Men becoming fathers via assisted reproduction have a significantly higher risk of prostate cancer
Men who used sperm injection had a 60% higher risk, and those who used in vitro fertilization had a 30% higher risk compared with men conceiving naturally
Men who become fathers through assisted reproduction techniques have a substantially high risk of prostate cancer and early-onset prostate cancer compared with men who conceive naturally.
Prostate cancer and male infertility are both very common disorders, which affect about 10% and 8%, respectively, of all men in Western societies.
For the study, fathers were grouped according to fertility status by mode of conception: 20,618 (1.7%) by in vitro fertilization (IVF), 14,882 (1.3%) by intra-cytoplasmic sperm injection (ICSI), and 1,145,990 (97%) by natural conception.
"The main conclusion of this study, comprising virtually all men fathering a child in Sweden during two decades, is that men who achieved fatherhood through assisted reproduction had a remarkably high risk of prostate cancer. Fathers who used ICSI had a 60% higher risk, and those who used IVF had a 30% higher risk, compared with men who conceived naturally," say the researchers in their findings published in The BMJ.
The increase in risk was most pronounced before the age of 55 years. According to the analysis, the risk of early-onset prostate cancer — diagnosed before the age of 55 — was substantially high for men fathering children through ICSI, a technology used for men with the most severe forms of infertility. They were 1.64 times more likely to have prostate cancer as compared with natural conception.
"In the study, men who had undergone ICSI treatment had a statistically significantly increased risk of prostate cancer (hazard ratio 1.64) compared with natural conception. IVF fathers also had a statistically significantly increased risk, but of lesser magnitude (hazard ratio 1.33) compared with natural conception. Moreover, both ICSI treated fathers, and IVF treated fathers had a statistically significantly increased risk of early-onset prostate cancer (hazard ratio 1.86 for ICSI; and 1.51 for IVF)," the findings state.
It adds, "Men who became fathers through assisted reproduction techniques (combined ICSI and IVF) had a statistically significantly increased risk of prostate cancer (odds ratio 1.44) and early-onset prostate cancer (1.63) compared with men achieving fatherhood naturally."
According to the research team from Sweden - Department of Translational Medicine, Lund University, Malmö; Department of Urology, Medical University Sofia, Sofia; and Reproductive Medicine Center, Skåne University Hospital, Malmö - the analysis suggests that these men might benefit from early screening and long term monitoring for prostate cancer.
"Men who achieved fatherhood through assisted reproduction techniques, particularly through ICSI, are at increased risk for early-onset prostate cancer and thus constitute a risk group in which testing and careful long term follow-up for prostate cancer may be beneficial," they recommend.
As prostate cancer and many forms of infertility are male sex hormone related, a possible link between them has been investigated previously. But study weaknesses have, so far, prevented researchers from drawing any firm conclusions. The research team, therefore, decided to compare the risk and severity of prostate cancer between men achieving fatherhood for the first time by assisted reproduction and men conceiving naturally.
The findings are based on data from national registers for over one million children born alive in Sweden during 1994-2014 to the same number of fathers.
The average age at childbirth was 37 years for both IVF and ICSI treated fathers, and 32 years for fathers who conceived naturally. Cancer registries were used to identify new cases of prostate cancer up to 20 years after childbirth.
"For many infertile men, fatherhood is still possible through the use of powerful assisted reproductive techniques. For men with very few sperm (oligozoospermia) or spermatozoa with poor progressive motility (asthenozoospermia), the only option for fatherhood is intracytoplasmic sperm injection (ICSI), in which a sperm is injected into an egg, and the embryo put back into the uterus. This is also the only possibility for men with azoospermia, from whom gametes can be microsurgically gathered from the epididymis or testis," says the study.
It further says, "For men who do not have such severely deficient spermatogenesis, conventional in vitro fertilization (IVF), in which sperm are allowed to fertilize retrieved oocytes in a laboratory dish, is the standard procedure."
Of 1,181,490 fathers, 20,618 (1.7%) had undergone IVF during the study period, 14,882 (1.3%) had undergone ICSI, and 1,145,990 (97%) had conceived children by natural conception.
"Among men achieving fatherhood naturally, 3,244 (0.28%) were diagnosed as having prostate cancer, compared with 77 (0.37%) in the IVF group and 63 (0.42%) in the ICSI group. The risk of early onset of prostate cancer was also particularly high for men fathering children through ICSI. These increased risks remained after excluding men with a previous cancer diagnosis or who received testosterone replacement therapy," says the study.
In a linked editorial, researchers say that how male infertility could be linked biologically to the risk of prostate cancer is not yet clear, but abnormalities on the Y chromosome-linked to both infertility and prostate cancer, are a possibility. They warn that screening is controversial owing to lack of survival benefit and the harms from overdiagnosis and overtreatment that can follow a positive screening test.
"In the absence of a plausible mechanism of action or proof of causation, justifying screening for prostate cancer in all infertile men is difficult. However, further research on the possible future complications of male infertility would be welcomed by patients and will help clinicians to counsel all infertile men about their future health," say experts in the editorial.