OBGYN Step 2
NORMAL PHYSIOLOGIC CHANGES DURING PREGNANCY
System Clinical Finding
 ↑ GFR & Renal size
 ↓ BUN & serum Creatinine
 ↑ HCO3 renal excretion
–
(metabolic compensation)
 ↓ Serum [Na+] (↑ ADH secretion)
 Urinary frequency, nocturia
Renal / Urinary  Mild hyponatremia
 Physiologic hydronephrosis of
pregnancy
 Dilutional anemia (Normal Hb ≥
10.5 g/dl in T2)
 Gestational Thrombocytopenia
(late in pregnancy, i.e. NOT 1st
Hematology
trimester)
 Mild leukocytosis
 ↑ Prothrombotic Coagulation
Factors
Cardiovascular  ↑ Cardiac output & heart rate
 Chronic respiratory alkalosis with
metabolic compensation, ↑ PaO2
(usually 100 – 110 mmHg) & ↓
Pulmonary PaCO2 (usually 27 – 32 mmHg)
 pH typically 7.40 – 7.45 with
metabolic compensation (↓ serum
bicarb)
Endocrine  Possible Impaired Glucose
Tolerance & gestational diabetes
(if insulin resistance > pancreatic
hyperinsulinemia)
Mechanism
 ↑ Cardiac output & renal blood flow due to progesterone, & ↑ renal
excretion
 ↑ Renal blood flow & Urine ouput
 ↑ Urine output & sodium excretion
 Hormones reset threshold to ↑ ADH release from pituitary
 T1 – high progesterone levels cause ureteral dilatation and decreased
peristalsis → hydronephrosis
 T2 & T3 – Dextro–rotated uterus → compression of the ureters at the
pelvic brim→ bilateral kidney enlargement (Right hydronephrosis >
Left hydronephrosis) and bilateral renal dilatation of the renal pelvises
and proximal ureters
 ↑ ↑ plasma volume
 ↑ red blood cell mass
 ↓ Haemoglobin concentration
 ↓ Platelet count (count usually between 100,000 – 150,000 /mm3, but
never < 70,000/mm3 which is more suggestive of ITP which likely
predates pregnancy if seen in T1)
 Hormone–mediated ↓ in total protein S antigen & activity;
 ↑ in fibrinogen & coagulation factors
 ↑ Blood volume (plasma > RBC mass)
 ↓ Systemic vascular resistance
 Progesterone directly stimulates central respiratory centers to ↑ tidal
volume & minute ventilation
o ↑ Central respiratory drive (hyperventilation)
o ↓ PaCO2 (respiratory alkalosis), ↑ PaO2
 Increased production of Human placental lactogen (a
somatomammotropin responsible for fetal growth and nutrition) and
T3 (triiodothyronine) resulting in:
o Pancreatic Beta cell hyperplasia
o Increased insulin secretion
o Increased peripheral insulin resistance
 ↑ Total T3 & T4; Free T4 (thyroxine) unchanged or mildly ↑
o ↑ Total T4 levels (1.5x pre–pregnancy level) due to ↑ thyroxine–
binding globulin (TBG)
o Free T4 tends to be unreliably low due to assay artifact;
pregnancy–specific reference range has not been established
o Measurement of total T4 is preferred over free T4
o β –hCG (which shares a common alpha subunit with TSH and a
very similar beta subunit) stimulates thyroid hormone
production in T1, by direct stimulation of TSH receptors
o Estrogen stimulates thyroxine-binding globulin (TBG) production;
thyroid increases hormone production to maintain steady free
T4 levels
TSH decreased
o Increased β –hCG & thyroid hormone suppress TSH secretion in
1st trimester as β –hCG has a stimulatory effect on TSH receptors
 o May have initial mild hyperthyroid state
o Estrogen stimulates synthesis of TBG and decreases TBG
clearance, leading to increased pool of bound thyroid hormone.
Patients with normal thyroid reserve subsequently increase
thyroid hormone production to maintain free hormone levels.
o N.B. pre-existing hypothyroid patients are unable to increase
thyroxine (T3) production and are at risk of worsening
hypothyroid state and adverse fetal & maternal effects (e.g.
gestational HTN, preeclampsia, premature delivery,
postpartum hemorrhage)
 If on a stable dose of levothyroxine, dose should be
increased by ~30% (25 – 50%) over prepregnant baseline
 The dose should be adjusted subsequently (typically in 4–
week increments) based on TSH using pregnancy–specific
norms (Interval follow up and maintenance of Total T4)
 N.B. Discontinuation of thyroid replacement therapy during
pregnancy may result in miscarriage, stillbirth, preeclampsia,
or postpartum hemorrhage. Psychomotor and cognitive
impairment may also occur in the offspring of patients who
are sub optimally treated as placental transport of T4 is
necessary for early fetal CNS development

Maternal Hypothyroidism in Pregnancy

TSH  Low / suppressed during first trimester due to thyroid–stimulating actions of β –hCG
 Patients with primary hypothyroidism unable to increase thyroid hormone synthesize → unable
to saturate additional protein binding sites of elevated TBG levels (recall estrogenic states like
pregnancy & OCP use stimulate hepatic synthesis of TBG)
 Pregnancy reference range for TSH:
o T1: 0.1 – 2.5 μU/mL
o T2: 0.2 – 3.0 μU/mL
o T3: 0.3 – 3.0 μU/mL
Management  Increase levothyroxine dose by 30% immediately following positive β –hCG
 Monitor TSH & Total T4 levels every 4 – 6 weeks thereafter
o N.B. similarly with OCP use, serum TSH should be checked several weeks after initiating OCPs,
increasing levothyroxine dose to maintain TSH within normal range. OCP use induces a
relative hypothyroid state
 Adjust dosage to maintain TSH within pregnancy reference ranges by trimester

Thyroid Disease During Pregnancy

Normal changes Hyperthyroidism Hypothyroidism
Slight ↓
TSH ↓ (< 0.1 μU/mL) ↑ (> 4.0 μU/mL)
(0.1 – 4.0 μU/mL
No change (subclinical) or ↑ No change (subclinical) or ↓
Free T4 No change
(overt) (overt)
Total T4 ↑ ↑ Variable

Thrombocytopenia in Pregnancy
Gestational Isolated, mild thrombocytopenia (70,000 – 150,000 / mm 3) with no prior history of thrombocytopenia
Thrombocytopenia Pathophysiology
o Hemodilution
o Accelerated destruction of platelets
Occurs in 5 – 10% of pregnancies and is likely due to physiologic increases in plasma volume during
 pregnancy (i.e. dilutional effect)
Asymptomatic
No associated fetal thrombocytopenia
Diagnosis of exclusion; commonly T2 or T3 on routine CBC, but rarely can arise as early as 1 st trimester
Platelet counts usually normalize within 6 months of pregnancy or after delivery (i.e. self–limited),
management includes reassurance and observation
Repeat CBC postpartum to ensure resolution
Moderate to severe thrombocytopenia (< 100,000/mm 3)
Preeclampsia with Hypertension ± headache / scotomata
severe features / ± ↑ Creatinine, ↑ AST & ALT
HELLP syndrome In the absence of renal disease, the onset of proteinuria (at least 300 mg/24 hr) is the best indicator of
superimposed preeclampsia in a patient with chronic hypertension.
Isolated, moderate–to–severe (< 100,000/mm3)
Immune–mediated
Asymptomatic or mucosal bleeding / bruising
thrombocytopenia
Can be associated with SLE and other autoimmune disorders
(ITP)
Normal PT, aPTT
Thrombotic Severe (< 30,000 / mm3)
thrombocytopenic Neurologic symptoms (e.g. confusion, seizure), fever, abdominal pain, petechiae
Purpura (TTP) Normal PT, aPTT
Disseminated Moderate to severe (< 100,000/mm3)
Intravascular Bleeding (e.g. oozing intravenous sites) ± thrombosis
Coagulopathy (DIC) ↑ PT, ↑ aPTT, ↓ fibrinogen

 Contraindications to Neuraxial Labour Analgesia (“Spinal anesthesia” usually via epidural catheter)
o Severe thrombocytopenia (platelets < 70,000 / mm3)
o Rapidly dropping platelet count (often associated with preeclampsia with severe features)
o N.B. Increased risk of spinal epidural hematoma in these patients

Ultrasound Assessment of Gestational Age

Ultrasound parameter Gestational Age (weeks) Accuracy (days)
Gestational sac diameter 4.5 – 6 ±5–7
7 – 10 ±3
Crown–Rump Length
11 – 14 ±5
14 – 20 ±7
Biparietal diameter, head
21 – 30 ± 14
circumference, Femur Length
> 30 ± 21 – 28

Pregnancy & Exercise

Absolute contraindications  At–risk for preterm delivery due to:
o Amniotic fluid leak, premature rupture of membranes
o Cervical incompetence, Premature labour
o Multiple gestation
 At–risk for antepartum bleeding due to:
o Placental abruption or previa
o Persistent second– or third trimester bleeding
 With underlying conditions that may be exacerbated by exercise:
o Hypertensive disorders of pregnancy – Preeclampsia / gestational HTN
o Severe heart or restrictive lung disease
o Severe anemia
Unsafe Activities  Contact sports (e.g. basketball, ice hockey, soccer)
 High fall risk (e.g. downhill skiing, gymnastics, horseback riding)
 Scuba diving – risk of decompression injury & gas emboli in the fetus
o Normal pregnancies have been reported in women who participated in scuba
diving, so scuba diving is not an indication for elective abortion
  Hot yoga

 Implantation bleeding – physiological bleeding that occurs ~14 days after fertilization due to attachment of the
fertilized egg to the uterus lining. It is scant and painless
 Teenage Pregnancy
o Adolescents are at increased risk of adverse pregnancy outcomes
 Increased risk of perinatal mortality
 Increased risk of Preterm delivery
 Increased risk of premature and low birth weight infants
o Unsure if these outcomes are due to socioeconomic factors or biologic immaturity
 Several studies suggest unfavorable prognosis in adolescent pregnant women compared to
women aged 20 – 24, even after adjusting for socioeconomic risk factors, thus biologic
immaturity may play a role
o Children of adolescent mothers may be at increased risk of severe, socioeconomic outcomes, including
future cognitive disorders
o N.B. Adolescent pregnancy DOES NOT increase risk of congenital malformations

Patient Status Recommended Dose of Folic Acid

General Population 0.4 mg/day for ≥ 1 month before conception
through the first trimester
Women who take anticonvulsants or have a child with a neural tube defect 4 mg/day for ≥ 1 month before conception
 Folate deficiency in pregnancy can lead to inadequate cell turnover through the first trimester
in the closure of neural tube (normally occurs around 6 weeks
gestation) and incomplete formation
 Also women with HbSS (Sickle Cell Disease) at increased risk of
folate defiency

Vaccines during Pregnancy Routine Prenatal Laboratory Tests

 Tdap
o Indicated during T3 (≥ 28 weeks);
preferred as it facilitates both
maternal antibody response and
transfer of maternal antibodies
through placenta, providing passive
immunity to fetus
 Inactivated influenza (injectable is
Recommended
inactivated)
o Safe during every trimester of
pregnancy & during breastfeeding
o N.B. intranasal influenza is
contraindicated in pregnancy as it is
live–attenuated & theoretical risk of
congenital infection
 Rho(D) immunoglobulin
 Hepatitis B
 Hepatitis A
Indicated for
 Pneumococcus
High–risk
 Haemophilus influenzae
pregnancy
 Meningococcus
 Varicella–Zoster Immunoglobulin
Contraindicated  HPV (despite inactivated vaccine, lack of
information regarding safety)
 MMR
o Typically administered in immediate
 Rh(D) type, antibody screen
 Haemoglobin / Haematocrit, MCV
 Blood Group
 HIV, VDRL/RPR, HBsAg
 Rubella ± varicella immunity
 Pap smear (if screening indicated)
 Chlamydia PCR
Initial
 Urine Culture
Prenatal
 Urine Analysis (Protein, Ketones, Glucose etc)
Visit
 Haemoglobin / Haematocrit
 Antibody screen if Rh(D) negative – IDCT
24 – 28  50 g 1–hour glucose challenge test
weeks  Chlamydia PCR & HBsAg – Repeated in the 3rd
trimester in high–risk patients (e.g. intravenous
drug use, STI earlier in pregnancy)
35 – 37  Rectovaginal swab for Group B Streptococcus
weeks culture
 postpartum period to susceptible
mothers, to decrease the risk of
congenital infection in subsequent
pregnancies
 Live attenuated influenza
 Varicella

HIV management during pregnancy

 HIV RNA viral load at initial visit, every 2–4 weeks after initiation or change of therapy, monthly until
undetectable, then every 3 months
 CD4 cell count every 3 – 6 months
 Resistance testing if not previously performed
 ART initiation as early as possible and modified according to results of drug–resistance testing
Antepartum  Avoid amniocentesis unless viral load ≤ 1,000 copies/ml

 Drug of Choice (DOC) – raltegravir + tenofovir + emtricitabine (same as PEP DOC)
o If mom already on dolutegravir before & doing OK, and no need to change
o Efavirenz OK in pregnancy
o Only cobicistat / ritonavir based regimens are contraindicated
 Avoid artificial ROM, fetal scalp electrode, operative vaginal delivery (N.B. contraindicated in HIV, HBV, HCV)
 Viral load ≤ 1,000 copies/mL & CD4 count is high (> 500) → ART + delivery (due to low risk of vertical
transmission)
Intrapartum
 Viral Load > 1,000 copies/mL → ART + intrapartum zidovudine + caesarean delivery (due to high risk of
vertical transmission)
o Reduces perinatal HIV transmission by 50%, when maternal HIV viral load > 1000 copies/mL
 Mother – continue ART
Postpartum  Infant (maternal viral load ≤ 1,000 copies/mL): zidovudine
 Infant (maternal viral load > 1,000 copies/mL): multidrug ART

Amniotic Fluid Embolism

 Amniotic fluid enters the maternal circulation through endocervical veins, placental insertion site, or areas
of uterine trauma (e.g. caesarean incision site).
 Triggers massive anaphylactoid reaction and leads to an inflammatory response causing vasospasm,
Pathophysiolog
cardiogenic shock, hypoxemic respiratory failure, seizures and coagulopathy with DIC
y
 Hypoxia can lead to seizures and LOC
 Associated with a high risk of maternal and neonatal mortality and among survivors, a high risk of
significant neurologic sequelae
 Advanced maternal age
 Gravida ≥ 5 (live births or still births)
Risk Factors  Caesarean or instrumental delivery
 Placenta previa or abruptio placentae
 Preeclampsia
 Cardiogenic Shock – hypotension (< 90 mmHg)
Clinical  Hypoxemic respiratory failure
Presentation  Disseminated intravascular coagulation – purpuric rash
 Coma or seizures
 Respiratory and haemodynamic support
o Oxygen, intubation, mechanical ventilation
Treatment
o Vasopressors for hypotension
 ± transfusion

Prenatal Testing
Test Timing (weeks) Advantages Disadvantages
First trimester 9 – 13 Early screening Not diagnostic
combined test
Pregnancy–associated
plasma protein (PAPP–  low PAPP–A, & high β –hCG concerning for
A) increased risk of aneuploidy (e.g. trisomy 21)
 β –hCG  ↑ NT suggestive of Trisomy 21, &/or 13
Nuchal translucency
Cell–free fetal DNA ≥ 10 High sensitivity & specificity for aneuploidy Not diagnostic
Chorionic Villus Invasive; risk of spontaneous
10 – 13 Definitive karyotypic diagnosis
Sampling abortion
Second Trimester Screens for neural tube defects & aneuploidy
Quadruple Screen
Maternal serum alpha–  High maternal serum AFP associated with
fetoprotein 15 – 22 neural tube defects Not diagnostic
Estriol  Low maternal serum AFP & β –hCG & high
 β –hCG estriol & inhibin A = Trisomy 21
Inhibin A  All 4 markers low = Trisomy 18
Invasive; risk of membrane
Amniocentesis 15 – 20 Definitive karyotypic diagnosis rupture, fetal injury &
pregnancy loss
Cannot identify all
Second Trimester Measure fetal growth, evaluates fetal anatomy,
18 – 20 abnormalities; some findings
Ultrasound confirms placenta position
are of uncertain significance

 Indications for Caesarean Section (C – Section Indications)

o Maternal Indications
 Absolute disproportion:
 Small maternal pelvis, making vaginal birth impossible
 Maternal pelvic deformity:
 Anatomical malformation, making vaginal birth impossible. Pelvic abnormalities that
preclude engagement or interfere with descent of the fetal presentation in labor  
 Eclampsia and HELLP syndrome:
 Life–threatening complication of pregnancy, usually leading to cesarean delivery
 Previous C–section, particularly with recurrent indication / uterine surgery:
 Previous Classical C–section
 Previous Full – thickness myomectomy
o If uterine cavity was entered during myomectomy or previous gynecological
surgery (can lead to uterine rupture)
 Two Previous LSCS
 LSCS less than 18/12 to 2 years go
 Obstructive lesions in the lower genital tract
 Malignancies (e.g. cervical cancer)
 Large vulvovaginal condylomas
 Obstructive vaginal septa
 Leiomyomas of the lower uterine segment
o Interfere with engagement of the fetal head
 Certain cardiac or pulmonary conditions conditions that preclude normal valsalva done by
patients during a vaginal delivery 
 Mitral Stenosis
 Cerebral Aneurysm or AV malformation
 Previous traumatic vaginal deliveries resulting in shoulder dystocia, 3rd degree perineal tears,
vaginal fistula formation
 Uterine rupture:
 Acute situation threatening the life of both mother and fetus, requiring immediate
delivery by cesarean section
  Chorioamnionitis (amniotic infection syndrome):
 Infection of the placenta and possibly of the fetus, requiring immediate delivery
 Failure to progress in labor (prolonged labor, secondary arrest):
 Delayed delivery or cessation of labor can result in an adverse outcome for the fetus or
newborn
 Failed Operative Vaginal Delivery
 Bad obstetric history
 Following vaginal repair operations (colporrhaphy) for bladder descent, stress incontinence or
repair for second degree uterine prolapse (Manchester repair)
 Gross pelvic contraction resulting from nutritional def., trauma and rare inherited diseases e.g.
HbSS and bony infarcts (uncommon)
 HIV in Pregnancy
 HIV infected Women with a viral count above 1,000 should be offered cesarean delivery at
38 weeks (or earlier if they go into labor)
o Offer c-section if low CD4 counts and high viral titres Or
o Offer c-section before this time if they go into labour
 C-section, before labor or without prolonged rupture of membranes, appears to further
lower the risk for neonatal transmission if mother being treated with Anti- retrovirals
 Caesarean section for obstetric indications only if on HAART
o Do not offer a CS on the grounds of HIV status to prevent mother-to-child
transmission of HIV to:
 Women on highly active anti-retroviral therapy (HAART) with a viral load of
less than 400 copies per ml
 Women on any anti-retroviral therapy with a viral load of less than 50
copies per ml.
o Inform women that in these circumstances the risk of HIV transmission is the same
for a CS and a vaginal birth.
 Herpes in Pregnancy
 all patients with active or symptomatic herpes infection are candidates for cesarean
delivery
o Fetal Indications
 Malpresentations (Abnormal Presentation) &/or Abnormal Lie – includes non-vertex
presentations
 Preterm breech presentations – risk of traumatic injury
 Non–frank breech term fetuses (less likely to engage, risk of PROM and cord prolapse)
 Brow, Face, Shoulder, Compound
 Transverse Lie, Oblique Lie
 Twin gestation with 1st twin in breech or both locked
 Twin gestation with 2nd twin in breech ( relative indication)
 Multiple pregnancies where the 1st twin is non-vertex and the second is distressed OR there is
distress and cervix is not fully dilated.
 Certain congenital malformations or skeletal disorders E.g. anencephaly, hydrocephaly
 Fetal neural tube defects
 Some cases of hydrocephalus
 Some skeletal dysplasias
 Infection
 Prolonged acidemia
 Fetal Macrosomia: Fetal weight > 4 - 4.5 Kg
 Presumed fetal distress evidenced by
 Meconium stained liquor
 CTG abnormalities- non reassuring and non–remediable fetal heart rate / tracings and
conditions not favorable for delivery
 o Abnormal Fetal tracing/ Low Biophysical Profile (e.g. hypoxia or deceleration in
fetal heart rate during or after contraction)
o Tachycardia
 Abnormal fetal scalp pH (less than 7.20)
 Erythroblastosis Fetalis (anemia from Rh incompatibility)
 Severe IUGR
 Umbilical cord prolapse:
 Prolapse of the umbilical cord between the head of the fetus and the vaginal opening,
which can lead to fetal asphyxia
 C–section avoids
o Compression
o Hypoxia and brain injury ( possible cerebral palsy, mental retardation)
o Ascending infection if labour is prolonged
o Materno–fetal Indications
 Abnormal placentation &/or APH
 Placenta previa
 Placenta accrete
 Abruptio placentae
 Vasa Previa
 Abnormal labor due to cephalopelvic disproportion

COMPLICATIONS OF CAESAREAN SECTIONS

Intraoperative Infections
complications Organ injury (bladder, intestines, ureter, etc.)
Risks associated with anesthesia
Need for blood transfusions – hemorrhage
Hysterectomy as a treatment for severe bleeding, e.g. from placenta praevia
Neonatal Trauma
Postoperative Thromboembolic complications
complications Adhesions, Bowel obstruction
Persistent pain
Infection – wound, endometritis
Hemorrhage
Caesarean Hysterectomy indicated if
§ Uncontrollable post partum haemorrhage
§ Unrepairable rupture of the uterus
§ Operation for cervical cancer
§ Couvelaire uterus – retroplacental blood may penetrate through the thickness of the wall
of the uterus into the peritoneal cavity
§ Morbidly adherent placenta with uncontrollable bleeding from the placental bed
Risks for Intrauterine growth retardation and preterm delivery
subsequent Spontaneous abortion
pregnancies Ectopic pregnancy
Stillbirth
Uterine rupture
Infertility
Placenta previa, increta, or accreta and associated risks e.g., need for blood transfusion or
hysterectomy

 Antihypertensives in Pregnancy
 o First line
 Beta Blockers (labetalol)
 Calcium channel blockers (nifedipine)
 Hydralazine
 α –Methyldopa
o Second line
 Clonidine
 Thiazide diuretic
o Contraindicated
 ACE inhibitors, Angiotensin II Receptor Blockers
 Associated with fetal hypocalvaria and renal agenesis, oligohydramnios
 Direct renin inhibitors
 Nitroprusside
 Mineralocorticoid receptor antagonists (spironolactone)
 Aside: Statins contraindicated
 Associated with congenital malformations
 Hepatitis C in Pregnancy
o Generally Asymptomatic but potential complications include
 Gestational Diabetes
 Cholestasis in pregnancy
 Preterm delivery
 Chronic HCV → progression to cirrhosis
o Incidence of vertical transmission of HCV 2–5%
o Risk factors for sexual transmission include practices that increases risk for microtrauma and blood
exposure (e.g. men who have sex with men, multiple partners, HIV co–infection)
o Maternal Management
 Ribavirin is teratogenic & should be avoided
 No indication for barrier protection in sero–discordant, monogamous relationships
 Risk of transmission for sexually–transmitted HCV infection in this population is <0.1%
 Hepatitis A & B vaccination (inactivated [killed] vaccines are both safe to administer during
pregnancy)
o Prevention of vertical transmission
 Vertical transmission strongly associated with maternal viral load
 Caesarean delivery not protective
 Scalp electrodes should be avoided
 Breastfeeding should be encouraged unless maternal blood present (e.g. nipple injury)
 Labour
o Stages of Labour
 1st stage of labour – begins with onset of regular contractions & lasts until complete (10 cm)
cervical dilation.
 Latent phase (0 – 6 cm dilatation): when cervix dilates slowly and has no defined expected
rate of cervical change
 Active phase (≥ 6 – 10 cm dilation): when the cervix dilates rapidly with a normal
progression of ≥ 1 cm every 2 hrs
nd
 2 stage of labour – 10 cm cervical dilation to fetal delivery
 Affected by parity and use of neuraxial anesthesia
rd
 3 stage of labour – time between birth of baby and delivery of placenta and membranes
o Disorders of the active phase of labour
 Labour Protraction
 Slower than expected cervical change (i.e. cervical dilation rate ¿ 1cm every 2 hrs)
 ± Inadequate contractions
 o N.B. ideally adequate contractions should occur every 2 – 3 minutes & ≥ 200 – 250
Montevideo units [MVUs]
 Place an intrauterine pressure catheter to measure contraction frequency and intensity
(force) to determine adequacy of contractions
 Tx – IV oxytocin for labour augmentation if contractions are found to be inadequate (i.e.
< 200 MVUs [i.e. uterine contractions in a 10–minute interval])
 Active labour arrest
 No cervical change for ≥ 4 hours with adequate contractions (≥ 200 MVUs), OR
 No cervical change for ≥ 6 hours with inadequate contractions
 Etiology
o Uterine (e.g. inadequate [hypotonic] contractions)
o Fetal (e.g. malposition [such as occiput posterior], macrosomia)
o Pelvic (e.g. deformity, contracted pelvis, fracture)
 Treatment – Caesarian delivery (as delaying delivery increases maternal–fetal morbidity
[e.g. intraamniotic infection, postpartum haemorrhage])

o Second Stage Labor Arrest

 Insufficient fetal descent with fully dilated cervix (10 cm) after pushing for:
 ≥ 3 hours if nulliparous
 ≥ 2 hours if multiparous
 Risk Factors
 Maternal obesity
 Excessive pregnancy weight gain
 Diabetes mellitus
 Etiology
 Cephalopelvic disproportion (most common cause)
 Fetal Malposition (any deviation from occiput anterior, e.g. occiput transverse)
contributes to CPD
 Inadequate contractions
 Maternal exhaustion
 Management
 Operative vaginal delivery
 Caesarean delivery
o An operative vaginal delivery (e.g. forceps–assisted vaginal delivery) is performed to expedite delivery
for category III tracings or maternal exhaustion during 2nd stage of labour (10 cm dilation until fetal
delivery)
o Trial of Labour after Caesarean (TOLAC) contraindicated for:
 Classical cesarean delivery (vertical incision)
  Prior abdominal myomectomy with uterine cavity entry or that was extensive
 N.B. not contraindicated for abdominal myomectomy withOUT uterine cavity entry or low
transverse cesarean delivery (horizontal incision)
 Immediate Postpartum Period (i.e. Hours to Days)
o Physiologic Changes & Clinical Manifestations
 Increased oxytocin levels (endogenous & administered)
 Causes uterine contraction, which compresses the placental bed vessels and protects
against postpartum hemorrhage
 As the uterus involutes, it rapidly decreases in size, becoming firm and palpable 1 – 2 cm
above or below the umbilicus
 Involution also generates subsequent lochia (shedding of uterine decidua & blood), which
initially appears bloody with small clots (lochia rubra), and can continue for several weeks
 Increased Prolactin Levels
 Stimulate breast milk excretion & milk letdown over the course of hours to days
 Infant suckling further increases maternal prolactin & oxytocin levels (i.e. positive
feedback)
 Breast engorgement
 Decreased Estrogen & Progesterone Levels
 May cause transient, postpartum rigors (shivering) / chills, with subsequent mild
hyperthermia / low–grade fever in first 24 hours after delivery
 Peripheral edema
o Routine Care
 Rooming–in / lactation support
 Serial examination for uterine atony / bleeding
 Perineal care
 Voiding trial
 Pain management
 Pubic Symphysis Diastasis
o Risk Factors
 Fetal macrosomia & traumatic delivery (e.g. shoulder dystocia and McRoberts Maneuvre with
suprapubic pressure → may also cause femoral nerve injury due to hyperflexion of the thigh)
 Multiparity
 Precipitous labour
 Operative vaginal delivery
o Presentation
 Difficulty ambulating ± waddling gait
 Radiating suprapubic pain to back, hips, thighs or legs, and is exacerbated by walking
 Pubic symphysis tenderness
 Intact neurologic examination
o Management
 Conservative – most patients recover within 1st 4 weeks postpartum
 NSAIDs
 Physical Therapy
 Pelvic Support
 Shoulder Dystocia
o Obstetric emergency – Failure of usual obstetric maneuvres to deliver fetal shoulders
o Risk Factors
 Fetal macrosomia (EFW > 4.5 kg [9.9 lbs])
 Maternal obesity
 Excessive pregnancy weight gain
 Gestational diabetes
 Post–term pregnancy (≥ 42 weeks gestation; Postdatism)
 o Warning signs
 Protracted labour
 Retraction of fetal head into the perineum after delivery (turtle sign)
o Neonatal Complications
 Brachial plexus injuries / Brachial Plexopathies
 Klumpke palsy (“Claw hand”)
o MCP joint hyperextended, Wrist extension, IP joints flexed
o Forearm supinated
 Erb–Duchenne Palsy (“Waiter tip”)
o Upper arm adducted & internally rotated
o Elbow extended
o Forearm pronated
o Wrist & fingers flexed
 Clavicular or humeral fractures
 Hypoxic encephalopathy from perinatal asphyxia
o Maternal Complications
 4th degree (e.g. rectal prolapse) perineal lacerations
 Postpartum hemorrhage
 Pubic Symphysis Diastasis
o Management – BE CALM
 B – Breathe, do not push; lower the head of the bed
 E – Elevate legs & hyperflex hips, thigh against abdomen, which flattens the sacral promontory
and decreases obstruction through the bony pelvis (McRoberts)
 C – Call for help – nurses, anesthesiologists, pediatricians, another physician
 A – Apply suprapubic pressure – downward, and lateral to release anterior shoulder
 L – EnLarge vaginal opening with episiotomy to facilitate extra maneuvres
 M – Maneuvres
 Deliver posterior arm
 Rotate posterior shoulder (Woods Corkscrew) – apply pressure to anterior aspect of the
posterior shoulder
 Adduct posterior fetal shoulder (Rubin) – apply pressure to the posterior aspect of the
anterior shoulder
 Mother on hands & knees – (Gaskins “All Fours” Maneuvre)
 Replace fetal head into pelvis for caesarean delivery (Zavanelli maneuvre)
 Erb’s Palsy (Brachial Plexus Birth Palsy, Obstetric Brachial Plexopathy)
o Usually upper nerves in the brachial plexus that are affected.
 injury of the 5th & 6th cervical roots, is by far the most common manifestation of this disorder
 Often right sided or bilateral
o Etiology
 usually a stretching injury from a difficult vaginal delivery
 some rare cases reported following C–sections
o Risk Factors – prolonged and difficult labor culminating in a traumatic delivery
 Large for gestational age (macrosomia)
 Multiparous / Multifetal pregnancy
 Difficult presentation
 Shoulder dystocia
 Forceps delivery
 Breech position
 Prolonged labor
o Clinical Features
  Infant with upper arm paralysis holds the affected arm in a characteristic position, reflecting
palsies of the involved shoulder abductors & external rotators, forearm flexors and supinators,
and wrist extensors. In addition, the Moro, biceps, and brachioradialis reflexes are absent.
Narakas Classification
Group Characteristics Roots
Group I (Duchenne– “Waiter’s Tip” Deformity – Paralysis of deltoid and biceps with intact wrist and C5–C6
Erb's Palsy – upper digital flexion/extension.
lesion)  Affected arm hangs limp, adducted & internally rotated, with elbow extended,
pronation of the forearm, and flexion of the wrist (“waiter’s tip”)
 Grasp reflex intact, but biceps and brachioradialis reflexes are absent.
 C5 deficiency
o Axillary nerve – deltoid (arm abduction), teres minor (external rotation)
weakness
o Suprascapular nerve – supraspinatus (arm abduction), infraspinatus (external
rotation) weakness
o Musculocutaneous nerve – biceps and brachialis weakness
 C6 deficiency
o Radial nerve – brachioradialis, supinator weakness
 Best Prognosis for spontaneous recovery – most cases of Erb-Duchenne palsy will
resolve with conservative management
o Complete recovery may take up to 2 years
Group II Paralysis of deltoid, biceps, and wrist and digital extension. C5–C7
(Intermediate Intact wrist and digital flexion.
Paralysis)
Group III (Total Flail extremity without Horner's syndrome C5–T1
Brachial Plexus Palsy)
Group IV (Total Flail extremity with Horner's syndrome C5-T1
Brachial Plexus Palsy
with Horner's
syndrome)

Klumpke’s Palsy  Rare in obstetric palsy; usually cause by Upward traction of the arm) C8, T1
(“Claw Hand”; Lower  Mechanism – Usually arm presentation with subsequent traction / abduction
lesion; N.B. Not in from trunk
Narakas Classification)  Deficit of all of the small muscles of the hand (ulnar and median nerves)
 “Claw hand”
o Wrist in extreme extension because of the unopposed wrist extensors
o Hyperextension of MCP due to loss of hand intrinsics
o Flexion of IP joints due to loss of hand intrinsics
 Poor prognosis for spontaneous recovery
 frequently associated with a preganglionic injury and Horner's Syndrome

 Down’s Syndrome – quad screening

o Low maternal serumα –fetoprotein, high β –hCG, low estriol, high inhibin A

Maternal serum α –fetoprotein (MSAFP / maternal serum AFP)

