Association between PFAS compounds in follicular fluid and POR and the intervention effect of Qizi Yusi Tang: a study based on targeted PFAS quantification analysis

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Abstract
Background: This study employs high-throughput targeted PFAS quantification analysis to analyze per- and polyfluoroalkyl substances (PFAS) metabolites in follicular fluid from women with Kidney Deficiency-Liver Stagnation Pattern poor ovarian response (POR) and IVF controls with normal ovarian reserve. Furthermore, we examine PFAS metabolite alterations in POR patients before and after intervention with kidney-tonifying and liver-soothing herbal medicine to suggest that PFAS compounds, particularly PFBA, are significant metabolic markers associated with the Kidney Deficiency-Liver Stagnation Pattern in POR. Methods: This study enrolled 93 patients undergoing in vitro fertilization and embryo transfer (IVF-ET). Participants were divided into three groups: (1) the non-herbal intervention group (POR-NON group, n =31); (2) the control group (POR-CON group, n =31); and (3) the herbal medicine intervention group (POR-TCM, n =31). And ultra-high performance liquid chromatography-triple quadrupole mass spectrometer (UHPLC-QTRAP MS) was used to detect metabolites in the three groups of samples. Results: Patients with Kidney Deficiency-Liver Stagnation Pattern POR showed significantly higher levels of PFBA in follicular fluid compared to IVF controls with normal ovarian reserve (P < 0.01). The level of PFBA in follicular fluid was significantly lower in patients with Kidney Deficiency-Liver Stagnation Pattern POR who received QZYST intervention (POR-TCM group) than in those who did not receive intervention (POR-NON group) (P < 0.05). QZYST intervention significantly reduced Kidney Deficiency-Liver Stagnation Pattern scores in POR patients compared to both baseline (P < 0.001) and the POR-NON group (P < 0.05). The POR-TCM group demonstrated significantly improved number of oocytes retrieved (P < 0.05) and two-pronuclei (2PN) zygotes (P < 0.05), along with significantly fewer cycles with no transferable embryos (P < 0.05) compared to the POR-NON group. Conclusions: Patients with Kidney Deficiency-Liver Stagnation Pattern POR exhibited significantly elevated levels of PFAS compounds in follicular fluid compared to IVF controls with normal ovarian reserve. Compared with the control group, patients who received QZYST intervention showed improvements in TCM syndrome manifestations and key clinical outcomes, and significantly lower PFBA levels were observed in the follicular fluid of the TCM intervention group than in those without intervention.

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