DISORDERS OF OVULATION

It includes:
2. Anovulation 2. LPD 3.LUFS

PHYSIOLOGIC CONSIDERATIONS

Chronology of follicle growth during the human menstrual cycle

• In the Follicular phase
• Ovulation occurs by the end of the follicular phase
• During the luteal phase
• If fertilization of the Graafian follicle does not occur
• If pregnancy occurs

.Diagram showing LH/FSH surge

 :AETIOLOGY OF ANOVULATION

I. Physiological causes:
•Before puberty
•During pregnancy
•After the menopause
•Some women during lactation
•Short periods after puberty and before the
menopause.
II. Iatrogenic causes:
•Contraceptive pills.
•Large doses of oestrogen, gestagens or combined
oestrogen/progesterone therapy.
III. Pathological causes:
1. Hypothalamic factors:
a. Organic lesions: (brain tumour, scarring).
b. Functional disorders:
- Polycystic ovarian disease (PCOD).

- Hyperprolactinemia.
- Iatrogenic as phenothiazine, reserpine.
- Congenital; Kallman’s syndrome.
C. Psychological factors:
- Stress or psychiatric disease.

- Anorexia nervosa

- Pseudocyesis.
2. Pituitary factors:
• Pituitary insufficiency (Sheehan’s syndrome or Simmond’s
disease).
• Pituitary tumours:

- Acidophil adenoma (gigantism-acromegaly).

- Basophil adenoma
(Cushing’s syndrome).

- Chromophobe adenoma (non-functioning or prolactinoma).

3. Ovarian factors (Peripheral defect)
1.Gonadal Dysgenisis (Turner syndrome)

2. Insensitive ovary syndrome.

3. Premature ovarian failure.
4. Ovarian tumours (especially functioning tumours).
5. Bilateral surgical removal of the ovary
6. Destruction of the ovary (Inflammation - radiation -
chemotherapy).
DIAGNOSIS OF OVULATION
2. Symptoms Suggestive of Ovulatory Cycles
• Ovulation pain
• Ovulation bleeding
• Investigations for Detection of Ovulation
• Basal Body Temperature (BBT) chart changes

• Hormonal assays
• Folliculometry
• Cervical mucous changes
• Vaginal cytology
• Premenstrual endometrial biopsy (PEB)
• Demonstration of a corpus luteum within the ovary during laparoscopy
 TREATMENT OF ANOVULATION
• Clomiphene Citrate (CC)
• CC is a non-steroid compound closely related to diethylstilbestrol (DES)
• Acts by competing with endogenous E2 at the hypothalamic receptors levels
Indications for treatment with CC:
 Intact hypothalamic pituitary axis and normal FSH:
• PCOD,
• Post-pill amenorrhea,
• Luteal phase defect, and
• Adrenal hyperfunction
Side effects of CC:
• Vasomotor flushes, headache and visual symptoms, breast and abdominal
discomfort.
• Ovarian hyperstimulation (grade I-II), with resultant pelvic pain and discomfort.
• Increased risk of multiple pregnancies (10%).
• Abortion and preterm labour are more common in stimulated rather than natural
cycles.
2. Human Menopausal Gonadotrpins (HMG)
• It is prepared from urine of postmenopausal women.
• The commercial preparation contains 75 IU FSH, 75 IU LH.
Indications of HMG:
5. Poor or no response to CC (clomid failure),
6. Cases with hypogonadotropic anovulation
7. Cases with hypothalamic disorders with abnormal or blunted Gn-RH
release.
Side effects of HMG:
• Ovarian Hyperstimulation Syndrome (OHSS):

• Multiple pregnancies
3. Human chorionic Gonadotropins (hCG)
4. Combined CC and HMG
5. Gonadotropin Releasing Hormone Gn-RH
6. LH-RH Analogues
7. Tamoxifen
8. Cyclofenil
9. Bromocryptine
10. Thyroid extract
11. Cortisone
12. Surgical measures for induction of ovulation (Ovarian
Drilling)
Definition: cycles with a short interval between ovulation and menstruation
(less than 11 days) in which peak value of progesterone are either normal
or more commonly decreased.
Causes:
3. Inadequate release of FSH during follicular phase of cycle.
4. Inadequate FSH/LH ratio at time of ovulation.
5. Hyperprolactinemia.
6. Induction of ovulation by clomiphene citrate (not related to the drug rather
than endogenous gonadotropins release).
7. Synthetic progestogen has luteolytic action.

Diagnosis
• Biphasic BBT: with a short interval between ovulation and menstruation
(<11 days).
• Dated PEB: It should be taken high from the fundus, 1-2 days prior to
menses. Secretory changes with an endometrial lag 2 days or more behind
the cycle is diagnostic.
• Serum progesterone level in midluteal phase (5-10 ng/ml) are only
suggestive.
Treatment of LPD
1. Progesterone:
•Progesterone in oil 1.25 mg IM/day, 3 days after ovulation till the
time of menses.
•17 alpha hydroxy progesterone caproate 250 mg IM, 3 days after
ovulation.
2. Human chorionic gonadotropin (hCG):
HCG stimulates CL production of Progesterone (2500 IU days 4-6-8-
10 postovulatory).
3. Bromocriptine:
It is the drug of choice in cases of luteal phase defect with
hyperprolactinemia.
4. Clomiphene citrate (CC):
50 mg/day for 5 days starting from 5th day of cycle in cases of
inadequate FSH release during luteal phase.

Treatment of ULFS:
•(clomid + HCG)
•(HMG + HCG)
•First described by Stein and
Leventhal in 1935.
•The classic Stein Leventhal
syndrome presents with
amenorrhea, hirsutism,obesity and
infertility.
Enlarged ovaries with pearly white smooth surface as
seen during laparoscopy

PATHOGENESIS:
• Hyperandrogenism plays a central role in the syndrome:
• Hypothalamic and/or pituitary defect: Increased LH secretion
• Ovarian enzyme defect: Aromataze enzyme deficiency
• Suprarenal defect: Congenital adrenal hyperplasia
• Insulin resistance and hyperinsulinemia.
Sequelae of hormone disturbances and clinical picture in PCO:
a) Hyperandrogenism:
• Arrest of follicular growth → anovulation.
• Stimulation of hair growth → hirsutism.
• Increased estrone levels from peripheral conversion in fatty tissues.
b) Hyperestrogenism:
• Irregular uterine bleeding
• Endometrial hyperplasia
• Endometrial carcinoma

INVESTIGATIONS:
• LH/FSH ratio: If > 2, it is suggestive of PCOS.
• Endocrine profile:
• Elevated free testosterone level
• Decreased SHGB
• High plasma oestrone and androstenedione
• Increased fasting insulin
• Ultrasound: (Adam's criteria). The peripherally arranged multiple small
• Laparoscopy: The ovaries are enlarged with pearly follicles (Necklace appearance)

white smooth surface.

TREATMENT OF PCOS (depends on the presenting symptom):
• Weight reduction
• For menstrual irregularities: Cyclic progestagen therapy from day 17 to 26 of
the cycle).
• For infertility (induction of ovulation)
• Clomiphene citrate, HMG/HCG, or recombinant FSH and LH can be used.
• Anti-diabetic drugs in cases of insulin resistance (e.g. metformin 500 mg
t.d.s.).
• Corticosteroid therapy is used to suppress ACTH production.
• Surgical treatment aims at decreasing ovarian androgen production
(Laparoscopic ovarian drilling).

4. For hirsutism:
• Anti-androgens as cyproterone acetate
• Cosmetic therapy (Depilation or electrolysis)