Modern Review-Disease

MODERN REVIEW

A woman typically will have about 500 menstrual cycles in her lifetime. Disorders of the
menstruation are a common Gynecological problem that requires most frequent medical care
in a reproductive-aged woman. The average duration of bleeding during menstruation is
between four to six days, but the normal range in women can be from as little as two days up
to eight days. As mentioned earlier, the average amount of menstrual blood loss is 30 mL
and greater than 80 mL is considered abnormal 1.
Features of Artava Kshaya2 correlates well with Hypomenorrhea, Oligomenorrhoea,
and up to some extent secondary amenorrhea. As these diseases are very nearer to Artava
Kshaya, it is necessary to know Patho-Physiology of these diseases according to modern
consideration. Thorough knowledge of the etiopathology is also mandatory for the
Management of Artava Kshaya.

Oligomenorrhoea Meaning of Yathochitakale Adarshanam is

infrequent interval, which is a feature of
Oligomenorrhoea where interval is more than 35
days.

;Fkksfprdkys Secondary “Adarshanam” or “Yathochitakale Adarshanam”

vn”kZue amenorrhea symptom can be considered as absence or
irregularity of menses. Hence, Secondary
amenorrhea can be included under broad umbrella of
Artava Kshaya.
vYirk Hypomenorrhea The word “Kshaya’ itself and “Alpata” indicates-
less quantity of Menstrual blood, correlating it to
Hypomenorrhea where bleeding is scanty i.e., less
than 20ml.

HYPOMENORRHOEA
When the blood flow during menstruation is unduly scanty and lasts for less than 2 days, it
is called Hypomenorrhoea.3
OLIGOMENORRHOEA
Menstruation having an interval of more than 35 days and which remains constant at that
frequency is called Oligomenorrhoea.3
SECONDARY AMENORRHOEA
Secondary Amenorrhea is a disease where there is an absence of menstruation for six
consecutive months or more then it.3
Over the past decade it has become abundantly clear that many terms which are used
to describe menstrual symptoms and causes of abnormal menstrual bleeding are ill defined
and confusing.4 The International Federation of Gynecology and Obstetrics (FIGO) 5
Menstrual Disorders Working Group recommended to abandon and discard the long-used,
ill-defined, and confusing terms and proposed the well-defined and alternate terms.6
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ABNORMAL UTERINE BLEEDING (AUB) 7 -

‘‘Nonstructural’’ causes of abnormal uterine bleeding (AUB) can be classified under three
definable headings:
(1) Disorders of Endometrial Origin (disturbances of the molecular mechanisms responsible
for regulation of the volume of blood loss during menstruation)
(2) Disorders of the Hypothalamic-Pituitary-Ovarian axis
(3) Disorders of Hemostasis (Coagulopathies)

HYPOMENORRHEA may also be classified 8 into

1. Functional (Hormonal Insufficiency or Over-stimulation)
2. Organic
According to another classification, three other forms of organic Hypomenorrhea are
described:
(1) Endometrial Tuberculosis
(2) Intrauterine Adhesions
(3) Endometrial Insufficiency (Sclerosis)

Revised Recommendations of Clinically Important Bleeding Patterns Based on an

Analysis of Menstrual Data from >1000 Normal Women9

1. No bleeding: No days of bleeding/spotting entered throughout the reference period

2. Prolonged bleeding: 10 days in one episode
3. Frequent bleeding: >4 episodes in one 90-day reference period
4. Infrequent bleeding: 17 days within one 90-day reference period
5. Irregular bleeding: A range of varying lengths of bleeding-free intervals >17 days
within one 90-day reference period
Suggested ‘‘Normal’’ Limits for Menstrual Parameters in the Mid-Reproductive
Years10

CLINICAL DIMENSIONS OF DESCRIPTIVE NORMAL

MENSTRUATION AND MENSTRUAL TERMS LIMITS
CYCLE
Menstruation and menstrual cycle (5–95th
percentiles)
Frequency of menses (days) Frequent <24
Normal 24–38
Infrequent >38
Regularity of menses, cycle to cycle
Variation over 12 months (days) Absent No bleeding
Regular Variation 2–20
days
Irregular Variation >20
days
Duration of flow (days) Prolonged >8.0
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 Modern Review-Disease
Normal 4.5–8.0
Shortened <4.5
Volume of monthly blood loss (mL) Heavy >80
Normal 5–80
Light <5

HYPOMENORRHOEA

DEFINITION

Uterine bleeding that lasts for two days or less, if not pathological, is
Hypomenorrhea. Quantitative definition states that the menstrual bleeding in which amount
of blood flow is less than 20 ml per cycle, is termed as Hypomenorrhea.

