PMID- 38150316 OWN - NLM STAT- MEDLINE DCOM- 20231229 LR - 20231229 IS - 1552-9924 (Electronic) IS - 0091-6765 (Print) IS - 0091-6765 (Linking) VI - 131 IP - 12 DP - 2023 Dec TI - Associations between Phthalate Metabolite Concentrations in Follicular Fluid and Reproductive Outcomes among Women Undergoing in Vitro Fertilization/Intracytoplasmic Sperm Injection Treatment. PG - 127019 LID - 10.1289/EHP11998 [doi] LID - 127019 AB - BACKGROUND: Phthalates have been reported to impair fertility in various studies. However, evidence exploring the associations between phthalate metabolites in follicular fluid (FF) and reproductive outcomes is lacking. OBJECTIVES: To investigate the associations between phthalate metabolite concentrations in FF and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes among women recruited from a fertility clinic. METHODS: We included 641 women undergoing IVF/ICSI treatment from December 2018 to January 2020. The levels of eight phthalate metabolites, including monoethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), were quantified in FF collected on the oocyte retrieval day. Associations between quartiles of individual phthalate metabolite concentrations and nine IVF/ICSI outcomes, including oocyte yield, mature oocyte number, two distinct pronuclei (2PN) zygote number, fertilization rate, blastocyst formation rate, implantation, clinical pregnancy, miscarriage, and live birth, were estimated with generalized linear models. The effects of phthalate mixtures on IVF/ICSI outcomes were assessed using Bayesian kernel machine regression (BKMR) models. RESULTS: After adjusting for relevant confounders, elevated quartiles of MBzP, MEHHP, and MEHP in FF were inversely associated with the numbers of retrieved oocytes, mature oocytes, and 2PN zygotes (all p for trends < 0.10). In comparison with the lowest quartile, the highest quartile of molar sum of di(2-ethylhexyl) phthalate metabolites (SigmaDEHP) was associated with a reduction of 9.1% [95% confidence interval (CI): - 17.1%, - 0.37%] and 10.3% (95% CI: - 18.8%, - 0.94%) in yielded oocyte and mature oocyte numbers, respectively. Furthermore, the BKMR models revealed inverse associations between phthalate mixtures and the numbers of retrieved oocytes and mature oocytes. We generally found null results for implantation, clinical pregnancy, miscarriage, and live birth. DISCUSSION: Certain phthalate metabolites in FF are inversely associated with the numbers of retrieved oocytes, mature oocytes, and 2PN zygotes among women undergoing IVF/ICSI treatment. https://doi.org/10.1289/EHP11998. FAU - Yao, Wen AU - Yao W AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. FAU - Liu, Chong AU - Liu C AUID- ORCID: 0000-0003-2014-6464 AD - Department of Environmental Health, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Qin, Dan-Yu AU - Qin DY AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. FAU - Yuan, Xiao-Qiong AU - Yuan XQ AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. FAU - Yao, Qing-Yun AU - Yao QY AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. FAU - Li, Ni-Jie AU - Li NJ AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. FAU - Huang, Yong AU - Huang Y AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. FAU - Rao, Wen-Tao AU - Rao WT AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. FAU - Li, Yu-Ying AU - Li YY AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. FAU - Deng, Yan-Ling AU - Deng YL AD - Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. AD - Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. FAU - Zeng, Qiang AU - Zeng Q AD - Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. AD - Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. FAU - Li, Yu-Feng AU - Li YF AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. LA - eng PT - Journal Article DEP - 20231227 PL - United States TA - Environ Health Perspect JT - Environmental health perspectives JID - 0330411 RN - 6O7F7IX66E (phthalic acid) RN - FU2EWB60RT (mono-(2-ethylhexyl)phthalate) RN - 0 (Environmental Pollutants) RN - 0 (Phthalic Acids) SB - IM MH - Pregnancy MH - Humans MH - Male MH - Female MH - Sperm Injections, Intracytoplasmic MH - *Abortion, Spontaneous MH - Follicular Fluid/metabolism MH - Bayes Theorem MH - *Environmental Pollutants MH - Semen/metabolism MH - Fertilization in Vitro MH - *Phthalic Acids/metabolism MH - Environmental Exposure PMC - PMC10752415 EDAT- 2023/12/27 18:42 MHDA- 2023/12/29 06:43 PMCR- 2023/12/27 CRDT- 2023/12/27 12:02 PHST- 2023/12/29 06:43 [medline] PHST- 2023/12/27 18:42 [pubmed] PHST- 2023/12/27 12:02 [entrez] PHST- 2023/12/27 00:00 [pmc-release] AID - EHP11998 [pii] AID - 10.1289/EHP11998 [doi] PST - ppublish SO - Environ Health Perspect. 2023 Dec;131(12):127019. doi: 10.1289/EHP11998. Epub 2023 Dec 27.