 Measured at 15 – 20 weeks gestation as a screening test
↑ MSAFP (> 2.5 MoMs) ↓ MSAFP
 Open Neural Tube Defect – open spina  Aneuploidies (e.g. trisomy 18,
bifida, Anencephaly trisomy 21)
 Ventral Wall Defects – omphalocele,
gastrochisis
 Multiple Gestations
 Congenital nephrosis
 Dermatologic disorders
 Tumours
 Improper fetal dating
  If an obstetric USS fails to identify a fetal malformation in a patient with elevated AFP levels, amniocentesis can
be performed. Amniotic fluid AFP, along with acetylcholinesterase, is measured. Elevations in both predict a
neural tube defect with high positive predictive value.
 Teratogens in pregnancy
o Retinoids (e.g. topical tretinoin)
 Vitamin A derivatives used in acne that interfere with Hox signaling pathways
o Renal dysplasia (fetal renal toxicity), fetal hypocalvaria, persistent patent ductus arteriosus & neonatal
death – common in 2nd and 3rd trimester fetal exposure to ACE inhibitors; ARBs also contraindicated due
to similar mechanism of action
 Renal dysplasia can lead to pulmonary hypoplasia, limb contractures, growth restriction or cord
compression due to oligohydramnios → poor fetal outcomes
o Sacral agenesis (i.e. caudal regression syndrome) exclusively in infants of diabetic mothers
o Thyroid hypoplasia – complication of inadvertent fetal radioactive iodine exposure
o Skeletal lesions – congenital syphilis due to inflammatory response (e.g. periostitis, osteochondritis) to
Treponema pallidum spirochetes in highly vascular bone (e.g. Hutchinson teeth)
o Methotrexate – competitively inhibits dihydrofolate reductase
 Teratogenic effects in 1st trimester
 Cardiovascular, urinary and neural tube defects
 Skeletal development abnormalities
 Contraindicated in pregnancy except for situations of cancer therapy with no better alternative
and ectopic pregnancy
o Methimazole teratogenic in 1st trimester (should switch to propylthiouracil in hyperthyroidism)
 Scalp defects, tracheoesophageal fistula, & choanal atresia
 Often switched back to methimazole in 2nd trimester as propylthiuracial associated with liver
failure / hepatotoxicity
o Radioiodine therapy is absolutely contraindicated during pregnancy – ablate the fetal thyroid gland
o Warfarin – nasal and limb hypoplasia (6 – 12 weeks gestation)

Fetal Postmaturity Syndrome (Fetal Dysmaturity Syndrome)

 Postterm placental insufficiency
Etiology o Occurs in fetuses deliver ≥ 42 weeks
o Placental function deteriorates after 40 weeks
 Small for gestational age
 Wrinkled, peeled skin
 Long, thin body
Clinical  ↓ Subcutaneous fat
Findings  Long fingernails
 ↓ Lanugo hair
 ↑ Scalp hair
 Meconium – stained placenta
 Hypoxia
Antenatal  Oligohydramnios
complications  Umbilical cord compression
 Fetal heart complications (e.g. late decelerations)
 Meconium aspiration (
Neonatal  Respiratory distress
complications  Hypoglycemia
 Seizures

Anticoagulation in Pregnancy
Optimal
Anticoagulant Route Maternal Considerations Fetal Effects
Timing
  Ease of use, predictable effect None
 Avoid in severe renal insufficiency
Low Molecular o N.B. LMWH is cleared renally only
Throughout
Weight Heparin Subcutaneous Prolonged LMWH is preferred over UFH, with
pregnancy
(LMWH) exception of renal insufficiency, as UFH is
associated with increased bone density loss,
bleeding & thrombocytopenia
 Used in renal insufficiency None
Unfractionated Subcutaneous Before o N.B. UFH is cleared renally AND hepatically
Heparin (UFH) or IV delivery  Best for high – bleeding risk (term pregnancy,
surgery)
 Absolute contraindication in 1st trimester  Teratogenic (bone &
 Sometimes used in 2nd & 3rd trimester for cartilage)
Preconception
Warfarin Oral patients with mechanical heart valve  Fetal bleeding
& postpartum
throughout
pregnancy

 Mechanical valves have several advantages over bioprosthetic valves, including durability and lower risk of
failure
o Patients with mechanical valves require lifelong anticoagulation (e.g. warfarin), and antiplatelet therapy
(e.g. aspirin)
 Warfarin should be avoided in first trimester due to teratogenicity, but may be used in 2 nd and 3rd
trimester in high – risk patients but is replaced by UFH in the last few weeks in pregnancy.
 Warfarin prophylaxis can be resumed during breastfeeding as it does not accumulate in
breast milk
 Aspirin in generally safe in pregnancy but should be discontinued temporarily at the time of
delivery due to increased risk of bleeding
o Patients with bioprosthetic valves do not require lifelong anticoagulation. Warfarin is typically prescribed
for only 3 months following bioprosthetic valve replacement surgery. Aspirin should be continued
indefinitely
 Tobacco Use during Pregnancy
o Obstetric Complications
 Spontaneous abortion
 Congenital anomalies
 Preterm PROM
 Placenta Previa
 Preeclampsia
 Abruptio placentae
 Low Birth Weight
 Fetal Demise
o Neonatal Complications
 Diabetes Mellitus
 Asthma
 Obesity
 Sudden Infant Death Syndrome
 Post–exposure prophylaxis in sexual assault
o Chlamydia – Azithromycin
o Gonorrhea – Ceftriaxone
o Trichomonas vaginalis – Metronidazole
o HIV – multidrug regimen (e.g. tenofovir – emtricitabine with raltegravir)
 Patients who seek care within 72 hours of assault may also benefit from HIV prophylaxis after
individualized counseling on the risks and benefits of therapy
o Hepatitis B – HBV vaccine ± HBV immunoglobulin
  PEP with HBV vaccine is dependent on vaccination status
 HBV immunoglobulin is not indicated if previously vaccinated against hepatitis B
 In non-immune patients, HBV vaccine is administered after exposure & HBV immunoglobulin is
added if assailant may be Hepatitis B positive
o In addition to PEP, women with negative pregnancy test are offered emergency contraception (e.g. oral
levonorgestrel [Plan B])
o Serologic testing is recommended for Syphilis at initial evaluation, and repeat serologies obtained at 6
weeks and 3 months
 Pregnancy risk / complications due to Hypertension
o Maternal
 Super–imposed preeclampsia
 Postpartum haemorrhage
 Gestational Diabetes
 Abruptio Placentae
 Caesarean delivery
o Fetal
 Fetal Growth Restriction
 Perinatal mortality
 Preterm delivery
 Oligohydramnios

Preeclampsia
New–onset HTN (SBP ≥ 140 mmHg &/or DBP ≥ 90 mmHg) + at ≥ 20 weeks’ gestation, without pre-existing
hypertension
Definition
AND
Proteinuria OR systemic involvement (signs of end organ damage)
High risk
o Prior preeclampsia (particularly with severe features at < 37 weeks’ gestation)
o Chronic kidney disease
o Chronic hypertension
o Diabetes mellitus
o Multiple gestation
o Autoimmune disease
Moderate risk
Risk Factors
o Obesity
o Advanced maternal age
o Extremes of Age (<18 – 20 yrs or >35 – 40 years – 2x than 20-29 years)
o Ethnicity: African Americans, Hispanic
o Nulliparity (2 – 3 x more likely)
N.B. Cigarette Smoking protective*
o ↓ 30-40% - dose-related effect
o *However, ↑ risk of fulminant disease if preeclampsia does occur
SBP ≥ 160 mmHg, or DBP ≥ 110 mmHg on 2 occasions taken ≥ 4 hrs apart while on bed rest** (unless
antihypertensive tx is initiated prior)
o ** Acute onset, persistent (≥ 15 min) severe-range HTN constitutes a hypertensive emergency
(inadvisable to wait 4 hours)
Thrombocytopenia (<100 ×109 /L or < 100,000/mm3)
Renal Insufficiency
Severe Features
o Serum [Cr] > 1.1 mg/dL (97 μmol/l ) or
o Doubling of conc. in absence of other renal disease
Impaired Liver Function – Elevated serum transaminases ≥ 2x ULN
Pulmonary Oedema
New – onset cerebral or visual symptoms
o Flashing lights, Blurred vision, scotomata, altered mental status, severe headache
 Cerebrovascular disorder characterized by:
o Preeclampsia + generalized tonic-clonic seizures &/or coma (convulsive phase of preeclampsia)
o Without pre-existing neurologic d/o
Eclampsia o N.B. ~ 10% of eclamptic seizures develop before overt proteinuria
Often preceded by premonitory events
o Hyperreflexia, Severe headaches, LOC, facial twitching
o N.B. May occur in absence of warning signs
3 Possible Scenarios for Chronic HTN:
↑ BP known to predate pregnancy
↑BP prior to 20 weeks gestation* (particularly in 1 st trimester)
Chronic HTN in
o if pre-pregnancy BP unknown
pregnancy
o Diagnosis of Chronic HTN during pregnancy requires 2 measurements taken ≥ 4 hours apart
o *Should also consider atypical or early-onset GHTN and/or early preeclampsia
↑BP persisting > 12 weeks postpartum
Chronic HTN with 2 Possible scenarios for diagnosis
super – imposed o Chronic HTN + development of proteinuria after 20 weeks, or
Preeclampsia o Chronic HTN + proteinuria before 20 weeks’ gestation with evidence of end-organ dysfunction
Maternal Complications Fetal & Neonatal Complications
CNS
Oligohydramnios
o Central effects – Headache, N/V, visual
Decreased Uteroplacental perfusion
disturbances, hyperreflexia
IUFD (Intrauterine Fetal Demise)
o Convulsions and coma (Eclampsia)
Asymmetric IUGR
o Hypertensive encephalopathy
Absent or reversed end–diastolic flow in umbilical
o Intracerebral haemorrhage artery (Doppler USS)
o Cerebral edema Complications associated with preterm birth
o Cortical blindness o Respiratory distress syndrome (RDS)
o Cranial Nerve palsies o Intraventricular haemorrhage (IVH)
o Cerebrovascular accident o Bronchopulmonary dysplasia (BPD)
 ↑ risk of intracerebral & subarachnoid o Patent ductus arteriosus (PDA)
hemorrhage o Necrotizing enterocolitis (NEC)
 ↑ ↑ risk with DIC or HELLP
o Retinopathy of prematurity (ROP)
 Loss of cerebral autoregulation → Vasogenic
o Sepsis
edema
Perinatal morbidity & mortality
 SBP better than DBP or MAP at predicting
Preterm Delivery 2o to maternal & fetal complications
adverse events
Complications Hypoxic & Neurologic injury
 Most hemorrhagic (93%) & postpartum
Eyes
o Increased excitability in Retina 2o to hypoxia
o Visual disturbances, Scotomata Renal
Retinal Detachment (rare) o Glomerular endotheliosis
Cardiopulmonary o Reduced GFR (Increasing Serum Cr, K+, urea)
o Pulmonary edema, ARDS o Proteinuria
o Future Hypertension o AKI (tubular / cortical necrosis)
o N.B. CVS effects have high mortality o ATN (rarely)
Placenta o Uric acid filtration decreased
o Placental ischemia o Increased Serum Uric Acid
o Placental Abruption o Oliguria / Anuria
Hematologic Liver
o Decreased plasma volume o Periportal haemorrhages, hepatocellular necrosis
o Hemoconcentration o Periportal inflammation
o Hemolysis, Thrombocytopenia, DIC o Subcapsular haematoma, Hepatic capsule rupture
o HELLP Syndrome

Investigations CBC – in particular Hb, Hct, Plt – Haemolysis, thrombocytopenia

 Peripheral Blood Smear
U&E’s – BUN (normal or sl ↑), Cr
Uric acid > 4.5 – 5.0 mg/dL suggestive of preeclampsia
LFTs – ALT, AST, LDH, Albumin
Coagulation Profile – PT, PTT, fibrinogen (particularly if thrombocytopenic)
Urinary Assays
o Urine Dipstick
o Urine protein/creatinine ratio or 24-hour urine collection
o Total urinary protein
MSU – r/o infective causes of proteinuria
CT Abdomen – Subcapsular haemotoma
CT Brain – non-contrast: r/o Intracerebral or subarachnoid haemorrhage
Daily fetal movement count
Fetal Heart Rate
NST ± BPP (if non-reassuring NST)
o GHTN: Weekly NST
o Preeclampsia: Bi-weekly NST
o NST indicated if SFH < 3cm for GA or if decreased fetal movement
Ultrasound
o Fetal growth / biometry
o AFI (Amniotic Fluid Index)
o Doppler U/S
 Umbilical cord – severity of IUGR
 Maternal Uterine Artery Doppler
 MCA
Patients with new diagnosis of preeclampsia should be admitted due to increased risk of progression to
severe features
Delivery for term patients
o Delivery is the definitive treatment to prevent maternal complications such as seizure, stroke, renal
or hepatic damage, and death
Patients with severe features:
o Seizure Prophylaxis – Magnesium Sulphate IM or IV (N.B. MgSO4 contraindicated in Myasthenia
Management Gravis – see below)
o Antihypertensive medications for BP ≥ 160/110 mmHg persisting for ≥ 15 minutes:
 Labetalol IV, Hydralazine IV, or Nifedipine PO
o Corticosteroids can be administered to accelerate fetal lung maturity in anticipation of preterm
delivery (e.g. patients with ≤ 37 weeks with severe features or fetal compromise [e.g. fetal growth
restriction])
 Prophylactic corticosteroid administration is recommended even without amniocentesis for
patients < 34 weeks’ gestation with high risk preterm delivery due to fetal lung immaturity
Myasthenia Gravis and Preeclampsia with severe features
 Magnesium Sulfate contraindicated due to risk of precipitating myasthenic crisis (e.g. oropharyngeal
muscle weakness, respiratory failure requiring intubation)
 Seizure prophylaxis with valproic acid (instead of Magnesium sulfate) in these patients
Low–dose aspirin at 12 – 28 weeks’ gestation (but optimally before 16 weeks), then continued daily until
Prevention
delivery

 In the absence of renal disease, the onset of proteinuria (≥ 300 mg/24 hr) is the best indicator of
superimposed preeclampsia in a patient with chronic hypertension.
 HELLP Syndrome
o Severe form of preeclampsia
o Life–threatening and associated with numerous complications:
 Preeclampsia
 ARDS (acute respiratory distress syndrome)
 Disseminated intravascular coagulation
  Prematurity
o Pathogenesis
 Abnormal placentation → triggering systemic inflammation and activation of the coagulation
system and complement cascade
 Circulating platelets are consumed and MAHA is particularly detrimental to the liver
 Resulting hepatocellular, centrilobular necrosis, hematoma formation and thombi in the portal
capillary system cause elevated liver enzymes, liver swelling and distension of Glisson’s capsule
o Clinical Features
 Preeclampsia
 Nausea, vomiting
 Right upper quadrant abdominal pain
o Laboratory Findings
 Microangiopathic Hemolytic Anemia (MAHA)
 Indirect hyperbilirubinemia, ↑ LDH, ↓ Haptoglobulin
 RBC fragments (‘helmet cells’ aka schistocytes) on peripheral blood smear
 Elevated Liver Enzymes (serum transaminases)
 Low Platelet Count (thrombocytopenia)
o Treatment
 After maternal stabilization, delivery is the only definitive treatment
 HELLP–associated coagulation disturbances are corrected spontaneously after delivery
 Prophylactic platelet transfusions can be considered for platelets < 20,000/mm 3
 For caesarean delivery, preoperative platelet transfusion can be considered for platelets <
40,000 / mm3
 Magnesium sulphate infusion for seizure prophylaxis
 Antihypertensive drugs (if BP > 160/105 mmHg)
 Patients with gestational and pregestational diabetes are at risk of adverse fetal outcomes with suboptimal
glucose control. Even mild elevations of glucose are detrimental during pregnancy and labour.
o Recommended fasting blood glucose level in the peripartum period is 72 – 126 mg/dL (4 – 7 mmol/L)
o Levels higher than this are associated with fetal hypoglycemia following delivery due to glucose–induced
insulin production in the fetus
o However insulin requirements typically decrease during active labour due to muscle contractions
o Also insulin resistance decreases rapidly following delivery of the placenta, and patients with gestational
diabetes mellitus may not need any postpartum antidiabetic treatment
o If patient has been taking intermediate acting NPH, recommend full dose the night before induction of
labour with monitoring of blood glucose every 1 – 2 hours, and administration of short acting insulin if
glucose > 126 mg/dL
o In patients treated with long–acting basal analogues (e.g. detemir, glargine), reduce dose to 50 – 70% on
night before induction of labour
o In patients treated with multiple insulin injections, the morning dose of the intermediate– or long–acting
insulin should be decreased by at least 50% before the induction of labour
o A light meal is typically allowed before the active phase of vaginal delivery; however if patients are not
eating or drinking, intravenous dextrose may be warranted
 Gestational Diabetes
o Pathophysiology – Human placental Lactogen (placenta–mediated increases in peripheral insulin
resistance)
 ↑ Human placental lactogen (2nd trimester)
 Peptide hormone secreted by syncytiotrophoblast
 Physiologic maternal insulin resistance in 2nd & 3rd trimesters and compensatory
stimulation of pancreatic beta cell insulin production (GDM occurs if pancreatic function
unable to overcome physiologic insulin resistance)
o Increase glucose providing adequate nutrition to a growing fetus
  Factors that oppose insulin action during pregnancy
 ↑ Placental hormones (2nd trimester) –
o hPL, placental insulinase, Glucagon, ↑ Plasma cortisol
o Progesterone
 Further aggravated by ↑body weight and ↑ caloric intake during pregnancy
 Pre-gestational diabetes becomes worse during pregnancy
 GDM develops when pancreatic insulin output cannot overcome the effect of these hormones
 3 – 5% unable to maintain normoglycaemia
 Since pregnancy worsens the pathology of preexisting diabetes. This leads to:
 Exacerbation of nephropathy
 Exacerbation of retinopathy
o Diabetic retinopathy worsens in ~15% of pregnant patients with preexisting
diabetes, some proceeding to proliferative retinopathy and loss of vision if the
process remains untreated by laser coagulation
 Further weakening of the immune system leading to increased infections
 Increased risk of ketoacidosis and coma
o Screening
 24 – 28 weeks gestation
 1-hr 50g glucose challenge test
 3-hr 100g glucose tolerance test
 Patients with risk factors (e.g. obesity, previous GDM, previous macrosomic infant) should be
screened early in pregnancy, then rescreened at 24 – 28 weeks if initial screen is negative
o Neonatal Complications due to Excessive Maternal Hyperglycemia
 First Trimester – Congenital Anomalies
 CNS – Open Neural Tube Defects e.g. anencephaly, macrocephaly
 Cardiac (congenital heart disease) –
o Cardiomyopathy, TGA, VSD, ASD
o Coarctation of aorta (more typically associated with Turner Syndrome)
o Hypoplastic Left Ventricle – pre–gestational DM
 Renal – Hydronephrosis, Renal agenesis, Ureteral duplication
 MSK
o Sacral agenesis (pathognomonic)
o Caudal regression sequence
 GI – Duodenal atresia, Small left colon syndrome
 Chromosomal abnormalities
o Typically due to Advanced Maternal Age
o Down’s Syndrome
 Others – single umbilical artery
 Spontaneous Abortion, IUFD (intrauterine fetal demise)
 Second & Third Trimester
 Fetal Hyperglycemia & Compensatory Fetal Hyperinsulinemia
o Organomegaly
o Transient Hypertrophic Cardiomyopathy
 Hypertrophic Interventricular septum usually asymptomatic, but if LVOT is
obstructed → congestive heart failure
 Respiratory distress [tachypnea, nasal flaring, retractions]
 Tachycardia
 Hypoxia
 Heart murmur
 Cardiogenic pulmonary edema
  Insulin triggers glycogen synthesis, and excess glycogen and fat are
deposited within the myocardium
 Increased oxidative stress of the interventricular septum may
contribute to this selective thickening
 Echocardiogram findings normalize within a year
 Most children recover within a few weeks without surgery, even if they
have symptoms
o Metabolic
 ↑ Metabolic demand → fetal hypoxemia → ↑ erythropoiesis →
Polycythemia
 Neonatal hypoglycemia
 Neonatal Hypocalcemia
 Neonatal Hyperbilirubinemia
o LGA, Macrosomia → Shoulder Dystocia
 Brachial plexopathy
 Clavicle fracture
 Perinatal asphyxia
o Polyhydramnios (AFI > 24 cm)
 IUGR – particularly with pre-existing DM (i.e. pre – gestation)
 Increased Perinatal morbidity and mortality
o Prematurity
o Respiratory Distress Syndrome
o Spontaneous Abortion & Stillbirth
o Hypothermia 2o to prematurity & insufficient fat
o Maternal Complications
 Obstetric Complications – PIH, Pre-eclampsia
 Pre-GDM >> GDM
o Vasculitides or comorbid chronic HTN
 Diabetic Emergencies
 Risks of DKA and coma
o Hypoglycemia esp. early in pregnancy
 Nausea and Vomiting may interfere with caloric intake
 Autonomic neuropathy
 End–organ Involvement or deterioration –
 Nephropathy, proliferative retinopathy
 Micro/macroangiopathy
 Infections – vaginal candidiasis
 Delivery
 Prolongation of labour & increased instrumentation rates
 Traumatic births – e.g. shoulder dystocia leading to perineal injuries
 Operative Delivery
 Polyhydramnios – PROM, Cord Prolapse
 Infections – puerperal sepsis
 Postpartum
 Increased risk of developing DM later in life
 Past hx of GDM increases the risk of recurrence in subsequent pregnancies
o Management
 1st line – dietary modifications
 2nd line – insulin, metformin, glyburide
o Target blood glucose goals
 Fasting < 95 mg/dL (5.3 mmol/L)
  1–hr postprandial ≤ 140 mg/dL (7.8 mmol/L)
 2–hr postprandial ≤ 120 mg/dL (6.7 mmol/L)
o Postpartum Management
 Fasting glucose at 24 – 72 hr
 2–hr 75g OGTT at 6– to 12–week visit post–delivery
 If screening is negative, repeated screening should occur at 3–year intervals
 Risk of developing Type 1 Diabetes (T1DM) in offspring of parents with T1DM is higher than in general
population
o If mother has T1DM, risk for offspring is approximately 3%
o If father has T1DM, risk for offspring is approximately 6%
o Reason for higher risk in paternal T1DM is unclear
o Incidence of T1DM in siblings having the same HLA type is 15%, while the incidence of siblings having
completely different HLA types is 1%
 Prostaglandins maintain the patency of the ductus arteriosus to allow blood flow to the systemic circulation
o Prostaglandins indicated for ductal dependent lesions (e.g. Hypoplastic Left Ventricle, transposition of the
great arteries) and provide immediate symptomatic improvement while awaiting surgery
 Peripartum Cardiomyopathy
o Rare, idiopathic complication of pregnancy that results in left ventricular systolic heart failure in women
during the peripartum period
o Potentially life–threatening condition that requires urgent evaluation, diagnosis, and intervention
 Treatment similar to other forms of heart failure
o Epidemiology
 Incidence – rare, 0.04-0.10% of live births
 Onset between 36 weeks’ gestation and 5 months postpartum
 Usually occurs within 1 month postpartum
 Risk factors
 Pre–eclampsia or eclampsia
 Pregnancy–induced or pre–existing hypertension
 Advanced maternal age
 Multiple gestation
 High parity
 Black / African-American
o Pathogenesis –
 Largely idiopathic, may be related to systemic angiogenic imbalance, elevated oxidative stress,
and impaired VEGF signaling during pregnancy
o Prognosis
 More than 50% of patients recover within 6 months with medical treatment
 6–10% mortality; earlier diagnosis associated with improved survival
o Clinical Manifestations – basically congestive heart failure
 Chest pain + heart failure symptoms
 Exertional dyspnea, cough, orthopnea, paroxysmal nocturnal dyspnea
 Bilateral lower extremity edema
 ± Abdominal fullness (e.g. ascites, tender hepatomegaly)
 Jugular venous distension
 Displaced apical pulse
 Bilateral basilar crackles
 S3 gallop
o Investigations
 Elevated B–type natriuretic peptide (BNP)
 ECG – sinus tachycardia, non-specific ST or T abnormalities
  CXR – Enlarged cardiac silhouette, pulmonary vascular congestion, Kerley–B lines, Interstitial
edema
 Echocardiogram – decreased LV ejection fraction
o Management
 Management approach similar to management of heart failure except teratogenic medications
(e.g., ACE Inhibitors, angiotensin receptor blockers (ARBs), aldosterone receptor antagonists) are
avoided in pregnant women
 Conservative
 Spontaneous vaginal delivery preferred mode of delivery for hemodynamically stable
patients
 Medical
 Loop Diuretics
o indication – symptomatic treatment if evidence of pulmonary edema
 β–blockers
o indication – long term management in all patients after adequate compensation of
heart failure
 Hydralazine and nitrates
o Hydralazine – direct arterial vasodilator (reduced afterload)
o Long – acting nitrates (e.g. isosorbide mononitrate) – predominant venous dilator
(reduced preload)
o patients who cannot take ACE–inhibitors or ARBs (i.e. during pregnancy)
 Cardiac Glycoside (e.g. digoxin)
o Indication – systolic heart failure in peripartum period and persistent symptoms
despite adequate diuresis and vasodilatory therapy
 If postpartum
o ACE Inhibitors or ARBs (contraindicated in antepartum period)
o Spironolactone or eplerenone (contraindicated in antepartum period)
 Surgical
 Immediate delivery via cesarean section indicated if:
o severe heart failure
o hemodynamic instability refractory to treatment
 Complications of Cyanotic Heart Disease in Pregnancy
o Maternal
 Thromboembolism
 Fluctuations in systemic vascular resistance (heart failure, cerebral vascular changes)
o Fetal
 Spontaneous abortion ( 20 – 40%)
 Premature Labour
 Intrauterine growth restriction
 Perinatal mortality
o For instance, pregnancy in the setting of Eisenmenger syndrome (permanent right–to–left shunt reversal
after unrepaired VSD, ASD or PDA with cyanosis), pulmonary hypertension, or other congenital heart
disease is associated with significant risk of maternal and fetal morbidity and mortality (up to 50%)
 Maternal mortality can occur during gestation, labour or delivery; however, most maternal
deaths occur in the immediate postpartum period (1st week postpartum), when rapid
hemodynamic shifts (e.g. increased systemic vascular resistance) occur, for which the heart isn’t
able to compensate.
 Decreased systemic vascular resistance, which occurs as a normal physiologic adaptation to
pregnancy, can exacerbate the right–to–left shunt and worsens hypoxemia, cyanosis & heart
failure
  Elective termination during first trimester (safest; performed in hospital setting) should be
discussed due to the markedly high risk of death to the woman and the fetus
 Patients with Eisenmenger syndrome are encouraged to use reliable contraception
 1st line options include long – acting reversible contraception (e.g. subdermal progestin
implants, intrauterine device)
 N.B. estrogen – containing contraceptives are contraindicated due to increased risk of
thromboembolism

Absolute Contraindications to pregnancy

 Pulmonary Arterial Hypertension
 Peripartum cardiomyopathy with residual LV dysfunction
 Heart Failure with LVEF < 30%
Conditions in which pregnancy is
 Severe coarctation
contraindicated
 Severe mitral stenosis
 Severe symptomatic aortic stenosis
 Severe aortic dilatation (e.g. Marfan’s Syndrome)
 Recommend against pregnancy at preconception counselling visit
 If pregnant, discuss abortion; if abortion declined, regular Cardiology Follow – Up
Management o Multidisciplinary care with cardiology, pulmonology and maternal fetal medicine
o In general, caesarean delivery is not automatically recommended because it is
associated with a higher mortality rate than vaginal delivery

 Septic Pelvic Thrombophlebitis

o Risk Factors
 Ceasarean delivery
 Pelvic Surgery
 Endometriosis
 Pelvic Inflammatory Disease (PID)
 Pregnancy, postpartum period
 Malignancy
o Pathophysiology
 Hypercoagulability
 Pelvic venous stasis and dilation
 Endothelial damage from infection and/or trauma during surgery (Vascular Trauma)
 Infection – chorioamnionitis / endometritis
o Clinical Features
 Fever unresponsive to antibiotics
 No localizing signs / symptoms
 Negative infectious evaluation
 Diagnosis of exclusion – negative Blood Cx, Urine Cx, normal urinalyis
o Treatment
 Anticoagulation
 Broad-spectrum antibiotics

Postpartum Endometritis
Etiology Polymicrobial infection of uterine decidua is most common etiology of puerperal fever
Direct inoculation of the uterine cavity by vaginal flora during labor or delivery
Risk Factors Most important risk factor is route of delivery – contamination of uterine cavity, prolonged rupture of
membranes, & presence of sutures or other foreign objects
o Caesarean delivery
 Postpartum endometritis occurs after 15 – 30% of caesarean deliveries (especially those
performed after labor commences or after rupture of membranes)
 o Operative vaginal delivery – endometritis occurs after 3% of vaginal births
Chorioamnionitis
Group B Streptococcus colonization
Prolonged Rupture of membranes
Cigarette smoking
Low Socioeconomic status
Maternal Diabetes
Clinical Features Fever > 24 hr postpartum
Uterine fundal tenderness
Purulent lochia / Foul–smelling vaginal discharge
Treatment Empiric IV Clindamycin & gentamicin for polymicrobial coverage – tx continued till afebrile > 24 hrs
o Adequate coverage for beta–lactamase producing anaerobes
Neither blood nor endometrial cultures are required for diagnosis, but further evaluation is indicated if
there is no clinical improvement after 48 hours of antibiotic therapy

