Peptídeo INSL3 como marcador de atividade das células da Teca Ovariana em ciclos de fertilização in vitro

Abstract

Insulin-like peptide 3 (INSL3) is a member of the insulin-like peptide family that includes, insulin itself, the growth factors IGF1 and IGF2 and relaxin. INSL3 synthesis has been identified within the innermost layer of bovine and human theca cells in antral follicles. The aim of this study was to evaluate serum levels of the INSL3 peptide as a biomarker of theca cell function and as a predictor of ovarian response to gonadotropin stimulation in IVF cycles. Ninety-one women with indication for in vitro fertilization (IVF) treatment at the Hospital das Clínicas of UFMG were prospectively included. Blood samples were collected before the start of ovarian stimulation with gonadotropins and on the day of egg retrieval, when a follicular fluid sample was also collected. INSL3 concentrations were measured in the biological samples using an enzyme-linked immunosorbent assay. Plasma INSL3 levels were significantly increased after controlled ovarian stimulation. However, plasma levels were consistently higher than levels detected in follicular fluid, suggesting the possible existence of extragonadal sources of the peptide. Participants with INSL3 levels above the median had higher antral follicle counts, better response to ovarian stimulation, and a higher number of mature oocytes retrieved per unit of gonadotropin used. On the other hand, plasma INSL3 measurement before stimulation demonstrated low predictive accuracy for the number of oocytes retrieved (AUC: 0.555), being surpassed by traditional markers such as antral follicle count (AUC: 0.851) and age (AUC: 0.759). Although plasma INSL3 levels after ovarian stimulation are associated with a better ovarian response, its pre-stimulation predictive value is limited. The findings suggest that INSL3 may reflect the functional activity of theca cells during stimulation, but it is not a reliable biomarker for the isolated prediction of ovarian response before treatment initiation. The higher systemic concentration compared to follicular fluid also raises the hypothesis of extragonadal production of INSL3, which should be investigated in future studies.