Grand Rounds

Are Men Who Become Fathers Through IVF More Likely to Be Diagnosed with Prostate Cancer?

BACKGROUND AND PURPOSE:

Previous evidence suggests a possible link between infertility and prostate cancer risk
Al-Jebari et al. (BMJ, 2019) compared severity of prostate cancer between men undergoing ART vs those conceiving naturally

National register-based cohort study
Participants
- Fathers to children born alive in Sweden
- Grouped by mode of conception
Groups
- IVF
- ICSI
- Natural conception
Primary outcomes
- Prostate cancer diagnosis
- Age of onset
- Androgen deprivation therapy (serving as proxy for advanced or metastatic malignancy)

Total of 1,181,490 fathers
- IVF: 20,618
- ICSI: 14,882
- Natural conception: 1,145,990

IVF group
- Prostate cancer diagnosis: 0.37%
- Mean age at onset: 55.9 years
ICSI
- Prostate cancer diagnosis: 0.42%
- Mean age at onset: 55.1 years
Non-assisted means
- Prostate cancer diagnosis: 0.28%
- Mean age at onset: 57.1 years
ART conception was significantly associated with increased risk of prostate cancer vs natural conception
- ICSI: Hazard ratio (HR) 1.64 (95% CI, 1.25 to 2.15)
- IVF: HR 1.33 (95% CI, 1.06 to 1.66)
ART conception was also associated with increased risk of early onset disease (>55 years)
- ICSI: HR 1.86 (95% CI, 1.25 to 2.77)
- IVF: HR 1.51 (95% CI, 1.09 to 2.08)
Men who conceived through ICSI and developed prostate cancer received androgen deprivation therapy (proxy for metastatic disease) at rates similar to natural conception (P=0.07)

Fathers who used ICSI to conceive had a 60% higher risk for prostate cancer (especially early onset) vs natural conception | IVF associated with a 30% higher risk compared with men who conceived naturally
The authors suggest that men with infertility who achieve fatherhood through ART are a risk group for prostate cancer and screening may be beneficial
Authors acknowledge study limitations including
- Study did not include infertile men who could not father children | Mean age at follow up only 45 years so study could not assess lifetime risks
An accompanying editorial suggests male infertility possibly related to abnormalities in the Y chromosome could explain the increased cancer risk
- However, the authors of the editorial go on to state that

In the absence of a plausible mechanism of action or proof of causation, justifying screening for prostate cancer in all infertile men is difficult

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