 Anemia in pregnancy defined by CDC as

o Hb < 11 g/dL in 1st and 3rd trimester, and < 10.5 g/dL in 2nd trimester
o Severe anemia can lead to poor tissue perfusion with lactic acidosis, and an anion gap metabolic acidosis
 Antiepileptics (AEDs) in Pregnancy / Epilepsy in Pregnancy & Breastfeeding / Seizures in Pregnancy
o Although AED use during pregnancy is associated with an increased risk of congenital abnormalities, over
90% of women with epilepsy have a normal pregnancy
 Maternal & Fetal Complications
 Abruptio placentae / hemorrhage
 Spontaneous abortion
 Preeclampsia
 Preterm Labor
 Mortality
 Injury
 Fetal complications from antiepileptics
 Cleft palate
 Congenital defects
 Neural tube defects
 Skeletal abnormalities
o Continuation of the current effective AED regimen is most appropriate course of action (i.e. changes to
AED regimen should not be made after confirmation of pregnancy)
 N.B. Valproate is the only exception to this rule (Valproic acid has the highest teratogenicity). If
possible, patients should be switched to an alternative effective regimen approximately 6 months
before a planned pregnancy. It is preferable to switch to a single drug at the lowest possible dose
in order to limit teratogenicity
 N.B. However do not switch regimens after confirmation of pregnancy
o Prenatal supplementation with high – dose folic acid starting as early as possible (optimally before
conception) is recommended for women taking carbamazepine or valproate. The standard dose can be
used in patients taking other anti–epileptic medications
o Serum alpha – fetoprotein screening, amniocentesis, or USS – early detection of major fetal anomalies
 If present, pregnancy can be terminated or an optimal management strategy can be planned
o Taking AEDs is NOT a contraindication to breastfeeding. Breastfeeding should be encouraged in
women with epilepsy.
 All AEDs are excreted in breastmilk in measurable amounts, but the belief is that the benefits of
breastfeeding outweigh the risk of exposure of the infant to AEDs.
 Ethosuximide reaches 90% of its plasma concentration in milk
 Valproate reaches 5 – 10% of its plasma concentration in milk
  There is no evidence that taking AEDs while breastfeeding is associated with adverse long–term
effects or changes in susceptibility to epilepsy
 Sedative AEDs (e.g. benzodiazepines, and phenobarbital) can sometimes cause the child to be
irritable & sleepy; discontinuation of breastfeeding & re–attempt after 1 week may be necessary
 Multifetal Gestation (Twin Pregnancies and higher orders)
o Types
 Monochorionic, monoamniotic – 1 placenta, 1 amniotic sac
 Lack dividing intertwin membrane
 Monochorionic, diamniotic – 1 placenta, 2 amniotic sacs
 “T sign” at intertwin membranes
 Dichorionic, diamniotic – 2 placentas, 2 amniotic sacs
 Most common twin gestation, and have the fewest pregnancy complications of the twin
gestation types
 “Twin peak sign” or “Lambda sign” (fused placenta with thick intertwin membrane and
placental projection where intertwin membrane meets the placenta)
 Or 2 visually separate placentas
o Risk factors
 Increasing maternal age
 Fertility–enhancing therapies (e.g. ovulation induction with clomiphene citrate)
 Increased parity
 Family History
o Maternal Complications
 Hyperemesis gravidarum
 Increased T1 nausea and vomiting may be early indicators of twin pregnancy, and are
likely due to elevated hCG and progesterone levels
 Preeclampsia
 Gestational Diabetes Mellitus
 Iron–deficiency anemia
o Fetal Complications
 Congenital anomalies
 Fetal growth restriction
 Preterm delivery
 Malpresentation (e.g. Breech)
 Monochorionic twins – Twin-twin transfusion syndrome
 Monoamniotic twins – Conjoined twins; cord entanglement
o Delivery mode for diamniotic twin gestation (determined by presentation & weight)
 Vertex / Vertex presentation – Vaginal delivery (assuming normal category 1 heart tracing)
 Vertex / Breech presentation
 Vaginal* or caesarean based on physician’s experience / comfort with breech extraction
o *A caesarean delivery is recommended if estimated weight of non–presenting twin
is < 1500 g (3lb 5 oz) or ≥ 20% the estimated fetal weight of the presenting twin,
and non – reassuring fetal heart monitoring of either twin during labour
 Breech / Vertex or Breech / Breech Presentation – Caesarean delivery
 Internal podalic version – set of maneuvres used prior to delivering a non – vertex second twin
who is still a candidate for vaginal delivery. Entails manipulating the fetus inside the uterus from
transverse or oblique lie to a breech presentation to grasp the feet and deliver it breech per
vagina
o Indications for Caesarean delivery of twins
 Monochorionic / monoamniotic twins (Monoamionicity)
 Malpresentation of twin A
 Non–reassuring FHR tracing of either twin during labour
 Intrahepatic cholestasis of pregnancy
 o Clinical Features
 Develops in 3rd trimester
 Generalized pruritus
 Pruritus worse on hands & feet
 No associated rash
 Right Upper Quadrant pain
o Laboratory Abnormalities
 ↑ Total bile acids (cholic acid and chenodeoxycholic acid) > 10 μmol/L
 ↑ Transaminases (< 2x normal), ↑ ALP
 ± ↑ Total & direct bilirubin
 Hepatitis serology to rule out hepatitis
 Anti–smooth muscle and antimitochondrial antibodies (to rule out autoimmune liver disease)
o Obstetric risks
 Intrauterine fetal demise, fetal growth restriction
 Preterm delivery (Premature labor and increased preterm birth rates)
 Meconium–stained amniotic fluid
 Neonatal respiratory distress syndrome
 Recurrence in following pregnancies (40–60%)
o Management
 Regular fetal assessment (e.g. non–stress test)
 Delivery at 37 weeks gestation, particularly if total bile acids ≥ 40 μmol/L, or at time of diagnosis
if term
 Ursodeoxycholic acid
 Anti–histamines
 Fully reversible postpartum
 Hyperemesis Gravidarum
o Severe, persistent nausea and vomiting of pregnancy that results in weight loss and dehydration
o Pathophysiology
 Elevated β –hCG and progesterone concentrations from a large placental volume;
 β –hCG → increased nausea
 Elevated progesterone levels relax smooth muscle tone of lower esophageal sphincter (i.e.
gastroesophageal reflux) and stomach (i.e. delayed gastric emptying) → increased nausea
o Risk Factors
 Hydatidiform mole
 Multifetal gestation
 Hx of hyperemesis gravidarum
 More common in young women during 1st pregnancy
 Tobacco use – protective against hyperemesis gravidarum (due to increased metabolism of
estrogen)
o Clinical Features
 Severe, persistent vomiting (in T1 &/or early T2 typically)
 > 5% loss of pre–pregnancy weight
 Dehydration (delayed capillary refill, dry mucous membranes, tachycardia)
 Orthostatic Hypertension
 ± Transient hyperthyroidism (“thyrotoxicosis of hyperemesis – ↑ β –hCG, which shares similar
alpha subunit to TSH)
o Lab findings – results from protracted vomiting
 Hypochloremic metabolic alkalosis
 Hypokalemia
 Hypoglycemia
 Elevated serum aminotransferases
 Haemoconcentration
  Ketonuria on urinalysis (prolonged hypoglycemia and subsequent ketoacidosis)
 TFTs indicated if overt signs of hyperthyroidism (e.g. tremor, heat intolerance, enlarged thyroid
or nodule)
o Treatment
 Admit to hospital
 IV Antiemetics & intravenous fluid rehydration and electrolyte repletion
 Glucose + Thiamine supplementation
 Glucose infusion prior to thiamine supplementation may precipitate Wernicke’s
Encephalopathy (altered mental status – encephalopathy, oculomotor dysfunction –
nystagmus, gait ataxia)
 Wernicke’s encephalopathy in pregnancy is associated with increased risk of spontaneous
abortion; thiamine supplementation may decrease the risk
 Acute Fatty Liver of Pregnancy
o Acute hepatic failure in 3rd trimester or early postpartum period due to dysfunction of fatty acid β –
oxidation
o Clinical Features
 Typically 3rd trimester
 Nausea, Vomiting
 Abdominal Pain
 Encephalopathy
o Investigations
 Significant elevations in liver markers (↑ AST, ↑ ALT)
 Leukocytosis (↑ WBC), ↓ platelets
 Prolonged PT & PTT
 Hypoglycemia
 Acute Kidney Injury
 Liver synthesis parameters: ↓ ↓ clotting factors , ↓ ↓ Cholinesterase
 Imaging: rule out other diagnoses (e.g., liver hematoma)
o Therapy: immediate Cesarean (C)-section
 Sickle Cell Disease in pregnancy
o Prenatal Care
 Baseline 24–hour urine for total protein at initial prenatal visit
 Baseline chemistry panel
 Serial urine culture
 Pneumococcal vaccination
 High-dose folic acid supplementation (4mg PO OD)
 Due to risk of neural tube defects in fetus (e.g. prior affected pregnancy, use of folate
antagonist medications)
 Typical folic acid dosing is 0.4mg PO OD in most prenatal vitamins
 Aspirin
 Serial fetal growth ultrasound
o Obstetric Complications
 Spontaneous abortion
 Preeclampsia, eclampsia
 Abruptio placentae
 Antepartum bleeding
 Increased risk of painful crises
 Increased metabolic demands and hypercoagulable state during pregnancy →
microvascular occlusions from RBC sickling, decreased perfusion and tissue ischemia
 Incidence typically increases with gestational age
 can occur in 1st trimester especially if there are other precipitating factors (e.g. stress,
nausea/vomiting, dehydration)
 o Fetal complications
 Fetal growth restriction
 Oligohydramnios
 Preterm birth
o Management
 Close antenatal surveillance (e.g. serial growth ultrasound, umbilical artery Doppler Ultrasound)
or monitoring of fetal well–being and delivery planning
 Pseudocyesis
o False belief of being pregnant associated with physical signs and symptoms of early pregnancy
o Epidemiology
 Age of onset: typically 20–39 years
 More common among women who wish to conceive & have a history of several prior failed
attempts
o Pathophysiology
 Likely occurs when the somatization of stress affects the hypothalamic–pituitary–ovarian axis and
causes early pregnancy symptoms, or when bodily changes (e.g. weight gain, amenorrhea) are
misinterpreted → non–psychotic patient who believes she is pregnant
o Clinical features:
 Breast tenderness, weight gain, amenorrhea, morning sickness, mild abdominal enlargement
 Belief is often strong enough that a patient misinterprets a negative home pregnancy test as
being positive
o Diagnostics: undetectable β-hCG, empty uterus with thin endometrial stripe on pelvic USS
o Management:
 Gently inform the patient that she is not pregnant
 Provide counseling and psychotherapy if needed
 Spontaneous Abortion – Pregnancy loss before viability (< 20 weeks, Embryo Fetal weight < 500g)
o Risk Factors
 Advanced Maternal Age
 Previous spontaneous abortion
 Substance abuse – tobacco, alcohol and cocaine use
o Etiology
 Fetal –
 Chromosomal Abnormality, Aneuploidy, structural abnormality mosaicism
 Congenital anomalies – due to chromosomal, genetic inheritance, teratogen exposure,
DM, Drugs, Toxins
 Trauma – due to Chorionic villus sampling, amniocentesis, blunt trauma (rare in early
pregnancy due to protection by abdomen)
 Maternal –
 Uterine structural abnormality – Bicornuate, septate, Fibroid, Adhesions, uterine
leiomyoma
o Miscarriage rate of 60% with septate uterus (more commonly 1st than 2nd trimester
miscarriages). While the embryo can implant on the uterine septum, there is an
altered blood supply to the septum that can result in abnormal implantation,
which can lead to pregnancy loss
 Management – Hysteroscopic metroplasty
 Important to differentiate bicornuate vs. septate uterus, as laparotomy is
needed for bicornuate uterus
 Maternal Infection (Listeria, toxoplasma, parvovirus B19, rubella, herpes, CMV, ZIKA)
 Maternal Disease – Endocrine (Thyroid Disorder, Cushing’s, PCOS, Diabetes Mellitus)
 Corpus luteum dysfunction
 Thrombophilia – SLE, anti–phospholipid syndrome
o Clinical Features
 Lower abdominal pain + vaginal bleeding
 N.B. In miscarriage, pelvic pain comes after the bleed, whereas in ectopic, abdominal pain
comes before the bleed
 N.B. a positive β –hCG in complete abortion is common because it may take up to 6 weeks to
become undetectable
 Abortion types / Classification
 Missed Abortion
o No vaginal bleeding
o Closed cervical os
o No fetal cardiac activity or empty sac
 Threatened Abortion
o Vaginal bleeding
o Closed Cervical os
o Fetal Cardiac activity; often have an associated sub–chorionic hematoma
(abnormal collection of blood between placenta and uterus)
o Expectant management with outpatient observation; serial USS until either
symptoms resolve, or progression to a complete abortion
 Inevitable Abortion
o Vaginal bleeding
o Dilated Cervical os
o Products of conception may be seen or felt at / above cervical os
o TVUS – non–viable gestation in lower uterus
 Incomplete Abortion
o Vaginal bleeding
o Dilated cervical os
o Some products of conception expelled & some remain
 Complete Abortion
o Vaginal bleeding
o Closed cervical os
o Products of conception completely expelled – i.e. empty uterus & normal adnexa
on TVUS
o Diagnosis
 TVUS
 β –hCG
 Single value not useful – provide baseline in case of ectopic & serial measurements
required
 Baseline 500 IU and fall of >21% 48 hrs
 5000 IU/L fall >35% 48 hrs
 RhD ABO
 IDCT
 Serum Progesterone < 5ng/ml
 Hysterosalpingography, Saline infusion sonohysterography
o Treatment options
 Expectant –
 Reserved for:
o Spontaneous abortions <12 weeks GA
o Stable Vital signs
o No signs of Infection
 Duration of management is for 4 weeks after which surgical evacuation is suggested
 Majority of expulsion occurs in 2 weeks
  Medical induction (misoprostol [Prostaglandin E1] ± mifepristone)
 Mifepristone is an antiprogesterone agent that primes the uterus for misoprostol, a
synthetic prostaglandin that causes uterine contractions and explosion of retained
products of conception
 Suction Curettage if infection or hemodynamic instability
o Additional management
 Rho(D) immune globulin if mother rhesus negative
 Pathology examination – products of conception sent for histological analysis to rule out
gestational trophoblastic disease and chorionitis
o Complications
 Haemorrhage
 Retained products of conception
 Septic abortion
 Uterine perforation
 Intrauterine adhesions
 Septic Abortion
o Can occur as a complication of any type of abortion but usually a complication of elective abortion under
non – sterile conditions.
 Complicated form of miscarriage occurring when retained products of conception results in a
intrauterine infection due to ascending vaginal flora (e.g. anaerobes, gram–negative bacilli,
gram–positive cocci) in the context of prolonged bleeding or recent instrumentation (e.g. from a
termination procedure)
o Risk Factors
 Most frequently follows elective abortion
 With non–sterile technique or incomplete procedure outside of health care setting
 Missed, incomplete or inevitable abortion (rare)
 Spontaneous abortion
 Pregnancy with IUD in situ
o Clinical Features
 Fever, Chills, Malaise
 Lower Abdominal pain
 If Septicemia & Septic Shock – fever, tachycardia, hypotension
 Heavy vaginal bleeding – Malodorous, bloody &/or purulent vaginal discharge (sanguinopurulent)
 Enlarged, boggy, tender uterus
 Dilated cervix
 Complications – If untreated, infection can spread into the myometrium thereby causing
widespread infection
 Myometrial infection / necrosis
 Acute Respiratory Distress Syndrome
 Disseminated intravascular syndrome
 Salpingitis, peritonitis
 Septicemia, Septic Shock
 Death
o Investigations
 Positive Urine β –hCG
 Abdominopelvic USS – Echogenic mass
 Retained products of conception, increased vascularity, intrauterine echogenic material
with blood flow
o Consistent with inflammation and infection from retained products of conception
 Thick endometrial stripe
o Management
 Assess the stability of the patient
  Blood and endometrial / cervical cultures
 IV fluids
 Broad–spectrum antibiotics
 IV until 48 hrs afebrile
o Monotherapy with piperacillin / tazobactam or imipenem
o Triple therapy – clindamycin + gentamicin ± ampicillin
 Oral dosing to complete 14 day course
 Suction Curettage for uterine evacuation – Surgical Evacuation of uterine contents promptly after
stabilization and commencing IV antibiotics
 Removes nidus of infection
 Increased risk or perforation
 Increased risk of adhesions
 Hysterectomy
 Indications
o No response to antibiotics
o Development of pelvic abscess
o Signs of clostridial sepsis (e.g. crepitus of pelvic tissue, radiographic evidence of air
in the uterine wall)
 Subchorionic Hematoma
o Abnormal collection of blood due to bleeding between the endometrium (uterine wall) and the
gestational sac
 Caused by a partial separation of the chorion (the outer amniotic membrane) from the uterine
wall.
o Risk Factors
 Anticoagulants
 Infertility treatment
 Uterine malformation (e.g. uterine septum, leiomyoma)
 History of recurrent pregnancy loss
o Often an incidental finding during routine ultrasound but can present but can present with vaginal
bleeding
 TVUS – crescent shaped hypoechoic regions adjacent to the gestational sac; most commonly
identified source of first – trimester bleeding
 Majority of patients have uncomplicated pregnancies, and management is expectant
o Expectant Management until symptoms resolve or additional findings develop
 Re–evaluated with repeat TVUS in one week ± serial USS
 No known therapeutic interventions
o Complications
 Spontaneous abortion (i.e. miscarriage at < 20 weeks gestation)
 Risk correlates to larger hematoma size, maternal age, and earlier gestational age
 Preterm delivery, preterm premature rupture of membranes, and growth restrictions are also
known to occur more associated with first trimester bleeding of any cause
 Abruptio placentae
 Preeclampsia
 Fetal Growth Restriction
 Intrauterine Fetal Demise
 Ectopic Pregnancy
o Implantation of fertilized ovum outside the uterine endometrium
o Localization
 Fallopian tube (96% of cases): ampulla (80%) >> isthmus (12%) > fimbriae (5%) > interstitial
pregnancy (e.g., cornual pregnancy; 2%)
 Ovary (3% of cases)
  Abdomen (1% of cases)
 Cervix (very rare)
o Heterotopic pregnancy – rare condition when at least two pregnancies are present simultaneously at
different implantation sites and only one located in the uterine cavity. Majority diagnosed in T1
o Risk Factors
 Anatomic alteration of the fallopian tubes is the main cause of ectopic pregnancy.
 A history of PID
 Previous ectopic pregnancy
 Past surgeries involving the fallopian tubes
 Endometriosis
 In Utero Exposure to DES (diethylstilbestrol)
 Bicornuate uterus
 Non–anatomical risk factors
 Intrauterine device (IUD)
 History of infertility
 Hormone therapy
o Clinical Features – classic triad of abdominal /pelvic pain + amenorrhea + vaginal bleeding
 Signs and symptoms present ~4 – 6 weeks after their LMP
 Abdominal or pelvic pain, adnexal tenderness, & Vaginal bleeding
 Ectopic Pregnancy – Pelvic pain precedes vaginal bleeding
 Miscarriage – Vaginal bleed precedes pelvic pain
 Signs of pregnancy: amenorrhea, nausea, breast tenderness, frequent urination, bluish
discolouration of the vulva (Chadwick’s sign of pregnancy)
 Tenderness in the area of the ectopic pregnancy
 Cervical motion tenderness, closed cervix
 Enlarged uterus
 N.B. Interstitial pregnancies tend to present late, at 7–12 weeks of gestation, because of
myometrial distensibility
 Tubal rupture
 Acute, sudden–onset & severe lower ABD pain (acute abdomen – rebound & guarding)
 Signs of hemorrhagic shock: e.g., tachycardia, hypotension, syncope
 More common in interstitial pregnancy
 Blood loss typically originates from hole in fallopian tube
o Diagnosis
 Urine β –hCG positive
 ↑ Serum Quantitative β –hCG
 β-hCG discriminatory level: β-hCG level at which an intrauterine pregnancy should be
visible on ultrasound. Cutoff is typically β –hCG ≥ 1,500 mIU/L
o UWorld 2022 is using 3,500 IU/L as the discriminatory level
o Inability to visualize pregnancy on ultrasound at the discriminatory level strongly
suggests ectopic pregnancy.
 N.B. Multiple pregnancies may have higher β–hCG levels.
 Serial β–hCG measurements if clinically stable, suspected ectopic & non–diagnostic TVUS
 If β–hCG ≥ 1,500 mIU/L & TVUS does not show an IUP, ectopic likely, but unconfirmed,
therefore → repeat hCG & TVUS in 48 hours
 If β–hCG ¿ 1,500 mIU/L & no IUP or extrauterine pregnancy on TVUS → repeat hCG in 48
– 72 hours
 Findings after 48 hours
o Intrauterine pregnancies: β–hCG increases by ≥ 50% in 99% of patients.
 Normal doubling time for β–hCG is 2.2 days (i.e. doubles ~ every 48 hours)
 Once β-hCG ≥ 1,500 mIU/L, repeat TVUS to confirm intrauterine gestation
sac
o Ectopic pregnancies: ~70% of patients show an insufficient increase or a decrease
in β–hCG;
 48 hr rise < 66% suggestive of Ectopic or failing intrauterine pregnancy
 Spontaneous abortion: ~90% of patients have a decrease of β–hCG ≥ 35%
 CBC: Anemia may be seen in patients with vaginal bleeding or ruptured ectopic
 GXM: ABO & Rh testing to identify patients who might need Rho immunization
 LFT, BMP: to determine baseline liver and renal function
 Abdominopelvic USS (TVUS & transabdominal) –
 Empty uterine cavity in combination with a thickened endometrial lining
 Possible extra–ovarian adnexal mass (bulge / cyst in adnexa)
 Tubal ring sign (blob sign, aka bagel sign): an echogenic ring that surrounds an
unruptured ectopic pregnancy
o Adnexal mass can have increased doppler flow, i.e. Peripheral hyperemia /
vascularity (“ring of fire sign”) surrounding an adnexal gestational sac, fetal pole,
or fetal heart beat
o N.B. ring of fire sign more commonly seen with corpus luteal cysts
 If ruptured ectopic, TVUS may show echogenic fluid (blood) in the posterior cul–de–sac
(rectouterine pouch of Douglas – most dependent position in pelvis), around the adnexa,
& in upper abdomen (Morrison’s pouch, aka Hepatorenal space)
o Blood in Morrison’s pouch suggests > 500 cc of free blood is present in abdomen
 Exclude Differential Dx (e.g. appendicitis, ruptured corpus luteal cyst – unlikely as it would
also show intrauterine gestation on TVUS)
o Management
 Medical Treatment
 Methotrexate – inhibits folate–dependent steps in DNA synthesis to terminate the rapidly
dividing ectopic pregnancy
o Single–dose Regimen, Two–dose regimen or Multidose regimen
 β –hCG <3600 IU/L: Single Dose Protocol
 β –hCG >3600 IU/L: Two Dose Protocol
o β–hCG monitoring / Follow – up:
 If β–hCG levels increase or plateau during weekly follow up, consider
persistent ectopic pregnancy.
o Indications
 Uncomplicated ectopic pregnancies
 Hemodynamically stable & no evidence of ectopic ruptured mass (tubal
serosa intact)
 Quantitative β–hCG ≤ 5,000 mlU/mL
 Some recommend limiting Methotrexate protocol to <2000 mIU/ml
 Adnexal mass size < 3.5 cm
 No fetal heartbeat
 Reliable patient, able to follow up for appointments and laboratory studies
 No history of renal disease, liver disease, or cytopenia
o Absolute contraindications
 Pulmonary, renal, hepatic, or hematologic disease
 Active Lung Disease
 Blood dyscrasias
 White Blood Cell Count <3000 (Leukopenia)
 Platelet Count <100,000 (Thrombocytopenia)
 Severe Anemia
  Liver disease or ↑ AST
o Methotrexate has hepatotoxicity potential
 Renal Disease or ↓ CrCl <50 ml/min/1.73 m3
o Methotrexate is renally excreted
 β–HCG >5000 mIU/ml
 Breastfeeding / Lactation
 Methotrexate sensitivity
 Immunodeficiency
 Peptic ulcer disease
 Ruptured ectopic pregnancy
 Poor compliance
 Fetal cardiac activity noted on USS
 Ectopic mass >3.5 – 4 cm
 Gestational Sac >3.5 cm
 Rh Anti-D immunoglobulin (Rhogam) for Rh–negative patients (particularly if bleeding)
 If β –hCG > 1,500 and TVS shows adnexal mass, ectopic pregnancy confirmed. Proceed to the
following management options:
 Methotrexate for haemodynamically stable patient with β –hCG < 5,000 IU/L, tubal
mass < 3.5 cm, and no fetal cardiac activity.
o Contraindications: renal failure, liver failure, and breastfeeding
o Laparoscopy is also effective in these patients
 Laparoscopy for hemodynamically stable patients with β –hCG > 5,000 IU/L, tubal mass
> 3.5 cm, and/or fetal cardiac activity
 Surgical Treatment – Exploratory laparoscopy (preferred) or Laparotomy
 Indications
o Hemodynamic instability in suspected cases of ectopic pregnancy
o Symptoms of impending rupture (e.g., pelvic pain)
o Signs of intraperitoneal bleeding
o Risk factors for rupture
o Contraindications for MTX
o Unsuccessful medical treatment
o A concurrent surgical procedure (e.g., bilateral tubal blockage) is necessary.
o The patient has indicated a preference for surgical treatment.
o In pregnancy of unknown location if the location is still uncertain after 7–10 days
 Consider earlier laparoscopic exploration for high-risk patients (e.g.,
previous ectopic pregnancy).
 Expectant management
 Asymptomatic patients with very low β–hCG levels may experience spontaneous
resolution of ectopic pregnancy without medical or surgical treatment.
 Indications
o Minimal symptoms
o No evidence of ectopic mass on TVUS
o Low/decreasing levels of β–hCG
 Considerations during expectant management
o Patients should receive extensive counseling on the risks of complications.
o Close surveillance is mandatory.
o β –hCG should be obtained every 48 hours until a decrease is confirmed, then
weekly until negative.
 Conversion to medical or surgical therapy
o Increasing symptoms
o β –hCG levels increase or plateau
 Hydatidiform Mole / Gestational Trophoblastic Disease / Molar Pregnancy
o Non–viable, abnormal gestation composed of hypertrophic and hydropic placental trophoblastic villi that
cause a marked elevation in β –hCG (> 100,000 IU/L)
 Result of abnormal fertilization of an empty ovum by either 2 sperm, or 1 sperm whose genome
then duplicates
 Premalignant – risk of development into choriocarcinoma
o Complications
 Pre–eclampsia
 Thyroid Disease
 Choriocarcinoma
 Surgical Complications – bleeding, anesthesia
 Recurrent Hydatidiform Mole
o Clinical Presentation
 May have atypical preeclampsia presentation < 20 weeks
 likely due to abnormal placental spiral artery development causing placental
hypoperfusion, placental ischemia, & maternal HTN
 Abnormal vaginal bleeding ± hydropic
villi tissue
 Uterine enlargement > gestational age
 Abnormally ↑ β –hCG levels
 Theca lutein ovarian cysts
 Hyperemesis gravidarum
 Preeclampsia with severe features
 Hyperthyroidism (e.g. hot flashes,
tachycardia, smooth warm skin, ↓ TSH)
 hCG has α & β subunits which
mimic TSH structure → ↑ T3 &
T4
o Risk Factors
 Extremes of maternal age (≤ 15 & ≥ 35
years)
 Additionally, age > 40 with
Hydatidiform mole at risk of more severe complications
 History of hydatidiform mole
 History of miscarriage
 Vitamin A deficiency (e.g. Roux–en–Y surgery)
o Pathophysiology
 Complete Mole
 Does not contain any fetal or embryonic parts
 Caused by fertilization of an empty egg that does not carry any chromosomes →
(Physiological) Haploid chromosome set contributed by the sperm is subsequently
duplicated.
o In rare cases, the formation of a complete mole may also result from simultaneous
fertilization of an empty egg by two sperms.
 Fetal karyotypes
o 46XX: more common (∼ 90% of cases)
o 46XY: less common (∼ 10% of cases)
 Partial Mole
 Contains fetal or embryonic parts in addition to trophoblastic tissue
 Caused by fertilization of an egg containing a haploid set of chromosomes with two
sperms (each of them containing a haploid set of chromosomes as well)
 Fetal karyotypes: 69XXX, 69XXY, 69XYY
 o Diagnosis
 Enlarged uterus + heterogenous cystic mass with anechoic, cystic spaces (“Snowstorm”
appearance on USS)
 Quantitative serum β –hCG
 Histologic evaluation of uterine contents –
 Hyperplastic and hydropic trophoblastic villi ± fetal or embryonic tissue
o Management
 Dilation & suction curettage, after which preeclampsia resolves
 Serial Serum Quantitative β –hCG post evacuation – marker of disease progression &/or remission
 Weekly initially until undetectable
 Once undetectable, monthly monitoring of β –hCG levels x 6 months
o If β –hCG is increasing/plateauing, or newly detectable β –hCG levels → diagnostic
of gestational trophoblastic neoplasia
o If β –hCG undetectable for 6 months (can take up to 8 weeks after uterine
evacuation), surveillance complete, can attempt pregnancy
 Contraception for 6 months
 Choriocarcinoma
o Aggressive, metastatic form of gestational trophoblastic neoplasia
o Risk Factors
 Advanced maternal age
 Prior complete hydatidiform mole
 Most commonly follows hydatidiform mole
 N.B. Can occur after a normal gestation or spontaneous abortion
o Clinical Features
 Presents < 6 months after pregnancy
 Amenorrhea or abnormal uterine bleeding
 Pelvic pain / pressure
 Symptoms from metastases (lung, vagina)
 Pulmonary metastases – chest pain, haemoptysis, dyspnea
 Vaginal metastases – bloody or purulent vaginal discharge
 Uterine mass
o Investigations
 Elevated quantitative β –hCG level
 CXR – staging (rather than CT Scan); most consistent with metastasis (multiple infiltrates)
o Treatment
 Chemotherapy or hysterectomy
 SLE nephritis in Pregnancy
o Risk factors for SLE flare complicated by nephritis
 Pregnancy and postpartum period, particularly in patients with history of lupus nephritis
 Discontinuation of hydroxychloroquine
 Active disease prior to conception
o Clinical Presentation
 Edema, HTN & proteinuria (overlapping features with preeclampsia)
 Malar Rash
 Arthritis
 Hematuria
o Laboratory Findings
 Nephritic range proteinuria
 Urinalysis with RBC & WBC cast
 ↓ Complement Levels
 ↑ ANA titres
 o Diagnosis – Renal Biopsy
o Obstetric Complications
 Preterm birth
 Caesarean delivery
 Preeclampsia
 Fetal Growth Restriction
 Fetal Demise
 Symptomatic Cholelithiasis in pregnancy
o Pathophysiology
 Pregnant women at increased risk of gallstones due to pregnancy – related hormonal changes
which supersaturate bile with cholesterol and decrease gallbladder motility
 ↑ Biliary cholesterol excretion (estrogen)
 ↓ Gallbladder motility (progesterone)
 Gallstones that form during pregnancy are rarely symptomatic, and are usually discovered
incidentally during prenatal ultrasound
 Asymptomatic patients require no treatment, as most pregnancy – related gallstones
resolve spontaneously within 2 months of delivery
o Clinical Features
 Recurrent, postprandial epigastric / RUQ pain, particularly those with concomitant obesity
 RUQ ultrasound with echogenic foci (gallstones or biliary sludge)
o Management
 Conservative (e.g. pain control for biliary colic)
 Cholecystectomy usually delayed until the postpartum period (for complicated, recurrent cases)
 If symptoms cannot be controlled with supportive care, cholecystectomy is often
performed in the 2nd trimester

Parvovirus B19 infection in pregnancy

Asymptomatic (most common)
Clinical Flulike symptoms with lace – like erythematous rash on trunk and extremeties
Presentation Acute, symmetric arthralgia / arthritis
Transient pure red cell aplasia, aplastic crisis
Acute Infection
o B19 IgM antibodies in immunocompetent
Diagnosis o NAAT for B119 DNA in immunocompromised
Previous Infection: B19 IgG antibodies
Fetus: PCR analysis of amniotic fluid for B19 DNA
Fetal Demise
Fetal
Aplastic Anemia
Sequelae
Hydrops Fetalis
Prenatal Serial Ultrasounds
management Middle Cerebral Artery Doppler measurements
Treatment Severe anemia: Intrauterine blood transfusion

 Sheehan Syndrome
o Pathogenesis
 Obstetric Hemorrhage complicated by hypotension
 Post–partum pituitary infarction
o Clinical Features
 Lactation failure (↓ prolactin)
 Amenorrhea, hot flashes, vaginal atrophy (↓ FSH, LH)
Fatigue, bradycardia (↓ TSH)
Anorexia, nausea, abdominal pain, weight loss, orthostatic hypotension (↓ ACTH &
normokalemia; secondary adrenal insufficiency & hyponatremia)
 Adrenal cortex in tact → aldosterone synthesis is unaffected
 Decreased lean body mass (↓ growth hormone)
 Syndrome of Inappropriate Antidiuretic Hormone (SIADH) – recall cortisol acts as an ADH
inhibitor
 Secondary Amenorrhea
o Absence of menses for:
 ≥3 cycle intervals in a patient who has previously had regular periods, or
 ≥ 6 consecutive months if she has previously had irregular periods e.g. oligomenorrhoea
 N.B. Pregnancy is the most common cause
o Gonadotropin Control of Ovarian & Endometrial Cycles:
 Increased estradiol increased cell sensitivity to FSH
 Pre-ovulatory Follicular phase (day 1 – 14; variable ± 7 days)
 Follicular phase GnRH pulsatility characterized by increased frequency and decreased
amplitude. Higher pulse frequency preferentially stimulates LH , whereas lower frequency
favours FSH secretion. FSH secretion is critical in initiation of follicular recruitment
 characterized by increased estradiol creates a positive feedback loop resulting in an LH
surge just prior to ovulation
 Post–ovulatory Luteal Phase (day 14-28; fixed)
 Empty follicle becomes corpus luteum under the influence of LH
 Increased progesterone & estradiol → negative feedback → decreased GnRH and
subsequently decreased FSH & LH
o ↑ progesterone in middle to late luteal phase of menstrual cycle maintains
endometrial lining and prepares it for implantation
o If fertilization & implantation occurs, developing blastocyst begins to produce hCG
and rescues the corpus luteum, thus maintaining progesterone production
o In absence of fertilization, corpus luteum regresses
 Decreased levels of Estradiol and progesterone → decreased negative
feedback inhibition of HPO–axis
o Etiology
 Hypothalamic Amenorrhea (35%)
 Defect in GnRH Pulse Production
o Dysfunction of HPO axis (most common)
 Excessive Physical Activity
 At risk of estrogen deficiency sequelae – infertility, vaginal atrophy,
breast atrophy, osteopenia
 “Female athlete triad” = amenorrhea + disordered eating +
osteopenia
 Nutrition–related –
 Anorexia nervosa, Bulimia
 Nutritional deficiencies – celiac disease, low body fat mass
 Rapid Weight loss (≥ 10% below ideal BW)
 Psychogenic & Emotional stress – e.g. Stress induced by chronic illness
 Hyperprolactinemia
 Drug–induced (<1%)
o Antipsychotics, antidepressants – TCAs, SSRIs, MAOI’s
o Anticonvulsants – Carbamazepine, Valproic Acid
 o Prokinetics (GI motility agents) – Metoclopramide,
Domperidone
o Antihypertensives – α–methyldopa, Reserpine, Verapamil
o Opiates
o H2 Antagonists
o Marijuana
o Others – chemotherapeutics, physotigmine, fenfluramine
 Pseudocyesis
o Drug–induced GnRH suppression
 Opioids
 Glucocorticoids
 GnRH analogues e.g. Danazol
 Defect in GnRH transport (i.e. Stalk transection or compression)
o Head injury, cranial radiation, tumours
o Sellar Mass / Lesions (Neoplasms &/or Infiltrative)
 Neoplasms – Hypothalamic Harmartoma, Craniopharyngiomas etc.
 Infiltrative & Infectious Processes – Sarcoidosis, hypophysitis, abscess
 Cystic lesions – Rathke’s cleft cyst
 Vascular lesions –AV fistula of cavernous sinus, aneurysm etc.
 Other Causes
o Idiopathic hypogonadotropic hypogonadism (more commonly 1o amenorrhea)
 Hypopituitarism (17%)
 Pituitary Adenomas / Tumours
o Lactotroph Adenomas (13%)
 Prolactinomas – Prolactin-secreting pituitary adenomas
 90% of 2O amenorrhea due to pituitary problems
o Other non-prolactin secreting adenomas
 Corticotroph adenomas i.e. Cushing’s Disease (1%)
 Acromegaly
o Non–functioning macroadenomas
o Nonadenomatous Tumours of the Pituitary & Sella Turcica
 Meningioma (of the sella)
 Germinoma, glioma
o Empty Sella Syndrome (1.5%)
 Pituitary infarct / apoplexy
 Sheehan’s syndrome (1.5%)
 Infarction, Infiltrative lesions
 Iatrogenic – Surgical ablation, Radiation
o Hemosiderosis
 Thalassemia major
o Isolated gonadotropin deficiency
 Ovarian and Ovulatory Dysfunction (40%)
 Hyperadrogenism
o PCOS (30%; Multifactorial)
 Oligomenorrhea (50%)
 Amenorrhea (20%)
 Assoc. w/ T2DM in adolescence
o Androgen-secreting ovarian tumour
 GnRH–resistant ovary syndrome (Savage syndrome)
o Non–autoimmune
o FSH–resistance → sparse Follicles
  Inhibin–secreting ovarian tumours – e.g. ovarian fibrothecoma (rare)
 Ovarian Failure – ↑ FSH, ↓ Estrogen
o Primary Ovarian Insufficiency (POI) or Premature Ovarian Failure (POF) – 10%
 persistent amenorrhea at age < 40 years associated with a
hypergonadotropic state that affects 1–5% of women
 Hypoestrogenic symptoms – e.g. hot flashes
 Etiology
 Premature natural menopause – Idiopathic
 Iatrogenic
o Pelvic Irradiation
o Alkylating chemotherapy (e.g. cyclophosphamide)
o Post–oopherectomy; also wedge resections & bivalving
 Autoimmune Oophritis
o SLE
o Blizzard Syndrome (PAS type 1)
o Schmidt Syndrome (PAS type 2)
 Post–infection (e.g. mumps oophritis – rare)
 Specific gene defects – e.g. Fragile X (FMR1 premutation),
Galactosemia
 Gonadal Dysgenesis
o Karyotypic abnormalities
- Mosaic Turner’s syndrome (45, XO, XX)
 Management –
 Estrogen therapy (with progestin if intact uterus to reduce risk of
endometrial cancer)
o May be contraindicated if specific risk factors (e.g. history of
breast cancer)
o Estrogen replacement should be continued till the average
age of menopause, around age 50
o Postmenopausal estrogen / progesterone therapy is
associated with significant risks (e.g. VTE, CAD), but the
absolute risks are substantially lower in young patients with
POI, and the benefits far outweigh the risks for most
patients
o Spontaneous & Physiologic – post–menopausal
 Uterus (7%) – Acquired Causes
 Asherman’s syndrome (symptomatic intrauterine synechiae)
o Complicated D&C
 Vigorous elimination of endometrium Following PPH, miscarriage or
elective abortion complicated by infection
o Post Uterine–surgery
 Metroplasty, myomectomy, caesarean section
o Infection related to an intrauterine device
o Tuberculous endometritis
 Cervical stenosis
o Iatrogenic – cryotherapy, cone biopsy, LLETZ / LEEP, D&C
o 2o to neoplasia (cervical or endometrial) or infection
 Systemic (<1%)
 Other Endocrine etiologies
o Hypothyroidism or hyperthyroidism
o Cushing’s Syndrome, Addison’s disease
 o Androgen-secreting adrenal tumour
o Adult–onset (‘Non-classical’) CAH (21–hydroxylase deficiency is the most common
cause)
o T1DM – Amenorrhea prevalence ↑’s with poor glycemic control
o Exogenous androgen use
 methyl-T or injected
 DHEA (food supplement)
 Infections (TB, syphilis, encephalitis / meningitis, sarcoidosis)
 Chronic renal failure
 Chronic Liver Disease
 Malnutrition, Obesity
 Haemosiderosis
 Maturity-onset adrenal hyperplasia
 Recently published women’s health initiative studies show that older postmenopausal women on hormone
replacement therapy are at an increased risk for myocardial infarction, deep vein thrombosis, strokes and breast
cancer. The findings of this study do not apply to younger patients with premature ovarian failure. Hormone
replacement therapy in the form of conjugated equine estrogen and medroxyprogesterone (either cyclic or
continuously; estrogen & progesterone combination helps to prevent endometrial cancer versus estrogen only
regimen) with careful monitoring can be safely used in younger patients without any excessive cardiovascular
risk
o Treatment with bone – specific agent indicated for significantly low bone density (i.e. osteomalacia and
osteoporosis) due to high risk of fractures
 Estrogen will improve bone mineral density and improve hypoestrogenic symptoms of POF (e.g.
hot flashes)
 Improvement in her bone density and reduction in her bone turnover will significantly reduce risk
of fragility fractures

