Human chorionic gonadotropin is produced by the human placenta and excreted into the urine, whence it can be extracted and purified. It is a glycoprotein consisting of a 92-amino-acid α subunit virtually identical to that of FSH, LH, and TSH, and a β subunit of 145 amino acids that resembles that of LH except for the presence of a carboxyl terminal sequence of 30 amino acids not present in LH. Choriogonadotropin alfa (rhCG) is a recombinant form of hCG. Because of its greater consistency in biologic activity, rhCG is packaged and dosed on the basis of weight rather than units of activity. All of the other gonadotropins, including rFSH, are packaged and dosed on the basis of units of activity. Both the hCG preparation that is purified from human urine and rhCG can be administered by subcutaneous or intramuscular injection.
The gonadotropins and hCG exert their effects through G protein-coupled receptors. LH and FSH have complex effects on reproductive tissues in both sexes. In women, these effects change over the time course of a menstrual cycle as a result of a complex interplay among concentration-dependent effects of the gonadotropins, cross-talk of LH, FSH, and gonadal steroids, and the influence of other ovarian hormones. A coordinated pattern of FSH and LH secretion during the menstrual cycle (see Figure 40–1) is required for normal follicle development, ovulation, and pregnancy.
During the first 8 weeks of pregnancy, the progesterone and estrogen required to maintain pregnancy are produced by the ovarian corpus luteum. For the first few days after ovulation, the corpus luteum is maintained by maternal LH. However, as maternal LH concentration falls owing to increasing concentrations of progesterone and estrogen, the corpus luteum will continue to function only if the role of maternal LH is taken over by hCG produced by syncytiotrophoblast cells in the placenta.
A. Ovulation Induction
The gonadotropins are used to induce follicle development and ovulation in women with anovulation that is secondary to hypogonadotropic hypogonadism, polycystic ovary syndrome, and other causes. Because of the high cost of gonadotropins and the need for close monitoring during their administration, they are generally reserved for anovulatory women who fail to respond to other less complicated forms of treatment (eg, clomiphene; see Chapter 40). Gonadotropins are also used for controlled ovarian stimulation in assisted reproductive technology procedures. Currently, a number of different protocols use gonadotropins in ovulation induction and controlled ovulation stimulation, and new protocols are continually being developed to improve the rates of success and to decrease the two primary risks of ovulation induction: multiple pregnancies and the ovarian hyperstimulation syndrome (OHSS; see below).
Although the details differ, all of these protocols are based on the complex physiology that underlies a normal menstrual cycle. Like a menstrual cycle, controlled ovulation stimulation is discussed in relation to a cycle that begins on the first day of a menstrual bleed (Figure 37–3). Shortly after the first day (usually on day 2), daily injections with one of the FSH preparations (hMG, urofollitropin, or rFSH) are begun and continued for approximately 8–12 days. In women with hypogonadotropic hypogonadism, follicle development requires treatment with a combination of FSH and LH because these women do not produce the basal level of LH that is required for normal follicle development. The dose and duration of gonadotropin treatment are based on the response as measured by the serum estradiol concentration and by ultrasound evaluation of ovarian follicle