Embryo Transfer Guidelines Reduced Multiple Births Without Harming Live Birth Rate

DENVER — After 2017 guidelines recommended single embryo transfer in most situations, the multiple birth rate dropped by 58%, according to a large national registry study.

Moreover, single embryo transfer increased by 62% while the cumulative live birth rate per retrieval cycle remained the same, reported Katie Baker, MD, of Women and Infants Hospital and the Warren Alpert Medical School of Brown University in Providence, Rhode Island, during a presentation at the American Society for Reproductive Medicine (ASRM) annual meeting.

Baker explained that the incidence of multiple births began rising in the 1980s, partially because of assisted reproductive technology (ART). The twin birth rate rose by 79% from 1980 to 2014, averaging a 2% annual rise. In 1998, the ASRM and the Society for Assisted Reproductive Technology (SART) first issued guidance on the recommended maximum number of embryo transfers to reduce multiple gestations, which are riskier than singleton pregnancies.

“The goal of ART is to achieve a singleton gestation,” Baker noted.

This initial guidance led to a decreased incidence of higher order multiples, though twin gestations remained common. After the guidelines were updated in 2013 to model changes in practice patterns, the twin rate declined for the first time by 1% in 2014.

In 2017, the ASRM and the SART updated the guidelines again with limits on the number of embryos to transfer, with the goal of reducing the multiple birth rate. They specifically recommended single embryo transfer for patients with a favorable prognosis under the age of 38 and for all patients undergoing transfer of a euploid embryo.

Baker said she and her team sought to “determine whether there were changes in the multiple birth rate and the single embryo transfer rate after the publication of the 2017 ASRM/SART guidelines.”

They found that after the guidelines were implemented, the multiple birth rate significantly decreased from 15.4% to 7.1% (adjusted OR 0.578, 95% CI 0.558-0.599), and the single embryo transfer rate significantly increased from 56.3% to 78.1% (aOR 1.488, 95% CI 1.464-1.512).

The cumulative live birth rate remained stable at 40.8% before the guidelines and 45.9% after (aOR 1.005, 95% CI 0.989-1.021).

A subset analysis of cycles with and without the use of preimplantation genetic testing for aneuploidy (PGT-A) yielded similar results, as did a subset analysis excluding 2017 (since the guidance came out mid-year).

Ultimately, Baker concluded that these guidelines indeed “limited the number of embryos to transfer and successfully promoted the reduction of multiple gestations, while continuing to maximize the live birth rate.”

“These guidelines have played a crucial role in advancing the standards for safe and effective IVF [in vitro fertilization] care in the United States,” she added.

For this study, the researchers used data from the 2014-2020 SART Clinical Outcomes Reporting System (CORS) to identify autologous IVF cycles and linked thaws. They analyzed 758,578 retrieval cycles with 515,733 linked frozen embryo transfers. Analyses were adjusted for age, smoking, race, parity, geographical region, infertility diagnosis, total gonadotropin dose, use of intracytoplasmic sperm injection, number of 2 pronuclei, embryo stage at transfer, and use of PGT-A.

Exclusion criteria included age older than 42, cryopreserved oocyte thaw cycles, and oocyte and embryo banking cycles. Baseline characteristics were similar before and after the guidelines. The primary outcome was the multiple birth rate per live birth, and secondary outcomes included the single embryo transfer rate and the cumulative live birth rate per retrieval cycle.

Baker noted a few limitations to the study, such as the inability to categorize favorable versus poor patient prognosis and the use of single embryo transfer instead of elective single embryo transfer due to the potential inaccuracy in that reporting.

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