New approach to polycystic ovary syndrome and other forms of anovulatory infertility

Anovulation can be classified in the clinic on the basis of serum hormone assays. Low gonadotropins along with low estrogen concentrations are suggestive of a central origin of the disease, whereas low estrogen levels along with elevated gonadotropins indicate a primary defect at the ovarian level. Most anovulatory patients (approximately 80%) present with serum FSH and estradiol levels within the normal range (World Health Organization class II). Polycystic ovary syndrome (PCOS) is a common but poorly defined heterogeneous clinical entity. Historically, characteristic ovarian abnormalities represented a hallmark of the syndrome. Because several etiological factors may lead to a similar end point (i.e., polycystic ovaries), the development of a clinically applicable classification of the syndrome has proven difficult. Clinical, morphological, biochemical, endocrine, and, more recently, molecular studies have identified an array of underlying abnormalities and. added to the confusion concerning the pathophysiology of the disease. Despite the vast literature regarding the etiology and classification of PCOS, no consensus has been reached regarding the validity of criteria used to diagnose the syndrome. For instance, the significance of elevated serum luteinizing hormone (LH) concentrations, insulin resistance or polycystic-appearing ovaries assessed by ultrasound for PCOS diagnosis remains uncertain. In contrast, hyperandrogenism and chronic anovulation generally are believed to be mandatory diagnostic features. Patients with PCOS might visit a dermatologist for hirsutism, a generalist, or internist for complaints related to obesity or a gynecologist for irregular or absent bleeding. However, most patients seek the care of a gynecologist because of cycle abnormalities (oligomenorrhea) and infertility. In PCOS, serum FSH and estradiol (E-2) levels are usually found to be within the (broad) normal ranges, whereas LH may either be normal or elevated. Because PCOS with normal or high LH does not seem to represent different clinical entities, it seems justifiable to consider this syndrome as a subgroup of WHO II patients, although estrogen levels may be tonically elevated in these patients. This review will focus on characteristics of the heterogeneous group of WHO-II patients in an attempt to identify factors involved in the etiology and possible ovulation induction outcome of PCOS.