Prediction tool to aid clinicians in determining optimal number of oocytes to expose to sperm: Study

The number of assisted reproductive technology (ART) cycles conducted each year continues to climb. As the effectiveness of ART has greatly improved over the last few decades, more high-quality embryos are being created in each cycle, and a live birth is achievable with fewer embryos.

Patients must choose between discarding the embryos, donating them to the embryology laboratory for teaching purposes, donating them to another patient, or paying to store the embryos in perpetuity. Patients can feel conflicted about this decision, so continue paying for storage of cryopreserved embryos indefinitely.

Surplus cryopreserved embryos also pose a dilemma for ART clinics. As the number of cryopreserved embryos increases, clinics are faced with logistical and financial strains in having to indefinitely store embryos while struggling to contact patients for their instruction on disposition. Recently, the Ethics Committee of the American Society for Reproductive Medicine updated its guidelines around unclaimed embryos, emphasizing the financial and decision challenges that surplus embryos raise for patients and ART programs.

One strategy to limit the number of surplus embryos is to limit the number of embryos created in the first place. This can occur by limiting the number of oocytes exposed to sperm and freezing or discarding the unexposed oocytes. Despite the recognized growing problem of surplus embryos and the option of oocyte vitrification, per current standards of care, clinics expose all oocytes to sperm (either with conventional insemination or intracytoplasmic sperm injection) in an ART cycle, because there currently is no validated method by which a clinic can determine how many oocytes to attempt to fertilize that will optimize patient outcomes. Of course, not all oocytes exposed to sperm result in transferable embryos and not all embryo transfers result in a live birth.

To answer the requests of patients and clinicians who seek to limit the number of surplus embryos created, authors Katharine F. B. Correia and team addressed the lack of evidence-based guidance in this area by developing a prediction algorithm according to patient and ART cycle characteristics. This prediction algorithm can aid clinicians in determining the optimal number of oocytes to expose to sperm. Optimal number is defined as enough oocytes exposed to sperm to preserve the chance of live birth while minimizing the number of surplus embryos created. The hypothesis was that authors could develop an algorithm that would provide a suitable estimate for the optimal number of oocytes to be exposed to sperm. This knowledge at the time of insemination would allow patients and clinicians to prioritize reducing the number of surplus embryos when that is an element of their decision process.

This diagnostic study used data from member clinics of the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System between 2014 to 2019. A total of 410719 oocyte retrievals and 460577 embryo transfer cycles from 311237 patients aged 18 to 45 years old who initiated their first oocyte stimulation cycle between January 1, 2014, and December 31, 2019, were included. Data were analyzed from February to June 2022.

Female patient age, anti-mullerian hormone level, diminished ovarian reserve diagnosis, number of oocytes retrieved, and the state where the clinic is located were included in the final models. The algorithm was based on 3 models with outcomes: (1) day of transfer; (2) proportion of retrieved oocytes that become usable blastocysts; and (3) number of blastocysts needed for transfer for 1 live birth to occur.

The median (IQR) age at stimulation cycle start was 35 (29-32) years and the median (IQR) number of oocytes retrieved was 10 (6-17). The likelihood of recommending that all oocytes be exposed to sperm increased with age; less than 20.0% of retrievals among patients younger than 32 years and more than 99.0% of retrievals among patients older than 42 years received recommendations that all oocytes be exposed to sperm. Among cycles recommended to expose fewer than all oocytes, the median (IQR) numbers recommended for 1 live birth were 7 oocytes (7-8) for patients aged less than 32 years, 8 (7-8) for patients aged 32 to 34 years, and 9 (9-11) for patients aged 35 to 37 years.

In this diagnostic study, to support patients and clinicians who wish to limit the creation of surplus embryos, authors developed an evidence-based prediction tool to determine how many oocytes should be exposed to sperm to optimize live birth rates but minimize the number of surplus embryos. The results suggest that fewer oocytes than the number retrieved could be exposed to sperm to get 1 live birth in more than half of ART stimulation cycles among patients younger than 38 years old and in about 20.0% of stimulation cycles among patients 38 to 40 years old. For nearly all patients older than 40 years, all oocytes retrieved should be exposed to sperm.

Patients and ART clinics are caught in a tangled web of quickly changing federal and state laws. It is unclear whether patient autonomy for personal decisions regarding using, storing, and/or discarding embryos will be possible. 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. 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. This diagnostic study allows patients and clinicians a tool to minimize embryo creation if they deem it appropriate for their practice setting and personal preference.

Source: Katharine F. B. Correia; Stacey A. Missmer; Rachel Weinerman; JAMA Network Open. 2023;6(1):e2249395.

doi:10.1001/jamanetworkopen.2022.49395