CAUSES OF HYPOMENORRHOEA

The etiological factors of hypomenorrhea and oligomenorrhea are more or less the
same. These can be classified as 11-

1. FAMILIAR & CONSTITUTIONAL TRAITS: -

As in most cases scanty menstruation characterizes the whole menstrual life of a woman and
is to be regarded as a constitutional trait of no significance. It rarely has a pathological basis.
Constitutional scanty menstruation is perhaps best explained by assuming the presence of an
unusual arrangement, or relative insensitivity of the endometrial vascular system.

i. In those, where the occupation requires a great mental strain.

ii. In those, whose muscular and skeletal development are of the masculine type
as in some women athletes.
iii. In those, who lead a luxurious, inactive, overfeed existence.

2. UTERINE CAUSES

1) Uterine Hypoplasia: 12
Rarely small area of endometrium may be responsible for scanty menstruation.
Though, this is not a common cause of hypomenorrhea.
2) Destruction of Endometrium:
The endometrium may be destroyed by infections, traumatic over-curettage or due to
myomectomy or other plastic operations on the uterus.
3) Refractory Endometrium.

3. HORMONAL CAUSES

Disturbance of the endocrine system may lead to scanty menstruation without

altering the cycle. Scanty menstruation, however, occasionally seen as a forerunner to
amenorrhea. It can also occur with long term use of hormonal preparations like low-dose
oral contraceptive as a result of progressive endometrial atrophy, Obesity and Hirsutism.

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4. NERVOUS AND EMOTIONAL FACTORS

Psychological factors may fail to suppress a stable ovarian and uterine cycle
completely and sometimes succeed only in regarding the amount of flow. The best example
is Pseudocyesis which is frequently characterized by scanty periods rather than Amenorrhea.

5. OVARIAN CAUSE
Unilateral oophorectomy or partial resection of the ovaries may lead to scanty blood
flow during menstruation.

6. GENERAL ILL HEALTH AND ANEMIA

There are some causes altering the endocrine stimulus to the endometrium, when it
occurs. After child birth, hypomenorrhea is frequent due to prolonged lactation. In some
cases, sever post-partum hemorrhage causes partial necrosis of the pituitary 1 and
hypomenorrhea is due to inadequate pituitary stimulus.

OLIGOMENNORHOEA

DEFINITION
Oligomenorrhoea can be arbitrarily defined as the cycle in which the inter menstrual
period is longer than 35 days. Menstruation may be both infrequent and irregular, or may be
regularly infrequent.
CAUSES OF OLIGOMENNORHOEA
Infrequent menstruation and Amenorrhea have essentially similar symptoms and identical
causes; the difference is only in the degree.11
1. CONSTITUTIONAL AND PHYSIOLOGICAL
Oligomenorrhoea can be familial. The bleeding can be ovular in type, which means that the
ovarian cycle is drawn out or temporarily arrested at some phases. As a rule, the luteal phase
tends to be constant at 14 days; it is the follicular phase which is either lengthened or
shortened.
Infrequent menstruation sometimes follows the Menarche and preceded the Menopause;
it then marks the gradual waxing and waning of the endometrial cycle, and is physiological.
2. HORMONAL
It may occur due to under activity of the ovary and this is reflected in the secondary sexual
characters. Hypoplasia of the uterus and a history of a late Menarche, are therefore to be
looked for. The ovarian disturbance is often secondary to hypothalamic, pituitary, thyroid or
adrenal dysfunction, so the patient may have the stigmas of obesity, squat figure, hirsutism
and low fertility.
3. CHROMOSOMAL
An underlying sex chromosome abnormality such as an XXX arrangement is occasionally
found.
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CAUSATIVE FACTORS OF SECONDARY AMENORRHOEA 13

Physiological cause Pregnancy

Lactation
Hypothalamic cause Major environmental stress.

