometriosis
• Intra-operative staging because endometriosis doesn’t correlate with symptoms
Treatment
Treatment depends on
1. Age
2. Severity of symptoms
3. Desire for future fertility
4. Extend of disease

Treatment Options
Non-surgical Treatment Pharmacological 1. Non-hormonal
Treatment 1. NSAIDs for pain relief
• E.g. Ibuprofen (Sapofen), Naproxen (Naprosyn), Mefenamic acid
(Ponstan)
• Useful in women trying to conceive
• Start 2 days before menstruation
• SEs: Gastric ulcer
2. COX-2
• E.g. Celebrex, Vioxx
• Not as effective as NSAIDs but lower risk of gastric ulcer

2. Hormonal (useful if patients don’t want to conceive)

1st line: OCP
1. Cyclic / Continuous estrogen-progestin
2. Progestin: IM medroxyprogesterone (Depo Provera) or PO dienogest
(Visanne®)
3. Mirena® IUS

2nd line: GnRH & Danazol

1. GnRH agonist e.g Leuprolide (Lupron®), LHRH, Goserelin
• MOA: Suppresses pituitary
• Hypoestrogenic SEs: Hot flashes, vaginal dryness, reduced libido
• Must not use > 6 months due to prevent osteoporosis &
menopausal symptoms
• If use > 6 month, must include add-back therapy
2. Danazol (Danocrine® / Danol)
• MOA: weak androgen
• Metabolized in liver
• SEs: Androgenic (weight gain, fluid retention, acne, hirsutism,
voice change) & hypoestrogenic
• Contraindication: Liver disease, severe HTN, CHF, impaired renal
function

Surgical Treatment Conservative 1. Ablation / Resection of implants

Surgical Treatment 2. Lysis of adhesions
3. Ovarian cystectomy of endometriomas
4. Laser vaporization
5. Helium beam coagulation
6. Excision of endometriosis deposits

Radical / Definitive Hysterectomy ± BSO ± f/up with medical treatment for pain control
Surgical Treatment
N.b. GnRH agonist
• Example: Leuprolide (Lupron®), LHRH, Goserelin
• MOA: After initial agonistic action (flare response), down-regulation & desensitization of the pituitary: hypogonadotrophic,
hypogonadal state
• Indication
1. No response to OCP s or progestins
2. Recurrence of symptoms after initial improvement
• Side effects: Symptoms of estrogen deficiency
1. Hot flushes
2. Insomnia
3. Loss of libido
4. Vaginal dryness
5. Emotional instability
6. Depression
7. Headache
8. Loss of BMD
• Add-back therapy
− E.g. Bisphosphonates (ethidronate), oestrogen-progesterone combination, tibilone
− Aim: To prevent demineralization of bone & menopausal symptoms
− GnRha should not be given as a single agent for >6 months without add-back therapy
− Rationale: There is a threshold serum estrogen concentration that is low enough that endometriosis is not stimulated but
high enough that hypoestrogenic symptoms are prevented

Question: Is laparoscopy required before medical management of pelvic pain?

Answer:
Not always necessary
Management of the pain is required whether or not endometriosis is the cause
All managements aim to decrease inflammatory conditions in the pelvis
Endometriosis can be strongly suspected when there is:
• Severe dysmenorrhea unresponsive to NSAID
• On palpation of the uterosacral ligs & rectovaginal septum: tenderness and nodularity OR
• US: endometrioma
In these situations, laparoscopy for diagnosis is not necessary before medical
 FIBROID (LEIOMYOMA)
Definition
Benign smooth muscle tumour of the uterus arises from myometrium

Epidemiology
• Diagnosed in approximately 40-50% of pre-menopausal women >35 yr
• More common in African Americans, where they are also larger and occur at earlier age
• Most common gynecological tumour
• Minimal malignant potential (1:1,000)
• Typically regress after menopause; enlarging fibroids in a postmenopausal woman should prompt consideration of
malignancy
• 50% of leiomyosarcomas originate from within fibroids

Risk Factors
Increased risk Decreased risk
• Premenopausal women age 35-45, after menopause • Multiparity
fibroids usually shrink • Late menarche
• Nulliparous • Exercise
• Race (African & Caribbean descent) • High intake of green vegetables
• FHx • Cigarette smoking
• Obesity • Progesterone-only contraceptive
• Eating habits: Red meat, ham
• Early menarche, late menopause
• DM
• HTN

Pathogenesis
Genetic • Fibroids are usually monoclonal
• 40% include chromosomal abnormalities
1. Translocations between chromosomes 12 and14.
2. Deletions of chromosome 7
3. Trisomy of chromosome 12 in large tumors
• 60% include undetected mutation

Hormone Oestrogen
• Found more with hyper estrogenic states like obesity, increases after ERT therapy in menopausal women,
endometriosis, endometrium ca, anovulatory infertility & early menarche
• Oestrogen stimulates monoclonal smooth muscle proliferation

Progesterone
• Progesterone stimulates production of proteins that inhibit apoptosis
• Highest mitotic counts are found in fibroid cells when progesterone concentration is also high

Growth factor • Growth factors produced locally by smooth muscle cells & fibroblasts promote growth of fibroids primarily
by increasing extracellular matrix
• Examples
1. Tumor Growth Factor β (TGF-β)
2. Basic-Fibroblast Growth Factor (bFGF)
3. Epidermal Growth factor (EGF)
4. Platelet Derived Growth Factor (PDGF)
5. Insulin-Like Growth Factor (IGF)
6. Vascular Endothelial Growth Fator (VEGF)
7. Prolactin (PRL)
Natural History of Fibroids
• Most fibroid grow slowly - 9% growth rate over 12 months, more depending on growth factors rather than hormones
• Growth rate decreases after age 35 yrs in white women, but not in black
• Most of them regress with onset of menopause
• Rapid growth in premenopausal women → Suspect pregnancy
• Rapid growth in postmenopausal women ± pain & bleeding → Suspect sarcoma
• Rapid uterine fibroid growth in premenopausal age almost never indicate sarcomatous change
• 0.5% women with pre-exisiting fibroid may develop pain and bleeding in their postmenopausal age, as their fibroid might
have under gone sarcomatous changes
• Fibroids may become calcified in menopausal women
• Fibroids may develop variety of degenerative changes

Degenerative Changes
1. Subserosal fibroid → Sessile → Pedunculated → Torsion → Acute abdominal pain
2. Detached → Wandering fibroid → Get attached to other peritoneal structure → Parasite Fibroid
3. Hyaline degeneration
4. Fatty degeneration
5. Red degeneration (Aseptic Necrobiosis) → In pregnancy, postpartum
• Red degeneration occurs most frequently during pregnancy in which it becomes tense and tender and causes severe
abdominal pain with constitutional upset and fever. Fibroid becomes reddish with a particular fishy smell. Leucocytosis
and raised ESR may be present but this is an aseptic condition. Examination of fibroid shows thrombosed vessel
6. Saponification
7. Cystic degeneration
8. Calcification (Visible on x ray)
9. Hemorrhagic, torsion
10. Sarcomatous changes What is parasitic fibroid?
11. Infection/ulceration of pedunculated fibroid Rarely, a extruded fibroid gets
12. Association with endometrial Ca, endometriosis, follicular enlargement of ovaries. detached from uterus and
13. Inversion of uterus attaches to a vascular organ
(omentum or bowel). This
Classification of Fibroid fibroid is called parasitic fibroid
1. Subserosal or wandering fibroid.
2. Intramural
3. Submucosal
Most symptomatic type; patient usually presented with AUB & infertility
4. Pedunculated
5. Cervical
FIGO Leiomyoma Sub-Classification System
Pathology
Macroscopic view • Leiomyomas are pseudoencapsulated solid tumors, well demarcated from the surrounding myometrium
• Well circumscribed white firm mass surrounded by false capsule formed by compressed uterine muscle
• Vessels that supply blood to tumor lie in capsule and send radial branch to tumor hence central part of
tumor is comparatively less vascular,thereby degenerative changes are noticeable in center
• Calcification at the periphery & spreads inwards along the vessels (Tombstone)
• Cut surface shows whorled appearance

Microscopic view • Microscopically, these appear as smooth muscle cells in longitudinal or cross-section intermixed with
fibrous connective tissue. Vascular structures are few, and mitoses are rare.
Clinical Feature
Symptoms
1. Majority asymptomatic — often discovered as incidental finding on pelvic exam or U/S
2. Abnormal uterine bleeding: Dysmenorrhea, menorrhagia, metrorhagia, polymenorrhea (esp submucosal fibroids)
3. Pelvic pain
• Congestive & spasmodic dysmenorrhea; colicky in nature & may radiate to lower back
• Acute pain → Torsion, haemorrhage & degeneration of fibroid
• Chronic pain
4. Pressure symptoms
• Pelvic pressure/heaviness
• Urinary frequency and urgency
• Acute urinary retention → Hydronephrosis, hydroureter
• Intestinal obstruction: Bloating, cannot pass flatus, constipation
5. Infertility, recurrent abortion — Especially if fibroid distorts uterine cavity (submucosal fibroid)
6. Abdominal lump
• Rapid growth
• Pseudo Meig’s syndrome
7. 2° symptoms
• Anaemia due to blood loss
• Vaginal discharge
• Obstetric complications: Abortion, preterm labour, premature delivery, abruption placenta, IUGR

Signs on PE
1. General Examination → Assess v/s for pallor, signs of malignancy
2. Abdominal Examination → Abdominal mass, signs of malignancy (hepatomegaly, ascites)
• Fibroid with uterus >12-14w of gestation is well palpable per abdomen; may be as big as term pregnancy
• Non-tender
• Firm in consistency
• Freely mobile — up and down, side-to-side till it incarcerates in pelvis
• Irregular surface
• Nodular
• No Braxton Hick contractions
• No palpable fetal parts, movements and no fetal heart sound
• Uterine soufflé due to increased blood supply to uterus may be audible, it has to be differentiated from umbilical soufflé
3. Pelvic Examination
• Speculum Examination → Visualize cervix & take a Pap smear TRO cervical pathology
• Digital Vaginal Examination → Test for cervical excitation (if present suspect PID)
• Bimanual palpation → Assess uterus size, surface, mobility or mass (uterine or adnexal)

Causes of Menorrhagia in Uterine Fibroid

1. Increase TSA/V
• Fibroid (esp submucous type) will grow and stretch the uterine cavity. This will increase total surface area of the
endometrium. More tissues need to be shed during menstruation & thus leading to menorrhagia
2. Endometrial hyperplasia
3. Congestion & dilation of venous plexus
4. Imbalance in prostaglandin production as fibroid as been shown to release prostacyclin
5. Disturbance in uterine contractility

Complication of Fibroid
1. Degeneration
2. Torsion
3. Inversion of uterus
4. Capsular haemorrhage
5. Infection
6. Associated endometrial carcinoma
7. Obstetric complications: Abortion, preterm labour, premature delivery, abruption placenta, IUGR

Differential Diagnosis
1. Uterus: Uterine fibroids, pregnancy, adenomyosis, endometrial ca or sarcoma, haematometra / pyometra, bicornuate uterus
2. Ovary & fallopian tube: Tubo-ovarian masses, endometriosis, ovarian cyst, ovarian ca
3. Other: Full bladder, ectopic pregnancy
Investigation
1. History & Physical Examination
2. Baseline investigation
• FBC → Look at Hg level to rule out anaemia, polycythaemia
• Blood grouping & crossmatch → For transfusion if necessary
• ESR, CRP → Inflammatory markers
• Serum glucose (RBS, FBS, HbA1C) → To rule out Diabetes Mellitus
• RFT → Serum urea & creatinine esp to assess renal function
• Urine test → Albuminuria, glycosuria & deposit
• UPT → To rule out pregnancy
3. Investigation To Confirm Diagnosis: Imaging
• TVS / TAS → To confirm diagnosis and assess location of fibroids
• HSG, SSG → Useful for rule out other uterine pathology e.g polyps & fibroids
• MRI → Allows evaluation of number, size location & proximity to bladder, rectum, tubal opening in uterine cavity and
endometrium, thus helping in planning surgery
• Hysteroscopy
4. Other Investigation
• Endometrial biopsy → To rule out uterine cancer for abnormal uterine bleeding (esp. if age >40)
• Dilatation and curettage → To rule out endometrial cancer
• Intravenous pyelogram → To trace course of ureter to avoid injury during surgery & to rule out renal abnormalities

Treatment

Indication for Treatment

Asymptomatic fibroid:
1. Infertility caused by cornual blocking or abortion caused by submucous fibroid
2. Fibroid more than 12 weeks size or a pedunculated fibroid which can undergo torsion
3. Fibroid causing pressure on ureter
4. Rapidly growing fibroid
5. If the nature of tumour cant be assessed clinically
Symptomatic fibroid: → All symptomatic fibroid needs treatment which can be medical or surgical
Treatment Options
Non-surgical Treatment Conservative Treatment 1. Treat anaemia if present → Fe supplement, blood transfusion
2. Watch & wait
Indications:
1. Symptoms absent or minimal
2. Fibroids <6-8 cm or stable in size
3. Not submucosal (submucosal fibroids are more likely to be
symptomatic)
4. Currently pregnant due to increased risk of bleeding (follow-
up U/S if symptoms progress)
Pharmacological Treatment 1. Non-hormonal:
(to treat HMB) • Anti-Prostaglandin (Mefenamic acid, Ibuprofen)
• Tranexamic acid (Cyklokapron®)
2. Hormonal:
• OCP
• Depo-Provera
• Mirena
• GnRH agonist: leuprolide (Lupron®), danazol (Danocrine®)
3. Ulipristal acetate: Partial progesterone receptor agonist
Surgical Treatment 1. Myomectomy (hysteroscopic, transabdominal, or laparoscopic): preserves fertility
(for failed medical 2. Hysteroscopic resection of fibroid and endometrial ablation for menorrhagia
therapy) 3. Hysterectomy ± BSO
Note: avoid operating on fibroids during pregnancy (due to high vascularity & potential pregnancy
loss); expectant management usually best
Other Uterine artery embolization (UAE)
• Shrinks fibroids by 50% at 6 mo
• Improves menorrhagia in 90% of patients within 1-2 mo
• Not an option in women considering childbearing
Treatment Regime for Fibroids
 PELVIC ORGAN PROLAPSE (POP)
Definition
• Prolapsus (Latin) = A slipping forth, the falling or slipping out of place of a part or viscus
• POP = Abnormal descent or herniation of pelvic organs from their normal attachment sites or their normal position in pelvis
• Often accompanied by urinary, bowel, sexual & local pelvic symptoms
• Common condition affecting women today as life expectancy is gradually increasing

History of POP
• First recorded on Kahun papyri ~ 2000 BC
• Numerous non-surgical methods described by Hippocrates
• 98 BC Soranus of Rome described removal of prolapsed uterus when it became black
• Vaginal Hysterectomy
− Described by Willouby in 1670
− Self performed by a peasant woman named Faith Raworth
− Pulled down the cervix and slashed off the prolapse with a sharp knife
− Survived haemorrhage but had Urinary Incontinence for the rest of her life
Why urinary incontinence? → Slashing off the protruding pelvic prolapse may have cut the bladder causing urinary
incontinence

Epidemiology
Man et al 1997 Prevalence varies widely between studies due to different numerator (criteria) and denominator (populations)
Prevalence (increased with age) 3.9%
Olsen et al 1997 Lifetime risk of prolapse surgery
By the age 60
By the age of 80

Causes of POP
1. Pregnancy
• Stretches & tears of endopelvic fascia, levator muscles & perineal body
• Partial pudendal & perineal neuropathis
• Impaired nerve transmission to the muscles of pelvic floor leading to further sagging & stretching
2. Vaginal childbirth
• Traumatic childbirth
• Large babies
• High parity
• Prolonged second stage of labour
• Instrumental delivery
3. Menopause – reduced oestrogen level, which plays important role in maintaining uterine & pelvic muscles structure
4. Increased abdominal pressure
• Chronic cough – COAD, asthma etc
• Sneezing
• Straining – haemorrhoids, urinary stones
• Occupational – requiring heavy lifting e.g. labor works etc
• Obesity
5. Abnormal connective tissue disorders

Type of POP
1. Urethrocele
2. Cystocele
3. Enterocele
4. Rectocele
5. Uterine prolapse
6. Vaginal vault prolapse
Anatomical Background
• Support of uterus
1. General support of the uterus = Cardinal ligament of Mackenrodt & uterosacral ligaments
2. Pelvic floor support = Levator ani & coccygeus muscles
3. Pubo-urethral & cervical ligament
o Level of uterus support (DeLancey 1992)

DeLancey’s Level of Support & the Type of Defect

POP has same concept as herniation of pelvic structures, where repair is pointed towards correction of defect
Level 1 • Apical – UV descent
• Vaginal vault descent
• Enterococele

Level 2 • Cystocele
• Rectocele

Level 3 • Perineal body deficiency

• USI
• Urethrocele
Degree of Uterine Prolapse

Four Different Systems for Classification of POP

1. Porges Severity system (1963)
2. Baden-Walker Vaginal Grading System (1972)
3. Beecham Grading System (1980)
4. Pelvic Organ Prolapse Quantification System (POPQ by ICS, AUGS, SGS – 1996)

POPQ
POPQ

First published in 1996, an article by Bump et al presents a standard system of terminology approved later by the International
Continence Society (ICS), the American Urogynaecologic Society (AUGS), and the Society of Gynaecologic Surgeons (SGS) for
the description of female pelvic organ prolapse and pelvic floor dysfunction

• Created in an effort to provide objectivity to POP quantification

• Measures the points in relation to the hymenal ring
• Nine specific points of measurement are obtained in relation to the hymenal ring
• 6 vaginal points (Aa, Ba, C, D, Ap, and Bp) = measured during Valsalva manoeuvre
• Points above hymen = negative
• Points below hymen = positive
• Genital hiatus (gh) represents the size of the vaginal opening
• Perineal body (pb) represents the distance between the vagina and the anus
• Total vaginal length (tvl) is measured by reducing the prolapse and measuring the depth of vagina

POP-Q Staging Criteria

Stage Criteria Explanation
0 Aa, Ap, Ba, Bp = -3cm and C or D ≤ - (tvl – 2) cm No prolapse is demonstated
I Stage 0 criteria not met & leading edge < -1cm The most distal portion of the portion is more than
1cm above the level of hymen
II Leading edge ≥ - 1cm but ≤ + 1cm The most distal portion of prolapse is 1cm or less
proximal or distal to plane of hymen
III Leading edge > +1cm but < + (tvl – 2) cm The most distal portion of prolapse is more than 1 cm
below the plane of hymen but protrudes no further
than 2 cm less than the totl vaginal length in cm
IV Leading edge ≥ (tvl – 2) cm Essentially complete eversion of the total length of
the lower genital tract is demonstrated

Average Grid Without Prolapse

Degree of Uterine Prolapse

n.b. Note the descent of cervix which is accompanied by stretching of the ligaments & by supravaginal elongation of the cervix

Assessment of Patient with Pelvic Prolapse

History Taking
Patient Information → Age, Parity, Occupation
Obstetric History →Big baby, instrumental deliveries, difficulties, tears
Menopause → Age, HRT
Associated Symptoms → Urinary & bowel symptoms
Urinary Symptoms Bowel Symptoms
Frequency Constipation
Urgency Straining
Incontinence – stress, urge, mixed Incomplete evacuation
Nocturia Digital reduction/digitate
Incomplete emptying Incontinence of flatus, liquid stool, or solid stool
Hesitancy / obstruction to flow Incontinence
Dribbling
Digital correction
Dysuria/ Haematuria
Pain → Low back, vaginal heaviness
Sexual History → Sexual function, active / inactive, difficulty, dyspareunia, vaginal flatus
Quality of life → How it affect the life (exercise, daily routine, shopping etc)?
PMHx → HTN, DM, IHD, Asthma, COPD
Drug History
Surgical History → Prolapse, incontinence, others
Social History → Occupation, allergies, smoking, alcohol
Family history → Similar condition in family

Physical Examination
General PE → Obesity, weight, BP, RR
Abdominal PE → Masses, ascites
Pelvic PE → Dorsal or Sims position, using either bivalve or Sims speculum
Investigation
1. UFEME, C+S → In cases with urinary symptoms
2. Urodynamic studies → In cases associated with stress incontinence, also for pre-op assessment
3. IVU & cystoscopy → To delineate course of ureters & detect vesical pouch
4. Pelvic & abdominal US → If suspected pelvic or periabdominal mass or hydronephrosis
• New imaging: 3D/4D ultrasound to visualize pelvic floor dynamics have shown the defects clearly
• Identify causes of defect – prevention of pelvic floor injury
• New surgical devices in pelvic floor reconstruction / repair

Management
Consider:
1. Severity of symptoms
2. Family completed
3. Predisposing factors: Obesity, chronic cough, constipation etc
4. Fitness for surgery
5. Request for permanent cure

Treatment Option:
1. Conservative Treatment / Non-surgical Treatment
• Manage risk factors:
1. Stop smoking
2. Avoid heavy lifting
3. Weight loss
4. Bladder training
5. Eliminate / Stabilize chronic cough or other medical conditions predispose to POP
• Manage POP
1. Physiotherapy: Pelvic floor exercise
2. Pessaries – must change every 6 months
Indication:
Unfit for surgery (age or other illness)
Doesn’t want surgery
Pregnant
Family not complete

2. Surgical Treatment
• Aim: Surgical repair of prolapse & to restore function (mobility, social & sexual function of the patient)
• Example:
Apical-Uterovaginal descent 1. Vaginal Hysterectomy
2. Manchester repair
Conservative = Pessaries & 3. Anterior transobturator mesh/sling
pelvic floor exercises 4. Hysterosacrocolpopexy

Vaginal Vault Prolapse 1. Sacrospinous fixation (SSF)

n.b 2. Sacrocolpopexy (Abdominal – laparotomy/laparoscopy)
May occur following 3. New surgical technique uses Prolene mesh (posterior intravaginal sling)
hysterectomy
Older type of vaginal repair
unsatisfactory
High recurrence rates
Enterocele 1. Sacrospinous fixation (SSF)
2. Sacrocolpopexy (Abdominal – laparotomy/laparoscopy)
3. Posterior repair with ligation of sac
4. Uterosacral plication
5. PIVS/ Apogee/Prolift (mesh kits)

Cystocele 1. Standard anterior colporapphy

Anterior compartment 2. Kelly’s repair (recurrence rates 30-40%)
prolapse – cystocoele 3. Defect specific repair
(central, lateral , distal & 4. Mesh reinforced repair
proximal) & urethrocoele 5. Anterior Transobturator Mesh sling (Perigee / Elevate etc)

Rectocele Posterior repair:

1. Levator ani plication,
2. Rectovaginal septum – defect specific repair
n.b.
• Mesh repair in posterior compartment has not met with similar success as ant compartment
• It was found that the native tissue repair gives similar success rate
• No problems with erosion when compared to mesh
 URINARY INCONTINENCE
Definition
• Involuntary loss of urine
• Demonstrable leakage
• Social or hygienic problems

Physiology of Micturition
Urine storage & release are controlled by CNS through reflexes that coordinate the activity of
1. Bladder (smooth muscle)
2. Urethra (smooth & striated muscle)
3. Pelvic floor striated muscle

Neural Control of Micturition

Predisposing Factors
• Faecal impaction
• Decreased mobility
• Confusional state
• Drugs – Diuretics, hypnotics

Type of Urinary Incontinence

1. Stress incontinence
2. Dextrusor overactivity
3. Urinary retention with overflow – uncommon
4. Fistula – vesicovaginal or ureterovaginal fistula
5. Congenital abnormalities – ectopic ureter
Clinical Presentation
• Loss of urine with activity: Incontinence on coughing, laughing or sneezing
• Urgency: Irresistible desire to pass urine & urge incontinence is associated with that desire
• Nocturnal enuresis
It is essential to establish how these symptoms affect patient’s lifestyle

Stress vs Urge Incontinence

Initial Assessment for Urinary Incontinence

1. History & PE
2. Urinalysis & other basic tests
3. Urodynamic testing
4. Cystourethroscopy

Incontinence History Taking

• HOPC
− Onset
− Frequency
− Need of absorbent products – number, type
− Associated symptoms – WISE FUN, haematuria, pain, vaginal dryness, dyspareunia
− Precipitating factors: Cough, exercise, medications, childbirth, surgery, pelvic estrogen status
− Fluid intake – time, amount, type
− Urine output – time, amount, color
− Urine leakage – time, amount, precipitating event (sneeze, cough etc), associated symptoms
− Previous treatment & effects on incontinence
• PMHx: DM, Diabetis Insipidus, psychogenic polydipsia
• PSx
• Drug Hx: Diuretics, anti-hypertensive (alpha-blockers)
• SHx
• FHx: FHx of urological malignancy
Physical Examination
General Examination
Abdominal Examination Mass
Pelvic Examination • Prolapse
• Mass
• Atrophy
• Perineal skin condition
• Paravaginal support
• Palpation of anterior vaginal wall & urethra
• Quantify degree of pelvic relaxation
• Assess ability to perform & strength of voluntary pelvic muscle contraction
• Determine degree of eostrogenization of pelvic structures
Rectal Examination • Mass
• Sphincter tone at rest & active
• Voluntary contraction
• Perineal sensation
• Feacal impaction
Sacral neurological • Sensation
• Reflex = Anal wink (S2-S5) & bulbocavernosus (S2-S3)
• Foot movements
• Voluntary contraction of anal sphincter
• Lower extremity muscle strength

Investigation
• Urinalysis – bacteriuria, haematuria, pyuria, glycosuria, proteinuria
• Other Basics Tests
1. Postvoidal residual
− In those who can void, incomplete bladder emptying is diagnosed by postvoid catheterization or USG (bladder scan)
showing elevated residual urine volume
− Straight catheter with 14 French catheter & 2% xylocaine jelly
2. Stress Test / Cough Test
− Objectively confirms stress incontinence
− Usually performed at 300cc bladder or max bladder capacity
3. Pad Test → Quantify urine loss
4. Simple Cystometry
− Known as flow cystometry
− Clinical diagnostic used to evaluate bladder function
− The resulting chart generated from cystometric analysis is know as cystometrogram (CMG)
− CMG plots volume of liquid emptied from bladder against intravesical pressure
5. Urodynamic Assessment
− Urodynamic assessment is a study that investigate both bladder filling & voiding phases
− Example:
1. Filling urodynamic assessment (cystometrogram)
2. Voiding urodynamic assessment

Cystometogram (Filling Urodynamic Assessment)

• The bladder is filled via a urethral catheter with sterile saline at room temperature running at100mls/min
• Detrusor pressure (pressure within the bladder) is measured
• As the bladder is an intra-abdominal organ, the actual pressure in the bladder = detrusor pressure + intra-abdominal pressure
• Detrusor pressure is measured indirectly by measuring the pressure in the bladder & subtracting the intra-abdominal
pressure, which is measured by vaginal or rectal catheter
• Indications:
1. Symptoms of both stress & urge incontinence
2. Any patient who has failed to respond to medical or surgical treatment
• Disadvantages: Loss of dignity & risk of introducing infection

Voiding Urodynamic Assessment

• A urodynamic assessment during voiding where the measurement include total volume voided, the peak flow of urine voided,
the detrusor activity required to produce the flow
• Demonstrate residual urine eg bladder filled by 500ml but voided 350ml
 Stress Urinary Incontinence

Genuine stress incontinence Detrusor over-activity /

Overactive bladder

Genuine Stress Incontinence

Definition
• Leaking of urine in the presence of raised intra-abdominal pressure (e.g. sneezing, coughing, laughing) & absence of detrusor
activity
• Total bladder pressure will be raised but detrusor pressure is unchanged
• Occurs when there is weakness of the proximal & distal urethral sphincter mechanism

