Why single embryo transfers in IVF sometimes result in twins

The reasons why IVF treatment sometimes results in twin or triplet births – even though only one embryo is used – have been found by the largest study to date on single embryo transfer (SET) and multiple pregnancy.

'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,' said study author Dr Keiji Kuroda of the Sugiyama Clinic Shinjuku and Juntendo University Faculty of Medicine in Tokyo, Japan. 

Transferring just one embryo at a time is recommended to reduce rates of multiple pregnancies from IVF, as such pregnancies pose risks to both mothers and babies; increasing rates of maternal mortality, preterm births and low birth weight.

However, despite performing SET, multiple pregnancies do happen due to a phenomenon known as 'zygotic splitting', when one embryo divides resulting in twins or triplets. It is more prevalent following SET than in spontaneous conception.

The reasons for this were unclear until now. The new study identifed risk factors for zygotic splitting following SET.

The most significant factors were: using blastocyst culture whereby embryos are matured in the lab for several days prior to implantation; assisted hatching whereby a small hole is made in a layer of proteins surrounding the embryo to help its attachment to the uterine wall; and the use of frozen-thawed embryos rather than fresh embryos.

The study, published in Human Reproduction, analysed data from 937,848 cycles of SET from the Japanese assisted reproductive technology national registry database. The researchers were able to identify the true cases of zygotic splitting by counting the births in which the number of fetuses outweighed the number of gestational sacs (a large fluid cavity surrounding an embryo).

'Big data makes a big difference,' said Professor Peter Braude, emeritus professor of obstetrics and gynaecology at King's College, London, who was not involved in the research. The true prevalence of zygotic splitting was calculated to be just 1.36 percent, which is 'reassuring' according to Professor Braude.

The Japan Society of Obstetrics and Gynaecology recommended the use of SET in 2008, and by 2015 usage had increased by 80 percent and the prevalence of multiple pregnancies from IVF dropped from 10.7 to 3.2 percent.

Although some embryo manipulation techniques were identified as risk factors for zygotic splitting, Dr Kuroda also pointed out that technologies have been improving.

'The use of single embryo transfer has increased worldwide, the prevalence of zygotic splitting has not,' he said. 'This may be because ART techniques and also the cultures in which blastocysts are matured in the lab, have improved over recent years, reducing the stress on the embryo and leading to a decrease in the risk of zygotic splitting.'

He added: 'So, there may be no need to avoid embryo manipulations such as blastocyst culture, in order to select the single most viable embryo.'