Ovarian Stimulation Effects on Ghrelin Secretion and Reproductive Potential

Finely regulated Ghrelin (Ghrl) secretion is essential during early pregnancy, as infra or supraphysiologic levels can be detrimental. Since oestrogens stimulate Ghrl synthesis, ovarian stimulation (OS) might increase ghrelinemia, thus being detrimental for fertility. The aim of this work was to evaluate whether OS increases ghrelinemia and associates with maternal endocrine and immune biomarkers and reproductive success.

The 97 women undergoing assisted reproduction were grouped as follows: OS: undergoing OS and fresh embryo transfer (n = 35); FET: undergoing frozen embryo transfer in a cycle different from that of OS (n = 25) and, OD: undergoing embryo transfer in oocyte donation cycles (n = 37). At embryo transfer day, several endocrine and immune biomarkers were assessed.

OS patients showed significantly higher serum estradiol, progesterone and Ghrl, than those not stimulated. Patients that suffered miscarriage showed significantly lower concentrations of sex-hormones, with a similar trend for Ghrl, that deserves further investigation. Moreover, OS patients showed decreased frequencies of circulating T cells and reduced ratios of uNK/NK cells, which significantly associated with serum levels of sex-hormones. Besides, ROC curves identified cut-off values predictive of clinical pregnancy and/or miscarriage for peripheral counts of uNK cells, T cells, and uNK/NK cells ratio.

As hypothesised, OS significantly increased serum Ghrl in correlation with sex-hormone levels. These last, significantly associated with maternal immune response and reproductive outcome. Although Ghrl exhibited a similar profile, it did not reach statistical significance, indicating the need for further investigation. Additionally, the identification of maternal immunological cut-off values holds significant clinical relevance.