Causes
1. Pregnancy – Vaginal delivery may cause denervation of pudendal nerve & damage to the supporting tissues of urethra
2. Prolapse – Prolapse is not a cause of GSI but deficiency of the supporting tissues which causes prolapse & also GSI
3. Menopause – Lack of oestrogen reduces the maximal urethral closure pressure. This results in a higher pressure in bladder &
GSI occurs
4. Collagen disorders
5. Obesity
No single aetiology

Treatment
Non-surgical Treatment Conservative Treatment
• Alter magnitude of intra-abdominal pressure
1. Cough control: Stop smoking, treat underlying pulmonary conditions, treat allergies
2. Weight loss
3. Exercise modification
4. Reduce heavy lifting
5. Avoid chronic straining with constipation
• Behavioral therapy: Alter fluid & voiding habits (bladder training)
1. Suggest appropriate amount of total fluid per day (2-3L per day is sufficient)
2. Avoid caffeinated & alcoholic beverages
3. Regular voiding intervals
− Consider prophylactic voiding every 2-3h during day (assuming normal fluid intake)
− Adjust voiding frequency based on bladder diary to keep voided volume <350-400cc
• Pelvic floor rehabilitation (exercise)
1. Requires motivated patient
2. At least 3-4 months
3. Patient must be able to correctly perform a voluntary pelvic muscle contraction
4. Patient must strengthen the muscle AND recruit the muscle contraction during increases in
intra-abdominal pressure
5. Most helpful in mild stress incontinence that occurs with cough or sneeze; less effective for
exercise-induced incontinence
• Vaginal cones
1. Adjuvants to pelvic muscle exercises
2. Used in women who are unable or minimally able to generate a pelvic muscle contraction
3. Gives patient goal & ability to determine if performing contraction correctly

Pharmacological Treatment:
1. Collagen injection at bladder neck
2. T. Duloxetine (Serotonin & noradrenaline re-uptake inhibitor)
Blocks reuptake of serotonin (5-HT) & NAD
⇩
Increases activation of α-1 adrenergic & 5-HT2 receptors
⇩
Increases pudendal nerve activity
⇩
Strengthens sphincter contraction
⇩
Helps to prevent urine leakage when pressure is exerted on the bladder
Surgical Treatment 1.
n.b
Surgery doesn’t replace
physiological
mechanism but support
bladder neck & proximal
urethra & prevents
incontinence associated
with raised intra-
abdominal pressure
2.
3.
TensionlessVaginal Tape (TVT)
• Minimally invasive
• Can be done under spinal anaesthesia or GA
• Retropubic method
• Prolene mesh is inserted transvaginally at the level of mid-urethra using 2 trocars
• 90% success rates
• Complications:
1. Vascular injury
2. Vessel, bowel or bladder injury
3. Voiding difficulties
4. Erosion of tape through urethra
5. Tape too tight
6. Urge incontinence
Burch Colposuspension
• Very common prior to introduction of TVT (used to be gold standard)
• Can be done either as open or laparoscopic surgery
• Suprapubic procedure in which non-absorbable sutures are placed retropubically to
approximate the paravaginal tissues to ileopectineal ligament
• Success rate 80-90% (70% at 15 years post-op)
• Complications: Voiding difficulties, prolapse, detrusor over-activity
Suburethral Slings / Midurethral Slings
• Sling is placed like a hammock between 2 areas of the abdominal wall. Passed from
abdominal wall, under urethra & back to abdominal wall

Non-Surgical vs Surgical Procedures

Non-Surgical Procedure
• Less invasive
• Cure rates low but improvement often seen
• Can be used in women considering further childbearing
• Response dependent on patient compliance
Surgical Procedure
• Higher cure rates
• Response less dependent on patient compliance
• Recommended that childbearing be completed
• Invasive with risk of intra-operative & post-operative
complications that can lead to new problems (voiding
dysfunction, urge incontinence)
Detrusor Over-Activity / Overactive Bladder (OAB)
• Urinary incontinence occurs because of involuntary contraction of detrusor muscle
• Detrusor muscles contracts before its time forcing urine to be expelled
• 2nd most common cause of urinary incontinence in women
• Total bladder pressure & detrusor pressure will be equally elevated at the time of incontinence

Cause
• Unknown
• May be stimulated by infection
• Sensitive bladder: Urge induced by running tap / water, cough etc
• Bladder capacity reduced (normal 350-450ml)
• Occasionally it can be pathological as a result of neuropathy (multiple sclerosis) or bladder neck obstruction

Clinical Presentation
• Urge incontinence: Unable to reach toilet without becoming incontinent following urge to void
• Frequency: Voiding > 8 times per day (normal 6-8 times)
• Urgency: Sudden desire to void
• Nocturia ≥ 2 times per night

Diagnosis
• High suspicion based on symptoms – confirm diagnosis before urodynamic studies
• Filling cystometogram

Treatment
Non-surgical Treatment Conservative Treatment
• Alter magnitude of intra-abdominal pressure
1. Cough control: Stop smoking, treat underlying pulmonary conditions, treat allergies
2. Weight loss
3. Exercise modification
4. Reduce heavy lifting
5. Avoid chronic straining with constipation
• Pelvic floor exercise
• Behavioral Therapy (bladder retraining)
− Aims to re-establish central control of bladder
− Biofeedback & bladder retraining are slow but in highly motivated women have 80% success
rates
− Principle of Bladder Retraining
1. Exclude frequency
2. Explain diagnosis to patient & rationale of the intervention
3. Instruct patient to void every 2h during the day. Explain that she shouldn’t void in
between, she must wait or be incontinent
4. Give praise when the 2 hourly voiding is successfully achieved & then extend the tome
at half hourly intervals
− Medical treatment can be used to augment behavioural therapy
• Electrical stimulation

Pharmacological Treatment:
1. Anticholinergic agents: Oxybutynin (Ditropan), Tolteridine (Detrusitol), Propiverine
(Mictonorm), Trospium (Spasmolyt), Solifenacin (Vesicare), Fesoterodine (Toviaz), Mirabegron
• The neurotransmitter, which causes detrusor muscle to contract is ACh, therefore
anticholinergics inhibit detrusor muscle contraction
• 70% have improvement of symptoms
• SEs: Dry mouth, blurred vision, constipation
2. Tricyclic antidepressants (also have anticholinergic action & can be used)
3. Local oestrogen injection at bladder neck (small role)

Surgical Treatment • Reserved for women with severe symptoms that have not responded to conservative treatment
• Options:
1. Cystoscopy + Intravesical Botox
2. Clam Ileocystoplasty
3. Urinary Diversion Procedures
Fistulae
• Definition: Abnormal communication between 2 epithelial surfaces
• Example:
1. Vesicovaginal fistula
2. Ureterovaginal fistula
• Cause:
1. Obstructed labour
2. 2° to cervical malignancy (most common)
3. SEs of radiation
• Clinical Presentation: Symptoms of incontinence all the time
• Treatment: Surgical repair if possible, but post radiation may require ileal conduit
 CONTRACEPTION
History Taking
History taking in women requesting contraception
• Ask reasons for attendance & explore signs & symptoms
• Sexual History
− Frequency
− Last sexual intercourse (LSI) – date, sites of exposure, condom use
− Previous sexual partners – as for LSI
− Previous STIs
• Menstrual History (for woman): LMP, age of menarche, menstruation period, cycle length, regularity
• Contraception: Current & past use, and any difficulties with the current method
• Social History: Smoking & drinking history, motivation & socioeconomic factors
• Reproductive factors: Future reproductive intention

Pearl Index
• Defined as the number of women who becomes pregnant in terms of per 100 women years of use.
• Pearl Index is a measure of reliability of the method.
• Pearl Index of COCP is less than 1. It means, if 100 women took the pill for one year, less than one woman would get
pregnant
• Pearl Index of Hormonal Contraception
− Combined E/P OCP (PI<0.1)
− Low dose Progestogen (PI=3)
− Injectable Progestogen (PI=0.1)
− Post-coital contraception (PI=1-4)

Type of Contraception
Barrier methods 1. Male condoms (latex, non-latex and deproteinised latex varieties)
2. Female condoms
• Diaphragms (latex, silicone)
• Cervical cap (silicone)
• Dams (latex, non-latex)

Combined hormonal contraception 1. Combined oral contraceptive pill (COCP)

2. Combined transdermal patch (CTP)
3. Combined vaginal ring (CVR)

Progestogen only contraception 1. Progestogen-only Pills (POP)

2. Progestogen-only Implants (Depo Provera)
3. Progestogen-only Injectable Contraception (Implanon, Norplant)

Emergency contraception 1. Levonorgestrel-releasing intrauterine system (LNG-IUS)

2. Levonorgestrel (LNG)
3. Ulipristal acetate (UPA)

Intrauterine contraception 1. Copper intrauterine device (Cu-IUD)

2. Levonorgestrel-releasing intrauterine system (LNG-IUS)

Sterilization 1. Male sterilisation (vasectomy)

2. Female sterilisation (tubal occlusion, hysterectomy, salpingooopherectomy, TAHBSO)
Behavioral Methods • Types
1. Calendar method
− Requires regular cycles
− Monitor for at least 6 cycles first
− Fertile period: [shortest cycle-18] to [longest cycle-11]
2. Basal body temperature
3. Cervical mucus (Billings technique)
• Mode of action of behavioral method: avoid intercourse during calculated fertile period
• Advantages: Free, no side effect
• Disadvantages: Not very effective, require willingness to abstain during fertile period,
needs motivation & record keeping
Barrier Methods
Male 1. Male Condom
• Make sure its not expired
• Use one at a time! No more than one condom should be worn simultaneously by one person and the male
and female condom should not be used simultaneously for the same act of intercourse.
• Place it only on erected penis
• Stay away from vagina then only remove the condom!

Female 1. Female Condom

• They are lubricated sheaths that are inserted into the vagina before sex
• Female condoms can have a ring or sponge within the closed end of the sheath. The open end of the sheath,
which remains outside the vagina, is formed either by a larger ring or flexible ‘V’ frame.
• Care should be taken when handling condoms as sharp objects such as fingernails, teeth or jewelry, which
can tear them
2. Cervical cap
3. Diaphragm

Male condom Female condom

Cervical cap Diaphragm

Combined Hormonal Contraception
• Mechanism of action: Inhibit ovulation via action on HPO axis to reduce LH & FSH
• Type
1. Combined oral contraceptive pill (COCP)
2. Combined transdermal patch (CTP)
3. Combined vaginal ring (CVR)

Combined oral contraceptive pill (COCP)

• Combined ethylestradiol (20-35mcg) & a progestogen
• Given continuously for 21 days & 7 days are placebo
• Need to take at the same time everyday
• Mechanism of action:
1. Prevents ovulation by suppressing FSH and LH levels
2. Alteration of the endometrium and creates a hostile cervical mucus to the spermatozoa (progestogen)
3. Alters Tubal motility
• Non-contraceptive benefits:
1. Reduces menorrhagia
2. Reduces dysmenorrhea
3. Reduces incidence of PID
4. Reduces ovarian cyst
5. Reduces endometriosis
6. Reduces risk of endometrial & ovarian ca but increases breast & cervical ca
• Side effects
Oestrogenic Progestronic
1. N&V 1. Weight gain
2. Breast discomfort / 2. Acne
tenderness 3. Oily skin
3. Vaginak discharge 4. Vaginal dryness
4. Fluid retention 5. Loss of libido
5. Headache
6. Migraine
7. Depression
• Contraindications
1. Previous VTE
2. Previous cholestasis or active liver disease
3. Previous oestrogen responsive cancer
4. Recent trophoblastic disease
5. Unexplained vaginal bleeding
6. Pregnancy
7. Migraine with aura is usually an absolute CI.
8. Smoking is a CI if woman > 35 years of age
• Solutions
Oestrogenic side effect → Change to pill with lower dose oestrogen
Progestagenic side effect → Change to pill with newer generation progestogen e.g. Yasmin
Break-through bleeding → Higher dose oestrogen or may need a triphasic pill

Combined transdermal patch (CTP) — Evra

• Contains Oestrogen & Progestogen
• Patches are applied weekly for 3 weeks, after there which there is a patch-free week.
• MOA: similar to OCP

Combined vaginal ring (CVR) — Nuva Ring

• Flexible ring 54mm.
• Contains Oestrogen and Progestogen
• Worn continuously for 3weeks
• Similar action as OCP
Progestogen-only Contraception
Progestogen-only Pills • Contains: Levonogestrel, desogestrel, norethisterone or lynestrenol
• Commonly use in Malaysia: NORIDAY (norethisterone 0.35mg)
• Must be taken at same time every day, if >3h late need extra contraception for next 7 days
• Mechanism of action
1. Suppress ovulation
2. Action on endometrium (making it thin and atrophic) & cervical mucus (making it hostile to
ascending sperm)
• Indications
1. Breastfeeding
2. Older age
3. Cardiovascular risk factors: high blood pressure, smoking and diabetes
4. History of oestrogen-dependent cancer
5. Intolerant or contraindicated to oestrogen

Progestogen-only Implanon (Etonorgestrel 68mg)

Implants (subdermal • Subdermal implant 40mm X 2mm road, inserted on day 1-5 of the menstrual cycle into non-
implant) dominant arm in between the head of biceps & triceps
• Consist of single silastic rod, inserted subdermally under LA into the upper arm
• It releases the progestogens etonogestrel 25-70mg daily
• Change every 3 years
• It last for 3 years and thereafter can be easily removed and a further implant inserted if requested
• Uses
1. Alleviate dysmenorrhea
2. Infrequent bleeding
3. Treat acne
4. Headache

Norplant (Levonogestrel)
• 6 rods placed subdermally in arm
• Sustained release of Levonogestrel
• Change every 5 years

Progestogen-only • Example
Injectable Contraception 1. Medroxyprogesterone acetate (Depo-provera) 150mg
2. Norethisterone enanthate (NET-EN) 200mg
• Injections given IM in the gluteal region
• Given every 12 weeks (Last for 12 weeks with 2-week grace period thereafter)
• Mechanism of Action
1. Inhibits ovulation
2. Effect on cervical mucus, making it hostile to sperm penetration
3. Induces endometrial atrophy
• Most women develop very light or absent period.
• Uses
1. Improve PMS
2. Treat painful or heavy periods
3. Useful for forgetful women
• Advantages
1. Highly effective and convenient
2. Can be used during lactation
3. Can be used in: Endometriosis, Menorrhagia, Dysmenorrhea, Endometrial hyperplasia
• Side effects
1. Delay in return of fertility – may take around 6 months longer to conceive compared to a
woman who stops COCP
2. Weight gain of around 2-3kg in the first year of use
3. Persistently irregular periods
4. Depression
5. Long term use (>2 years) can lead to decreased bone density
Intrauterine Contraceptive Device (IUCD)
Copper-bearing intrauterine device (Cu-IUD)
• Licensed for use for up to 10 years
• Non hormonal contraception
• Can be used as emergency contraception
• 99% effective
• Mechanism of action:
1. Copper has a toxic effect on sperm and ova hence it inhibits fertilisation straight away
(copper which is a foreign object so endometrium will release leukocyte and prostaglandin which are both hostile to
sperm and zygote)
2. Inhibit sperm migration in the upper genital tract
3. Causes local inflammatory reaction in endometrium
• Side effects:
1. Major drawback – causes menorrhagia
2. Risk of miscarriage and ectopic
3. Risk of infection
4. Cramping pain first 24hrs
5. Vaginal discharge
• Contraindications:
1. Pregnancy
2. Current STI or PID
3. Valvular heart disease
4. Copper allergy
5. Heavy period
6. Laceration / Perforation

Levonorgestrel-releasing intrauterine system (LNG-IUS) / Mirena®

• Type
1. Mirena®
• Contains 52mg Levonorgestrel (blue in colour)
• Progestogen releasing rod, releases 20mcg per day for 5 years
2. Jaydess
• Contains 13.5mg Levonorgestrel (pink in colour)
• Progestogen releasing rod, releases 10mcg per day for 3 years
• Mechanism of action:
1. Thickens cervical mucus so reduces sperm penetration
2. Thins endometrium
3. Local inflammatory reaction
4. Inhibits implantation
5. Inhibits fertilization
6. Inhibit sperm function
• Failure rate: Most effective contraceptive, failure rates <2/1000
• Non-contraceptive use
1. Helps to reduce periods in menorrhagia
2. Provide sufficient control pain caused by endometriosis or adenomyosis
3. Reduces endometric lesions in pelvis and rectovaginal septum and adenomyosis in uterine wall/
4. To oppose oestrogen in HRT
5. To oppose effects of Tamoxifen on endometrium
• Side effects
1. Amenorrhoea (20%)
2. Irregular bleeding (up to 6 months)
3. PMS–like symptoms (rarely)
4. If contraception occurs, there is risk of ectopic pregnancy
• Contraindication
1. Pregnancy
2. Pelvic Inflammatory Disease (PID)
3. Uterine / Cervical Malignancy
4. Progestogen-sensitive tumours, eg breast cancer
5. Unknown vaginal bleeding
6. Active vaginal infection
7. Previous STD exposure in 3 months time
8. Hepatic impairment
Emergency Contraception (Post-coital contraception / Morning after pill)
Methods Class Recommended dose Indications
Copper-bearing Intrauterine IUD retained until pregnancy Within the first 5 days(120 hours)
intrauterine device contraceptive method excluded (e.g. onset of period) or following first UPSI in a cycle or within 5
(Cu-IUD) for licensed duration of IUD (5–10 days from the earliest estimated date of
years) ovulation
Levonorgestrel Progestogen hormone 1.5 mg single oral dose Licensed for use within 72 hours of UPSI
(LNG) or contraceptive failure
Ullipristal acetate Progesterone receptor 30 mg single oral dose Licensed for use within 120 hours of UPSI
(UPA) modulator or contraceptive failure

Sterilisation
Male Sterilization (Vasectomy)
• Technique
1. No-scapel vasectomy under local anaesthesia
2. Outpatient surgical procedure
• Need to wait for 3 months after procedure before sterility sets in completely

Female Sterilization (Tubal Ligation)

• When to perform
1. Patient is sure she is not pregnant
2. Follicular phase of menstrual cycle
3. Postpartum sterilisation (PPS)
4. Post-abortion
• Technique
1. Via mini laparotomy or laparoscopy:
− Pomeroy technique
− Filshie clip
− Falope ring
− Tubal plug
2. Via laparoscopy: Tubal plug anchored in proximal portions of the tube to incite fibrosis
 TERMINATION OF PREGNANCY (TOP) & ABORTION
GUIDELINE ON TERMINATION OF PREGNANCY (TOP) FOR HOSPITALS IN THE MINISTRY OF HEALTH
(2009)

Abortion Law in Malaysia: Penal Code

Sections 312 to 316 of the Penal Code deal with matters concerning miscarriages and injuries to unborn children.

Penal Code Section 312 – 316

312: Causing miscarriage
313: Causing miscarriage without women consent
314: Death caused by act done with intent to cause miscarriage. If act done without women’s consent
315: Act done with intent to prevent child being born alive or to cause it to die after birth
316: Causing death of a quick unborn child by an act amounting to culpable homicide

Section 312: Those who cause a woman with a child to miscarry can be sentenced up to three years imprisonment or
fined, or both, if convicted. If the woman is quick with child (defined as around the fourth month of pregnancy), the
accused can be sentenced up to seven years imprisonment, and fine.

Section 313: Whoever commits the offence defined in section 312, without the consent of the woman, whether the woman
is quick with child or not, shall be punished with imprisonment for a term which may extend to twenty years, and shall
also be liable to fine.

Section 314: Whoever, with intent to cause the miscarriage of a woman with child, does any act which causes the death
of such woman, shall be punished with imprisonment for a term which may extend to ten years, and shall also be liable to
fine; and if the act is done without the consent of the woman, shall be punished with imprisonment for a term which may
extend to twenty years.
Explanation—It is not essential to this offence that the offender should know that the act is likely to cause death.

Section 315: Whoever before the birth of any child does any act with the intention of thereby preventing that child from
being born alive, or causing it to die after its birth, and does by such act prevent that child from being born alive, or
causes it to die after its birth, shall, if such act is not caused in good faith for the purpose of saving the life of the mother,
be punished with imprisonment for a term which may extend to ten years or with fine or with both.

Section 316: Whoever does any act under such circumstances that if he thereby caused death he would be guilty of
culpable homicide, and does by such act cause the death of a quick unborn child, shall be punished with imprisonment
for a term which may extend to ten years, and shall also be liable to fine.
(Explanation: A, knowing that he is likely to cause the death of a pregnant woman, does an act which, if it caused the
death of the woman, would amount to culpable homicide. The woman is injured, but does not die; but the death of an
unborn quick child with which she is pregnant is thereby caused. A is guilty of the offence defined in this section.)

Exceptions under Penal Code

• Termination of pregnancy can be carried out if:
A medical practitioner registered under the Medical Act 1971 who terminates the pregnancy of a woman if such
medical practitioner is of the opinion, formed in good faith

The continuance of pregnancy involves risk to the life of the pregnant woman, or

Injury to the mental or physical health of the pregnant woman, or

The risk being greater than if the pregnancy were terminated

• With reference to Penal Code, abortion is only permitted if it is meant to the save the life of the woman and to preserve her
physical and mental health.Termination of pregnancy is still prohibited even:
1. If it was a result of rape or incest,
2. In cases of fetal impairment
3. For other economic or social reasons.
Terminology
Abortion Expulsion or removal of an embryo or fetus from the uterus at a stage of pregnancy when it is
incapable of independent survival (500g or 22 weeks gestation). It may be spontaneous miscarriage,
or induced (TOP) for medical or social reasons.

Unsafe Abortion A procedure for terminating an unwanted pregnancy either by persons lacking the necessary skills,
or in an environment lacking the minimal medical standards, or both

Unwanted Pregnancy Pregnancy that was not planned for or not desired by the couple or the mother at the time of
conception. Sometimes this may be due to an abnormality of the fetus or of an illness in the mother.

Termination of Pregnancy Procedures to remove an embryo or fetus where the pregnancy is less than 22 weeks of gestation or
if the gestation is unknown, where the fetus is estimated to be less than 500g

Termination of Pregnancy – Standard Operating Procedure

Pre Requisite:
a. Patients can be seen at any private or public health institution but the procedure should only be done in a setting with
Gynaecologist (Specialist) support (this is also in accordance with the Private Health Care Act). This is to ensure that the
procedure can be done properly and if complications should occur, these complications can be picked up quickly.

b. While by law, only one medical registered practitioner is required to assess if a termination of pregnancy is, it is
suggested that in a Government Hospital setting, two doctors, one of whom is a specialist should concur that the
Termination of Pregnancy is necessary and that continuation of the pregnancy would involve risk to the life of the
pregnant woman, or injury to the mental or physical health of the woman, greater than if the pregnancy was terminated.
(For mental health reasons, an opinion from a psychologist or psychiatrist is not needed unless it is deemed necessary by
the attending doctor ie because of severe depression or suicidal risk)

c. A full clerking and examination has been done to determine any coexisting health issues and this should include a
general mental health assessment. This assessment and examination must be adequately documented.
Pre-TOP Management
1. Counseling
2. Blood test & other investigations
3. Ultrasound scanning
4. Prevention of infective complication
5. Consent

1. Counseling (refer next page)

Clinicians should provide greater support to the physical and emotional needs of those women who require termination of
pregnancy. Care pathways for additional support, including access to social services, should be made available.

a. Clinicians caring for women requesting abortion should try to identify those who require more support in decision
making than can be provided in the routine clinic setting (such as those with a psychiatric history, poor social support or
evidence of coercion).
b. It has been recommended that an opt out period of 48 hours following first counseling should be practiced. This means
that the termination should not be carried out until at least 48 hours after first counseling by the health care professional.
This will allow the couple or the women to be sure of their/her decision to proceed with the termination and to have
further counseling if needed. A delay of 48 hours should not affect the termination of pregnancy procedure but may have
a huge impact on the mental status of the woman post abortion. (Appendix 3)
c. In addition, if religious views are needed, the couple/woman should be referred to the necessary authorities for further
counseling. A summary the Fatwa and of the religious views from the MCCBCHST are appended with this document
(Appendix 7A & 7B).

2. Blood Tests and other investigations

a. Pre-abortion assessment should include the following:
• Measurement of Hg concentration
• Determination of ABO and rhesus blood groups screening for red cell antibodies
• If indicated, testing for other conditions such as haemoglobinopathies, HIV, and hepatitis B and C, in the light of
clinical features, individual risk factors, or local prevalence.
• Other investigations as deemed necessary for the safe conduct of anaesthesia and surgery specific for the patient
(ECG, CXR, Renal Profile, Liver Function Tests, Echocardiogram etc.)
b. It is not cost effective to routinely cross-match blood for patients undergoing termination of pregnancy, however a Group
and Save would be recommended.
c. If the woman has never had a Pap Smear, the clinician should utilize the opportunity for cervical screening as well.

3. Ultrasound scanning
Ultrasound scanning is not an essential pre-requisite before termination. It is indicated where gestation is in doubt, or where
extra-uterine pregnancy or molar pregnancy is suspected. The scanning should be in a setting and manner sensitive to the
woman’s situation, and should not be undertaken in an antenatal department together with other women undergoing routine
antenatal care, if possible.
The image of the fetus on the screen need not be shown to the mother unless she requests to do so.

4. Prevention of Infective Complications

Antibiotic prophylaxis, where necessary, should be administered to minimise the risk of post-TOP infective morbidity. For
example in pregnant women with chronic rheumatic heart disease and valvular involvement, the regimens advised should be
followed (refer guidelines Management of Heart Disease in Pregnancy by KKM, Level 9, Antibiotic Guidelines KKM 2008)
A single stat dose of a broad-spectrum antibiotic may be given at the time of initiating the Termination of Pregnancy for low
risk patients

5. Consent
a. Written consent should be from the women herself. However for Muslim couples, consent from the husband is also
necessary as per Fatwa.
b. Married non-Muslim women should also be encouraged to discuss the termination of pregnancy with her husband.
c. If the girl is underaged (less than 18 years of age), consent should be sought from her parents or her guardians. If no
guardians can be contacted, then consent should sought from a child protector or from the State.
d. In a woman who is of unsound mind or who may be mentally challenged, consent should be from her parents or guardian
or in life threatening situations, from the doctors caring for her.

