Men too have a ticking biological clock, and it matters most in IVF treatments
Women are used to being warned about their biological clocks. As a woman goes from her 20s to her 30s to her 40s sans having kids, she’s likely to hear more and more people warn her about the pregnancy risks, but now, a new research has shown that it’s not only the female fertility clock that’s ticking. The study from the USA in IVF couples shows quite clearly that live birth outcome is clearly affected by the age of the male partner and that in certain younger female age groups, where the effect of age is less potent, the chances of live birth can be appreciably reduced by the man’s increasing age.
“Our study found an independent effect of male age on the cumulative incidence of live birth,” said investigator Laura Dodge from Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, USA. The study was an analysis of all IVF cycles performed at a large IVF centre in the Boston region between 2000 and 2014, a total of almost 19,000 cycles performed in 7,753 couples. The female partners in these cycles were stratified according to four age bands: under 30, 30-35 years, 35-40 years, and 40-42. Men were stratified into these same four age bands, with an additional band of 42 and over.
As expected, the cumulative live birth rate (measured from up to six cycles of treatment) was lowest in those couples where the female partner was in the 40-42 age band, and in this group the age of the male partner had no impact, demonstrating the dominant detrimental effect of female age. However, within the other bands of female age, the cumulative incidence of live birth was significantly affected by male partner age and was found to decline as the man grew older.
For example, in couples with a female partner aged under 30, a male partner aged 40-42 was associated with a significantly lower cumulative birth rate (46%) than a male partner aged 30-35 (73%). Similarly, in couples with a female partner aged 35-40 years live birth rates were higher with a younger than with an older male partner. “Generally,” explained Dodge, “we saw no significant decline in cumulative live birth when women had a male partner the same age or younger. However, women aged 35-40 did significantly benefit from having a male partner who is under age 30, in that they see a nearly 30% relative improvement in cumulative incidence of live birth when compared to women whose partner is 30-35 – from 54% to 70%.”
“Where we see significant decreases in the cumulative incidence of live birth is among women with male partners in the older age bands. For women age 30-35 having a partner who is older than they are is associated with approximately 11% relative decreases in cumulative incidence of live birth – from 70% to 64% – when compared to having a male partner within their same age band.”
Commenting on the results, Dodge noted that in natural conceptions increasing male age is associated with a decreased incidence of pregnancy, increased time to pregnancy, and increased risk of miscarriage. The mechanisms, she added, are unclear but may include impaired semen parameters, increased DNA damage in sperm, and epigenetic alterations in sperm that affect fertilisation, implantation, or embryo development.
“However,” said Dodge, “both the results of this study and prior work show that female age has a larger effect on fertility than male age. While the effect of female age on fertility is overwhelmingly due to increased rates of chromosomal abnormality, the proposed mechanisms in the effect of male age on pregnancy are more subtle. When we looked at the effect of female age alone, we saw a 46% relative decrease from ages under 30 to 40-42, but when we looked at male age alone, we saw a 20% relative decrease over the same age span.”
Can men with younger female partners do anything to compensate for this age effect in IVF? “It’s hard to say without knowing the precise mechanisms involved,” said Dodge. “Most preconception advice for men focuses on semen quality, though studies suggest that this likely cannot fully ameliorate the effects of male reproductive ageing. So in the absence of clear evidence of the mechanisms, the best preconception advice we can offer is to maintain a healthy lifestyle.” The study will be presented at the 33rd Annual Meeting of ESHRE in Geneva.
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