Abstract Study question What is phytoestrogen exposure impact on the reproductive outcomes of women undergoing IVF treatment? Summary answer Increased urinary and follicular fluid phytoestrogen concentration were associated with better IVF outcomes. What is known already The impact and safety of phytoestrogens, plant-derived isoflavones with estrogenic activity predominantly present in soy, on female reproductive health and on IVF outcomes continues to be hotly debated. Numerous studies suggest healthy benefits of phytoestrogen consumption: protection against reprotoxic substances, reductions in breast and other cancers, fibroids, menopausal symptoms, cardiovascular disease, inflammation, and metabolic syndrome and obesity. However, many studies suggest a harmful effect due to the endocrine-disruptor properties of phytoestrogens in both male and female reproductive tissues. Its impact on IVF treatments success is still understudied. Study design, size, duration 60 women attending IVI-RMA New Jersey undergoing IVF with single-embryo transfer (SET) of euploid good-quality blastocyst after PGT analysis were recruited. Patients underwent PGT-SET cycles following standard protocols. Concentrations of two phytoestrogens (daidzein and genistein) were measured in follicular fluid (FF) and urine collected at oocyte pick-up (UOP) and urine collected at transfer day (UT). These measurements were correlated with IVF clinical outcomes. Participants/materials, setting, methods Participants were aged 18-42 years old 18.5-29.9 kg/m2 BMI. Measure of both phytoestrogens’ concentration in follicular fluid and urine samples collected at two different time-points was performed by UPLC-MSMS, with internal standards. Urine phytoestrogen concentrations were normalized by creatinine, measured by Jaffe reaction. Generalized linear models were employed to explore IVF outcomes association, estimated as percentile 20th to 80th increase (95% confidence intervals), among log-transformed phytoestrogen concentration. Both unadjusted and age-BMI-adjusted models were applied. Main results and the role of chance In fully adjusted models, higher sum of phytoestrogen concentration in follicular fluid (FF) were significantly associated with higher estradiol at hCG [1.31 (1.04, 1.65), p = 0.023]; whereas the sum of creatinine-corrected phytoestrogens measured in oocyte pick-up urine (UOP) were significantly associated with higher MII oocytes number [1.29 (1.07, 1.56), p = 0.008] and higher fertilized oocytes number [1.34 (1.10, 1.64), p = 0. 004]. Regarding clinical IVF outcomes, in fully adjusted models a higher follicular fluid and oocyte pick-up urine phytoestrogens concentration was significantly associated with higher implantation ratio [8.60 (1.09, 68.03), p = 0. 023] for FF, and [5.01 (0.96, 26.21), p = 0. 05] for UOP; higher clinical pregnancies ratio [5.58 (1.31, 23.73), p = 0.017] for FF, and [3.25 (0.99, 10.63), p = 0.045] for UOP; higher live newborns ratio [5.58 (1.31, 23.73), p = 0.017] for FF, and [3.25 (0.99, 10.63), p = 0.045] for UOP; and higher number of women with live newborns among those who started treatment [4.29 (1.28, 14.38), p = 0.016] for FF, and [2.83 (0.99, 8.07), p = 0.047] for UOP. Limitations, reasons for caution Further studies are needed to confirm this association in other populations, including the measurement of other estrogenic isoflavones and its metabolites. Wider implications of the findings This is the first work evaluating the association between phytoestrogens concentrations in different biofluids and IVF reproductive outcomes. Our results, using an euploid SET, suggest a beneficial effect of phytoestrogen consumption in women undergoing IVF treatment, further studies are needed to assess the benefit of phytoestrogen supplementation on IVF outcomes. Trial registration number -
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