History of Infertility Holds Potential as New Cardiovascular Biomarker


The findings show a greater association with less ideal cardiovascular health scores for those who experienced their first infertility before age 35.

A history of infertility could be a new biomarker for predicting cardiovascular health in individuals who are female, according to results of a study published in JAMA Network Open. The study authors stated that these findings could be important for screening and prevention before disease onset.

According to the study authors, there is evidence suggesting reproductive traits might be able to help predict future cardiometabolic health. Further, infertility and cardiovascular disease (CVD) have common risk factors, including tobacco use, diet quality, and excess adiposity, according to the study investigators. The study authors wanted to determine if infertility could be a clinical marker for CVD screening and prevention. They aimed to see if infertility was associated with lower Life’s Essential 8 (LE8) scores, a validated composite score of cardiovascular health from the American Heart Association.

3 Key Takeaways

  1. A history of infertility in females could serve as a novel biomarker for predicting cardiovascular health, as suggested by the findings of a study published in JAMA Network Open.
  2. The study aimed to investigate if infertility could be a valuable clinical marker for screening and preventing cardiovascular disease before disease onset.
  3. Individuals with a history of infertility exhibited lower Life’s Essential 8 scores, specifically in the biomedical domain and blood biomarker subdomain.

In the study, investigators used data from Project Viva, which enrolled individuals at less than 22 weeks’ gestation from 1998 to 2002 from the Atrius Harvard Vanguard Medical Associated. The individuals included had health insurance or Medicare, lived in the greater metropolitan Boston area, and many had a college education, according to the study authors. Follow-up visits were conducted from 2017 to 2021, with a mean of 18.3 years after the index delivery.

At enrollment, individuals responded to questionnaires asking whether they were actively attempting to conceive and the number of menstrual cycles before conception. Individuals also reported on past pregnancies at midlife, including months to conceive, assisted reproductive treatment, and infertility diagnosis. Investigators also reviewed medical records, infertility diagnoses, and claims for infertility services, including assisted reproductive technology and fertility medication. CVD risk was evaluated with LE8, according to the study authors.

The investigators included 468 individuals in the analysis, with 73.8% being college graduates, 32.8% with a history of smoking, and 66.4% with an income over $70,000. There was a mean age of 50.6 years and 34.2% had a history of infertility. Overall mean LE8 scores were 76.3, with 76.5 for behavioral domain, 76 for biomedical domain, and 78.9 for blood biomarker subdomain. In the study, an overall score from 80 to 100 was considered high cardiovascular health, 50 to 79 was moderate, and 0 to 49 was low. The national mean for individuals aged 20 to 79 years is 68.1, according to the study authors.

The study authors reported that among individuals with an infertility history, the overall LE8 score was 2.94 points lower, the biomedical domain was 4.07 points lower, and the blood subdomain was 5.98 lower. In an analysis conducted for infertility with binary LE8 scores, the primary results were supported by decreased odds for all 3 previous scores.

Additionally, investigators conducted 2 separate analyses that showed fasting glucose was 6.31 mg/dL and hemoglobin A1C was 0.23% higher for those with a history of infertility when compared to those without. However, investigators found that a history of infertility was not associated with other biomedical factors or behavioral components, according to the results of the study.

Furthermore, the study authors reported that there were greater associations for those who experienced their first infertility before age 35 years compared to those who were at 35 years or older.

They also acknowledged limitations of the study including all individuals had insurance, health care, and were from the same geographical area and higher mean of LE8 scores compared to the national mean.


Nichols AR, Rifas-Shiman SL, Switkowski KM, Zhang M, et al. History of Infertility and Midlife Cardiovascular Health in Female Individuals. JAMA Netw Open. 2024;7(1):e2350424. doi:10.1001/jamanetworkopen.2023.50424

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