USC Fertility


Altered Sex Ratio after IVF. Is it real?

You may have heard that after IVF you are more likely to have a boy. There is some truth to that. During an IVF cycle, the embryos are cultured for a few days in the laboratory before they are transferred back into the woman’s uterus. The day of transfer is not set in stone, and you can put the embryos back any time between the 2nd and 5th day without comprising pregnancy rates. Extending the duration of culture allows the embryos to progress to the “blastocyst stage” which typically occurs on day 5. There are some advantages for some patients to wait to day 5 before the transfer; however the embryo must remain in culture media longer.

Research has shown that if you wait for the embryo to reach the blastocyst stage before transfer, instead of performing the transfer at day 3, that sex ratio of the embryos is altered so that there are a higher percentage of male babies. Animal data has shown the increase in altered sex ratio in multiple species. The thought was that in animal models, male embryos develop faster, and therefore look better on day 5 and are more likely to be chosen by the embryologists for the transfer.

In humans, research has shown a slight trend to an altered sex ratio if embryos are kept in culture media longer, with approximately 55-57% of pregnancies being male with day 5 transfers compared to closer to 50-51% males with day 3 transfers.

We have long known that extended culture can alter certain genetic modifications of the DNA that routinely occur during that time period. Some of these abnormal genetic modifications can lead to rare diseases called imprinting disorders.

A new study just published in Proceedings of the National Academy of Sciences (PNAS), demonstrates that genetic modifications due to extended culture, may be the cause of the altered sex ratio (not the speed at which the embryos develop).

The researchers elegantly showed the following:

  1. The presence of alterations in the genetic modifications of mice embryos that led to abnormal development in female embryos (which ultimately leads to the altered sex ratio).
  2. By correcting these alterations they were able to rescue the female embryos, and restore a balanced sex ratio.
  3. By altering a supplement in the culture media they were also able to rescue the female embryos and restore a balanced sex ratio.

This study is important because it makes us rethink our hypothesis of why the altered sex ratio is occurring and provides a potential solution to fix it. In addition, these findings show that the extended culture environment truly impacts embryo gene expression and ultimately embryo development.

More research needs to be done to corroborate these exciting findings and confirm them in human studies.

Until then, don’t count on getting a boy just by going through IVF, the altered sex ratio, if truly there, is very slight. So it is still pretty close to flipping a coin as to whether you will have a girl or a boy.

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