Risk factors for atypical hyperplasia and endometrial cancer in the infertility population: a case-control study

OBJECTIVE: To estimate the incidence and identify risk factors for atypical endometrial hyperplasia (AH) and endometrial cancer (EC) in American women undergoing infertility evaluation. DESIGN: Case-control study. SETTING: Academic reproductive endocrinology and infertility practice. PATIENT(S): Female patients (18–50 years) seeking infertility evaluation from January 1, 2009 to December 1, 2018. Patients with known genetic predisposition to cancer or prior cancer diagnosis were excluded. Cases were defined as patients diagnosed with AH or EC during infertility workup (n = 22). Controls without AH or EC were randomly selected in a 10:1 ratio (n = 220) from all women undergoing infertility evaluation in the same year. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Incidence of AH or EC and odds of AH or EC accounting for age, race, body mass index (BMI), and ovulatory dysfunction. RESULT(S): Twenty-two cases of AH or EC were identified among 11,569 women undergoing infertility evaluation (incidence 2 per 1,000 women, 95% confidence interval [CI] 1.2–2.9 per 1,000). Of these women, 68% had a BMI ≥30 kg/m(2) compared with 25% of controls. In multivariable analyses, women with a BMI ≥30 kg/m(2) were 5.9 times more likely to be diagnosed with AH or EC (adjusted odds ratio 5.9, 95% CI 2.0–17.2). Women with ovulatory dysfunction were 3.4 times more likely to be diagnosed with AH or EC (adjusted odds ratio 3.4, 95% CI 1.1–10.1). CONCLUSION(S): The incidence of AH and EC in a population of women undergoing infertility evaluation is 10 times that in the general population of premenopausal women. Obesity is the strongest independent risk factor for AH and EC in women with infertility.