Sperm DNA fragmentation and advanced female age

Researchers in a 2021 study found that older women showed worsened IVF outcomes using sperm with high DNA fragmentation, possibly due to compromised DNA repair activity in the older egg.

Male infertility is usually diagnosed on the basis of a semen analysis. This looks at different parameters of the semen, including sperm concentration, motility and morphology. Having low quality semen can negatively impact IVF outcomes.

Sperm DNA fragmentation (SDF) is another measure of sperm quality, although one that is less accepted by medical professionals. This is for a few reasons but is mainly because there is no standardized way of running SDF tests (so consistency in reporting is an issue) and thereโ€™s not much good evidence that address SDF and IVF outcomes.

SDF is caused mainly by reactive oxygen species (ROS) that occur naturally in your body that cause breaks in sperm DNA. Environmental factors and lifestyle choices can influence the amount of ROS which can increase SDF.

But no fear! Because damaged DNA in sperm can be corrected by the oocyte. The oocyte has DNA repair activity, and is believed to be able to repair DNA damage in sperm.

Like most things in the egg, DNA repair activity may decrease with age, and a 2021 study by Setti et al. wanted to see if this was the case!

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This single center, retrospective study was performed between 2017 and 2019. They looked at three groups of women based on age (285 women <36, 147 women 37-40, and 108 women >40) and compared IVF outcomes when using ICSI with low SDF sperm (<30% using the sperm chromatin dispersion SCD method) or high SDF (>30%).

When comparing low and high SDF sperm, women <36 AND women 37-40 had:

  • No differences in fertilization
  • No differences in the number of high quality Day 3 embryos or blastocysts
  • No differences in pregnancy rates

However, women >40 had:

  • Fewer high quality Day 3 embryos with high SDF sperm (54.4% for low SDF vs 33.1% for high SDF)
  • A lower blastocyst conversion with high SDF (49.6% of embryos developed to blast vs 30.2%)
  • Fewer high quality blastocysts with high SDF (70.6% vs 44.6%)
  • A lower pregnancy rate for high SDF (20.0% vs 7.7%)

So women who were >40 and used high SDF sperm had worse outcomes compared to women with low SDF sperm. This group also performed worse than the younger age groups.

The authors think that these differences are due to DNA repair activity being impaired with advanced age. So older women have less DNA repair activity and canโ€™t repair damaged sperm, which makes embryo quality/pregnancy outcomes lower.

However, an issue is that they didnโ€™t test this directly. They found an association with worsened outcomes and advanced age/high SDF sperm, but they canโ€™t say for sure that this was due to reduced DNA repair activity. What if thereโ€™s something else involved?

Also, itโ€™s interesting that they didnโ€™t find any difference in the younger groups, considering high SDF is linked to worsened IVF outcomes. So SDF might be more of an age-related factor to consider.

Reference

Setti AS, Braga DPAF, Provenza RR, Iaconelli A Jr, Borges E Jr. Oocyte ability to repair sperm DNA fragmentation: the impact of maternal age on intracytoplasmic sperm injection outcomes. Fertil Steril. 2021 Jul;116(1):123-129. doi: 10.1016/j.fertnstert.2020.10.045. Epub 2021 Feb 13. PMID: 33589137.

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About Embryoman

Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Masterโ€™s in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.


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