Figure 1: Evaluation of Secondary Amenorrhea

 Infertility
 Couple’s inability to conceive after ≥ 12 months of appropriately timed intercourse (i.e. on cycle days 9 – 16)
without conception
 For women age > 35, evaluation occurs after ≥ 6 months of infertility
Etiology Diagnostic Test
 Semen analysis (non – invasive, low cost test; first step in infertility evaluation)
Male Factor o Sperm volume, pH, concentration, motility and morphology
o If abnormal analysis → intrauterine insemination or in vitro fertilization
Ovulatory Function  Midluteal phase (day 21) progesterone
 Day 3 FSH & estradiol levels
 Clomiphene citrate challenge test
Ovarian reserve
 Antral follicle count
 Anti–Müllerian hormone
Fallopian Tube Patency  Hysterosalpingogram
Uterine Cavity Evaluation  Sonohysterogram

Anogenital Warts (condyloma acuminata) in children Vulvar Cancer

Etiology Human papillomavirus infection (HPV 6 & 11) Persistent HPV infection (HPV 16 & 18)
transmitted via direct genital contact Chronic inflammation
Transmission Sexual abuse Risk Factors
Autoinoculation from other sites o Chronic Tobacco Use
Heteroinoculation from a caregiver (e.g. diaper changes) o Vulvar lichen sclerosus
Prenatal or perinatal o Immunodeficiency (e.g. HIV)
Adults o Prior cervical cancer
o Chronic tobacco use o Vulvar / cervical intraepithelial neoplasia
o Immunosuppression (e.g. HIV)
Clinical Multiple Pink/flesh–coloured lesions ranging from smooth, Vulvar pruritus, irritation & pain
Features flattened papules & plaques, to exophytic, verrucous / Vulvar plaque
cauliflower–like growths Abnormal bleeding – unifocal, erythematous
Located on the internal or external vulvar, vaginal and anal friable plaque or ulcer, on labia majora typically
regions in women Dyspareunia, dysuria
Asymptomatic (most common) Inguinal lymphadenopathy
Pruritic, friable lesions (may causes bloody spotting), Reddish, blackish, and/or whitish patches of
burning, tenderness, vaginal discharge and pain, depending discoloration
on location Diagnosis - Biopsy
o Large lesions can interfere with defecation, vaginal
intercourse, and vaginal delivery
Visual inspection with application of acetic acid (lesions
should turn white)
Spontaneous regression can occur but is uncommon
Managemen Sexual abuse assessment, especially age ≥ 4 Colposcopy & Biopsy
t Often self–resolving First–line treatment: local excision and surgical
If Symptomatic or unresolved disease → topical treatments resection (radical vulvectomy)
(e.g. podophyllotoxin, trichloroacetic acid therapy) and Radiotherapy and/or palliative chemotherapy:
surgical removal when disease metastasizes to peripheral lymph
Anogenital warts in Adults nodes or other organs
o Topical Chemical – 1st–line
 Podophyllin resin (C/I in breastfeeding)
 Not indicated for internal use, and should not be
used during pregnancy
 Trichloroacetic acid
 Destroys lesion by protein coagulation
 Repeated application may be necessary as
 clearance rate is not particularly high
o Topical Immunologic – Imiquimod, imidazoquinoline
(topical interferon)
 Contraindicated in breastfeeding
o Surgical – Cryotherapy, laser therapy, local excision
Prevention Adults – Vaccination, Barrier contraception 

CERVICAL CANCER SCREENING – Pap Smear (Papanicolaou test)

Demographics Screening Guidelines
Immunocompromised
(HIV, SLE, organ
Onset of sexual intercourse
transplant patients on
Initially every 6 months x 2 (i.e. 2 screenings in first year), then annually
immunosuppressants
)
Age < 21 No screening (N.B. screening is initiated at age 21 regardless of age of onset of sexual activity)
Age 21 – 29 Cytology every 3 years if negative

Negative cytology (for intraepithelial lesion or malignancy) & absent/insufficient endocervical /

transformation zone (EC/TZ) → routine screening
o Considered unsatisfactory sample if it is unlabeled, contains < 5000 well–visualized squamous cells,
or has obscuring inflammation or blood

Management of Atypical Squamous cells of undermined significance (ASC–US) or Low–grade

Squamous Intraepithelial Lesion (LSIL)
o Age 21 – 24 → Repeat Pap Smear in 1 year
 HPV infection tends to be transient in this population and malignant transformation is rare; thus
colposcopy only indicated if patient demonstrates ASC–US or LSIL on 3 consecutive Pap smears
 ASC–US is most common cervical cytologic abnormality, but risk of invasive cervical cancer is
low, as 40 – 60% are not associated with high–risk HPV infection
o Age ≥ 25 → HPV DNA testing
 Samples collected for both cytology and reflex HPV DNA. If cytology negative, HPV DNA sample
discarded
 If ASC–US + HPV DNA positive → Colposcopy
 If ASC–US but HPV DNA negative → HPV DNA testing + 3 – yearly pap smear

Management of Atypical Squamous cells, cannot rule out high–grade squamous intraepithelial lesion
(ASC–H), atypical glandular cells (AGC), or High–grade Squamous Intraepithelial Lesion (HSIL)
o All require colposcopy (ASC–H is associated with premalignant lesions) – 20% probability of
acquiring invasive cervical cancer if left untreated
 Some patients can proceed directly to a loop electrosurgical excision procedure (LEEP), an
excision of the cervical transformation zone and surrounding endocervix; these are women who
are age ≥ 25, are not pregnant, and have completed childbearing
o If colposcopy unsatisfactory → diagnostic excisional procedure (conization or loop electrosurgical
excision)
 No CIN 2 or 3 → follow–up colposcopy and cytology at 6 and 12 months
 If CIN 2 or 3 → see treatment guidelines below
Age 30 – 65 Cytology every 3 years OR
Cytology PLUS HPV testing every 5 years

If negative cytology & absent or insufficient EC/TZ → HPV testing

o If negative HPV testing → routine screening
o If positive HPV testing → cytology + HPV test in 1 year OR PV genotyping
Age ≥ 65 No screening if negative prior screens and not high risk for cervical cancer
Hysterectomy (with No screening if no history of high – grade precancerous lesion, cervical cancer, or exposure to
cervix removed) diethylstilbestrol
 Cervical Conization (scalpel [cold knife conization] or electrocautery [loop electrosurgical excision procedure])
o Indications – Cervical intraepithelial neoplasia grades 2 & 3**
 **Observation preferred for CIN 2 in young women, especially < 25 years with desire for
pregnancy
 Cytology and colposcopy every 6 – 12 months for 1 year
 HPV & tobacco use are important risk factors for CIN & Squamous cell carcinoma of the cervix
 Acetowhite changes on colposcopy
o Complications
 Cervical stenosis → secondary dysmenorrhea, or secondary amenorrhea
 Cervical incompetence & Preterm birth
 Preterm premature rupture of membranes
 Second trimester pregnancy loss
 Management of CIN 3
o Not currently pregnant →
 LEEP (Loop electrosurgical excision procedure)
 Cold Knife conization – Both diagnostic and therapeutic procedure
 Ablative therapy – Cryoablation / Cryosurgery, Laser Ablation
o If specimen margins are clear of disease and no evidence of invasion is found, Pap testing with HPV
contesting 1 and 2 years post–procedure
o N.B. HPV co-testing is otherwise performed to triage low-grade abnormalities on Pap smear, including
atypical squamous cells of undetermined significance and low-grade intraepithelial lesions (LSILs), which
may or may not be due to HPV infection.
 However HPV is the cause of high-grade intraepithelial lesions (HSILs), so HPV co-testing is not
necessary to be performed. Further evaluation of HSIL results is required with colposcopy and
biopsy due to risk of malignancy
 Cervical Cancer
o Risk Factors for Cervical Cancer
 Infection with high–risk HPV strains 16, 18, 33, 35
 Early onset of sexual activity
 OCP use
 Multiple or high-risk sexual partners
 History of sexually transmitted disease
 Immunosuppression
 Low socioeconomic status
 Tobacco use
o Management
 Direct biopsy
 Excision, radiation, or CTX depending on disease extent
 Human Papillomavirus
o Disease Associations
 Cervical Cancer
 Vulvar & vaginal cancers
 Anal cancer
 Penile cancer
 Oropharyngeal cancer
 Anogenital warts
 Recurrent Respiratory papillomatosis
o Vaccine Indications
 All female and male patients* age 11 – 26 (but may be given to those age 9 – 45)
 *Including those with hx of genital warts, abnormal Pap cytology, or positive HPV DNA
test
  Catch-up vaccination should be offered for patients who are either unvaccinated or did not
complete the series
 NOT indicated in pregnant women

Vaginal Cancer
Age > 60
Human Papillomavirus infection
Risk Factors
Tobacco use
In utero Diethylstilbestrol (DES) exposure (clear adenocarcinoma only)
Vaginal bleeding
Malodourous vaginal discharge
Clinical Features Irregular, vaginal lesion – plaque or ulcer located in upper third of posterior vagina
± Pelvic pain, urinary symptoms (e.g. hematuria), bulk symptoms (e.g. constipation)
are suggestive of metastatic disease
Vaginal biopsy – evaluates depth of invasion of atypical cells & differentiates
Diagnosis between vaginal intraepithelial neoplasia (i.e. non–invasive) & vaginal cancer (i.e.
invasive)
Surgery ± chemoradiation
Treatment
o Radical hysterectomy, vaginectomy, pelvic lymph node dissection

Prepubertal Vaginal Bleeding

Cause Key Features
Presents in neonatal period (within 1 st two weeks of life; may last for several days)
Lasts < 1 week
Maternal withdrawal of Examination otherwise normal
estrogen Sloughing of endometrial lining → self-limited, mucoid, vaginal bleeding
Effect of maternal estrogen may also lead to temporary breast bud & external
genitalia engorgement during 1st month of life
Usually unintentional from fall
Trauma Can be a sign of sexual abuse
Genital examination may show laceration / abrasion
Rare
Malignancy (e.g. vaginal
Presents age < 3
rhabdomyosarcoma,
Can present as a Genitourinary mass (grape – like structures protruding through the
Sarcoma botryoides [a
vagina)
type of embryonal
Typically vaginal and exclusively diagnosed in infants
rhabdomyosarcoma)
May visualize protruding vaginal nodules resembling grapes
Prepubertal girls
Vaginal spotting
Malodourous vaginal discharge
No signs of trauma (e.g. lacerations)
No vulvar symptoms (e.g. pruritus, erythema) & otherwise normal examination
Vaginal Foreign Body Toilet paper most common object. Other retained objects include small toys and
rubber bands
Management
o Warm irrigation or cotton swab to remove objects that are easily visualized in
frog – leg or knee–chest position
o Vaginoscopy under sedation / anesthesia

Emergency Contraception (EC)

 Pregnancy status determines eligibility
o Positive pregnancy test → not candidates for EC because implantation already has occurred
o In contrast, patients with a negative pregnancy test are still at risk for intended pregnancy and are candidates
Method Timing after intercourse Efficacy Contraindications
Copper – containing 0 – 120 hr > 99%  Acute pelvic infection
intrauterine device  Severe uterine cavity distortion
 Wilson disease
 Complicated organ transplant failure
52 mg Progestin–releasing Breast Cancer
IUD 0 – 120 hr > 99% Active Pelvic Infection
Severe Uterine Cavity Distortion
Ulipristal acetate 0 – 120 hr (up to 5 days)
 Progestin receptor blocker (administer as soon as
98 – 99% None
that delays ovulation & possible as effectiveness
impairs implantation decreases with time)
Oral Levonorgestrel 0 – 72 hr 92 – 98% None
OCPs*
(Combined estrogen /
progestin OCP containing
levonorgestrel or norgestrel) 0 – 72 hr 47 – 89% None
 High estrogen content
typically causes intolerable
ADRs (e.g. severe nausea)

 Routine screening for Syphilis with rapid plasma regain (RPR) indicated for high – risk individuals:
o Men who have sex with men
o Patients with co-existing HIV infection
o History of incarceration
o Sex workers
o Pregnant women are also routinely screened
 COMMON CONTRACEPTION SIDE EFFECTS
Method MOA
 Suppression of pituitary
gonadotropin secretion,
thereby inhibiting ovulation
 Progestogenic component
increases cervical mucus
viscosity → impaired
permeability & sperm
transport
 Progestin suppresses LH and
impairs ovulation
 Progestins have known
Combined Hormonal
effects on tubal transport
Contraceptives
(reduced cilia action), thereby
(pills, patch, ring)
narrowing or eliminating the
potential fertilization window
 Estrogenic component
impairs folliculogenesis via
negative feedback on FSH,
potentiates the effects of
progestins (allowing for lower
progestin doses to be used),
and stabilizes the
endometrium (improving
bleeding patterns)
DMPA  Suppression of FSH and LH
(Depo Medroxyprogesterone levels via inhibition of
Acetate) gonadotropin secretion,
Side Effects
 All: breakthrough bleeding,
breast tenderness & nausea,
headache
o 2 – 3 x increased risk of VTE
compared to non–users
(estrogen alters hemostasis)
o ↑ risk of cervical intraepithelial
neoplasia & cervical cancer, &
slight ↑ risk of breast cancer
 ↑ risk returns to normal
within 10 years of OCP
discontinuance
 Estrogenic effects – breast
tenderness, nausea, headaches,
& moodiness; typically resolve
over time
 Patch: Local skin irritation & rash
in application site
 Ring: Vaginal irritation or
discharge (leukorrhea)
Drug Interactions:
 Antiepileptic – Carbamezapine,
phenobarbital, phenytoin,
topiramate
 Antibiotic – rifampin
 Antifungal – Griseofulvin
 Antiretroviral – Protease
inhibitors (lopinavir, ritonavir),
NNRTIs (Efavirenz, nevirapine)
 Lansoprazole
 Tacrolimus
 Bosentan
 Initial irregular bleeding
 Amenorrhea within 6–12 months
 Short – term, reversible bone
Contraindications
 < 4 weeks postpartum (breastfeeding)
 < 21 days postpartum (not breastfeeding)
 Smoker ≥ 35 years (≥ 15 cigarettes/day)
 Vascular disease
 Stage II HTN (BP ≥ 160 / 100 mmHg)
 Acute DVT/PE
 History of DVT/PE, not receiving anticoagulant
therapy, with higher risk for recurrent VTE (e.g.
previous DVT in pregnancy, estrogen-dependent
DVT, antiphospholipid antibody syndrome)
 Major surgery with prolonged immobilization
 Known thrombophilia (e.g. APA)
 Current &/or history of IHD
 History of stroke
 Complicated valvular heart disease (pulmonary
hypertension, risk of atrial fibrillation, history of
subacute bacterial endocarditis)
 Systemic lupus erythematosus with positive (or
unknown) antiphospholipid antibodies
 Migraine with aura
 Peripartum cardiomyopathy with
moderately/severely impaired cardiac function
 Peripartum cardiomyopathy with normal/mildly
impaired cardiac function <6 months
 Current breast cancer
 Severe decompensated cirrhosis
 Hepatocellular adenoma
 Malignant hepatoma
 Complicated solid organ transplantation (graft
failure, cardiac allograft vasculopathy)
 Confirmed or suspected pregnancy
 Breast malignancy
 Prolonged use (> 2 years) not recommended

thereby eliminating the LH
surge:
o Inhibits ovulation &
follicular maturation
o Thickens cervical mucous
(less permeable to sperm)  Headache & dizziness
o Inhibits tubal motility
(reduced cilia action)
*Progestin only injectable,
o Inhibits endometrial
e.g. Depo-Provera
proliferation (less receptive  Depressed Mood, breast
to implantation)
Some studies suggests
reduced incidence of painful
crisis in Sickle Cell Disease by  Ulipristal acetate
stabilizing RBC & preventing  Aminoglutethimide (Cushing
sickling
 Progestins suppress
luteinizing hormone (LH) and
in turn block ovulation
 Blocks secretion of ovulatory
type cervical mucous
o Thickens cervical mucous
(less permeable to sperm)
Progestin Implant
Producing a thin, atrophic
(e.g. Jadelle, Implanon)
endometrium, precluding
implantation
Reducing the ciliary action of
the fallopian tube, preventing
sperm and egg transport
Diminishing the function of
the corpus luteum
Progestin IUD  Prevention of fertilization
mineral density loss (caution in
adolescents & perimenopausal
women)
o Adolescents on DMPA should
take calcium & vitamin D
supplementation, and perform
weight–bearing exercises
 ± Delayed return to fertility (up
to 12 months)
 ± Weight gain
tenderness
Drug Interactions (Few):
Syndrome)
 NO interaction between DMPA
and antiretroviral therapy.
 Irregular, unpredictable bleeding
 Acne (but may also improve
Acne)
 Depression
 Weight Gain
 Loss of Libido
 Mood Changes (emotional
lability, depression)
 Fertility is restored rapidly
following cessation of progestin–
only implants (c.f. Depo–
Provera)
 Risk of migration & difficult
removal (typically removed after
5 years)
 Risk of numbness and paresthesia
over anteromedial aspect of
forearm
 Initial irregular bleeding &
generally
 < 6 weeks post–partum
 Multiple risk factors for arterial cardiovascular
disease (older age, smoking, DM, HTN &
dyslipidemias)
 IHD (Current or Hx of), HTN (SBP > 140 mmHg, &
DBP > 90 mmHg)
 DM: Microvascular complications & other Vascular
Disease or DM > 20 years duration
 Liver: Hepatocellular adenoma, Hepatoma
 Hx of VTE (MEC 2), Current / Acute VTE (MEC 3)
 Rheumatic Diseases: Positive APA, Severe
thrombocytopenia (MEC 3 – I*), on
immpunosuppresive therapy (MEC 2/3*)
 Unexplained Vaginal Bleeding
 Confirmed or suspected pregnancy
 Breast malignancy
 Cirrhosis (severe, decompensated) – (MEC 3)
 Liver tumours – Benign hepatocellular adenoma or
malignant (hepatoma) – (MEC 3)
 Past & no evidence of current Breast Ca > 5 years
(MEC 3)
 Acute DVT / PE (MEC 3)
 Current & h/o IHD (MEC 3 – C*) Stroke (h/o CVA) –
(MEC 3 – C*)
 Positive or unknown antiphospholipid antibodies
(MEC 3)
 Migraine with aura at any age (MEC 3 – C*; without
aura: MEC 2)
 Unexplained vaginal bleeding before evaluation
(MEC 3)
 Pregnancy
  LNG–IUS contains a progestin
reservoir on its vertical stem
that slowly releases hormone
 Weak foreign body reaction &
(Levonorgestrel, LNG–IUD / endometrial changes that
Mirena or Jaydess) include endometrial
decidualization and glandular
Duration of efficacy: 3 – 7 atrophy
years  Changes amount & viscosity
of cervical mucus (barrier to
sperm penetration)
 Treats HMB, endometrial
hyperplasia, endometriosis
 Prevention of fertilization (&
inhibition of implantation if
post–fertilization – works as
emergency contraception)
 Foreign body & Cu2+ in
endometrial cavity causes
biochemical & morphological
endometrial changes.
oCu2+ adversely affect sperm
Copper IUD
motility, transport, & the
acrosomal reaction so
Duration of efficacy: 10 – 12
fertilization rarely occurs.
years
oCu2+ enhances the
inflammatory response and
is toxic for sperm, and
reduce ability of sperm to
penetrate cervical mucus
oTubal transit is affected and
apoptosis of the released
ovum is accelerated, which
decreases fertile window.
 Current pelvic inflammatory disease (PID) or
cramps
purulent cervicitis
 Amenorrhea
 Puerperal sepsis
 Hormonal symptoms, such as
 Immediately post–septic abortion
acne, breast tenderness,
 Known distorted uterine cavity
headaches, and altered mood
 Abnormal vaginal bleeding that has not been
that women
adequately evaluated
 Risk of Infection (PID risk
 Cervical or endometrial cancer awaiting treatment
increased slightly in the first 3
 Malignant trophoblastic disease with persistently
weeks after insertion)
elevated β –hCG and active intrauterine disease
 Potential for Uterine perforation,
 Pelvic tuberculosis
 Nulliparity associated with
 Current or Past history progestin receptor–positive
increased risk of expulsion
breast cancer > 5 years ago (LNG–IUS)
 Severe decompensated cirrhosis, hepatocellular
 Longer or heavier menses (up to adenoma, or malignant hepatoma (LNG-IUS)
↑ st
65% during the 1 year of use)  Wilson Disease or Copper Allergy (Copper IUD)
 Risk of Infection (PID risk  Complicated solid organ transplantation (i.e., graft
increased slightly in the first 3 failure, rejection, cardiac allograft vasculopathy)
weeks after insertion)
 Potential for Uterine perforation,
 Nulliparity associated with
increased risk of expulsion
 Ectopic pregnancy with an
intrauterine contraceptive (IUC)
is rare, but when a pregnancy
occurs with an IUC in situ, it is an
ectopic pregnancy in 15% to 50%
of the cases.
 In women who conceive with an
intrauterine contraceptive (IUC)
in place, early IUC removal
improves outcomes but does not
entirely eliminate risks
 Combined Oral contraceptives (Estrogen–Progesterone Contraceptives): Benefits & Risks
o Benefits
 Decreased risk of ovarian & endometrial cancer
 Pregnancy prevention
 Menstrual regulation (e.g. anovulation, dysmenorrhea, anemia)
 Hyperandrogensim treatment (e.g. hirsutism, acne)
o Drug Interactions
 Decreased OCP efficacy with CYP450 inducers
 Antiepileptic medications – phenytoin, carbamazepine, ethosuximide, phenobarbital,
topiramate
 Alternative antiepileptic drugs with no interaction – gabapentin, valproate
o Side Effects & Risks
 Breakthrough bleeding (most common; associated with low estrogen doses)
 Breast tenderness, nausea, bloating
 Amenorrhea
 Hypertension
 OCPs can cause mild ↑ BP & sometimes (in up to 5% of patients) leads to overt HTN
 Unclear mechanism; possibly due to estrogen–mediated increase in hepatic
angiotensinogen synthesis or other effects on the renin–angiotensin–aldosterone system
 Risk of HTN increases with duration of OCP use, and is elevated in those who have a family
history of hypertension or who developed hypertension in a previous pregnancy
 Venous thromboembolism disease
 Increased risk of cervical cancer & slight increased risk of breast cancer
 The increased risk returns to normal within 10 years of OCP discontinuance
 Liver disorders (e.g. hepatic adenoma)
 Increased triglycerides (due to estrogen component)
 Stroke, Myocardial Infarction (both very rare)
 N.B. although weight gain as an ADR is a common perception, several studies have shown no
significant weight gain
 Adenomyosis
o Pathogenesis
 Abnormal endometrial tissue within the uterine myometrium
 The ectopic endometrial tissue induces myometrial hyperplasia and hypertrophy
o Risk Factors
 Age > 40 years
 Multiparity
 Prior uterine surgery (e.g. myomectomy, caesarean delivery)
o Clinical Features
 Dysmenorrhea (due to endometrial proliferation in the myometrium)
 Heavy menstrual bleeding (due to increased surface area of the myometrium)
 ± Symptomatic anemia (e.g. fatigue, tachycardia)
 Chronic pelvic pain
 Diffuse uterine enlargement / uniformly enlarged uterus (e.g. globular uterus)
 ± Uterine tenderness

o Diagnosis
 Clinical Presentation
 MRI & Pelvic USS – Thickened myometrium
 Confirmed by histopathology
o Treatment
  Hysterectomy
 Medical management if not yet completed childbearing
 Progestins (e.g. progestin IUD, medroxyprogesterone acetate)
 However, adenomyosis does not completely respond to medical therapy

Anovulatory Uterine Bleeding

 Non–cyclical unopposed estrogen
o In early puberty, the immature HPO axis produces insufficient amounts of GnRH → inability to
mount an LH surge for ovulation
o When ovulation fails to occur, the corpus luteum does not form, progesterone production
Pathogenesis does not occur, and the normal synchronized endometrial sloughing triggered by
progesterone withdrawal (i.e. menses) does not happen
 Endometrial proliferation
 Estrogen breakthrough bleeding (dyssynchronous sloughing of varying portions of the
endometrium)
 Within 2 years post menarche
Clinical  Irregular, heavy bleeding
Features  Without premenstrual symptoms (e.g. No cramping, nausea, or breast tenderness)
 Normal physical examination
 Reassurance / observation; typically resolves within 1 – 2 years of menarche with maturation of
Managemen
HPO axis)
t
 ± Hormonal therapy

 Genitourinary Syndrome of menopause (Atrophic vaginitis)

o Pathophysiology
 Both age–related ovarian depletion (i.e. menopause) and surgical removal of the ovaries (e.g.
bilateral salpingo–oophorectomy) result in estrogen deficiency that affects the urogenital tissue
and causes associated urinary symptoms of atrophic vaginitis
 Reduced estrogen associated with menopause → decreased blood flow in the bladder trigone,
reduced collagen, reduced elasticity (which are all estrogen–sensitive tissues)
 Urogenital atrophy, which can induce urinary incontinence (urgency followed by
immediate loss of urine)
 Due to proximity of the bladder to the vaginal epithelium, the bladder trigone and
urethral epithelium may also atrophy
 Reduced glycogen content of vulvovaginal tissues → loss of vaginal lactobacilli and an elevated
pH, which increases risk of recurrent UTIs
 Thin vulvar vaginal skin with reduced elasticity & loss of vaginal tissue pliability → thin,
easily denuded vulvovaginal epithelium that causes dysuria when in contact with urine
o Symptoms
 Vulvovaginal dryness, irritation, pruritus
 Dyspareunia
 Vaginal bleeding
 Urinary incontinence & nocturia, recurrent UTI
 Pelvic pressure
o Physical examination
 Narrowed introitus
 Pale mucosa, ↓ elasticity, ↓ rugae (smooth, non–rugated vaginal epithelium with areas of patchy
erythema)
 Petechiae, fissures
 Loss of labial volume (labial retraction)
 Minimal vaginal discharge with pH > 4.5 (due to decreased lactic acid production from low
glycogen content)
o Treatment
 Non–hormonal vaginal moisturizer & lubricant (1st line)
 Topical vaginal estrogen (2nd line; indicated if no symptoms of relief or if severe symptoms)
 Transdermal Estrogen Patch
 Menopause
o Permanent cessation of menses (absent menses ≥ 12 months) at median age of 51 when loss of ovarian
function leads to hypoestrogenemia and its sequelae
o Clinical Manifestations
 Symptoms last for a few years until the cessation of menses (peri – menopausal period)
 Vasomotor symptoms (e.g. hot flashes, night sweats, sleep disturbances)
 Oligomenorrhea / amenorrhea
 Decreased libido
 Depression
 Cognitive decline
 Vulvovaginal atrophy – vaginal dryness, dyspareunia
 Osteoporosis
o Investigations – ↑ FSH (if diagnosis of menopause is uncertain)
o Treatment of Menopause
 If Mild Vasomotor Symptoms
 Behavioral modifications (e.g. wearing layers, weight loss)
 If Moderate / Severe Vasomotor Symptoms (Sleep disturbance, worsening fatigue, and hot
flashes e.g. awakening with sheets soaked in sweat)
 Topical vaginal estrogen (low dose vaginal estrogen therapy)
 If no contraindications to estrogen → systemic hormonal therapy
o Estrogen only (e.g. transdermal estrogen patch) if no uterus (e.g. hysterectomy)
 Preferred because estrogen + progesterone therapy has small increased
risk of breast cancer with long–term (> 3 – 5 years) use
o Estrogen + Progestin (e.g. COCs) if intact uterus
 If Contraindications to Estrogen* (e.g. Breast Cancer, Coronary Artery Disease,
Endometrial Cancer, Liver Disease, Thromboembolism)
o Non–hormonal Therapy (e.g. SSRIs – paroxetine, SNRIs – venlafaxine)
o In patients refractory to SSRIs or C/I to paroxetine (e.g. current tamoxifen use),
clonidine or gabapentin may be used
 However these medications may have intolerable side effects, including
hypotension (clonidine) and headache / dizziness (gabapentin)
Effects of Combined Estrogen / Progesterone Menopausal Hormone Therapy
Beneficial Detrimental Neutral
Menopausal symptoms (e.g. hot flashes, Venous thromboembolism Cognition / dementia
vaginal atrophy) Breast cancer Endometrial cancer (increased with
Bone mass / fractures Coronary artery disease (age ≥ 60) unopposed estrogen)
Colon cancer Ischemic Stroke, although the absolute Ovarian cancer
Type 2 Diabetes Mellitus (DM II) – risk is small in women age < 60 All – cause mortality (age ≥ 60)
possibly due to decrease insulin o N.B. increased risk is not eliminated
resistance by management of blood pressure or
All – cause mortality (age < 60) other traditional stroke risk factors
Gallbladder Disease

 Anovulatory Uterine Bleeding in Menopausal transition

o Pathophysiology
  After age 40, the absence of ovulation (anovulation) is physiologic as gradual oocyte depletion &
abnormal follicular development lead to failure of progesterone secretion from the ovaries
 However, endometrium may continue to proliferate due to estrogen, which leads to inconsistent
menstrual bleeding
o Clinical Features
 Periods of amenorrhea followed by irregular unpredictable bleeding
o Evaluation
 Endometrial biopsy for any of the following conditions
 Age ≥ 45 with suspected anovulatory uterine bleeding
o Risk of endometrial hyperplasia and cancer increases with age and long periods of
anovulation
 Age < 45 with risk factors of unopposed estrogen (e.g. obesity, PCOS), failed medical
management, or persistent abnormal uterine bleeding
 Endometrial hyperplasia and cancer cannot be distinguished clinically as bleeding can range from
spotty to heavy
 In perimenopausal women, pelvic USS for endometrial thickness is not useful as hormonal
activity is still present and endometrial thickness is variable
o Treatment – all options offer endometrial protection from unopposed estrogen
 Cyclic progestin therapy
 Low – dose oral contraceptive pill
 Levonorgestrel Intrauterine device
 Cyclic hormonal therapy

