Pregnancy complications in women with polycystic ovary syndrome: importance of diagnostic criteria or of phenotypic features?

Sir, We read with great interest the retrospective matched cohort study recently published in Human Reproduction by Kollmann et al. (2015) aimed to evaluate the prevalence of adverse maternal and neonatal outcomes in different populations of women with polycystic ovary syndrome (PCOS) diagnosed according to the three main recommendations of the National Institute of Health (NIH), of the European Society of Human Reproduction and Embryology (ESHRE)/American Society of Reproductive Medicine (ASRM) and of the Androgen Excess and PCOS Society (AE-PCOS). A high prevalence of pregnancy complications was observed in all PCOS populations, irrespectively from the criteria adopted to diagnose the PCOS. Although today it is unknown the exact mechanism(s) involved in the pathogenesis of pregnancy complications in PCOS, the combination of genetic, environmental, clinical and biochemical characteristics, every one closely related with an increased risk of pregnancy complications, seems to play a crucial role (Palomba et al., 2015). One of the main predictors of pregnancy complications is the pregestational body mass index (BMI) (Palomba et al., 2015). It is very intriguing to note the lack of difference in BMI among populations with different PCOS criteria (Kollmann et al., 2015), albeit populations with PCOS diagnosed according to the ESHRE criteria include mild PCOS phenotypes that are characterized by less metabolic alterations. Since metabolic abnormalities are closely related to the risk of pregnancy complications (Palomba et al., 2015), the results were probably biased by small or atypical populations studied with particular regard for specific PCOS phenotypes. In the Kollman study (Kollmann et al., 2015), information crucial to validate the conclusions were not provided. The proportion of ovulatory women can modify the prevalence/incidence of pregnancy complications in subjects with PCOS diagnosed according by EHSRE/ASRM criteria directly and/or indirectly. Oligoanovulation is a critical factor of subfertility in PCOS (Legro et al., 2013) and a strong predictor of pregnancy complications irrespective of PCOS diagnosis (Messerlian et al., 2013; Pinborg et al., 2013). Recently, Brosens and Benagiano (2015) published a very interesting and provocative Clinical Opinion on the menstrual preconditioning for the prevention of pregnancy complications in women with PCOS in which they support the potential role of menstrual shedding on the genesis of the increased incidence of the obstetric and/or neonatal complications observed in women with PCOS. Our prospective controlled data (Palomba et al., 2010) on a well-selected population of women with PCOS diagnosed according to ESHRE criteria who became pregnant naturally, showed a higher risk for adverse pregnancy outcomes in patients with the full-blown and non-polycystic ovary morphology (PCOM) phenotypes than in those with the non-hyperandrogenic and ovulatory phenotypes. Additional analyses with the general linear model univariate procedure demonstrated that only ovarian dysfunction and biochemical hyperandrogenism affect obstetric or neonatal outcomes, increasing significantly the risk for obstetric or neonatal complications (Palomba et al., 2014). Another prospective case–control study (Palomba et al., 2014), aimed to evaluate the impact of different phenotypes of PCOS on early trophoblast invasion and placentation, demonstrated a higher rate of macroscopic and microscopic abnormalities among women with full-blown and non-PCOM phenotypes than in the ovulatory and non-hyperandrogenic phenotypes. On the other hand, no data on the proportion of patients who had natural or medically assisted conceptions, critical information for this kind of analysis, are also available in Kollman's study (Kollmann et al., 2015). Many data available in the literature underline that the use of fertility drugs for inducing ovulation and of assisted reproductive technologies, including intrauterine insemination, are strong predictors of maternal and/or neonatal complications (Nakashima et al., 2013; Pinborg et al., 2013; Malchau et al., 2014). In conclusion, we think that the extreme variability in pregnancy complications in women with PCOS among phenotypes make the differences among diagnostic criteria not detectable. On the other hand, from a scientific and clinical point of view each women with PCOS should be carefully characterized in all its diagnostic and non-diagnostic (including anthropometric characteristics and reproductive history) features (Orio and Palomba, 2014) in order to define and grossly quantify her obstetric/neonatal risk.