Birth rates for women who underwent assisted reproduction using fresh donor oocytes were significantly higher than for women who used cryopreserved-thawed embryos, based on data from more than 33,000 women.
Cryopreserved-thawed embryo transfers in donor oocyte cycles have gained in popularity in recent years for reasons including “convenience, elimination of the need for synchronization between donor and recipient cycles, and/or increasing utilization of preimplantation genetic testing for aneuploidy,” wrote Iris G. Insogna, MD, of Brigham and Women’s Hospital, Boston, and colleagues.“ However, to date, no comparison of pregnancy outcomes has been made between transfers of fresh embryos and cryopreserved-thawed embryos derived exclusively from fresh donor oocytes,” they said.
In a retrospective cohort study published in JAMA, the researchers identified 33,863 women who underwent IVF cycles using freshly retrieved oocytes with a total of 51,942 embryo transfer cycles; 15,308 fresh embryo transfer cycles, and 36,634 cryopreserved-thawed embryo transfer cycles.
Overall, the live birth rate was 56.6% for cycles involving fresh donor oocytes compared to 44.0% for cycles with cryopreserved-thawed embryos, with an adjusted relative risk of 1.42 after the researchers controlled for donor age, day of embryo transfer, use of gestational carrier, and assisted hatching. Demographics were similar between women who received fresh vs. cryopreserved-thawed embryos including median age (42 years for both), gravidity (1 for both), parity (0 vs. 1), and body mass index (24.5 vs. 24.4 kg/m2).
Clinical pregnancy rates for women with fresh vs. cryopreserved-thawed embryo transfers were 66.7% and 54.2%, respectively, and miscarriage rates were approximately 9% for both groups.
The average number of embryos transferred was similar between the groups, and blastocysts were transferred in 92.4% and 96.5% of fresh embryo and cryopreserved-thawed embryo transfer cycles, respectively.
The finding that, in cycles using fresh donor oocytes, fresh embryo transfer yielded higher birth rates than transfer of cryopreserved-thawed embryo transfer “was in contrast to previous investigations of cycles using autologous oocytes that demonstrated higher live birth rates following cryopreserved-thawed embryo transfers,” the researchers noted.
Live birth rates remained higher in cases of fresh embryo transfer when preimplantation genetic testing for aneuploidy (PGT-A) was performed, they added.
The study findings were limited by several factors, including the retrospective design and lack of data on potential confounding factors in the donor population, such as age, ethnicity, BMI, and smoking status, the researchers said. However, the results have implications for clinical practice by providing informed counseling information, given the significantly greater complexity of preparing a fresh transfer of an embryo from a fresh donor oocyte, the researchers noted. In addition, “given the considerable financial investment, these data may influence patient decision-making regarding transferring a fresh embryo derived from a fresh donor oocyte vs. cryopreserving all embryos a priori for convenience,” they said. More data on the cost-effectiveness of fresh vs. cryopreserved-thawed embryo transfer in the study population also would help guide clinical practice, they said.
Prospective studies needed to confirm potential
“For women who use autologous oocytes, there is increasing evidence for improved pregnancy rates by frozen embryo transfer (FET) rather than fresh, particularly in women with good ovarian response to gonadotropins,” Mark P. Trolice, MD, of the University of Central Florida, Orlando, said in an interview. The current study was important because it examined “whether the same concept applies with the use of embryos from donor oocytes,” he said.
Dr. Trolice, director of Fertility CARE: The IVF Center, in Orlando, said he was surprised by the study findings. The study “contradicts the experience in cycles using autologous oocytes,” he said. “Fresh embryo superiority remained after a subgroup analysis of first embryo transfers for fresh and frozen cycles as well as for embryos that underwent PGT-A (preimplantation genetic testing for aneuploidy, typically resulting in FET cycles, although a small percentage of cycles underwent fresh embryo transfer), yielding no difference to non-PGT-A fresh cycles. This reinforces the prior evidence for lack of improvement following PGT-A in women less than age 35 years,” he noted.
“Coincidentally, the same findings were discovered using the same SART [Society for Assisted Reproductive Technology] database (from 2013 to 2015), namely fresh embryo transfer from donor oocytes was more likely to result in a live birth – 55.7% versus 39.5%,” said Dr. Trolice. “An abstract presented at the 2017 ASRM annual meeting also used the SART data base (from 2003 to 2014) and demonstrated live birth rates from fresh transfer of embryos using donor oocytes were 15%-20% higher than those from frozen embryo transfers,” he noted.
“In summary, the use of fresh embryos from donor oocytes consistently appears to have superior pregnancy outcomes compared with frozen embryos; a nearly 13% absolute difference in this recent study,” said Dr. Trolice. The strengths of the study included the primary outcome of live births and the heterogeneity, with cycles taken from all participating U.S. SART clinics, Dr. Trolice noted. Limitations included the “retrospective design with the inherent risk of selection bias and the lack of information on the embryo freezing method, i.e., the older ‘slow-freeze’ or the more advanced and popular method of vitrification,” he added. “Randomized, prospective studies are needed to more accurately address this important issue,” he emphasized.
The study received no outside funding. Lead author Dr. Insogna disclosed part-time work as an assistant physician for Teladoc Health. Dr. Trolice had no relevant financial conflicts to disclose.