There Informed Consent Form for Termination of Pregnancy should be used — refer next page
Medical Abortion Counseling Model:
• Discuss pregnancy options and ensure that the decision to have an abortion is informed, voluntary and un-coerced.
• Compare the advantages and disadvantages of medical versus surgical abortion. Explain the differences; timing of the visits;
known side effects of the medications; what to expect during the process and at home
• Ask what the patient already knows about medical abortion
• Ask about any previous abortion experience(s) and fears or anxieties
• Discuss time off from other responsibilities (work, childcare, etc.)
• Explain the basic clinical procedures
• Discuss the potential teratogenicity of misoprostol and emphasize that once the drugs have been administered, the abortion
should be completed either medically or surgically
• Clarify the time commitment and the two office visits
• Discuss issues of confidentiality and social and physical support
• Discuss the amount of pain and bleeding associated with the abortion process, including possible heavy bleeding with clots
and passage of products of conception
• Instruct the patient on the use of all medications including self-insertion of vaginal misoprostol and use of pain medication. o
Advise the patient regarding substances to avoid (e.g. aspirin and alcohol.)
• Discuss sexual abstinence until abortion is confirmed
• Be very sensitive to patients who learn they are not eligible for a medical
• Abortion
• Offer contraceptive counseling
• Review aftercare instructions, including emergency contact information and what symptoms warrant a call to the on-call
provider

Sources: Breitbart, V.(2000) Counseling for medical abortion. American Journal of Obstetrics and Gynecology Aug; 183 (2), pp
S26-33 Counseling Guide for Clinicians Offering Medical Abortion: Planned Parenthood of New York City, Inc., 1996.
 Method of Termination
Method Available
Medical Method
• Currently, the agents used in medical abortion are:
1. Methotrexate
2. Misoprostol
3. Mifepristone
• Misoprostol is not recommended to be used since
termination of pregnancy is not a listed indication, so that
its use is off-label, and in addition, there is a danger of
rupture of the uterus.
• Mifepristone has not been registered for use in Malaysia.
• Medical abortion can be offered at an earlier stage than a
suction procedure, being most successful within 49 days of
the last menstrual period. Vaginal ultrasonography is
recommended for ensuring accurate gestational age.
• Surgical evacuation of the uterus is not routinely required
following mid-trimester medical abortion, being
undertaken where there is clinical evidence that the
abortion is incomplete.
Surgical Method
1. Menstrual aspiration
Menstrual aspiration, done within 1-3w of missing a
period, involves using a syringe to remove the
pregnancy from the lining of the uterus. It is effective
in emptying the uterine cavity and as effective as
standard vacuum aspiration.
2. Suction and Curettage
Suction and curettage, can be carried out up to 12
weeks of pregnancy. A suction device inserted into the
uterus removes the contents of the uterus.
3. Dilatation and Evacuation
The cervix is dilated with a hegar dilator or use of
laminaria tent overnight, or by ripening the cervix
with using prostaglandin (cevergam pessary 1 mg 4
hours before the procedure), and the pregnancy
removed with sponge/oval forceps, followed by
curettage. This is not the method of choice, since it is
associated with complications such as bleeding and
cervical injury.
4. Extra amniotic saline infiltration
Normal saline is infiltrated extra-amniotically using a
foley’s catheter. Although widely used, there is not
much evidence to support its efficacy and safety.
The method of termination should be made after discussion with the couple. The actual technique employed would depend on the
period of gestation and the condition of the cervix as seen below.
Condition of cervix
• Nulliparous cervix prostaglandin is recommended for cervical priming
• Multiparous cervix prostaglandin maybe used for cervical priming
• Prostaglandin of choice is Gemeprost 1 mg vaginally, 3 hours prior to procedure
• Misoprostol 400 micrograms administered vaginally 3 hours prior to surgery or 600 mg administered orally 36-48 hours prior
to surgery may also be used for cervical ripening where available.
• If prostaglandin is contra indicated, priming of the cervix can be done using Laminaria Tent or with a cervical ripening
balloon.

Period of Gestation

Between 5-9 weeks: Medical abortion is preferred method when drugs listed below are available
a. Mifepristone 600mg orally, plus 24-48 hours later vaginal misoprostol 800µg (may be
followed by smaller vaginal misoprostol 3-6 hourly if needed)
b. Mifepristone 600mg plus gemeprost 1mg vaginally between 1-3 days later
c. In Malaysia where mifepristone is unavailable, gemeprost (1mg every 3-6 hours up to 3 doses
in 24 hours) or misoprostol alone (80-85% effective) (800µg vaginally daily dose up to 5 days
until abortion occurs, or total of 2400µg vaginally every 3-12 hours with 3 application is
reached)
d. Alternatively, Methotrexate plus misoprostol (>90% effective): 50mg/m2 IM followed by
800µg of misoprostol between day 5 –day 7. Misoprostol dose is usually repeated after 24 hour
if abortion has not occurred.
Between 7-14 weeks • Suction evacuation (vacuum aspiration/suction curettage) under local or general anaesthesia,
preceded by priming of cervix with PGE1 analogue or hydrophilic/osmotic dilator or mechanical
dilators (as per local protocol)
• Manual vacuum aspiration (<10 weeks): using Karman cannula, 50 ml IPAS syringe, paracervical
block with 1% lignocaine 10-20mls.
Between 14-22 weeks a. Medical termination of pregnancy:
i. Gemeprost alone 1mg every 3-6 hours up to 3 doses in 24 hours (up to 18 weeks size uterus).
ii. IM carboprost: 250µg deep IM can be repeated every 2 hours, up to total 1250µg (can be used
together with multiple osmotic dilators)

If Misoprostol is available then:

i. Mifepristone 200mg followed after 24-48 hours by misoprostol 800µg vaginally plus
misoprostol 400µg 3 hourly up to 4 doses orally
ii. Misoprostol alone: 400µg vaginally every 3 hours for 5 doses

b. Surgical evacuation is possible in an experience and trained hands up to 18-19 weeks gestation if
medical methods fail.

Summary
1st Trimester TOP Medical Method
1. Misoprostol + Mifepristone OR
2. Misoprostol / Gemeprost alone OR
3. Methotrexate + Misoprostol

Surgical Method
1. Suction and curettage (S&C) under GA/LA preceeded with cervical priming e.g. Misoprostol
especially in nulliparous where difficult cervical dilatation is expected
2. Manual vacuum aspiration

2nd Trimester TOP Medical Method

1. Misoprostol + Mifepristone OR
2. Misoprostol / Gemeprost alone OR
3. Methotrexate + Misoprostol

Surgical Method
1. Surgical termination by Dilatation & Evacuation (D&E)
Differences between Medical & Surgical Abortion

Possible Complications of TOP

1. Haemorrhage
2. Uterine perforation
3. Uterine rupture
4. Cervical trauma
5. Failed abortion
6. Post-abortion infection
• Genital tract infection, including PICDof varying degrees of severity, occurs in up to 10% of cases. The risk is reduced
when prophylactic antibiotics are given or when lower genital tract infection has been excluded by bacteriological
screening
7. Future reproductive outcome
• No proven association between induced abortion and subsequent ectopic pregnancy, placenta praevia or infertility.
Abortion may be associated with a small increase in the risk of subsequent miscarriage or preterm delivery
8. Psychological sequelae
• Some studies suggest that rates of psychiatric illness or self-harm are higher among women who have had an abortion
compared with women who give birth and to non-pregnant women of similar age. It must be borne in mind that these
findings do not imply a causal association and may reflect continuation of pre-existing conditions
9. Breast cancer
• Induced abortion is not associated with increased risk of breast cancer
10. Analgesia
• Some women will require analgesia after surgical abortion or during and after medical abortion. Requirements for
analgesia vary and there is no benefit in routine administration of prophylactic analgesics.
Post-TOP Management
1. Rhesus prophylaxis
All non-sensitised RhD negative women should be given Anti-D immunoglobulin G (250 IU before 20 weeks of gestation
and 500 IU thereafter), by IM injection into the deltoid muscle, within 72 hours of abortion

2. Post-abortion information and follow up

a. Discharge notes providing sufficient information about the abortion procedure should be provided to the patient to allow
another practitioner elsewhere to deal with any complications
b. Written account of possible symptoms, indicating those that require urgent medical attention should be given to the
woman.
c. 24-hour telephone helpline number to use if they feel worried about pain, bleeding or high temperature
d. Access to urgent clinical assessment and emergency admission when necessary should be readily available.
e. A 2 week follow-up appointment should be given to assess possible complication post TOP and for counseling where
necessary. Counseling for contraception should also be given at this time.
f. Referral for further counselling to women who are at risk of long-term post-abortion distress. This should include women
who are:
i. Ambivalent before the abortion
ii. Lack of a supportive partner / family
iii. Psychiatric history
iv. Religious/cultural belief that abortion is wrong

3. Contraception following abortion

a. Future contraception should be discussed with each woman and partner and chosen method of contraception should be
initiated immediately after abortion where possible.
b. Intrauterine contraceptive device (IUCD) can be inserted immediately after a first- or second trimester termination of
pregnancy.
c. Sterilisation can be safely performed at the time of induced abortion but combined procedures are associated with higher
rates of failure and should be best done as an interval procedure where possible

Organisation of Service
a. Any woman considering undergoing induced abortion should have access to clinical assessment and
b. Appropriate information and support should be available for those who consider, but do not proceed to abortion
c. The earlier in pregnancy an abortion is performed, the lower the risk of complications
d. Services should therefore offer arrangements (as in Algorithm), which minimize delay.
1. Telephone referral system from general practitioners
2. Direct access from referral sources outside the government healthcare system
e. Suggested service arrangements are as follows
1. Women requesting abortion are provided with an assessment appointment as soon as possible or within two weeks of
referral
2. Women can undergo the abortion within 1-2 weeks of the decision to terminate pregnancy but a minimum 48 hours opt
out period is recommended.
3. In the absence of specific medical, social or geographical contra- indications, termination of pregnancy may be managed
on a day- case basis.
4. When TOP not performed, appropriate counseling must be offered throughout the pregnancy and after delivery.
This should include referral to the social welfare department for single mothers or for mothers who may require further
support. This is necessary to ensure that the mother does not subsequently abandons the baby or resorts to infanticide.
5. The role of a trained counselor is emphasized and the hospital should ensure that counselors are trained with post-
abortion issues.
 ECTOPIC PREGNANCY
Definition: Implantation of conceptus outside endometrial cavity

Risk Factors
1. History of tubal inflammation e.g. PID, endometriosis
2. History of tubal surgery e.g. previous tubal reconstructive surgery or previous tubal sterilization in past 1-2 years
3. Pregnancy with IUCD insitu (higher risk of ectopic pregnancy if pregnancy does occur while patient is using IUCD)
4. Use of ART — associated with higher risk of heterotrophic implantation i.e. simultaneous intrauterine pregnancy & ectopic
pregnancy
5. Previous ectopic pregnancy
6. Congenital abnormality of Fallopian tube
7. Smoking

Consequent of Ectopic
1. Spontaneous resolution up to 60-70%
2. Tubal abortion
3. Rupture
4. Chronic ectopic pregnancy

Site

Extra-uterine sites: Intra-uterine sites:

1. Tubal (98%; below is from most to least common) 1. Cervical
• Ampullary 2. Cornual
• Isthmus 3. Interstitial
• Infundubular & fimbrial
2. Ovarian
3. Abdominal
4. Intraligamentous
5. CS scar

Natural History of Tubal Pregnancy

1. Absent of decidual membrane in tubal mucosa → fertilised ovum will embedded in the muscular wall of the tube → take up
maternal blood vessels → necrosis of muscle + connective tissue
2. Tubal muscle wall has no capacity of uterine muscle → tubal pregnancy always end in rupture
Important to diagnose early!
History (Symptoms)
Classical triad of symptoms in ectopic pregnancy:
Missed menses (POA) + PV bleeding + Lower abdominal pain

• PV bleeding can originate from bleeding from a tubal ectopic pregnancy or from shed endometrial lining due to insufficient
pregnancy hormones provided by an ectopic pregnancy to support the endometrium
• Ruptured ectopic pregnancy
− Diffuse abdominal pain (acute abdomen)
− Shoulder tip pain from phrenic nerve irritation due to blood in upper abdomen
− Dizziness, syncope & fainting episodes if massive intreperitoneal bleeding

Physical Examination (Signs)

• May be asymptomatic
• General Examination − Signs of hypovolaemic shock
− Pallor
− Hypotensive
− Tachycardia

• Abdominal Examination − Enlarged uterus (distended abdomen usually 8 weeks gestation)

− Abdominal tenderness
− Shifting dullness if intraperitoneal bleeding

• Pelvic Examination − Bluish cervix with os close

− Cervical excitation (cervical motion tenderness)
− Adnexal mass / tenderness

Differential Diagnosis of Early Pregnancy Bleeding

Gynaecologic related Non-gynaecologic related
1. Threatened, inevitable or incomplete miscarriage 1. Acute appendicitis
2. Gestational trophoblastic disease 2. Diverticulitis
• Molar pregnancy 3. Pyelonephritis
• Choriocarcinoma 4. Ureteric colic
3. Ruptured corpus luteal cyst 5. Acute pancreatitis
4. Ovarian cyst – ruptured or torsion 6. Perforated peptic ulcer disease
5. Acute PID
6. Endometriosis
7. Red degeneration of fibroid (but not commonly seen in
pregnancy with pre-existing fibroids of significant size)
8. Bleeding from local cause e.g. cervical tumour, trauma or
FBs

Diagnosis
1. History — Signs & symptoms of pregnancy, usually 8 weeks gestation, PV bleeding preceded by lower abdominal pain.
UPT test is positive. If ruptured: acute abdomen, dizziness or fainting episodes
2. Physical Examination — May be asymptomatic, signs of hypovolaemic shock (hypotensive, tachycardia), abdominal
tenderness, shifting dullness, bluish cervix with os close & cervical excitation. Adnexal mass / tenderness
3. Ultrasound & serum βhCG
• Fluid in pouch of Douglas (POD) + empty uterus + positive UPT = Diagnostic of ectopic pregnancy
• USS may able to visualize non-ruptured ectopic gestational sac as “double ring sign”
• Visualization of intrauterine pregnancy doesn’t rule out concomitant non-ruptured ectopic pregnancy i.e. heterotropic
implantation
• Unless an adnexal sac with fetal pole & cardiac activity is visualized, accurate interpretation of USS findings requires
correlation with serum βhCG level
• Intrauterine gestatiational sac is detected when serum βhCG > 1000 iu using TVS and 5000 iu by using TAS (TVS is
more preferred compared to TAS since it only diagnostic if serum βhCG > 5000 iu)
• Suspect ectopic pregnancy if serum βhCG > 1500 iu & no intrauterine gestational sac present on TVS
4. Laparoscopy — Can be both diagnostic & therapeutic for ectopic pregnancy

Other Investigation
• Ix to Aid Management: FBC, Coagulation Profile, Blood group & cross match
• Ix TRO Other Causes: Imaging, hysteroscopy, DD&C, etc
   TVS
   

  Indeterminate Intra-uterine
  pregnancy
Ectopic pregnancy  
- fluid in POD with
empty uterus
- Ectopic gestational
sac   Measure serum β-hCG

   

 >1500 IU/L  <1500 IU/L

   

Suggestive Ectopic pregnancy, or currently   Repeat in 48hrs

  pregnancy of unknown location
     

β-hCG plateau or β-hCG doubling  β-hCG falling β-hCG more

  suboptimal rise   effect   than double

       

Follow up until Miscarriage,

Ectopic pregnancy,   IUP is
  repeat TVS  
weekly until β-
demonstrated hCG is ‘-’ Look for
signs of
molar
pregnancy
Treatment for Non-Ruptured Ectopic Pregnancy
1. Expectant Management
2. Medical Management
3. Surgical Management

Expectant Management
• It is an option for
1. Clinically stable women with minimal symptoms & a pregnancy of unknown location
2. Clinically stable women with an USS diagnosis of ectopic pregnancy & decreasing serum βhCG, initillay less than 1000
iu/L
• Criteria for expectant management
1. Serum βhCG < 2000 iu/L, which should then potentially decline
2. Haemoperitoneum <50 ml
3. Tubal mass <2 cm
4. Absence of recognisavle fetal parts on USS
Absence of clinical symptoms
5. Haemodynamically stable

IN CLINICAL SETTING EXPECTANT MANAGEMENT IS NOT PRACTICE ANYMORE DUE TO ITS POTENTIAL
RISK TO THE MOTHER

Medical Management: Methotrexate

• Single-dose IM Methotrexate 50mg/m2
• Usually half the dose in each buttock (i.e. 25mg each buttock)
• Serum hCG levels are checked on day 4 & day 7
→ If hCG levels fall ≥15% between day 4 & 7, continue follow up on a weekly interval to ensure ≥15% fall every 7 days
until hCG titres are undetectable (may take 1-3 months)
→ If hCG levels have failed to fall by more than 15% between day 4 & 7, a further 50mg/m2 dose is given

Advice Given to Patient

1. Patient should be given clear information (preferably written) about possible need for further treatment & adverse effects
following treatment
• Further treatment may be needed:
1. If hCG levels have failed to fall by more than 15% between day 4 & 7, a further 50mg/m2 dose is given
2. If worsening symptoms (treatment failure), advisable to perform surgical treatment irrespective of hCG level
• SEs of MTX
1. Pain within 1st week of receiving treatment due to tubal abortion or tubal distention from hematoma formation
(normal; can be controlled with PCM)
2. Conjunctivitis, dermatitis, alopecia
3. Stomatitis, gastritis, enteritis
4. Penumotitis
5. Eleveated liver enzymes
6. Bone marrow suppression
2. Patient should be able to return easily for assessment at any time during follow up
3. Patient must avoid food & vitamins containing Folic acid, NSAIDs & alcohol during treatment period
4. Offer effective contraception for at least 3 months after treatment to allow wash out (MTX is teratogenic)

Criteria to Meet for MTX Treatment

1. hCG level < 3000IU/L
2. Minimal symptoms
3. US reveal no fetal heart & gestational sac ≤ 3cm in its greatest diameter, no free fluid in POD
4. Good understanding & compliance
5. Haemodynamically stable
6. No contraindication to MTX (breastfeeding, immunodeficiency, PUD, active pulmonary disease, renal or hepatic
insufficiency, coexisting pregnancy, allergy to MTX)

Advantages of Medical Treatment

1. Avoid surgical risks; less invasive
2. Preserve future fertility
Surgical Management
Type of Surgical Approach
Haemodynamically stable patient → Laparoscopy
Not haemodynamically stable patient → Laparotomy

Terminologies
1. Salpingectomy = Removal of entire Fallopina tube
2. Partial Salpingectomy = Removal of portion of Fallopian tube; surgery to rejoin the tube at later time may be performed

3. Salpingotomy = Operative identification of ectopic pregnancy in-situ.

• Procedure
o Injection of vasoconstrictive agents
o Incision made parallel to the axis of the tube along its antimesenteric border over site of implantation
o Gentle removal of products of conception using hydrodissection
o Primary closure of incision by using Vicryl 7-0
• Risk of residual trophoblastic tissue with salpingotomy / salpingostomy therefore need to repeat serum bhCG to confirm
decline in hCG level
• Serum bhCG should be done serially post-op; one immediately after op & 2nd reading after 48h
• If failed to decline, MTX therapy is indicated
4. Salpingostomy = Similar procedure to salpingotomy but the incision site is left to heal by itself

Options for Surgical Management

• All ectopic pregnancy is surgically treated with total or partial salpingectomy
• Partial salpingectomy is reserved for cases where implantation is at mid-ampullary portion with a possibility of ≥ 6cm of
function tube left after resection
• Salpingotomy or salpingostomy is only indicated when:
1. Patient desire to conserve her fertility
2. Patient is haemodynamically stable
3. Tubal pregnancy is accessible & unruptured
4. In the presence of contralateral tubal disease (contralateral tube is unhealthy)

Treatment for Ruptured Ectopic Pregnancy

1. KNMB
2. ABCs
3. 2 large IV bore for IV access using 16G Branula
4. IV fluid resuscitation
5. Urgent blood group & cross match (GXM) at least 4 pints whole blood
6. Initial investigation: Take essential bloods for FBC, CP (PT & aPTT), do UPT ± Pelvic US
7. CBD
8. Inform anesthetist & proceed with emergent surgical intervention
• (Laparotomy / laparoscopy) salpingectomy or salpingostomy
• Procedure of choice in ruptured ectopic is usually salpingectomy
 MISCARRIAGE
Definition
WHO (Epidemiological): Expulsion of conceptus / fetus weighing <500g or <24weeks gestation
Biological: Expulsion of conceptus <28weeks gestation or before fetal viability is achieved

Type of Miscarriage
1. Induced miscarriage Commonest admission to gynaecological ward,
2. Spontaneous miscarriage usually presented with bleeding in early pregnancy
1. Threatened miscarriage  
2. Inevitable miscarriage
3. Incomplete miscarriage
4. Complete miscarriage
5. Missed miscarriage
6. Septic miscarriage

Terminologies
Threatened Miscarriage Early pregnancy bleeding with closed cervix and viable pregnancy. It may or may not followed by
loss of pregnancy

Inevitable Miscarriage Abortion in progress with cervical dilatation but POC hasn’t been expelled

Incomplete Miscarriage Early pregnancy bleeding with cervical dilatation; some but not all POC have been passed

Complete Miscarriage All POC have been passed and patient may be asymptomatic and uterus has already revert to normal
at time of presentation

Missed Miscarriage Also known as “fetal demise” or “intrauterine demise”

Fetus died and is retained in utero together with placenta and membranes. US reveal a non-viable
fetus with no FCA despite CRL ≥ 7mm
(N.b. UPT may be still +ve; placenta can still produce hCG even after fetal death)

Anembryonic Miscarriage Also known as “blighted ovum” or “empty sac”

Pregnancy in which a gestational sac develops without embryo and yolk sac or in other word,
without embryonic structures (anembryonic)
US findings: IUGS ≥ 20mm without fetal pole

Septic Miscarriage Incomplete miscarriage complicated by infection of uterine contents usually after illegal abortion.
Common organisms are E.coli, Streptococci & anaerobes

Biochemical Pregnancy A pregnancy indicated by presence of serum hCG but stops growing and resolves before it becomes
large enough to see it with ultrasound. Not long after fertilization and implantation, the pregnancy
stops developing – usually due to a severe chromosomal abnormality within the pregnancy.

N.b. Diethlstilbestrol (DES) Exposure in Pregnancy

• DES is a synthetic form of estrogen hormone prescribed to pregnant women between 1940 and 1971 to prevent miscarriage,
premature labor, and related complications of pregnancy
• In 1971, researchers linked prenatal DES exposure to clear cell adenocarcinoma of cervix and vagina
• The US Food and Drug Administration (FDA) subsequently withdrew approval of DES as a treatment for pregnant women
• Individuals who were exposed to DES during their mothers' pregnancies are commonly referred to as “DES babies”
• Complication to DES daughters
1. Clear cell adenocarcinoma of cervix & vagina
2. Formation of atypical cells e.g. atypical glandular cells, dysplasia, CIN & squamous intraepithelial lesions (SILs).
3. Breast carcinoma
4. Abnormal structural changes of female reproductive tracts
5. Pregnancy complications: Premature birth, ectopic pregnancy, miscarriage, pre eclampsia etc
• Complication to DES sons
1. Epididymal cyst
2. Undescended testis
3. Hypospadias
• DES is now known to be an endocrine-disrupting chemical, one of a number of substances that interfere with the endocrine
system to cause cancer, birth defects, and other developmental abnormalities. The effects of endocrine-disrupting chemicals
are most severe when exposure occurs during fetal development.
Threatened Miscarriage
History Taking Small amount PV bleeding without POC
No abdominal pain
Physical Examination Signs of anaemia absent
Uterus size is equal to date
Cervical os close
Ultrasound Findings Ultrasound reveals a viable intrauterine pregnancy, fetal cardiac activity seen

Inevitable Miscarriage
History Taking Large amount PV bleeding without POC
Abdominal pain present
Physical Examination Signs of anaemia present
Uterus size is equal to date
Cervical os open without POC seen at os
Ultrasound Findings Ultrasound reveals an intrauterine pregnancy, which may be viable or not viable

Incomplete Miscarriage
History Taking Large amount PV bleeding with/without POC
Abdominal pain present
Physical Examination Signs of anaemia present
Uterus size is smaller than date
Cervical os open with POC seen at os
Ultrasound Findings Ultrasound reveals a non-viable pregnancy with no fetal cardiac activity
Retained POC seen within uterus & at cervical os
Thick endometrial lining

Complete Miscarriage
History Taking History of PV large amount PV bleeding with POC, absent at time of presentation
History of abdominal pain that comes with PV bleeding, absent at time of presentation
Physical Examination No anaemic signs
Uterus smaller than date (uterus reverts back to pre-pregnancy conditions)
Cervical os close
Ultrasound Findings Empty uterus with normal uterine lining

Missed Miscarriage = Early fetal demise (Anembryonic pregnancy) = Blighted ovum

History Taking Asymptomatic
Physical Examination Nil
Ultrasound Findings Ultrasound reveals a non-viable intrauterine pregnancy with no FCA despite CRL ≥ 7mm

Septic Miscarriage
History Taking PV bleeding + PV discharge
Abdominal pain
History of instrumentation of uterus e.g amniocentesis or illegal abortions
Physical Examination Signs of infection: febrile (temp>37°C), tachycardia, tachypnic
Uterus smaller than date
Cervical os open with POC seen at os plus purulent PV discharge
Cervical motion and adnexal tenderness
Ultrasound Findings Ultrasound reveals a non-viable pregnancy with no fetal cardiac activity
Retained POC within uterus or at cervical os.
Thick endometrial lining
Summary
Threatened Inevitable Incomplete Complete Missed Septic
PV bleeding Fresh, Fresh, large Fresh, large History of passing large Absent PV bleeding
scanty amount amount amount of fresh blood, absent +
during presentation PV DISCHARGE
Abdominal Absent Present Present History of abdominal pain, Absent Present
pain absent during presentation
Passage of Absent Absent Present History of passing POC, Absent Present
POC absent during presentation
Cervical Os Close Open Open Close Close Open
Uterine size Equal to Equal to date Smaller than Smaller than date Smaller than Smaller than date
date date date
Ultrasound Finding

TVUS of an intrauterine pregnancy. The yolk sac is clearly TVUS showing intrauterine gestation at 59 days LMP.
visible with the thickening of the embryo seen along its lateral Calliper’s clearly mark a CRL of 17mm. Yolk sac can also be
border seen.

US finding of a normal intrauterine pregnancy. Yolk sac, TVUS scan image showing empty IUGS of 13mm (5w+1d).
embryo and amnion are visible This is suggestive of anembryonic miscarriage (= blighted
ovum or missed miscarriage). N.b. It is advisable to repeat US
scan after 1 week to 10 days TRO delayed development of embryo

TVUS scan images showing

intrauterine gestational sac. This
pregnancy is of 10w gestational age
according to LMP but the poorly
developed embryo measures only 6mm
in size, which is equivalent to 6w+2d
and shows no FCA. These US findings
suggest embryonic demise or missed
miscarriage.
TAS image shows an inevitable miscarriage. The gestational TVUS image shows an inevitable miscarriage. There is a low-
sac containing a dead embryo presenting at an open cervical os. lying gestational sac
Miscarriage is inevitable. The balloon of a Foley catheter is
evident in the bladder.