Selective Estrogen Receptor Modulators (SERMs)

Drugs  Tamoxifen
o Estrogen antagonist in breast
o Estrogen agonist in endometrium and bone
 Raloxifene
o Estrogen antagonist in breast and endometrium (N.B. may worsen hypoestrogenic
symptoms e.g. hot flashes)
o Estrogen agonist activity in bone
Mechanism of action  Competitive inhibitor of estrogen binding
 Mixed agonist / antagonist activity
Indications  Prevention of breast cancer in high–risk patients
 Tamoxifen: prevention & treatment of estrogen receptor positive breast cancer (1 st line in
premenopausal women to prevent recurrence)
o Should be continued for 5 years as adjuvant therapy for hormone receptor positive
breast cancer, unless significant ADRs or toxicities
 Raloxifene: postmenopausal osteoporosis (less effective than alendronate); prevention
(NOT treatment) of breast cancer
 Toremifene: Treatment (NOT prevention) of breast cancer
 Ospemifene: Treatment of vaginal atrophy
 Clomiphene: Treatment of ovulatory failure
Contraindications  Current or prior VTE disorders (e.g. PE, DVT, renal vein thrombosis)
Adverse Effects  Hot flashes (induces menopause)
 Venous thromboembolism
 Endometrial hyperplasia and carcinoma (tamoxifen only – secondary to agonist activity)
o No routine gynecologic surveillance indicated unless symptomatic of abnormal PV
bleeding or vaginal symptoms
o Most of these cancers are localized, stage 1 lesions, typically in women > 50 years old
 Vulvar lichen Planus
o Clinical Features
 Women age 50 – 60
 Vulvar pain or pruritus
 Dyspareunia
 Acute vaginal inflammation that causes friable vaginal mucosa and a serosanguinous vaginal
discharge
 Erosive Variant (most common)
 Erosive, glazed lesions with white border (Glazed, brightly erythematous vulvar erosions
with a border of serpentine–appearing, white striae [i.e. Wickham striae] that typically
cause vulvar pain, pruritus and dyspareunia)
 Vaginal involvement ± stenosis
 Associated oral ulcers
o Lacelike, reticular erosions on the gingivae and palate that cause painful oral
ulcers, and plaque formations on the tongue
 Papulosquamous variant:
 Small pruritic papules with purple hue
o Diagnosis – vulvar punch biopsy (clinical features of vulvar lichen planus may overlap with vulvar cancer)
o Treatment – High–potency topical glucocorticoids
 Vulvar Lichen Sclerosus
o Benign, chronic inflammatory disease that commonly causes thinning of the vulvar skin in
hypoestrogenic populations (e.g. prepubertal girls, postmenopausal women); it is particularly common in
those with an autoimmune disease (e.g. DM type I)
o Epidemiology
 Prepubertal girls
 Perimenopausal or postmenopausal women
o Clinical Features
 Chronic irritation and scratching transformed initially thinned skin to thickened, white vulvar
plaques (i.e. lichenification) with associated erosions, often with perianal thickening with
fissures in a classic figure 8 pattern
 Thin, white, wrinkled skin over the labia majora / minora; atrophic changes that may
extend over the perineum & around the anus
 Excoriations, erosions, fissures from severe vulvar & perianal pruritus & burning
 In severe cases, normal anatomic structures may be obliterated or atrophied, leading to loss of
the labia minora and clitoral hood retraction
 Dyspareunia
 Urinary symptoms – dysuria, nocturia
 Dyschezia (painful defecation)
 Anal fissures & constipation (2O lichenification of perianal region)
 Typically no vaginal involvement (c.f. vulvar lichen planus)
o Investigations
 Vulvar punch biopsy of adult–onset lesions to exclude vulvar cancer (which can occur in patients
with prolonged or persistent lichen sclerosus)
 N.B. children have no associated malignancy risk and can be diagnosed clinically
o Treatment
 Super–potent corticosteroid ointment (e.g. clobetasol)
 Decreases chronic inflammation
 May also prevent disease prevention to vulvar intraepithelial neoplasia or vulvar cancer
 ± Topical emollients for daily symptom management
 Fused Labia minora due to Labial adhesions
o Epidemiology – most commonly prepubertal girls due to low estrogen production
 o Pathophysiology
 Inflammation from poor hygiene, infection (e.g. vaginitis), irritation (e.g. diaper rash), or trauma
(e.g. straddle injury) also contributes to the development of adhesions
o Clinical Features
 Labial adhesions can be partial (involving a portion of the labia) or complete
 Partial adhesions can be asymptomatic
 Vaginal pain or pull
 Adhesion covering the urethral meatus can also cause an abnormal urinary stream and increased
risk for recurrent UTIs due to urine accumulation
o Treatment
 Topical estrogen is 1st line therapy for those with symptoms
 Mild, asymptomatic adhesions require no treatment
 Urinary Tract Infection
o Pathogenesis
 Escherichia coli (most common for acute cystitis, both pregnant and non – pregnant)
 Less common pathogens –
 Staphylococcus saprophyticus (young sexually active female)
 Proteus mirabilis
 Klebsiella pneumoniae
 Ascending infection
 Risk factor in women > men (short length of urethra and proximity to vagina and rectum)
o Clinical Features
 Dysuria, Urinary Urgency and Frequency, Haematuria
 Cystitis usually afebrile
 Suprapubic pain = cystitis
 Flank Pain = pyelonephritis
 ± Urinary incontinence due to bladder spasm
o Diagnosis
 Urinalysis
 Pyuria
 Leukocyte esterase positive (indicates WBCs in bladder due to cystitis)
 Nitrites positive (variable; depends on inoculation time, pathogen type, urine pH changes)
 ± Haematuria
 Bacteriuria on urine culture
 Urine pregnancy test prior as many antibiotics are teratogenic; if pregnancy, a urine culture is
also repeated 1 week after antibiotic treatment to ensure resolution
 Recall bacteriuria during pregnancy is associated with an increased risk for complications
such as acute pyelonephritis and acute respiratory distress syndrome
o Treatment – antibiotics (e.g. nitrofurantoin, Bactrim [TMP–SMX / trimethroprim–sulfamethoxazole])
 Empiric treatment typical for cystitis
 UTI antibiotics in pregnancy
 Recommended –
o Amoxicillin–clavulanate, cephalexin, fosfomycin
o Nitrofurantoin (T2 & early T3 only)
 Avoid in T1 (risk of orofacial clefts in T1) AND
 Avoid in late T3 / at term (association with neonatal hemolytic anemia)
 Contraindicated –
o Tetracyclines
 Teeth discoloration and poor enamel formation; impair fetal long bone
development
o Fluoroquinolones
  Toxic to fetal cartilage development
o Trimethoprim – sulfamethoxazole
 Contraindicated in 1st and 3rd trimesters
 Neural tube defects, cardiac defects, cleft palate
 Secondary to Folate antagonist properties of trimethoprim
 Use in late T3 is associated with neonatal kernicterus
o Gentamicin (an aminoglycoside; irreversible congenital deafness)
 Asymptomatic Bacteriuria with GBS (Streptococcus agalactiae) in Pregnancy
o Less common than E. Coli
o High risk of progression to cystitis and /or pyelonephritis
 Due to effects of progesterone on the upper urinary tract (e.g. smooth muscle dilation, ureteral
enlargement, vesicoureteral valve dysfunction
o Presence suggest significant genital colonization with Group B Streptococcus, which is associated with
increased risk of preterm labour and premature birth
o Treat immediately with 10 – day course of antibiotics
 Penicillin G or Cephalexin (both considered safe to fetus)
 Repeat urine culture after completing treatment course
 Pyelonephritis in pregnancy
o Risk Factors
 Asymptomatic Bacteriuria
 Pre-gestational DM
 Age < 20
 Nulliparity
 Tobacco Use
 Acute pyelonephritis more common in Pregnancy
 Physiological maternal immunosuppression during pregnancy
 Progesterone–induced ureteral dilatation, ureteral valve laxity, and bladder compression
from gravid uterus
o Common Pathogens
 E. coli (most common)
 Klebsiella
 Enterobacter
 Group B Streptococcus
o Clinical Features
 Cystitis (e.g. dysuria, suprapubic tenderness)
 Fever, chills
 Maternal and fetal tachycardia
 Costovertebral angle tenderness
o Complications
 Maternal –
 Preterm Labor
 ARDS
 Sepsis
 Fetal – Low Birth Weight
o Treatment
 IV hydration & IV antibiotics
 Empiric Treatment – broad–spectrum β –lactam antibiotics (e.g. ceftriaxone, cefepime)
 Once patients remains afebrile for 48 hours with symptomatic improvement, transition to
oral antibiotics (e.g. cephalexin, amoxicillin–clavulanate, low–dose Nitrofurantoin,
Fosfomycin) for 10 – 14 days
  N.B. After treatment completion, daily antibiotic suppressive therapy (e.g. low–dose
nitrofurantoin, cephalexin or amoxicillin) is initiated and maintained until 6 weeks
postpartum to prevent recurrence
 If patient does not improve for 48 – 72 hours of IV antibiotics → renal USS to evaluate for
renal abscess, or nephrolithiasis
 Supportive therapy

Acute Cystitis & Asymptomatic Bacteriuria during pregnancy

Clinical Features Management
 Positive urine culture (≥ 100,000 [i.e. 10 ] CFU/mL)
5
 Obtain sample for urine culture prior to
bacteria in clean catch urine sample in absence of initiating therapy & adjust antibiotic as
urinary symptoms needed
 Screening at initial prenatal visit  Due to high risk of persistent bacteriuria
Asymptomatic
 Risk Factors – pre–gestational DM, Hx of UTI, & treatment failure, urine Cx is repeated
Bacteriuria
Multiparity for test of cure, one week after
 Treatment decreases progression to cystitis & treatment completion
pyelonephritis, & fetal complications (e.g. preterm
birth, low birth weight, perinatal mortality) Treatment – 1st line
 Symptomatic patient with positive urine culture  Oral Cephalexin for 3 – 7 days
 Complicated UTI  Amoxicillin–clavulanate for 3 – 7 days
Acute Cystitis  Fosfomycin as single dose
Treatment – 2nd line
 Nitrofurantoin for 5 – 7 days

Treatment of Acute Cystitis & Pyelonephritis in Non–pregnant women

 Nitrofurantoin for 5 days (avoid in suspected pyelonephritis or creatinine clearance < 60 mL/min
 Trimethoprim–Sulfamethoxazole for 3 days (avoid if local resistance > 20%)
Uncomplicated
 Fosfomycin single dose
Cystitis
 Fluoroquinolones only if above options cannot be used
 Urine culture needed only if initial treatment fails
 Fluoroquinolones** (5 – 14 days), extended – spectrum antibiotic (e.g. ampicillin / gentamicin)
Complicated
for more severe cases
Cystitis*
 Obtain sample of urine culture prior to initiating therapy & adjust antibiotic as needed
 Outpatient: Fluoroquinolones (e.g., ciprofloxacin, levofloxacin)
Pyelonephritis  Inpatient: Intravenous antibiotics (e.g. fluoroquinolones, aminoglycoside ± ampicillin)
 Obtain sample for urine culture prior to initiating therapy & adjust antibiotic as needed
* Associated with diabetes, pregnancy, renal failure, urinary tract obstruction, indwelling catheter, urinary procedure
(e.g. cystoscopy), immunosuppression, & hospital–acquired
** Do not use Fluoroquinolones in pregnancy (toxic to developing cartilage). Consider cefpodoxime, cephalexin,
amoxicillin-clavulanate & fosfomycin

 Renal Colic In Pregnancy

o Paroxysmal, severe flank pain that radiates to the
labia suggestive of nephrolithiasis
o Nausea, vomiting, dysuria, hematuria, and pyuria
o Nephrolithiasis most common during 2nd and 3rd
trimester
o Predisposing Factors
 Increase in urinary calcium excretion
 Urinary stasis
 Decreased bladder capacity in pregnancy
 o Risk Factors
 Obesity
 Hyperparathyroidism
 Diabetes Mellitus
 Irritable Bowel Syndrome
 History of nephrolithiasis outside of pregnancy
o Management of nephrolithiasis in pregnancy
 Supportive and pain control PRN. Most stones pass spontaneously
 Nephrolithiasis that is complicated by persistent obstruction, intractable pain, or UTI may require
surgical management
DISORDERS OF SEX DEVELOPMENT
5–alpha reductase deficiency
Pathogenesis  46 XY genotype
 Autosomal recessive
 Impaired testosterone to DHT conversion
→ Failure of DHT–dependent virilization of
external genitalia & Impaired virilization
during embryogenesis
 Normal male testosterone & estrogen levels
Clinical  Phenotypically female at birth
Features  Male internal genitalia (e.g. testes, vas
deferens etc.)
o Undescended male testes within labia
majora
 Female external genitalia (e.g. blind–ending  Primary amenorrhea
vagina)
 Virilization at puberty (↑ testosterone @
puberty)
o Clitoromegaly (phallic growth)
o Increased muscle mass
o Testicular descent, development of male
gender identity
o Male–pattern hair development
o Nodulocystic acne
o Absent breast development (testosterone
binds to breast androgen receptor and
inhibits breast tissue proliferation)
 Normal / ↑ testosterone, ↓ DHT (elevated
testosterone–to–DHT ratio)
 Estrogen levels are normal
 Normal / ↑ LH
Management  Female gender identity: gonadectomy;
estrogen substitution therapy upon
completion of longitudinal growth
 Male gender identity: testosterone
substitution
Figure 2: Renal Colic in Pregnancy
Androgen Insensitivity Syndrome (AIS)
 46 XY genotype
 X–linked mutation → Defective androgen receptor
prevents virilization during embryogenesis
o Peripheral testosterone resistance → failure to
develop male external genitalia
 Functioning testes present → characteristic fetal &
pubertal development associated with AIS
o During fetal AIS embryogenesis, testes produces anti–
Mullerian hormone (AMH) and testosterone
o AMH causes regression of Müllerian structures (i.e.
uterus, upper one–third of vagina)
o In contrast, testosterone has no activity on peripheral
tissues due to resistant androgen receptors, and male
external genitalia fail to develop, defaulting to female
external genitalia (e.g. lower two–thirds of vagina)
 Phenotypically female at birth
 Female external genitalia
 Genotypically male – 46, XY karyotype
 Male internal genitalia
 Absent uterus, cervix & upper 1/3 of vagina
 Tall stature
 Absent (or minimally present) axillary & pubic hair
 Breast development at puberty
o Free testosterone is aromatized to estrogen, resulting
in breast tissue proliferation and tall stature
 Cryptorchid testes (may be found in abdomen, inguinal
canal or labia majora)
o Increased risk of testicular cancer (e.g. dysgerminoma,
gonadoblastoma), due in part to an elevated
intraabdominal temperature that causes abnormal
spermatogenesis & aberrant germ cell differentiation
 ↑ testosterone, estrogen, LH (vs sex chromosome
disorders).
 Gender identity / assignment counselling
 Gonadectomy (malignancy prevention, potential benefits
on androgen–stimulated puberty [e.g. attainment of
adult height])
 Estrogen therapy may be used to maintain feminization in
 patients with AIS after gonadectomy

 Mullerian Agenesis (Mayer-Rokitansky-Küster-Hauser Syndrome)

o Pathogenesis
 46, XX karyotype
 Mullerian (i.e. Paramesonephric) duct system defect
 Abnormal development of uterus, cervix, & upper one–third of vagina
 External genitalia develop from different precursor (i.e. genital tubercle) and patients have
normal female external genitalia and lower two–thirds of the vagina
o Clinical Features
 Primary amenorrhea
 Normal secondary sexual characteristics (e.g. breast development, normal stature)
 Normal female external genitalia
 Normal axillary and pubic hair development
 Blind vaginal pouch (lower two–thirds of vagina)
 Absent or rudimentary uterus
 Bilateral functioning ovaries present (FSH normal)
 Normal estrogen levels
o Management
 Evaluate for renal tract abnormalities such as duplicated ureters (e.g., renal ultrasound)
 Vaginal dilation (surgical or non–surgical) to create a functional vagina for sexual intercourse
 Primary Amenorrhea Evaluation
o Primary amenorrhea = absence of menarche in girls age ≥ 13 with no secondary sexual characteristics (or
girls age ≥ 15 with secondary sexual characteristics, e.g. axillary / pubic hair)
o Initial evaluation is pelvic ultrasound
 Uterus Absent → investigate Karyotype
 46 XY = androgen insensitivity
 46 XX = Mullerian agenesis (blind vaginal pouch on exam)
 Uterus Present → investigate FSH
 helps distinguish between central and peripheral causes of amenorrhea in HPO axis:
o Low FSH suggest hypothalamic (↓ GnRH) or pituitary (↓ FSH secretion / production)
cause → investigate TSH, Prolactin
 ↑ TSH, ↑ Prolactin → Hypothyroidism
 Normal TSH, ↑ Prolactin → Prolactinoma
 Normal TSH & Prolactin → Functional Hypothalamic amenorrhea (may also
cause secondary amenorrhea)
 Risk Factors – Excessive physical training, Very low calorie diet or
starvation, Weight loss, Chronic illness, Stress & depression,
Anorexia Nervosa results in:
o ↑ Ghrelin, Neuropeptide Y, CRH, GABA & beta–endorphins &
↓ Leptin → ↓ GnRH, LH, FSH, Estrogen
o Consequent amenorrhea, low estrogenic state, bone loss
 Female athlete triad:
o Low energy availability with or without disordered eating,
o Menstrual dysfunction
o Low bone density
 Treatment
o Behavioural (e.g. increased caloric intake)
o Estrogen repletion (if non–pharmacologic tx has failed)
  For those unable or unwilling to treat underlying
etiology (e.g. unable to decrease stress levels, refuse
to modify exercise patterns)
o Normal FSH
 Imperforate Hymen – peripheral cause that does not affect HPO axis
 Bulging, bluish membrane between the labia (i.e. blue intralabial
mass) around time of expected menarche
 Cyclic abdominal pain + primary amenorrhea
o Uterine enlargement (e.g. tender suprapubic mass) can lead
to bulk symptoms (e.g. anorexia, constipation, weight loss)
 Mild abdominal tenderness & small, rounded, palpable mass in
pelvic area
o Hematocolpos – vaginal retention of menstrual blood
behind the imperforate hymen @ puberty
o N.B. Can be diagnosed in the neonatal period; newborns
have elevated estrogen levels that can result in
accumulation of vaginal discharge behind the hymen (e.g.
mucocolpos)
 Normal pubertal development
 An untreated imperforate hymen can cause retrograde menses
through the fallopian tubes and lead to intraabdominal adhesive
disease
 Tx - hymenectomy
 Transverse Vaginal Septum
 Malformation of urogenital sinus & Mullerian ducts
 Hematocolpos is palpable over abdomen, but no bulging bluish
membrane
 Septum may appear as blind vaginal pouch
o High FSH suggest peripheral cause (i.e. ovarian; lack of ovarian estrogen and
inhibin production) → Karyotype
 46, XX = Primary ovarian insufficiency
 45, XO = Turner’s Syndrome

Diagnostic Findings of Amenorrhea

Disease GnRH LH FSH Estrogen TSH Prolactin
Menopause ↑ ↑ ↑ ↓ normal normal
Functional Hypothalamic Amenorrhea (Hypothalamic
↓ ↓ ↓ ↓ normal normal
hypogonadism)
Prolactinomas ↓ ↓ normal ↑
Polycystic Ovarian Syndrome ↑ normal ↑ normal normal
Hypothyroidism ↓ ↓ ↓ ↑ ↑
Primary ovarian insufficiency
↑ ↑ ↑ ↓ Normal Normal
(hypergonadotropic hypogonadism)
Exogenous estrogen use ↓ ↓ ↓ ↑
Norm
Asherman Syndrome Normal Norma Normal Normal Normal
a
Amniotic fluid index (AFI; Normal: 8 – 24 cm) varies with gestational age and peaks at 30 – 32 weeks gestation before gradually
declining; during 3rd trimester AFI ≤ 5cm is always abnormal
Polyhydramnios (AFI ≥ 24 cm; single deepest
Oligohydramnios (AFI ≤ 5cm)
pocket ≥ 8cm)
Early gestation oligohydramnios concerning for fetal  Esophageal / Duodenal atresia
etiologies  Tracheoesophageal fistula will impair fetal
o Aneuploidy swallowing and removal of amniotic fluid
o Renal Agenesis (decreased fetal urination)  Anencephaly
o Posterior Urethral Valves  Multiple Gestation
o Fetal congenital infections (e.g. CMV)  Diabetes Mellitus
nd rd
2 & 3 trimester  Congenital Infection
o Uteroplacental insufficiency (with concomitant fetal
Etiology growth restriction & decreased fetal urine output)
 Chronic HTN, Preeclampsia
 SLE
 Abruptio Placentae
 NSAIDs
o Maternal causes
 Dehydration
 Rupture of membranes (with normal fetal
growth)
Meconium Aspiration  Fetal malposition (e.g. breech)
Preterm delivery  Umbilical cord prolapse
Umbilical cord compression  Preterm Labor
 Uterine overdistension may cause inflammation,
Complications
prostaglandin release, uterine irritability, and
increased risk of PTL
 Preterm premature rupture of membranes
 Postpartum uterine atony

 Indications for prophylactic administration of anti-D immunoglobulin for Rh(D)–negative patients*

o *N.B. antepartum prophylaxis is not indicated if the father is Rh(D) negative
 At 28–32 weeks’ gestation
 < 72 hours after delivery of Rh(D) positive infant OR spontaneous abortion
 Ectopic pregnancy
 Threatened abortion
 Hydatidiform mole
 Chorionic villus sampling, amniocentesis
 Abdominal trauma
 2nd– & 3rd–trimester bleeding
 External cephalic version
o Anti–D immunoglobulin masks Rh(D) antigens on fetal RBCs, thereby preventing maternal anti–D
antibody production and alloimmunization
 Rh Alloimmunization / Rh Isoimmunization
o Pathophysiology
 Evidence of fetomaternal mixing of fetal Rh+ & maternal Rh– blood during 1st Pregnancy
 Fetal Rh+ RBCs enter maternal bloodstream & generate maternal anti–D antibodies
 Mixing can occur during other fetomaternal risk states →
o Ectopic pregnancy
o Dilatation & Curettage (D&C)
o Placental abruption
o Placental previa
o Miscarriage (spontaneous or induced abortion)
o Amniocentesis
 o External cephalic version
 Paternal blood type is Rh positive
 Pregnancy 2 or after inciting event (e.g. Pregnancy 1 after placental abruption)
 Anti–Rh(D) antibodies cross placenta & cause lysis of fetal RBCs → Hemolytic Disease of
the Fetus / Newborn
o Hydrops fetalis due to Rh incompatibility
o Postnatal
 Neonatal anemia
 Hepatosplenomegaly
 Neonatal jaundice (usually within 24 hrs of birth) → Risk of Kernicterus
 Hypoxia
 Prematurity
o Investigations & Management
o Maternal –
 CBC, Blood Group, Rh Status
 If Rh negative mother, Indirect Coombs Test [IDCT] x2 (@ 1st booking, & @ 20 weeks)
 ≥1:32 – 1:64 is considered significant and suggests sensitization
o 1:16 requires additional surveillance (indeterminate)
o Initial positive antibody screen at booking with titre 1:2 suggest previous anti–D
antibody developed from prior pregnancy
o More than 4 – fold rise in antibody titres is concerning for a significant risk of
hemolytic disease and should prompt fetal evaluation for anemia and hydrops
fetalis
 Repeat every 4 weeks up until 38 weeks; increased frequency of testing, if test is
positive, and fetus is monitored closely for any complications
o Non–invasive – Fetal Middle Cerebral Artery Ultrasound (Fetal MCA Doppler USS)
& Doppler Studies at 2–week intervals
 High peak velocity correlates well with severe fetal anemia
 > 1.5x median = moderately affected fetus
 >1.55x median = severely affected fetus
o Invasive –
 Amniocentesis & Spectrophotometry of Amniotic Fluid (light @ 450 nm)
 Liley’s Chart
o Zone 3 - severely affected fetus; delivery dependent on
resources of neonatal ICU (NICU) – intrauterine transfusions
(<30-32 weeks) to increase Hb before taking pregnancy to
term
o Zone 2 - moderate disease; “grey zone”, monitor to 32
weeks to determine possible delivery
o Zone 1 - mildly affected or no disease; can take pregnancy
to term and deliver at term
 If fetus is preterm, cordocentesis or percutaneous umbilical cord blood
sampling to directly assess fetal haematocrit
 Intrauterine transfusions are generally performed between 18 & 35 weeks’
gestation; after 35 weeks, the risk/benefit ratio favors delivery of a fetus
with evidence of severe anemia
 Fetal vein cannulated and blood infused
 use 60 – 120 ml of O negative, CMV–negative, washed, leukocyte–
reduced, irradiated pRBCs @ < 34 weeks’ gestation, followed by
delivery of fetus at 34–35 weeks
 At 28 weeks, if IDCT negative → administer IM 300 μg of anti–D Immunoglobulin
 o N.B. anti – D immune globulin should not be administered to a sensitized patient
due to lack of efficacy
 40 week visit – If > 12 weeks have elapsed since anti–D Ig administration, consideration
should be given to administer 300 μg anti–D immunoglobulin at 40 weeks’ gestation
o Peripartum anti–D immune globulin indicated to reduced risk of Rh(D)
isoimmunization due to fetomaternal transfusion during delivery
 Postpartum –
o If infant / neonate is Rhesus D positive → all Rh D negative mothers should receive
300 μg of Rh(D)Ig (Rhogam) IM within 72 hours of delivery
 Rossette Test
o Qualitative test the helps determine the presence of feto–maternal hemorrhage.
o If negative, standard dose of anti – D immune globulin should be administered
o If positive, the amount of hemorrhage can be evaluated using the Kleihauer–Betke
test, to determine necessary dose adjustments for anti – D immune globulin
 Kleihauer–Betke test (or fetal red cell stain) using flow cytometry – used to measure fetal
cells in maternal circulation
o Generally indicated when there is a large antepartum hemorrhage in a Rh –
negative mother
o Procedure
 RBCs from maternal circulation fixed to a slide
 Slide exposed to acidic pH solution
 Maternal hemoglobin (A) lyses and fetal hemoglobin (F) remains
 Lab technician reports % of fetal cells
 Anti – D immune globulin dose is calculated using the % of remaining fetal
cells
 Mothers who are NOT candidates for RhIg
o A D-negative woman whose infant is D-negative
o Any D-positive woman
o A D-negative woman known to be immunized to D antigen
o Other Ag (not Rh D Ag) associated with HDFN
o Fetal –
 Haemoglobin levels vary between normal to very low
 Reticulocytosis (reticulocytes aka polychromatic macrocytes increased) and increased numbers of
nucleated red blood cells (see Blood film below)


 Spherocytosis (especially in ABO incompatibility > Rh HDN; present in both conditions)
 Neutrophilia
 ABO, Rhesus grouping
 Direct Coombs’ Test (DCT)
 With Rhesus incompatibility – positive DCT due to anti-D antibodies
 With ABO incompatibility – DCT is usually only weakly positive or negative
o Fetal red cells have few A & B antigens; if less than critical value, may result in
negative test
 Unconjugated (Indirect fraction) hyperbilirubinemia, increased LDH, increased AST
 o Treatment of Hemolytic Disease of the Newborn
 Intrauterine transfusion (see earlier)
 Hyperbilirubinemia – phototherapy, exchange transfusion (if Hb < 10)
 IVIG in severe cases – blocks Fc receptors of reticuloendothelial system
 The risk of transverse limb abnormality, a complication of chorionic villous sampling, is greatest when the age
of gestation is less than 9 weeks, and lowest when its greater than 11 weeks
 Percutaneous umbilical sampling
o High – risk procedure that samples fetal blood to confirm severe fetal anemia when suspected on
ultrasound (e.g. elevated MCA Doppler USS, hydrops fetalis)
 Small for Gestational Age / Fetal Growth Restriction
o Definition – Ultrasound EFW < 10th percentile or birth weight < 3rd percentile for gestational age;
associated with increased risk of intrauterine demise and neonatal morbidity / mortality (e.g. preterm
delivery)
o Risk Factors
 Maternal factors
 Preeclampsia
 Malnutrition
 Placental insufficiency
 Multiparity
 Drug Use
 Fetal Factors
 Genetic factors (e.g. constitutionally small, with fetal growth appropriate for maternal size
& ethnicity)
 Chromosomal abnormalities
 Congenital infections
 Inborn errors of metabolism
o Intrauterine Growth Restriction (IUGR) can be:
 Estimated fetal weight < 10th percentile or birth weight < 3rd percentile for gestational age
 Most pregnancies complicated by fetal growth restriction still result in live, late preterm
or term deliveries; however, they are at high risk for stillbirth and require close
monitoring. There serial antenatal testing is performed to monitor fetal wellbeing.
 Symmetric / Type I – height, weight, and head circumference are all equally affected
 Onset – 1st trimester
 Etiology – Chromosomal Abnormalities, Congenital infection
o Aneuploidy – Trisomy 13, 18, 21
o TORCH infections (e.g. toxoplasmosis, cytomegalovirus)
o Cigarette Smoke / nicotine
o Alcohol
o Heroin
o Ionizing radiation
 Clinical Features – Global growth lag
 Asymmetric / Type II – weight is affected more than height and head circumference
 Umbilical Artery Doppler Ultrasound – uteroplacental insufficiency, Preeclampsia
 Etiology – Uteroplacental Insufficiency, Maternal Malnutrition → inadequate fetal
nutrition and oxygenation
o Russell–Silver Syndrome
o Maternal vasculopathy (e.g. Hypertension, Pre–gestational Diabetes)
o Tobacco Use
 Clinical Features – “Head–sparing” growth lag (i.e. abdominal growth restriction is more
pronounced due to fetal adaptations to chronic placental insufficiency)
 Management
  Monitor / treat complications (e.g. hypoglycemia, hypothermia, polycythemia)
 Regular nonstress testing
o Normal antenatal testing (e.g. reactive NST, normal BPP) suggests low risk of
stillbirth within one week of the test date. In contrast, abnormal findings may
necessitate immediate intervention (e.g. delivery) to prevent fetal acidosis and
stillbirth
 Weekly Biophysical Profiles
o USS evaluations of amniotic fluid and fetal activity (e.g. tone, movement)
o Indicator of fetal renal perfusion, acid – base status, and oxygenation
 Serial umbilical artery Doppler sonography
o Monitor for decreased umbilical artery blood flow and increased vascular
resistance, which indicate deteriorating placental function and decreased fetal
oxygenation
 Serial growth ultrasounds
o Potential complications for SGAs
 Hypothermia – decreased subcutaneous fat and impaired thermoregulation
 Hypoglycemia
 decreased glycogen stores
 N.B. VLBW infants (<1.5 kg) may have hyperglycemia due to low insulin secretion, but
hypoglycemia is more likely in an LBW (<2.5 kg) or low–normal weight infants weighing
2.6 kg (5th percentile)
 Hypocalcemia – Decreased transfer of calcium across placenta
 Polycythemia – due to increased EPO secretion in response to fetal hypoxia
 Complications of inappropriate pregnancy weight gain
o Excessive weight gain
 Gestational Diabetes
 Fetal Macrosomia
 Caesarean delivery
 Increased risk of hypertension and preeclampsia due to increased systemic vascular resistance
o Inadequate weight gain
 Fetal growth restriction
 Preterm delivery
o Recommendations for weight gain in pregnancy is dependent on pre–pregnancy BMI
 Underweight (BMI < 18.5 kg/m2) are advised to gain 12.7 – 18.1 kg (28 – 40 lb) during pregnancy
 Normal (BMI: 18.5 – 24.9 kg/m2) are advised to gain 11.4 – 15.9 kg (25 – 35 lb) during pregnancy
 Overweight (BMI: 25 – 29.9 kg/m2) are advised to gain 6.8 – 11.4 kg (15 – 25 lb) during pregnancy
 Obese (BMI ≥ 30 kg/m2) are advised to gain 5 – 9 kg (11 – 20 lb) during pregnancy
 Anemia of Prematurity
o Etiology
 Impaired erythropoietin production
 Short RBC life span
 Iatrogenic blood sampling (frequent phlebotomy in NICU)
o Pathophysiology
 Physiologic RBC nadir is expected and occurs at age 2–3 months in term infants
 In preterm infants, however, low EPO levels are exacerbated by short RBC life span (40 – 50 days)
and frequent phlebotomy in NICU
o Clinical Manifestations
 Usually asymptomatic
 Tachycardia, apnea, poor weight gain
o Laboratory Findings
 ↓ Hb, ↓ Hct & ↓ reticulocyte count
  Normochromic, normocytic anemia
o Treatment
 Minimize blood draws
 Iron supplementation
 Iron deficiency is not part of the pathogenesis, however infants with insufficient iron
intake may have difficult recovery from anemia of prematurity due to impaired
erythropoiesis
 RBC Transfusions – can be given if the infant is symptomatic but will further suppress EPO levels
and delay recovery
 Supplemental EPO is not effective in preventing the need for transfusions

