Fresh Embryo Transfer May Offer Higher Live Birth Rates Than Freeze-All Strategy in Low-Prognosis IVF Patients: Study

"In our randomized controlled trial, women with a low prognosis for successful pregnancy through in vitro fertilization had a higher live birth rate with fresh embryo transfer than frozen embryo transfer," the researchers wrote. "Women with a low prognosis for IVF may benefit more from fresh embryo transfer and should consider it as a preferred option in the future."

The researchers note that despite advancements in IVF technology, managing women with a low prognosis remains a clinical challenge. Defined by the POSEIDON criteria as those with fewer oocytes retrieved (≤9) or poor ovarian reserve, nearly 40% of women undergoing IVF fall into this category, experiencing significantly lower cumulative live birth rates. While embryo cryopreservation was initially developed to preserve surplus embryos, the elective freeze-all strategy has gained popularity to optimize pregnancy outcomes and reduce ovarian hyperstimulation risks. However, its benefits for low-prognosis women remain unclear. Daimin Wei, Key Laboratory of Reproductive Endocrinology, Ministry of Education, Shandong University, Jinan, China, and colleagues determined whether frozen embryo transfer improves live birth rates compared to fresh transfer in this population.

For this purpose, the researchers conducted a pragmatic, multicenter, randomized controlled trial across nine academic fertility centers in China. A total of 838 women with a low prognosis for IVF, defined by ≤9 oocytes retrieved or poor ovarian reserve, were enrolled. Participants were randomly assigned (1:1) to undergo fresh or frozen embryo transfer. In the frozen embryo transfer group, all embryos were cryopreserved for later transfer, while the fresh embryo transfer group received embryos immediately after oocyte retrieval.

The primary outcome was live birth at ≥28 weeks gestation, with secondary measures including pregnancy outcomes, birth weight, and maternal or neonatal complications.

The following were the key findings of the study:

• The live birth rate was lower in the frozen embryo transfer group (32%) than the fresh embryo transfer group (40%), with a relative ratio of 0.79.
• The clinical pregnancy rate was also lower in the frozen embryo group (39%) than in the fresh embryo group (47%), with a relative ratio of 0.83.
• The cumulative live birth rate was lower in the frozen embryo transfer group (44%) compared to the fresh embryo transfer group (51%), with a relative ratio of 0.86.
• There were no significant differences in birth weight, incidence of obstetric complications, or risk of neonatal morbidities between the two groups.

The researchers conclude that the trial, along with previous studies, highlights that the benefits and risks of the freeze-all strategy vary based on ovarian response. Future research should focus on identifying clinical characteristics and biomarkers in serum or the endometrium to better predict the optimal transfer strategy for women undergoing IVF. Further studies are needed to determine the ideal number and stage of embryos for fresh transfer in low-prognosis patients to achieve a singleton pregnancy.

The findings suggest that fresh embryo transfer may offer a higher live birth rate than frozen embryo transfer in this group. Strategies that prevent fresh transfers, such as accumulating embryos through back-to-back cycles or routine preimplantation genetic testing for aneuploidy, require further investigation.

"Unlike previous findings in women with a good prognosis, this study indicates that a freeze-all strategy results in lower live birth rates for those with a low prognosis. Therefore, the routine use of the freeze-all approach in this patient group is not supported," the researchers wrote.

Reference: BMJ 2025;388:e081474