TVUS image shows an incomplete miscarriage. The absence of GS and presence of POC are typical of incomplete miscarriage

Speculum examination showing presence of POC at open US finding: Empty uterus, which is highly suggestive of
cervical os in a case of incomplete miscarriage complete miscarriage
Cause
Fetal 1. Chromosomal abnormalities
(More common in • Aneuploidy = Trisomy (Down syndrome), monosomy (Turner), triploidy / tetraploidy
1st trimester) • Structural chromosomal abnormalities – common in recurrent miscarriage
2. Developmental defects
• Neural tube defect (NTD)
• Cleft palate
• Cyclopia
• Amniotic bands
• Syrinomelia
• Caudal regression

Maternal Local Maternal Factors

(More common in 1. Uterine abnormalities
2nd trimester) • Acquired = Submucous fibroid, endometrial polyp, Asherman’s syndrome
• Congenital = Septate or bicornuate uterus
N.b. Bicornuate vs Septate Uterus
Bicornuate Uterus Septate Uterus
• Indented external surface of fundus • Normal external surface
• Cavities widely separated • Cavities are not separated but are close to
• Cause: Partial fusion of Mullerian ducts each other
• Cause: Defect in canalization or resorption of
midline septum between Mullerian ducts
2. Cervical incompetence
• Definition: Painless cervical dilatation & effacement that is not a/w contraction
• Cause: Cervical surgery, traumatic deliveries e.g. instrumental, cervical trauma (DD&C or S&C)
and Diethylstilbestrol (DES) exposure

HSG showing 3 type of uterine abnormalities

General Maternal Factors

1. Advanced maternal age >40 years old
2. Maternal medical conditions = DM, thyroid diseases, SLE, chronic renal failure, APS, PCOS
3. Maternal infections = TORCH infections, Mycoplasma, Ureaplasma, Listeria, Brucella, Syphilis
4. Maternal substance use = Smoking, alcohol, drug abuse
5. Immunological factors = Abnormal alloimmune response resulting in failure to accept fetus for
duration of normal pregnancy

Placental 1. Haemorrhage in decidua basalis

2. Hydrophic degeneration of placental villi

Unknown Causes
Management of Spontaneous Miscarriage

General Management
1. Confirm the pregnancy by history taking, physical examination and ultrasound scan
2. Rule out gestational trophoblastic disease and ectopic pregnancy
3. If ultrasound scan shows continuing pregnancy, reassurance that risk of future miscarriage is <20% and no increased risk
of fetal abnormality
4. Non-sensitised (Rh) negative women should receive anti-D immunoglobulin in the following situation:
• Ectopic pregnancy
• All miscarriages where uterus is evacuated either via surgical or medical evacuation
• Miscarriage
<12 — give anti-D only for threatened miscarriage when bleeding is heavy or associated with pain
>12 — give anti-D to all types of miscarriages
5. Tissue obtained at the time of miscarriage should be examined histologically to confirm pregnancy and to exclude
ectopic pregnancy or gestational trophoblastic disease
6. All professional should be aware of the psychological sequalae associated with miscarriage and should provide support
and follow-up as well as access to formal counseling when necessary

Threatened Miscarriage
1. Take detailed history and perform physical examination to confirm pregnancy and if yes, confirm threatened miscarriage
2. Do ultrasound scan to confirm pregnancy viability and to rule out other possible causes e.g. ectopic pregnancy, GTD and
other forms of miscarriages
3. If ultrasound scan shows continuing pregnancy, reassures patient that pregnancy will progress in 80% of cases
4. Advice adequate rest at home / hospital
5. Advice patient to avoid coitus and douching
6. If admitted to ward, observe for progression to incomplete or missed miscarriage and discharge if no PV bleeding within 12-
24h
7. Give anti-D for non-sensitised Rh –ve mothers
<12w — give anti-D for threatened miscarriage only when bleeding is heavy or associated with pain
>12w — give anti-D to all types of miscarriages
8. Gives medical leave up to 2 weeks
9. TCA immediately if increasing PV bleeding & abdominal pain & to bring POC if passed out for confirmation

Incomplete and Inevitable Miscarriages

1. Take detailed history and perform physical examination to confirm pregnancy and if yes, confirm incomplete / inevitable
miscarriage
2. Do ultrasound scan to confirm diagnosis and to rule out other possible causes e.g. ectopic pregnancy, GTD and other forms of
miscarriages
3. 2 large IV bore needles for IV access
4. IV fluid resuscitation
5. Draw blood for FBC to assess degree of bleeding and GXM
6. IV ergometrine 0.5mg if no contraindication
7. Give analgesic for pain relief (IM Pethidine 1mg/kg max 100mg)
8. POC removal
• Remove POC at cervical os using sponge forceps where possible
• Arrange for surgical evacuation (suction & curettage) of retained POC in OT under GA (preferred method). Cervical
priming may be needed to soften cervix
• Medical evacuation using Misoprostol + Mifeprististone is indicated if there is GA risk and retained fetal parts >14w size
which may render surgical evacuation unsafe
• All POC must be sent for HPE
9. Give anti-D for non-sensitized Rh –ve mothers for all type of miscarriages where uterus is evacuated either via surgical or
medical evacuation
10. Patient can be discharged within 24h of ERPOC if she is stable
11. Gives medical leave up to 1 weeks
12. Counsel patient before discharge on:
• Probable cause of miscarriage
• Resumption of coitus once bleeding stop
• Contraception for 3 months
• Follow up in 6 weeks at health clinic
Complete Miscarriage — generally doesn’t need any treatment
1. Reassurance and psychological support to patient
2. Analgesics if only required

Missed Miscarriage
1. Take detailed history and perform physical examination
2. Do UPT to confirm pregnancy
3. Do ultrasound scan to confirm diagnosis and to rule out other possible causes e.g. ectopic pregnancy, GTD and other forms of
miscarriages
4. Perform baseline blood investigations and screen for coagulopathy
• FBC → Hb, WCC and platelets
• Coagulation Profile → INR, PT and aPTT
• GSH 2 pints
5. Arrange for surgical evacuation (suction & curettage) of retained POC in OT under GA (preferred method)
<12w → Cervical priming with Cervagem pessary 1mg insertion followed by surgical evacuation after 2h
>12w → Cervical priming with Cervagem pessary 1mg 4 hourly insertion for 3-5 doses
6. All POC must be sent for HPE
7. Give anti-D for non-sensitized Rh –ve mothers for all type of miscarriages where uterus is evacuated either via surgical or
medical evacuation
8. Patient can be discharged within 24h of ERPOC if she is stable
9. Gives medical leave up to 1 weeks
10. Counsel patient before discharge on:
• Probable cause of miscarriage
• Resumption of coitus once bleeding stop
• Contraception for 3 months
• Follow up in 6 weeks at health clinic

Septic Miscarriage
1. Take detailed history and perform physical examination to confirm diagnosis
2. Do ultrasound scan to confirm diagnosis and to rule out other possible causes e.g. ectopic pregnancy, GTD and other forms of
miscarriages
3. 2 large IV bore needles for IV access
4. IV fluid resuscitation
5. Draw blood for FBC to assess degree of bleeding and GXM
6. Start IV antibiotic prophylaxis after taking vaginal swab, HVS and blood culture
IV Cefoperazone 1g 12 hourly or IV Cefuroxime 750mg 8 hourly plus IV Metronidazole 500mg 8 hourly
OR
IV Augmentin 1.2g 8 hourly plus IV Gentamicin 3-5mg/kg/day plus IV Metronidazole 500mg 8 hourly
7. Arrange for surgical evacuation (suction & curettage) of retained POC in OT under GA
• Must be done by experienced doctor after 12h of adequate antibiotic therapy
• Urgent surgical evacuation (<12h of adequate antibiotic therapy) can only be done if profuse PV bleeding
8. IV antibiotics should be continued until patient is afebrile for at least 48h then substitute with oral antibiotics for 10 days
(should be given at least 7 days)
9. Adjust antibiotic therapy according to C+S results once they are out and if unresponsive treatment i.e. persistent fever after
48h
10. Anticipate complications of septic miscarriage and treat accordingly. They are:
• Pelvic abscess
• Septic shock and complication of shock e.g. acute renal failure
• Chronic PID
• Uterine synechiae
 RECURRENT MISCARRIAGES
Definition: ≥3 consecutive miscarriages

Epidemiology
• Increasing in trend up to 1% of pregnancy
• More than 3 consecutive miscarriage highly suggest an underlying problem leading to miscarriage and therefore, further
investigation must be carried out to look for the cause
• Earlier investigations and referral should be considered in special cases:
1. Advanced maternal age
2. History of infertility
3. Remarkable obstetric history e.g. PID or ectopic pregnancy

Causes — Based on Penang Protocol, the causes can be broadly classified into:
1. Endocrine = DM, thyroid diseases, SLE, chronic renal failure, PCOS
2. Genetic = Parental chromosomal rearrangement (i.e reciprocal translocation or Robertsonian translocation) and embryonic
chromosomal abnormalities
3. Infective = TORCH infections, Syphilis, Bacterial vaginosis
4. Anatomical = Cervical incompetence, uterine abnormalities
6. Immunological = APS, thyroid antibodies
7. Inherited thrombophilia defect
8. Idiopathic = Unexplained recurrent miscarriages

Causes of 1st & 2nd Trimester Losses

1st Trimester Losses PACE U 2nd Trimester Losses CABUT
P = PCOS C = Cervical incompetence
A = APS A = Asherman’s syndrome
C = Chromosomal abnormalities esp. structural B = BV
E = Endocrine disorders e.g. DM, Thyroid diseases U = Uterine abnormalities
U = Uterine abnormalities either congenital or acquired T = Thrombophilias

Others: SLE, hyperprolactinaemia

History Taking
Obstetric History
• Maternal age
• Miscarriage(s) — number, when, at what gestational age, method of evacuation (spontaneous, surgical or medical evacuation)
• History of traumatic deliveris e.g. instrumental (cervical incompetence)
• If 2nd trimester miscarriage, ask about cervical incompetence
− Diagnosis of cervical incompetence is clinical, usually based on history
− 2nd-trimester miscarriage
− Preceded by spontaneous rupture of membranes
− Bulging membranes through the cervix prior to onset of labour
− Painless and progressive cervical dilatation
− Fetus alive during miscarriage
− History of traumatic deliveries, cervical surgery, cone biopsy, LLETZ or cervical trauma (D&C or S&C)

Gynaecological History
• History of uterine abnormalities either congenital or acquired
• History of uterine instrumentation
• History of cervical surgery, cone biopsy or cervical trauma (D&C or S&C)
• History of genital tract infections e.g. BV

Past Medical History

• DM, Thyroid diseases, PCOS, SLE or chronic renal failure
• History of APS?
• Well controlled? Compliance to medication & follow up?

Social History
• Smoking, heavy drinker & drug abuse

Family History
• Inherited Thrombophilia
• FHx of DM, Thyroid diseases, SLE, PCOS

Physical Examination
General Examination
• Signs of SLE e.g. moon face, buffalo hump, central obesity etc
• Signs of PCOS e.g. hyperandrogenism
• Signs of thyroid diseases e.g. goiter
• Signs of bleeding disorders e.g. bruises, petechiae or echymoses

Abdominal Examination
• Nothing much, signs of fibroid if any

Pelvic Examination
• Signs of genital tract infection e.g. vaginal discharge
• Polyps or fibroids if any
Investigations

OVERVIEW
1. Detailed history & physical examination
2. Blood test
• Antiphospholipid antibody screen for ACA, LA and anti-β2 glycoprotein (if available)
• PCOS screen for serum testosterone & SHBG
• Thrombophilia screen (only if 2nd trimester miscarriage)
− FV Leiden, FII (prothrombin gene mutation) and protein S deficiency
• DM and thyroid diseases screen (only if indicated by history & PE)
− MGTT for DM, TFT for thyroid diseases
3. Karyotyping for both partners
• Cytogenic analysis
• If abnormal cytogenic analysis, perform parental peripheral blood karyotyping
4. Imaging test: Pelvic US
5. Infective screen for TORCHES & BV

Investigations
1. Detailed history & physical examination

2. Antiphospholipid antibody screen

• Must be screen in:
o All women with more than three 1st trimester miscarriages
o All women with one or more 2nd trimester miscarriages
• Criteria for diagnosis: Revised Sapporo Classification 2006 (at least 1 clinical + at least 1 lab criteria)

• To diagnose APS, it is mandatory that the woman has 2 positive tests at least 12 weeks apart for either Lupus
anticoagulant or anticardiolipin antibodies (ACA) of IgG and/or IgM class present in a medium or high titre over 40 g/l
or ml/l, or above the 99th percentile

3. PCOS screen by Rotterdam Criteria: Diagnosis is confirmed by 2 out of 3 criteria after exclusion of other etiologies
1. Biochemical or clinical evidence of hyperandrogenism
• Biochemical: Total Testosterone > 70ng/dL, Androstenedione > 245 ng/dL, DHEA-s > 248 ug/dL
• Clinical: Acne, hirsutism, acanthosis nigrans
2. Ovulatory dysfunction: Amenorrhea or oligomenorrhea
3. Polycystic ovaries on ultrasound shows at least one ovaries with
• 12 follicles 2-9mm diameter in each ovary
• Ovarian volume >10ml

4. Thrombophilia screen for 2nd trimester miscarriage only

• The screening includes factor V Leiden, factor II (prothrombin) gene mutation and protein S deficiency

5. DM and thyroid disorders screen

• ONLY IF INDICATED BY HISTORY & PE
 • MGTT for DM
• TSH for thyroid diseases

6. Karyotyping (both partners)

• To detect chromosomal abnormalities e.g. balanced translocation or Robertsonian translocation
• Cytogenetic analysis should be performed on POC of the 3rd & subsequent consecutive miscarriage(s)
• Parental peripheral blood karyotyping should be performed if POC reports an unbalanced structural chromosomal
abnormality

7. Pelvic ultrasound to assess uterine anatomy

• Must be performed in:
o All women with more than three 1st trimester miscarriages
o All women with one or more 2nd trimester miscarriages
• Suspected uterine anomalies may require further investigations to confirm the diagnosis, using hysteroscopy, laparoscopy
or 3D pelvic ultrasound

8. Infective screen
• Screening for TORCHES is not useful in investigation of recurrent miscarriages
• Screening & treatment for BV in early pregnancy among high risk women with previous 2nd trimester miscarriage may
reduce risk of recurrent loss and preterm delivery
Treatment (for subsequent pregnancy)
Causes Treatment
Unexplained recurrent Unexplained recurrent miscarriage
miscarriage • Good prognosis for future pregnancy outcome
• 75% chance of a eventual live birth in subsequent pregnancy
• However, prognosis worsens with increasing maternal age & number of previous miscarriages,
which are 2 independent risk factors for a further miscarriage
• Rx
1. Supportive care
2. Progesterone
3. Aspirin
− Usually prescribed for women with unexplained recurrent miscarriage
− Given alone or in combination with heparin
− This empirical treatment is unnecessary and should be resisted (RCOG, UK April 2011)
Environmental factors Rx: Lifestyle modification
• Stop smoking
• Stop drinking alcohol
• Regular exercise and reduce weight if obese
Genetic Rx: Essentially no treatment available
Uterine abnormalities Rx: Surgical correction of uterine abnormalities
• Uterine surgery may correct the abnormality, but may not necessarily improve the prognosis
• Ironically, these procedures may cause intrauterine adhesions and, thus, reduce fertility
Cervical incompetence Rx: 2 options; cervical surveillance or cervical cerclage
1. Serial cervical sonographic surveillance
• Start at 14-16 weeks
• Every 2 weeks as long as cervical length >30mm
• Increase frequency to weekly if 25-29mm
• If <25mm before 24 weeks, consider cerclage
2. Cervical cerclage
• After 12-14w POA
• Types: McDonald or Shirodkar
• A/w potential hazards that are related to the surgery and the risk of stimulating uterine
contractions and, hence, should only be considered in women who are likely to benefit

Endocrine Rx: Optimum control of the conditions

• DM → Diet control, s/c insulin if diet control fails to keep patient normoglycaemic
• Hypothyroidism → Thyroxine
• PCOS → Metformin
• Luteal Phase Defect (LPD) → Progesterone
− Progesterone is essential for implantation and maintenance of pregnancy
− A defect in Corpus luteum causes impaired progesterone production
− LPD cannot be diagnosed during pregnancy; a consistently short luteal phase duration is the
most reliable diagnostic criterion.
APS Rx: Low dose aspirin & heparin until 36w of pregnancy
Thrombophilia Rx: LMWH e.g. clexane
Infective factors • Syphilis: Penicillin
• Bacterial Vaginosis: Metronidazole
 HYPEREMESIS GRAVIDARUM (HG)
Definition — based on RCOG guidelines
• Nausea & vomiting of pregnancy (NVP) is very common and it should only be diagnosed when onset is in the first trimester
of pregnancy and other causes of nausea and vomiting have been excluded
• HG is a severe type of NVP, which has got deleterious effect on the mother & affect her daily life activities. It can cause
weight loss, dehydration, acidosis from starvation, alkalosis from loss of hydrochloric acid in vomitus & hypokalemia
• HG can be diagnosed when there is protracted NVP with the triad of more than 5% pre-pregnancy weight loss, dehydration
and electrolyte imbalance

Risk Factors
1. High serum hCG: multiple or molar pregnancies
2. Genetics: FHx of hyperemesis gravidarum
3. Female gestation
4. Hyperthyroidism
5. Young age
6. Primigarvida
7. History of hyperemesis gravidarum in previous pregnancy
8. History of migraine headache
9. History of motion sickness

Protective Factors against HG

1. Smoking
2. Male gestation

Pathophysiology
1. Hormonal
• High hCG in multiple & molar pregnancy
• High oestrogen
• High progesterone → Relaxation of lower oesophageal sphincter & impaired gastric motility
2. Dietary deficiency
• Low carbohydrates intake leads to depletion of glycogen & thus increases fat metabolism. More ketone bodies are
formed, which are excreted through urine / breath
• Vitamin B6 & B1 deficiency
3. Psychogenic → psychological stress increases the symptoms
4. Genetic → More likely to develop hyperemesis gravidarum if there is FHx
5. Allergic or immunological basis → may be related to products secreted by ovum
6. Liver dysfunction → liver cannot adapt high level of hormones during pregnancy
7. H. pylori infection

History Taking (Symptoms)

1. Vomiting
• Insidious onset
• Occurs in 1st pregnancy & in early month of pregnancy
• Increasing in amount & frequency
• Occurs independent of food & is spread throughout the day
• Nothing causes or relieves the vomiting; it doesn’t subside
• Everything taken in is rejected; vomitus mainly contain digested food particles no blood or bile
• Retching & nausea persist in between vomiting
2. Associated symptoms
• Loss in appetite, weight loss
• Epigastric pain
• Excess salivation (ptyalism)
• Diminished urinary quantity (oliguria)
• Constipation
• Lethargy, confined to bed
• Mental confusion with loss of memory of recent event
• Sleeplessness, restlessness
3. Risk factors — as mentioned above
4. Quantify severity using PUQE score
5. Exclude other causes of vomiting e.g.
 • Multiple pregnancies
• Gestational trophoblastic disease (GTD)
• Medical causes: Pyelonephritis, UTI, raised ICP, DM with DKA, AGE
• Surgical causes: Appendicitis, pancreatitis, PUD, I/O

Physical Examination (Signs)

1. General Examination:
• Signs of dehydration: Decreased skin turgor, dry mucous membrane, sunken eye
• Vital signs: ↑PR, ↑RR, ↑temperature, ↓BP, SpO2
• Weight
• Lethargic looking
• Jaundice
2. Abdominal examination
• Perform obstetric physical examination
• Usually no clinical findings
3. Other examination as guided by history

Differential Diagnosis
PUGE Score for Severity of N&V

Complications
1. Neurological
• Wernicke encephalopathy—thiamine deficiency
• Korsakoff’s psychosis
• Peripheral neuritis
• Pontine myelinolysis
2. GIT
• Esophageal rupture (Boerhaave syndrome)
• Oesophageal tear (Mallory-Weiss tear)
• Stress ulcer in stomach
3. Renal failure
4. Convulsions
5. Coma

Indication for hospital admission

1. Severe dehydration
2. Development of ketonuria
3. Significant weight loss > 10%
4. Unable to tolerate orally
5. Electrolyte imbalance

Investigation
Hyperemesis gravidarum work up:
1. Confirm pregnancy & at the same time exclude other gestational related causes
2. Assess severity of dehydration
3. Investigate most likely cause of dehydration based on history
4. Assess the complication of severe N&V
Imaging Test Pelvic US
1. To confirm pregnancy
2. To establish number of fetus (multiple pregnancy can cause HG)
3. To exclude hydatiform mole
4. To exclude other conditions: appendicitis, pancreatitis etc

Biochemical Tests Blood tests:

FBC Haematoconcentration lead to ↑Hg, ↑RBC & ↑haematocrit
↑WCC if infection
Serum electrolytes ↓Na+, ↓K+ & ↓Cl- due to vomiting
RFT ↑urea & ↑creatinine

Urine tests:
Urinalysis Oliguria
Dark coloured due to concentrated
Acidic pH
High specific gravity with acid reaction
Ketonuria (quantify as +1 or more)
Proteinuria
Diminished of absence of Chloride
MSU Exclude UTI
Other Investigation Not routinely done, only if indicated based on history
1. RBS → Exclude DM & if diabetic, exclude DKA
2. TFT → Exclude thyroid disorders, which can cause N&V
3. LFT → Exclude liver diseases e.g. hepatitis or cholestatic liver disease
4. Serum amylase → Exclude pancreatitis
5. OGDS → Exclude PUD, hepatobiliary infections
6. H.pylori rapid test → Exclude H. pylori infection

Investigation for complication of disease

1. Fundoscopy may reveal retinal haemorrhage & detachment
2. ECG if hypokalemia since it can cause arrhythmias

Treatment
Treatment Principle = Symptomatic Treatment
1. To control vomiting
2. To correct fluid & electrolyte imbalance
3. To prevent complications of severe N&V
4. Care of pregnancy

Treatment
1. Reassurance, bed rest
2. Rehydrate patient & correct fluid & electrolyte imbalance
• 2 large IV bore for IV access
• IV fluid resuscitation → IV line 1 pint 4 hourly NS & Hartmann with or without KCL 3gm / day if patient cannot tolerate
orally, dehydrated & urine acetone positive
3. Monitor patient
• Vomit chart
• I/O chart
• Daily urine acetone
• Weight charting
4. Antiemetic best to avoid; if required
• IV Metoclopramide 10mg TDS
• Tab ancoloxin 11/11 BD or Tab Metoclopramide 10mg TDS
5. Avoid spicy food & oily food
6. Encourage frequent & small meal i.e. biscuits, fruits, fruit juice
7. Discharge only if patient tolerating orally, negative urine acetone, normal I/O & electrolytes
 n.b. METABOLIC ALKALOSIS

Type of metabolic imbalance associated with vomiting = METABOLIC ALKALOSIS

Pathophysiology of Metabolic Alkalosis in Severe Vomiting

• Prolonged vomiting causes loss of HCL & produces an increase of HCO3 in the plasma to compensate for the lost Cl-
• This results in hypokalemic hypochloremic metabolic alkalosis.
• Alkalosis shifts the intracellular potassium to the extracellular compartment, and the serum potassium is increased
factitiously.
• With continued vomiting, the renal excretion of potassium increases in order to preserve sodium.
• The adrenocortical response to hypovolemia intensifies the exchange of potassium for sodium at the distal tubule, with
subsequent aggravation of the hypokalemia.
• It is best corrected by using NS with added KCL or Hartmann’s solution only

Most Common IV Crystalloid Solutions

Normal Saline 5% Dextrose Saline Hartmann’s Solution / Ringer’s Lactate
Na+ 154 mmol Nil 131
Cl- 154 mmol Nil 111
K+ Nil Nil 5
HCO3 Nil Nil 29
Ca2+ Nil Nil 2
Lactate Nil Nil 29
Glucose Nil 50g/1L DS Nil
 POLYCYSTIC OVARIAN SYNDROME (PCOS)
Also known as Stein-Leventhal syndrome

History
Polycystic ovaries was 1st described in 1953 as a cause of anovulation in women seeking treatment for subfertility by Stein &
Leventhal

Epidemiology
• Commonest endocrine disorder in women of reproductive age
• Affects 6-7% of population
• Higher incidence in certain ethnic group (South Asian origin)

Definition
Rotterdam Criteria: Diagnosis is confirmed by 2 out of 3 criteria after exclusion of other etiologies
4. Biochemical or clinical evidence of hyperandrogenism
• Biochemical: Total Testosterone > 70ng/dL, Androstenedione > 245 ng/dL, DHEA-s > 248 ug/dL
• Clinical: Acne, hirsutism, acanthosis nigrans
5. Ovulatory dysfunction: Amenorrhea or oligomenorrhea
6. Polycystic ovaries on ultrasound shows at least one ovaries with
• 12 follicles 2-9mm diameter in each ovary
• Ovarian volume >10ml

Other Diagnostic Criteria for PCOS

1. National Institutes of Health / NIH (1990) — must include all of the following:
• Chronic anovulation
• Biochemical or clinical evidence of hyperandrogenism and exclusion of other causes
2. Rotterdam Criteria (2003)
3. Androgen Excess Society / AES (2006) — must include all of the following:
• Ovarian dysfunction (oligomenorrhea or anovulation) or polycystic ovaries or both
• Biochemical or clinical evidence of hyperandrogenism

Exclusion of Other Differential Diagnoses (Rotterdam Criteria)

1. Hyperprolactinaemia
2. Hypothyroidism
3. Non-classical congenital adrenal hyperplasia
4. Ovarian & adrenal tumour (androgen secreting tumours)
5. Cushing’s syndrome
6. Drugs: Danazol, OCPs
7. Other causes of amenorrhea

Clinical Form
1. Primary PCOS – Stein-Leventhal syndrome
2. Central form of PCOS i.e. 2° to hypothalamic disfunction
3. Combined form of PCOS i.e. developed 2° to CAH

Cause
1. The exact cause of PCOS is unknown, but experts believe it is related to the production of an excess amount of androgens, a
group of male sex hormones (Hyperandrogenism)
2. Insulin resistence — Excess insulin leads to insulin resistance, which in turn decreases ability to use insulin effectively results
in hyperinsulinemia
3. Heredity — Greater chance of having PCOS if 1° relatives have PCOS
4. Intrauterine androgen exposure — Conditions before birth in the mother’s womb can be a factor contributing to PCOS
Pathophysiology
Hypothalamus / neuroendocrine
dysfunction

Metabolic impairment Insulin resistance & hyperinsulinemia

⇩
Interact with insulin receptor itself in the ovaries
⇩
Insulin causes ovaries to make more androgen
⇩
Androgens excess
⇩
PCOS
Adrenal Gland / Ovaries Primary defect of genes regulating steroidogenesis (cytochrome P450c17)
n.b. cyt P450c17 catalyses the step of progesterone 17α hydroxyprogesterone to
androstendione
⇩
P450c17 enzyme hyperactivity
⇩
Alteration in androgen biosynthesis (steroidogenesis)
⇩
Androgen excess
⇩
PCOS
Ovaries Primary defect in genes regulating folliculogenesis
⇩
Ovarian folliculogenesis dysfunction
⇩
Follicular arrest

Obesity & PCOS

Does being overweight cause PCOS
or does PCOS result in obesity?
• Both are possible
• PCOS produce too much insulin,
which causes hyperinsulinaemia
resulting in Type 2 DM &
obesity
• By being obese, it can lead to
insulin resistance &
hyperinsulinaemia, which will
cause androgen excess & PCOS
Clinical Features
Symptoms
• Menstrual irregularities: abnormal patterns of menstruation attributed to chronic anovulation
− Oligomenorrhea (menstruation at interval >35 days)
− 2° amenorrhea (absence of menstruation > 6 months)
− Infertility (due to anovulation)
• Hyperandrogenism
− Hirsutism: Excess body hair in a male distribution pattern e.g. upper lip, chin, around nipples, lower abdomen
Graded by Ferriman Gallwey system
<8 normal
8-15 mild hirsutism n.b. Patient with PCOS doesn’t become virilised
>15 moderate – severe hirsutism  
− Acne vulgaris
− Seborrhea
− Androgenic alopecia (Ludwig score)
• Insulin resistance
− Acanthosis Nigrans: dark pigmented patches on skin in areas of the nape of neck, inner thigh & arms
− Skin tages
− Impaired glucose tolerance
− Obesity

Ferriman Gallwey System for Hirsutism

Signs
• Hyperandrogenism
• Hyperinsulinaemia
• Hypercholesterolaemia
• Type 2 Diabetes Mellitus
• High LH level
• High BP
• Polycystic ovaries on ultrasound

Hirsutism vs Virilization
Important to differentiate from hirsutism
• Definition: Development of exaggerated masculine characteristics, usually in women, often as a results of overproduction of
androgens
• Usually caused by adrenal tumour
• So, if hyperandrogenism becomes extreme, virilization occurs
• Characterised by:
1. Masculinization
2. Severe hirsutism of rapid onset
3. Male pattern balding
4. Deep voice
5. Clitomegaly

