Associations betweenPhthalateMetaboliteConcentrationsinFollicularFluidand Reproductive OutcomesamongWomenUndergoing in Vitro Fertilization/ Intracytoplasmic SpermInjectionTreatment

BACKGROUND: Phthalates havebeenreportedtoimpairfertilityinvariousstudies. However, evidenceexploringtheassociationsbetweenphthalate metabolites infollicular fluid (FF) andreproductiveoutcomesislacking. OBJECTIVES: To investigatetheassociationsbetweenphthalatemetaboliteconcentrationsinFFand in vitro fertilization/intracytoplasmic sperminjection (IVF/ICSI) outcomesamongwomenrecruitedfromafertilityclinic. METHODS: We included641womenundergoingIVF/ICSItreatmentfromDecember2018toJanuary2020. Thelevelsofeightphthalatemetabolites, including monoethylphthalate(MEP), mono-isobutylphthalate(MiBP), mono-n-butyl phthalate(MBP), monobenzylphthalate(MBzP), mono(2ethylhexyl) phthalate(MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate(MEHHP), mono(2-ethyl-5-oxohexyl) phthalate(MEOHP), andmono(2ethyl-5-carboxypentyl) phthalate(MECPP), werequantified inFFcollectedontheoocyteretrievalday. Associationsbetweenquartilesofindividual phthalate metaboliteconcentrationsandnineIVF/ICSIoutcomes, includingoocyteyield, matureoocytenumber, twodistinctpronuclei(2PN) zygote number, fertilizationrate, blastocystformationrate, implantation, clinicalpregnancy, miscarriage, andlivebirth, wereestimatedwithgeneralizedlinear models. Theeffects ofphthalatemixturesonIVF/ICSIoutcomeswereassessedusingBayesiankernelmachineregression(BKMR) models. RESULTS: After adjustingforrelevantconfounders, elevatedquartilesofMBzP, MEHHP, andMEHPinFFwereinverselyassociatedwiththenumbers ofretrievedoocytes, matureoocytes, and2PNzygotes(all p for trends<0:10). Incomparisonwiththelowestquartile, thehighestquartileof molar sumofdi(2-ethylhexyl) phthalatemetabolites(RDEHP) wasassociatedwithareductionof9.1%[95% confidence interval(CI): -17:1%, -0:37%] and10.3%(95% CI: -18:8%, -0:94%) inyieldedoocyteandmatureoocytenumbers, respectively. Furthermore, theBKMRmodelsrevealed inverse associationsbetweenphthalatemixturesandthenumbersofretrievedoocytesandmatureoocytes. Wegenerallyfoundnullresultsforimplantation, clinicalpregnancy, miscarriage, andlivebirth. DISCUSSION: Certain phthalatemetabolitesinFFareinverselyassociatedwiththenumbersofretrievedoocytes, matureoocytes, and2PNzygotes among womenundergoingIVF/ICSItreatment. https://doi.org/10.1289/EHP11998