ANTEPARTUM HAEMORRHAGE
Epidemiology Placenta Previa
 Presence of the placenta in lower
uterine segment, which might lead
to partial or full obstruction of the  Preeclampsia / eclampsia
neck of the uterus with high risk of  Abdominal trauma
hemorrhage (rupture of placental
vessels) and birth complications
 Risk Factors
Etiology /
o Multiparity
Pathophysiolog
o Advanced maternal age (≥ 35)
y (Risk Factors)
o Prior caesarean delivery or
curettage
o Prior placenta previa
o Previous / recurrent abortion
o Short interpregnancy interval
Clinical Features  Classification
o Low-lying placenta: lower edge
of the placenta lies less than 2 cm
from the internal cervical os
o Marginal previa: placenta
reaches the internal cervical os
o Partial previa: placenta partially
covers the internal cervical os
o Complete previa (total previa):
placenta completely covers the
internal cervical os
 Sudden, Painless, bright red
vaginal bleeding (heavy &
persistent) occurring with or
without contractions
 Usually occurs in T3 before ROM,
stops spontaneously after 1–2
hours, and recurs during birth
 During labour, contractions or
cervical manipulation can shear the
placenta off the cervix → massive
maternal hemorrhage
 Signs of maternal shock (e.g.
hypotension, tachycardia) typically
present prior to severe fetal
Placental Abruption
(Abruptio Placentae)
 Maternal hypertension (most
common)
 Prior placental abruption
 Cocaine & tobacco use
 PPROM
 Maternal age: < 20 years and > 35
years
 Occurs most often in T3
 Sudden-onset painful vaginal
bleeding (80%)
 Abdominal or back pain
 High-frequency, low-intensity
contractions
 Hypertonic contractions (rigid
tender uterus)
 Risk of Disseminated Intravascular
Coagulation (DIC) proportional to
the area of placental detachment
 Risk of Hypovolemic shock
 Fetal complications – hypoxia,
preterm delivery
Vasa Previa
 Fetal Vessels overlying the
cervix (located in the
membranes near the
internal os of the cervix,
putting them at risk of
injury if the membranes
rupture)
 Risk Factors:
o Placenta previa
o Multiple gestations
o Multiparity
o In vitro fertilization
o Placental anomalies (e.g.,
bilobate or succenturiate
placenta, velamentous
umbilical cord insertion)
 Painless, minimal vaginal
bleeding with ROM or
contractions, primarily
reflecting fetal blood loss
 Fetal distress (e.g., fetal
bradycardia; decelerations
or sinusoidal pattern on FHR
tracings)
 Fetal exsanguination &
demise within minutes (N.B.
as total fetal blood volume
is low [~250ml or 1 cup),
even minimal bleeding can
lead to complications)
 N.B. No ABD pain, no loss of
fetal station
 compromise
 Usually no fetal distress
 Speculum exam – verify or quantify
vaginal bleeding (N.B. Digital
cervical examination and
intercourse are contraindicated)
 Transabdominal (placental location)
followed by Transvaginal USS
(optimal visualization 2 – 3 cm away
from the cervix & angle of vagina
Investigations prevents USS probe from entering
the cervical canal –
o Placental encroaching cervical
opening
o Transabdominal – high false–
positivity rate for detecting
placenta previa
 Reactive NST initially as most of
bleeding is maternal in origin
Management  Lower Segment Caesarean delivery
indicated after 36–37 weeks
 If GA < 37 weeks and severe, active
bleeding OR evidence of fetal
distress: stabilization and
emergency cesarian section
 If GA < 37 weeks and no active
bleeding AND no evidence of fetal
distress: expectant management
 If Rh(D) negative mother and Rh(D)
positive infant, administer anti-D-
immunoglobulin up to 72 hrs
postpartum
 Vaginal delivery should never be
attempted outside the operating
room in a patient with placenta
previa. Induction of labor and/or
vaginal delivery may be performed
in the operating room if the mother
is hemodynamically stable, fetal
cardiac status is reassuring, and the
placenta lies > 2 cm away from the
internal os on ultrasonography
 Primarily by clinical presentation  Typically diagnosed on fetal
 Vaginal exam contraindicated (may anatomy USS at 18-20
worsen bleeding) weeks; Transabdominal or
 Ultrasound (not required for transvaginal ultrasound
diagnosis), to rule out placental with color Doppler shows
previa; may show retroplacental fetal vessels overlying the
hematoma internal os and decreased
 Fetal heart rate monitoring (e.g. blood flow within fetal
decelerations) vessels
 CBC, coagulation factors  Induction of labour is
CONTRAINDICATED
 Hemodynamic control: monitor  3rd trimester in-patient
vital signs, maintain airways, management with planned
volume resuscitation, type and Caesarean delivery at 34-35
crossmatch blood weeks (i.e. prior to onset of
Correct coagulopathy if necessary contractions or membrane
RhD prophylaxis in RhD negative rupture)
mothers  Emergency Caesarean
Normal fetal findings & a Delivery if signs of fetal
hemodynamically stable mother distress
o Observation, bed rest, regular
control
o Up to the 34th week of
pregnancy
 Fetal lung maturity induction
with corticosteroids (e.g.,
betamethasone)
 If necessary, tocolysis (e.g.,
nifedipine, β2-adrenergic
agonist)
 Aim for a normal delivery
o 34th to 36 th week
 Active uterine contractions
present: vaginal delivery
 No contractions + no signs of
fetal distress + bleeding has
stopped: expectant
management and observation
o All pregnancies are delivered if
acute abruption occurs after 36th
weeks.
In acute symptoms & a live fetus –
emergency cesarean section
independent of gestational age
unless vaginal delivery is impending
In acute symptoms and intrauterine
fetal death
o Induction of vaginal delivery
 through pharmacologic uterine
contraction inducers and
opening of the amniotic sac
o An emergency cesarean section
must be performed if there is a
maternal risk; due to severe
bleeding or slow progression of
the birthing process, even in
cases of intrauterine fetal death.
 Preterm Delivery  Intrauterine fetal death (occurs in 
∼ 12% of cases)
 Maternal DIC and hypovolemic
shock
 Couvelaire uterus –
Complications o Retroplacental hemorrhage may
extend through the uterus into
the peritoneum
o Myometrium is weakened, with
possible subsequent uterine
rupture during contractions

Endometrial Hyperplasia / Cancer Vaginal Cancer

Risk Factors Excess Estrogen Age > 60
o Obesity / Elevated BMI (most common risk factor) HPV 16 & 18 infection
o Chronic anovulation / PCOS Chronic Tobacco use
o Nulliparity o Decreases immune response and prevents
o Early menarche or late Menopause viral clearing → continued viral replication
o Tamoxifen use and metaplastic changes within the vaginal
Protective factors squamous cell epithelium
o In ovulatory patients, an increase in progesterone In utero Diethylstilbesterol (DES) exposure [clear
protects against unopposed endometrial proliferation by cell adenocarcinoma only; i.e. not squamous cell
down–regulating estrogen receptors & regulating mitosis carcinoma]
o COCs and progestin–only contraceptives
o Tobacco use – likely by stimulating estrogen metabolism
in the liver and decreasing serum estrogen levels
Clinical Heavy, prolonged, intermenstrual &/or postmenopausal Vaginal bleeding
Features bleeding Malodorous vaginal discharge
Irregular vaginal lesion
o Irregular plaque or ulcer in upper third of
posterior vagina
Metastatic disease – pelvic pain, haematuria &
bulk symptoms (e.g. constipation)
Evaluation Endometrial biopsy (Gold Standard) Vaginal Biopsy – depth of invasion &
Pelvic USS (postmenopausal women) – thickened management options
endometrial stripe (≥ 5 mm)
Treatment Hyperplasia: progestin therapy or hysterectomy Surgery ± chemoradiation
Cancer: hysterectomy

 Uterine Sarcoma
o Risk Factors
 Pelvic Radiation
 Tamoxifen use
 Postmenopausal women
o Clinical Features
  Abnormal / postmenopausal bleeding
 Uterine mass (enlarged, irregularly, shaped uterus)
 Bulk symptoms – constipation, pelvic pain or pressure
 Ascites (e.g. free fluid in posterior cul–de–sac)
o Diagnosis
 Ultrasound ± additional imaging
 Endometrial biopsy
 Histopathology of surgical specimen
o Treatment
 Hysterectomy ± Adjuvant chemotherapy, radiation therapy

Breastfeeding benefits & contraindications

Benefits Contraindications
 Active untreated tuberculosis (mothers may breastfeed after 2
weeks of anti-tuberculin therapy)
 Maternal HIV infection (in developed countries where formula
is readily available)
 Herpetic breast lesions
 More rapid uterine involution & decreased  Varicella infection < 5 days prior to or within 2 days of delivery
postpartum bleeding  Specific maternal medications
 Faster return to pre–partum weight  Chemotherapy or ongoing radiation therapy
Maternal  Improved child spacing (Natural  Active abuse of street drugs or alcohol / Active substance use
contraceptive) disorder
 Improved maternal–infant bonding o In contrast, patients on a stable methadone regimen (to
 Reduced risk of breast & ovarian cancer treat opioid use disorder) can be encouraged to breastfeed
without needing to decrease or discontinue methadone
treatment. This is because methadone concentrations in
breastmilk are low, are unrelated to the maternal dose, and
rarely cause adverse effects (e.g. neonatal respiratory
depression)
 Improved immunity
 Improved gastrointestinal function
 Decreased infections:
o Otitis media
Infant o Gastroenteritis  Galactosemia
o Respiratory illnesses
o Urinary tract infections
 Decreased risk of childhood cancer, type I
diabetes mellitus & necrotizing enterocolitis
 Ovarian Torsion & Adnexal Torsion
o Partial or complete rotation of the ovary around the infundibulopelvic (suspensory ligament of the ovary)
and utero–ovarian ligaments, which obstructs the ovarian blood supply
 Right sided torsion is more common due to long length of the right utero–ovarian ligament &
because the rectosigmoid colon occupies the space around the left ovary
o Most commonly affects women of reproductive age
o Risk Factors
 Preexisting Ovarian Mass, particularly if large (≥ 5 cm)
 70% of non – pregnant women with purely cystic pelvic masses that are < 10 cm have
spontaneous resolution
o Surgical removal during T2 pregnancy is indicated for adnexal cysts that are larger
than 5 cm & persist over time because these have high risk of rupture,
hemorrhage, and torsion, all of which may lead to preterm delivery
 Elective surgical removal delayed till 2nd trimester to reduce risk of fetal
complications
 Women of reproductive age
 Infertility treatment with ovulation induction
 Pregnancy
o Clinical Features
 Sudden–onset, moderate–to–severe pelvic pain
 Nausea & vomiting, possible low grade fever
 ± Palpable, unilateral & tender adnexal mass (N.B. Difficult to appreciate in obesity, ≥ 30 kg/m2)
 Abnormal vaginal bleeding is UNCOMMON
o Investigations
 CBC, U&Es
 Fever + leukocytosis may indicate possible adnexal necrosis
 Urine & Serum β –hCG to exclude ectopic pregnancy
 Abdominal & Pelvic USS with color Doppler
 Enlarged and edematous ovary / adnexal mass with localized tenderness and signs of
impaired ovarian blood flow on Doppler
o Treatment
 Emergency Laparoscopy with detorsion + Ovarian cystectomy
 Salpingo–oophorectomy if obvious adnexal necrosis or suspected ovarian malignancy
o Complications
 Untreated ovarian torsion may lead to chronic pelvic pain, infertility, hemorrhage, or peritonitis
or sepsis
 Post–Dural puncture headache
o Pathophysiology
 Unintentional dural puncture during neuraxial anesthesia → CSF leakage, low CSF pressure →
slight herniation of brain and brainstem
 Quincke’s method developed to lower risk
o Clinical Features
 Frontal or occipital headache
 Within 6 – 72 hours of lumbar puncture or neuraxial anesthesia
 Positional (worse when upright [whether sitting or standing], improves when supine)
 Neck stiffness
 Photophobia, diplopia
 Hearing loss, tinnitus
 Nausea, vomiting
o Management
 Typically self–limited (2 – 15 days)
 Epidural blood patch
  Oral caffeinated beverages – e.g. pepsi
 Low Back Pain During Pregnancy
o Common in pregnancy, especially in 3rd trimester
 Mechanical back pain (i.e. achy back pain that is worse with activity and relieved by rest)
 In pregnant women, Nocturnal, position–dependent pain is common and usually benign
 However patients should be assessed for non–mechanical causes of pain (e.g. preterm labour,
pyelonephritis)
 Worrisome features include:
o Neurologic deficits (e.g. bladder / bowel incontinence)
o Fever
o Recent epidural anesthesia
o Constant, non–positional, nocturnal back pain in non–pregnant suggests possible
malignancy or epidural abscess; however, in pregnancy….
o Etiology
 Enlarged uterus → exaggerated lordosis
 Joint / ligament laxity from ↑ progesterone / relaxin
 Weak abdominal muscles → decreased lumbar support
o Risk Factors
 Excessive weight gain
 Chronic back pain
 Back pain in prior pregnancy
 Multiparity
o Imaging – not indicated
o Management
 Behavioural modification (e.g. wearing supportive shoes, firm mattress)
 Heating pads
 Analgesia
 Vaginismus (Genito–pelvic Pain/Penetration Disorder)
o Common cause of dyspareunia
o Diffuse pain associated with vaginal penetration (e.g. intercourse, speculum exam), due to repeated
involuntary pelvic floor contractions
o Nil association with menses
o May cause psychological distress and have an identifiable cause e.g. vaginal trauma
 Significant patient anxiety and avoidance of examinations → underreported
 Aversion from anticipated pain of sexual activity
o Management – mixed modality
 CBT – desensitization therapy
 Couples therapy and sex education
 Pelvic floor physical therapy, kegel exercises
 Vaginal dilators
 Localized provoked vulvodynia (formerly vestibulodynia)
o Pain & tenderness to superficial touch of the vestibule on external pelvic examination
 Postpartum urinary retention – inability to void ≥ 6 hours after vaginal delivery (or ≥ 6 hours after catheter
removal from caesarean delivery)
o Inability to sense the need to void, loss of micturition reflex, bladder atony (e.g. palpable overdistended
bladder with suprapubic fullness and tenderness) & urinary retention
 Overflow incontinence (e.g. involuntary dribbling of urine) can occur due to bladder pressure
rising above urethral pressure
o Risk Factors
 Primiparity
 Regional neuraxial anesthesia (e.g. epidural anesthesia)
  Operative vaginal delivery
 Perineal injury (e.g. pudendal nerve injury from prolonged labour – perineal stretching &
swelling)
 Cesarean delivery
o Clinical Features
 Small–volume voids or inability to void
 Incomplete bladder emptying (urinary tenesmus)
 Dribbling of urine
o Management
 Self–limited condition
 Intermittent catheterization – most patients regain bladder function after catheterization
 Delivery planning for a non–viable fetus
o Fetal diagnosis
 Acardia
 Anencephaly
 Bilateral renal agenesis
 Holoprosencephaly
 Intrauterine fetal demise
 Pulmonary Hypoplasia
 Thanatophoric dwarfism
o Obstetric management
 Vaginal delivery
 No fetal monitoring
o Neonatal management
 Palliative care if not stillborn
 Intrauterine Fetal Demise = fetal death at ≥ 20 weeks gestation
o Diagnosis – absence of fetal cardia activity on ultrasound
o Risk Factors
 Most commonly occurs in uncomplicated pregnancies
 Fetal growth restriction
 Abnormal fetal karyotype
 Tobacco use
o Management
 20 – 23 weeks
 Dilation & evacuation or
 Vaginal delivery*
 ≥ 24 weeks
 Vaginal delivery* (regardless of fetal presentation – e.g. vertex, breech)
 *Caesarian delivery by maternal choice if history of prior classical caesarean / myomectomy
 Caesarean delivery associated with increased morbidity & mortality c.f. vaginal delivery
o Complication
 Coagulopathy after several weeks of fetal retention
 Short interpregnancy interval – < 6 – 18 months from delivery to next pregnancy
o Complications
 Maternal anemia
 PPROM (possibly due to persistent genital tract infection)
 Preterm delivery
 Low Birth Weight
 Risk factors of post–term pregnancy
o Prior post–term pregnancy
o Nulliparity
 Preventing neonatal group B Streptococcus infection (Streptococcus agalactiae; e.g. early–onset sepsis, pneumonia)
Antenatal screening  Screening (Rectovaginal culture) at 35 – 37 weeks’ gestation
Indications for intrapartum  GBS bacteriuria or GBS UTI in current pregnancy (regardless of treatment) – high risk of
prophylaxis vertical transmission due to heavy maternal genitourinary GBS colonization / bacterial load
o Asymptomatic GBS bacteriuria is also associated with ↑ risk of preterm labour &
premature birth
 GBS–positive rectovaginal culture in current pregnancy (generally obtained at 35 – 37 weeks)
 Unknown GBS status PLUS any of the following:
o < 37 weeks’ gestation
o Intrapartum fever (≥ 38 OC [100.4 OF])
o Rupture of membranes for ≥ 18 hours
Prior infant with early–onset neonatal GBS infection; a sibling with invasive GBS disease
Intrapartum prophylaxis  IV penicillin, ampicillin (1st line)
 2nd line if mild penicillin allergy (e.g. maculopapular rash, low risk of anaphylaxis) –
(Should be given ≥ 4 hours Cephalosporin e.g. cefazolin (1st gen): lower risk of cross–reactivity but achieve the same high
prior to delivery) bactericidal concentration in amniotic fluid without fetal toxicity
 If severe penicillin allergy (h/o of urticaria & respiratory distress, i.e. high risk of anaphylaxis):
o Clindamycin if isolates sensitive to clindamycin &/or erythromycin
o Vancomycin if resistant to Clindamycin &/or erythromycin, or in individuals whose
sensitivities are unavailable
 However because vancomycin does not reach bactericidal concentrations in the
amniotic fluid, infants of patients treated with vancomycin require additional
neonatal observation and evaluation
 Generally vancomycin, clindamycin and other antibiotics are not considered
adequate intrapartum antibiotic prophylaxis due to increasing bacterial
resistance and slower distribution in tissue
 If antibiotic prophylaxis (ampicillin, penicillin or cefazolin) given ≥ 4 hours prior to delivery
&/or if ≥ 37 weeks’ gestation AND Rupture of membranes ¿ 18 hours → Observe neonate ≥
48 hours
o Otherwise CBC with differential, Blood culture, then observe neonate ≥ 48 hours
o Monitor neonate for signs of infection (e.g. lethargy, poor feeding, temperature
instability)
 N.B. Neonates of gestational age > 35 weeks who are well appearing with inadequate
intrapartum GBS prophylaxis warrant observation alone due to lower risk of infection than
those who appear ill or are premature. Observation involves serial examinations and vital
signs monitoring over 36 – 48 hours
 Due to high – risk of infection, neonatal blood cultures with or without IV antibiotics are
indicated regardless of prophylaxis in the following circumstances:
o Clinical signs of neonatal infection (e.g. temperature instability, lethargy)
o Maternal fever during labour and delivery
o Gestational age < 35 weeks with delivery prompted by signs of possible infection (e.g.
preterm labour)

Premature Prelabour Rupture of Membranes (PPROM) Late– & Post–term Pregnancy

Definition Membrane rupture at < 37 weeks prior to labour onset Late–term: ≥ 41 weeks gestation
Although pathophysiology is multifactorial, PPROM is likely Post–term: ≥ 42 weeks gestation
due to a subclinical infection
Risk Factors History of PPROM in prior pregnancy Prior post–term pregnancy
Tobacco use Nulliparity
Conditions that overdistend membrane (e.g. polyhydramnios, Obesity
multifetal gestation) Age ≥ 35 years
Conditions that inflame or weaken the membranes Fetal anomalies (e.g. anencephaly)
o Genitourinary infection (e.g. Asymptomatic bacteriuria,
Bacterial vaginosis, Gonorrhea)
  As bacteria spreads to uterus due to close proximity, the
intrauterine bacterial enzymatic activity may cause
contractions (by stimulating prostaglandin release) or
increase membrane fragility (by degrading collagen or
activating inflammatory cytokines), resulting in either
preterm labour or PPROM
o Antepartum bleeding (T1 bleeding)
 Extremes of maternal age (< 17 years, > 35 years) are
associated with PTL and PPROM
Clinical Gush or slow leak of fluid from the vagina Pathophysiology – Risk of decreased
Features Absent uterine contraction placental function due to age–related
Investigations Vaginal pooling of fluid from cervix (in posterior fornix) placental changes (e.g., infarctions,
Nitrazine–positive (blue) fluid – pH > 6 (blue) suggestive of calcifications) → increased placental
amniotic fluid) vascular resistance
Ferning pattern on microscopy – suggestive of amniotic fluid Progressive placental dysfunction can lead to
N.B. Fetal fibronectin (found at choriodecidual interface) in uteroplacental insufficiency and chronic
vaginal sampling at 24 – 34 weeks gestation used to identify fetal hypoxemia → central nervous system
patients with preterm contractions who are at high risk for suppression and intrauterine demise
preterm delivery. It is not performed in PPROM because the
risk of preterm delivery is high and, therefore does not
change management
Management Expectant management Frequent Fetal monitoring (e.g. non–stress
o < 34 weeks (reassuring): Bed rest + prophylactic latency test, USS for amniotic fluid volume)
antibiotics (e.g. ampicillin & azithromycin), corticosteroids o Patients with findings suggestive of
(betamethasone), Fetal surveillance (e.g. serial fetal USS, uteroplacental insufficiency, such as
non–stress tests) late decelerations or oligohydramnios,
 Ampicillin covers group B Streptococcus, aerobic GNB, require delivery to prevent IUFD
and anaerobes Delivery prior to 43 weeks gestation
 Azithromycin covers Ureaplasma
 Uncomplicated, i.e. if no evidence of chorioamnionitis
(e.g. fetal tachycardia, uterine tenderness) or
deteriorating fetal/maternal status at 22 – 34 weeks
gestation
 If lecithin/sphingomyelin < 2.0, can administer
betamethasone up to < 36 weeks gestation –
promotion of fetal lung maturity (e.g. pneumocyte
development, surfactant release)
 Typically delivered at 34 weeks (when the risk of
complications outweighs the neonatal benefit of
continuing pregnancy); however, if complications
develop (e.g. placental abruption) then earlier delivery
is indicated
Delivery
o < 34 weeks (non–reassuring / complication):
 Delivery + Corticosteroids (↓ risk of neonatal ARDS,
fetal lung hypoplasia or immaturity) + Magnesium (if <
32 weeks for fetal neuroprotection) + intraamniotic
infection treatment (ampicillin + gentamicin)
 E.g. if evidence of chorioamnionitis, fetal / maternal
compromise (placental abruption, cord prolapse)
 Magnesium sulphate – fetal neuroprotection (i.e.
cerebral palsy risk reduction)
o 34 to < 37 weeks:
 Delivery + GBS prophylaxis (e.g. penicillin G) ±
Corticosteroids
 N.B. Tocolysis (e.g. nifedipine, indomethacin) is
 contraindicated in PPROM because contractions often
indicate a complication (e.g. intraamniotic infection,
placental abruption) that requires delivery or intervention
Complications Preterm Labor Fetal / neonatal
Intraamniotic infection (Chorioamnionitis) o Macrosomia (≥4.5 kg [9.9lb])
Placental abruption (abruptio placentae) o Oligohydramnios (AFI < 5cm, or single
o Decreased amniotic fluid volumes (AFI < 5cm) lead to deepest pocket < 2cm)
uterine decompression; this causes maternal decidual o Dysmaturity syndrome
vessels to shear, resulting in bleeding and separation of o Intrauterine Fetal Demise
the placenta from the uterus Maternal
o As abruption enlarges, risk of fetal hypoxia (and possible o Severe obstetric lacerations
demise) or maternal haemorrhage (and possible DIC) o Caesarean delivery
Umbilical cord prolapse o Postpartum haemorrhage

 Preterm Labour
o Risk Factors
 Prior spontaneous preterm delivery (confers ~ 20% risk for future spontaneous preterm
 Multiple gestation; In vitro fertilization
 Short cervical length
 Cervical surgery (e.g. cold knife conization)
 N.B. a loop electrosurgical excision procedure (LEEP) may or may not confer a risk of
preterm delivery. Cervical laser ablation does not increase that risk
 Cigarette use
 Obesity
 Advanced Maternal Age
o Management
 Regular contractions
 If cervical change → fetal fibronectin NOT indicated
 If no cervical change →
o If 34 – 37 weeks gestation → fetal fibronectin NOT indicated
o If < 34 weeks gestation → fetal fibronectin indicated
 A positive FFN test is a strong predictor of delivery within the next week &
an indication for administration of antenatal corticosteroids (e.g.
betamethasone)
 A negative FFN test have a low likelihood of delivery within the next 2
weeks and can resume routine prenatal care and expectant mangement
 Gestational Age 34 0/7 to 36 6/7
 ± IM Betamethasone or Dexamethasone
o Dexamethasone 6mg IM, q12hr × 2 days or
o Betamethasone 12mg IM, q24hr hours apart × 2 days
o Antenatal corticosteroids reduces risk of infant respiratory distress syndrome and
intraventricular hemorrhage
o N.B. intramuscular administration of steroids provides stable and predictable
concentration of the drug in the blood that is required to achieve the desired fetal
effects
 Penicillin if GBS positive or unknown
 Gestational Age 32 0/7 to 33 6/7
 IM Betamethasone or Dexamethasone
 Tocolytics – Nifedipine (1st line tocolytic at 32 – 34 weeks)
o inhibits calcium entry into cells, thereby causing myometrial relaxation
o ADRs –
 Peripheral vasodilation → flushing, headache;
  Decrease in systemic vascular resistance can result in hypotension, reflex
tachycardia and palpitations
o N.B. Indomethacin contraindicated at ≥ 32 weeks due to risk of oligohydramnios
and premature closure of fetal ductus arteriosus
 Penicillin if GBS positive or unknown
 Gestational Age < 32
 IM Betamethasone / Dexamethasone for fetal lung maturity (promotes pneumocyte
development and inducing surfactant production)
o Decreases incidence of neonatal respiratory distress syndrome
o Decreases risk of intraventricular hemorrhage, necrotizing enterocolitis, systemic
infection, and overall neonatal morbidity and mortality
 Tocolytics – Indomethacin (1st line tocolytic at < 32 weeks)
o Non–specific cyclooxygenase inhibitor used for tocolysis between 24 & 32 weeks
o Decreases prostaglandin synthesis and leads to fetal vasoconstriction (e.g.
premature closure of the ductus arteriosus).
 The subsequent decreased renal perfusion and fetal oliguria can result in
oligohydramnios (i.e. AFI ≤ 5 cm in T3), particularly with prolonged
administration; therefore patients typically receive indomethacin for ≤ 48
hours. The associated oligohydramnios is usually transient, and resolves
without intervention once the medication is discontinued
o Indomethacin Contraindicated at 32 – 34 weeks due to potential ductus arteriosus
closure and oligohydramnios
o ADR –
 Maternal – gastritis, platelet dysfunction
 Fetal – Oligohydramnios, closure of ductus arteriosus
 MgSO4 for fetal neuroprotection (decrease risk of cerebral palsy)
 Penicillin if GBS positive or unknown – to decrease the risk of neonatal group B
Streptococcal infection
 Other tocolytics e.g. terbutaline (beta agonists), nifedipine (CCB)
 Administered to the relax the uterus when contractile abnormalities such as tachysystole
(> 5 contractions in 10 minutes) or tetanic contractions (contractions lasting > 2 minutes)
are causing fetal heart rate abnormalities
 Beta agonists (e.g. Terbutaline, ritodrine) are used infrequently due to USFDA black box
warning of ADRs (maternal tachycardia / arrhythmia, myocardial ischemia, and pulmonary
edema). Additionally, beta agonists can worsen maternal hyperglycemia and are
contraindicated in poorly controlled diabetes.
o Terbutaline – short – term tocolytic: in-patient use
 Cervical Incompetence / Cervical Insufficiency
o Risk Factors
 Collagen abnormalities (e.g. Ehlers–Danlos Syndrome)
 Uterine abnormalities (e.g. septate uterus, bicornuate uterus)
 Cervical conization or loop electrosurgical excision procedure
 Prior mechanical cervical dilatation (e.g. D&C, pregnancy termination)
 Obstetric injury (prior obstetric cervical laceration from delivery)
o Clinical Features – Diagnosis based on any one of the following criteria:
 ≥2 Prior consecutive, painless, 2nd trimester losses (history based), which typically presents with
mild symptoms (e.g. vaginal discharge, light spotting, painless cervical dilatation) followed by
precipitous delivery OR
 Painless cervical dilation in the current pregnancy ± amniotic sac bulging at the os (i.e.
examination based) OR
 A 2nd trimester (T2) short cervix on TVUS (≤ 2 cm without hx of preterm labour or ≤ 2.5 cm with a
hx of prior preterm delivery; i.e. ultrasound-based) – strong predictor for preterm labour
 o Screening & Prevention
 Serial (Weekly) Cervical length
measurement by TVUS
 Indicated for monitoring of
patients with history of
preterm delivery (due to
causes other than cervical
insufficiency) or those with
incidentally diagnosed short
cervix (≤ 2.5 cm) on USS
 Progesterone Administration
 Cerclage placement during T2 (after
1st trimester in case of genetically
abnormal pregnancy loss which
would result in 1st trimester loss)
o Management
 During pregnancy, progesterone maintains uterine quiescence and protects the amniotic
membranes against premature rupture
 Supplementation with exogenous progesterone decreases rate of labour in patients with
short cervices or a history of preterm birth
 Vaginal Progesterone indicated in if at risk of preterm delivery with incidental shortened
cervix (≤ 2 mm) between 16–24 weeks gestation and no history of preterm delivery
 Patients with prior spontaneous preterm delivery (i.e. PPROM, preterm labour) should
receive IM hydroxyprogesterone to decrease the risk of recurrence starting in T2 and
undergo serial TVUS for cervical length measurements.
o N.B. not indicated in patients who underwent preterm delivery for other
indications (e.g. preeclampsia with severe features, fetal growth restriction)
o If TVUS reveals a short cervix, cerclage placement may be indicated
 History–based cervical insufficiency are treated with prophylactic cerclage in early T2
(12 – 14 weeks); suture is removed at term to allow vaginal delivery
 Placental Abruption
o Heavy vaginal bleeding
o Non-reassuring fetal heart rate tracing (e.g. minimal variability, decelerations)
o Uterine tachysystole (e.g > 5 contractions in a 10 minute period)
 Intraamniotic Infection (Chorioamnionitis)
o Fulminant polymicrobial infection of the amniotic sac, fetus, cord, and placenta from ascending vaginal
flora
o Risk Factors
 PROM (> 18 hours)
 PPROM
 Internal fetal / uterine monitoring devices
 Repetitive vaginal examinations
 Presence of genital tract pathogens
o Clinical Features / Diagnosis
 Maternal Fever PLUS ≥ 1 of the following:
 Fetal tachycardia (> 160/min) for at least 10 min
 Maternal Leukocytosis
 Maternal Tachycardia
 Malodourous or Purulent amniotic fluid, vaginal discharge
 Uterine tenderness, pelvic pain
o Management
  Broad–spectrum antibiotics (e.g. ampicillin, gentamicin, clindamycin)
 Delivery, to remove source of infection (Immediate induction &/or augmentation of labour
regardless of gestational age)
 Caesarean delivery is reserved for standard obstetric indications (e.g. non–reassuring fetal
tracing, breech presentation, prior uterine surgeries)
 Antipyretics and IV fluids – reduce maternal fever and improves fetal tachycardia
 Tocolytics contraindicated regardless of gestational age
 Antibiotics for neonate + CBC, Blood Cx, & LP
o Complications
 Maternal – postpartum haemorrhage, endometritis, sepsis, DIC
 Neonatal – preterm birth, pneumonia, encephalopathy
 Antepartum Fetal Surveillance
o Assesses fetal status and identify those at risk for hypoxemia and subsequent fetal demise
o A reactive NST – indicates adequate fetal oxygenation and uteroplacental blood flow
 During a 20–minute interval, there are 2 FHR accelerations that peak at ≥ 15 beats per minute
above baseline and last ≥ 15 seconds
 Reactive NST has high negative predictive value for fetal compromise, no additional test required
o Nonreactive NST = does not meet criteria for reactivity
 Concerning for fetal hypoxemia and acidemia; however, the most common cause of a
nonreactive NST is a quiet fetal sleep cycle (which lasts ≤ 40 min)
 A nonreactive NST is extended (e.g. 40 – 120 min instead of typical 20 min) to ensure fetal activity
outside of quiet sleep is captured
 Due to high false-positive, nonreactive NSTs are further evaluated with either a biophysical
profile or contraction stress test before concluding that the fetus may be hypoxemic and needs
intervention
o Intrapartum fetal heart rate monitoring – Non-stress Test
 Early Decelerations
 Symmetric to contraction
 Nadir of deceleration corresponds to peak of contraction
 Gradual (≥ 30 sec from onset to nadir)
 Etiology
o Fetal Head Compression; likely the result of a fetal
autonomic response to the alterations in intracranial
pressure caused by contractions
o Can be normal fetal tracing
 Late Decelerations
 Delayed compared to contraction
 Nadir of deceleration occurs after peak of contraction
 Gradual (≥ 30 sec from onset to nadir)
 Recurrent late decelerations = late decelerations in ≥ 50% of contractions
 Etiology – uteroplacental insufficiency (transient fetal hypoxemia during contractions)
o Placental abruption
o Post–term Pregnancies
o Uterine tachysystole (> 5 contractions per 10-minute interval) → inadequate
recovery time (resumption of blood flow) between contractions
 May cause fetal compromised (e.g. hypoxemia, acidemia) due to
interruption of intervillous blood flow
 Can occur in spontaneous labour, however there is an increased risk of
tachysystole with induced or augmented labour (e.g. uterotonic agents)
  Management – lateral maternal positioning, tocolysis and discontinuation
of uterotonic agents (e.g. oxytocin) until excessive uterine activity and
resulting fetal decelerations resolve