Complication of PCOS
1. Infertility — 2° to anovulation
2. Endometrial hyperplasia & carcinoma — 2° to unopposed oestrogenic stimulation of endometrium
3. Breast cancer
4. Metabolic consequences — Increased risk of
• Cardiovascular disease (CHA2DS2-VASc score)
• Dyslipidaemia
• Type 2 Diabetes Mellitus (screen: HbA1C or OGTT)
• Obesity
• Hypertension
• Sleep apnoea
Investigations
Investigation to confirm diagnosis
Investigation for complication of
disease
Investigation TRO other cause
Biochemistry Test
1. Total Testosterone (TT): Increased
2. Free Testosterone (FT): Increased
3. Free Androgen Index: (FAI): Increased
4. Sex-Hormone Binding Globulin (SHBG): Decreased
5. Others
1. LH, FHS & LH/FSH ratio: LH >10IU/ML, LH/FSH >2.5
2. Androsterone: Increased
3. Dehydroepiandrosterone-Sulfate (DHEA-S)
4. Anti Mullerian Hormone (AMH): Increased
Imaging Test
1. Pelvic ultrasound
• To evaluate ovarian morphology
• Transvaginal US in women, abdominal US in children
• Polycystic ovaries: 12 or more peripherally placed follicles with increased ovarian
volume > 10ml
• Typical appearance: String of pearls
Biochemistry Test
1. Blood glucose: HbA1C, OGTT, FBG
2. Lipid profile: LDL, HDL, triglyceride
3. Tumour markers: CEA, βhCG, AFP & CA125
Imaging Test
1. CT Thorax/Abdo/Pelvic – only if metastasized endometrial ca
Biochemistry Test
1. βhCG — TRO pregnancy
2. Serum prolactin — TRO hyperprolactinaemia
3. TFT (TSH, free T4) — TRO hypothyroidism
4. DHEA-S & 17-OHP — TRO non-classical CAH or androgen-secreting tumour
5. Serum cortisol & 24h urinary cortisol — TRO Cushing’s disease
6. IGF-1 — TRO acromegaly
Imaging Test
1. MRI brain – only if suspicious of brain tumour esp. prolactinoma
Treatment (Goal Specific)
Menstrual Irregularities 1. Lifestyle modification (Diet, regular exercise & weight loss) to decrease peripheral estrone
formation
2. OCP monthly or cyclic progestin therapy (Provera) to protect endometrium
3. Tranexamic acid for menorrhagia only
4. Add metformin if high BMI
Infertility 1. Ovulation Induction
• Options: Clomiphene Citrate (Clomid) or GnRH agonist (FSH, HMG) + Metformin
• OI needs careful monitoring (follicle scan, estradiol level) to prevent OHSS & multiple
gestation
2. Assisted Reproductive Technology (ART)
• Intrauterine Insemination (IUI)
• In Vitro Fertilization (IVF)
• Intra Cytoplasmic Sperm Injection (ICSI)
• Donor sperm, eggs or embryos
3. Surgical: Laparoscopic wedge resection or ovarian drilling
Hirsutism 1. Hair removal: Creams / Laser / Electrolysis
2. Weight reduction: improves hirsutism
3. OCP containing an antiandrogen:
• Diane 35® (contains cyproterone acetate, which also improve acne)
• Yasmin® (contains drospirenone & ethinyl estradiol)
4. GnRH agonist (Lupron): only use for <6 months since many SEs
5. Anti-androgens: use with contraceptives
• Spironolactone (androgen receptor blocker); in-utero risk: incomplete virilization of male
fetus
• Finasteride (5α-reductase inhibitor); in-utero risk: male fetus hypospadias
• Flutamide (androgen reuptake inhibitor)
• Cyproterone acetate-ethinylestradiol
Metabolic derangement 1. Lifestyle modification: Diet, regular exercise & weight loss
2. Metformin
• Improve insulin resistance
• Decreases hyperinsulinaemia
• Improves menstrual irregularities & infertility
Comorbidities – screen & 1. Prevention of CVD & DM
manage comorbidities • Lifestyle modification: Diet & regular exercise & weight loss
• Metformin: If DM, metabolic syndrome otherwise limited use
• Statin: If hyperlipidaemia
2. Monitor & protect endometrium
• Ultrasound ± endometrial sampling
• HRT / OCP with anti-oestrogen effect

Treatment in women who want to conceive & those who don’t want to conceive
Pregnancy or OI is desired
Anovulatory / Infertility → 1st line: Clomiphene citrate
Insulin resistance →1st line: Metformin
st
Obesity →1 line: Lifestyle modification
Hirsutism →1st line: Electrolysis & light-based therapies
Acne →1st line: Topical cream
Pregnancy or OI isn’t desired
Anovulatory / Menstrual irregularities → 1st line: OCP inc
Mirena®
Insulin resistance →1st line: Metformin
Obesity →1st line: Lifestyle modification
Hirsutism →1st line: OCP, 2nd line: spironolactone
monotherapy, light-based therapies, Finasteride
Acne →1st line: Topical cream, 2nd line: Spironolactone
 GESTATIONAL TROPHOBLASTIC DISEASE

Definition (RCOG Guideline No 38, 2010)

Gestational trophoblastic disease (GTN) is a spectrum of trophoblastic diseases that includes:
1. Complete molar pregnancy
2. Partial molar pregnancy
3. Invasive mole
4. Choriocarcinoma
5. Placental site trophoblastic tumour
The last 2 may follow abortion, ectopic or normal pregnancy

WHO Classification of GTN

Malignant neoplasms of various type of
trophoblast
1. Choriocarcinoma
2. Placental site trophoblastic tumour
3. Epithiliod trophoblastic tumour
Malformation of chorionic villi that are
predisposed to develop trophoblastic
malignancies
1. Hydatiform moles – complete,
partial or invasive
Benign entities that can be confused with
these other lesions
1. Exaggerated placental site
2. Placental site nodule

Histological Classification (PGH Protocol)

Hydatiform Mole (Benign tumour) Gestational Trophoblastic Neoplasia (Malignant tumour)
1. Complete hydatiform mole 1. Persistent trophoblastic disease
2. Partial hydatiform mole 2. Invasive mole
3. Choriocarcinoma
4. Placental site trophoblastic tumour (PSTT)
5. Epitheliod trophoblastic tumour (ETT)
 HYDATIFORM MOLE

Complete hydatiform mole Partial hydatiform mole

Complete Hydatiform Mole

• Definition: A benign trophoblastic tumour (but can develop into malignant GTDs) characterised by abnormal conceptus
without an embryo / fetus only trophoblastic tissue present with gross hydrophic swelling of the placental villi & vesicles
formation
• Comprised both trophoblastic & syncytial elements
• It is avascular
• May either resolve or may progress to invasive mole or choriocarcinoma
• A classic mole resemble a bunch of grapes on pelvic USS
• Produces a very high level of hCG resulting in serious effects:
1. Excessive pregnancy symptoms = N&V, hyperemesis gravidarum
2. Hyperthyroidism (hCG is analogous to TSH)
3. May cause formation of theca-lutein cyst of the ovaries
• May be complicated by pre-eclampsia in early pregnancy (before 20w)
• CHM may be developed from one of the following:
Androgenic diploid Monospermic CHM (a) = Fertilization of an empty ovum by a haploid sperm (23X) followed by
reduplication of the 23X set giving a completely homozygous diploid genome of 46XX derived
entirely paternally
(n.b. A complete homozygous diploid genome of 46YY is never seen because at least one X
chromosome is essential for cell survival)

Dispermic CHM (b) = Fertilization of an empty ovum by two sperms (either 23X or 23Y) resulting
in a heterozygous diploid genome derived entirely paternally

Biparental diploid (c) Fertilization of a normal ovum by a sperm but somehow still results in complete mole formation.
This form of is usually seen in hereditary recurrent hydatiform moles associated with NLRP7
mutations, chromosome 19 or KHDC3L mutation.

Partial Hydatiform Mole

• A benign trophoblastic tumour (but can develop into malignant GTDs) characterised by a developing fetus with placental
tissues showing typical changes of hydropic swelling & vesicles
• Doesn’t produce as much hCG as complete hydatiform moles
• May be complicated by pre-eclampsia just like in CHM but later in pregnancy (around 17-22w)
• May be developed from one of the following:
Biparental triploid Dyspermic PHM = Fertilization of a normal ovum by 2 sperms resulting in a triploid genome (69XXX,
(d) 69XXy or 69XYY)

Monospermic PHM = Rarely fertilization of a normal ovum by a sperm carrying an unreduced diploid
paternal genome 46XY, resulting in a triploid genome (69XXY)
Investigation
• Diagnostic ix: UPT in dilution, serum β-hCG (pre-evacuation value) & pelvic US
• Ix for complication:
1. Anaemia → FBC
2. Trophoblastic embolization → CXR
3. Pre-eclampsia → FBC, RFT, LFT, Coag & uric acid, urine dipstick ± 24h urinary collection
4. Thyrotoxicosis → TFT
5. Dehydration → Urea & creatinine, serum electrolytes
Management
1. General assessment: ABC
2. KNBM
3. 2 large IV bore for IV access
4. Pre-op assessment:
• Risk assessment: Cardiac disease, HTN, pulmonary disease, DM, coagulopathies
• Lab investigation: FBC (Hg), Coagulation Profile, U+E, ECG, CXR & urinalysis
• Urgent GXM / GSH
5. Prepare patient for suction curettage (suction evacuation) under GA Hysterectomy is another surgical
• Put up Oxytocin drip in OT; 40 U in 1 pint D5% management option for hydatiform
• Suction curettage is done under ultrasound guidance mole especially if it is associated with
• Transfuse blood if necessary malignant form of GTN
• Continue Oxytocin drip for another 4h at 20dpm
6. Patient may be discharge the next day but the following must be done:
• Evaluate post-evacuation β-hCG by plotting β-hCG quantified result on a graph S&C ≠ D&C
• CXR to be done & finding recorded S&C = Vacuum aspiration of intra-
• Counsel patient & husband on contraception & follow-up uterine contents performed for
1. Contraception: Barrier method, OCP preferably once β-hCG normalized termination of pregnancy or for early
2. Follow-up incomplete spontaneous abortion
− One week, then
− 2-weekly for 3/12, then D&C = Dilatation of cervic os &
− Monthly for 3/12, then curettage of endocervical ±
− 3-monthly for 1 year, then endometrium tissue for HPE, to halt
− Yearly for life uterine bleeding, to terminate
pregnancy, or to remove tissue
Follow-up for Patient with Hydatiform Mole following incomplete spontaneous
• Timing is as mentioned above abortion
• Why?
1. To determine when pregnancy can be allowed → After completed f/up or after 1 year post CTx
2. To detect persistent trophoblastic disease (GTN) → If it is persistent, D&C ± CTx is advised (RCOG guideline)
• At each visit:
1. History → LMP, resumption of menses, AUB, haemoptysis, review HPE
2. Physical Examination → General, Abdomen & Pelvic Examination including speculum & vaginal exam
3. Investigation → Monitor Hb & serum β-hCG at every visit
4. Plot β-hCG quantified result
5. Placenta for HPE in subsequent pregnancy

Criteria for Chemotherapy after hydatidiform mole

1. High β-hCG level > 20,000IU/l or urine level > 30,000IU/l more than 4 weeks after evacuation
2. Progressively rising β-hCG levels at anytime of 2 determinants after evacuation.
3. β-hCG levels rising for 2 successive weeks
4. β-hCG constant (plateau) for 3 successive weeks
5. β-hCG levels elevated at 15 weeks postevacuation
6. Rising β-hCG titer after reaching normal levels.
7. Raised hCG levels 6 months after evacuation even if falling
8. Persistent uterine bleeding and positive hCG levels
9. Histological diagnosis of choriocarcinoma
10. Evidence of CNS, renal, hepatic, GIT or pulmonary metastasis > 2cm in diameter or >3 in number
 GESTATIONAL TROPHOBLASTIC NEOPLASIA
Invasive Hydatiform Mole (Chorioadenoma Destruens)
• A form of hydatiform mole in which the hydropic villi invade myometrium or blood vessels or are transported to extra-
uterine sites
• Locally invasive & mostly confined to uterus. Less likely to have distant metastases to lungs, vulva, broad ligament & brain
• Clinical features:
1. PV bleeding GTN
2. Abdominal swelling (intrauterine bleeding & theca lutein cyst) Metastasis sx → Choriocarcinoma
3. Intra-peritoneal bleeding (perforation through myometrium wall) No mets sx only local sx → Invasive mole
4. Persistently elevated serum β-hCG
5. If sepsis occurs → Abnormal vaginal discharge / acute pelvic pain
• Diagnosis of invasive mole is usually made retrospectively on histological confirmation after a hysterectomy performed for
persistent serum β-hCG elevation following treatment for a complete mole

Choriocarcinoma
• Malignant form of GTN that arises from trophoblastic tissues
• Comprises both cytotrophoblast & syncytiotrophoblast that is grossly appear as a haemorrhagic friable mass but with no
identifiable villi
• May be non-gestational related (i.e. arising from germ cell tumour) or gestational related (i.e occur following any form of
pregnancy)
CHM (50%) – MOST COMMONLY OCCURS FOLLOWING CHM
Abortion (25%)
Normal pregnancy (22%)
Ectopic pregnancy (3%)
• Clinical features: Most commonly presented with metastasis symptoms, which are due to spontaneous bleeding at metastasis
sites
• Widespread haemotogenous metastasis:
1. Lungs: Haemoptysis, dyspnea, cough, chestpain
2. Vagina: PV bleeding, abnormal vaginal discharge, fleshy mass on VE
3. Liver: Epigastric or RUQ pain, abnormal LFT
4. Brain: Focal neurological deficit showing haemorrhagic lesions in the brain, symptoms of raised ICP
5. GIT: Hematochezia
• Produce high level of β-hCG (tumour marker)

FIGO Classification of GTN Staging

Stage 1 Disease confined to the uterus Diagnosis is made based on rising serum β-hCG level with
lesions confined to uterus

Stage 2 GTN extends outside the uterus but is limited to genital GTN extends to vaginal or pelvis or both but is still
structures e.g. adnexae, vagina, broad ligament confined to pelvic cavity

Stage 3 GTN extends to lungs, with or w/out genital tract Diagnosis is made based on rising serum β-hCG level with
involvement pulmonary lesions seen on CXR

Stage 4 GTN metastases to all other sites Patients have advanced disease involving brain, liver,
kidney & GIT
These patients are in the high risk category because the are
most likely to be resistant from CTX
The histologic pattern of choriocarcinoma is usually present
& disease commonly follows after non-molar pregnancy

Prognostic Scoring System for GTN

1. FIGO Staging System
2. WHO Prognostic Scoring System
3. Modified Bagshawe Score
4. Modified WHO Prognostic Scoring System adapted by FIGO
FIGO / WHO Modified Prognostic Scoring for GTN

Investigation WHO / FIGO Scoring System for GTN

• Diagnostic ix: UPT in dilution, serum β-hCG & pelvic US Score ≤6 → Low risk → Good Prognosis → Single-agent CTx
• Ix for complications of disease: Score ≥ 7 → High risk → Poor Prognosis → Multi-agent CTx
1. Anaemia → FBC
2. Pre-eclampsia → FBC, RFT, LFT, Coag & uric acid, urine dipstick ± 24h urinary collection
3. Thyrotoxicosis → TFT
4. Dehydration → Urea & creatinine, serum electrolytes
• Ix for staging of disease (Imaging ix):
1. CXR — cannon ball metastasis
2. CT TAP; if not available to hepatobiliary & renal ultrasound
3. CT Brain
4. Lumbar puncture for CSF β-hCG quantification
− If suspect brain mets but CT brain is –ve, consider lumbar puncture for CSF β-hCG quantification
− β-hCG doesn’t readily cross BBB, may suggest CNS involvement
− A ratio of plasma β-hCG:CSF β-hCG <40 indicates metastases

Management
1. Chemotherapy — mainstay of treatment for GTN
• Should be done in Specialised Unit
• Management depends on FIGO / WHO Prognostic Scoring
− Women with scores ≤ 6 are at low risk and are treated with single-agent IM methotrexate alternating daily with
folinic acid for 1 week followed by 6 rest days
− Women with scores ≥ 7 are at high risk and are treated with IV multi-agent chemotherapy, which includes
combinations of methotrexate, dactinomycin, etoposide, cyclophosphamide and vincristine.
− Refer table below:
Low Risk (score ≤ 6) Single Agent Chemotherapy — MTX / Folinic Acid / Actinomycin-D
High Risk (score ≥ 7) Multiple Agent Chemotherapy — EMACO
E → Etoposide
M →MTX
A → Actinomycin-D
C → Cyclophosphamide
O → Oncovin (Vincristine)
2. Surgical Intervention: Hysterectomy under CTx cover only if indicated:
• Poor response to CTx in disease that is confined to uterus
• Emergency procedure when there is uncontrolled bleeding
• Completed family (no future pregnancy plan)
• Local resection of easily accessible or chemo-resistant solitary metastases
3. Liver & brain mets
• Chemo-resistant mets (liver & brain mets) require local resection of tumour or radiotherapy
 GENERAL CLINICAL FEATURE FOR GTD
Sign Symptoms
General Examination • Amenorrhea
• Signs of anaemia (PV bleeding) • Spontaneous abortion: lower abdominal pain accompanied
• Signs throphoblastic embolization: respiratory distress, by irregular & heavy PV bleeding ± passage of molar
DIC vesicles (resembling a bunch of grapes)
• Signs of pre-eclampisa: hyperreflexia, papiloedema on • Symptoms of high hCG:
fundoscopy, oliguria / anuria, RUQ tenderness 1. Excessive N&V
• Signs of hyperthyroidism: goiter, exophthalmos, lid 2. Hyperemesis gravidarum
retraction, lid lag etc • Symptoms of pre-eclampsis:
1. Frontal headache ± aura
Abdominal Examination 2. Blurred vision
• Uterus size: larger than dates in CHM but smaller than 3. Flashlights
dates in PHM 4. N&V
• Fetal heart rate: Absent in both but may be present in PHM 5. Epigastric pain
with viable fetus • Symptoms of hyperthyroidism:
• Liver tenderness (choriocarcinoma with liver mets) 1. Palpitations
2. Weight loss
Pelvic Examination 3. Heat intolerance
Speculum exam: 4. Tremor
• Cervical os may be open with blood coming through • Symptoms of metastasis (only for choriocarcinoma):
(spontaneous abortion) 1. Lungs: Haemoptysis, dyspnea, cough, chest pain
• May see grape-like molar vesicles in the vagina 2. Vagina: PV bleeding, abnormal vaginal discharge,
• May see firm discolored vaginal mass (choriocarcinoma fleshy mass in vagina
with vaginal mets) 3. Liver: Epigastric or RUQ pain
4. Brain: Neurological deficit due to haemorrhagic
Bimanual exam: lesions in the brain, symptoms of raised ICP
• May feel adnexal mass on bimanual palpation (theca lutein 5. GIT: Hematochezia
cyst)

Other Examination (if suspect choriocarcinoma)

1. Respiratory examination
2. Neurological examination
3. Rectal examination

Pelvic ultrasound showing a typical snowstorm appearance in Pelvic ultrasound showing molar mass & viable fetus in partial
complete hydatiform mole hydatiform mole

Diagnostic Investigation
GENERAL INVESTIGATION FOR GTD
1. +ve UPT in high dilution
(n.b. in hydatiform mole, hCG level is too high that UPT couldn’t detect it giving a false
negative result. UPT in dilution should be ordered for the patient in order to diagnose
hydatiform molar pregnancy)
2. Serum β-hCG is very high for early pregnancy, normal / slightly elevated if PHM
3. Pelvic ultrasound
• CHM: no fetus (classic “snowstorm appearance” due to swelling of villi; theca lutein
cyst is common
• PHM: fetal parts may be seen, fetal anomalies, fetal heartbeat may be absent, hydropic
swelling of placenta seen as multiple echogenic regions & focal intrauterine
hemorrhage

n.b. IHC strongly positive for placental alkaline phosphatase (PLAP) in PHM

Investigation for complication 1. Anaemia

1. Anaemia • FBC — Hg level
2. Trophoblastic • Blood group & crossmatch (GXM) Blood tests & GXM are also
embolization • Coagulation profile done for the purpose of pre-
3. Pre-eclampsia 2. Trophoblastic embolization → CXR op assessment in case if
4. Thyrotoxicosis 3. Pre-eclampsia patient losses too much blood
5. Dehydration • Blood ix: FBC, LFT, RP, CP, Uric acid doing D&C
• Urine ix: Urine dipstick, 24h urinary collection  
4. Thyrotoxicosis — TFT
5. Dehydration
• RFT — Urea & creatinine
• U+E

Investigation for staging (for Blood ix

GTN) 1. FBC
2. RFT
3. LFT
4. TFT (TSH)
5. Serum β-hCG

Imaging ix
5. CXR — cannon ball metastasis
6. CT TAP; if not available to hepatobiliary & renal ultrasound
7. CT Brain
8. Lumbar puncture for CSF β-hCG quantification
• If suspect brain mets but CT brain is –ve, consider lumbar puncture for CSF β-hCG
quantification
• β-hCG doesn’t readily cross BBB, may suggest CNS involvement
• A ratio of plasma β-hCG:CSF β-hCG <40 indicates metastases

OVERVIEW OF MANAGEMENT FOR GTD

Benign GTD Malignant GTD
1. S&C + sent tissue for HPE 1. CTx Regime based on WHO / FIGO scoring system
2. Follow-up & monitor post evacuation serum β-hCG ≤6 → Single-Agent CTx
3. If persistent GTD or HPE shows malignant cells: ≥7 → Mutiple-Agent CTx EMACO
• D&C Treatment is continued, in all cases, until the hCG level
• CTx has returned to normal and then for a further 6 consecutive
• Hysterectomy weeks
2. Hysterectomy under CTx cover only if indicated
3. Liver & brain mets are chemo-resistant → local resection
of tumour or RTx
 GYNAECOLOGICAL NEOPLASM
VULVA
Vulva Pathology
1. Lichen Sclerosis et atrophicus
2. Lichen Simplex Chronicus
3. Bartholin cyst
4. Vulval Intraepithelial Neoplasia (VIN)
5. Vulval neoplasm
Benign Malignant
Papillary Hidradenoma Squamous cell carcinoma
Condyloma Acuminatum Paget’s disease
Melanoma

LICHEN SCLEROSIS ET ATROPHICUS

Definition
Chronic inflammatory skin condition of the vulva characterized by:
• Subepithelial fibrosis
• Atrophy
• Scarring

Epidemiology
• Common in females
• For males, more common in uncircumcised or incompletely circumcised men and boys
• May present at any age
• No known race predilection
• Associated with subsequent malignancies

Clinical features
• Can be asymptomatic
• Ivory-white elevations that may be flat and glistening.
• Marked itching — most common symptom
• Thinning and shrinkage of the genital area
• Painful coitus, urination, and defecation
• Males = whitish thickening of the foreskin, which cannot be retracted easily (phimosis)

Microscopic / Pathological features

• Thinned epidermis – atrophy of dermis
• Hydropic degeneration at basal layer
• Sclerotic stroma
• Dermal inflammation
• Hyperkeratosis
• Lymphocyte infiltration in dermis

Diagnosis – No specific diagnosis

• Often undiagnosed or misdiagnosed as thrush
• Microscopy of affected vulvar skin taken by biopsy to look for features that develop in patients with chronic itch

Treatment - There is no definitive cure

1. Behavior change = good hygiene and minimizing scratching of the affected area
2. Potent topical steroids
• Example = Clobetasol propionate or mometasone furoate
• Relieve symptoms and prevent scarring
• However, LS is a chronic disease so topical steroids may need to be continued as maintenance therapy
LICHEN SIMPLEX CHRONICUS
Definition = White lesion that develops as a result of chronic scratching

Epidemiology
• Characterized by chronic scratching
• It is common in children, who chronically scratch insect bites and other areas

Gross features (sign)

White lesion due to chronic scratching

Microscopic features
• Acanthosis
• Hyperkeratosis
• Variable inflammatory infiltrate of the dermis

Pathogenesis
• It may begin with something that rubs, irritates, or scratches the skin, such as clothing.
• This causes the person to rub or scratch the affected area. Constant scratching causes the skin to thicken.
• The thickened skin itches, causing more scratching, causing more thickening.
• Affected area may spread rapidly through the rest of the body.
• The skin may become leathery and brownish in the affected area.
• This disorder may be associated with atopic dermatitis (eczema) or psoriasis.
• It may also be associated with nervousness, anxiety, depression, and other psychological disorders

Treatment
• Treatment is aimed at reducing itching and minimizing existing lesions
• May be treated with a lotion or steroid cream (such as Betamethasone) applied to the affected area of the skin

BARTHOLIN CYST
• Bartholin vulvovaginal glands
• Cause = Ducts obstructed, which can give rise to inflammation
• Cyst looks like mucocoele and are benign
• Occasionally produces abscesses
• Lined by transitional or flattened epithelium

VULVAL INTRAEPITHELIAL NEOPLASIA (VIN)

Definition = Dysplasia of the vulva, which remain above the basement membrane of the epidermis of the vulva

Grade (Low grade = VIN1; high grade = VIN2 and 3)

Grade Dysplasia Depth of epithelial involvement
VIN1 Mild dysplasia Involves lower 1/3rd of epithelium
VIN2 Moderate dysplasia Involves lower 2/3rd of epithelium
VIN3 Severe dysplasia, carcinoma in situ Involves >2/3rd of epithelium

Progression to SCC
• SCC can follow if VIN3 is not treated
• Precancerous change presents as multicentric white or pigmented plaques on vulva (may only be visible at colposcopy)
• Progression to cancer rarely occurs with appropriate management
• Risk of progression to invasive tumour increases with
− Age
− Immunosuppression

Differentiated VIN
• Not HPV related
• Affect tumour suppressor gene p53
• Develop quickly on the background of inflammation – leukoplakia

Treatment
1. Local excision (i.e. superficial vulvectomy ± split thickness skin grafting to cover defects if required)
2. Ablative therapy (i.e. laser, cauterization)
3. Local immunotherapy (imiquimod)
VULVAL NEOPLASM
Benign Malignant
Papillary Hidradenoma Squamous cell carcinoma
Condyloma Acuminatum Paget’s disease
Naevus Melanoma
Fibroma
Hemangioma

BENIGN VULVAL NEOPLASM

Papillary Hidradenoma
• Histologically similar to intraductal papilloma of the breast
• Occurs along milk line
• Extopic mammary tissue
• Macroscopic feature = Circumscribe ± ulceration
• Microscopic feature = Tumour with tubular duct, double lining with columnar and myoepithalial cell

Condyloma Acuminatum
• Wart
• Papilloma = Finger like projection with vascular core
• Cause = HPV6 and HPV11
• Covered by squamous epithelium
• Microscopic feature = Acanthosis, parakeratosis, hyperkeratosis, koilocytosis (HPV infection)
NB Koilocyte = squamous epithelial cell that has undergone structural changes

MALIGNANT VULVAL NEOPLASM

Epidemiology
5% of genital tract malignancies
90% SCC; remainder melanomas, basal cell carcinoma, Paget’s disease, Bartholin’s gland carcinoma

Classification
Type I Type II
• HPV-related (preceding VIN) • Not HPV-related (preceding Lichen Sclerosis et
• More likely in younger women atrophicus)
• 90% of VIN contain HPV DNA (usually types 16, 18) • Associated with current or previous vulvar dystrophy
• Usually postmenopausal women

Risk Factors
1. HPV infection
2. VIN

Clinical Features
• Asymptomatic at diagnosis
• Most lesions occur on the labia majora, followed by the labia minora (less commonly on the clitoris or perineum)
• Localized pruritus or lesion most common
• Less common: raised red, white or pigmented plaque, ulcer, bleeding, discharge, pain, dysuria

Route of spread
1. Local spread to adjacent structures
2. Lymphatic spred to groin lymph nodes (usually inguinal then to pelvic nodes)
3. Hematogenous

Investigations
± colposcopy & ALWAYS biopsy any suspicious lesion

Prognosis
• Depends on stage – particularly nodal involvement (single most important predictor followed by tumour size)
• Lesions >4 cm associated with poorer prognosis
• Overall 5 yr survival rate: 79%
Squamous Cell Carcinoma
• Most common malignancy in older women
• Relatively uncommon in relative to cervix
• Types
1. HPV related (preceding VIN)
2. Not HPV related (preceding Lichen Sclerosis et atrophicus)
• Prognosis depends on
− Depth of invasion
− Lymphovascular space invasion (LVSI)
• Stage = TNM system or FIGO system.
• Unlike the cervix, even superficial vulval cancers are high risk and may give rise to widespread lymph node spread

