Gonadotropin Therapy Anovulatory PCOS patients who fail to ovulate or conceive with oral agents should be considered for ovulation induction with exogenous gonadotropin injections. Evening medication administration allows for morning monitoring and midday decision making. Monitoring involves serum estradiol levels and transvaginal ultrasound measurements of follicle development. Typical protocols monitor at baseline, 4 to 5 days after treatment initiation, then every 1 to 3 days until follicular maturation (expected follicle growth is 1 to 2 mm daily after achieving 10 mm diameter) (180). Given the goal of promoting growth of a single mature follicle, low initial gonadotropin doses of 37.5 to 75 IU per day are generally recommended, with increases in doses by 50% of the previous dose after 7 days if no follicle greater than 10 mm is observed (141,180). Typical treatment duration is 7 to 12 days, but some patients require longer medications regimens for adequate stimulation. The maximum required gonadotropin dose seldom exceeds 225 units per day. Ovulation triggering with hCG is recommended for gonadotropin cycles and is used when one or two follicles are 16 to 18 mm in diameter and the E2 level per dominant follicle is 150 to 300 pg/mL. Ovulation can be expected 24 to 48 hours after the hCG trigger. GnRH agonists such as leuprolide (500 μg subcutaneously) can be used to trigger ovulation, but they require progesterone supplementation following administration. Intercourse should be recommended within 24 to 48 hours of ovulation triggering or IUI 24 to 36 hours after triggering (180). Testing for pregnancy should be performed 15 to 16 days after ovulation triggering and the cycle reviewed if pregnancy testing is negative. Gonadotropin dosage in future cycles should be altered if the prior response was inadequate or excessive.
Gonadotropin Preparations Several gonadotropin preparations are available. Human menopausal gonadotropin (HMG) is derived from human urine and includes approximately equivalent FSH and LH (derived from hCG) activity of 75 IU each. Current formulations of HMG and FSH can be administered either subcutaneously or intramuscularly. FSH-only preparations may be derived either from urine or via recombinant methods and are packaged either as lyophilized powder or premixed-liquid cartridges/pens. With the exception of highly purified urinary FSH, which has an FSH activity of 82.5 IU per ampule, all other products contain 75 IU of gonadotropin when supplied in ampules. All preparations of FSH are highly purified, with minimal to no batch-to-batch variation and a high level of safety regardless of the derived source. Despite being differentially marketed as follitropin-α and -β, these recombinant FSH preparations still contain combinations of 1-α and 1-β glycoprotein chain. Rather, they differ in their posttranslational modifications and processes for purification. Recombinant LH is available in syringes delivering 75 IU (156). For PCOS patients, FSH alone (either recombinant or urinary) appears to be sufficient in the gonadotropin preparation, although LH is not harmful (180) (Table 32.8). Contraindications to gonadotropin therapy are listed in Table 32.9.