Polycystic ovary syndrome: Abnormalities and management with pulsatile gonadotropin-releasing hormone and gonadotropin-releasing hormone analogs Marco Filicori, MD, Carlo Flamigni, MD, Elisabetta Campaniello, MD, Maria Cristina Meriggiola, MD, Laura Michelacci, MD: Alessandro Valdiserri, MD, and Paola Ferrari, BSc Bologna, Italy Ovulation induction with pulsatile gonadotropin-releasing hormone achieves high ovulatory and pregnancy rates in hypogonadotropic hypogonadism while limiting the occurrence of ovarian hyperstimulation and multiple pregnancy. However, this form of therapy is apparently less effective in polycystic ovary syndrome. The administration of a gonadotropin-releasing hormone analog for 4 to 8 weeks before the initiation of pulsatile gonadotropin-releasing hormone ovulation induction can temporarily correct endocrine abnormalities of polycystic ovary syndrome, such as excessive luteinizing hormone and androgen secretion, and improve ovulatory and pregnancy rates in these patients. For optimal results, this pretreatment should probably be repeated before each pulsatile gonadotropin-releasing hormone ovulation induction cycle. Obesity is associated with a lower success rate, and spontaneous abortion remains a prominent complication in polycystic ovary syndrome even after gonadotropin-releasing hormone analog suppression. With this regimen the risks of ovarian hyperstimulation and multiple pregnancy are virtually abolished. Thus, pulsatile gonadotropin-releasing hormone appears to be highly effective and safe for ovulation induction in patients with polycystic ovary syndrome also, provided that this treatment is preceded by pituitary-ovarian suppression with a gonadotropin-releasing hormone analog. (AM J OBSTET GVNECOL 1990;163:1737-42.) Key words: Pulsatile gonadotropin-releasing hormone, polycystic ovary syndrome, GnRH analog, ovulation induction Polycystic ovary syndrome is a disorder frequently encountered among patients seen in gynecologic and reproductive endocrine clinics. Common complaints of polycystic ovary syndrome include hirsutism, obesity, menstrual disorders (mainly oligomenorrhea), and in- fertility. Anovulation is common and ovulation induc- tion is often resorted to for treatment of infertility in this disorder. Several hormones are secreted abnormally in poly- cystic ovary syndrome (Fig. 1). Excessive androgen levels are common and cause acne and hirsutism; ele- vated intraovarian androgens also affect folliculogen- esis and may participate in the pathogenesis of ano- vulation. I Although large amounts of excessive andro- gens and androgen substrate appear to be produced by the ovary, the adrenal gland may contribute sub- stantially to hyperandrogenism in polycystic ovary syn- drome. 2 A high pituitary output of luteinizing hormone From the Center for Chronobiology of Reproduction, Reproductive Medicine Unit, and Prenatal Diagnosis Unit: Department of Ob- stetrics and Gynecology, University of Bologna. Reprint requests: Marco Filicori, MD, Fisiopatologia Riproduzione, Clinica Ostetrica e Ginecologica, Via Massarenti 13, 40138 Bologna, Italy. 610124545 (LH) is a frequent finding in polycystic ovary syndrome. The episodic secretion of LH is deranged; LH peaks are of greater amplitude than in normal women in the follicular phase of the menstrual cycle.'"" Excessive fre- quency of gonadotropin-releasing hormone (GnRH)- induced LH pulses may also be present,3. 1. 7 although this feature is still the subject of some controversy.5. 6 Pituitary sensitivity is also increased so that large amounts of gonadotropins are secreted when the pi- tuitary gland is challenged with exogenous GnRH 8 ; this derangement is probably responsible for the elevation of LH pulse amplitude present in polycystic ovary syn- drome. Excessive androgen levels indirectly affect gonado- tropin secretion through various mechanisms. Andro- stenedione is peripherally converted to estrone; an- drogens also lower sex hormone-binding globulin levels so that increased amounts of unbound androgens and unbound 17[3-estradiol are present in polycystic ovary syndrome. 9 These high estrone and free 17[3- estradiol levels may act at the pituitary level to increase LH and follicle-stimulating hormone (FSH) reserve. This vicious cycle of high LH output, excessive andro- gen secretion, and elevated weak estrogen levels par- ticipates critically in the maintenance of deranged hor- 1737