Sperm aneuploidy in recurrent pregnancy loss

Researchers in a 2020 study found that sperm from males in couples with recurrent pregnancy loss were more likely to be aneuploid, potentially leading to the diagnosis.

Recurrent pregnancy loss can be defined as having 3 or more losses.

Aneuploidy is thought to be a leading cause for miscarriage, and occurs when either the egg or sperm cell contain an irregular number of chromosomes. These are passed onto the embryo, which inherits this abnormal chromosome number and may cause the embryo to miscarry.

The egg has been frequently put in the spotlight as a source of this aneuploidy, and this might help explain why IVF success rates decrease with advanced age and lowered egg quality. Not too much attention has been given to sperm, especially as it relates to aneuploidy.

Sperm also need to contribute their fair share of chromosomes to the embryo, and Fakhrabadi et al. (2020) wanted to see if there was any relationship between aneuploidy in sperm cells in couples with RPL.

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Study details

The RPL group consisted of 50 males, the control group was 15 , and they were all between 25 and 55 years (average was 34-37).

Aneuploidy of sperm was evaluated using fluorescent in-situ hybridization (FISH). This technique only allows a certain number of chromosomes to be evaluated and counted – they used chromosomes 13, 18, 21, X and Y, because these can give rise to live births with associated syndromes.

Results

In terms of semen parameters between the RPL and control groups:

• No difference in sperm motility (~42-44%).
• Sperm counts were significantly lower in the RPL group (85.7 million) compared to the control (110.98 million).
• Sperm morphology was lower in the RPL group (4.66%) compared to the control (6.26%).

In terms of aneuploidy screening with FISH, they found different numbers of chromosomes. In sperm, we expect to see one copy of each chromosome and anything different than a single copy is abnormal. 5000 sperm were analyzed: 2500 from the RPL group, and 2500 from the control group.

• 32.3% of the sperm from the RPL group were missing a chromosome, compared to 4.2% in the control group.
• 11.9% of RPL sperm had an extra chromosome compared to 1.0% in the control.
• In total 44.5% of RPL sperm were aneuploid compared to 5.3% in the control.

The RPL group contained men that had both normal semen and abnormal semen, so they compared these. The abnormal semen contained a higher rate of aneuploidy (50.67%) compared to normal semen (41%). For reference, the control had 5.3% aneuploidy.

They also compared the age of the men and the incidence of aneuploidy:

• In the RPL group, sperm aneuploidy was highest between ages 35-39 (31.9%).
• In the control group, aneuploidy was highest between ages 35-39 (53.6%).

Conclusions

This study found that in couples with RPL, the males had dramatically higher rates of aneuploidy in their sperm (44.5%) compared to sperm from men in non-RPL couples (5.3%).

Even males with a normal semen analysis had high levels of aneuploidy (41%) compared to those with abnormal semen analyses (50.57%) in RPL couples. So even in normal sperm, about half were aneuploid!

This suggests that sperm aneuploidy may be a common event in RPL couples and may account for the diagnosis.

One of the faults of this paper is the lower sample size (only 50 men were used in the RPL group, and 15 in the control group). They also did not address why younger men (35-39) had the highest incidence of aneuploidy. It would also be interesting to see if these aneuploid sperms contributed to aneuploidy in embryos, or if this error is corrected in the embryo.

Reference

Pourfahraji Fakhrabadi, M., Kalantar, S.M., Montazeri, F. et al. FISH-based sperm aneuploidy screening in male partner of women with a history of recurrent pregnancy loss. Middle East Fertil Soc J 25, 23 (2020). https://doi.org/10.1186/s43043-020-00031-6

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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 Master’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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