For some time, fertility experts have widely agreed that it is better to transfer a single embryo to a woman’s womb during IVF treatments. This technique helps prevent problems associated with multiple pregnancies, such as fetal death, miscarriage, premature delivery, and low birthweight. However, even when just one embryo is transferred, some women become pregnant and give birth to twins or, in rare cases, triplets. So, how is this possible?

A new study published in the journal Human Reproduction is the largest ever to look at the prevalence and causes of this phenomenon. Researchers have been able to determine that the proportion of multiple pregnancies after a single embryo transfer is 1.6%. Of these, 1.36% are the result of a process known as zygotic splitting.

The massive study analyzed 937,848 single embryo transfer cycles and highlights factors that could increase the chance of a multiple pregnancy. Some of these factors include using frozen embryos and a technique known as assisted hatching. This is a technique in which a small opening is created in a layer of proteins around an embryo in order to help it hatch out and attach to the womb.

One of the authors on the study, Dr. Keiji Kuroda from the Sugiyama Clinic Shinjuku and Juntendo University Faculty of Medicine in Japan, said, “As a result of our findings, clinicians may want to consider whether they should counsel couples about the small increase in the risk of multiple pregnancies as a result of zygotic splitting associated with some embryo manipulations.”

After a sperm cell fertilizes an egg, it becomes a zygote. This contains all the genetic information from both parents that is needed to create a new person. Soon, this cell divides into more cells, known as blastomeres, until the embryo is formed. Zygotic splitting occurs when a zygote divides into two or more zygotes that individually develop into unique embryos. This leads to a set of identical twins or triplets known as “monozygotic”.

Of the 1.36% of cases of multiple pregnancy, there were 4,310 twins and 109 triplets. The researchers found that using frozen embryos for single embryo transfer resulted in a 34% higher risk of multiple pregnancy. Moreover, maturing blastocysts in the lab before embryo transfer increased the risk by a shocking 79%. Assisted hatching was related to a 21% increase.

Dr. Kuroda said, “Blastocyst culture was associated with the highest risk of zygotic splitting out of the three risk factors we identified. Embryo selection using a computer-automated time-lapse image analysis test and transferring zygotes when they are just starting to divide may be solutions to decreasing the risk.”

Despite the fact that this study looked at Japanese patients only, Dr. Kuroda is confident that the findings should be true among all countries and races. He says, “I have not seen any data on racial differences in zygotic splitting.”

When considering options for fertility treatment, IVF is being used more and more commonly around the world. Results of this study will help make couples more aware of possible outcomes before pursuing certain treatments.


Based on AAAS scientific and journalistic ed.

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