Study explores male and female influence on embryo euploid rates

A 2024 study explored the male and female factors that are associated with embryo euploid rates, finding that male characteristics had a minor influence.

Female age is considered one of the strongest contributors of euploidy in the embryo, mainly because the egg is paused in meiosis for such a long time.

But there isnโ€™t much data on the contribution of male characteristics on aneuploidy!

This post is a summary of a study by Fouks et al. (2024). The point of this study was to see if there was an association between embryo euploid rates and male and female characteristics. They didnโ€™t simply compare euploidy rates, instead they used different statistical tests to look for relationships.

To help understand the results show below, โ€œcoefficientsโ€ are numbers that tell us how much a specific factor, like female age or BMI, impacts the likelihood of an embryo being euploid.

  • Negative Coefficient: If the number is negative (like for female age or prior ART cycles), it means that as this factor increases, the likelihood of the embryos being euploid decreases. For example, as female age increases, the chance of having euploid embryos goes down.
  • Positive Coefficient: If the number is positive (like for BMI), it means that as this factor increases, the likelihood of the embryos being euploid also increases.
  • Size of the Coefficient: The bigger the number (whether positive or negative), the stronger the impact on euploidy.

Letโ€™s get to it!

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Male characteristics seem to play a small role in euploid rates

In their first analysis, consisting of 8484 patients, they compared male and female patient characteristics and euploid rates:

  • As female age increased, the chance of euploidy decreased (coefficient: -0.05321, p< 0.001).
  • As the number of previous cycles increased, the chance of euploidy decreased (coefficient: โˆ’0.06165, p< 0.001). So patients who had more previous cycles had a lower chance of getting a euploid.
  • To a smaller degree, increases in the number of eggs retrieved, the number of days using gonadotropins, and the number of immature eggs were associated with a increase in euploidy (coefficients were smaller than the other factors, at โˆ’0.01831, 0.017, and 0.013, respectively).
  • There was an association with male age, however the author (in a personal communication) noted that it was hard to separate male age and female age in their models, because theyโ€™re often linked.
  • While some semen parameters (like sperm count) showed an association with euploidy, when female age was considered, these effects were very small and likely not clinically significant.

In their second analysis, consisting of 35,797 embryos, they compared embryo variables to aneuploidy:

  • Female age was again found to be a strong predictor for euploidy (coefficient: โˆ’0.1244, p< 0.001).
  • To a smaller degree, embryos created using ICSI were less likely to be euploid, compared to those created using conventional IVF (coefficient: โˆ’0.0129, p< 0.001). The authors note that while ICSI is associated with lower euploidy rates, the reasons behind using ICSI (such as lower sperm quality) could be contributing factors.
  • To a smaller degree, a higher number of normally fertilized 2PN zygotes was associated with a higher chance of euploidy (coefficient: 0.0173, p< 0.001).
  • To a very small degree, an increase in the daily dose of gonadotropins was associated with a decrease in euploidy (coefficient: โˆ’0.0005, p< 0.001).
  • Again, while male age was associated with euploidy, it was linked to female age and hard to separate. Other male factors, like sperm count, motility and concentration were also associated with euploidy, and these effects were even smaller when age was taken into account.

In their third analysis, they matched patients that either had only euploid or only aneuploid embryos. These patients had three or more embryos biopsied.

  • Patients with 100% euploid embryos had fewer prior cycles than patients with 100% aneuploid embryos (p< 0.001).
  • Patients with 100% euploidy had more eggs retrieved (p= 0.033).
  • Patients with 100% euploidy had more normally fertilized zygotes (p= 0.01).
  • There was no difference in female age, male age, or any semen characteristics (volume, concentration, motility, etc.).

Conclusions

In general, this study found that female age and the number of previous cycles were the strongest predictors for euploidy: patients who were older, or who had a history of more cycles, had a lower chance of an embryo being euploid.

Other factors, like the number of eggs retrieved, the use of ICSI vs conventional IVF, and the dose of gonadotropins had smaller effects on euploidy.

Male age was also associated with euploidy, but because male age and female age are strongly linked, it was hard to separate their effect.

Semen parameters, like sperm count and motility, showed a small association with euploidy, and these effects were very small when age was considered.

There isnโ€™t much data on the paternal contribution of aneuploidy on the embryo. One study, which I reviewed here, found that paternal origin aneuploidy accounted for about 10% of embryo aneuploidy.

The authors note that factors such as sperm DNA fragmentation (not measured here), variability in semen samples, and the possibility that lower quality sperm may lead to fewer blastocysts might also affect the results.

A limitation of this study is that three PGT labs were used to test the biopsies with different cutoffs for aneuploidy (mostly 20-30%). Another bigger limitation, in my opinion, is that there was no mosaic reporting. Therefore, rather than a study of euploid vs aneuploid, this study is really a comparison between euploid and non-euploid embryos (ie. <20-30% aneuploid cells vs >20-30% aneuploid cells, with this latter group including both mosaic and aneuploid embryos).

However, mosaics with 20-80% aneuploid cells occur at a rate of about 15%, so the majority of these non-euploid embryos may be aneuploid. The authors also point out that their monthly live birth rates after transfering a euploid didnโ€™t change over the study period, suggesting that the different testing labs were identifying euploids to a similar degree.

Related studies

To learn more about this topic, you can check out a number of studies referenced in this study below (5 links):

Reference

Fouks Y, Vaughan D, Sripada V, Penzias AS, Bortoletto P, Sakkas D. Do sperm factors influence embryonic aneuploidy? Long live the oocyte. Hum Reprod. 2024 Oct 1:deae224. doi: 10.1093/humrep/deae224. Epub ahead of print. PMID: 39352944.

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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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