When should elective single embryo transfer be considered with IVF?

ASRM and SART have also recently issued a “committee opinion” on a phenomenon that has attracted great attention in the field of assisted reproduction- “elective single embryo transfer” (eSET).

eSET is defined as the transfer of a single embryo at the cleavage (day 2-3) or blastocyst (day 5-6) stage that is selected from a larger number of embryos. Historically, physicians had a tendency to transfer more embryos to compensate for a low implantation rate. However with multiple improvements over time, such as optimized embryo culture and stimulation protocols, implantation rates have improved and the practice of transferring multiple embryos was revisited. The rationale was that single embryo transfer is really the only effective way to minimize multiple pregnancy rates. Over the last decade, there has been a trend towards a lower number of transferred embryos, with an increase in single embryo transfer numbers- this has resulted in a drastic reduction of higher order multiple pregnancy rates.

Worldwide, there is a great variation in the use of eSET. In America, the rate of eSET is about 10%, in Europe about 20% with a wide regional variation (eg. Sweden 69%, Finland 50%, Denmark 33%). This range can be explained by healthcare system differences, variability in insurance coverage for IVF, legal factors, local guidelines and cultural differences. In Sweden, where there is a high rate of eSET because of legal / insurance / cultural factors, one of the largest studies on eSET was performed and published in the “New England Journal of Medicine” in 2004. 661 patients with a favorable prognosis either had a transfer of 2 embryos at once, or a transfer of one embryo from a fresh cycle, followed by a transfer of a thawed embryo if the fresh cycle did not work. At the end of the study, a similar number of women were pregnant in each group, 43% in the group with the double embryo transfer were pregnant, versus 39% in the single embryo transfer group. However, the rate of multiple pregnancy was only 0.8% in the eSET group versus 33.1% in the other group. These results were confirmed in other studies, some of which were prospective randomized trials and others that were retrospective, including the observation of decreased multiple pregnancy rates after the introduction of eSET programs in some practices.

Probably the most striking difference in multiple pregnancy rates was observed in a study from Colorado that was published in “Fertility and Sterility” in 2004. In this study, 48 good prognosis patients were randomized to receive either one or two embryos at the blastocyst stage, when the embryologist had monitored the embryos for a longer period of time, with an opportunity to select the very best embryos. The pregnancy rate in the double embryo transfer (DET) group was 76%, compared to a (still very respectable) pregnancy rate of 61% in the eSET group. However, almost half of the patients in the DET group had twins (47%), whereas none of the patients in the eSET group did (0%).

All these observations have led to a lively debate about the topic of eSET. Given that multiple pregnancies, with the resulting consequences of increased health issues in mothers and newborns, clearly represent a burden to society and healthcare systems, experts have pushed for increased use of eSET in patients with a good prognosis. As one prominent European doctor put it in an editorial: “Replace as many embryos as you like, one at a time”.

Challenges to more universal acceptance of eSET are potential increases in cost for the patient, limitations of our methods to select the best embryos, and in some places, the capacity to freeze extra embryos. Clinics may also be worried about their statistics, because “success rates” are reported per cycle and not per patient. Efforts to decrease the multiple pregnancy rates may also not be valued enough by patients, because of a lack of awareness of multiple pregnancy risks in the general public.
Ultimately, evidence-based education for providers and patients and a thorough counseling discussion between the couple and their IVF doctor are crucial, so that the desired end result of pregnancy is achieved in as many patients as possible, while maximizing the chances of a healthy outcome for the mother and her infant.