Specific factors predict the response to pulsatile gonadotropin-releasing hormone therapy in polycystic ovarian syndrome

Ovulation induction is particularly challenging in patients with polycystic ovarian syndrome (PCOS) and may be complicated by multifollicular developm ent. Pulsatile GnRH stimulates monofollicular development in women with ano vulatory infertility; however, ovulation rates are considerably lower in th e subgroup of patients with PCOS. The aim of this retrospective study was t o determine specific hormonal, metabolic, and ovarian morphological charact eristics that predict an ovulatory response to pulsatile GnRH therapy in pa tients with PCOS. Subjects with PCOS were defined by chronic amenorrhea or oligomenorrhea and clinical and/or biochemical hyperandrogenism in the absence of an adrenal or pituitary disorder. At baseline; gonadotropin dynamics were assessed by 10-min blood sampling, insulin resistance by fasting insulin levels, ovaria n morphology by transvaginal ultrasound, and androgen production by total t estosterone levels. Intravenous pulsatile GnRH was then administered. Durin g GnRH stimulation, daily blood samples were analyzed for gonadotropins, es tradiol (E-2), progesterone, inhibin B, and androgen levels, and serial ult rasounds were performed. Forty-one women with PCOS underwent a total of 144 ovulation induction cycl es with pulsatile GnRH. Fifty-six percent of patients ovulated with 40% of ovulatory patients achieving pregnancy. Among the baseline characteristics, ovulatory cycles mere associated with lower body mass index (P < 0.05), lo wer fasting insulin (P = 0.02), lower 17-hydroxyprogesterone and testostero ne responses to hCG (P < 0.03) and higher FSH (P < 0.05). In the first week of pulsatile GnRH treatment, E-2 and the size of the largest follicle were higher (P < 0.03), whereas androstenedione was lower (P < 0.01) in ovulato ry compared with anovulatory patients. Estradiol levels of 230 pg/mL (844 p mol/L) or more and androstenedione levels of 2.5 ng/mL (8.7 nmoL/L) or less on day 4 and follicle diameter of 11 mm or more by day 7 of pulsatile GnRH treatment had positive predictive values for ovulation of 86.4%, 88.4%, an d 99.6%, respectively. Ovulatory patients who conceived had lower free test osterone levels at baseline (P < 0.04). In conclusion, pulsatile GnRH is an effective and safe method of ovulation induction in a subset of patients with PCOS. Patient characteristics associ ated with successful ovulation in response to pulsatile GnRH include lower body mass index and fasting insulin levels, lower androgen response to hCG, and higher baseline FSH. In ovulatory patients, high free testosterone is negatively associated with pregnancy. A trial of pulsatile GnRH therapy may be useful in all PCOS patients, as E-2 and androstenedione levels on day 4 or follicle diameter on day 7 of therapy are highly predictive of the ovul atory response in this group of patients.