Stephen Franks

Induction of ovulation with clomiphene citrate in women with polycystic ovary syndrome: the difference between responders and nonresponders *

To identify why some women with polycystic ovary syndrome (PCO) fail to respond to clomiphene citrate (CC), the authors have monitored the endocrine and ovarian response to CC 100 mg/day given for 5 days. Of 40 cycles studied in 27 women, 73% were ovulatory. In 8 of 9 anovulatory women, there was no follicular development despite a significant rise in serum gonadotrophin concentrations within 3 to 5 days of starting CC. There were no significant differences between the ovulatory and anovulatory groups in the peak response of either luteinizing hormone (LH) or follicle-stimulating hormone (FSH). The authors conclude that, in women with polycystic ovaries, the most common reason for the failure to ovulate is an absent ovarian response to an appropriate rise in serum FSH.

Comparative Androgen Production from Theca Cells of Normal Women and Women with Polycystic Ovaries

The most consistent biochemical characteristic of patients with polycystic ovary syndrome (PCOS) is hyperandrogenemia (1). Although there is evidence of hypersecretion of both ovarian and adrenal androgens in PCOS, the predominant source of excess androgen production is the ovary. Thus, in women with PCOS, suppression of pituitary-ovarian activity by the administration of a long-acting agonist analogue of gonadotropin-releasing hormone (GnRH), results in reduction of serum androstenedione and testosterone concentrations to levels equivalent to those in menopausal or ovariectomized subjects (2). The major question, however, is whether ovarian hyperandrogenism reflects increased exposure to luteinizing hormone (LH) (and, perhaps, insulin) or whether it is indicative of a primary ovarian disturbance in androgen production. The fact that there is a relatively poor correlation of LH and testosterone (3)—indeed, serum androgen concentrations may be elevated in the face of normal levels of both LH and insulin—suggests that the latter is more likely. To date there have been few studies that have examined androgen production from monolayer cultures of human theca cells, and none that has attempted to compare results in normal women and PCO patients in this system (reviewed in 4). Our hypothesis was that excessive androgen production by polycystic ovaries is due to an intrinsic disorder of either basal androgen biosynthesis by theca cells and/or increased responsiveness to LH, or other secretagogues such as insulin and insulin-like growth factors. The purpose of these studies was, therefore, to compare androgen production by thecal (and stromal) tissue from PCO with that observed in tissue from normal ovaries.

CHAPTER 28 – Ovarian Function in Assisted Reproduction

This chapter focuses on superovulation regimens used in assisted reproduction technology (ART) and their potential risks are analyzed in terms of their effect on ovarian function. An overview of normal ovarian folliculogenesis is first presented as a prerequisite to analyzing the impact of exogenous gonadotropins, gonadotropin-releasing hormone (Gn-RH) analogs and antagonists, and other drugs used in ART on ovarian response, oocyte quality, and pregnancy outcome. Increasing knowledge of the physiology of human ovarian function has helped refine treatment regimens for controlled ovarian stimulation in women undergoing assisted reproduction. The emergence of recombinant human gonadotropins for human use and the development of antagonists of Gn-RH has allowed “fine-tuning” of the endocrine environment, leading up to egg collection and improved the prospect of better outcome in terms of pregnancy rates and, most importantly, for both fetal and maternal health. It has also proven possible to control the abnormal endocrine environment in women with polycystic ovary syndrome to lower the risk of ovarian hyperstimulation and to maximize the chances of a successful pregnancy.

Evidence Against a Role for the Growth Hormone-Insulin-Like Growth Factor System in the Polycystic Ovary Syndrome

Evidence that has accumulated from both clinical and in vitro studies suggests that each of the elements of the growth hormone (GH)-insulin-like growth factor I (IGF-I) system can affect the function of the human ovary (1). When administered in vivo, GH exerts a gonadotropic action on ovarian folliculogenesis; this effect is accompanied, although not necessarily mediated, by changes in circulating IGF-I (1–3). Studies in vitro have shown that GH has a direct, stimulatory effect on granulosa cell steroidogenesis (1, 4, 5), supporting the concept that it has the potential to act as a cogonadotropin under physiological conditions (1).