Algorithm developed to limit number of excess embryos created in assisted reproduction

Researchers developed a prediction tool that may help to limit the number of surplus embryos created with IVF while maintaining the likelihood of live birth.

Assisted reproductive technology (ART) cycles commonly result in embryos that are ultimately unused, which means couples must decide whether to discard the unused embryos, donate them for teaching purposes or to other people, or pay for the embryos’ indefinite storage, according to study background. ART clinics also face financial and logistic challenges with storing unused embryos indefinitely.

In June, the overturning of Roe v. Wade presented a new problem for unused embryos produced with ART.

“With the ruling overturned, numerous states are considering ‘Personhood Legislation’ that seeks to define the start of human life at fertilization,” Katharine F. B. Correia, PhD, an assistant professor of statistics at Amherst College in Massachusetts, and colleagues wrote in JAMA Network Open. “If this occurs, ART clinics may worry about potential legal risks involved in handling or discarding surplus embryos. These concerns may have substantial impacts on how ART is practiced, and ART clinics may desire to limit embryo creation due to potential legal implications.”

Algorithm development

Correia and colleagues used national data from the Society for ART (SART) Clinical Outcome Reporting System (CORS) to identify 311,237 women aged 18 to 45 years who began their first oocyte stimulation cycle between 2014 and 2019. SART CORS patient-level data were randomly and equally assigned to a training data set, which was used to develop the prediction tool, and to a testing data set, which was used to evaluate the tool’s performance.

The prediction tool consisted of three models. The first model predicted the likelihood of a day 5 blastocyst transfer vs. an embryo transfer. The second model calculated the proportion of oocytes that become usable blastocysts by dividing the sum of the number of blastocysts transferred and the number of blastocysts frozen by the number of oocytes retrieved. The third model calculated the patient-level number of blastocysts transferred that were needed for one live birth to occur.

Models considered female patient age, state where the ART clinic was located, anti-Müllerian hormone level, diagnosis of diminished ovarian reserve and number of oocytes retrieved.

Results

There were 410,719 oocyte retrievals and 460,577 embryo transfer cycles included in the study. The median age was 35 years (interquartile range [IQR], 29-32), and the median number of retrieved oocytes was 10 (IQR, 6-17). Most embryo transfers (73.2%) occurred on day 5 or later, and 69.7% of day 5 transfer or freeze cycles involved blastocysts vs. embryos.

The models predicted that 43.4% of oocyte retrievals were day 3 transfers, and therefore recommended all oocytes be exposed to sperm. For the 57.6% of cycles predicted to be day 5 transfers, the median number of oocytes that needed to be exposed to sperm to produce one live birth were:

• seven (IQR, 7-8) among women younger than 32 years;
• eight (IQR, 7-8) among women aged 32 to 34 years; and
• nine (IQR, 9-11) for women aged 35 to 37 years.

Overall, the models were less likely to recommend that fewer oocytes than retrieved be exposed to sperm as a woman’s age increased. For example, the models recommended that fewer oocytes than retrieved be exposed to sperm for 80% of women younger than 32 years and for less than 2% of women aged 41 to 42 years.

“The current political environment may force transformation of ART practices in which the number of embryos created must be minimized to avoid discarding or abandoning embryos,” Correia and colleagues wrote. “Clinicians will have to consider the clinical success, logistic and financial practice of multiple rounds of egg thawing, fertilization and transfer against the legal implications and loss of personal autonomy regarding surplus embryos. Our diagnostic study allows patients and clinicians a tool to minimize embryo creation if they deem it appropriate for their practice setting and personal preference.”