Infertility treatment in females can be described under three main categories: (a) Medical; (b) Surgical; © Assisted Reproduction techniques (ART).
Ovulation induction – The successful therapy of ovulatory disorders is the most dramatic advancement in gynaecological endocrinology. Today if lack of ovulation is the only cause operating in a particular couple, the chances of conception with treatment equals that of normal fertile population. Super-ovulation strategies and ART have improved the rates of success in every normo-ovulatory women.
Clomiphene Citrate (CC) – Clomiphene is an orally active nonsteroidal agent distantly related to diethylstilbestrol. CC is a week estrogen and modifies hypothalamic activity by affecting concentration of intracellular estrogen receptors. CC therapy does not directly stimulate the ovaries but supports a sequence of events that form the physiological features of a natural cycle. In other words, it resets the disturbed hypothalamo-pituitary-ovarian axis in cases of polycystic ovarian disease (PCOD). In contrast, CC acts as an antagonist in uterus, cervix and vagina which may be responsible for many CC failures. Absent or infrequent ovulation is the chief indication for CC therapy. Cases of ovarian failure are unresponsive to any form of ovulation induction. Patients who are more likely to respond to clomiphene are anovulatory women who have normal gonadotrophin and estrogen production but do not cycle and women with inadequate luteal phase. Women who are deficient in gonadotroph ins and are hypoestrogenic can not be expected to respond to CC. In normally cycling women a few cycles of CC treatment may be justified and do improve results in cases of infertility of no demonstrable cause by correcting certain minor ovulatory dysfunctions.
CC is given in 50-100 mg dose starting on 3rd day of a spontaneous or induced withdrawal bleed. The administration of CC early in the cycle favors multiple follicular recruitment and reduces the antiestrogenic effects on uterus. Dose can be increased up to 200-250 mg per day. However, maximum pregnancies are achieved at 50-100 mg dose. Monitoring of cycle with basal body temperature chart, LH kits or USG is highly desirable to evaluate the efficacy of cycles. In properly selected cases, 80% women can be expected to ovulate and approximately 40% become pregnant. Of these, 5% pregnancies may be multiple almost entirely twins. There have been some reports of high order multiple pregnancies and hyper-stimulation. Minor side effects include vasomotor flushes (10%), abdominal distension, bloating, pain, soreness, breast discomfort, nausea, vomiting, visual symptoms, headache, dryness and loss of hair.
CC and dexamethasone (DEX) – Patients with hirsutism and high circulating androgen concentrations are more resistant to CC. DEX 0.5 mg to blunt the night-time peak of ACTH is added to decrease the adrenal and intra-ovarian androgens. Sometimes, dramatic response can be obtained. However, indiscriminate and long term use of this potentially harmful drug should be avoided.
CC and Bromocriptine (BRC) – Elevated prolactin levels interfere with the normal function of the menstrual cycle by suppressing the pulsatile secretion of GnRH. This is manifested clinically by ovulatory dysfunction ranging from subtle ovulatory dysfunction to total suppression of ovarian activity with hypoestrogenic amenorrhoea. Bromocriptine (BRC) is a dopamine antagonist which directly inhibits pituitary secretion of prolactin. It is a highly successful treatment of hyperprolactinaemic anovulation and may be combined with CC or gonadotrophin’s for more resistant cases. Normoprolactinaemic galactorrhoea also responds well to BRC. Normoprolactinaemic anovulatory cycles sometimes respond to addition of BRC. However, results are controversial and extended empirical therapy should be avoided.
Eltroxin (Elt) – Hypothyroidism, even if subclinical, should be treated and monitored to achieve euthyroid state. Empiric use of thyroid extract or eltroxin is of no use.
Metformin – Orally active anti-diabetic agent is the latest addition to adjuvent drugs. It acts by lowering insulin resistance and improved peripheral utilization of glucose. In obese, hirsute women, metformin with diet control may significantly reduce weight and improve results of ovulation induction.
Gonadotrophins – Pituitary gonadotrophins are available as purified preparations extracted from urine of post-menopausal women. Some commercial preparations are listed below:
|1||Human Menopausal Gonadotrophin (HMG) Menotropin||75 I.U.||75 I.U.|
|2.||Urofollitropin (FSH)||75 I.U.||1 I.U.|
|3.||Highly Pure FSH (FSH-hP)||75 I.U.||1 I.U.|