Phthalate metabolites in urine and follicular fluid in relation to menstrual cycle characteristics in women seeking fertility assistance.

BACKGROUND: Phthalates have been shown to disrupt the estrous cycle in animal studies. However, epidemiological research investigating their associations with menstrual cycle characteristics is limited. OBJECTIVE: To explore the relationships between phthalate exposure and menstrual cycle characteristics among women seeking fertility assistance. METHODS: We determined the levels of eight phthalate metabolites in both follicular fluid (FF) and urine specimens collected from 441 women in the Tongji Reproductive and Environmental (TREE) cohort, using high-performance liquid chromatography and tandem mass spectrometry. Information about menstrual cycle parameters was obtained through a questionnaire. The impacts of individual and joint exposure to phthalates on menstrual cycle characteristics were assessed using multivariable linear regression, Poisson regression, and quantile g-computation approaches. RESULTS: After adjusting for relevant covariates, we found that per log10-unit increase in mono(2-ethylhexyl) phthalate (MEHP) level in urine specimens was associated with a decrease of 0.20 days (95 % CI: -0.37, -0.03) in bleeding duration. We also observed that mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) and the sum of di(2-ethylhexyl) phthalate (DEHP) metabolites (∑DEHP) concentrations in FF samples were inversely related to cycle length [ß = -1.92 (95 % CI: -3.10, -0.75) and -1.87 (95 % CI: -3.56, -0.19), respectively]. However, we generally observed null associations between phthalate metabolites and irregular cycle, dysmenorrhea, hypomenorrhea, or cycle length variation. Furthermore, we also found that phthalate metabolite mixtures in FF and urine were generally unrelated to menstrual cycle characteristics. CONCLUSION: Our findings suggest that some DEHP metabolites in FF and urine are inversely associated with menstrual cycle length and menstrual bleeding duration in women attending a fertility center.

Associations between Phthalate Metabolite Concentrations in Follicular Fluid and Reproductive Outcomes among Women Undergoing in Vitro Fertilization/Intracytoplasmic Sperm Injection Treatment.

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 (ΣDEHP) 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.

The association between caffeine and alcohol consumption and IVF/ICSI outcomes: A systematic review and dose-response meta-analysis.

INTRODUCTION: The objective of this study was to evaluate the association between caffeine and alcohol consumption and in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) outcomes. MATERIAL AND METHODS: The protocol was registered in the PROSPERO database on May 23, 2021 (registration number: CRD42021256649), and updated on August 4, 2022. Two researchers performed a literature search in the PubMed, Embase, and MEDLINE databases for articles published before July 15, 2022 independently. Studies investigating the association between caffeine and alcohol consumption and IVF/ICSI outcomes were included, and studies reporting the consumption amount were analyzed using a one-stage robust error meta-regression-based method to explore potential dose-response relation. Funnel plot was used to assess publication bias if more than 10 studies were included. RESULTS: Twelve studies on caffeine consumption and 14 studies on alcohol consumption were included in the systematic review, of which seven and nine were eligible for the meta-analysis. These studies included 26 922 women and/or their spouses who underwent IVF/ICSI treatment. Women's and men's caffeine consumption was not significantly associated with the pregnancy rate (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.85-1.12; OR 0.93, 95% CI 0.75-1.14; respectively) and the live birth rate (OR 0.98, 95% CI 0.89-1.08; OR 0.98, 95% CI 0.86-1.12; respectively) of IVF/ICSI. Maternal alcohol consumption was negatively associated with pregnancy after IVF/ICSI treatment (OR 0.83, 95% CI 0.69-1.01). Paternal alcohol consumption was negatively associated with partner's live birth after IVF/ICSI treatment (OR 0.88, 95% CI 0.79-0.99). Compared with abstainers, the chance of achieving a pregnancy after IVF/ICSI treatment decreased by 7% for women who consumed 84 g alcohol per week (OR 0.93, 95% CI 0.90-0.98), and the chance of partners achieving a live birth decreased by 9% for men who consumed 84 g alcohol per week (OR 0.91, 95% CI 0.88-0.94). CONCLUSIONS: There was no association between caffeine consumption and pregnancy or live birth rate of IVF/ICSI. Women's alcohol consumption was associated with decreased pregnancy rate after IVF/ICSI treatment when weekly consumption was greater than 84 g. Men's alcohol consumption was associated with decreased live birth rate after IVF/ICSI treatment when weekly consumption was greater than 84 g.