Ovarian Stimulation Effects on Ghrelin Secretion and Reproductive Potential

Abstract

Objective: Finely regulated Ghrelin (Ghrl) secretion is essential during early pregnancy, as infra or supraphysiologic levels can be detrimental. Since estrogens stimulate Ghrl synthesis, controlled ovarian hyperstimulation (COH) might increase ghrelinemia, thus being detrimental for fertility. The aim of this work was to evaluate whether COH increases ghrelinemia and associates with maternal endocrine and immune biomarkers and reproductive success. Design: Ninety seven women undergoing assisted reproduction were grouped as follows: COH: undergoing COH and fresh embryo transfer (n=35); FET: undergoing frozen embryo transfer in a cycle different from that of COH (n=25) and, OD: undergoing embryo transfer in oocyte donation cycles (n=37). At embryo transfer day, several endocrine and immune biomarkers were assessed. Results: We found that COH patients showed significantly higher serum estradiol, progesterone and Ghrl, than those not hyperstimulated. Patients that suffered miscarriage showed significantly lower concentrations of sex-hormones, with a similar trend for Ghrl, that deserves further investigation. Moreover, COH 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. Conclusions: As hypothesized, COH significantly increased serum Ghrl and sex-hormone levels, which significantly associated with maternal immune response or 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.