Post-ICSI prostate cancer risk not caused by procedure
The increased risk of prostate cancer, particularly early-onset prostate cancer, among subfertile men who undergo intracytoplasmic sperm injection (ICSI) does not appear to be due to the procedure, according to a nationwide, registry-based study from Sweden.
“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,” said study author Yahia Al-Jebari, a PhD student at the Department of Translational Medicine, Lund University, Malmö, Sweden, who presented the findings at ESHRE 2018.
Based on data from the Swedish Medical Birth Register, the Swedish Cancer Registry, and the Swedish Quality Register for Assisted Reproduction, Al-Jebari and co-authors identified 1,181,490 men who became first-time fathers between 1994 and 2014, 20,618 and 14,882 of whom had undergone in vitro fertilization (IVF) and ICSI, respectively. Men who became fathers via natural conception formed the control group (n=1,145,990). A total of 3,384 prostate cancer cases were diagnosed, 77, 63, and 3,244 in the IVF, ICSI, and control groups, respectively.
Overall, men who underwent ICSI had a 47 percent higher risk of prostate cancer compared with controls (hazard ratio [HR], 1.47, 95 percent confidence interval [CI], 1.15–1.89; p=0.002), with an almost threefold risk of developing early-onset prostate cancer (diagnosed at age ≤50 years; HR, 2.94, 95 percent CI, 1.84–4.71; p<0.001). However, men who underwent ICSI did not have an elevated risk of late-onset prostate cancer (diagnosed at age >50 years) compared with controls. [ESHRE 2018, abstract O-191]
After excluding men with a prior cancer diagnosis (before conception), the risk of prostate cancer was still elevated in men who had undergone ICSI (HR, 1.32, 95 percent CI, 1.01–1.72; p=0.045), as was the risk of early prostate cancer (HR, 2.54, 95 percent CI, 1.52–4.24; p<0.001).
The elevated risk of prostate cancer did not extend to men who became fathers via IVF (HR, 1.14, 95 percent CI, 0.91–1.43; p=0.25 vs controls), with no risk observed for early prostate cancer either (HR, 1.06, 95 percent CI, 0.57–1.98; p=0.86).
Previous findings on the link between prostate cancer and childlessness have been contradictory, said Al-Jebari, with some studies suggesting that childlessness is associated with a reduced risk of prostate cancer, [Int J Cancer 2005;115:994-997; Sci Rep 2016;6:19210] while others point to a link between infertility and an increased risk prostate cancer. [Cancer 2010;116:2140-2147]
“In Sweden … ICSI is foremost applied in couples with male factor infertility, so only a few decades ago before the advent of ICSI, these men would likely be childless. Conversely, standard IVF is usually used in couples where the woman has hampered fertility,” said Al-Jebari.
“[W]e 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,” he said.
One possible reason for the elevated risk of prostate cancer in men who undergo ICSI is a latent preclinical tumour, said Al-Jebari. “A latent preclinical tumour may impair a man’s fertility for many years. He is then treated with ICSI and the malignancy then progresses, and he is diagnosed with prostate cancer,” he said.
“Early-onset prostate cancer is generally considered to be more aggressive. ICSI men are a strictly defined patient group already in contact with the healthcare system. The possible benefits of targeted screening and general health checks of ICSI men should definitely be considered,” he concluded.