Weight change – Obesity and anorexia nervosa.

Pseudocyesis

Supracellar tumour compressing the hypothalamus.

Pituitary cause Sheehan’s syndrome.

Inappropriate prolactin production

1. Prolactin producing microadenoma
2. Primary hypothyroidism
3. Chest injury and chest surgery
4. Drugs like tricyclic antidepressants, oral contraceptive pill
or estrogen therapy, domperidone, chlopromide,
cimetadine

Space occupying lesion e.g. Craniopharyngioma.

Post-surgery or post radiation

Cushing’s syndrome

Acromegaly
Other pituitary tumours

Ovarian cause Poly cystic ovarian syndrome

Premature ovarian failure

Androgen producing ovarian tumour

After bilateral oophorectemy, ovarian cystectomy or wedge

resection of ovaries.

Post irradiation and post chemotherapy

Resistant ovarian syndrome

Chromosomally incompetent ovarian failure like X monosomy or

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 Modern Review-Disease
an extra X

Galactosaemia
Chronic renal failure
Hypo-hyper thyroidism

Adrenocortical hyperplasia and tumour

Uterine cause Surgical removal of the Uterus in young age

Synechia as a result of
i. Puerperal sepsis
ii. Septic abortion
iii. Endometrial tuberculosis

Absence of endometrium.
i. Post infective
ii. After vigorous curettage
iii. Post pill atrophy

Secondary Amenorrhea may be due to abnormal hormonal levels. The major causes are
summarized as-14

FSH LEVEL (LOW OR various eating disorders, stress, excess exercise

NORMAL)
Nonspecific hypothalamic
Chronic anovulation (PCOS)
Hypothyroidism
Cushing syndrome
Pituitary tumor/empty Sella
Sheehan syndrome
HIGH FSH LEVEL: GONADAL 46,XX
FAILURE
Abnormal karyotype
HIGH PROLACTIN LEVEL
ANATOMIC Asherman syndrome
HYPERANDROGENIC STATES Nonclassical CAH (congenital adrenal hyperplasia)
Ovarian tumor
Undiagnosed

METHODS OF ESTIMATION OF MENSTRUAL BLOOD LOSS

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 Modern Review-Disease
Although a women’s subjective estimation of her blood loss may be an appropriate
screening method yet there are other methods that are more accurate for assessment of blood
loss.

1. COUNTING THE NUMBER OF DAYS OF MENSTRUATION

The number of days of menstrual bleeding has been used to assess menstrual loss. Rybo et
al. (1966) demonstrated that 78% of the total menstrual loss occurred by the second and
91% by the third day of menses.8 When measurement of length of menstruation was
compared with the actual measurement of the menstrual blood loss, only 45% of the women
who bled for more than seven days had a measured loss of more than 80 ml.15
But exceptions are there, a woman having a menstrual flow of more than 4 days can
be actually having the quantitative blood loss less than 20ml.With such a low sensitivity,
this test cannot be considered as the accurate diagnostic criteria for blood loss.

2. COUNTING THE NUMBER OF SANITARY PRODUCTS

Normally a woman tends to use a greater number of menstrual products during a heavy
period compared with a scanty cycle. Therefore, it seems obvious that counting the number
of sanitary products can be a easy method for quantification of menstrual blood loss.
However, studies have clearly shown that the most important determinants for the number of
sanitary products used were the woman’s personal hygiene practices, frequency of attention
to menstrual flow and financial resources.16, 17
Another limitation of this method is a wide range of variation in absorbency in
different brands of sanitary products. In a study assessing the absorbency of 15 different
types of commercially available sanitary pads and tampons, the amount of blood absorbed
by the products varied from 0.55 ml to 111.99 ml. 17. The number of sanitary products used
by a woman might be a good indicator of a change in the pattern of menstrual loss, as long
as she continues to use the same brand. However, it is not a perfect tool to quantify the
blood loss.

