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NEW YORK (Reuters Health) – Infertility in women is associated with a higher risk of developing cancer, though the absolute risk is very low, at 2%, researchers say.

“The results need to be interpreted with caution,” Dr. Gayathree Murugappan of Stanford Hospital and Clinics in Palo Alto, California told Reuters Health by email. “The findings of our study were associative, not causative. Our hope is that in the future we will be able to understand the etiologies of the risk associations we uncovered.”

“For example, is there a common underlying mechanism that can cause cancer and infertility? This will help providers more adequately counsel infertile women about the health risks they face,” she said.

Using an insurance claims database, Dr. Murugappan and colleagues studied 64,345 infertile women identified by diagnosis, testing or treatment from 2003 to 2016, and compared them to 3,128,345 fertile women seeking routine gynecologic care.

As reported online March 13 in Human Reproduction, after adjustment for age at first visit, nulliparity, race, smoking, obesity, number of visits per year and highest level of education, infertile women had an overall higher risk of developing cancer compared to fertile women (2.0% vs. 1.7%; adjusted hazard ratio = 1.18).

Infertile women were also at higher risk for uterine cancer (0.10% vs. 0.06%; aHR = 1.78); ovarian cancer (0.14% vs. 0.09%; aHR 1.64); lung cancer (0.21% vs. 0.21%, aHR = 1.38); thyroid cancer (0.21% vs. 0.16%; aHR = 1.29); leukemia (0.10% vs. 0.06%; aHR = 1.55) and liver and gallbladder cancer (0.05% vs. 0.03%; aHR = 1.59).

In a subset of women who became pregnant and had a delivery during enrollment, risks for uterine and ovarian cancer were similar between infertile and fertile women, and the risk of uterine cancer was similar between groups in a subgroup analysis that excluded women with polycystic ovary syndrome and endometriosis.

Dr. Brooke Hodes-Wertz, a reproductive endocrinologist and infertility specialist at NYU Langone Health’s Fertility Center, said in an email to Reuters Health, “The issue of whether infertility treatments or infertility patients in general have higher risk of malignancies has been hard to study.”

“Looking at insurance coding and claims doesn’t give you the complete picture for many reasons,” she noted. “Patients with different infertility diagnoses act very differently and have different profiles. It is hard to lump them all together and make strong conclusions.”

“In addition, counting (someone who has undergone) fertility testing as an infertility patient isn’t a great way of selecting infertility patients,” she said. “Fertility testing is often requested by patients not trying to conceive, but (who) want a better understanding where their fertility is if they are considering delaying childbearing.”

“These results are preliminary and patients should be aware that there is a possibility that there is more risk but we aren’t sure of a mechanism, the results are limited and the overall risk is still very low,” Dr. Wertz concluded.


Hum Repro 2019.

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