BENEFITS OF CONTINUOUS PHYSIOLOGICAL PULSATILE GONADOTROPIN-RELEASING-HORMONE THERAPY IN WOMEN WITH POLYCYSTIC OVARIAN SYNDROME

Objective: Can continuous pulsatile GnRH from one ovulatory cycle to a nother enhance the endocrine milieu of women with polycystic ovarian s yndrome (PCOS)? Design: Five women with well-characterized, clomiphene citrate (CC)- and hMG-resistant PCOS were treated with a 100 ng/kg pe r bolus of IV pulsatile GnRH (Lutrepulse; Ortho Pharmaceutical Corpora tion, Raritan, NJ) every 90 minutes for two consecutive ovulatory cycl es. Weekly vaginal ultrasonography and daily blood sampling for LH (mI U/mL), FSH (mIU/mL), E(2) (pg/mL), and P (ng/mL) were performed. These data were compared with a control group of normally cycling women. Re sults: First ovulatory cycles on therapy were characterized by signifi cantly increased mean follicular phase LH = 88 (arbitrary units area u nder the curve [AUC]) compared with second cycles (28 mean AUC units) and controls (13 mean AUC units). Luteal phase E(2) (3,081 mean AUC un its) 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 E(2) secretion was elevated in second cycles when comp ared 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 se cretion in the second cycles. Two singleton pregnancies were achieved in the second cycle. Conclusions: Low-dose pulsatile IV GnRH can succe ssfully induce ovulation in women with PCOS who have failed to conceiv e on all previous conventional therapy (CC, hMG, and/or GnRH agonist, and hMG). Continuous cycle-to-cycle physiological GnRH replacement nor malized the endocrine parameters of second cycles. Women with PCOS, ev en when ovulatory on pulsatile GnRH, do not display entirely normal go nadotropin and sex steroid dynamics.