We have read with great interest the Clinical Opinion recently published on menstrual preconditioning for the prevention of pregnancy complications in women with polycystic ovary syndrome (PCOS). This paper provides a very interesting and provocative view on 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. Moreover, it seems to be more of a personal viewpoint than a clinical opinion because many statements/topics are not adequately balanced, especially for a reader without sufficient experience in the field.

At the moment, anovulation should be considered as the only cause of infertility in PCOS because only few and sparse data with strong clinical evidence are available in the literature regarding the role of other potential cofactors. Similarly, all scientific societies are in agreement that women with PCOS cannot be definitively considered at increased risk of spontaneous abortion because scientific data on the relationship of PCOS and abortion are still weak.

The beneficial effects of metformin on pregnancy complication risk are very limited, even if all available data demonstrated the short- and long-term safety of metformin on the offspring. However, in women with PCOS and a body mass index lower than 32 kg/m ² , metformin can be as effective as clomiphene citrate (CC). The authors cited in their paper a previous prospective, nonrandomized study published by us in 2007 comparing metformin and CC (administrated at increasing dose regimen), highlighting no difference between the 2 strategies. However, our previous randomized controlled trial showed the superiority of metformin in terms of reproductive outcomes when compared with CC administered using a standard regimen (150 mg daily).

The analysis of the effects of CC and metformin on the uterus showed an improvement, unlike CC, of the endometrial/subendometrial vascularity under power Doppler assessment in patients with PCOS who ovulated with metformin. In addition, preliminary data suggest that uterine artery velocimetry during the first and mid–second trimester can be useful in predicting pregnancy complications in PCOS patients.

Finally, very interesting data from the subanalysis of the Pregnancy in PCOS I trial demonstrated better reproductive outcomes in patients who did not have progesterone-induced endometrial shedding. On the other hand, the risk of pregnancy complications in women with PCOS seems to be significantly influenced by the menstrual (oligoanovulatory) pattern and is not increased in subjects with ovulatory phenotype.