Use of fertility medications and cancer risk: a review and update

Abstract

Structured Abstract Purpose of Review There is increasing use of fertility medications for ovulation induction and ovarian stimulation for in vitro fertilization in the treatment of female infertility. In this review, recent literature regarding the association between fertility medication and cancer risk is reviewed. Recent Findings Several important publications have recently addressed the relationship between use of fertility medications and cancer risk. There are methodological limitations to many of these studies, including unique challenges in studying rare cancers that often develop several years after the time of fertility medication exposure. While infertility per se is a risk factor for some female cancers, including breast, endometrial, and ovarian cancer, most studies do not show a significant risk of these cancers with the use of fertility medications. Some studies, however, have shown a possible increased relative risk of borderline ovarian cancer, although the increased absolute risk is small without a clear causal relationship. Summary The collective data regarding the risk of developing cancer from use of fertility medications are reassuring, although several methodological issues in these studies limit definitive conclusions.

Melanoma Following In Vitro Fertilization: Co-incident or Coincidence?

“…However, studies have also noted an increased risk of malignancy associated with in vitro fertilization; the use of fertility medications has been observed to modestly increase the risk of borderline ovarian cancer and high doses or multiple cycles of clomiphene citrate may increase the risk of endometrial cancer. However, breast, cervical, colon, and thyroid cancer do not appear to be more frequent in women who had prior in vitro fertilization [11][12].…”

“…Melanoma risk has been found to be higher in nulliparous women [13]. However, most retrospective studies evaluating the occurrence of melanoma after the use of fertility drugs have not shown an increase risk of this malignancy [11][12][13]. Yet, melanoma has occurred in women following in vitro fertilization [14]; indeed, melanoma risk has been noted to be greater in women aged 30 years and older-as compared to women less than 30 years of age-at first birth following in vitro fertilization [13].…”

Current Resources for Evidence‐Based Practice, November/December 2019

“…This fact underpins the theory of why fertility drugs may lead to ovarian cancer. The incessant ovulation theory posits that uninterrupted rupture of the ovarian epithelium damages the epithelial cells, leading to dysplastic change, as also occurs in women who never have pregnancies to interrupt ovulation . Additionally, the polyovulation achieved with fertility drugs may lead to more ovarian epithelial trauma .…”

“…The incessant ovulation theory posits that uninterrupted rupture of the ovarian epithelium damages the epithelial cells, leading to dysplastic change, as also occurs in women who never have pregnancies to interrupt ovulation . Additionally, the polyovulation achieved with fertility drugs may lead to more ovarian epithelial trauma . This theory may be in doubt because of the fact that women with other multiovulatory patterns do not have increased risk of cancer and the recognition that ovarian tumors can arise from the fallopian tubes.…”

“…This theory may be in doubt because of the fact that women with other multiovulatory patterns do not have increased risk of cancer and the recognition that ovarian tumors can arise from the fallopian tubes. Another theory is that increased gonadotropin levels act either directly or with raised estrogen levels to cause malignant changes . Lastly, it could be that incipient ovarian cancer is a predisposing cause of infertility.…”