**2. Fertility in patients with polycystic ovary syndrome**

PCOS is considered the most common cause of anovulation, being responsible for 70% of cases of anovulatory infertility [9]. Infertility is a significant complaint among women with PCOS, being reported in 72% of women with PCOS compared with 16% in women without PCOS. However, it seems that the number of children of women with PCOS is similar with those without, suggesting that treatment for infertility is effective [10].

It was also showed that 44% of women with unexplained infertility are probable PCOS cases, underlying that the subtle clinical phenotypes in some of the patients can be the cause of misdiagnosis and, therefore, inappropriate diagnosis and treatment [11].

It seems that the criteria used for diagnosis can also impact the prevalence of infertility which is higher in women with polycystic ovary morphology in patients diagnosed according to Androgen Excess Society criteria (21,7%), while in patients diagnosed according to Rotterdam criteria infertility is present in only 6% of them [5].

Older studies report that 78% of infertile women with PCOS respond to clomiphene citrate (CC) administration [12], with only the remaining 22% requiring alternative therapies, suggesting that anovulation is not the only cause of infertility in PCOS patients. Indeed, even after restoration of ovulation, PCOS patients still have reduced cumulative pregnancy rate and higher rates of implantation failure [13]. Even in cycles with excellent embryos selected for transfer, the success of in vitro fertilization in PCOS patients remain low [14]. In animal models the transfer of blastocysts from normal mice to DHEA-induced PCOS mice resulted in a reduced implantation rate [15]. Moreover, patients with PCOS had an increased risk of miscarriage with reported rates between 30 and 50% of all conceptions [16, 17]. In addition, PCOS seems to be responsible for more than 30% of cases of recurrent miscarriages [18].

Since oocytes and embryo quality do not seems to be the cause of low implantation and pregnancy rate in PCOS patients as demonstrated by donor oocyte models [19, 20], the decreased receptivity of the endometrium seems more probable. Indeed, accumulating data support the hypothesis that endometrium of PCOS patients is affected probably as a consequence of hormonal imbalance. Thus, unopposed estrogens, hyperinsulinemia, hyperandrogenism and the members of insulin-like growth factor family were reported as possible contributors to endometrial pathology in PCOS [21]. Factors associated with unexplained recurrent pregnancy loss like high serum levels of free testosterone and LH, decreased luteal phase progesterone and delayed endometrial development [22] are also found in PCOS patients, suggesting their involvement in the high miscarriage rate in PCOS.

Several abnormalities of the endometrium were reported in PCOS women. Thus, endometrial gene expression and sex hormone receptors, co-receptors, adhesion molecules expression and endometrial markers were reported to be abnormal [23].
