Low-dose human chorionic gonadotropin therapy can improve sensitivity to exogenous follicle-stimulating hormone in patients with secondary amenorrhea.

OBJECTIVE: To assess the effect of supplementing an ovulation induction regimen of highly purified FSH with LH activity in the form of low-dose hCG therapy. DESIGN: Case report. SETTING: The Reproductive Endocrinology Center at the University of Bologna, Bologna, Italy. PATIENT(S): A woman with weight-related secondary hypogonadotropic amenorrhea. INTERVENTION(S): The patient was treated first with highly purified FSH alone and then received highly purified FSH in combination with low-dose hCG therapy (50 IU/d). MAIN OUTCOME MEASURE(S): Pelvic ultrasound examinations, serum E2 levels, duration of treatment, total dose of highly purified FSH, and outcome of treatment. RESULT(S): The concomitant administration of low-dose hCG and highly purified FSH markedly reduced the duration of treatment and the dose of highly purified FSH, and resulted in a quadruplet pregnancy in a patient in whom several previous ovulation induction procedures had been unsuccessful. CONCLUSION(S): Supplementation of an ovulation induction regimen with an agent that has LH activity can enhance FSH-induced folliculogenesis and markedly reduce costs in women with hypogonadotropic hypogonadism. However, this increased response can be associated with complications such as multiple gestation.

Luteinizing hormone activity supplementation enhances follicle-stimulating hormone efficacy and improves ovulation induction outcome.

Although FSH is essential to stimulate ovarian folliculogenesis, increasing physiological and clinical evidence suggests that moderate LH stimulation may also be critical for optimal follicle and oocyte development. Conversely, a clinical trend exists toward conducting controlled ovarian hyperstimulation (COH) in a LH-depleted environment, as recently developed gonadotropin preparations are devoid of LH activity, and endogenous LH is suppressed with GnRH analogs in most COH cycles. To investigate the role of LH activity during COH we supplemented highly purified (HP) FSH with low dose hCG in GnRH agonist-suppressed women. Twenty normoovulatory women were pretreated with a GnRH agonist and after 2 weeks were randomly assigned to receive HP FSH (150 IU/day) alone (group A; 10 patients) or combined with hCG (50 IU/day; group B; 10 patients). The HP FSH dose was increased after 14 days only in cases of inadequate response. Treatment was monitored with pelvic ultrasound and daily hormone determinations. None of the patients of group B and 8 of group A required more than 14 days of treatment and increments of the FSH dose. Folliculogenesis and 17beta-estradiol (E2) secretion progressed more rapidly and evenly in group B. Although preovulatory follicle number and E2 concentrations were comparable, patients in group B required a shorter stimulation time (12.5+/-0.6 vs. 17.3+/-0.7 days in group A; P < 0.0001) and a lower HP FSH dose (1725+/-84 vs. 2670+/-164 IU in group A; P < 0.0001). Serum levels of LH, E2, progesterone, and testosterone did not differ between the 2 groups; serum FSH was higher in group A. We conclude that LH activity promotes folliculogenesis in synergy with FSH in the mid- to late follicular phase and that low dose hCG coadministration optimizes COH by 1) enhancing FSH action, 2) accelerating ovarian follicle development, 3) shortening COH duration, 4) lowering HP FSH requirements, and 5) reducing COH cost. Thus, moderate LH activity in the follicular phase plays a positive physiological and clinical role in folliculogenesis and ovulation induction.