Follicular fluid hormonal profile and cumulus cell gene expression in controlled ovarian hyperstimulation with recombinant FSH: effects of recombinant LH administration

PURPOSE: Down-regulation with gonadodropin-releasing agonist (GnRH-a) protocol during IVF stimulation leads to a severe endogenous LH suppression, which may affect the follicular development. The aim of the study was to evaluate the effects of recombinant LH (r-LH) administration, during late follicular development stages, in recombinant FSH (r-FSH) stimulated cycles on follicular fluid (FF) parameters and on cumulus cell quality. METHODS: Twenty patients undergoing IVF were stimulated in a long GnRH agonist protocol with r-FSH alone or with r-LH supplementation when the leading follicle reached diameter of 14 mm. FF was collected at the time of oocyte retrieval from 32 follicles ≥ 18 mm. Serum FSH, LH, estradiol (E(2)), and progesterone (P(4)) were evaluated on the day of hCG administration. Intra-follicular E(2), P(4), AMH and TGF-β were assayed. Total RNA from 18 individual cumuli was isolated for gene expression analyses. RESULTS: R-LH increased FF P(4) levels. FF TGF-β levels and PTGS2 and HAS2 expression in cumulus cells (CCs) positively correlated with increased P(4) levels observed in FFs, while a negative correlation was found between P(4) and AMH levels. CONCLUSIONS: FF positive correlation between P(4) and TGF-β levels and CC expression of PTGS2 and HAS2 suggest an association with a better follicle quality. In addition, our data suggest that late follicular phase r-LH supplementation leads to a more advanced stage of follicular maturation.