Paget’s Disease
• Extramammary Paget’s disease
• Originates from sweat gland and gives rise to an intraepidermal adenocarcinoma
• Accounts for ~1% of vulvar malignancies
• Rare association with underlying invasive cancer
• Common in older, postmenopausal women
• Clinical feature = red, crusted skin lesion
• Microscopic feature
− Single / cluster of cells with large pale cytoplasm (Paget cell)
− Clear halo – separates from surrounding cells
− Granular cytoplasm – PAS +ve
− Scattered throughout the epidermis
• Can resemble melanoma histologically

Melanoma
• Rare
• Prognosis related to depth of invasion
• Initially confined to epithelium
• Resemble Paget’s disease
 VAGINA
Vaginal Pathology
1. Developmental anomalies
2. Vaginitis
3. Gartner duct cysts
4. HPV infection
5. Vaginal neoplasm
• Squamous cell carcinoma
• Adenocarcinoma
• Embryonal rhabdomyosarcoma (sarcoma botryoides)
• Secondary Mestastasis

DEVELOPMENTAL ANOMALIES = MULLERIAN AGENESIS

VAGINITIS
Common causes:
• Candida
• Trichomonas
• Herpes Simplex
• Gardnerella

GARTNER DUCT CYSTS

• Remnants of Wolffian duct, seen lateral vaginal wall
• Non-mucing secreting
• Endometriosis may be seen
• Treatment: conservative unless symptomatic

VAGINAL NEOPLASM
Squamous cell carcinoma
• Cause = HPV
• Precursor = Vaginal Intraepithelial Neoplasia (VaIN)
• VaIN is classified in the same way as CIN and VIN
VaIN 1 Mild dysplasia
VaIN 2 Moderate dysplasia
VaIN 3 Severe dysplasia/carcinoma in situ
• Most common site is upper 1/3 of posterior wall of vagina
• Clinical Features
− Asymptomatic
− Painless PV discharge (often foul-smelling)
− Painless PV bleeding especially during/post-coitus
− Urinary and/or rectal symptom 2° to compression

Adenocarcinoma • Accounts for a very small amount of vaginal malignancies

• Most are metastatic, usually from cervix, endometrium, ovary, or colon
• Most primaries are clear cell adenocarcinomas
− Extremely rare now
− 2 types: non-DES and DES syndrome

Embryonal • Tumour of infants and young children

rhabdomyosarcoma
(sarcoma botryoides)
• Generally presents as a rounded polypoid (grape-like) soft tissue mass that may protrude
from the vagina.
• The malignant cells resemble primitive skeletal muscle
• Cambium layer beneath the vaginal epithelium containing tumour cells
• Can occur in many other areas of the body, but its prognosis is better if it occurs in a genital
location

Secondary metastasis • Direct spread from cervix and endometrium

• Distant spread less common
 FALLOPIAN TUBE
Fallopian Tube Pathology
1. Ectopic pregnancy — refer notes for ectopic pregnancy
2. Inflammation = PID, Salpingitis Isthmica Nodosa, Infection
3. Fallopian Tube Neoplasm
Benign Malignant
Leiomyoma Adenocarcinoma
Teratoma
Adenomatoid tumour
4. Others = Endosalpingiosis & paratubal cyst

INFLAMMATION (OVERVIEW)
Infection (Common)
Pelvic inflammatory disease
Salpingitis Isthmica Nodosa
• Cause: Bacterial infection
1. Ascending infection followed by STI
2. Followed by invasive surgical procedures
• Definition = inflammatory process in which the fallopian the presumed source
• Inflammtion may result in fusion, scarring of the lumen and tube obstruction
• Diverticulosis of the Fallopian tube
• Nodular thickening of the narrow part of the uterine tube, due to inflammation

FALLOPIAN TUBE NEOPLASM

• Least common site for carcinoma of female reproductive system (0.3%)
• Usually serous epithelial carcinoma
• Recently considered to be origin of serous ovarian cancer
• More common in fifth and sixth decade
• Clinical Features
− Classic triad (present in minority of cases, but very specific)
1. Watery discharge (most specific) = “hydrops tubae profluens” ƒ
2. Vaginal bleeding or discharge in 50% of patients
3. Crampy lower abdominal/pelvic pain
− Most patients present with a pelvic mass
• Treatment = As for malignant epithelial ovarian tumours

BENIGN NEOPLASM
Leiomyoma Benign tumour of the smooth muscle surrounding the fallopian tube
Teratoma RARE – Mostly mature cystic teratoma
Adenomatoid tumour • Most common benign tumour of the fallopian tube, thought to be essentially mesothelium inclusion
• Typically incidental, benign findings in middle age or elderly women who have operation for
another reason
• Macroscopic feature = Small, grey-white/yellow nodules just underneath the serosa
• Microscopic feature
− Gland-like cystic
− Microcystic spaces line by flattened cells or cords
− Tubules lined by cuboidal cell

MALIGNANT NEOPLASM = ADENOCARCINOMA

• Serous carcinoma > endometrioid
• Risk factor = 15% have germ line BRCA1 / BRCA2 mutation
• BRCA1 / BRCA2 mutation = precursor for serous tubal intraepithelial carcinoma
• With the discovery of precursor lesions in the fallopian tube, we now believe that most serous ovarian tumours represent
metastases to the ovary form the fallopian tube lesions

OTHER FALLOPAIN TUBE PATHOLOGY

Endosalpingiosis • Definition = condition in which fallopian tube-like epithelium is found outside the fallopian tube
• Unknown aetiology
• Develops from transformation of coelomic tissue
• It is often an incidental finding and is not usually associated with any pathology
Paratubal cyst Cyst of Morgagni = Appear as pedunculated, often tiny, frequently multiple cysts connected to the
fimbriae of the fallopian tubes
 CERVIX
Normal Anatomy of Cervix
• Cervix is the lower portion of uterus
• Connects vagina with main body of uterus, acting as a gateway between them.
• Anatomically & histologically, cervix is distinct from uterus, and hence we consider it as a separate anatomical structure
• Composed of two regions
Ectocervix • Portion of cervix that projects into vagina
• Lined by stratified squamous non-keratinized epithelium
• Opening in ectocervix (external os) marks the transition from ectocervix to endocervical canal
Endocervical • The more proximal, and ‘inner’ part of the cervix
canal • Lined by a mucus-secreting simple columnar epithelium
• Endocervical canal ends at internal os
• Function
1. Facilitates passage of sperm into uterine cavity, achieved via dilation of external & internal os
2. Maintains sterility of upper female reproductive tract
− Cervix & all structures superior to it, are sterile
− This ultimately protects uterine cavity & upper genital tract by preventing bacterial invasion
− This environment is maintained by frequent shedding of endometrium, thick cervical mucus & a narrow external os
• Arterial Supply = Uterine artery
• Venous Drainage = Uterine vein
• Lymphatic Drainage = Iliac, sacral, aortic & inguinal lymph nodes

Transformation Zone
• The border at which columnar epithelium changes into
squamous epithelium is called squamocolumnar junction
(SCJ)
• Area between old & new SCJ = Transformation Zone (a
zone of columnar epithelium that is undergoing a gradual
change into squamous epithelium)
• Transformation zone is the place where most cervical
abnormalities occur, both malignant and non-malignant. It
is for this reason that it is critical to make sure that both
squamous and columnar cells are gathered from the
transformation zone when making a Pap smear
• Position of transformation zone changes with age
Before puberty, transformation zone lies inside
endocervical canal
After puberty, during the fertile years, transformation
zone moves more in the direction of ectocervix
In the post-menopausal years, , transformation zone
recedes back into endocervical canal
HPV
Virus structure
• HPV is dsDNA virus
• Can infect cutaneous and mucosal epithelium
• Low risk viruses (HPV6, HPV11) = anogenital warts
• High risk viruses (HPV16, HPV18) = SCC cervical cancer and cancer precursor
− Other high risk HPV viruses = 45, 31, 33, 52, 58 and 35
− Less common cervical adenocarcinoma and its precursor adenocarcinoma in situ is also a/w high risk HPV
• The HPV genome encodes 2 nucleocapsid proteins (L1 and L2) and at least 6 early proteins (E1, E2, E4, E5, E6, E7) that
allow the replication of viral DNA and assembly of the viral particles
• Sub classification of HPV is based on DNA sequence of L1 protein; over 130 genotypes have been isolated

Epidemiology of HPV infection

• Adolescents and young adults are at higher risk for HPV and other STI
• Peak exposure = late teens and early twenties – related to high risk sexual behavior
• Younger women are increased risk – produce less cervical mucous, have larger transformation zone and more frequently have
cervical ectropion

HPV and Cervical cancer

• HPV = Viral oncogene, associated with cervical cancer (pre-cancerous lesion)
• HPV infection = STI
• Without HPV, cervical cancer = rare
• If it is not cleared, HPV infection will persist
• Cervical cancer will develop if precancerous disease doesn’t regress
− Many CIN1 / LSILs / low grade lesions regress
− Many CIN2-3 / HSIL / high grade lesions progress
• Latent period between CIN & invasive carcinoma, possibly influenced by environmental factors e.g. smoking
• Sequence = infection > CIN1 > CIN2 > CIN3 > Cancer
• CGIN (Glandular Cervical Intraepithelial Neoplasia) = abnormal glandular cells that line the inside of the cervix
• CIN causes SCC cervical cancer
• CGIN causes cervical adenocarcinoma
Pathophysiology of Cervical cancer by HPV

• If viral DNA becomes integrated into host DNA, malignant transformation may occur
• 5-10% will develop pre-cancerous changes in the cervix as the virus becomes integrated into host DNA
• HPV proteins E6 and E7 inactivates tumour suppressor gene p53 and RB to allow precancerous changes to develop

Cervical intraepithelial Neoplasia (CIN)

• CIN = cervical dysplasia – abnormal cells found on top of the surface of the cervix
• CIN is not cancer, and it is usually curable.
• Grade of CIN is classified in similar manner to VaIN, VIN and AIN
Grade Dysplasia Pathologic feature Depth of epithelial involvement
CIN1 Mild dysplasia • Koilocytic atypia Involves lower 1/3rd of epithelium
• Maturation occurs above this (normal)

CIN2 Moderate dysplasia Maturation is seen in upper 1/3rd Involves lower 2/3rd of epithelium

CIN3 Severe dysplasia • No epithelial maturation is seen Involves >2/3rd of epithelium

/carcinoma in situ • Abnormal proliferation occupies full
thickness of cervical epithelium
• Abnormal mitotic activity
• Low grade = CIN1; high grade = CIN2 and 3
• Microscopic features
− Nuclear enlargement, typically hyperchromatin with irregular nuclear contours
− Pleomorphism
− Extend through full thickness of squamous epithelium
− Koilocytes
• Koilocytes
− Histological markers for HPV infection
− Related to expression of viral E4 protein
− Large, irregular (raisin-like / raisinoid) nuclei with rope-like chromatin
− Often bi- or multinucleation and variation in nuclear size is common

ThinPrep pap smear with group of normal cervical cells on left

and HPV-infected cells showing features typical of koilocytes:
enlarged (x2 or x3) nuclei and hyperchromasia.
• Treatment of CIN
1. Excision biopsies
− LLETZ, cone biopsies and hysterectomies
− Allow confirmation of the abnormalities
− Reduce cervical cancer risk and recurrence
− 95% currative
2. Ablation of lesional tissue = Rarely used in many countries

Cervical Glandular intraepithelial Neoplasia (CGIN)

• Also called adenocarcinoma in situ (AIS)
• Precursor for cervical adenocarcinoma
• Not graded – always considered as high-grade lesion
• Microscopic feature
• Abnormal gland with abnormal nuclei
• Hyperchromatic nuclei and enlarged with corase chromatin
• Single or multiple nucleoli
• Frequent mitotic figures and apoptotic bodies
• If ACIS / CGIN if untreated, may progress to invasive adenocarcinoma
• Treatment of CGIN = same as CIN
Screening of Cervical Cancer: Pap smear

History
• Pap smear is developed by George Papanicolao (1883-1962)
• In 1939 – Papanicolao set up a clinic to collect cells from asymptomatic women in collaboration with Herbert F. Traut, MD, a
gynecologic pathologist at Cornell
• Their findings were published in 1943 monograph titled, “Diagnosis of uterine cancer by the vaginal smear.”
• This was the evolution of the ‘PAP smear’
• In 1954, Papanicolaou published the “Atlas of Exfoliative Cytology”

Aim of Cervical Screening

1. To detect changes (dyskaryosis) in the exfoliated cells consistent squamous intraepithelial lesion (SIL)
2. To identify pre-malignant changes (cervical intraepithelial neoplastic lesions) on cervix consistent with the abnormal
cytology
3. To provide early treatment for premalignant lesion to prevent malignant transformation

Type of Pap smear

Conventional Pap smear
A wooden spatula is used to take cervical cell sample, which is
then manually smeared onto slide, wet-fixed in 95% ethanol or
cytospray, and sent to the laboratory for staining and screening.
Liquid base cytology
A cytobrush is used to take cervical cell sample, which is then
put into liquid medium for suspension before automated thin
layer / monolayer slide preparation. Examples: ThinPrep test
smear and SurePathTM (formerly known as AutoCyte PREP)

Satisfactory Pap smear samples should contain:

• Sufficient mature & metaplastic squamous cells to indicate adequate sampling from the whole of transformation zone
• Sufficient endocervical cells to indicate that:
− The upper limit of the transformation zone was sampled
− To provide a sample for screening of adenocarcinoma and its precursors

Who to screen?
In Malaysia, all women who are, or who have been sexually active, between the ages of 20 and 65 years, are recommended to
undergo Pap smear testing. If the first two consecutive Pap results are negative, screening every three years is recommended

When to perform?
• Any time after the cessation of the period
• Avoid taking smear during menstruation
• Avoid in the presence of obvious vaginal infection
• Avoid within 48 hours of use of vaginal creams or pessaries or douching
• Avoid within 24 hours of intercourse
• Avoid lubrication or cleaning of cervix with preliminary pelvic examination
Management of Pap smears results (Penang Protocol)
Pap Smear Results Action
Normal smear Repeat every 3 years after 2 normal annual smear

Unsatisfactory smear Repeat after 3/12, treat infection & give a course of local oestrogen therapy if cytology
reported atrophic smear
Refer for colposcopy if similar findings in 3 consecutive smears

Inflammatory smear Treat with antifungal, antibiotic or antiviral according to organisms involved
Refer for colposcopy if similar findings in 3 consecutive smears

ASCUS (Atypical squamous cell of Repeat in 6/12

undetermined significance) Refer for colposcopy if similar findings of ASCUS in 2 consecutive smears

Refer for colposcopy (no need to repeat Pap smear in 6/12) if:
• ASCUS + Positive High-Risk HPV DNA
• ASC-H
• Immunocompromised

LGSIL (Low grade squamous Repeat in 6/12

intraepithelial lesion) Refer for colposcopy if similar findings of LGSIL in 2 consecutive smears

Refer for colposcopy (no need to repeat Pap smear in 6/12) if:
• Poor compliance
• Immunocompromised
• Positive High-Risk HPV DNA
• History of CIN

HGSIL (High grade squamous All these need URGENT referral for colposcopy
intraepithelial lesion)

AGUS (Atypical glandular cells)

Adenocarcinoma in situ All these need URGENT referral for colposcopy

Squamous cell carcinoma

Adenocarcinoma
Presence of endometrial cells Always do endometrial sampling by Pipelle or EUA hysteroscopy & DD&C
 CERVICAL CARCINOMA
Definition = Invasive carcinoma that arises from the cervical epithelium

Epidemiology of Cervical Carcinoma

• Cervical cancer is the 4th leading cause of female cancer in female in the world and is the 2nd most common cancer in women
aged 15 to 44 years.
• In Malaysia, cervical cancer is in the top 5th most common female cancers; and 2nd most common in women aged 15 to 44
years
• HPV is the most common cause of cervical cancer

Classification
1. Cervical squamous cell carcinoma 80% (precursor = CIN3)
2. Cervical adenocarcinoma 15% (precursor = adenocarcinoma in situ, CGIN)
3. Others
− Cervical neuroendocrine carcinoma
− Cervical adenosquamous carcinoma
n.b.
• Both SSC and adenocarcinoma are related to HPV infection.
• Advanced tumors often invade through the anterior uterine wall into the bladder, blocking the ureters.
• Hydronephrosis with postrenal failure is a common cause of death in advanced cervical carcinoma

Risk Factors
1. HPV infection especially HPV Type 16 & 18
2. Cigarette smoking
3. OCP
4. Immunosuppression e.g. HIV
5. Increase parity
6. Early onset of sexual activity
7. Multiple sexual partners
8. A high-risk sexual partner e.g. a partner with multiple sexual partners or known HPV infection
9. History of STDs e.g. Chlamydia trachomatis, genital herpes
10. Presence of cancer a/w HPV e.g. history of vulvar or vaginal squamous intraepithelial neoplasia or cancer
11. Low socioeconomic status

Route of Spread
Direct spread • Lateral — Parametrium, Meckenrodts ligament, lateral pelvic wall
• Superior — Endometrium
• Inferior — Upper part of the vagina, inguinal lymph nodes
• Anterior — Bladder
• Posterior — Along uterosacral ligament in which sacral plexus is involved causing sciatica

Nerve sheaths and ureteric wall are not penetrated by cancer cells
Invasion to rectum is very rare because of Pouch of Douglas
Lymphatic spread • Primary group of LN — paracervical, obturator, internal iliac & external iliac, sacral group
• Secondary group of LN — common iliac, aortic, inguinal

Haematogenous spread Lung, liver, brain & bone

Clinical Presentations (Symptoms)

1. Asymptomatic — incidental findings on Pap smear
2. Local symptoms
• Abnormal PV bleeding e.g. postcoital bleeding, postmenopausal bleeding & intermenstrual bleeding
• Vaginal discomfort
• Purulent vaginal discharge
3. Symptoms due to local invasion
• Renal: Frequency, dysuria, haematuria, urinary incontinence & PV leaking of urine (fistula formation), abdominal mass
and colicky loin to groin pain (hydronephrosis)
• Rectal: Tenesmus, altered bowel movement, diarrhea
4. Metastatic symptoms
• Constitutional symptoms: unintentional weight loss, loss of apetite, PUO
 • Lung: haemoptysis, dyspnea
• Liver: RUQ pain, abdominal mass
• Brain: headache, N&V, focal neurological deficits
• Bone: Bone pain, pathological fractures

Findings on Physical Examination (Signs)

General Examination
• Signs of malignancy: Cachexia, lymphadenopathy, pleural effusions
• Signs of anaemia
Abdominal Examination
• Hepatosplenomegaly
• Ascites
Pelvic Examination
• Early signs: erosion & ulcers (hardness, irregularity, bleeds on touch)
• Late signs: Induration, friability, fixity & bleed on touch
− SCC = exophytic, fungating tumour
− Adenocarcinoma = endophytic, with barrel-shaped cervix
Rectal Examination
• Assess extend of local disease in rectovaginal exam
• May reveal thickened induration of uterosacral ligament

Diagnosis
The diagnosis of micro-invasive cervical cancer should be based on histological examination of removed tissue, preferably a cone
that includes the entire lesion of the cervix colposcopic directed biopsy of suspicious lesions is preferred histological confirm of
cervical cancer is mandatory

Investigation
Diagnostic Investigation Diagnosis of cervical cancer is histopathological. Algorithm:
1. Pap smear
2. If abnormal Pap smear, perform colposcopy
3. If abnormal colposcopy, take colposcopic directed biopsy by:
• Punch biopsy
− If diagnosed CIN 2 or 3 based on punch biopsy, can treat with local ablation by using
either CO2 laser vaporization, cryotherapy & cold coagulation
• Cone biopsy
• LEEP/LLETZ
− LEEP = Loop Electosurgical Excision Procedure
− LLETZ = Loop Excision of Transformation Zone
− Both are the same & are used interchangeably

Investigation for staging Staging of cervical cancer is clinical, supported by limited range of ix according to FIGO
of disease 1. Clinical examination (vaginal and rectal exam including EUA)
• Determine if lesion is visible clinically & if so, measurement of greatest diameter
• Determine presence & extend of involvement of vagina & parametrium
2. Endoscopy
• Cystoscopy → Look for local invasion to bladder
• Sigmoidoscopy → Look for local invasion to rectum
3. Imaging
• IVU → Look for hydronephrosis; need not have IVU if CT TAP is done
• CXR → Look for lung metastasis & pleural effusion
Ultrasound of liver & kidney → Look for distant metastasis to liver & hydronephrosis
• CT TAP → Look for distant metastasis to lung, liver & bone and nodal mets
• MRI brain → Look for brain metastasis
• PET scan

MRI, CT & PET scan help to evaluate extent of disease & detect nodal metastasis but do not influence
clinical FIGO stage of cervical cancer. They are often done to facilitate planning of radiation therapy.
Routine Investigation 1. FBC → Low Hg due to PV bleeding, pre CTx / RTx assessment
2. RFT → Raised urea & creatinine due to renal metastasis & hydronephrosis, pre CTx / RTx
assessment
3. LFT → Raised liver enzyme, low albumin due to liver metastasis, pre CTx / RTx assessment
4. Coagulation Profile → Pre CTx / RTx assessment

At present there are no reliable blood tumour markers for cervical cancer. CA 125 is only indicated to
monitor response to radiation treatment

Staging of Cervical Cancer = Clinical Staging

Staging Systems used:
1. TNM
2. FIGO

FIGO Staging for Cervical Carcinoma (Revised 2009)

Treatment

Treatment is decided based on:

1. Stage of disease
2. Age of patient
3. Sexual activity
4. Well being of patient (physically & mentally) / performance status
• Patient with clinically visible lesion on cervix needs cervical biopsy, not Pap smear
• All patients diagnosed with cervical carcinoma need EUA, cystoscopy & staging
• Surgical treatment is ideal for early stage of disease (stage 1 – 2A2)
• Radiotherapy is the mainstay of treatment for advance disease (stage 2B – 4) or any patient with early stage disease not
fit for surgical intervention

Treatment of Cervical Cancer Based on Malaysian CPG

FIGO Staging Treatment
IA1 Treatment Options:
1. Cold-Knife Cone Biopsy + Simple Sufficient if lymphovascular space invasion (LVSI)
Hysterectomy negative. If patient wishes to preserve fertility

2. Cold-Knife Cone Biopsy + Simple LVSI positive

Hysterectomy + Lymphadenectomy

3. Simple Hysterectomy + BSO Preferred treatment for the following patients:

1. Postmenopausal women
2. Patient with concomitant gynaecological diseases
requiring treatment such as leiomyoma &
endomteriosis
3. Poor compliance
4. Local excision (cone biopsy) not feasible or high
possibility of incomplete resection
5. Patient with co-existing adenocarcinoma in situ
(ACIS)
6. Patient who has completed family

4. Radiotherapy only If surgery not wanted by patient

IA2 Treatment Options:

1. Surgery for primary tumour is individualise, it can any of the following:
Radical Trachelectomy
or
Modified Radical Hysterectomy PLUS Pelvic Lymphadenectomy
or
Radical Hysteretcomy
2. Radiation only if surgery not wanted by patient

IB1 & IIA1 Treatment Options:

1. Radical Hysterectomy PLUS Pelvic Lymphadenectomt (Wertheim’s Hysterectomy)
2. Primary radiation therapy especially if nodes positive

IB2 & IIA2 These stages refer to patients with cervical lesion ≥ 4cm (Bulky Disease)
Treatment Options:
1. Neoadjuvant Chemotherapy followed by Radical Hysterectomy
2. Radiation Therapy / Chemoradiation followed by Extrafascial Hsyterectomy
3. Primary Concurrent Chemoradiation Therapy (CCRT)

IIB to IVA Full External & Intra-cavity Radiation Therapy

 
Radiotherapy
• Treatment of choice for cervical cancer stage 2B and above
• Types = External Beam Radiotherapy (EBRT) & Brachytherapy (BT)
• Common chemotherapy agents:
1. Cisplatin
2. Carboplatin
3. Paclitaxel
4. Gemcitabine
5. Topotecan
6. 5FU
7. Mitomycin C
• Radiotherapy can be used for:
1. Primary radical / curative — if patient with early stage of disease refuses surgical treatment
2. Pre-operative (neoadjuvant)
3. Post-operative (adjuvant) — refer below
4. Palliation

Chemotherapy
• Chemotherapy is a frequently used modality in cervical cancer.
• Chemotherapt can be used for:
1. Pre-operative (neoadjuvant) — not advised, doesn’t improve survival rate
2. Post-operative (adjuvant) — refer below
3. Concurrent chemoradiation therapy (CCRT)
− CCRT may act synergistically to improve the efficacy of radiotherapy, as well as having independent cell
cytotoxicity
− Drug of choice = IV Cisplatinum 30mg/m2 weekly during period of EBRT
4. Palliation — for advanced stage

Indication for Post-Operative Radiation Therapy / Chemoradiation

1. Lymph nodes metastasis
2. Narrow surgical margin <5mm
3. Involvement of lower uterine segment
4. Parametrium infiltration
5. High GOG score (>120) in patients with negative lymph nodes & clear surgical margin
6. Poor histology type such as adenosquamous, small cell neuroendocrine

Recurrent Cervical Cancer

• Treatment for recurrent cancer depends on
1. Mode of primary therapy
2. Extent and site(s) of recurrence
• Consider surgery if primary therapy was radiation whereas radiation if primary therapy was surgery
• Radical surgery in recurrent cancer requires pelvic exenteration
• The use of brachytherapy is limited to vaginal recurrences of <1cm in diameter and EBRT is used for larger tumour
• Consider palliative care

Palliative Care
1. Advanced disease with distant metastasis
2. Recurrent cancer
3. In very elderly patients,
4. In those with extreme medical conditions

Follow up
• Aim
1. To determine the patient's immediate response to the treatment employed
2. Identify treatment related complications.
3. Detection of persistent or recurrent disease
• Recommendation
Year 1-2 every 3 months
Year 3-5 every 6 months
Year 5+ annually
• Each visit should include
1. Palpation of supraclavicular lymph nodes
 2. Palpation of abdominen for paraaortic enlargement, hepatomegaly and unexplained masses
3. Vaginal and rectal examination to detect central & parametrial recurrence
4. Ask for complications
− Radical operations, which entail shortening of the vagina, can cause physical and psychosexual problems. Patients
should be asked about constipation or voiding impairment
5. External stomas, if any should be cared for appropriately
6. Carry out investigations: IVU & CXR

Special Situation
Adenocarcinoma • Similar treatment for squamous carcinomas
•
Invasive Cervical • Similar treatment for non-pregnant patient however, treatment depends on patient's wishes on
Cancer During continuation of pregnancy
Pregnancy • If fetal viability has not been achieved, and the lesion is stage 1A2, 1B or 2A, treatment may be radical
hysterectomy and pelvic lymphadenectomy, with the fetus left in-situ
• For patients whose pregnancies are close to fetal maturity, then caesarean section, radical hysterectomy
and bilateral pelvic lymphadanectomy is the treatment of choice for early lesions
• In patients with more advanced disease, radiotherapy may be considered

Prevention of Cervical Cancer

1° Prevention 1. Avoidance of precipitating & risk factors
2. Counseling
3. HPV Vaccination (Gardasil & Cervarix)
2° Prevention Cervical cancer screening by Pap smear
3° Prevention Treatment of cervical cancer to limit extension of disease