3. WEIGHING SANITARY PRODUCTS

Weighing used sanitary pads and subtracting the weight of the unused pads has been
proposed as a method of quantifying menstrual blood loss.18 This method would be a useful
tool if all menstrual fluid constituted blood. However, according to Fraser et al. (1985), the
proportion of blood in menstrual fluid varied widely among women, from 1.6% to 81.0%.
Blood only constitutes on average 36.1% of the total menstrual loss.19
A large amount of menstrual fluid comes from other sources including endometrial
tissue exudates, endometrial glands and cervical and vaginal secretions. The wide variation
in the composition of the menstrual loss is a limitation to the validity of this method as a
diagnostic tool in this context. In addition to the inaccuracy inherent in this method, it
requires that women collect and store all of their used sanitary products to be submitted for
weighing, which may not be acceptable or feasible for many women.
4. Attempts to standardize this type o evaluation have led to development o the pictorial
blood assessment chart (PBAC) 20. Scoring for the pictorial bleeding assessment
chart. Patients are counseled to evaluate the degree of saturation for each sanitary
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 Modern Review-Disease
product used during menstruation. The total number of points is tallied for each
menses. Points total greater than 100 indicate menorrhagia.

DIAGNOSIS

1. HISTORY
Initial questions to investigate about the pubertal tanner stages must be asked. The
cycle interval, duration, and amount of menstrual flow, menstrual pattern changes
are to be sought. Surgical history especially any prior pelvic surgery, intrauterine or
ovarian surgery along with radiation therapy, chemotherapy is also important. A
review of symptoms can also be helpful. For example, new-onset headaches, visual
changes, hirsutism and acne, bilateral milky breast discharge, hot flushes and vaginal
dryness may suggest the associated pathology.

2. PHYSICAL EXAMINATION
General appearance can be helpful to evaluate BMI, any eating disorder, any
developmental defect of the anterior pituitary gland etc. Bilateral breast examination,
examination of the genitalia including axillary and pubic area may help in
determination of various. Rectal and digital vaginal examination may help identify
any pelvic pathology especially related to uterus and ovaries.
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3. INVESTIGATIONS 21

Investigations to diagnose the cause of oligomenorrhea includes the following:  

a. BLOOD TESTS
 FSH Levels (for ovarian insufficiency)  
 TSH levels (for thyroid dysfunction- Hypo or hyperthyroidism)  
 Prolactin levels (to detect prolactinoma)
 LH levels; the ratio of FSH\LH is useful in diagnosing polycystic ovarian disease.  
 Free testosterone levels; increased in congenital adrenal hyperplasia and polycystic
ovarian disease.
 17 –OH levels; these are useful to diagnose congenital adrenal hyperplasia that may
be a cause of oligomenorrhea.  
 Overnight dexamethasone suppression test; is done to diagnose Cushing syndrome as
a cause of oligomenorrhea, especially if the patient presents with signs of this
condition.
 HbA1C

b. RADIOLOGIC INVESTIGATIONS

MR IMAGING OR CT SCANNING- to rule out Hypogonadotropic Hypogonadism,

any anatomic (delineation of complex uterine structures, such as a noncommunicating or
hypoplastic uterine horn.), CNS or pituitary gland abnormality. CT scan is useful with
suspicion of adnexal or adrenal masses.  MRI pituitary helps to confirm prolactinoma if
prolactin levels increase.  

SONOGRAPHIC EXAMINATION- Ultrasound of abdomen and pelvis; it may

indicate polycystic ovaries, signs of pelvic inflammation, and ascites.  TAS, TVS and Three-
dimensional (3-D) sonography may be advised as per the need and to rule out any pelvic
pathology

c. OTHERS:  
a) Endocervical swabs are taken if there are signs of pelvic inflammatory disease.
b) HSG or SIS - to detect intrauterine synechiae or any developmental anomalies
c) Urine pregnancy Test
d) Blood sugar level
e) Mantoux test
f) Karyotype

TREATMENT OF HYPOMENORRHOEA22

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Unless a significant causal abnormality is found, no treatment other than reassurance is
necessary. So far as the health and fertility are concerned, it usually does not matter whether
the menses last half an hour, half day or half a week.
Treatment Varies according to causes
1) Improvement of general health and reassurance
2) Endocrine – estrogen and progesterone are given cyclically if there is hypo-
ovarian function, as well as hypoplastic uterus.
3) In some cases, no treatment is of any value.
In addition to this, hypomenorrhea with infrequent menses needs investigation and treatment
like that for amenorrhea.