Variable Decelerations
 Can be, but not necessarily associated with
contractions
 Abrupt decrease in FHR (< 30 sec from onset to nadir)
 Decrease ≥ 15/min; duration ≥ 15 sec but < 2 min
 FHR rapidly returns to baseline as the umbilical cord is
decompressed
 Common after rupture of membranes and decrease in
amniotic fluid volume
 Etiology
o Umbilical Cord Compression
o Oligohydramnios
o Cord Prolapse
 Management – amnioinfusion, which increases intrauterine fluid volume to improve
variable fetal decelerations
 N.B. Fetal heart rate requires a mature sympathetic nervous system, which develops at 26 – 28
weeks gestation; therefore extremely premature fetuses (< 28 weeks gestation) often do not
demonstrate reactivity
o Biophysical Profile and Contraction stress test
 Further evaluation of patients with an uncomplicated pregnancy and nonreactive NST to
determine risk of hypoxemia and demise
 Contraction stress test (CST): measures FHR reactivity in response to uterine contractions
 Biophysical profile (BPP):
 a noninvasive test that evaluates the risk of antenatal fetal death, usually performed after
the 28th gestational week
 Measured parameters: each parameter receives a score of either 0 (abnormal) or 2
(normal) points. Ultrasound exam:
o Fetal movement
 2 points = ≥ 3 body or limb movements within a 30-minute period
o Fetal tone
 2 points = ≥ 1 episodes of a fetal extremity or fetal spine extension with
return to flexion
o Fetal breathing
 2 points = ≥ 1 rhythmic breathing episode(s) ≥ 30 seconds within a 30-
minute period
o Amniotic fluid volume
 2 points = A single deepest vertical pocket ≥ 2 cm with a horizontal
dimension ≥ 1 cm.
o NST (optional, not always performed)
  2 points = ≥ 2 episodes of FHR accelerations of ≥15 bpm and ≥15 seconds
associated with fetal movement within a 30-minute period
 Interpretation
o Total score ≥ 8 points: no signs of fetal compromise → reassurance
o Total score ≤ 4 points: potential fetal compromise → delivery is indicated (if
pregnancy duration is < 32 0/7 weeks, administer steroids and continue close
monitoring)
o Fetal Scalp stimulation and Vibroacoustic stimulation
 Used in patients with nonreactive NST (i.e. no accelerations) to provoke fetal movement, which
helps determine whether the non-reactivity is due to physiologic (e.g. fetal sleep cycle) or
pathophysiologic (e.g. acidosis) cause
 Fetal scalp stimulation is not performed in patients with decelerations, as it can exacerbate a
parasympathetic response, resulting in a prolonged deceleration or fetal bradycardia
o Umbilical Artery Doppler Ultrasound
 Performed in growth–restricted fetuses (<10% estimated fetal weight) to evaluate for placental
insufficiency and progressive fetal hypoxemia
Fetal Heart Tracing Patterns / Non-stress test
Category Features Management
Category I  Requires all of the following criteria:  Reassuring – expectant management
o Baseline 110 – 160 bpm  N.B. Reactive NST includes all the
o Moderate Variability (6 – 25 bpm) following criteria:
o No late or variable decelerations o Baseline variability
o ± Early decelerations o Moderate variability
o ± accelerations o Accelerations
 If ≥ 32 weeks = ≥2 in 20 minutes, each peaking ≥ o High negative predictive value for
15/min above baseline & lasting ≥ 15 seconds) fetal acidemia
 If < 32 weeks = ≥2 in 20 minutes, each peaking ≥
10/min above baseline & lasting ≥ 10 seconds)
Category II  Not category I or III (indeterminate pattern) 
Category III  ≥ 1 of the following characteristics:  Caesarean delivery
o Absent variability + Recurrent late decelerations
o Absent variability + Recurrent variable decelerations
o Absent variability + bradycardia
o Sinusoidal pattern

 Umbilical Cord Compression

o Fetal tolerance of impeded fetal–placental blood flow due to occlusion the umbilical blood vessels (and
subsequent hypoxemia and acidemia) correlates with the ratio of umbilical cord compressions to
contractions
 Intermittent umbilical cord compression, evidenced by variable decelerations with < 50% of
contractions, is typically well-tolerated by the fetus (i.e. no hypoxia), and does not require
intervention
 In contrast, umbilical cord compression with ≥ 50% of contractions (as evidenced by recurrent
variable decelerations) can result in a lack of fetal – placental blood flow, which the fetus cannot
tolerate, and causes hypoxemia and acidosis
 Management of recurrent variable decelerations – intrauterine resuscitation with
maternal repositioning (first – line), which may reduce cord compression & improve
fetal–placental blood flow
o If variable decelerations do not improve → amnioinfusion (instillation of saline
into the intrauterine cavity)
 Uterine rupture
 o Disruption of the wall of the uterus; would typically occur in patient with prior uterine surgery (e.g.
caesarean section, myomectomy) because weakened uterine scar tissue can separate with the force of
contractions
 Induction and augmentation increase risk of uterine rupture, especially if prior cesarean delivery
o Clinical Features
 Severe pain and abdominal tenderness
 Massive antepartum bleeding (i.e. intrabdominal, vaginal) due to highly vascular pregnant uterus
 Loss of fetal station (e.g. +1 to –3 station, i.e. fetus retreat upward)
 Loss of uterine contractions
 ± palpable, protruding fetal parts in the abdomen as an irregular protuberance
 Abnormal fetal heart rate tracing, including recurrent variable and late decelerations caused by
umbilical cord compression, and reduced uteroplacental blood flow, respectively
 Before delivery, the primary sign of uterine rupture is fetal bradycardia (most common)
 Elevation of presenting fetal heart
 Maternal Tachycardia
o Management – emergency laparotomy and caesarean delivery
Non–classic (Late–Onset) Congenital Classic Congenital Adrenal Hyperplasia
Adrenal Hyperplasia
Pathophysiology Autosomal recessive Severe 21 β -hydroxylase deficiency
Ashkenazi and white populations Inuit and Alaska native population
 ↓ 21 β -hydroxylase activity (mild)
o Results in impaired conversion of 17-
hydroxyprogesterone (17-OHP) to 11-
deoxycortisol
Normal glucocorticoids (cortisol) &
mineralocorticoids (aldosterone)
 ↑ Androgens
Clinical Features Present during adolescence or early Early onset
adulthood Females – ambiguous genitalia e.g. underdeveloped phallus
Normal external genitalia in both with an ectopic urethral meatus (i.e. hypospadias)
genotypes o Labioscrotal folds may be partially or completely fused
Early pubic / axillary hair growth o both salt–wasting & non–salt wasting
Severe acne Salt–wasting CAH (~67%)
Hirsutism & oligomenorrhea in girls o 7–14 days after birth
Infertility o FTT, vomiting, severe dehydration, hypotension & shock
Virilization is rare (e.g. clitoromegaly, (adrenal crisis & hypoaldosteronism)
deepening of the voice) Non–salt wasting CAH (~33%)
 ↑ Growth velocity & bone age o No signs of shock
 ↑ 17-hydroxyprogesterone level o Mineralocorticoid deficiency is less significant
Normotensive, no electrolyte o Males present with precocious puberty at age 2 – 4 years;
disturbances hypervirilized with palpable testes
 Simple virializing forms (childhood–onset)
o Genital ambiguities in toddler years
o Female psuedohermaphroditism (XX genotype)
 Clitoromegaly and/or curved, underdeveloped phallus
with displaced urethral meatus + uterus and ovaries
 Precocious puberty
 Virilization, menstrual irregularities, infertility
Diagnosis Exaggerated 17–OHP response on ACTH Metabolic acidosis
stimulation test Hyponatremia, Hyperkalemia
Hyperandrogenism Hypoglycemia
 ↓ Corticosterone & 11–deoxycorticosterone
 ↑ ↑ 17-OHP (part of neonatal screening in USA)
Treatment Glucocorticoid replacement in all forms Glucocorticoid replacement
 of CAH (lifelong daily regimen)
o Hydrocortisone in neonates and
children
o Prednisolone or dexamethasone in
adolescents and adults
Lifelong fludrocortisone therapy (aldosterone substitution)
NaCL (salt) supplements, esp. during infancy & childhood
Genital reconstructive surgery for girls
Salt–wasting CAH
o IV fluid resuscitation
o IV dextrose if severe hypoglycemia
o Immediate glucocorticoid replacement therapy

Causes of Hyperandrogenism in Women

Diagnosis
PCOS
Rotterdam Criteria (2003) – 2
out of 3 of the following:
 Hyperandrogenism
(clinical or biochemical Obesity (35 – 60%)
hyperandrogenemia)
 Polycystic ovaries on USS
(TVUS better than Pelvic)
 Ovulatory dysfunction
(chronic oligo- or
amenorrhea)
Clinical Features
Oligo-ovulation (Oligomenorrhea or secondary amenorrhea)± infertility (2O to
anovulation)
o PCOS is the most common cause of hyperandrogenic chronic anovulation
Hyperadrogenism (clinical or biochemical; e.g. hirsutism, acne, biochemical
hyperadrogenemia – testosterone and LH elevated, normal or high DHEAS)
Comorbidities:
o Associated with Metabolic Syndrome (e.g. insulin resistance / type 2 diabetes,
dyslipidemia, hypertension)
o Obstructive Sleep Apnea
o Nonalcoholic steatohepatis
o Infertility
o Endometrial hyperplasia / Cancer (due to increased peripheral estrogens)
Increased ovarian volume with polycystic ovaries on imaging
o 2.8x normal size (volume > 10 mL)
o Atretic follicles doubled – > 12 follicles/ovary @ 2 – 9 mm diameter + Stromal
echogenicity [Rotterdam criteria]
o ±“String of black pearls”
Other Investigations
o FSH, LH, TSH, Prolactin, DHEAS, 17-OH-P
o 2 hr OGTT, HbAIc, Lipid profile
 N.B. OGTT is gold standard in detecting DM II in PCOS patients because it is more
sensitive in detecting glucose intolerance than standard screening tests (e.g. fasting
glucose, HbA1C)
o In ‘lean’ PCOS, LH/FSH > 2* (however normal ratio does not exclude diagnosis)
o Screen for metabolic syndrome – Serial BMI, waist circumference, BP (> 130/85)
No evidence of another diagnosis
Several studies demonstrated that weight reduction in overweight and obese patients with
the syndrome is associated with restoration of ovulation, decrease in androgen
production, and pregnancy
Treatment – Goal–Specific
o Weight loss (first line) – restores ovulatory cycles, improves fertility, and decreases risk
of metabolic syndrome
o Calorie–restricted diet/ lifestyle management (first line)
o Metformin improves insulin sensitivity
o Chronic Oligo– or Anovulation – Cyclic progestin or low–dose CHCs ± metformin
 COCs and progestin – containing IUDs can prevent endometrial hyperplasia / cancer
o Infertility –
 Weight Loss + Clomiphene Citrate (estrogen receptor modulation → blocks action of
estradiol by depleting hypothalamic estrogen receptors → ↑ hypothalamic GnRH
release → increases pituitary FSH & LH release, which induces ovulation)
 Gonadotropins 3rd line
 Letrozole (aromatase inhibitor) for ovulation induction –
 MOA – Aromatase inhibitor → ↓ androgen–to–estrogen conversion by ovarian
granulosa cells (N.B. androgen produced in ovarian theca cells) → ↓ estradiol

Non–classic CAH (Non–classic
21–hydroxylase deficiency)
Androgen–secreting Ovarian
tumours, Ovarian hyperthecosis, Rapidly progressive (i.e., over weeks) hirsutism with virilization
adrenal tumors
Hyperprolactinemia
Cushing Syndrome
Acromegaly
Idiopathic Hirsutism
release in ovary → ↑ GnRH release from hypothalamus → ↑ FSH release from
anterior pituitary → formation of a dominant follicle & ovulation
o Follicular formation ↑ estrogen, which restores estrogenic negative feedback
& normalizes GnRH & FSH
 ADRs – dizziness, bloating, fatigue, headache, hot flashes
 Laparoscopic Ovarian Drilling
 IVF/ICSI ± Metformin (adjuvant therapy to ↓ risk of OHSS [Ovarian Hyperstimulation
Syndrome])
o Skin manifestations (e.g. acne, hirsutism) –
 OCPs / COCs ± antiandrogens (spironolactone, flutamide, finasteride)
 COCs suppress LH production in pituitary, thereby decreasing ovarian androgen
production; also increase sex hormone–binding globulin synthesis by the liver,
decreasing free testosterone levels
 Spironolactone is a androgen receptor antagonist used in those with inadequate
response to COCs; not used in those who wish to become pregnant due to risk of
fetal abnormalities
 GnRH agonists (lupron)
o Statins indicated if dyslipidemia
Similar to PCOS – Oligo-ovulation
Hyperadrogenemia
 ↑ 17-hydroxyprogesterone levels
Older age; more common in post–menopausal women
o Rapid onset hirsutism (< 1 year), particularly with virilization (e.g. temporal ‘male-
patterned’ balding, excessive muscular development, clitoromegaly, voice deepening)
o New-onset voice deepening (possibly irreversible) – sign of frank virilization as excess
androgens (e.g. testosterone > 150 ng/dL, DHEAS > 700 μg/dL) lengthen and thicken
the vocal cords, thereby changing the acoustic frequency & changing the voice
Typically have signs of insulin resistance (e.g. hyperglycemia, acanthosis nigricans)
 ↑ androgen levels (> 3x ULN) – testosterone, androstenedione, and
dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS; adrenals only); e.g. Sertoli-Leydig
o ↑ testosterone levels, and normal DHEAS → ovarian source (more common)
o ↑ testosterone & DHEAS levels → adrenal tumour (far less common)
o Low / normal LH & FSH – due to negative feedback by testosterone
Solid appearing, enlarged ovaries rather than multiple cysts
Amenorrhea
Galactorrhea
 ↑ prolactin levels
Cushingoid features – Obesity (usually of the face, neck, trunk, abdomen)
Increased libido, virilization, irregular menses
Non-suppressible dexamethasone suppression test
 ↑ 24-hour urinary free cortisol
Excessive growth (enlarging facial features, macroglossia)
Excessive body hair in women
 ↑ GH & IGF-1 levels
Normal menstruation
Normal serum androgens

 Evaluation of Precocious Puberty

o Early secondary sexual development* (in girls < 8 years or boys < 9 years)
 Bone Age Evaluation (radiographic assessment of hands and wrist to assess skeletal maturity) →
 Advanced Bone Age (i.e. > 1 year difference between bone age & chronological age) →
Evaluate Basal LH
o (recall premature elevated estrogen in cases of precocious puberty can lead to
premature epiphyseal fusion, and in turn, advanced bone age compared to
 chronological age; may initially have early pubertal growth splurts [i.e. increased
height velocity] but will often have shorter than expected adult height)
o Low Basal LH → GnRH stimulation test
 Low LH & FSH → Peripheral precocious puberty (Adrenal CT Scan or Pelvic
USS to evaluate)
 Ovarian or adrenal tumour
 Non–classic congenital adrenal hyperplasia
 McCune–Albright Syndrome is characterized by triad of:
o Polyostotic Fibrous dysplasia – typically unilateral
o Autonomous endocrine hyperfunction
 Gonadotropin–independent precocious puberty –
breast development, axillary & pubic hair
 Girls typically have premature vaginal bleeding and
breast development
o Irregular café au lait macules (‘Coast of maine’)
 High LH after GnRH stimulation → Central (Gonadotropin–dependent)
precocious puberty
o High Basal LH → Central precocious puberty (MRI brain to evaluate)
 Advanced Bone age, elevated FSH & LH and true precocious development
(e.g. breast development)
 Idiopathic precocious puberty
o Tx – GnRH agonist therapy, which prevents premature
epiphyseal plate fusion, and maximizes adult height
potential
 Endogenous hormone production
o FSH- or LH-secreting pituitary microadenomas
o GNRH-secreting hypothalamic hamartoma
 Indirectly affecting HPG-axis through mass effect or increased
intracranial pressure
o Craniopharyngioma
o pituitary hamartoma
o hypothalamic glioma
 Normal Bone Age (< 1 year difference between bone age & chronological age)
o Isolated Breast Development → premature thelarche
o Isolated Pubic Hair Development → Isolated Premature adrenarche
 Caused by early activation of adrenal androgens
 Body odour, oily skin, acne , pubic and axillary hair
 N.B. Estrogen and testosterone levels remain normal; therefore
there are no other signs of premature puberty (e.g. breast
development, testicular enlargement) or virilization (e.g.
clitoromegaly)
 Mildly elevated dehydroepiandrosterone sulfate is not sufficient to affect
skeletal growth; therefore bone age is normal in these patients
 Obese children are at high risk for precocious development as adiposity can
trigger excess insulin production, which then stimulates the adrenal glands
to produce sex hormones
 Isolated premature adrenarche is a risk factor for developing PCOS, type 2
DM, and metabolic syndrome, especially in obese patients
 Causes of Hyperandrogenism in Pregnancy (Gestational Hyperandrogenism)
o Placental Aromatase Deficiency
 Rare enzyme deficiency causing decreased conversion of testosterone / DHEAS to estradiol
  ↑ Dehydroepiandrosterone sulfate, DHEAS (> 700 mcg/dL)
 ↑ serum testosterone & androstenedione
 Masculinization of female (46,XX DSD) infants (ambiguous genitalia)
 No ovarian mass
 High maternal & fetal virilization risk (fetal androgens cross the placenta)
 Normal internal genitalia
 External virilization of fetus
o ambiguous external genitalia due to high levels of gestational androgens e.g.
clitoromegaly
o In adolescence, delayed puberty (delayed menarche), osteoporosis
o Undetectable estrogen levels (e.g., no breast development)
o High concentrations of gonadotropins → polycystic ovaries
 Resolution of maternal symptoms after delivery
o Luteomas of pregnancy
 Solid, unilateral / bilateral ovarian masses; large lutein cells which release androgens
 Moderate maternal virilization risk; high fetal virilization risk
 Spontaneous regression of masses after delivery
o Theca-Lutein Cysts
 Clinical Features
 Cystic / Multilocular, Bilateral, 10 – 15 cm ovaries
 Moderate maternal virilization risk; low fetal virilization risk
 Spontaneous regression of masses after delivery
 Pathogenesis – Ovarian hyperstimulation due to:
 Gestational Trophoblastic disease
 Multifetal gestation
 Infertility treatment
 Clinical Course – Resolve with decreasing β -hCG levels after delivery
o Sertoli – Leydig Tumour – secretes testosterone
 Solid unilateral ovarian mass
 High maternal & fetal virilization risk
 Surgery required (2nd trimester or postpartum)
 Either ovarian biopsy or oophorectomy indicated due to malignant potential
 Ovarian Hyperstimulation Syndrome (OHSS)
o Rare, but life-threatening complication of ovulation induction, occurring 1 – 2 weeks after induction (hCG
injection)
o Pathophysiology
 ↑ hCG enhances ovarian vascular permeability & capillary leakage due to overexpression of VEGF
 Massive, acute extravascular fluid shift (i.e. third spacing) and VEGF leakage into the
intraperitoneal cavity, leading to ascites and abdominal distension
o Clinical Features
 Nausea, vomiting, abdominal pain, rapid weight gain
 Ascites
 Respiratory distress – pleural effusions (tachypnea, decreased breath sounds)
 Intravascular volume depletion –
 Tachycardia, Hemoconcentration, leukocytosis
 Hypercoagulability, thromboembolism
 Hypovolemic shock in severe cases
 Electrolyte imbalances
 Multiorgan failure (e.g. renal failure – oliguria, anuria)
 Disseminated Intravascular Coagulation
 Death
 o Evaluation
 Fluid balance monitoring
 Serial CBC, electrolytes
 Serum hCG
 Pelvic USS – bilateral, enlarged cystic ovaries with multiple follicles + normal sized uterus with
thin endometrial lining
 CXR
 Echocardiography
o Management
 Correct electrolyte imbalances
 Paracentesis &/or thoracocentesis
 Thromboembolism prophylaxis

 Premenstrual Syndrome (PMS); Premenstrual Dysphoric Disorder (PMDD; severe variant of PMS)
o PMS – Recurrent physical & behavioral symptoms manifesting during luteal phase of menstrual cycle
 Resolve with menstruation
 Absence of secondary causes
 Severe: premenstrual dysphoric disorder (PMDD)
o PMS requires 5 systemic symptoms to meet criteria
o Association with future primary mood and anxiety disorders (e.g. Major Depressive Disorder), which is
also characterized by serotonergic dysfunction
 Lifetime risk of primary psychiatric disorder in patients with PMS approaches 80% and is elevated
in the years prior to and after PMS symptoms
 In PMDD, affective symptoms may be due to dysregulation of the serotonergic system – namely
abnormal neurotransmitter (serotonin) response to cyclic hormonal fluctuations of estrogen and
progesterone during the luteal phase of the menstrual cycle, which explains the effectiveness of
SSRIs
o Clinical Features
 Physical – Bloating, fatigue, headaches, hot flashes, breast tenderness
 Behavioural – anxiety, irritability, mood swings, decreased interest, decreased concentration,
decreased libido
 Symptom severity must reach point of socioeconomic impact (e.g. missed work) to qualify as PMS
or the more severe variant, PMDD
 Symptom onset begin a week prior to menses and resolve within a few days after menses start
 Patients are symptom free during the follicular phase
 Physical Exam – normal
 PMDD – severe variant of PMS with prominent irritability, hopelessness, depressed mood, self–
critical thoughts, anger and greater psychosocial impairment
o Evaluation – detailed menstrual diary over 2 – 3 menstrual cycles
 Prospective charting of daily mood and physical symptoms over 2 – 3 menstrual cycles
 Should demonstrate recurrence of symptoms during the luteal phase (i.e. 1–2 weeks prior
to menses) and resolution during the follicular phase (onset of menses, or a few days
thereafter)
o Cyclical pattern of overeating + mood ability + irritability
 Evaluation is aimed at eliminating mood disorders, and laboratory testing for
hypothyroidism, a common cause of fatigue – if symptoms occur irregularly or throughout
the menstrual cycle, a primary mood or personality disorder is more likely
o Treatment
 1st line – SSRI (daily or limited use during the luteal phase) e.g. fluoxetine, citalopram
 N.B. any single SSRI may fail in relieving symptoms in 1/3 of patients, so a trial of 2 nd SSRI
is usually warranted
 N.B. paroxetine is contraindicated in pregnancy
 o first trimester exposure may lead to congenital heart disease
nd
 2 line – Combined oral contraceptives (MOA: cause anovulation)
 N.B. however estrogen containing products would be contraindicated in certain patients
e.g. migraine with aura
 Eligible patients in whom contraception is a high priority may prefer starting with a trial of
combined OCPs rather than SSRIs
 N.B. progestin – only contraceptives are not effective
 Drospirenone + ethinyl estradiol (Yaz; Yasmin)
o drospirenone is a spironolactone analog
 anti–androgen and anti–mineralocorticoid effects
rd
 3 line – Gonadotropin–releasing hormone agonist (GnRH agonist) e.g. leuprolide
 ADRs – osteoporosis (due to suppression of endogenous estrogen production)
 Last line – Benzodiazepines – risk of sedation and dependence
 Primary Dysmenorrhea
o Common in adolescents (90%); Most women have decreasing symptoms with increasing age
o Etiology – excess production of prostaglandin F2a
o Risk Factors
 Age < 30 years
 BMI < 20 kg/m2
 Tobacco use
 Menarche at age < 12
 Heavy / long menstrual periods
 Sexual abuse
o Clinical Features
 Typically presents within 6 – 12 months of menarche
 Pain first 2–3 days of menses
 Crampy, bilateral, lower abdominal pain begins 1–2 days prior to onset of menses (as
uterine contractions initiate endometrial sloughing)
 Resolves a few days after onset of menses (as the endometrial lining thins)
 Nausea, vomiting, bloating, diarrhea – prostaglandin-induced gastrointestinal stimulation
 Fatigue, dizziness
 Normal physical / pelvic examination
o Management
 NSAIDs (inhibition of prostaglandin synthesis) – 2– 4 month trial (first line)
 Should be taken 2 – 3 days prior to onset of menses and continued throughout menstrual
cycle
 Combination oral contraceptives
 If refractory to NSAIDs, or if NSAIDs are not tolerated
 an option in sexually active patients due to suppression of ovulation, providing both
contraception and inhibition of prostaglandin release
 Patients with the following clinical features should be evaluated for secondary causes of dysmenorrhea
o Symptom onset at age > 25
o Unilateral (non–midline) pelvic pain
o No systemic symptoms (e.g. fatigue, nausea) during menses
o Abnormal uterine bleeding (e.g. intermenstrual bleeding, post–coital spotting)
o Pain that does not improve with NSAID use (very non-specific)
 Pelvic Congestion Syndrome
o Dull, ill-defined pelvic ache that worsens with intercourse and prolonged standing
o Pain prior to menses that is then relieved by menses
 Dysfunctional Uterine Bleeding
o Typically the result of anovulation
  In the absence of ovulation, no progesterone influence on the endometrium, so normal signal for
cyclic endometrial sloughing (menstrual bleeding) is absent.
 Estrogen as a trophic hormone on the endometrium, causes endometrial overgrowth that
ultimately outgrows its blood supply resulting in irregular sloughing that may be significant
(hemorrhage)
o Treatment
 Hormonal therapy to stabilize the endometrium
 Estrogen should be used in all patients who are actively bleeding as it promotes
hemostasis
o High – dose estrogen followed by progestin – treatment of choice
o OCPs 3 – 4 times the regular dose – alternative, for less severe cases
o Intravenous conjugated estrogen
 If unable to tolerate oral medications & in unstable patients with severe
bleeding as it can induce hemostasis rapidly
 Progestin–only therapy (medroxyprogesterone)
o Used in moderate PV bleeding when female unable to tolerate or have a
contraindication to estrogen therapy
 Dilatation & Curettage (rare)
 Rare situations when patient continues to bleed excessively despite hormonal treatment
or if contraindication to estrogen
 Endometriosis
o Estrogen–dependent condition that affects reproductive–age women
o Pathogenesis
 ectopic endometrial glands and stoma implanted outside the endometrium can cause pain due to
cyclic hemorrhage and accumulating fibrosis, which can distort normal pelvic anatomy and impair
fertility by obstructing oocyte release or sperm entry
 Location
 Ovaries (most common)
 Uterosacral ligaments
 Broad Ligaments
 Rectouterine pouch (pouch of Douglas; cul–de–sac)
 Uterus, fallopian tube
 Peritoneum
 Sigmoid Colon, Appendix, Cecum, and colon → potential for intestinal obstruction
o Risk Factors
 Family history
 Early menarche
 Nulliparity
o Can be asymptomatic
o Clinical Features – Suspected Endometriosis:
 Chronic pelvic pain after years of painless menstruation with severe dysmenorrhea
 Deep Dyspareunia
 Dyschezia
 Infertility / Subfertility
o Physical Examination
 Tenderness & nodules in rectovaginal septum, pelvic peritoneum, anterior and posterior cul-de-
sac, and uterosacral ligaments
 Immobile Uterus (Fixed, retroverted uterus)
 Cervical motion tenderness
 Adnexal mass (tender, fixed)
 Negative laboratory testing and normal ultrasound exclude other etiologies of chronic pelvic pain
  CT scan can may be performed to search for other etiologies of chronic pelvic pain but is
not the study of choice in highly suspected cases of endometriosis as it cannot reliably
delineate endometrial implants from other soft tissues
o Management
 Medical
 Combined hormonal or progestin-only contraceptives
o Considered 1st–line for pain due to endometriosis
 Gonadotropin-releasing hormone (GnRH) agonist indications
o 2nd–line treatment for endometriosis
o Mechanism – inhibits gonadotropin secretion which decreases FSH and LH levels
leading to a suppression of ovarian function
 Levonorgestrel–releasing intrauterine device (IUD)
o Another 2nd–line treatment for endometriosis
 Danazol (a synthetic androgen)
o not commonly used due to side–effects
o Mechanism – suppresses FSH and LH pituitary secretion
 Operative
 Laparoscopic ablation
o Surgery is the only definitive treatment and diagnostic modality
o Bipolar coagulation or laser vaporization
 Total abdominal hysterectomy& Salpingo–oopherectomy with lysis of adhesions
o In patients who have completed childbearing (or uninterested in preserving future
childbearing potential) with severe, disabling and recurrent disease
 Contraindications to Medical Therapy? Need for Definitive Diagnosis? History of Infertility?
Concern for malignancy or adnexal mass?
 If Yes → Laparoscopy (direct visualization, biopsy (histologic confirmation) and removal of
endometriotic lesions
o Unless estrogenic stimulation is suppressed, symptoms eventually return with the
regrowth of endometriosis
o Definitive treatment (if completed childbearing): hysterectomy and oophorectomy
o Laparoscopic resection of endometriosis, especially endometriomas (ovarian
endometriosis cyst, “chocolate cyst”, which is associated with impaired ovarian
function), improves conception rates
 If No → NSAIDs ± oral contraceptives; if failure of empiric therapy → Laparoscopy
 Pregnancy management of HSV
o Prior HSV infection?
 No → Exposure to infected HSV – partner?
 No → No testing or treatment needed
 Yes → HSV serology (HSV – 1 & HSV – 2) indicated – 96 – 100% sensitivity & 97 – 98%
specificity
o HSV serology positive → antiviral therapy (acyclovir, valcyclovir) beginning at 36
weeks up to delivery
o HSV serology negative → No testing or treatment needed
 Yes → Antiviral therapy (acyclovir, valcyclovir) beginning at 36 weeks until delivery, regardless of
symptoms
 HSV prophylaxis reduces asymptomatic viral shedding and outbreak recurrences
 Lesions / prodromal symptoms during labour
o Yes → Ceasarean delivery (i.e. indicated if infection is active at term)
 Lowers risk of vertical transmission compared to vaginal delivery with
active lesions or prodromal symptoms at time of delivery (1.2% versus 7%)
o No → Vaginal delivery, once on antiviral prophylaxis
  Patients with no prodromal symptoms or lesions have decreased risk of
vertical transmission
 N.B. Genital swab for HSV PCR have high sensitivity for confirming the presence of HSV particles
in patients with suspected herpetic lesions and those with asymptomatic shedding. However,
they would not detect HSV in patients with latent infection who could reactivate at time of
delivery
 Differential Diagnosis of Vaginitis
Bacterial Vaginosis Trichomoniasis Candida vaginitis
Diagnosis
(Gardnerella vaginalis) (Trichomonas vaginalis) (Candida albicans)
Imbalance in normal vaginal bacterial
flora associated with increased
DM
Gardnerella vaginalis, Mycoplasma
o women with recurrent
hominis, and anaerobic bacteria, along
vulvovaginal candidiasis
with corresponding decrease in
infections (≥ 4 episodes per
hydrogen-peroxide producing
year) & signs of DM (e.g.
lactobacilli
nocturia, urinary
Risk Factors Women having sex with women 
frequency) should be
Vaginal douching
evaluated with HbA1c
Tobacco use
Immunosuppression
Complications
Pregnancy
o ↑ risk of preterm birth
OCPs
o ↑ risk of acquisition of HIV, herpes
Antibiotic use
simplex virus type 2, gonorrhea,
chlamydia & trichomoniasis infection
Present in 1/3 of all pregnancies
Thin off–white, homogenous vaginal
discharge with fishy odor Thin, yellow-green
No inflammation malodorous, frothy discharge
Thick, cottage cheese
Amsel Criteria (≥ 3 of the findings) Vulvovaginal inflammation →
discharge adherent to vaginal
o Discharge as described above pruritus, dyspareunia,
wall
Examination o Vaginal pH > 4.5 vulvovaginal erythema
Vaginal inflammation →
o Clue cells (irregularly bordered Strawberry cervix
vulvar pruritus, vulvovaginal
vaginal epithelial / squamous cells (erythematous & friable
erythema
coated with sheets of small bacteria, macular lesions = punctate
Gardnerella vaginalis) haemorrhages)
o Positive whiff test (amine, fishy
odour with 10% KOH)
pH > 4.5
Normal pH (3.8 – 4.5)
Laboratory findings Amsel Criteria as above Motile trichomonads
Pseudohyphae
(flagellated, ovoid protozoa)
Metronidazole or tinidazole
(even if asymptomatic)
Oral Metronidazole (500mg PO BD x
treat sexual partner
1/52) or Oral clindamycin, regardless
avoid sexual intercourse for a
Treatment of pregnancy status Fluconazole
week (to prevent reinfection)
Boric acid & clindamycin for recurrent
and alcohol consumption
BV
(due to possible disulfram–
like reaction)
↑
 risk of preterm birth, premature
rupture of membranes & spontaneous
abortions (N.B. efficacy of treatment in
reducing preterm labour is
Complications controversial)  
 ↑ risk of acquisition of HIV, Herpes
simplex virus type 2 (HSV 2),
gonorrhea, chlamydia & trichomonas
infections

