History of infertility and risk of gestational diabetes mellitus: a prospective analysis of 40,773 pregnancies
Open accessAbstract
Studies of delayed conception and risk of gestational diabetes (GDM) are sparse, although common underlying mechanisms are plausible, including insulin resistance and inflammation. The association between a history of infertility and GDM was assessed prospectively among 40,773 eligible pregnancies in the US Nurses' Health Study II cohort (1989-2001). Biennial questionnaires provided updated information on infertility and several lifestyle and health-related characteristics. Multivariable log-binomial models with generalized estimating equations were used to compute risk ratios and 95% confidence intervals, adjusting for age, prepregnancy body mass index (weight (kg)/height (m)(2)), and additional potential confounders. GDM occurred among 1,405 (5.2%) women. A prepregnancy history of infertility was reported by 5,497 (20.5%) participants and was significantly associated with a 39% greater risk of GDM (risk ratio (RR) = 1.39, 95% confidence interval (CI): 1.24, 1.57; P < 0.001). Underlying reasons for infertility associated with GDM included ovulation disorders (RR = 1.52, 95% CI: 1.23, 1.87; P < 0.001) and tubal blockage (RR = 1.83, 95% CI: 1.20, 2.77; P = 0.005). The association of cervical mucus disorder with GDM was of borderline significance (RR = 1.70, 95% CI: 0.88, 3.30; P = 0.11). Endometriosis (RR = 1.27, 95% CI: 0.70, 2.31; P = 0.43) and male factor infertility (RR = 1.12, 95% CI: 0.78, 1.61; P = 0.55) were not associated with GDM risk. These novel findings suggest that infertility, particularly from ovulation disorders and tubal blockage, is associated with an increased GDM risk. Further research is needed to identify mechanisms or common underlying metabolic dysfunction explaining these observations.
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Infertility due to tubal disease has been positively associated with risk of gestational diabetes.
“In addition, we have previously found positive associations between infertility due to tubal disease and risk of other cardio-metabolic conditions including gestational diabetes (24) and type 2 diabetes (Tobias, under review for publication).”
From Infertility, fertility treatment, and risk of hypertension (2015) · cites this paper as [24]
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Soria-Contreras, D. C., Perng, W., Rifas-Shiman, S. L., Hivert, M., Oken, E., & Chavarro, J. E. (2022) · Figshare · doi:10.6084/m9.figshare.20267374
Wang, J., Liu, Q., Deng, B., Chen, F., Liu, X., & Cheng, J. (2021) · Figshare · doi:10.6084/m9.figshare.13550700
Afaneh, I., Hussien, A. M., Jabareen, M., Abdallah, J., Abudaowd, S., Fasfoos, A., Abbas, A., Alhalayqa, O., & Maraqa, B. N. (2026) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-025-02083-y
Wyatt, S., Sørbye, L. M., Kvalvik, L. G., Singh, A., & Skjærven, R. (2026) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.1111/aogs.70366
- Authors
- Tobias, D. K., Chavarro, J. E., Williams, M. A., Buck Louis, G. M., Hu, F. B., Rich-Edwards, J., Missmer, S. A., & Zhang, C.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Tobias, D. K.
- Zhang, C.
- Venue
- American Journal of Epidemiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-08-15
- Volume
- 178
- Issue
- 8
- Pages
- 1219-1225
- ISSN
- 0002-9262 (ISSN-L)
- 1476-6256
- PMC
- PMC3792729
- OpenAlex
- W2138956810
- Cited by
- 54
- References
- 40
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 6 · 2022: 6 · 2021: 6 · 2020: 4 · 2019: 3 · 2018: 5 · 2017: 5 · 2016: 2 · 2015: 6 · 2014: 2 · 2013: 1
- FWCI
- 4.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- Locations
- American Journal of Epidemiology (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association (7‐12‐MN‐34)
- Brigham and Women's Hospital
- National Institutes of Health (HHSN275201000020C, DK46200)
- U.S. Public Health Service (HSN275201000020C)
- National Cancer Institute (CA50385, R01CA050385)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058845, P30DK046200, P30 DK46200-18, DK58845)
- National Institute of Child Health and Human Development (HHSN275201000020C, CA50385)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (# HHSN275201000020C)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Assisted Reproductive Technology and Twin Pregnancy
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Health and Technologies
- Keywords
- infertility, gestational diabetes mellitus, ovulatory dysfunction, tubal occlusion, endometriosis, male factor infertility, pre-pregnancy body mass index, insulin resistance, inflammation, Nurses' Health Study II
- MeSH terms
- Adult, Female, Humans, Infertility, Female, Pregnancy, Prospective Studies, Risk Factors, Odds Ratio, Diabetes, Gestational
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