TREATMENT OF OLIGOMENORRHOEA23

If the patient is normal and not suffering from infertility no treatment is necessary. If in
addition infertility is a problem, treatment may require inducing or increasing the frequency
of ovulation.
a) If any causes, treatment depends upon the cause
b) Improvement of general health by diet, haematinics, rest.
c) Endocrine deficiency, if any, should be corrected.

Hypomenorrhea with infrequent menses (oligomenorrhoea) needs investigations and

treatment like that for amenorrhea.

GENERAL TREATMENT OF AMENORRHOEA24

The cause of amenorrhea should be removed. In the absence of organic disease, the patient
should be told that amenorrhea as such causes no harm to the well-being of the patient.
Treatment should be in this case directed to induce ovulation and to cause pregnancy. If the
patient is desirous of restoring menstrual function cyclical hormone therapy may be tried.

ACTIVE TREATMENT

1. Re-assurance and psychotherapy are very useful in amenorrhea due to psychogenic

and environmental causes.
2. Adequate and balanced diet is must.
3. Drug amenorrhea is treated by withdrawal of that drug.
4. Severe uterine hypoplasia is treated by the improvement of the health by weight gain
and haematinics if the patient is malnourished.
5. If obesity, body weight reduction by appropriate measures is recommended.

TREATING THE UNDERLYING MEDICAL CONDITIONS

1. Associated Pulmonary tuberculosis and diabetes mellitus should be treated
effectively.
2. In anorexia nervosa hospitalization, proper feeding, insulin and largactil may be
used.
3. Amenorrhea caused by pituitary and other endocrinal causes should be referred to
concerned physician or endocrinologist.
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4. If hyperthyroidism is the cause, then it is treated with antithyroid drugs,
radioactive iodine or thyroidectomy.
5. If the etiology is Cushing syndrome, then it is treated with medication that blocks
excess cortisol overproduction example, ketoconazole, mitotane, and metyrapone.
6. Prolactinomas, if small, can be treated with dopamine agonists example,
bromocriptine, and cabergoline.  

HORMONAL THERAPY :25

1) Estrogen therapy

Gonadal dysgenesis (Turner’s syndrome) is treated by cyclical estrogen therapy for

indefinite period to develop secondary sex characters. It can be given to inhibit and release
of anterior pituitary and this may directly result in ovulation.

2) Estrogen and Progesterone therapy

Replacement therapy is indicated in hypo-estrogenic woman who is not a candidate
for induction of ovulation. The indications are hypothalamic amenorrhea, gonadal
failure particularly in young, and postgonadoctomy woman. Cyclical Estrogen –
Progesterone therapy is given as in premature menopausal syndrome.
SURGICAL MANAGEMENT
Surgical intervention should be done as per need.
1. Surgery may be necessary in the case of adnexal and adrenal tumors.
2. Thyroidectomy may be necessary for hyperthyroidism.
3. If prolactinoma is large enough to produce compressive symptoms, it may require
surgical removal.

 TREATMENT OF THIN ENDOMETRIUM

Since a thin endometrium is a multifactorial condition, its management should be cause-

related, with the aim of increasing endometrial receptivity and simplifying implantation.
However, improving endometrial growth in patients with thin endometrium is very
challenging; several regimens have been tried in the literatures.

