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Why single embryo transfer during IVF sometimes results in twins or triplets

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The reasons why a single embryo transfer during an IVF can sometimes result in twins or triplet births have been investigated and calculated by researchers and published by the Human Reproduction, one of the world’s leading medicine journals.

A single embryo transfer to a woman’s uterus during assisted reproduction treatment (ART) is safer than several embryos in order to avoid a multiple pregnancy, because of the risks associated with it.

Researchers have analysed 937,848 Single Embryo Transfer (SET) cycles – and have highlighted factors that could increase the risks. These include using frozen thawed embryos for SET, maturing the fertilised egg (blastocyst) in the laboratory for five or six days before SET, and assisted hatching, in which a small hole is created, the zona pellucida to help the embryo hatch out and attach itself to the wall of the woman’s uterus.

Furthermore, the study has brought to light why even when a SET is performed, some women still become pregnant with twins or even triplets.

It was calculated that the proportion of multiple pregnancies after SET is 1.6%, while 1.36% of multiple pregnancies after SET occur as a result of a process called zygotic splitting, when one embryo divides resulting in twins or triplets. It is more prevalent following SET than in spontaneous conception.

A zygote is the fertilised egg cell that results from a man’s sperm fertilising a woman’s egg, and it contains all the genetic information from both parents to form a baby. It soon starts to divide and subdivide into many more cells called blastomeres, which eventually form the embryo.  Zygotic splitting happens between days two and six when the zygote divides, usually into two, and each zygote continues to develop into an embryo, leading to identical twins (or triplets if it separates into three). These are known as “monozygotic” twins (or triplets).

Japanese scientists examined nearly a million cycles of SET carried out in Japan between 2007 and 2014 and which were reported to the Japanese ART national registry (more than 99% of all ART treatment cycles have been noted in this registry since 2007). After SET using fresh or frozen and then thawed embryos, there were nearly 277,000 clinical pregnancies (29.5%), including 4,310 twins (1.56% of pregnancies) and 109 triplets (0.04% of pregnancies). The prevalence of true zygotic splitting was 1.36%, and the researchers found that, compared to singleton pregnancies, using frozen-thawed embryos increased the risk of zygotic splitting embryos by 34%, maturing the blastocysts in the lab for a few days before embryo transfer increased the risk by 79%, and assisted hatching by 21%.

The researchers findings were to show that 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.

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