The Use of Single Embryo Transfer (SET)
There is no doubt that single embryo transfer (SET) is safer and equally effective when long-term measures of effectiveness are used. Hence, a uniform policy of single embryo transfer should be advocated by everyone. Multiple pregnancy rates after ART should not be higher than those following natural conception. For this to happen, there needs to be a joint approach by IVF Clinics, policymakers, funders, and patients.
Over 7 million babies have been born worldwide by the use of in vitro fertilization (IVF) in just over 40 years. Though an extremely successful treatment, the biggest complication of IVF has been a high multiple pregnancy rate. This was due to the transfer of multiple embryos in the hope that at least one of them will be implanted. Hence, multiple embryos transferred in the hope of maximizing pregnancy lead to an exponential surge in the proportion of multiples in pregnancies as a result of IVF. It was found that the only way of reducing multiple pregnancy is to transfer one embryo.
With the widespread use of IVF, it became clear that twins are in a much higher proportion, and something has to be done about it to reduce the risks associated with multiple births, which can lead to both short—and long-term health problems in the babies born, higher risk to the mother during pregnancy and delivery, as well as significant costs to health care. Single embryo transfer was suggested as a way forward.
Single embryo transfer is when one embryo is transferred. Single embryo transfer could be an elective single embryo transfer (eSET), when a woman opts to reduce the risk of a multiple birth by having one embryo transferred in a treatment cycle despite having more available. Non-elective single embryo transfer (not-eSET) is when it is available for transferring only one embryo. Double embryo transfer (DET) is when two embryos are transferred to a woman’s uterus at the same time.
Evidence of Clinical Effectiveness
There have been several randomized trials comparing single versus double embryo transfer. An individual patient data meta-analysis 6 on eight trials showed that live birth rate in a fresh IVF cycle was lower after single 27% than double embryo transfer 42%. Adjusted odds ratio 0.50, 95% confidence interval 0.39-0.63, as was the multiple birth rate 2% versus 29%.
An additional frozen single embryo transfer, however, resulted in a cumulative live birth rate similar to double embryo transfer 38% versus 42%, with a minimal cumulative risk of multiple birth 1% versus 32%. The odds of term singleton live birth was five times higher after single embryo transfer as compared to after double embryo transfer.
Evidence of Cost Effectiveness
Like clinical effectiveness, there are difficulties with the cost-effectiveness model of single versus double embryo transfer. It depends on whose perspective it is calculated from (health care or patient or clinic providing IVF treatment or society), the time horizon it is measured for 5 years or 10 years or lifelong, and what is being measured. It is important when most IVF treatment is funded by patients themselves, whereas complications and implications of IVF treatment are usually dealt with by the public system.
Future for Single Embryo Transfer
Twins should no longer be an acceptable risk of assisted reproduction. The multiple pregnancy rate after natural conception is 2%. There is no reason, if a policy of single embryo transfer for all is followed, the multiple pregnancy rate should be any more than this. There are still arguments for using single embryo transfer only for younger women. However, multiple pregnancies in older women will be associated with more obstetric risks, which is all the more reason to avoid multiple pregnancies. Hence, a blanket policy of single embryo transfer for all is justified in today’s world.
Some argue that if the embryos are poor quality, one can put two embryos back. However, what is not clear is whether the implantation of one gets affected by another. What may be better in these cases is that (a) if there are two poor-quality embryos on Day 3, to extend to the blastocyst and transfer if any of them develop to blastocyst and (b) if there are two poor-quality embryos on Day 3, to extend culture to Day 6, and if there is a blastocyst it can be frozen and thawed at a later date for transfer.
The aforesaid is important, as a prediction as to which embryo will implant is poor. There have been cases reported with twins when even poor-quality embryos were put back.
With advances in embryo selection, the ability to freeze and thaw embryos successfully with vitrification, and better understanding of IVF programs and embryo-endometrial synchrony, one can argue that there is no indication for transferring more than one embryo at any age and at any embryo quality. Hence, in the future, only single embryo transfer should be practiced. This is irrespective of whether it is cost-effective or not, as this is the only way multiple pregnancy rates can be reduced.
There is no need for further research in this area, as it is clear that it is only single embryo transfer that can prevent multiple pregnancies. The question mark should be on how best to select these embryos to reduce time to pregnancy.
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