Cases of inadequate endometrium thickness are treated with oral estradiol. As the

endometrium is a hormone dependent tissue estrogen supports endometrial proliferation by
causing spiral artery contraction and decreasing oxygen tension in the functional layer.26

Various studies related to it are summarized as-

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The best method for prescription of estradiol is oral administration. In a study, extended
administration of estradiol valerate during controlled ovarian hyperstimulation (COH) cycles for
14–82 days, improve the mean endometrial thickness from 6.7 to 8.6 mm as well as significant
increase of pregnancy rate (38.5 vs. 4.3%) 27. According to a meta-analysis results, administration
of pure ethinyl estradiol (EE) for treatment of thin endometrium, increase the endometrial
thickness in comparison to patients whom used placebo. Moreover, the best result was achieved
while EE administration is starting on 7th–10th day of menstrual cycle with the dose of 0.02–
0.05 mg/day for 5 days 28. As the highest serum and endometrial level of estrogen occur
after vaginal administration, it is considered as the desirable route in cases that do not response to
the other ways. Therefore, Cetinkaya and colleagues administered estrogen vaginally 25 mg daily
from 4th day of the cycle for 15 days in Clomiphene citrate induced cycle. They reported
significant increase in endometrial thickness on the day of ovulation in estrogen + clomiphene
citrate group compare to the group where only Clomiphene citrate was used, but there was no
difference in pregnancy rate 29.

In the same way another study compared oral and vaginal administration of estradiol
among donor oocytes recipients. The results showed an increase in endometrial thickness as well
as ongoing pregnancy rate when vaginal estradiol administration extended to 4–6 weeks in women
who failed to achieve acceptable endometrial thickness after oral estradiol administration30 .

Oral estrogens were also used for endometrium preparation in FET, where prior IVF failure
was believed to be due to thin endometrium. Jimenez and colleagues administered oral estradiol
2 mg three times a day from day 1st for 12 days. They stated satisfactory development of
endometrium in 67% patients31.

REFERENCES MODERN REVIEW

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 Modern Review-Disease
1. Hallberg L., et al. Menstrual blood loss study. Variation at a population different
ages and attempts to define normality. Acta Obstet Gynecol Scand. 1966;45(3):320–351.
2. vkrZo{k;s ;Fkksfprdkys vn‛kZue~ vYirk ok ;ksfuosnuk pA (Su.Su.15/16 )pg no 77
3. Book of Gynaecology including Contraception D.C. Dutta Edited by Hiralal Konar
3rd edition 2001, Published by NEW CENTRAL BOOK AGENCY (P) LTD Pp 604 pg no
179
4. Woolcock JG, Critchley HOD, Munro MG, Broder MS, Fraser IS. Review of the
confusion in current and historical terminology and definitions for disturbances of menstrual
bleeding. Fertil Steril 2008;90(6):2269–2280
5. The FIGO Recommendations on Terminologies and Definitions for Normal and
Abnormal Uterine Bleeding Ian S. Fraser, M.D.,1 Hilary O.D. Critchley, M.D.,2 Michael
Broder, M.D.,3 and Malcolm G. Munro, M.D.4
6.

