Abstract

Abstract Study question Which follicular fluid (FF) autoantibodies influence oocyte quality and its fertilization potential in the settings of IVF-ICSI? Summary answer The measured follicular fluid levels of anti-thyroperoxidase and anti-aromatase antibodies are associated with lower number of mature oocytes and fertilization rate in IVF-ICSI cycles. What is known already Nowadays it is known that there is clear correlation between serum and follicular fluid antibody levels indicating their ability to pass freely through blood-follicle barrier. It is believed that anti-thyroid antibodies may exert direct toxic effect on the growing follicle and adversely affect the quality of future embryo due to the direct interaction with zona pellucida antigens, disordering its functional role and, consequently, altering oocyte fertilization and developmental potential. However, at this point no cases of anti-aromatase antibody detection in the follicular fluid of women undergoing fertility treatment have been reported. Study design, size, duration A prospective cohort study including 90 patients undergoing IVF-ICSI was performed at the Department of ART, The D. O. Ott Research Institute of Obstetrics and Gynecology from September 2018 to March 2020. During oocyte retrieval only the first aspiration including cumulus-oocyte complexes (COC) were used for the study. After COC removal, the pre-ovulatory FF was centrifuged at 2000×g for 10 min. The cell-free supernatants were divided into aliquots and stored at 80 oC until assay. Participants/materials, setting, methods FF investigation included anti-thyroperoxidase (AT-ТРО, BlueGene, Сhina, E01T0531) and anti-aromatase (anti-ARO, Cloud-Clone Corp., USA, AEC319Hu) antibodies detection using commercial ELISA kits. The threshold value for each antibody was calculated as 3*SD from the mean values of patients investigated. Thus, the study group included 52 women with FF autoantibodies ≥ (M + 3*SD) (if at least one marker positive), the comparison group comprised 38 women with FF autoantibodies < (M + 3*SD). Main results and the role of chance In the study group, the number of mature oocytes was notably lower than in the comparison group (6.5 (3.5; 9.5) vs 9 (8; 11); P < 0,01). A significant inverse correlation between follicular fluid AT-TPO (rs =-0.5; P < 0.05) and anti-ARO (rs =-0.5; P < 0.05) antibody levels and the number of mature oocytes was revealed in all investigated samples. In addition, despite no difference in the rate of mature oocytes between the groups (84% vs 88%, P > 0.05) it negatively correlated with anti-ARO FF (rs =-0.4; P < 0.05) among all the participants. Evaluation of oocyte fertilization rate using a linear regression analysis showed its significant dependence on the follicular fluid anti-aromatase antibody levels (R = 0,33; P < 0,01). Limitations, reasons for caution Small sample size Wider implications of the findings Further studies with larger sample size evaluating anti-ARO antibodies are needed in order to understand its origin and effect on early steps of human reproduction. Trial registration number not applicable

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