Benefits of continuous physiological pulsatile gonadotropin-releasing hormone therapy in women with polycystic ovarian syndrome

Abstract

Objective: Can continuous pulsatile GnRH from one ovulatory cycle to another enhance the endocrine milieu of women with polycystic ovarian syndrome (PCOS)?

Design: Five women with well-characterized, clomiphene citrate (CC)- and hMG-resistant PCOS were treated with a 100 ng/kg per bolus of IV pulsatile GnRH (Lutrepulse; Ortho Pharmaceutical Corporation, Raritan, NJ) every 90 minutes for two consecutive ovulatory cycles. Weekly vaginal ultrasonography and daily blood sampling for LH (mIU/mL), FSH (mIU/mL), E2 (pg/mL), and P (ng/mL) were performed. These data were compared with a control group of normally cycling women.

Results: First ovulatory cycles on therapy were characterized by significantly increased mean follicular phase LH = 88 (arbitrary units area under the curve [AUC]) compared with second cycles (28 mean AUC units) and controls (13 mean AUC units). Luteal phase E2 (3,081 mean AUC units) was significantly increased in first cycles compared with second cycles (880 mean AUC units) and controls (1,562 mean AUC units in PCOS). Luteal phase E2 secretion was elevated in second cycles when compared with normal but not significantly. The changes occurring between the first and second ovulatory cycles in women with PCOS resulted in a more physiological overall pattern of gonadotropin and sex steroid secretion in the second cycles. Two singleton pregnancies were achieved in the second cycle.

Conclusions: Low-dose pulsatile IV GnRH can successfully induce ovulation in women with PCOS who have failed to conceive on all previous conventional therapy (CC, hMG, and/or GnRH agonist, and hMG). Continuous cycle-to-cycle physiological GnRH replacement normalized the endocrine parameters of second cycles. Women with PCOS, even when ovulatory on pulsatile GnRH, do not display entirely normal gonadotropin and sex steroid dynamics.