HPV Vaccine
• Both vaccines use recombinant HPV L1 proteins that are identical to HPV virions but no viral DNA core
• Gardasil vaccine
− Quadrivalent vaccine against HPV type 6, 11, 16 and 18
− Manufactured by Merck
• Cervarix vaccine
− Bivalent vaccine against HPV type 16 and 18 only
− Manufactured by GlaxoSmithKline
• Should be administered before onset of sexual activity (i.e. before exposure to virus) for optimal benefit of vaccination
• May be given at the same time as hepatitis B or other vaccines using a different injection site
• Not for treatment of active infections
• Most women will not be infected with all four types of the virus at the same time, therefore vaccine is still indicated for
sexually active females or those with a history of previous HPVinfection or HPV-related disease
• Conception should be avoided until 30 d after last dose of vaccination
 OVARY
Anatomy
Structure
• Surface: The surface layer of the ovary is formed by simple cuboidal epithelium, known as germinal epithelium.
• Cortex: The cortex (outer part) of the ovary is largely comprised of a connective tissue stroma. It supports thousands of
follicles. Each primordial follicle contains an oocyte surrounded by a single layer of follicular cells.
• Medulla: The medulla (inner part) is composed of supporting stroma and contains a rich neurovascular network which enters
the hilum of ovary from the mesovarium

Ligaments
1. Suspensory ligament of ovary: fold of peritoneum extending from the mesovarium to the pelvic wall. Contains neurovascular
structures.
2. Ligament of ovary: extends from the ovary to the fundus of the uterus. It then continues from the uterus to the connective
tissue of the labium majus, as the round ligament of uterus

Vascular Supply = Ovarian arteries (a branch of abdominal aorta) & ovarian branch of uterine artery

Venous Drainage = Ovarian veins, L→Left renal vein R→IVC

Lymphatic Drainage = Para-aortic nodes

Innervation = Sympathetic & parasympathetic → Ovarian & pelvic plexuses

Physiology
• Composed of ovarian follicles (sac-like structure) with oocyte surrounded by follicles
• Shape = almond shape
• The functional unit of the ovary is the follicle.
• A follicle consists of an oocyte surrounded by granulosa and theca cells
• LH acts on theca cells to induce androgen production.
• FSH stimulates granulosa cells to convert androgen to estradiol (drives the proliferative phase of the endometrial cycle).
• Estradiol surge induces an LH surge, which leads to ovulation (marking the beginning of the secretory phase of the
endometrial cycle).
• After ovulation, the residual follicle becomes a corpus luteum, which primarily secretes progesterone (drives the secretory
phase which prepares the endometrium for a possible pregnancy).
• Hemorrhage into a corpus luteum can result in a hemorrhagic corpus luteal cyst, especially during early pregnancy.
• Degeneration of follicles results in follicular cysts. Small numbers of follicular cysts are common in women and have no
clinical significance.
 OVARIAN CYST
Introduction
• An ovarian cyst is a sac or pocket filled with fluid or other tissue that forms on the ovary
• It is normal for a small cyst to develop on the ovaries
• In most cases, cysts are harmless and go away with time on their own. In other cases, they may cause problems and need
treatment
• Rarely, a few cysts may turn out to be malignant (cancerous). For this reason, all cysts should be checked by your health care
provider

Type of ovarian cyst

Non-Neoplastic Ovarian Cyst Neoplastic Ovarian Cyst
1. Functional Cysts (most common) Benign Ovarian Cyst
• Follicular cyst Epithelial origin Serous tumour
• Corpus luteum cyst Mucinous tumour
• Theca lutein and granulosa lutein cyst Endometriod tumour
• Polycystic ovarian syndrome (PCOS) Brenner tumour
2. Cyst of mesothelial origin = Germinal inclusion cyst Germ cell origin Cystic teratoma (Dermoid cyst)
3. Cyst of inflammatory conditions Gonadoblastomas
• Tubo-ovarian abscess from PID Sex cord, stromal Granulosa-theca cell tumours
• Endometrioma a.k.a. chocolate cyst origin Sertoli-Leydig cell tumour
Fibroma

Malignant Ovarian Cyst

Epithelial origin Serous tumour
Mucinous tumour
Endometriod tumour
Brenner tumour – rarely malignant
Clear cell tumour
Germ cell origin Immature teratoma
Dysgerminoma
Endodrmal sinus tumour
Choriocarcinoma
Embryonic carcinoma
Sex cord, stromal Granulosa cell tumours
origin

Germinal inclusion cyst • Formed by the invagination of ovarian surface mesothelium into cortex or stroma of the ovary
• Cystic enlargement results from accumulation of serous fluid secreted by the mesothelium

Follicular cyst • Develop from partially-developed follicles that undergo atresia

• Extremely common
• Mostly physiological & will undergo spontaneous regression
• May be multiple

Corpus luteum cyst • MOST COMMON CYST IN PREGNANCY

• Develop after corpus luteal hematoma formed after ovulation
• Lined by lutenizined granulosa cells with theca cells in deeper layers
• If persistent, continued secretion of progresterone results in delayed menstruation presenting as
continuous PV bleeding
• May rarely rupture & results in massive intraperitoneal haemorrhage

Theca lutein cyst • Formed by intensely lutenized theca interna cells when corpus luteum is under influence of hCG
• Usually small but may be multiple & large especially when associated with multiple gestation,
GTD & patient on GnRH therapy

Dermoid cyst • Dermoid cyst = Benign (mature) cystic teratoma

• May be present from birth but grow during a woman’s reproductive years
• May be found on one or both ovaries
• Dermoid cysts form from a type of cell capable of developing into different kinds of tissue
Risk Factors
1. Infertility treatment – Patients being treated for infertility by ovulation induction with gonadotropins or other agents, such as
clomiphene citrate or letrozole, may develop cysts as part of ovarian hyperstimulation syndrome
2. Pregnancy – In pregnant women, ovarian cysts may form in the second trimester, when hCG levels peak
3. Hypothyroidism – Because of similarities between the alpha subunit of TSH and hCG, hypothyroidism may stimulate ovarian
and cyst growth
4. Maternal gonadotropins – The transplacental effects of maternal gonadotropins may lead to the development of neonatal and
fetal ovarian cysts
5. Cigarette smoking – The risk of functional ovarian cysts is increased with cigarette smoking; risk from smoking is possibly
increased further with a decreased body mass index
6. Tubal ligation – Functional cysts have been associated with tubal ligation sterilizations

Complications = OVARIAN CYST ACCIDENTS

1. Torsion of pedicle
• Involves rotation of ovarian vascular pedicle, causing obstruction to venous and, eventually, arterial flow & infarction
• Patient presents with intense pelvic pain ± symptoms of shock
2. Rupture of ovarian cyst
• Ovarian cyst rupture commonly occurs with corpus luteal cysts
• May be occur in the following conditions:
1. Following torsion of pedicle
2. During bimanual examination
3. During labour when cyst is impacted within pelvis
4. Spontaneous rupture

Clinical Presentation (Symptom)

1. Asymptomatic — ovarian cyst may be picked up incidentally on radiographic studies
2. Pressure symptoms
• Bloating, early satiety, abdominal distention
• Constipation, tenesmus (from rectal compression)
• Urinary symptoms: frequency, urgency, nocturia (from bladder compression)
• Pelvic pain
• Dyspareunia (if mass sits in POD)
3. Symptoms of ovarian cyst accident
• Intense pelvic pain due to torsion
• Haemodynamic shock due to cyst rupture esp corpus luteal cyst
− Generalized abdominal pain
− Board-like rigidity (peritonitis)
− Anaemia
− Low BP, high PR
4. Menstrual disturbances
• Menorrhagia
• Oligomenorrhea / amenorrhea (corpus lutein cyst)
• Post-menopausal bleeding
5. Metastatic symptoms
• Constitutional symptoms: Unintentional weight loss, loss of appetitie
• GIT metastasis: N&V, inanition & colicky abdominal pain (carcinomatosis peritonei resulting in ileus)
• Liver metastasis: RUQ pain, abdominal swelling
• Lung metastasis: Haemoptysis, dyspnea

Physical Examination — refer ovarian carcinoma

Investigation
1. Blood test
• FBC — Hg (assess severity of anaemia), WCC, platelet
• Tumour marker — CA 125 (used complementarily with pelvis US to risk-stratify any cyst found), CEA, αFP & β-hCG
• Others depending on DDx: TFT, PID work up, etc
2. Pregnancy test — may be +ve if corpus luteum cyst
3. Imaging test = Pelvic ultrasounds scan, CT Scan
• If benign, perform diagnostic & therapeutic laparoscopy
• If malignancy is highly suspicious, perform exploratory laparotomy
Treatment
Non-surgical 1. Watchful waiting
(conservative) • If pre-menopausal women and small functional cyst (2cm to 5cm)
• Must follow up with ultrasound & CA 125 serial monitoring
2. OCP
• To reduce the risk of new cysts developing in future menstrual cycles
• To reduce the risk of developing ovarian cancer

Surgical 1. Cystectomy + intraoperative frozen section

• If low RMI & benign features on ultrasound
• Contralateral ovary must be examined to exclude bilateral lesions
2. Exploratory laparotomy if high RMI

Differential Diagnosis of Adnexal Mass

 OVARIAN CARCINOMA
Important Key Words
• Most lethal cancer of gynaecological malignancy with overall survival of 25%
• Peak age 50-70 with 60-70% of patients present with disease spread beyond the pelvis
• Generally asymptomatic unless pressure symptoms
• Spread is intraperitoneal especially involving omentum
• Secondaries to ovary (Krukenburg) usually from GIT, breast & endometrial carcinoma
• Staging is always surgical–pathological, based on findings during exploratory laparotomy

Risk factor
• Increased number of ovulatory cycles
− Nulliparous
− Late age at menopause
• Genetic predisposition
− FHx of breast cancer (BRCA1/BRCA2) – most common
− FHx of HNPCC / Lynch syndrome – a/w ovarian tumour (endometrioid tumour and clear cell adenocarcinoma)
− FHx of cancer of bowel, breast and/or ovary
• Oncogenes / Tumour suppressor genes mutation
− BRCA1/BRCA2
− Her2
− P53
• Gonadal dysgenesis
• Long term oestrogen therapy (HRT)

Protective factor
• OCP – postulated to be due to decreased ovulatory cycles, which decreases incidence of ovarian epithelial damage &
regenerative proliferation
• Prophylactic salpingo-oophorectomy – postulated to be due to prevention of unknown causative agent from entering the
peritoneal cavity through lower genital tract

Route of Spread
1. Direct invasion
2. Lymphatic spread to pelvic & para-aortic nodes
3. Haematogenous spread to lung, liver
4. Transcoelomic spread to POD, paracolic gutters, diaphragm, liver capsule, omentum, bowel serosa & mesenteric
• Tumour exfoliates cells that disseminate & implant throughout peritoneal cavity
• Distribution of intraperitoneal metastases tends to follow circulatory path of peritoneal fluid

Clinical Presentation (Symptom)

4. Asymptomatic — ovarian mass may be picked up incidentally on radiographic studies
5. Pressure symptoms
• Bloating, early satiety, abdominal distention (due to tumour growth & malignant ascites)
• Constipation, tenesmus (from rectal compression)
• Urinary symptoms: frequency, urgency, nocturia (from bladder compression)
• Pelvic pain
• Dyspareunia (if mass sits in POD)
6. Menstrual disturbances (usually due to functional stromal tumour)
• Menorrhagia
• Oligomenorrhea / amenorrhea
• Post-menopausal bleeding
7. Metastatic symptoms
• Constitutional symptoms: Unintentional weight loss, loss of appetitie
• GIT metastasis: N&V, inanition & colicky abdominal pain (carcinomatosis peritonei resulting in ileus)
• Liver metastasis: RUQ pain, abdominal swelling
• Lung metastasis: Haemoptysis, dyspnea
8. Symptoms related to primary malignancy
• Breast primary: lump, nipple discharge, inverted & displaced nipple, and history of breast ca
• GI primary: GI bleeding, altered bowel habit, tenesmus, colicky abdominal pain etc
• Endometrial primary: Abnormal uterine bleeding, abdominal distention
Physical Examination (Sign)
General Examination • Signs of anaemia
• Cachexia
• Lymphadenopathy: Virchow’s node, inguinal lymphadenopathy

Respiratory Examination Pleural effusion, lung nodules (dull percussion, decreased vocal resonance)

Breast Examination Lump, Peau’d orange, abnormal contour, nipple retraction & displacement, nipple discharge &
axillary lymphadenopathy

Abdominal Examination • Abdominal mass / distention

• Hepatosplenomegaly (metastasis)
• Shifting dullness (malignant ascites)

Pelvic Examination • Speculum examination: Assess cervix for presence of blood

• Bimanual palpation: Assess uterine size, adnexal mass & their mobility with respect to cervix
Rectovaginal Examination Assess mass in POD

Classification
Ovarian tumours can be subclassified based on tissue of origin. Why? – Because they are distinct entities / different disease
prognosis and response to treatment

Metastatic Tumor
• Primary sites:
1. Most are from mullerian primaries = Uterus, fallopian tube, contralateral ovary, pelvic peritoneum
2. Others = GIT (colon, stomach, biliary tract, pancreas) and breast
3. Krukenberg tumours from GI and breast
• Suspect if
− Small, bilateral ovarian tumour – both ovaries are enlarged
− More ovarian surface involvement than stroma
− Mucinous tumour
Other Classification Systems for Ovarian Cancer
1. Novak’s Classification 1967 — depends primarily on 2 fundamental factors; benign or malignant and solid or cystic. Thus the
borderline tumors, solid tumors with cystic degeneration and predominantly cystic tumors with solid areas fall into grey zone.
2. International Federation of Gynecology and Obstetrics (FIGO) histological classification
3. World Health Organization (WHO) Classification of Ovarian Tumors

SURFACE EPITHELIAL TUMOURS

• Commonest type of ovarian carcinoma & out of all surface epithelial tumour, serous type is the commonest
• Mullerian origin and derived from coelomic epithelium that lines the ovary
• Coelomic epithelium embryologically produces the epithelial lining of the fallopian tube (serous cell), endometrium and
endocervix (mucinous cell)
• CA-125 = serum marker to monitor treatment response and screen for recurrence

Classification
Benign • No metastatic potential
• Non-invasive and demonstrate minimal cytologic atypical change
• Example
1. Serous cystadenoma
2. Mucinous cystadenoma
3. Serous cystadenofibroma
4. Adenofibroma
5. Benner tumour
Bordeline • Tumours that have some features of malignancy such as proliferation and high grade cytologic
atypia but lack stromal invasion (low malignant potential)
• Most commonly serous and mucinous type
• 5 year survival > 95%
• Recurrence in 5-12% especially where implants are seen
Malignant • Most common ovarian carcinoma 70%
• Associated with BRCA and p53 gene mutations
• Typically present at advanced stage hence poor prognosis
• Many are associated with tubal intraepithelial carcinoma of the fallopian tube
• Microscopic features
− Papillae or micropapillae
− Psammoma bodies
− Other features of neoplasia
− Invasion

Type
Serous tumour • Contains clear fluid
(Cystic) • Often bilateral COMMONEST TYPE OF OVARIAN CANCER  
• Around age of menopause
• Molecular / cytogenetics description
− Low-grade carcinomas (grade 1) mostly express BRAF and KRAS mutations
− High grade invasive carcinomas (grade 2 and 3) express nonsynonymous p53 mutations
Mucinous tumour • Large tumour
(Cystic)   • Multiloculated & filled with mucin
• If ruptured pseudomyxoma peritonei
• 1° is RARE, always metastatic mucinous tumour
− Primary site = Appendix, colon, pancreas
− Macroscopic feature
o Bilaterality – both ovaries enlarged
o Nodular surface
o Pseudomyxoma peritoneii or ovarii – typically a/w appendix tumour
− Different cytokeratins may help localized the 1° tumour to GIT (Cytokeratin 7- and 20+)
Endometrioid tumour • 2nd most common type of surface epithelial tumour
• Arises form endometriosis
(endometrioid • Up 1/3 have simultaneous tumour in the endometrium
adenocarcinoma) • Microscopic feature = tubular gland resembling endometriosis, characteristic squamous morules
NB: Endometriosis
− Precursor for ovarian carcinoma
 − Ovarian tumour types with endometriosis
1. Endometrioid 28%
2. Clear cell 49%
3. Mucinous 4%
4. Serous %
Clear cell tumour • Macroscopic feature =Polypoid masses that protrude into the cyst.
• Microscopic feature = clear cells (that contains glycogen) and hobnail cells, The pattern may be
glandular, papillary or solid
• Poor prognosis
• Can be a/w endometriosis
Benner tumour • Benign but it can be an endometrial pathology since it is hormone producing
• Occur in reproductive life
• May be associated with endometrial hyperplasia
• May coexist with mucinous cystadenoma
• Microscopic feature = Transitional cell (bladder-like cell), may have microcyst

Serous carcinoma of ovary. They partly solid & partly cystic. Gross appearance of mucinous ovarian neoplasm
The tumors are multiloculated & filled with mucin

Mucinous tumour Endometriod tumour

Benign Brenner tumour Clear cells containing glycogen (hobnail cells)

 GERM CELL TUMOUR
• Derived from germ cells
• More common in younger females and young adult (reproductive age)
• Most common is benign cystic teratoma – but malignant forms exist
• Very similar to testicular tumour
• Tumour subtypes mimic tissues normally produced by germ cell
1. Fetal tissues = cystic teratoma and embryonal carcinoma
2. Oocytes = Dysgerminoma
3. Yolk sac = Endodermal sinus tumour
4. Placental tissues = Choriocarcinoma

Classification
Benign (mature) • Mature cystic teratoma
− Dermoid cyst
− Bilateral 10%
− Unilateral = skin, bone, cartilage, teeth, hair, keratin, tissue resembling mature adult-
type tissue
• Struma ovarii
− Ectopic thyroid tissue – can produce hyperthyroidism
Malignant (Immature) • Immature teratoma
• Can cause
− Squamous carcinoma
− Carcinoid
− Thyroid carcinoma
• Resembling fetal tissue
• The greater the amount of immature tissue, the greater the risk of spread
• Seen in younger patient

Type
Teratoma • Solid
• Dermoid cyst (Benign cystic teratoma)
• Monodermal (e.g struma ovarii, carcinoid)

Dysgerminoma • Ovarian “seminoma”.

(Malignant) • Microscopic feature
− Large, clear cytoplasm and central nuclei (resemble oocytes)
− Fibrous tissue
− Lymphocyte
• Uncommon – seen in childhood and young adult
• All are malignant
• No endocrine function
Yolk sac tumour • Endodermal sinus tumour = mimic yolk sac
(Malignant) • Serum AFP = tumor marker
• Microscopic features
− Schiller duval body (glomerulus-like structure)
− Hyaline droplets
• Rapid growth and agrressive
Choriocarcinoma • Malignant tumour composed of trophoblast and syncytiotrophoblasts
(Malignant) • Mimics placental tissues but villi are absent
• Can only be an ovarian 1° if prepuberty
• hCG = tumour marker (secreted by syncytiotrophoblast)
• Aggressive
• Metastasis via haematogenous spread all over the body
Mixed germ cell
tumour
Embryonal carcinoma • Malignant tumour composed of large primitive celss
Malignant • Aggressive with early metastasis
 SEX CORD-STROMAL TUMOURS
• Derived from ovarian mesenchyme
• Can produce hormone
• Clinical features = premature menarche, breast and endometrial carcinoma and virilisation (from testosterone)
• Often yellow in color, which indicates hormone-producing tumour
Granulosa-theca cell • Example
tumor − Granulosa cell tumour (adult / juvenile type) – coffee bean shaped nuclei, central
nuclei grooves
Granulosa cell = Benign − Fibroma-thecoma tumour group
Theca cell = Malignant o Example
1. Sclerosing stromal tumour
2. Stromal tumour with minor sex cord elements
o Usually unilateral
o Microscopic features = fibroblast and thecal cells
o A/w ascites and hydrothorax
• Epidemiology
− Accounts for 5% of all tumour
− 2/3 occur in postmenopausal women
• Produce hormone
• Oestrogen – in older women, often a/w endometrial hyperplasia, breast disease,
endometrial ca
• Androgenic steroid = virilising effect
• Macroscopic feature
− Usually unilateral
− Any size
− Yellow if produce hormones
• Microscopic feature = Most are composed entirely of granulosa cells or a mix of
granulosa and theca cells
Granulosa component Thecoma component
• Small cuboidal cells • Clusters or sheets of cuboidal
• Cord, sheets or strands to polygonal cells
• Call-Exner bodies
Fibroma • Benign tumour of fibroblasts
• A/w pleural effusions and ascites
• Meigs syndrome = combination of ovarian fibroma, ascites and pleural effusion
• Syndrome resolves with removal of tumour
Sertoli-stromal cell • Composed of sertoli cells that form tubules and Leydig cells (between tubules) with
tumour; characteristic Reinke crystals
• May produce androgen (androblastomas) = a/w hirsutism and virilisation
• Example
1. Sertoli cell tumour
2. Leydig cell tumour
3. Retiform
4. Mixed
Sex cord tumour with
annular tubules
Gynandroblastoma
Steroid (lipid) cell
tumour
FIGO staging system (2014)
• Stage I – confined to the ovaries
Ia – unilateral
Ib – bilateral
Ic – ascites present or ovarian capsule breached
• Stage II – extension to other pelvic structures.
• Stage III – abdominal peritoneum involved.
• Stage IV – distant metastases
Investigation
Diagnosis of ovarian cancer is made only after intraoperative frozen section; hence pre-operative workup primarily focuses on
evaluating the likelihood of malignancy, which will determine whether or not exploratory laparotomy is needed

Pre-Operative Investigation
1. Detailed history and physical examination to look for risk factors for malignancy

2. Baseline Investigation for Pre-Operative Work-Up

• FBC: Hg, WCC & Platelet
• GXM
• RP: Urea & creatinine
• LFT: Liver enzymes & albumin
• Coag: INR, PT & aPTT
• ECG
• CXR

3. Serum Tumour Markers

CA 125 • Secreted by cells of mesothelial origin; most useful for non-mucinous epithelial ovarian tumour
• False negative in pre-menopausal women
1. Fibroid
2. PID
3. Endometriosis
4. Pleural & pericardial inflammation
αFP Germ cell tumour marker (yolk sac tumour)
β-hCG Germ cell tumour marker (choriocarcinoma)
CEA Mucinous ovarian tumour marker
LDH Germ cell tumour marker
Suspect non-germ cell tumour in older age group, hence CA 125 & CEA are sufficient
Suspect germ cell tumour in younger age group (<40), hence LDH, αFP & β-hCG are sufficient

4. Radiological Investigation
Pelvic ultrasound • 1st line investigation
• TVUS is more preferable than TAS due to its increased sensitivity
• To look for ultrasound features of malignancy
Malignant Benign
Multilocular cyst Unilocular cyst
Irregular solid areas Cystic, no solid area, smooth wall
Septation No septation
At least 4 papillary projection Presence of acoustic shadowing, no papillary projection
Very strong blood flow No blood flow
Largest diameter ≥ 100mm Largest diameter ≤ 100mm
Bilateral Unilateral
Ascites No ascites
• May help to determine whether or not further investigation are needed
MRI Pelvis • Not perform on routine basis due to high cost & limited availability
• Only useful when ultrasound findings are unclear
• Higher specificity over ultrasound
CXR To look for signs of lung metastasis i.e. canon ball lesion
CT TAP • To look for distant presence of distant metastasis e.g. liver, lung, GIT & nodal metastases
• If presence, it is mandatory to do exploratory laparotomy + omentectomy + peritoneal washout &
cytology

5. Investigation for possible primaries

• Uterine primary: Endometrial biopsy or sampling
• Breast primary: Mammogram
• GI primary: Faecal occult blood ± endoscopy
Risk Malignancy Index
• RMI is an appropriate tool for patient referral
• RMI combines 3 presurgical features
1. Serum CA-125 (CA-125)
2. Menopausal status (M); and
3. Ultrasound score (U)
• The RMI is a product of the ultrasound scan score, the menopausal status and the serum CA-125 level (IU/ml) as follows:

RMI = U x M x CA-125

Ultrasound score (U)

• The ultrasound result is scored 1 point for each of the following characteristics:
1. Multilocular cysts
2. Solid areas
3. Metastases
4. Ascites and
5. Bilateral lesions
• Scores:
U = 0 (for an ultrasound score of 0)
U = 1 (for an ultrasound score of 1)
U = 3 (for an ultrasound score of 2–5)

Menopausal Status (M)

• The menopausal status is scored as
1 = premenopausal
3 = postmenopausal
• Postmenopausal can be defined as women who have had no period for more than one year or women over the age of 50 who
have had a hysterectomy

Serum CA-125 (S)

Serum CA-125 is measured in IU/ml and can vary between zero to hundreds or even thousands of units.
Treatment

OVERVIEW
Perform exploratory laparotomy in cases where ovarian malignancy is suspected
⇩
Careful inspection of all peritoneal structures
⇩
Ascitic fluid cytology
⇩
If no gross diseases beyond ovaries → TAHBSO + Biopsy
If gross diseases beyond ovaries → Debulking surgery (cytoreduction)
⇩
Followed by 6 cycles of adjuvant chemotherapy depending on final stage & HPE results
⇩
If recur during / after cycles – start 2nd line of chemo (add a stronger chemo drug)

Exploratory Laparatomy
Objectives
1. Staging of disease — prognosis & treatment depend upon surgical findings & subsequent stage
2. Cytoreduction (debulking)

Treatment Principle
• Midline, vertical incision
• Careful inspection of all peritoneal structures, liver, spleen, large & small bowel, stomach & diaphragm
• Ascitic fluid (150-200ml) must be obtained, if no ascites then peritoneal washout must be done. Sample is sent for HPE &
cell block for malignant cell
• If no gross diseases beyond ovaries, perform TAHBSO + take biopsies from omentum and pelvic & para-aortic lymph node
• If gross disease beyond ovaries, perform debulking surgery (goal is leave no residual tumours or implants)
• Appendicectomy may be performed in both cases
• Patient must be counseled regarding possibility of bowel resection & colostomy
• If young patient — consider conservative exploratory laparotomy involving unilateral salpingo-oophorectomy instead of
TAHBSO and offer Frozen section
• The need for adjuvant chemotherapy depends on final stage & HPE results
− All debulking surgery must be followed by 6 cycles of chemotherapy
− If debulking surgery is not required, chemotherapy may still be needed if HPE results reveal epithelial or germ cell
tumuor. The common standard regime is as follows:
Epithelial Ovarian Carcinoma = Paclitaxel / Carboplatin
Germ Cell tumour = Bleomycin / Etoposide / Cisplatin

Chemotherapy
Pre-chemo assessment includes:
1. FBC
2. RP inc Ca2+ & Mg2+
3. LFT
4. Tumour markers: CA 125, CEA, αFP & β-hCG
5. 24hour urinary creatinine clearance

Follow up after completion of chemotherapy

• Patient should be seen in Gynae-Oncology Clinic
Once every 3 months in the 1st year
Once every 4 months in 2nd year
Once every 6 months in 3rd to 5th year
Annually thereafter if no evidence of recurrent
• Tumour markers should be taken one week prior to visit
• During each visit, other than general examination, an abdominal & pelvic scan must be performed to look for ascites or pelvic
mass

Definition & Terminologies
Natural / Spontaneous
Menopause
Induced / Iatrogenic Menopause
Early Menopause
Premature Menopause
Perimenopause
Early Postmenopause
MENOPAUSE
The time of the final menstrual period (FMP) of a woman, confirmed after 12 months of
period of amenorrhea in the absence of any obvious causes
Permanent cessation of menstruation after induced termination of ovarian function
• Chemotherapy / Radiotherapy
• Bilateral oophorectomy (surgical menopause)
Menopause occurring at ≤ 45 years old
Menopause occurring at ≤ 40 years old
Period of time when menstrual cycle and endocrine changes occur around the time of natural
menopause (before FMP)
Period of time within 5years after the FMP

