Gonadotrophin stimulation for in vitro fertilization significantly alters the hormone milieu in follicular fluid: a comparative study between natural cycle IVF and conventional IVF

studyquestion: Is the steroid hormone profile in follicular fluid (FF) at the time of oocyte retrieval different in naturally matured follicles, as in natural cycle IVF (NC-IVF), compared with follicles stimulated with conventional gonadotrophin stimulated IVF (cIVF)? summaryanswer: Anti-Mullerian hormone (AMH), testosterone (T) and estradiol (E2) concentrations are � 3-fold higher, androstenedione (A2) is � 1.5-fold higher and luteinizing hormone (LH) is � 14-fold higher in NC-IVF than in cIVF follicles, suggesting an alteration of the follicular metabolism in conventional gonadotrophin stimulated IVF. whatisknownalready: In conventional IVF, the implantation rate of unselected embryos appears to be lower than in NC-IVF, which is possibly due to negative effects of the stimulation regimen on follicular metabolism. In NC-IVF, the intrafollicular concentration of AMH has been shown to be positively correlated with the oocyte fertilization and implantation rates. Furthermore, androgen treatment seems to improve the ovarian response in low responders. studydesign,size,duration: This cross-sectional study involving 36 NC-IVF and 40 cIVF cycles was performed from 2011 to 2013. Within this population, 13 women each underwent 1 NC-IVF and 1 cIVF cycle. cIVF was performed by controlled ovarian stimulation with HMG and GnRH antagonists. participants/materials, setting, methods: Follicular fluid was collected from the leading follicles. AMH, T, A2, dehydroepiandrosterone (DHEA), E2, FSH, LH and progesterone (P) were determined by immunoassays in 76 women. Aromatase activity in follicular fluid cells was analysed by a tritiated water release assay in 33 different women. For statistical analysis, the non-parametric Mann–Whitney U or Wilcoxon tests were used. main results and role of chance: In follicular fluid from NC-IVF and from cIVF, median levels were 32.8 and 10.7 pmol/l for AMH (P , 0.0001), 47.2 and 18.8 mmol/l for T (P , 0.0001), 290 and 206 nmol/l for A2 (P ¼ 0.0035), 6.7 and 5.6 pg/ml for DHEA (n.s.), 3292 and 1225 nmol/l for E2 (P , 0.0001), 4.9 and 7.2 mU/ml for FSH (P , 0.05), 14.4 and 0.9 mU/ml for LH (P , 0.0001) and 62 940 and 54 710 nmol/l for P (n.s.), respectively. Significant differences in follicular fluid concentrations for AMH, E2 and LH were also found in the 13 patients who underwent both NC-IVF and cIVF when they were analysed separately in pairs. Hormone analysis in serum excluded any relevant impact of AMH, T, A2, and E2 serum concentration on the follicular fluid hormone concentrations. Median serum concentrations were 29.4 and 0.9 mU/ml for LH (P , 0.0001) and 2.7 and 23.5 nmol/l for P (P , 0.0001) after NC-IVF and c-IVF, respectively. Positive correlations were seen for FF-AMH with FF-T (r ¼ 0.35, P ¼ 0.0002), FF-T with FF-LH (r ¼ 0.48, P , 0.0001) and FF-E2 with FF-T (r ¼ 0.75, P , 0.0001). The analysis of aromatase activity was not different in NC-IVF and cIVF follicular cells.