https://www.researchgate.net/profile/Malcolm_Munro/publication/51779246_The_FIGO_R
ecommendations_on_Terminologies_and_Definitions_for_Normal_and_Abnormal_Uterine
_Bleeding/links/55c3770d08aeca747d5f9492.pdf
7. 12 Munro MG, Critchley HOD, Fraser IS. The flexible FIGO classification concept
for underlying causes of abnormal uterine bleeding. Semin Reprod Med 2011;29(5):391–
399
8. American Journal of Obstetrics and Gynecology Volume 116, Issue 8, 15 August
1973, Pages 1058-1064 W.Z.PolishukM.D.abE.SadovskyM.D.abI.AviadM.D.ab
9. Belsey EM, Machin D, d’Arcangues C. The analysis of vaginal bleeding patterns
induced by fertility regulating methods. World Health Organization Special Programme of
Research, Development and Research Training in Human Reproduction. Contraception
1986;34(3):253–260
10. Snowden and Chistian,21 Belsey and Pinol,24 Treloar et al,25 and Hallberg et al26.
Each of these studies provides somewhat different data. Adapted from Fraser et al.2,3
11. Jeffcoate’s principles of Gynaecology Revised & updated by Pratap Kumar,
Narendra Malhotra 7thEdition 2008, Published by Jaypee Brother Medical Publishers (P)
LTD Pp 964 pg no 596 ,596
12. Howkin’s and Bourne Shaw’s Textbook of Gynaecology, Edited by VG Padubidri,
and Shirish N Daftary, 14th Edition 2008, Published by Elsevier, a division of Reed Elsevier
India Private limited Pp 483 pg no. 286
13. Book of Gynaecology including Contraception D.C. Dutta Edited by Hiralal Konar
3rd edition 2001, Published by NEW CENTRAL BOOK AGENCY (P) LTD Pp 604 pg no
439
14. Williams CHAPTER 16 Amenorrhea Pg 370
15. Rybo G. Menstrual blood loss in relation to parity and menstrual pattern. Acta Obst
Gynecol Scand 1966; 45 Suppl 7:25–45.
16. Higham JM, O’Brien PMS, Shaw RW.Assessment of menstrual blood loss using a
pictorial chart. Br J Obstet Gynaecol 1990;97:734–9.
17. Grimes DA. Estimating vaginal blood loss. J Reprod Med 1997; 22:1990–2.
18. Pendergrass PB, Scott JN, Ream LJ.A rapid noninvasive method for evaluation of
total menstrual blood loss. Gynecol Obstet Invest 1984;17:174–8.
19. Fraser IS, MaCarron G, Markham R, Resta T. Blood and total fluid content of
menstrual discharge. Obstet Gynecol 1985;65:194–8
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20. https://accessmedicine.mhmedical.com/content.aspx?
bookid=1758&sectionid=118168196
21. Jeffcoate’s principles of Gynaecology Revised & updated by Pratap Kumar,
Narendra Malhotra 7thEdition 2008, Published by Jaypee Brother Medical Publishers (P)
LTD Pp 964 pg no 590, 591
22. Jeffcoate’s principles of Gynaecology Revised & updated by Pratap Kumar,
Narendra Malhotra 7thEdition 2008, Published by Jaypee Brother Medical Publishers (P)
LTD Pp 964 pg no 596
23. Jeffcoate’s principles of Gynaecology Revised & updated by Pratap Kumar,
Narendra Malhotra 7thEdition 2008, Published by Jaypee Brother Medical Publishers (P)
LTD Pp 964 pg no 597
24. Jeffcoate’s principles of Gynaecology Revised & updated by Pratap Kumar,
Narendra Malhotra 7thEdition 2008, Published by Jaypee Brother Medical Publishers (P)
LTD Pp 964 pg no 592-595
25. Jeffcoate’s principles of Gynaecology Revised & updated by Pratap Kumar,
Narendra Malhotra 7thEdition 2008, Published by Jaypee Brother Medical Publishers (P)
LTD Pp 964 pg no 593-595
26. S.L. YoungOestrogen and progesterone action on endometrium: a translational
approach to understanding endometrial receptivity Reprod. Biomed. Online, 27 (5) (2013),
pp. 497-505
27. M.J. Chen, J.H. Yang, F.H. Peng, S.U. Chen, H.N. Ho, Y.S. YangExtended estrogen
administration for women with thin endometrium in frozen-thawed in-vitro fertilization
programs J. Assist. Reprod. Genet., 23 (7–8) (2006), pp. 337-342
28. R.F. Torres, A.E. Habana, L.G. TansengcoThe effect of estrogen supplementation on
the endometrium and pregnancy rate among infertile women treated with clomifene citrate:
a meta-analysis Fertil. Steril., 84 (2005), pp. S162-S163
29. K. Cetinkaya, S. KadanaliThe effect of administering vaginal estrogen to clomiphene
citrate stimulated cycles on endometrial thickness and pregnancy rates in unexplained
infertility J. Turk. Ger. Gynecol. Assoc., 13 (3) (2012), pp. 157-161 CrossRefView Record
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30. D.E. Tourgeman, C.C. Slater, F.Z. Stanczyk, R.J. PaulsonEndocrine and clinical
effects of micronized estradiol administered vaginally or orally Fertil. Steril., 75 (1) (2001),
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31. Jimenez PT, Schon SB, Odem RR, Ratts VS, Jungheim ES. A retrospective cross-
sectional study: fresh cycle endometrial thickness is a sensitive predictor of inadequate
endometrial thickness in frozen embryo transfer cycles. Reprod Biol Endocrinol. 2013;11:35

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