 Chlamydia & Gonorrhea in Women (Acute Cervicitis; Pelvic Inflammatory Disease, PID)
o Risk Factors
 Age < 15 – 25 years
  High–risk sexual behaviour
 Lack of barrier protection (~x2–fold increased risk of PID)
 Multiple sex partners (highest risk factor; x4.6 to 20 –fold increased risk of PID)
 History of previous episodes of PID (x2.3–fold increased risk; 1 in 4 women suffer recurrence)
 Noninfectious: foreign object, latex, Vaginal Douching increases risk of PID
o Etiology – Cervicitis most commonly caused by Chlamydia trachomatis and Neisseria gonorrhoeae
 Infections with these pathogens is most prevalent in women age < 25 years
o Clinical features
 Asymptomatic (most common)
 Acute Cervicitis
 Thick, yellow mucopurulent cervical / vaginal discharge
 Post–coital bleeding &/or Intermenstrual bleeding – friable cervix that bleeds easily on
contact
o Erythematous, friable cervix that easily bleeds on contact with swab
 Urethritis
 Progression to PID – gonococcal cervicitis predisposes to the upper reproductive tract (e.g.
uterus, fallopian tube) to polymicrobial infection
 Cervical motion tenderness (e.g. chandelier sign)
 Uterine, adnexal tenderness
 Complications
o Peri-hepatitis (Fitz-Hugh-Curtis Syndrome)
o Tubo–ovarian abscess
o Pyosalpinx
o Infertility
o Increased risk of ectopic pregnancy due to fallopian tube damage
 Other less common symptoms
 Dysuria, sterile pyuria
 Dyspareunia
 Vulvovaginal pruritus
o Diagnosis
 CBC, U&Es
 Investigate for other sexually transmitted infections if NAAT testing for C. trachomatis is positive
 HIV, Syphilis, HBV
 Nucleic acid amplification testing (confirmatory)
 In patients who are not sexually active, screening for C. Trachomatis may be omitted
 CT – guided aspiration of tubo–ovarian abscess
 Used to drain small, unilocular pelvic abscess and guide antibiotic therapy
o Indications for hospitalization for Pelvic Inflammatory Disease
 Pregnancy
 Inability to tolerate oral management &/or Failed outpatient management
 Inability to take PO antibiotics (N/V), lack of response to PO antibiotics
 Non–compliant with therapy
 Severe presentation (e.g. high fever, persistent vomiting & dehydration, leukocytosis)
 Fever > 102.2 OF, Severe Abdominal Pain
 Complications (e.g. tuboovarian abscess, peri–hepatitis, ectopic pregnancy)
o Management
 Acute Cervicitis – Empiric ceftriaxone + doxycycline (ceftriaxone + azithromycin in pregnancy)
 Delay of treatment increases the risk of ascending infection → pelvic inflammatory
disease & pregnancy complications (e.g. preterm birth)
 Treat sexual partners to prevent reinfection
 Advised to abstain from intercourse for 7 days following completion of treatment
  Complicated Gonorrhea (salpingitis, adnexitis, & PID in women; epididymitis & orchitis in men)
 Single-dose ceftriaxone IM + doxycycline PO for 10–14 days (anaerobic coverage)
 Empiric: Azithromycin + ceftriaxone
o Azithromycin monotherapy for NAAT–proven chlamydial cervicitis (however, due
to increasing antimicrobial resistance, dual therapy is recommended)
 Confirmed gonorrhea: Azithromycin + ceftriaxone
o Management – PID
 In-patient regimen for PID
 IV cefoxitin or cefotetan plus IV or PO doxycycline
o Oral doxycycline is preferred initially if patient is able to tolerate PO intake
 Alternative – IV clindamycin (anaerobic coverage) & IV gentamicin
 Switch to entirely PO antibiotics after 24 hours of sustained clinical improvement
 Outpatient regimen:
 Ceftriaxone IM (one dose) plus doxycycline PO x 14 days
 Cefoxitin IM (one dose) plus probenecid PO (one dose) plus doxycycline x 14 days
 Follow up within 72 hours to ensure improvement
 Add metronidazole to either regimen if:
 PID is complicated by tubo–ovarian abscess due to required additional anaerobic coverage
 Suspected bacterial vaginosis, trichomonas, pelvic abscess, or recent gynecologic
instrumentation
 Evaluate and treat the patient's sexual partners from the past 60 days
o Complications
 Hymenal and tubal synechiae, tubal motility disorders → infertility
 Gonococcal conjunctivitis (particularly in neonates; Neisserial Conjunctivitis)
 Perinatal transmission of Neisseria gonorrhoeae may lead to ophthalmia neonatorum
(gonococcal ophthalmic disease).
 Clinical Features
o Onset 2 – 7 days after birth.
o Pronounced swollen eyelids, purulent exudate with crusting; there may be a large
reservoir of pus below the crusts
o Rapid onset hyperemia and significant purulent drainage in both eyes, fever, and
preauricular lymphadenopathy.
 Treatment
o infection can threaten vision, prompt treatment with intravenous antibiotics
(ceftriaxone or ciprofloxacin) is important
o IV or IM 3rd generation cephalosporin (e.g., ceftriaxone or cefotaxime) for both
mothers and newborns.
 Ceftriaxone is contraindicated in premature neonates, neonates with
hyperbilirubinemia , and in neonates requiring calcium–containing IV
solutions (e.g., parenteral nutrition)
 Diagnosis – Cultures and gram stain (on blood, chocolate agar, and conjunctival scrapings)
or PCR
 Crede prophylaxis for newborns (topical erythromycin or tetracycline)
 In patients with pelvic inflammatory disease and IUD in–situ, IUD removal is not required; removal increases the
risk of unintended pregnancy and does not affect treatment outcomes
 Chlamydial conjunctivitis in Neonates
o C. trachomatis;serotypes D–K
o 5 – 14 days after birth
o Clinical Features – Watery/mucopurulent ocular discharge, eyelid swelling
o Diagnosis – Cultures and gram stain (on blood, chocolate agar, and conjunctival scrapings) or PCR
o Treatment
  Newborns: oral erythromycin or azithromycin
 Mother and at-risk contacts: oral azithromycin or amoxicillin (for 1 week)
Chlamydia in Pregnancy
 Universal screening at first prenatal visit
Screening
 High risk: repeat screening in 3rd trimester
 Age < 25
 History of STI
Risk Factors
 Recent New Partner
 History of Multiple Partners
 Preterm Prelabour Rupture of Membranes
Obstetric
 Preterm Labour
Complications
 Postpartum endometritis
 Neonatal conjunctivitis
Fetal Complications
 Neonatal pneumonia
Treatment  Azithromycin

 Bartholin Gland Abscess

o Bartholin glands are located bilaterally at the posterior vaginal introitus and have ducts that drain into the
vulvar vestibule at the 4 and 8 o’clock positions to provide vulvovaginal lubrication
o When duct becomes obstructed, a Bartholin duct cyst develops and infection of the cyst can lead to an
abscess
o Infection typically due to methicillin-resistant Staphylococcus aureus or Escherichia coli
o Clinical features
 Painful, swollen labial mass; pain with sitting or sexual intercourse
 Fever is not common
 Tender, fluctuant mass at base of labium majus that protrudes into the vagina
o Treatment
 Incision and drainage and Cx of the fluid
 Word catheter is placed in the abscess cavity to form a fistulous tract, which improves duct
drainage and reduces the risk of cyst / abscess recurrence
 Antibiotics typically not indicated but may be used for patients with high risk of complications
(e.g. systemic infection, pregnancy, immunosuppression)
 Marsupialization, a procedure that creates a new Bartholin gland duct, is more invasive and is
reversed for patients with recurrent abscesses
 Vaginal Foreign Body
o Clinical Features
 Prepubertal girls – common cause of vulvovaginitis in this population
 Vaginal Spotting (intermittent vaginal bleeding)
 Urinary symptoms (e.g. dysuria)
 Malodorous vaginal discharge
 No signs of trauma (e.g. lacerations)
 Toilet paper most common object; other objects (e.g. small toys, hair bands)
o Management – foreign body removal
 Warm irrigation
 Vaginoscopy under sedation / anesthesia; patient in the knee-chest or frog-leg position
 Postpartum Hemorrhage
o Early postpartum hemorrhage: ≥ 1000 mL total blood loss or loss of blood coinciding with signs and
symptoms of hypovolemia within 24 hours after delivery of the fetus or intrapartum loss
 ≥ 500 mL total blood loss after vaginal delivery
 ≥ 1000 mL total blood loss after caesarean delivery
  Primary postpartum hemorrhage may occur before delivery of the placenta and up to 24 hours
after delivery of the fetus.
o Complications of postpartum hemorrhage
 Anemia
 Sheehan syndrome or postpartum pituitary necrosis
 Anterior pituitary ischemia with delay or failure of lactation
 Blood transfusion
 Dilutional coagulopathy
 Fatigue
 Myocardial ischemia
 Orthostatic hypotension
 Postpartum depression
 Death from cardiovascular collapse
o Epidemiology
 ~ 3 – 5% of obstetric patients will experience postpartum hemorrhage, and are responsible for
25% of maternal deaths worldwide and 12% of maternal deaths in the United States
o Risk Factors
 20% of postpartum hemorrhage occurs in women with no risk factors
 Antepartum hemorrhage
 Prolonged or Induced / Augmented labor
 Chorioamnionitis
 Fetal macrosomia
 Maternal anemia
 Maternal obesity
 Multifetal gestation
 Polyhydramnios
 Grand Multiparity
 Operative vaginal delivery
 Preeclampsia
 Primiparity
o Etiology – 4 Ts
 Tone (70%) – uterine atony (most common cause of PPH)
 Brisk blood flow after delivery of the placenta unresponsive to transabdominal massage
should prompt immediate action including bimanual compression of the uterus and use of
uterotonic medications
 Massage is performed by placing one hand in the vagina and pushing against the body of
the uterus while the other hand compresses the fundus from above through the
abdominal wall
 Trauma (20%) – Perineal laceration, hematoma, inversion, rupture
 Episiotomy increases the risk of blood loss and anal sphincter tears;
o Avoid unless urgent delivery warranted & perineum is a limiting factor
 Vaginal and vulvar hematomas can present as pain or as a change in vital signs
disproportionate to the amount of blood loss.
o Small hematomas can be managed with ice packs, analgesia, and observation.
o Patients with persistent signs of volume loss despite fluid replacement, as well as
those with large (> 3 – 4 cm) or enlarging hematomas, require incision and
evacuation of the clot
 Uterine inversion is rare, occurring in only 0.04% of deliveries (see below)
 Tissue (10%) – retained tissue or invasive placenta
 Classic signs of placental separation include a small gush of blood, lengthening of the
umbilical cord, and a slight rise of the uterus.
  Mean time from delivery to placental expulsion is 8 – 9 minutes. Longer intervals
associated with an increased risk of PPH, with rates doubling after 10 minutes
o Retained placenta (i.e., failure of the placenta to deliver ≤ 30 minutes) < 3% of
vaginal deliveries. Consider manual removal using appropriate analgesia
o Pelvic USS – echogenic mass or absence of normal endometrial stripe (less
consistent finding)
 Treatment of invasive placenta (placent accreta, increta or percreta) can require
hysterectomy or, in select cases, conservative management (i.e., leaving placenta in place
or giving weekly oral methotrexate)
 Thrombin (1%) – coagulopathy
 Plt, PT, aPTT, fibrinogen level, fibrin split products (FDP), & quantitative d-dimer assay
 Suspect if blood fails to clots in bedside receptacles or red top tubes (no additives) within
5 to 10 minutes, oozing from puncture sites etc.
 Acquired
o Amniotic fluid embolism
o Consumptive coagulation secondary to excessive bleeding of any origin
o Disseminated intravascular coagulation secondary to abruption
o Fetal demise
o HELLP (hemolysis, elevated liver enzyme levels, and low platelet levels) syndrome
o Placental abruption
o Preeclampsia with severe features
o Sepsis
o Use of anticoagulants such as aspirin or heparin
 Chronic or congenital
o Hemophilia
o Idiopathic thrombocytopenic purpura
o Thrombotic thrombocytopenic purpura
o Von Willebrand disease
o Prevention – most effective strategy to prevent PPH is active management of 3 rd stage of labor (AMTSL)
 AMTSL also reduces the risk of a postpartum maternal Hb < 9 g/dL & need for manual removal of
the placenta.
 Components of this practice include:
 Administering oxytocin (Pitocin) with or soon after the delivery of the anterior shoulder
 Controlled umbilical cord traction with suprapubic counterpressure (Brandt–Andrews
maneuver) to deliver the placenta
o Reduces the incidence of less severe blood loss (500 to 1,000 mL) and reduces the
need for manual extraction of the placenta.
 Uterine massage after delivery of the placenta
o Clinical Features
 Healthy pregnant women can typically tolerate 500–1000 mL of blood loss without having signs
or symptoms.
 Tachycardia may be the earliest sign of PPH.
 Orthostasis, hypotension, nausea, dyspnea, oliguria, and chest pain may indicate hypovolemia
from significant hemorrhage
o Management
 Resuscitation
 Call for help
 Perform bimanual uterine massage
 Institute labor unit hemorrhage protocol
 Deliver oxytocin 20 IU in 1 L normal saline, infuse 500 mL over 10 minutes then 250 mL
per hour
  Provide oxygen by mask
 Monitor blood pressure, pulse, and urine output
 Two large-bore IV access
 CBC, GXM, ± PT/PTT/INR, FDP, D–dimer
 1st line agent – oxytocin, a uterotonic agent
 Prevention of PPH: 10 IU IM or 5 to 10 IU IV bolus
 PPH Tx: 20 to 40 IU in 1 L normal saline, infuse 500 mL over 10 minutes then 250 mL/hr
 MOA – Stimulates the upper segment of the myometrium to contract rhythmically,
constricting spiral arteries and decreasing blood flow through the uterus
 Contraindications and cautions
o Overdose or prolonged use can cause water intoxication
o Possible hypotension with IV use following cesarean delivery
 ADRs – rare
 2nd line uterotonic agents
 Carboprost (Hemabate), a prostaglandin F 2 α analogue; uterotonic agent:
o PPH Tx: 250 µg IM or into myometrium, q15–90 minutes for a total dose of 2 mg
o Avoid in patients with asthma (causes bronchoconstriction) or significant renal,
hepatic, or cardiac disease
o MOA – synthetic prostaglandin F 2 α analogue that improves uterine contractility by
increasing the number of oxytocin receptors and causes vasoconstriction
o ADRs – N/V/D
 Methylergonovine (Methergine)
o Treatment: 0.2 mg IM, repeat q2–4-hourly
o Avoid in hypertensive disorders of pregnancy, including chronic hypertension
o Use with caution in patients with HIV who are receiving protease inhibitors
o MOA – uterotonic drug that causes vasoconstriction and contracts smooth muscles
and upper and lower segments of the uterus tetanically
o ADRs – Nausea, vomiting, and ↑ BP
 Misoprostol (Cytotec), a prostaglandin E1 analogue
o Prevention: 600 µg orally (Use only when oxytocin is not available)
o Treatment: 800 to 1,000 µg rectally or 600 to 800 µg sublingually or orally
o Use with caution in patients with cardiovascular disease
o MOA – Causes generalized smooth muscle contraction
o ADRs – Nausea, vomiting, diarrhea, pyrexia, and shivering
 Adjunctive Therapy – antifibrinolytics
 Tranexamic acid (Cyklokapron)
o Adjunctive Therapy: 1 g IV x10 minutes, may be repeated after 30 minutes
o MOA – Inhibits breakdown of fibrin and fibrinogen by plasmin
o Contraindications and cautions
 Use within 3 hours of onset of bleeding
 Use with caution in patients with renal impairment and with other clotting
factors such as prothrombin complex concentrate
o ADRs - May increase risk of thrombosis and cause visual defects
 Severe postpartum hemorrhage
 Transfuse pRBCs, platelets, and clotting factors using massive transfusion or emergency
release protocol
o Massive transfusion protocols to decrease the risk of dilutional coagulopathy and
other postpartum hemorrhage complications have been established.
 Typically recommend 4U FFP & 1U Plt for every 4 – 6U pRBC used
 Consult anesthesia, surgery, and an intensivist
 Support BP with vasopressors
  Uterus–conserving treatments
o Uterine packing (plain gauze or gauze soaked with vasopressin, chitosan, or
carboprost [Hemabate])
o Artery ligation, uterine artery embolization
o B–lynch compression sutures
o Balloon tamponade.
 Hysterectomy – definitive treatment in women with severe, intractable hemorrhage.
o Aftercare
 Monitor for ongoing blood loss (preferably quantitative measurement) and vital signs
 Assess for signs of anemia (fatigue, shortness of breath, chest pain, lactation problems)
 Debrief with and listen to patients and staff regarding their experience with the emergency
 Many patients experience acute and posttraumatic stress disorders after a traumatic delivery.
 Uterine Inversion
o Uncommon but potentially fatal cause of postpartum hemorrhage (0.04% of deliveries)
o Risk Factors
 Nulliparity
 Fetal macrosomia
 Placenta accreta
 Placental villi attach directly to the myometrium → placenta fails to spontaneously
separate and deliver
 Typically only occurs in patients with prior caesarean section, myomectomy, or dilatation
and curettage
 Rapid labor and delivery
o Pathophysiology
 Excessive fundal pressure and traction on the umbilical cord before placental separation → fundus
collapses into the endometrial cavity and prolapses through the cervix
o Clinical Features
 Smooth, round bluish–gray mass protruding through the cervix or vagina
 Uterine fundus no longer palpable transabdominally
 Hemorrhagic shock
 Lower abdominal pain
 Hemorrhagic shock
o Management
 Aggressive fluid resuscitation
 Johnson method of reduction – Manual replacement of the uterus, by placing a hand in the
vagina and grasping the protruding fundus with the palm of the hand and pushing along the axis
of the vagina towards the cervix / posterior fornix. The uterus is returned to position by pushing it
through the pelvis and into the abdomen with steady pressure toward the umbilicus.
 Delay in reduction of the prolapse can make uterine replacement more difficult as the
uterus can become edematous and the cervix can contract around the inverted uterus
 Uterine relaxants (e.g. nitroglycerine, terbutaline, magnesium sulphate) can be
administered to aid in the replacement of the uterus if the initial attempt is unsuccessful
or contraction of the lower uterine segment (contraction ring) develops
 Laparotomy indicated to help facilitate uterine replacement if attempts at manual
replacement fail
 Placental removal & uterotonic drugs (e.g. oxytocin, misoprostol) after uterine replacement due
to risk of massive hemorrhage
 Uterine atony is commonly encountered after uterine replacement and subsequent
placental removal. Uterotonic agents cause uterine contraction and are administered to
prevent further hemorrhage and recurrence of prolapse
  As uterine relaxation is necessary for uterine replacement, administer uterotonic agents
after uterine replacement

Postpartum Uterine Atony (most common cause of PPH)

Risk Factors Uterine fatigue from prolonged, induced, or precipitous labour
Chorioamnionitis
Uterine overdistension (multiple gestation, fetal macrosomia [ ≥ 4500 g], polyhydramnios)
Retained placenta
Grand multiparity (≥ 5 prior deliveries)
Hypertensive Disorders
Clinical Features Most common cause of PPH (recall 4 Ts – tone, tissue, thrombosis/coagulopathy, trauma)
Enlarged, soft, boggy, poorly contracted uterus
Interventions Bimanual uterine massage & high–dose oxytocin (1 st line)
Correction of bladder distension
Misoprostol (prostaglandin E1 analog)
o used for induction of labour or as 2nd–line uterotonic agent for uterine atony
Tranexamic acid
o Antifibrinolytic that prevents blood clot breakdown and significantly decreases blood loss if
administered within 3 hours of delivery
o Used in PPH of any etiology (i.e. no absolute contraindications) – uterine atony, retain tissue or
placenta, uterine inversion, uterine rupture, laceration, haematoma, coagulopathy (vWD)
o Used with hypercoagulability (e.g. inherited thrombophilia) due to potential ↑ risk of
thromboembolism
Carboprost tromethamine (2nd line uterotonic agent; synthetic prostaglandin F2α analog)
o Stimulate contractions to increase uterine tone and decrease bleeding
o May cause bronchospasm, therefore contraindicated in asthma
Methylergonovine (2nd line uterotonic agent that stimulates contractions)
o Potent vasoconstrictor → contraindicated in hypertensive disorders due to increased risk of stroke
Intrauterine balloon tamponade
Possible surgical intervention (if atony unresolved)

 Retained Placenta
o Definition
 No placental expulsion within 30 minutes of infant delivery due to:
 Placental detachment failure (adherens)
 Morbid placental attachment (accreta)
 Placental entrapment (cervix closes prior to placental expulsion)
o Risk Factors
 Gestational age 24 – 27 weeks
 Stillbirth
 Placenta accreta
 History of prior retained placenta
o Complications
 Postpartum hemorrhage
 Endometritis
o Management
 Manual placenta extraction
 Dilation & curettage

URINARY INCONTINENCE
Type Symptoms Treatment
Stress Urinary  Leakage with increased intrabdominal pressure and  Lifestyle modification (e.g. weight loss)
Incontinence Valsalva maneuvre (coughing, sneezing, laughing,  Pelvic Floor Exercises (e.g. Kegel Exercises)
jogging)  Pessary
 ± anterior vaginal bulge (cystocele)  Duloxetine (SNRI)
 Substantial weakness of pelvic floor → urethral  Pelvic Floor Surgery (midurethral sling surgery)
hypermobility
 Risk Factors – grand multiparity, advanced age,
obesity, chronic high impact exercise (e.g. jogging)
 Urinalysis & post–void residual volume are normal
(< 150 mL in women, < 50 in men)
 Q–tip test – urethral hypermobility, a common
cause of Stress urinary incontinence
o Cotton swab placed inside the urethra to measure
the extent of urethral mobility during Valsalva
maneuvre
o Positive test has > 30O angle of movement
Urge Urinary  Sudden, overwhelming, or frequent need to void,  Lifestyle modification
Incontinence followed by immediate involuntary loss of urine  Bladder training
(Overactive  Detrusor overactivity causes inappropriate bladder  M2/M3 Antimuscarinic drugs (e.g. Oxybutynin,
Bladder) spasms & increased intravesical pressure tolterodine – nonselective M1, M2, M3; risk of
cognitive impairment; solifenacin) and β 3–
agonists (e.g. mirabegron) – relaxes bladder in
detrusor overactivity
o These drugs may worsen urinary retention
in patients with neurogenic bladder who
already have detrusor hypofunction
Mixed Urinary  Features of stress & urgency incontinence  Variable treatment depending on predominant
Incontinence symptoms
Overflow Urinary  Constant involuntary dribbling & incomplete  Identification & correction of underlying cause
Incontinence emptying  Cholinergic agonists (e.g. bethnachol) may aid
o Due to ↓ detrusor muscle contractility &/or bladder contraction and urethral relaxation
bladder outlet obstruction  Intermittent self–catheterization
o Urine accumulates, distends the bladder, and
increases intravesical pressure. Whenever
intravesical pressure exceeds urethral closing
pressure, urine dribbles out
o Constant urinary leakage, nocturia, & weak
urinary stream
 Post void residual volume >200 mL (normally < 50
mL)
 N.B. Pharmacologic urinary retention (e.g.
 anticholinergics, opioids, alpha–1 agonists) can
cause OUI and must be ruled out
 Bladder overdistention from incomplete bladder
emptying / bladder voiding dysfunction due to
detrusor underactivity
o e.g. Neurogenic bladder 2o to diabetic
neuropathy affecting parasympathetic S2–S4
nerves or HTLV/TSP, spinal injury, multiple
sclerosis, bladder outlet obstruction
o Decreased perineal sensation (e.g. neuropathy)
o Patients with underlying neuropathy can develop
overflow incontinence when additional risk
factors (e.g. antihistamines) result in
exacerbation
Vesicovaginal  Risk Factors Minor fistulas sometimes heal on their own with
Fistula o Pelvic Surgery (e.g. scarring from caesarean continuous bladder drainage, otherwise, repair
section) is surgical
o Pelvic Irradiation
o Prolonged Labour / Childbirth Trauma
o Genitourinary malignancy
o Poor tissue healing (e.g. diabetes mellitus,
smoking)
 Painless, continuous leakage of urine from the
vagina
 Patients may also have small–volume voids and
erythematous, pruritic vulvar skin from constant
contact with urine & need for frequent sanitary pad
changes
 Physical Examination – visible defects in anterior
vaginal wall on speculum exam
o Smaller fistulas, however, often appear as subtle
areas of red granulation tissue with fluid pooling
 Bladder Dye Testing – Methylene blue instilled in
bladder to diagnose urinary incontinence due to
vesicovaginal fistula
o Test considered positive if a tampon placed in the
vagina becomes blue after the dye is instilled in
the bladder
 Cystourethroscopy

 Pelvic Organ Prolapse (POP)

o Uterine prolapse occurs when pelvic floor musculature is unable to provide adequate support
 Ligaments can stretch and weaken over time
 round ligament
 ovarian ligament
 broad ligament
 uterosacral ligament – most important in preventing prolapse
 ~50% of women who have had children will develop pelvic organ prolapse
 Pathogenesis
 Incomplete prolapse – uterus drops part way down into the vagina & creates a bulge
 Complete prolapse – uterus slips down and protrudes out of the vagina
o Subtypes
 Cystocele – Bladder
 anterior vaginal prolapse
  may present with difficulty starting urine stream, feeling of incomplete emptying of
bladder, and frequency or urgency of urination
 ± stress urinary incontinence
 Rectocele –
 Displacement of rectum through posterior vaginal wall defect; typically caused by damage
to rectovaginal septum incurred during vaginal childbirth
 Enterocele – small intestines
 Procidentia – severe form of pelvic organ prolapse (POP) that includes herniation of the anterior,
posterior, and apical vaginal compartments through the vaginal introitus.
 Apical Prolapse – uterus, vaginal vault
o Risk Factors
 Exacerbated by periodic increases in intraabdominal pressure (e.g. laughing, chronic cough,
straining) and effects of gravity (i.e. symptoms worsen with prolonged standing)
 Obesity
 Multiparity
 Hysterectomy
 Postmenopausal age
 Ehlers – Danlos Syndrome
 Family History of Pelvic Organ Prolapse
o Clinical Presentation
 Pelvic Pressure
 Obstructed voiding
 Urinary retention, Urinary incontinence
 Constipation
 Fecal urgency, incontinence
 Sexual dysfunction, dyspareunia
o Management
 Weight Loss
 Appropriate for asymptomatic prolapse
 Pelvic Floor Exercises / Kegel Exercises
 Intravaginal estrogen cream – prevent tissue atrophy
 Vaginal Pessary + intravaginal estrogen cream
 Without estrogen, can cause chronic discharge & bleeding secondary to injury to vaginal
tissues
 Surgical repair – e.g. posterior colporrhaphy for symptomatic rectocele, sacrohysteropexy for
uterine prolapse
 Correction does not always provide symptomatic relief

Rectovaginal fistula
Pelvic irradiation
Obstetric Trauma (e.g. perineal laceration)
Pelvic surgery
Risk Factors
Colon Cancer
Diverticulitis
Crohn’s disease
Clinical Features Uncontrollable passage of gas &/or feces from the vagina
Physical examination
Fistulography
Diagnostic Studies
Magnetic Resonance Imaging
Endosonography

 Ovarian Tumours
  Risk Factors
1. Nulliparity or Decreased parity – dangerous because it means there has been incessant ovulation
2. Long fertile period ie early menarche and late menopause for the same reason
3. Post–menopausal, Cacausian
4. Family history
 BRCA1 is implicated in both breast cancer and ovarian cancer
 if mother had ovarian cancer then daughters at increased risk of developing both breast
cancer and ovarian cancer
 Lynch Syndrome
 Hx of breast, colon, ovarian, endometrial
5. Gonadal dysgenesis for the development of ovarian childhood malignancies and the rare
gonadoblastoma
6. Superovulation therapy for infertility treatment may also be a predisposing factor (controversial)
 Protective Factors – Anything which interrupts incessant ovulation
1. Pregnancy
2. OCP – specifically low dose COC (also protective for endometrial Ca)
 Slightly increased risk of breast cancer however, and cervical cancer

Granulosa Cell Ovarian Tumour Sertoli-Leydig Cell Epithelial ovarian carcinoma

Pathogenesis Sex cord-stromal tumour
Granulosa cells convert testosterone to  ↑ Testosterone
estradiol via aromatase and secretes
inhibin (which typically inhibits FSH)
o ↑ Estradiol
o ↑ Inhibin
Clinical Complex ovarian mass (Large adnexal Rapid-onset virilization & Most common histologic type of
Features mass)
Juvenile subtype
o Precocious puberty
Adult subtype (chronic, unopposed
estrogen)
o Breast tenderness
o Abnormal uterine bleeding
o Postmenopausal bleeding
(endometrial hyperplasia or
cancer)
Mass effect symptoms – abdominal
symptoms, ovarian torsion
Investigations Histopathology – Call Exner bodies
(cells in rosette pattern)
Management Endometrial biopsy (concomitant
Ovarian Tumour
Sex-cord stromal tumour Malignancy involving the ovary,
fallopian tube, and peritoneum;
histologically, abnormalities can begin
at any of these sites and present with
hallmark large ovarian mass and
widespread pelvic and abdominal
metastases regardless of primary
origin
Abnormal proliferation of tubal
epithelium
hyperandrogenism (< 1 ovarian cancer
year) Acute – SOB, obstipation / constipation
oVoice deepening with vomiting, abdominal distension
oBitemporal Male- Subacute – pelvic / abdominal pain,
pattern balding bloating, early satiety
oIncreased muscle mass Asymptomatic adnexal mass
oClitoromegaly Metastatic spread
oHirsutism o Nodularity along rectovaginal
oNodulocystic acne septum
Oligomenorrhea o Pleural effusion if spread to pleura
Unilateral, solid adnexal Deep vein thrombosis
mass
 ↑ testosterone (> 150  ↑ CA-125 done after pelvic USS based
ng/dL) on sonographic features and patient
Normal medical history
Dehydroepiandrosterone Pelvic USS findings – Solid mass, thick
sulfate, DHEAS (c.f. septations, ascites (peritoneal free
adrenal tumours e.g. fluid)
adrenocortical CT Scan – check for metastatic spread
carcinomas: ↑ DHEAS
[>700 mcg/dL])
Pelvic USS – complex
adnexal mass
Surgery (tumour staging) Exploratory Laparotomy and tumour
 endometrial cancer) debulking, followed by platinum-based
Surgery (tumour staging) chemotherapy

 Ovarian fibroma
o Benign tumour
o Middle aged women
o Hard chalky-white mass with whorled appearance
o Collagen-producing bundles of spindle cells
o Meigs’ Syndrome = Hydrothorax (usu. Right sided) + ascites + fibroma
o Gorlin Syndrome = nevoid basal cell nevus/carcinoma syndrome, is a condition that affects many areas
of the body and increases the risk of developing various cancerous and noncancerous tumors
 Development of > 2 basal cell carcinomas (cancer of outer layer of the skin) before the age of 20
 Cysts in the jaw
 Characteristic facial appearance
 Calcification of the falx (a variation in the appearance of the skull that is visible on X-rays)
 Pits in the palms and soles of the feet
 Macrocephaly (enlarged head size) 
 Rib or vertebral abnormalities
 Increased risk of medulloblastoma during childhood
 Increased risk of cardiac or ovarian fibromas (benign, or noncancerous, tumors)
 Circumstances in which minors (age < 18) can provide their own consent
o Medical Emancipation
 Emergency care (all states)
 STIs (all states)
 Mental health and substance abuse treatment
 Pregnancy care
 Contraception
o Legal emancipation
 Financially independent
 Parent
 Married
 Active military service
 High school graduate
o Note the age of legal and medical emancipation varies by state
 Contraindications to combined hormonal contraceptives
o Absolute
 Migraine with aura
 ≥ 15 cigarettes per day PLUS age ≥ 35
 Uncontrolled Hypertension ≥ 160/100 mmHg
 Heart disease
 Diabetes mellitus with end-organ damage
 Hx of thromboembolic disease (venous thromboembolism)
 Thrombophilia (e.g. Antiphospholipid antibody syndrome, factor V Leiden)
 Ischemic Heart Disease, History of stroke
 Breast cancer
 Active Hepatitis, severe cirrhosis & liver cancer
 Major surgery with prolonged immobilization
 < 3 weeks postpartum
o Relative
 Mild or medication–controlled hypertension
 Age ≥ 35 & smoking < 15 cigarettes/day
 Certain medications (e.g. lamotrigine, rifampin)
  Inherited thrombophilia carrier (& family member with thrombophilia plus thromboembolism)

Selective Estrogen Receptor Modulators

 Raloxifene
 Tamoxifen
 Competitive inhibitor of estrogen binding
 Mixed agonist / antagonist action in a tissue-specific fashion
Mechanism of Action
o Tamoxifen: estrogen antagonist in breast & Estrogen agonist in endometrium and bone
o Raloxifene: Estrogen antagonist in breast and endometrium & estrogen agonist in bone
 Prevention of breast cancer in high-risk patients
 Tamoxifen: adjuvant treatment of estrogen-receptor positive breast cancer
Indications o Tamoxifen may decrease (nut not increase) risk of ovarian cancer
o Tamoxifen does decrease blood lipid levels
 Raloxifene: postmenopausal osteoporosis
 Hot flashes (induces menopause due to thermoregulatory dysfunction in the anterior pituitary 2 O
to antiestrogenic activity in the CNS)
Adverse effects  Venous thromboembolism
 Tamoxifen only: Uterine Sarcoma, Endometrial hyperplasia & carcinoma (in postmenopausal
patients) & endometrial polyps (in premenopausal patients)
 Modifiable
o Prolonged Hormone replacement therapy
o Nulliparity
o Increased age at first live birth (age > 35 years)
o Alcohol consumption
o Obesity
o Breastfeeding has a protective effect on breast cancer with significant relative risk reduction
Breast Cancer Risk
for each year of breastfeeding
Factors
 Non-modifiable
o Genetic mutation or breast cancer in the first–degree relatives (e.g. BRCA)
o White race (highest rates compared to other race / ethnic groups)
o Increasing chronological age
o Early menarche or later menopause
 Menarche after age 13 is associated with reduced breast cancer risk due to a decrease
in lifetime estrogen exposure