Sub-fertile men who require their sperm cells to be injected directly into an egg for conceiving have a much greater risk of developing prostate cancer, particularly its early-onset form, according to a large Swedish study.
Although researchers rule out the procedure — intracytoplasmic sperm injection (ICSI) — as a direct cause of prostate cancer, they believe it could be a disease predictor.
The research, “Risk of prostate cancer in ICSI treated man,” was presented at the recent European Society of Human Reproduction and Embryology (ESHRE) meeting in Barcelona, Spain.
ICSI is used more commonly in couples dealing with male infertility, which may be due to factors such as low sperm counts, poor sperm mobility and quality, or no sperm in the male’s ejaculation. The technique involves the direct injection of sperm into eggs obtained from in vitro fertilization (IVF).
The research team from Lund University in Sweden compared the risk of being diagnosed with prostate cancer in fathers who underwent ICSI, to those who had a child by natural conception (controls) and fathers receiving routine IVF.
The scientists first identified all fathers and their first child born, between 1994 and 2014, through information collected from the Swedish Cancer Registry, the Swedish Medical Birth Register, and the Swedish Quality Register for Assisted Reproduction. Among nearly 1.2 million fathers, they found 3,211 prostate cancer cases.
Results showed that men who underwent ICSI had a 47 percent greater risk of prostate cancer than controls. Importantly, this risk was almost three-fold greater in men with prostate cancer diagnosed before age 50, which is considered “early onset.”
In turn, men receiving ICSI did not have greater risk of late onset prostate cancer, and men receiving routine IVF did not exhibit increased risk.
“The increased risk of prostate cancer is definitely not because of the ICSI treatment per se,” Yahia Al-Jebari, PhD, the study’s presenter, said in a press release.
“The results show immense risk for early-onset prostate cancer,” the investigators said, adding that this form of cancer is considered more aggressive.
Unlike the overall diagnosis of prostate cancer, its early onset form is rare. The scientists found only one per 1,000 in fathers diagnosed before age 50, but this rate increased to three per 1,000 in fathers treated with ICSI.
Prior research showed that men with severely impaired sperm production, for whom ICSI is the only available fertility treatment, have greater risk of prostate cancer than fertile men.
So, researchers hypothesize these men already may have a latent tumor by the time they undergo ICSI.
Other potential causes for the link between prostate cancer risk and male infertility include low levels of testosterone (hypogonadism), and using testosterone itself to treat hypogonadism. However, men receiving testosterone supplementation are tested more regularly, which may induce a bias in which prostate cancer is detected earlier.
Of note, unlike its broader use in other countries, ICSI is indicated only in Sweden for cases of men who cannot conceive through regular IVF. As a result, most fertile men receiving fertility treatments should be in the IVF group, Al-Jebari said, which means that the “ICSI fathers are highly selected and generally have very poor semen quality.”
Although Al-Jebari ruled out ICSI as a possible cause of cancer, he said it could predict disease, while male sub-fertility may be a risk factor. Also, as sub-fertile men are candidates for more general health checks, including PSA screening, they could benefit from early detection of prostate cancer.