Physiology
• Menopause occurs when the supply of oocytes become exhausted
• A newborn girl has 1.5million oocytes in her ovaries, 1/3 are lost before puberty
• During reproductive years 20-30 primordial follicles develop per cycle & become atretic
• A woman has an average 400 cycles during her lifetime; therefore the majority of oocytes are lost spontaneously (through
atresia) rather than through ovulation
• In perimenopausal years, the granulosa cells produce oestrodial but as menopause approaches this production are reduced
• The proportion of anovulatory cycles increases and progesterone production is reduced
• The fall in oestrogen results in loss of negative feedback & FSH & LH rise
• The relationship of the last period to the rise in FSH is not constant & FSH / LH levels may be raised for months / years
before menopause
• After the menopause the oestradiol production from the ovary is negligible
• Circulating androstenedione produced by the adrenals is converted to oestrone in adipose cells. Obese women therefore have
higher circulating oestrogen levels & are at greater risk of endometrial hyperplasia & cancer
• Oestrone is a less potent oestrogen than oestradiol
• Androstenedione & testosterone production continues from postmenopausal ovary

Clinical Consequences of Menopause

Short-Term Consequences Long-Term Consequences
1. Hot Flushes 1. Osteoporosis
2. Psychological symptoms: Mood disturbances, irritability, 2. Cardiovascular diseases & stroke
depression, insomnia, fatigue 3. Dementia
3. Dermatological symptoms: Loss of skin collagen 4. Endometrial hyperplasia & cancer
4. Menstrual changes: Irregular period • Frequency of anovulatory cycle in postmenopausal
5. Urogenital changes: Atrophic vaginitis, urinary women increases hence this lead to higher risk of
incontinence endometrial hyperplasia & cancer due to unopposed
oestrogenic effect on endometrium

Hot Flushes
• Average duration of each flush is 4 minutes
• Worst late perimenopausal period in
• Clinical Feature
1. Sudden, intense hot feeling over face & chest
2. ± Warning feeling or ‘aura’ beforehand
3. ± Palpitations, sweating, nausea, dizziness, anxiety, headache
4. Flushing & perspiration
5. Night sweats disturb sleep
6. Knock-on effects of tiredness / depression / poor performance
• Pathophysiology
2° to hormonal changes at menopause
⇩
Severity of symptoms Reduced oestrogen
related to suddenness of ⇩
onset of menopause i.e. Pulsatile release of increased levels of gonadotrophins (FSH & LH)
surgical menopause ⇩
  Hot flush
Menstrual Changes
• Periods become more irregular beginning from early perimenopausal period due to more frequent anovulatory cycles
• As a result of anovulation, continued unopposed oestrogenic effect on endometrial proliferation may also lead to menorrhagia
and polymenorrhea when menstruation does occur

Urogenital Changes
1. Atrophic vaginitis
• Lower oestradiol levels results in thinner skin at vulva & vagina, decreased secretions & loss of elasticity & cellular
glycogen
• Vagina shrinks in diameter & becomes more prone to splitting & tearing
• Patient may also complain of dyspareunia, unpleasant dryness or discharge
• Most common cause of postmenopausal bleeding
• Vaginal oestrogen cream / pessaries are effective
2. Bacterial vaginosis
• Reduced glycogen bad for lactobacilli, pH increases allowing colonization by anaerobic bacteria leading to bacterial
vaginosis
3. Urinary incontinence

Osteoporosis
• Oestrogen deficiency results in osteoclastic activity in bone to exceed that of osteoblasts, leading to increased rates of bone
loss following menopause
• 10-15 years following menopause, risk of fractures in women is 3-5x greater than men
• Bone loss is most marked at trabecular bone (vertebrae, femoral neck & wrist) → increased risk of fracture (vertebral
compression fracture, hip fracture, Colles’ fracture)
• Risk factors: Low BMI, smoking, caucasion

Cardiovascular Disease & Stroke

• Oestrogen deficiency formerly thought to be major contributor
• Risk factor: BP, cholesterol, weight, DM, FHx, smoking, low exercise, diet high in fats

History Taking
Menopausal symptoms
• General (hot flushes, mood changes)
• Menstrual changes (menstrual irregularities, abnormal uterine bleeding)
• Urogenital changes (dyspareunia, vaginal dryness, vaginal discharge, urinary incontinence)
Menstrual History
• LMP
• Age of menarche
• Menstruation period
• Cycle length
• Regularity
Gynaecological History
• Last Pap smear done + mammogram
• Contraceptive use
Obstetric History
• Previous pregnancies & related conditions
PMHx
• DM, HTN & dyslipidaemia
• CVR diseases (IHD, stroke)
• VTE
• Hepatic ± gallstone disease
• Hx of cancer esp breast cancer or gynaecologic
Past Surgical Hx of surgical intervention
Drug & allergies
SHx
• Smoking, drinking
• Functional status
FHx
• Hx of cancer esp breast cancer or gynaecologic
Physical Examination
General Examination
• Height, weight, BMI
• BP, quick cardiovascular examination
• Pallor (esp if AUB)
Breast examination
• Abdominal Examination
• Inspect for scars from previous abdominal & gynaecological surgeries
• Palpate for tenderness & masses
• Percuss for shifting dullness (if mass)
Pelvic Examination
• Inspect vulva for any pathology (POP, stress urinary incontinence after asking patient to cough)
• Speculum examination to visualize cervix & vaginal vault + Pap smear
• Bimanual palpation to assess uterine size & presence of adnexal masses

Diagnosis of Menopause
• Clinical diagnosis
• Made retrospectively when a woman has no menstruation for 1 year
• Serum FSH > 30 U/L usually indicative of menopause

Investigation
Baseline Investigation • FBC → Assess for anaemia esp if AUB, WCC if infection
• ESR, CRP → Inflammatory markers
• Lipid profile → Menopause increases risk of getting CVD disease & dyslipidaemia
• Serum glucose (RBS, FBS, HbA1C)

Investigation to • Serum FSH / LH → FSH > 30 U/L usually indicative of menopause

Confirm Diagnosis • Serum estradiol → Low level in menopausal women

Investigation for • FBC → Anaemia 2° to AUB, WCC if vaginitis

Complication of • Pelvic USG for endometrial thickness, endometrial biopsy via DD&C ± hysteroscopy (gold
Disease standard) → Endometrial hyperplasia & ca
• Urinalysis & urodynamic studies → Urinary incontinence
• DEXA scan → Osteoporosis

Screening Recommendations in Menopausal Women

1. Cervical Cancer Screening → Pap smear, if abnormal proceed with colposcopy
2. Breast Cancer Screening → Mammogram if > 40
3. Osteoporosis Screening → DEXA scan

Cervical Cancer Screening

Recommendations
• All women who are, or who have been sexually active, between the ages of 20 and 65 years
• Pap smear every 3 years provided results do not indicate otherwise (if 1st two consecutive Pap results are negative, screening
every 3 years is recommended)
• Last Pap smear at 65 years old provided results do not indicate otherwise (Pap smear is not necessary if age > 65)
Special considerations
• Virgo intacta (never had sexual intercourse before) do not need Pap smear but need to be counseled that they are not at zero
risk of getting cervical cancer
• Women who have taken HPV vaccination still nedd to follow standard Pap smear screening recommendations as vaccine do
not protect against every strain of HPV, just the most common ones

Breast Cancer Screening

Recommendations
• Mammography for women who are asymptomatic & have no RFs for breast cancer to begin from age 40 years old
• Mammography annually from 40-49 years old then once every 2 years from 50-65 years old
• After 65 years old, screening mammography may be less beneficial, hence no indication for further mammography on generic
basis
Special considerations
• Women on HRT have higher risk of breast cancer, hence should be screened annually from 40-49, then once every 2 years
from 50 years old until 5 years after cessation of HRT
• Women with increased risk of breast cancer i.e. BRCA gene, strong FHx; should have monthly breast self-exam + 6-monthly
clinical breast exam + annual mammogram beginning 5 years before the age of onset of the earliest breast cancer diagnosed
in the family

Osteoporosis Screening
• Recommendation: Dual energy X-ray absorptiometry (DEXA) scan of lumbar spine & hip for women to be performed above
the age of 65 years old
• DEXA scan yields 3 results:
1. BMD — average value 1.5g/cm3
2. T-score
o Number of SDs from average BMD of a healthy 30-year-old individual of same gender & ethnicity
o Used primarily to diagnose osteoporosis
o Osteopenia: T-score -2.5 to -1
o Osteoporosis: T-score ≤ -2.5
3. Z-score
o Number of SDs from average BMD of an age-matched control of the same gender & ethnicity
o Used primarily to determine presence of pathological causes of decreased BMD
o Z-score < -2 suggests presence of a pathological cause of osteoporosis e.g LT steroid use or hyperparathyrodism
• Example

• Calculation of fracture risk: WHO Fracture Risk Assessment Tool (FRAX)

• FRAX score indicates
• 10-year probability if hip fracture
• 10-year probability of major osteoporotic fracture
• It also useful as an adjunct to determine treatment or prevention of osteoporosis in combination with DEXA scan

Treatment
Treatment is symptom specific
1. General menopausal symptoms
2. Urogenital symptoms
3. Osteoporosis
4. Other Long-term Complications
• CVD
• Stroke
• Dementia
Treatment
General menopausal Conservative Treatment
symptoms 1. Cool showers, loose fitting clothes, cool environment
2. Relax, exercise, hobbies etc for mood changed
3. Psychological support & counseling
4. Acupuncture / Homeopathy

Pharmacological Treatment

Hormonal Principle: Oestrogen supplementation is the basis of HRT

Type
1. Oestrogen-only HRT for women with hysterectomy
2. Combination HRT for women with uterus e.g. COCP or Mirena IUCD

Mode of administration
PO, transdermal patches, s/c implants, topical (vaginal cream or pessaries)

Side Effects
1. Endometrial cancer
2. Breast cancer
3. Venous thromboembolism
4. Cardiovascular
5. Minor side effects: Nausea, breast tenderness

Contraindication
1. Any irregular vaginal bleeding that has not been fully investigated
2. Pregnancy
3. Venous thromboembolism
4. Liver disease
5. Breast cancer
6. Any oestrogen dependent tumour
Non-hormonal 1. Natural phyto-oestrogens (legumes plant)
(alternative to • Examples: Black cohosh, red clover
HRT for 3. Tibolone (STEAR)
menopausal • Selective tissue estrogenic activity regulator (STEAR)
symptoms) • It is a synthetic steroid that affects oestrogenic, progestogenic &
androgenic receptors
• It can be started > 2 years after FMP
• It is an alternative to higher dose oestrogen-progesterone preparations
4. Raloxifene (SERM)
• Selective estrogenic receptor modulator (SERM)
• It has oestrogenic effect on bone & lipid metabolism but minimal effect
on breast & uterine tissue
2. Clonidine: Central acting alpha agonist, which reduced vasomotor symptoms;
poor efficacy
3. Anti-depressant (Paroxetine)

Urogenital symptoms Conservative Treatment

1. Pelvic floor exercises
2. Pads / Incontinence diapers
3. Lubricant

Pharmacological Treatment
1. Topical oestrogen HRT (pharmacological option of choice for isolated urogenital symptoms in
menopause)
2. Systemic HRT (effective for urogenital symptoms but shouldn’t be used for this indication alone)

Surgical Treatment (esp for stress urinary incontinence)

1. Burch colposuspension
2. Tension-free vaginal tape
Osteoporosis Conservative Treatment
1. Healthy diet
2. Weight-bearing exercise ≥ 30 min/day
3. Good nutrition inc dietary Calcium
4. Stop smoking

Pharmacological Treatment
1. Ca2+ & Vitamin D supplementation
2. Bisphosphonates
3. Initial treatment of choice for women with diagnosed osteoporosis
4. Examples: Alendronate, Risedronate
5. SERM
• Raloxifene
o The best choice for both prevention & treatment of osteoporosis
o Good option for women who have been on HRT but would like to switch to an alternative
or those with FHx of breast ca (Raloxifene has no breast cancer risk just like HRT)
• Tamoxifen – not FDA approved for osteoporosis
6. HRT – many SES if long term used
7. Tibolone – many SES if long term used
8. Strontium ranelate
• An option that is good at reducing risk of vertebral fractures in postmenopausal osteoporotic
women & to a lesser degree, the risk of other osteoporotic fractures

Other Long-term 1. Manage risk factors

Complications 2. Screen for DM, HTN, dyslipidaemia, VTE
CVR, stroke, dementia 3. HRT is not recommended for prevention of these long term complications as HRT increases risk of
getting CHD, stroke & VTE
COMMON MEDICATION IN O&G
 COMMON PROCEDURES & INVESTIGATION IN O&G
Common Procedures & Investigations
1. Imaging: US (TAS & TVS)
2. Endometrial biopsy
• Pipelle endometrial biopsy
• Hysteroscopy + Dilatation & Curettage (D&C)
3. Colposcopy
4. Laparoscopy
5. Abdominal surgery
• Abdominal hysterectomy
• Salpingo-oophorectomy
• Myomectomy
• Tubal reconstructive surgery
• Abdominal sacrocolpopexy
• Burch colposuspension
6. Vaginal surgery
• Vaginal hysterectomy
• Anterior / Posterior colporrhaphy
• Sacrospinous ligament fixation
• Endometrial ablation
• Cervical treatment
− LLETZ
− Polypeptomy
− McDonald / Shirodkar suture

Imaging: Pelvic Ultrasound (TAS or TVS)

• Transabdominal US (TAS) or transvaginal US (TVS) is the imaging modality of choice for pelvic structures
• General uses for pelvic US:
1. May be used to identify pelvic mass (uterine, adnexal, cul-de-sac, ovarian masses e.g. solid or cystic)
2. Determine endometrial thickness & lining esp in women with postmenopausal bleeding or in cases where uterine
pathologies i.e endometrial hyperplasia or ca is suspected
3. Locate/characterize fibroids
4. Monitor follicles during assisted reproduction
5. Identify ectopic pregnancy, intrauterine pregnancy
− TVS provides better resolution of uterus and adnexal structures
− It detects early pregnancy if serum βhCG > 1000 IU/L whereas TAS can only detect pregnancy if serum βhCG >
5000 IU/L
• TAS vs TVS
TAS TVS
• Major technique for imaging in 2nd and 3rd trimester • Method of choice for
• Patient to have full bladder because 1. Monitoring infertility disorders
1. Pushes the uterus out of the pelvis 2. Diagnosis of ectopic pregnancy
2. Provides an acoustic window 3. Differentiation of normal and abnormal 1st trimester
3. Displaces pelvic bowel loop superiorly pregnancy
• Real-time ultrasound equipment includes: 4. Diagnosis of congenital anomalies in 2nd trimester
− Sector transducers, when access is limited • Patient to have empty bladder because uterus will be
− Linear curved array transducers, for less distortion pushed posteriorly out of the field of view of the
and greater field of view transducer
• Specially designed high frequency transducers
• Higher resolution images
• Favorable for obese patients or in early stage of
pregnancy
• Limitations include
1. Reduced beam penetration
2. More invasive nature of the technique
Endometrial Biopsy

Methods available
1. Aspiration curettage (Pipelle)
• Pipelle is a flexible polypropylene suction cannula with an outer diameter of 3.1mm
• It is performed in the office using an endometrial suction curette guided through the cervix to aspirate fragments of
endometrium
• Pre-treatment with misoprostol (Cytotec®) if nulliparous or postmenopausal to soften the cervix prior procedure
• Advantages: Outpatient procedure, no GA risks
• Disadvantages: It is a blind technique that may miss focal lesions, if biopsy is not diagnostic, may need D&C
• Other outpatient endometrial biopsy techniques: Vabra aspirator, Karman cannula, Novak or Kevorkian curette
2. Hysteroscopy ± Dilatation & Curettage (D&C)
• Passage of telescope per vagina through cervix to allow visualization of endometrial cavity
• “Dilation” refers to dilation of the cervix & “curettage” refers to scraping or removal of endometrial mucosa lining with
surgical instrument called a curette
• Type of anaesthesia: GA, Regional Anaesthesia or LA (paracervical block)
• Indications for D&C
Diagnostic Indications for D&C Therapeutic Indications for D&C
1. Postmenopausal bleeding 1. Removal of POC in abortion
2. AUB after failed medical therapy 2. Removal of endometrial polyp
(D&C are indicated in these 2 cases to exclude endometrial 3. Resection of submucosal fibroid
hyperplasia & ca) 4. Treatment of intrauterine adhesions / septum
3. Diagnosis of endometrial polyp 5. Treatment of molar pregnancy
4. Diagnosis of submucousal fibroid 6. Endometrial ablation (TCRE, rollerball etc) for
5. For investigation of infertility postpartum haemorrhage & HMB after failed
medical therapy

• D&C is the It is also used for removal of IUCD

• Complications:
1. Intrauterine adhesions
2. Cervical injury / trauma
3. Uterine perforation
4. Visceral injury if perforation occurs using a sharp instrument
5. Haemorrhage
6. Infection (rare)
Colposcopy

Definition
Colposcopy is a way of looking at the cervix through a special magnifying device called a colposcope. It shines a light into the
vagina and onto the cervix. A colposcope can greatly enlarge the normal view. This exam allows the health care provider to find
problems that cannot be seen by the eye alone.

Objectives
1. Determine the presence of invasive cancer
2. Localizes SCJ
3. Identifies the most severe disease for biopsy
4. Evaluate extend of disease

Indication & Contraindication of Colposcopy

Indication Contraindication
1. Abnormal Pap smear 1. Active, inflammatory cervicitis
2. Treatment & follow up of CIN 2. Non-cooperative patient
3. Bleeding disorders: Post-coital, post-menopausal & HMB 3. Postmenopausal patient who is not estrogen-primed
4. Persist vaginal discharge 4. Heavy menses
5. Unhealthy cervix
6. HPV +ve / external vulval warts
7. History of intrauterine DES exposure
8. Evaluation of sexually assault victims

Steps in Colposcopic Exam

1. Explain the procedure and obtain informed consent
2. Obtain a relevant medical history
3. R/O pregnancy
4. Perform bimanual exam if not already done
5. Examine vulva
6. Insert speculum
7. Examine cervix using low power (inflammation, infection, leukoplakia, punctation, mosaicism, abnormal vessels)
8. Obtain KOH/WP, cultures and/or pap, if needed
9. Use green filter and normal saline
• Green light is used for vascular
pattern of cervix. The green light
absorbs the red color & makes
the appearance of vessels black
• Abnormal blood vessel patterns:
10. Apply 5% acetic acid. Repeat Q 5 min.
11. Scan entire cervix with white light. Start with low power and move to higher magnification to document abnormal vascular
patterns
12. Use endocervical speculum if needed to view entire transformation zone
13. The entire TZ, including SCJ, and borders of all lesions must be visualized in order for colposcopy to be satisfactory
14. Apply Lugol’s iodine solution to aid in delineating potential biopsy site

Acetic acid Lugol’s solution

• Dehydrate cells • Iodine is taken up by normal cells with high glycogen
• Abnormal areas appear white (aceto-white) because of content
decreased glycogen • Non-staining is abnormal

Color changes after application of Lugol’s solution:

15. Perform endocervical curettage, if indicated:

• Glandular lesion
• Unsatisfactory colposcopy
• Normal colpoposcopy of ectocervix, yet abnormal cytology
• CONTRAINDICATED in pregnancy or active cervicitis
16. Mentally map abnormal areas
• Mild acetowhite < Intensely acetowhite
• No blood vessel pattern < Punctation < Mosaicism
• Diffuse vague borders < Sharply demarcated borders
• Follows normal contours of the cervix < “humped up”
• Leukoplakia – usually a very good (condylomata) or very bad sign
• Atypical vessels – usually cancer
• Normal iodine reaction (dark) < Iodine-negative epithelium (yellow)
17. Perform cervical biopsies, if necessary
• Biopsy posterior areas first
• A depth of 3 mm is adequate
• Biopsy area of the lesion with worst features and closest to SCJ, include the area with atypical vessels
18. Apply pressure and Monsel’s paste to bleeding sites after biopsy
19. Remove speculum and inspect vaginal walls, vulva, perineum, and perianal areas
20. Allow patient to recover
21. Document findings
22. Discuss findings with patient and give post-procedure instructions
Post-Procedure Instructions to Patient
1. No douching, intercourse, or tampons until spotting subsides
2. Return for foul odor or discharge, pelvic pain, profuse bleeding or fever
3. Tylenol, ibuprofen, or Aleve may be used for cramping (Patient may experience pain)
4. Otherwise, follow-up is usually 1-3 weeks to discuss histology results and definitive therapy
5. Encourage contraception once definitive therapy completed
6. Re-emphasize the relationship of cervical dysplasia with STDs, smoking, and non-monogamous sexual practices
7. Stress patients life-long risks of HPV infection

Complication
1. Bleeding; solution:
• Reapply Monsel’s solution
• Saturate the end of a tampon with Monsel’s and insert to provide pressure and astringent action for persistent oozing
• Cauterize the biopsy site
• Inject 1-2 cc of 2% lidocaine with epinephrine into the bleeding site
• Rarely, a cervical stitch of 4-0 absorbable suture across a deep biopsy site
2. Infection is rare but typically occurs on the 3rd or 4th day after biopsy
3. Avoid biopsy with active cervicitis
4. Pain can be minimized by caring and careful explanation of procedure, a warm room, NSAIDs given the night before and
morning of procedure (Avoid Aspirin)
5. Missing disease – lack of correlation between pap cytology and subsequent histology

n.b. Transformation Zone

Colposcopic Findings
Normal findings
Laparoscopy

Definition: The passage of a telescope into abdominal cavity to allow inspection of pelvic & abdominal organs

Indication
Diagnostic Indication Therapeutic Indication
1. Unexplained pelvic pain 1. Ovarian cystectomy (benign lesion)
2. Subfertility 2. Salphinostomy / Salpingotomy
• To inspect uterus, tubes & ovarian 3. Salphingectomy
• Chromopertubation: Dye is instilled per vaginam into 4. Salpingo-oophorectomy
the uterus to assess tubal patency 5. Sterilisation
3. Investigation of adnexal masses 6. Adhesiolysis
4. Staging of endometriosis 7. Hysterectomy (TLH, LAVH)
5. Diagnosis of ectopic pregnancy 8. Myomectomy
9. Advanced prolapse surgery

Procedure
1. General anaesthesia
2. Semi-lithotomy position
3. Bladder empties to avoid bladder injury
4. Cervix cannulated to facilitate anteversion of uterus & visualization of pelvic organs
5. Skin incision in umbilical base
6. Verres needle inserted in umbilical base until tip of needle in peritoneal cavity
7. CO2 insufflated via Verres to achieve intraperitoneal pressure of 20-25mmHg
8. Primary trocar is then inserted at umbilicus & allows passage of laparoscope
9. Secondary ports may be inserted under direct vision
10. Gas expelled & instrument withdrawn at completion of procedure

Complications
• Pre-op
1. GA complications e.g. cardiac & respiratory problems
2. Allergic reaction
3. Anaphylaxis
• Intra-op
1. Visceral injury e.g. perforation of hollow viscus & injury to solid internal organ
2. Vascular injury
3. Conversion to laparotomy
4. Infection
• Post-op
1. Adhesion
2. Wound dehiscence
3. Post-op haemorrhage
4. Hernia
5. VTE
Hysterectomy Abdominal surgery (Laparotomy)
Type 1. Abdominal hysterectomy
1. Abdominal hysterectomy (Total or subtotal) 2. Salpingo-oophorectomy
2. Vaginal hysterectomy 3. Myomectomy
3. Laparoscopic hysterectomy (TLH, LAVH) 4. Tubal reconstructive surgery
5. Abdominal sacrocolpopexy
Abdominal Hysterectomy 6. Burch colposuspension
• Type of abdominal hysterectomy:
1. A total hysterectomy involves removal of uterus & cervix Vaginal surgery
2. Subtotal hysterectomy implies that the cervix is conserved 1. Vaginal hysterectomy
• Specific Indications 2. Anterior / Posterior colporrhaphy
1. Uterine cancer → TAH ± BSO ± Lymphadenectomy 3. Sacrospinous ligament fixation
2. Ovarian cancer → TAH ± BSO ± Omentectomy ± Lymphadenectomy 4. Endometrial ablation
3. Menorrhagia refractory to medical or more conservative surgical therapy 5. Cervical treatment
4. Symptomatic uterine fibroids • LLETZ
5. Endometriosis refractory to less radical therapy • Polypeptomy
• Procedure • McDonald / Shirodkar suture
1. Suprapubic transverse incision (Pfannenstiel)
2. Lower midline vertical only if more extensive exposure is required (e.g. ovarian cancer / large fibroids)
3. Round ligaments, tubo-ovarian, uterine artery, uterosacral pedicles & vaginal angles clamped, cut & ligated
4. If the patient is younger than 45, ovaries are usually conserved provided there is no oestrogen-dependent malignancy or
ovarian pathology
• Complication
1. Haemorrhage
2. Blood transfusion
3. Visceral injury to the bladder, ureter, bowel
4. Infection
5. VTE (DVT / PE)
6. Acute menopausal symptoms if ovaries removed (surgical menopause)

Vaginal Hysterectomy
• When appropriate, vaginal hysterectomy is preferable to abdominal hysterectomy because of less morbidity & a shorter post-
op period
• Indications
1. 2nd or 3rd degree uterine prolapse
2. Any other benign indication for hysterectomy where the uterus is accessible per vaginum
• Contraindications
1. Genital tract malignancy
2. Uncertain ovarian pathology
3. Large uterine fibroids
4. Previous abdominal surgery leading to adhesions
• As a general rule, if there is any suspicion of malignancy or if there are likely to be pelvic adhesions it is recommended that
the hysterectomy should be performed abdominally
• Procedure
1. GA / Spinal anesthesia
2. Circumferential incision made on cervix
3. Bladder freed & dissected upwards
4. Peritoneal cavity is opened anteriorly (uterovesical pouch) & posteriorly (Pouch of Douglas)
5. Uterosacral, uterine artery & tubo-ovarian pedicles clamped, cut & ligated
6. Uterus removed & ovaries inspected to exclude significant ovarian pathology
7. Associated vaginal wall prolapse repaired
8. Vaginal vault closed
9. Vaginal pack & urinary catheter inserted
• Complications
1. Haemorrhage
2. Vault hematoma; may become infected
3. Urinary tract injury (bladder or ureter)
4. Vaginal shortening — particularly if pelvic floor repair performed & this can lead to dyspareunia

Patients must be counseled that in the event of intra-op complications or difficulty with access, conversion to abdominal
hysterectomy may become necessary
Myomectomy
• Removal of fibroids individually may be appropriate in a women who wishes to conserve her uterus
• This procedure is associated with greater blood loss than hysterectomy & the risk of transfusion is as high as 5-10%
• Risk of hysterectomy needs to be explained to the patient before doing myomectomy
• Cases with breach of endometrial cavity during myomectomy should have C-section in future due to risk of scar rupture in
labour

Pelvic Floor Repair

1. Anterior colporrhaphy (anterior repair)
• Designed to correct cystocoele or cysto-urethrocoele or without stress incontinence
• Involves excision of a portion of vaginal skin & placement of support sutures to pubocervical fascia
• Fascial sutures elevate & support bladder neck
• Excess vaginal skin excised & vaginal wall closed
• Urinary catheter placed for 24-48h postoperatively
• Complications:
− Urinary retention
− Vaginal shortening
− Bladder / urethral injury

2. Posterior colporrhaphy (posterior repair)

• Designed to repair a rectocoele
• Portion of posterior vaginal wall excised
• Underlying levator ani muscles exposed & joined with interrupted sutures in midline
• Complications: Dyspareunia — due to over-enthusiastic closure of levator ani muscles & removal of excess posterior
vaginal wall skin