In vitro fertilization and risk of breast and gynecologic cancers A retrospective cohort study within the Israeli Maccabi Healthcare Services

Capsule:
Among 87,403 infertile women, IVF was not significantly associated with breast or gynecologic cancers. Among women receiving four or more cycles, ovarian cancer was nonsignificantly elevated, supporting further risk monitoring.

Authors:
Louise A. Brinton, Ph.D., Britton Trabert, Ph.D., Varda Shalev, M.D., Eitan Lunenfeld, M.D., M.H.A., Tal Sella, M.D., Gabriel Chodick, Ph.D.

Volume 99, Issue 5, Pages 1189-1196, April 2013

Abstract:

Objective:
To assess long-term cancer risks associated with in vitro fertilization (IVF).

Design:
Record-linkage study.

Setting:
Health maintenance organization in Israel.

Patients:
A total of 87,403 women evaluated and/or treated for infertility on or after September 25, 1994 who developed cancer through June 22, 2011: 522 breast, 41 endometrial, 45 ovarian, 311 in situ cervical and 32 invasive cervical cancers were identified.

Intervention(s):
None.

Main Outcome Measures:
Hazard ratios (HRs) for specific cancers.

Results:
We found no significant relationships of IVF exposures to the risks of breast, endometrial or ovarian cancers. Compared to women with no fertility treatment, the HR associated with IVF was 1.58 (95% CI 0.75-3.29), with higher risk among those receiving 4+ cycles (1.78, 95% CI 0.76-4.13). There was also a non-significantly elevated risk for endometrial cancer among women who received 1-3 IVF cycles (1.94, 0.73-5.12), but additional cycles were associated with lesser risk. In contrast, in situ cervical cancer was significantly reduced and invasive cervical cancer non-significantly reduced among women receiving IVF as well as other fertility treatments.

Conclusions:
Our results regarding long-term effects were largely reassuring, but women receiving IVF should continue to be monitored given that the procedures involves potent ovulation stimulators and repeated ovarian punctures.

  • Audrey Gaskins

    While this study does address a pertinent question that remains somewhat unclear in the field I have a couple of questions for the authors. First, given the young age of the women included in this study I’m assuming the majority of breast cancers were pre-menopausal. However, if there were also post-menopausal breast cancers, it would be interesting to evaluate these outcomes separately since risk factors differ for these two types of cancers particularly in regards to hormonal exposures. Second, my biggest concern, is why so many women (~50%) were missing underlying fertility diagnoses? Why do the authors think this was not recorded in the EMR? I applaud the authors for attempting to control for some of the confounding by infertility diagnosis (yes/no) but there still remains the possibility of confounding by type of infertility diagnoses which could not be addressed in this paper due to the large amount of missing data.

  • This study addresses a highly relevant and heavily researched epidemiologic topic- risk of cancer in patients with infertility / after various infertility treatments. It impresses with its large “n”, good registry, and an interesting study design, comparing patients according to the type of fertility treatment they had. However, assessed outcomes are relatively rare, and that groups get very small when patients are split into exposure subgroups. Therefore I am not sure if there is something fundamentally new that this study adds to the literature (correct me if I am wrong!)- although it may further help us reassure patients about the safety of Infertility treatment in general. One other minor comment: I am curious that PCOS was defined by LH/FSH (>2.5) and maximum E2 level (<250)- I am not familiar with that definition. Can you comment? Thank you

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