We read with interest the clinical opinion paper on ovulation induction in women with polycystic ovarian syndrome (PCOS). PCOS remains an enigma in which the abnormalities in extra- and intra-ovarian factors exert a negative impact on the level of oocyte and embryo. We wish to highlight some points on the topic.

First, the data presented pertain to current aspects based on existing evidence; the clinical information derived from it can easily be applied by a general practitioner and not necessarily an expert in the field. Sufficient evidence on the treatment of PCOS with gonadotrophins is lacking though. Low-dose regimens have been suggested to ensure a limited number of follicles, resulting in monofollicular ovulation, pregnancy, and multiple live birth rates of 70%, 20%, and 5.7%, respectively. Of note, intense ovarian monitoring is required to reduce complications and secure efficiency. In addition, in cases of associated male infertility factor or unsuccessful ovulation induction, intrauterine insemination accompanying ovulation induction is a reasonable alternative treatment option not mentioned by the authors.

Second, we propose that additional emphasis be given to the importance of the alteration in the endometrial level as it constitutes a critical factor leading PCOS patients to lower implantation and higher miscarriage rates. Elevated estrogen, insulin, free insulin-like growth factor 1, and androgens, together with obesity, have also been suggested to contribute to these undesirable outcomes. Unfortunately, endometrial status is overlooked in PCOS patients, as infertility in these women is mainly due to lack of ovulation and subsequently, induction of ovulation becomes the main clinical target and interest of research.

Third, we would like to propose the following treatment modality: that of dexamethasone addition as cotreatment during ovulation induction with gonadotrophins. Data are scarce. The rationale behind this is that it can suppress or temporarily reduce the underlying factors mentioned above that contribute to the pathology of the syndrome. Interestingly, authors cite a Cochrane review on the addition of the substance, but to clomiphene, resulting in rising pregnancy rates.

Finally, we need to question if an appropriate strategy might be formulated so that these patients can be enrolled to in vitro fertilization more quickly, to avoid multiple pregnancies through elective embryo transfer strategies. More importantly, we maintain that research has to focus on and elucidate the molecular mechanisms involved not only in ovulation, but also in endometrial health in PCOS subfertile women, given the close functional association between the two.