Anovulation definition:
failure of expulsion of the ovum corona complex from the ovarian follicle.
Anovulation causes:
A. Physiological causes e.g.pregnancy.
B. Pathological causes: (Allpathologicalamenorrhea).
Hypothalamo- pituitary- ovarian axis disorders.
General causes and disorders.
C. Defective estrogen feedback:
E2 not fall enough early poor FSH response poor follicular growth.
E2 may not rise enough at mid cycle poor LH responseno LH peak.
D. Pharmacological causes
Drugs with estrogen component e.g. combined pills.
Anovulation diagnosis:
1. Infertility.
2. Menstrual disorders e.g. amenorrhea or oligohypomenorrhea.
3. Abnormal uterine bleeding.
4. Hirsutism and hyperandrogenic states.
Anovulation investigations: (detection of ovulation)
A. Symptoms suggestive of ovulation:
1. Regular cycles.
2. Painful cycles.
3. Regular premenstrual symptoms.
4. Midcyclic pain.
5. Midcyclic discharge.
6. Midcyclic spotting.
B. Tests suggestive of ovulation
1. Basal body temperature:
Idea: progesterone has a thermogenic effect of on the hypothalamus.
Method: * Temperature is obtained under basal conditions. * Temperature is recorded on a chart for 3 months.
Results: *Normally: biphasic (temperature ↑ by 0.2 – 0.4ºC).
*Abnormally: monophasic in anovulation.
Disadvantages: time consuming & not reliable.
2. Hormonal study:
Progesterone hormone:
In serum:
Timing: mid luteal (22nd day of an ideal cycle).
Result: a. < 3 ng /ml…..: anovulation.
b. 3 – 10 ng /ml: LPD.
c. >10 ng /ml…: normal ovulation.
In urine: Midluteal.
Pregnandiole is estimated (progesterone metabolite).
LH hormone (the only predictive test for ovulation).
In serum: Serial estimation by RIA every 3 hours.
In urine: serial estimation by midcyclic assay kits.
3. Ovarian study:
Folliculometry: serial vaginal U/S
monitors follicular development & detect
ovulation by fluid in Douglas pouch.
Laparoscopy: detects fresh corpus luteum.
4. Dated premenstrual endometrial biopsy:
Timing: * At 22nd day of the cycle if the cycles are regular.
* At 1st day of the cycle if the cycles are irregular.
Method: Endometrial strip is taken from the fundus by Novak’s or Sharman’s curette without dilatation and anesthesia.
Many advise dilatation and anesthesia to take full curettage especially from the cornu to exclude TB infection.
Values : Secretory endometrium corresponding to the date of biopsy: means normal ovulation.
Secretory endometrium lagging ≥ 2 days from the date of biopsy: means LPD.
Proliferative endometrium: means anovulation.
N.B.: if TB is suspected:
* Part of the biopsy is put in formalin for histopathology.
* Part of the biopsy is put in saline for bacteriology.
5. Cervical mucous studies:
Timing: in the 2nd half of the cycle.
Findings: thick, viscid, scanty, cellular, -ve fern test & -ve thread test.
6. Vaginal smear:
Timing: in the 2nd half of the cycle.
Findings: ↑ number of intermediate cells (vesicular nucleus, basophilic cytoplasm & folded edges).
Anovulation treatment:
A. Medical treatment: (induction of ovulation)
1. Clomiphene citrate (Clomid):
Chemistry: chemically estrogen like compound with both antiestrogen and week estrogenic effect.
Mechanism of action:
Central action: * Deprive endogenous estrogen from combining with estrogen receptors in the hypothalamus false sensation of hypoestrinism→ prevent –ve feedback on hypothalamus.
* So, the hypothalamus secretes GnRH secretion of pituitary gonadotrophins stimulate estradiol production from the growing follicle.
* The produced estradiol (from clomiphene effect), stimulate hypothalamus (+ve feedback) LH surge ovulation.
Peripheral action:
* Deprive tissues of genital tract from endogenous estrogen (competition) especially the cervix poor quality of the cervical mucus.
Indications:
1. Infertility caused by anovulation.
2. PCO.
3. Treatment of oligospermia in males.
Contraindications: liver diseases.
Dose:
50 – 100 mg from the 5th day of the cycle for 5 days.
From the 10th day, small dose of estrogen is added for 5 days to counteract the anti-estrogenic effect of clomiphene.
Results:
Ovulation is expected to occur 5 – 10 days after stoppage of clomiphene.
Success rate: 90 %. Intact hypothalamo-pituitary-ovarian axis is essential.
Side effects:
Ovarian hyperstimulation: very rare to occur with clomiphene alone & liable to occur in PCO.
Multiple pregnancies lead to ↑ risk of abortion & preterm labour.
Combination therapy:
1. Clomid + HCG.
2. Clomid + HMG+HCG (the best):
• Clomid is given until the follicle is 14 mm in diameter.
• Then, HMG is given until the follicle is 18 mm in diameter.
• Then HCG is given.
Alternative therapy (inferior to clomid):
* Cyclophenil.
* Tamoxifen.
2. Human menopausal gonadotrophins (HMG):
Preparation: from the urine of menopausal females.
Indication: *failure of clomid. *IVF.
Dose: *each ampoule contains 75 IU FSH & 75 IU LH.
*One ampoule daily IM injection is given starting from the 3rd day of the cycle.
*Response is evaluated on the 8th day by U/S & estradiol level.
Side effects: as clomid (↑incidence of ovarian hyperstimulation syndrome).
N.B.: purified FSH is valuable in PCO.
3. Human chorionic gonadotrophins (HCG):
Preparation: from the urine of pregnant females.
Indication: after stimulation of follicular growth by clomid or HMG.
Dose: 10,000 IU IM when the follicle is mature i.e.
a. U/S: the follicle is 18 mm in diameter: just before ovulation.
b. Estradiol level: 300-500 pg /ml just before ovulation.
Side effects: * If given before the proper time: LUF syndrome.
* If given after the proper time: ovarian hyperstimulation syndrome
4. GnRH:
• Indication: hypothalamic cases.
• Method: given every 60 – 120 minutes by automatic pump.
N.B.: GnRH analogues: • Indication: resistant PCO.
• Method: daily nasal spray or monthly injection.
• Action: longer half life than GnRH so, it produces pituitary suppression followed by induction of ovulation by HMG & HCG.
5. Bromocriptine: see hyperprolactinemia.
6. Thyroxin: in hypothyroidism.
7. Dexamethazone: in PCO.
B. Surgical treatment:
1. Laparoscopic drilling in PCO
2. Removal of functional ovarian tumours.