Women with PCOS who do not ovulate or become pregnant with clomiphene citrate, and women with hypogonadotropic hypoestrogenic anovulation, may be candidates for therapy with injectable gonadotropins. Available preparations include recombinant FSH and LH and products purified from the urine of menopausal women (FSH or FSH-LH combinations). Administration protocols and dosages vary widely and should be adjusted to individual needs. Safe administration requires careful monitoring of ovarian response with ultrasonography and, in some cases, serial estradiol measurements. In general, gonadotropins are administered at a dose of 50 to 150 IU per day by subcutaneous injection for 3 to 5 days, after which time estradiol and follicular monitoring commence. In most cycles, gonadotropin is administered for 7 to 12 days. Ovulation is triggered by subcutaneous or intramuscular injection of 5,000 to 10,000 IU hCG or subcutaneous injection of 250 μgof recombinant hCG once the lead follicle reaches 16 to 20 mm in diameter based on ultrasonographic assessments. Ovulation generally occurs approximately 38 to 40 hours after hCG administration. Luteal phase support is sometimes provided with the administration of progesterone supplementation or with additional injections of hCG.
The two major complications associated with induction of ovulation with gonadotropins are multiple pregnancy (10% to 30%) and ovarian hyperstimulation syndrome. The incidence of both of these complications can be reduced but not eliminated by careful monitoring. Cycles complicated by the recruitment of numerous follicles or by high estradiol levels may be canceled by withholding the ovulatory dose of hCG. Selected patients may be converted safely to in vitro fertilization. Because severe ovarian hyperstimulation syndrome is life-threatening and may lead to prolonged hospitalization, ovulation induction with gonadotropins generally is performed by experienced practitioners who devote a significant portion of their practice to the treatment of infertility.
Ovulation induction with pulsatile GnRH may be effective in patients who have chronic anovulation associated with low levels of estrogen and gonadotropins. For therapy to be successful, a functional ovary and pituitary gland must be present. Patients with ovarian or pituitary failure do not respond to GnRH therapy. To be effective, GnRH must be administered in a pulsatile fashion, either intravenously or subcutaneously by a programmable pump. Ovulation induction with GnRH, as compared with gonadotropins, is associated with a relatively low incidence of ovarian hyperstimulation and multiple births. In addition, the need for appropriate timing of the ovulatory dose of hCG is avoided because patients treated with pulsatile GnRH have an appropriately timed endogenous LH surge. Disadvantages are mainly related to maintaining the programmable pump and injection site and lack of availability of an appropriate pump in the United States. After ovulation, luteal phase support is necessary and may be provided with hCG, progesterone, or continuation of the GnRH therapy.
For women with overt POI (also known as premature ovarian failure, as noted above), there is no good evidence to suggest that any treatment can increase the chance of conception with autologous oocytes (85). Treatments that were tried include ovulation induction with clomiphene or gonadotropin, pretreatment with high-dose estrogen or gonadotropinreleasing hormone agonist followed by expectant management or gonadotropin stimulation, standard-dose hormone therapy followed by gonadotropin, and corticosteroid pretreatment followed by gonadotropin. Administration of dehydroepiandrosterone (DHEA) is suggested for women with POI (149). It is uncertain whether the benefit seen in preliminary reports will stand the test of time.