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Increasing paternal age may reduce IVF/ICSI success rate

Roshini Claire Anthony
18 Jul 2019

The likelihood of pregnancy following in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) is significantly reduced when male partners are aged 51 years and older, according to a retrospective study from the UK.

“Paternal age over 50 significantly affects the chance of success of [assisted reproductive technology],” said study author Dr Guy Morris from the Centre for Reproductive and Genetic Health, London, UK, and co-authors.

The study, presented at ESHRE 2019, was conducted at the aforementioned clinic in London, UK, and comprised 4,271 men (median paternal age 38 years) who were involved in a total of 4,833 cycles of IVF or ICSI between 2009 and 2018 due to all causes of subfertility. The men were categorized by age group (35, 36–40, 41–44, 45–50, and 51 years), with men and women aged <35 years forming the reference group.

Men older than 51 years were less likely to meet the World Health Organization semen analysis criteria than men younger than 51 years (42.1 percent vs 61.1 percent; p=0.001). [ESHRE 2019, abstract O-304]

About 42 percent of IVF/ICSI cycles resulted in clinical pregnancy. The likelihood of clinical pregnancy significantly declined with advancing maternal age (51.1 percent vs 21.7 percent for women aged 35 and 40 years, respectively; p=0.001).

There was also a reduction in clinical pregnancy rate with advancing paternal age (49.9, 42.5, 35.2, 32.8, and 30.5 years for men aged 35, 36–40, 41–45, 46–50, and 51 years, respectively).

Regardless of maternal age, the likelihood of pregnancy was significantly reduced when male partners were aged 51 years (odds ratio, 0.655, 95 percent confidence interval, 0.477–0.927; p=0.001).

“Paternal age up to 51 [years] did not seem to have a significant predictive impact on the chance of pregnancy, but it is over that [age] where there seems to be a detrimental effect,” said Morris. “[T]he data suggest that semen quality decreases with increasing age and that this decline mirrors the decline in IVF outcome,” he added.

“[I]n natural conception and pregnancy it is only recently that evidence of risks associated with later fatherhood has become available. These more recent studies contrast with decades of evidence of the impact that maternal age has on fertility outcomes,” said Morris.

“In the context of this emerging evidence for the deleterious effect of increasing paternal age, our data certainly support the importance of educating men about their fertility and the risks of delaying fatherhood,” he stressed.

He also pointed out that stories of male celebrities having children later in life “may give a skewed perspective on the potential risks of delaying fatherhood”, leading to the assumption that age does not affect male fertility. 

Nonetheless, the findings are limited by the retrospective observational design of the study, said Morris and co-authors. Furthermore, impact of paternal age may have been underestimated as 80 percent of men aged 51 years received ICSI treatment despite only 42 percent meeting the WHO semen analysis criteria.

Morris also cautioned against overinterpretation of the findings. “We know that [semen analysis] is a poor prognosticator for outcome of IVF treatment and [the reason could be] something along the lines of increasing DNA fragmentation,” he said, referring to previous studies that suggested an increase in DNA fragmentation with increasing age as well as lifestyle and other intrinsic factors. Some studies have also suggested that increasing levels of DNA fragmentation reduce the chance of IVF success, he said.

While the results are insufficient to place an upper age limit on male patients undergoing assisted reproduction, the results are “about empowering people to make the decisions that are right for them and giving them the best possible information so that they are able to make those decisions and have that discussion with their clinician about the potential impact on their chances,” said Morris.

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Older women with longer endogenous oestrogen exposure and hormone therapy use are at much higher odds of having favourable cognitive status in late life, a recent study suggests.
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