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Men treated for infertility with intracytoplasmic sperm injection (ICSI) had a significantly increased risk of early-onset prostate cancer, according to data from several large registries.

Use of ICSI to facilitate conception was associated with a 47% higher risk of prostate cancer as compared with men who conceived naturally. Analysis of cancer cases by age at diagnosis showed that men who underwent ICSI had almost a three-fold greater risk of developing prostate cancer before age 50 but not at older ages.

Despite the association with ICSI, the results did not implicate ICSI as the causative factor in early-onset prostate cancer, reported Yahia Al-Jebari, of Lund University in Sweden, and colleagues at the (ESHRE) meeting in Barcelona. Instead, the study added to existing evidence of an association between impaired sperm production and an increased risk of prostate cancer.

"The increased risk of prostate cancer is definitely not because of the ICSI treatment per se, which we know has no biological impact on the male," Al-Jebari said in a statement. "In Sweden, ICSI is reserved for men who cannot conceive through in vitro fertilization (IVF), and we would expect most fertile men having fertility treatments to be in the IVF group. So in this study, the ICSI fathers are highly selected and generally have very poor semen quality."

A separate ESHRE study suggested that infertility in women increases the risk of ovarian cancer, but that ovarian stimulation associated with IVF is not to blame, reported Anja Pinborg, MD, of Copenhagen University Hospital in Denmark.

ICSI and Prostate Ca

Previous studies yielded inconsistent data regarding the association between male infertility and prostate cancer. Registry-based studies showed a lower risk of prostate cancer among childless men as compared with men who were biological fathers, Al-Jebari's group noted. Other studies suggested that men with impaired fertility have an increased risk of prostate cancer as compared with fertile men.

To continue investigation of male infertility and prostate cancer, researchers analyzed data from birth, assisted reproduction, and cancer registries in Sweden. They identified all men who fathered children from 1994-2014 and compared those who conceived with the aid of ICSI or IVF versus men who conceived naturally. Follow-up continued to 2016.

The analysis included 1.2 million men, 52 million person-years of follow-up, and 3,211 prostate cancer diagnoses. The data showed that men who had undergone ICSI had a 47% increase in the hazard for prostate cancer versus the control group (95% CI 1.15 to 1.89, P=0.002). Conception via IVF did not increase the risk of prostate cancer versus natural conception (HR 1.14, 95% CI 0.91 to 1.43, P=0.25).

Stratification of the cancers by age at diagnosis showed that conception with the aid of ICSI increased the hazard for prostate cancer diagnosis before age 50 to 2.94 versus the control group (95% CI 1.84 to 4.71, P<0.001). ICSI was not associated with an increased risk of later-onset prostate cancer. After excluding men whose prostate cancer diagnosis occurred before conception, the hazard for prostate cancer remained elevated, overall (HR 1.32, 95% CI 1.01 to 1.72, P=0.045) and for early-onset disease (HR 2.54, 95% CI 1.52 to 4.24, P<0.001).

Al-Jebari acknowledged that relatively few men in the ICSI group developed prostate cancer (n=63) and that the trial did not include comparisons with men who had never fathered children.

IVF and Ovarian Ca

The study of IVF and ovarian cancer had its origin in a hypothesized association of the risk-increasing effect of IVF. Previous studies led to conflicting findings, Pinborg's group noted. Further confounding the issue, several studies showed that nulliparous women have an increased risk of ovarian cancer.

In an attempt to clarify the relationship between IVF and ovarian cancer, investigators analyzed data from the Danish National ART-Couple II (DANAC II) cohort, which includes all women receiving assisted reproductive technology (ART) in Denmark from 1994-2015. Each DANAC II woman was matched by age with 10 women with no history of ART. Follow-up in both groups continued until a first cancer diagnosis, death, loss to follow-up or Dec. 31, 2015.

Data analysis included 58,472 women who received ART and 549,210 who did not. Both groups had a low incidence of ovarian cancer, which was nonetheless higher in the women who had received ART (0.11% vs 0.06%, HR 1.20, 95% CI 1.10 to 1.31).

Subgroup analysis showed that female-origin infertility was associated with an ovarian cancer incidence in nulliparous women (HR 2.38, 95% CI 2.17 to 2.60) similar to that of nulliparous women in the non-ART control group (HR 2.03, 95% CI 1.89 to 2.19). ART for male-factor infertility or unexplained causes was associated with a reduced risk of ovarian cancer (HR 0.87, 95% CI 0.76 to 1.00).

ART's association with excess ovarian cancer risk reached a peak in the first 2 years after initiation of treatment and disappeared altogether after 12 years, suggesting possible detection bias during ART treatment.

Calling the data reassuring, Pinborg said in a statement, "I would advise infertile women contemplating ART treatment to go ahead. Ovarian stimulation itself is not introducing any excess risk of ovarian cancer."