Evidence map›Paper›PMID 41903804›Full record

ArticleF&S science2026

Follicular fluid per- and polyfluoroalkyl substances, metabolomics, and live birth after in vitro fertilization: a pilot study.

Elvira S Fleury, Emily L Silva, Elizabeth Peebles, Anna S Young, Catherine E Mullins, Douglas I Walker, Zifan Wang, Daniel W Cramer, Allison F Vitonis, Kathryn L Terry and 2 more

Abstract read
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Article in F&S science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Elvira S FleuryDepartment of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts. Electronic address: Elvira_fleury@g.harvard.edu.
Emily L SilvaDepartment of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
Elizabeth PeeblesDepartment of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
Anna S YoungGangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia.
Catherine E MullinsGangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia.
Douglas I WalkerGangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia.
Zifan WangDepartment of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
Daniel W CramerDepartment of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Allison F VitonisDepartment of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Kathryn L TerryDepartment of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Bo RuedaDepartment of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts; Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Shruthi MahalingaiahDepartment of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.

Funding

Novel biomarkers and pathways of persistent endometriosis-associated pain across the life courseR01HD111242 · NICHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Sawsan As-Sanie, Kathryn L. Terry · 2023 to 2026
$3.2M
Mapping the blood cancer exposome for environmental risk profiles of mature B-cell neoplasmsR01ES032831 · NIEHS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Douglas Ian Walker · 2022 to 2026
$2.3M
EPIDEMIOLOGIC AND BIOLOGIC PREDICTORS OF IVF SUCCESSR01HD032153 · NICHD · BRIGHAM AND WOMEN'S HOSPITAL · PI CRAMER, DANIEL WILLIAM · 1994 to 2002
$1.5M
Transcriptomic Changes during early endometriotic lesion developmentR01HD116742 · NICHD · HENRY FORD HEALTH + MICHIGAN STATE UNIVERSITY HEALTH SCIENCES · PI Gregory Willis Burns · 2025 to 2026
$1.4M
The role of neurotrophins in chronic pelvic pain and central sensitization among adolescents and women with endometriosisR21HD107515 · NICHD · MERRIMACK COLLEGE · PI SHAFRIR, AMY LEE · 2022 to 2023
$516k
Mapping the cosmetic chemical exposome and its role in female fertilityK99ES036289 · NIEHS · EMORY UNIVERSITY · PI YOUNG, ANNA SWIFT · 2024 to 2025
$251k
NICHD NIH HHS R01 HD032153NICHD NIH HHS R01 HD111242NICHD NIH HHS R01 HD116742NICHD NIH HHS R21 HD107515NIEHS NIH HHS K99 ES036289NIEHS NIH HHS R01 ES032831
6 · The paper itself

Abstract

objectiveTo evaluate the association between per- and polyfluoroalkyl substances (PFAS) in follicular fluid (FF) and live birth after in vitro fertilization (IVF) and characterize the FF metabolome in relation to both.

designRetrospective cohort. SUBJECTS: Thirty-six women who underwent IVF treatment at 1 of the 3 centers in Eastern Massachusetts between 1999 and 2003. EXPOSURE: Twenty-four PFAS were measured in FF retrieved from the first follicle aspirated during the first treatment cycle. The 8 PFAS detected in >90% of samples were evaluated.

main outcome measuresWe analyzed the FF metabolome using untargeted liquid chromatography high-resolution mass spectrometry. We used linear regression to estimate associations between FF PFAS and metabolic feature intensities, and logistic regression to estimate associations of FF PFAS and metabolites with live birth, adjusting for age and infertility type. We subsequently conducted pathway enrichment analyses and used a meet-in-the-middle approach to screen for overlapping metabolic pathways associated with FF PFAS and live birth.

resultsHigher FF perfluoroheptanesulfonic acid (PFHpS) was associated with lower odds of live birth (odds ratio = 0.42 [95% confidence interval: 0.15-0.97]). All other FF PFAS, except perfluorobutanesulfonic acid (PFBS), were also inversely associated with live birth, although confidence intervals included the null value. We evaluated 27,903 features detected in >25% of participant samples. For PFAS-feature associations, the top 5% of features for each PFAS were enriched for bile acid biosynthesis. Thirty-eight FF metabolic pathways enriched for features associated with live birth (yes/no) overlapped with pathways enriched for features associated with perfluorooctanoic acid (PFOA), PFHpS, or perfluorohexanesulfonic acid (PFHxS). These included pathways related to lipid (n = 11), carbohydrate (n = 9), and vitamin and cofactor metabolism (n = 6), among others.

conclusionHigher FF PFAS concentrations were associated with lower odds of achieving live birth, although most 95% confidence intervals included the null. Metabolic pathways enriched for features associated with live birth overlapping with those associated with FF PFAS were related to lipid, carbohydrate, vitamin, and cofactor metabolism. Although our sample size was small, our findings align with other studies characterizing environmental exposures in reproductive organs and using the metabolome to assess their impact on fertility.

Indexed as

Fertilization in VitroFluorocarbonsFollicular FluidLive BirthMetabolomicsAdultFemaleHumansMetabolomePilot ProjectsPregnancyRetrospective StudiesFluorocarbonsIVFMetabolomicsPFAS

Identifiers

PMID41903804
PMCPMC13657790

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