Fresh or frozen oocyte donation: is there a bad egg?
In the field of reproductive endocrinology, assisted reproductive technology (ART) has undeniably revolutionized modern medicine. First, the introduction of in vitro fertilization (IVF) in the 1970s provided a beacon of hope for couples struggling with infertility. Subsequently, the introduction of oocyte donation in the 1980s presented a new opportunity for family building to patients with diminished ovarian reserve, primary ovarian insufficiency, and recurrent implantation failure, as well as same-sex male couples and single men. In 2020, 7.4% of all IVF cycles in the United States used donor oocytes or embryos. Over the last several decades, there has been a notable shift in the selection of oocyte donors. Initially, donors were women who had undergone IVF themselves and were left with supernumerary oocytes at the time of retrieval. Today, most oocyte donors are voluntary fertile women, often motivated by altruistic reasons. Since 2012, the amelioration of oocyte cryopreservation techniques by vitrification significantly increased the use of frozen donor oocytes. Compared with fresh donor oocyte cycles, the availability of cryopreserved oocytes has reduced the financial cost and wait time for recipients, in addition to increasing the chances of identifying a donor who shares a similar ethnic background. Clinically, it has also eliminated the need for synchronization of donor and recipient cycles.
In a prior study that used data from the Centers for Disease Control and Prevention’s National ART Surveillance System, fresh and frozen donor oocytes yielded comparable live birth rates among patients undergoing fresh embryo transfer in 2013. That study was limited, however, by the lack of data on obstetric and perinatal outcomes. Another study used data from the 2012–2015 Society for Assisted Reproductive Technology Clinic Outcome Reporting System to demonstrate that the odds of live birth and good perinatal outcome (defined as a term delivery at 37 weeks or beyond and normal birthweight between 2,500 and 4,000 g) were slightly lower with frozen as compared with fresh donor oocytes. The main limitation of the second study was the exclusion of frozen embryo transfer (FET) cycles. To this day, the existing literature on perinatal outcomes from fresh and frozen donor oocytes remains sparse.
In this month’s edition of Fertility and Sterility, Braun et al. performed a retrospective cohort study using data from the National ART Surveillance System. The study aimed to examine trends, characteristics, and outcomes of donor oocyte embryo transfer cycles based on oocyte state (fresh or frozen) and the resultant embryo state. Additionally, the study investigated the association between oocyte state and the likelihood of a term, normal weight infant among singleton live births.
The analyses included 135,085 donor oocyte embryo transfer cycles performed from 2013 to 2020. During this time period, the proportion of FET cycles nearly doubled (from 42.3% to 76.6%), whereas the proportion of fresh embryo transfer cycles was more than halved (from 57.7% to 23.3%). Among fresh embryo transfers, the proportion that used frozen oocytes more than tripled (from 19.9% to 68.3%). Importantly, the proportion of cycles with single embryo transfer increased from 36.4% to 85.5%.
The investigators then examined a subset of 48,679 donor oocyte embryo transfer cycles performed between 2018 and 2020. The mean donor age was 26.8 years, although this field was missing for over one-third (35%) of cycles. The mean recipient age was 42.0 years, only slightly increased from the mean of 41 years in 2010. Interestingly, preimplantation genetic testing was performed in almost one-third (32%) of those cycles, although the existing evidence suggests increased cost with no improvement in live birth rate in this setting. Despite the increased utilization of frozen donor oocytes and the continuous improvement in laboratory techniques, the live birth rates were found to be lower with frozen as compared with fresh donor oocytes for both fresh (46.2%, 55.9%; adjusted relative risk, 0.83; 95% confidence interval, 0.79–0.87) and frozen (41.3%, 45%; adjusted relative risk, 0.94; 95% confidence interval, 0.91–0.98]) embryo transfer cycles. Among cycles resulting in a singleton live birth, however, oocyte and embryo state were not associated with the likelihood of a term, normal weight infant. Ultimately, fertility providers strive to assist patients in achieving their goal of bringing home a healthy infant, and these findings support the use of frozen donor oocytes as a safe alternative to fresh oocytes.
The primary strength of this study is undeniably the use of a large national database including almost all ART procedures in the United States, supporting the external validity of the findings. However, this study also has a few limitations. First, oocyte state was not reported for cryopreserved embryos until 2018. Second, because of the retrospective nature of the study and the large amount of missing data, some variables could not be included in the multivariable analysis. Lastly, the study did not compare all four oocyte and embryo states simultaneously, which could have provided further clinical guidance when counseling patients on outcomes
In summary, this national registry study demonstrated a dramatic shift in practice patterns among donor oocyte embryo transfer cycles in the United States from 2013 to 2020. The vast majority of these cycles are now FETs; furthermore, among the fresh embryo transfers, the majority are derived from frozen oocytes. Consistent with the American Society for Reproductive Medicine and Society for Assisted Reproductive Technology guidelines, single embryo transfers now account for over 85% of donor oocyte embryo transfers.
Live birth rates are slightly lower with frozen than with fresh donor oocytes, but perinatal outcomes are similar. This study validates the use of frozen donor oocyte cycles as a viable option that may provide flexibility and potentially reduce the burden on both donors and recipients without compromising perinatal outcomes. In conclusion, when it comes down to oocyte donation, fresh and frozen oocytes are both good eggs.
Source: Luce A. Kassi, M.D. Jennifer L. Eaton, M.D.;FertSert
https://doi.org/10.1016/j.fertnstert.2024.08.338
