Polycystic Ovarian Syndrome

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PCOS is the most common cause of anovulatory infertility. This syndrome was first described by Stein and Leventhal in 1935. The PCOS Rotterdam Consensus Conference recently defined PCOS as a clinical syndrome comprising any two of the three features: amenorrhea or oligomenorrhea; clinical or biochemical hyperandrogenism, and bilateral polycystic ovaries on ultrasound (45). Although no single biochemical test is diagnostic of PCOS, most patients showed a characteristic ovarian ultrasonographic appearance, namely the presence of > 10 follicles between 2 and 10 mm in diameter. On the other hand, ultrasonographically identified polycystic ovaries are a common finding in apparently normal women, with a prevalence of

20-23% (46,47). On careful review, menstrual irregularities and evidence of hyperandrogenism are frequently associated with the presence of polycystic ovaries in these apparently healthy women (48).

Infertile women with PCOS represent a difficult therapeutic problem for assisted reproductive techniques because they have a higher incidence of OHSS (refer following section) (49). On transvaginal ultrasound scanning, the prevalence of polycystic ovaries has been reported to be 25-33% in an assisted reproduction treatment population (50). These data underline the fact that polycystic ovaries are prevalent in infertile women who often lack the clinical characteristics of classical PCOS.

It has been proposed that a dysfunction of cytochrome P-450c 17a in PCOS leads to an increased 17-hydroxyprogesterone (17-OHP) response to a GnRH agonist-induced gonadotrophin rise (51). We investigated 106 IVF patients undergoing a boost stimulation regimen by correlating the ovarian ultrasound pattern with serum testosterone, 17-OHP, androstenedione, and estradiol responses and with the clinical outcome. There was a significantly higher prevalence of ovarian hyperandrogenism (serum testosterone >0.5 nmol/L after dexamethasone administration) in patients with polycystic ovaries (23%) compared with normal ovaries (7%). Patients with polycys-tic ovaries had approximately double the 17-OHP and estradiol responses to GnRH agonist. The number of oocytes retrieved was positively correlated with the estradiol responses. Although there was no difference in the total amount of FSH used between the patients with polycystic and normal ovaries, the median peak estradiol concentration was 1.6 times greater and the oocyte yield 2.3 times greater in patients with polycystic ovaries. The overall pregnancy rate per transfer was 32% and did not differ between patients with or without polycystic ovaries. We concluded from this study that the presence of polycystic ovaries on a vaginal ultrasound scan was the single most important marker for ovarian abnormality in an assisted reproduction patient population. Detection of polycystic ovaries predicts a subset of patients with abnormal ovarian androgen metabolism, exaggerated 17-OHP and estradiol responses to a GnRH agonist, and a higher oocyte yield. The ultrasonographic changes characteristic of PCO should be sought in all women undergoing assisted reproduction. In such cases, the ovarian-stimulating protocol is modified by reducing FSH starting dose (Table 1) and careful follow-up of serum E2 levels and follicular number and size.

IVF-ET is an effective therapy for PCOS patients who are refractory to ovulation induction in vivo even in the absence of other associated infertility factors (52). However, laparoscopic diathermy of the ovarian surface and hilum should precede an IVF attempt in these patients, as this procedure can reduce serum androgen concentration and normalize ovarian function. Following this procedure, spontaneous ovulation rate is about 90% and conception rates are 40-70% (53). Thus, many authors recommend this operation even before gonadotrophin treatment (54). Furthermore, it should be considered for patients who had difficulties in multifolliculogen-esis or had severe OHSS after IVF treatment (refer following section).

The overall conception rates per cycle in PCOS patients compared favorably to conception rates in patients with other infertility diagnoses (55-58). The use of GnRH agonist is associated with a significant reduction in the incidence of pregnancy loss and improvement in the cumulative pregnancy rates (58). Salat-Baroux et al. (55) found that the longer the period of pituitary desensitization (the long protocol vs. shorter ones), the lower the levels of circulating androgens. The current protocol for PCOS patients in Monash IVF is the long downregulation protocol with starting FSH dosage of 112 IU/day.

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