Endocrine Abstracts (2011) 26 S28.3

PCOS: treatment of infertility and prediction of success

Bart Fauser

University Medical Centre, Utrecht, The Netherlands.

Polycystic ovary syndrome is a complex genetic condition, diagnosed based on oligo/anovulation, hyperandrogenemia and polycystic ovaries. Moreover, these women frequently present with obesity, insulin resistance and other signs of metabolic disease. In a gynaecology practice, the great majority of PCOS women present with anovulatory infertility. In fact, it is often suggested that around 20–30% of all infertility is due to PCOS. The medical treatment aiming to restore normo-ovulatory cycles in anovulatory women should be referred to as ‘ovulation induction’. This approach is under increasing pressure in relation to the widespread use of assisted reproduction (ovarian hyperstimulation and intra-uterine insemination, or IVF) or surgical procedures such as laparoscopic ovarian cautery.

Recently, an ESHRE/ASRM sponsored consensus workshop on ovulation induction strategies in PCOS was organised in Thessaloniki, Greece (published in both Human Reproduction and Fertility Sterility in 2008). In brief, life style and diet changes should be recommended and actively encouraged to all obese PCOS women. Clomiphene citrate remains the first line drug of choice, despite relatively low efficacy. Several large, multi-center, comparative trials showed limited efficacy of insulin sensitising agents such as metformin for ovulation induction. Despite initial positive experience with aromatase inhibitors, well powered randomized trials need to show its effectiveness and safety before this compound can be recommended for large scale clinical use. As second line treatment both exogenous gonadotrophins or ovarian cautery can be applied depending on patient (and doctor) preference. The major shortcoming of even low-dose, step-up gonadotrophin protocols remains increased chances for multiple gestation. The drawback of the surgical approach is that surgery is needed and the relatively low efficacy, requiring additional ovulation inducing drugs is many women. However, multiple pregnancies following ovarian cautery are negligible. There is no need for IUI in addition to ovulation induction provided that sperm quality is normal.

IVF should generally be considered as third line treatment after failed ovulation induction. Ovarian hyperstimulation for IVF remains a challenge in PCOS patients, with a distinct tendency to over-respond. Overall, success rates are quite good, with the major benefit that multiple pregnancy can be prevented by the transfer of just a single embryo. Therefore, IVF may be considered an earlier treatment option in women of more advanced reproductive age.

Overall, ovulation induction treatment is effective and singleton live birth rates of over 70% have been reported. We have worked extensively on assessing possible predictors of treatment outcomes based on initial screening characteristics. Using multi-variate prediction models we could show that factors such as body mass index, high androgen levels, female age, and insulin resistance are fairly good predictors of both ovulation and pregnancy chances. Such approaches may help to render ovulation induction more patient tailored, helping to choose the best treatment option and individualize dosing.

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