FIGURE 37–3 Controlled ovarian stimulation in preparation for an assisted reproductive technology such as in vitro fertilization. Follicular phase: Follicle development is stimulated with gonadotropin injections that begin about 2 days after menses begin. When the follicles are ready, as assessed by ultrasound measurement of follicle size, final oocyte maturation is induced by an injection of hCG. Luteal phase: Shortly thereafter oocytes are retrieved and fertilized in vitro. The recipient’s luteal phase is supported with injections of progesterone. To prevent a premature luteinizing-hormone surge, endogenous LH secretion is inhibited with either a GnRH agonist or a GnRH antagonist. In most protocols, the GnRH agonist is started midway through the preceding luteal cycle.
development. When exogenous gonadotropins are used to stimulate follicle development, there is risk of a premature endogenous surge in LH owing to the rapidly increasing serum estradiol levels. To prevent this, gonadotropins are almost always administered in conjunction with a drug that blocks the effects of endogenous GnRH—either continuous administration of a GnRH agonist, which downregulates GnRH receptors, or a GnRH receptor antagonist (see below and Figure 37–3).
When appropriate follicular maturation has occurred, the gonadotropin and the GnRH agonist or GnRH antagonist injections are discontinued and hCG (3300–10,000 IU) is administered subcutaneously to induce final follicular maturation and, in ovulation induction protocols, ovulation. The hCG administration is followed by timed intercourse or intrauterine insemination in ovulation induction and by oocyte retrieval in assisted reproductive technology procedures. Because use of GnRH agonists or antagonists during the follicular phase of ovulation induction suppresses endogenous LH production, it is important to provide exogenous hormonal support of the luteal phase. In clinical trials, exogenous progesterone, hCG, or a combination of the two have been effective at providing adequate luteal support. However, progesterone is preferred for luteal support because hCG carries a higher risk of OHSS in patients with high follicular response to gonadotropins.
B. Male Infertility
Most of the signs and symptoms of hypogonadism in males (eg, delayed puberty, retention of prepubertal secondary sex characteristics after puberty) can be adequately treated with exogenous androgen; however, treatment of infertility in hypogonadal men requires the activity of both LH and FSH. For many years, conventional therapy has consisted of initial treatment for 8–12 weeks with injections of 1000–2500 IU hCG several times per week. After the initial phase, hMG is injected at a dose of 75–150 units three times per week. In men with hypogonadal hypogonadism, it takes an average of 4–6 months of such treatment for sperm to appear in the ejaculate in up to 90% of patients, but often not at normal levels. Even if pregnancy does not occur spontaneously, the number of sperm is often sufficient that pregnancy can be achieved by insemination with the patient’s semen (intrauterine insemination) or with the help of an assisted reproductive technique such as in vitro fertilization with or without intracytoplasmic sperm injection (ICSI), in which a single sperm is injected directly into a mature oocyte that has been retrieved after controlled ovarian stimulation of a female partner. With the advent of ICSI, the minimum threshold of spermatogenesis required for pregnancy is greatly lowered.
C. Outdated Uses