April 4, 2022
FACTS Infertility Awareness Series
Female Infertility and Comorbidities: A Research Review
By Szumei Leow
Executive Director’s Note: With National Infertility Awareness Week coming up the last week of April, we will feature a series of articles to raise awareness about infertility, the many aspects of health related to this condition and the important role fertility awareness-based methods may play in the diagnosis and treatment of infertility as well as some of the common underlying causes. We begin with a research summary by Szumei Leow, highlighting the link between infertility and other health conditions, including mental health disorders, malignancies, metabolic dysfunction, and cardiovascular disease. Ms. Leow summarized this research during the online FACTS fertility awareness elective now completed by over 400 students since the fall of 2020.
Infertility is a common affliction, with an estimated 8 to 12% of reproductive-age couples affected by the condition around the world. The most powerful negative predictive factor of infertility is increased age of the woman at the time of conception. As more women elect to postpone childbearing until later in life  more couples are feeling the effects of infertility. However, many other factors also influence a couple’s ability to conceive, including lifestyle and environmental factors. A 2016 study by Hanson et al. systematically reviewed published literature regarding the association between infertility and other health conditions, specifically psychiatric disorders, malignancy, metabolic dysfunction, and cardiovascular disease. The goal of the study was to identify links between female infertility and these conditions in order to gain further understanding about the long-term health effects and risks.
A literature review of PubMed/MEDLINE was conducted to identify articles related to infertility and its impact on women’s health. Of the 425 article titles reviewed, only 26 were determined to be highly relevant to the aims of the study and were included in the study. The primary inclusion criteria for reviewed studies was female infertility; however, many studies with populations of associated reproductive disorders such as PCOS and endometriosis were also included due to the close link between these diseases and infertility.
Summary of Results
Infertility and Mental Health
The association between infertility and mental health was evaluated in six of the 26 studies included in the review. Each found that women with a history of infertility had an increased risk of developing mental health disorders, including depression and anxiety. In four studies, the primary population consisted of women with PCOS, suggesting a correlation between PCOS and mental health disorders.
Infertility and Gynecologic Malignancies
The relationship between infertility and the development of gynecologic malignancy was of particular interest. Nine studies included in the review evaluated the link between infertility and the development of breast cancer; nine evaluated the association with ovarian cancer; and five evaluated the link with endometrial cancer. There was not strong corroboration of evidence linking infertility to breast cancer or ovarian cancer. However, four of the five studies evaluating the link between infertility and endometrial cancer found a strong relationship between the two, particularly if the woman was diagnosed with unexplained infertility or PCOS at a young age.
Infertility and Cardiovascular Health
Eight of the 26 studies evaluated the relationship between infertility and metabolic dysfunction or cardiovascular health, and all showed a correlation between infertility and increased cardiovascular risk, including higher myocardial infarction rates, higher insulin resistance, increased rate of metabolic syndrome, and increased risk for non-alcoholic fatty liver disease. Of the eight studies reviewed, six specifically included a population of women with PCOS.
“Studies showed a correlation between infertility and increased cardiovascular risk, including higher myocardial infarction rates, higher insulin resistance, and increased rate of metabolic syndrome.”
The results of this study suggest that women with infertility may be at higher risk to develop other health conditions, but these associated diagnoses may not present simultaneously with infertility. Therefore, identifying diseases that a woman is at higher risk of developing at the time of her infertility diagnosis can help both clinicians and patients make informed decisions about follow-up care and future screenings. It is important to note that referral to comprehensive medical care outside of immediate infertility treatment is an important aspect of caring for women with infertility, but appropriate follow-up can be hard to achieve in underserved populations and in developing countries where access to healthcare is limited.
Several studies investigated patients with PCOS as being at higher risk of developing additional health concerns. As PCOS can often cause infertility, it is hard to determine which diagnosis is the predisposing factor for developing these other associated health concerns. Correctly pinpointing the root cause of a woman’s infertility was a major hurdle for the researchers included in this literature review. Future studies would benefit from isolating specific subsets of women with infertility to better identify which causes of infertility are associated with specific health outcomes.
 Vander Borght M, Wyns C. Fertility and infertility: Definition and epidemiology. Clin Biochem. 2018;62:2-10. doi:10.1016/j.clinbiochem.2018.03.012.
 O’Brien Y, Wingfield MB. Reproductive ageing-turning back the clock?. Ir J Med Sci. 2019;188(1):161-167. doi:10.1007/s11845-018-1769-2.
 Hanson B, Johnstone E, Dorais J, Silver B, Peterson CM, Hotaling J. Female infertility, infertility-associated diagnoses, and comorbidities: a review. J Assist Reprod Genet. 2017;34(2):167-177. doi:10.1007/s10815-016-0836-8
About the Author
Szumei Leow is a fourth-year medical student attending Kansas City University. She will graduate in May 2022 and will begin her pediatrics residency at Children’s Mercy Hospital this summer. She hopes to empower her future patients by sharing the knowledge she gained about FABMs to help teenagers and young women understand and feel comfortable with their bodies.