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. 2023 Sep 1;34(5):759-766.
doi: 10.1097/EDE.0000000000001631. Epub 2023 Jul 31.

The Relationship of Preconception and Early Pregnancy Isoprostanes with Fecundability and Pregnancy Loss

Carrie J Nobles  1 , Pauline Mendola  2 , Sunni L Mumford  3 , Robert M Silver  4 , Keewan Kim  5 , Neil J Perkins  5 , Enrique F Schisterman  3
Affiliations

The Relationship of Preconception and Early Pregnancy Isoprostanes with Fecundability and Pregnancy Loss

Carrie J Nobles et al. Epidemiology. .

Abstract

Background: Although redox stress likely plays an important role in reproductive health, the utility of peripheral biomarkers of oxidative stress, such as isoprostanes, during the periconception period remains underexplored. We evaluated the relationship between isoprostanes during preconception and gestational week 4 and women's reproductive health outcomes.

Methods: The Effects of Aspirin in Gestation and Reproduction trial (2007-2011) enrolled 1228 women attempting pregnancy and followed them for up to 6 menstrual cycles and throughout pregnancy if they became pregnant. We measured creatinine-adjusted, log-transformed isoprostanes 8-iso-prostaglandin F 2α (8-iso-PGF2α), its metabolite 2,3-dinor-iPF2α-III, and stereoisomers 5-iso-PGF2α-VI and 8,12-iso-iPF2α-VI in urine during preconception and 4 weeks gestation. We evaluated pregnancy among participants in each menstrual cycle using human chorionic gonadotropin (hCG) and defined pregnancy loss as observed loss following positive hCG. We calculated fecundability odds ratios (FOR) and 95% confidence intervals (CI) using discrete-time Cox proportional hazards models and relative risk of pregnancy loss using adjusted log-binomial models.

Results: Higher preconception isoprostane levels were associated with lower fecundability [e.g., FOR = 0.89; 95% CI = 0.81, 0.97 per interquartile range (IQR) increase in 8-iso-PGF2α]. Among 797 pregnancies, isoprostane levels increased from preconception to 4 weeks gestation (e.g., mean difference = 0.12; 95% CI = 0.10, 0.14 ng/mL for 8-iso-PGF2α) and higher isoprostanes at 4 weeks gestation were associated with lower risk of pregnancy loss (e.g., RR = 0.79; 95% CI = 0.62, 1.00 per IQR increase in 8-iso-PGF2α).

Conclusions: Preconception urinary isoprostanes may identify redox stress pathways associated with lower fecundability. However, the increase in isoprostanes into gestational week 4 and the associated lower risk of pregnancy loss may suggest confounding by latent factors in early pregnancy.

Trial registration: ClinicalTrials.gov NCT00467363.

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Conflict of interest statement

The authors report no conflicts of interest.

References

    1. Lu J, Wang Z, Cao J, Chen Y, Dong Y. A novel and compact review on the role of oxidative stress in female reproduction. Reprod Biol Endocrinol RBE. 2018;16(1):80. doi: 10.1186/s12958-018-0391-5 - DOI - PMC - PubMed
    1. Basu S. Isoprostanes: novel bioactive products of lipid peroxidation. Free Radic Res. 2004;38(2):105–122. doi: 10.1080/10715760310001646895 - DOI - PubMed
    1. Holland N, Huen K, Tran V, et al. Urinary Phthalate Metabolites and Biomarkers of Oxidative Stress in a Mexican-American Cohort: Variability in Early and Late Pregnancy. Toxics. 2016;4(1). doi: 10.3390/toxics4010007 - DOI - PMC - PubMed
    1. Ambroz A, Vlkova V, Rossner P, et al. Impact of air pollution on oxidative DNA damage and lipid peroxidation in mothers and their newborns. Int J Hyg Environ Health. 2016;219(6):545–556. doi: 10.1016/j.ijheh.2016.05.010 - DOI - PubMed
    1. Eick SM, Meeker JD, Brown P, et al. Associations between socioeconomic status, psychosocial stress, and urinary levels of 8-iso-prostaglandin-F2α during pregnancy in Puerto Rico. Free Radic Biol Med. 2019;143:95–100. doi: 10.1016/j.freeradbiomed.2019.07.032 - DOI - PMC - PubMed

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