Reacción a "A large study finds genetic variants associated with pregnancy loss"

This is a very high-quality study: one involving 139,416 embryos and 22,850 couples who underwent an in vitro fertilization cycle with genetic testing of their embryos represents a large sample size.

Furthermore, the statistical methods applied are appropriate, with results consistent with known biology from animal studies, thus reinforcing the conclusions.

Age has always been considered the main limiting factor in female fertility, given the increasingly advanced age at which women become pregnant. However, we often find women of similar ages who experience greater infertility problems and a higher risk of producing embryos with chromosomal abnormalities and of miscarriage for no apparent reason.

This study opens a new avenue of research, suggesting that very specific variations in the parents' DNA could be the cause of the more frequent generation of embryos with altered genetic makeup, as an independent and complementary factor to age.

Apparently, the problem could stem from a malfunction of the genes responsible for maintaining chromosome cohesion. These connections are essential for precise chromosome segregation and tend to break down as women age, which is linked to a higher risk of infertility and miscarriage.

This study suggests that the origin of this malfunction could be due to a decrease in the expression of genes such as SMC1B, C14orf39, CCNB1IP1, and RNF212, which would lead to fewer recombinations in eggs and thus increase the risk of aneuploidies. This has been suggested in previous studies in animal models, which indicated that "few recombinations" favor errors in the embryo's genetics, but never before demonstrated on this scale.

Although the individual risk of each variant is low and there is no direct intervention, it can change practice, especially in research, by helping us prioritize genes and pathways for functional studies, improve aneuploidy risk models, and leverage PGT [preimplantation genetic testing] data as a great platform for studying human meiosis.

[Regarding possible limitations] It should be noted that the study is based on couples from in vitro fertilization cycles, not the general population, with the population bias that this implies.

Furthermore, the heritability explained by common variants is low, and the study does not adequately analyze rare or structural variants or environmental factors. Therefore, at this time, it is not useful for making a systematic, individual clinical prediction, although it helps to better understand the mechanisms of meiosis.