In vitro fertilization (IVF) has transformed reproductive medicine since its inception, with over 10 million children born via assisted reproductive technology (ART). The core of IVF treatment revolves around one key decision: when to transfer the embryo. Traditionally, embryos were transferred on day three, during the cleavage stage, but advancements have led to a shift toward day five or six, during the blastocyst stage. This article evaluates the efficacy of this change and its impact on live birth rates.
The Shift Toward Blastocyst Transfers
With the improvements in in vitro culture and cryopreservation techniques, many fertility clinics have transitioned to blastocyst-stage transfers. Why? Blastocysts, the embryo stage at day five or six, have a greater chance of implantation as they align more closely with the window of uterine receptivity. Additionally, only the most viable embryos tend to reach this stage, theoretically leading to better outcomes.
“Blastocyst transfers have shown better outcomes in terms of live birth rates after the first embryo transfer,” state the researchers. This shift in practice is based on the belief that extending the culture period leads to better embryo selection.
However, the researchers go on to add, “While blastocyst-stage transfers may show better immediate outcomes, we must consider the cumulative live birth rate, including both fresh and frozen embryo transfers, to determine the true effectiveness of this approach.”
What the Study Found
The study examined cumulative live birth rates in women undergoing IVF who had at least four embryos available. It compared the outcomes of blastocyst-stage versus cleavage-stage transfers in a large multicenter, randomized controlled trial. Cumulative live birth rate was defined as the rate per oocyte retrieval, including all frozen-thawed embryo transfers within a year.
Surprisingly, the cumulative live birth rate did not significantly differ between the two groups. The blastocyst group had a 58.9% cumulative live birth rate, compared to 58.4% in the cleavage-stage group. This small difference did not reach statistical significance (risk ratio 1.01, 95% confidence interval 0.84 to 1.22). However, there were some notable differences in secondary outcomes.
“Blastocyst transfers resulted in higher live birth rates after fresh embryo transfers and lower cumulative pregnancy loss rates,” say the researchers. Indeed, the blastocyst group had a higher live birth rate after fresh transfer (risk ratio 1.26, 95% confidence interval 1.00 to 1.58) and a lower cumulative pregnancy loss rate (risk ratio 0.68, 95% confidence interval 0.51 to 0.89).
Other Clinical Benefits and Risks
Beyond live birth rates, there are other clinical factors that influence the choice of embryo transfer timing. The study found that women in the blastocyst group required fewer embryo transfers to achieve a live birth compared to those in the cleavage group. On average, the number of transfers needed was 1.55 for the blastocyst group versus 1.82 for the cleavage group (P<0.001).
However, not all findings favored blastocyst transfers. The study also uncovered an increased risk of moderate preterm birth (32 to <37 weeks) in singleton pregnancies in the blastocyst group. The risk ratio for moderate preterm birth was 1.87, with a confidence interval of 1.05 to 3.34.
Despite the advantages of fresh transfers and reduced pregnancy loss, this increased risk of preterm birth raises important considerations for clinicians and patients alike. “It’s crucial to weigh these risks when deciding the best approach for each individual patient,” the authors note.
A Balanced Approach to Embryo Transfer
Given the findings of this study, it’s clear that the choice between blastocyst and cleavage-stage transfers is not black and white. While blastocyst-stage transfers may offer some benefits, particularly in reducing the number of transfers needed and lowering pregnancy loss rates, the cumulative live birth rate—perhaps the most important metric for patients—remains virtually the same between the two approaches.
“Our results suggest that for women with a good prognosis, both blastocyst and cleavage-stage transfers can lead to similar cumulative live birth rates,” conclude the researchers. The findings provide a nuanced perspective on embryo transfer policies, encouraging individualized treatment plans based on a patient’s unique circumstances and preferences.
Citation:
Cornelisse S, Fleischer K, van der Westerlaken L, et al. Cumulative live birth rate of a blastocyst versus cleavage stage embryo transfer policy during in vitro fertilisation in women with a good prognosis: multicentre randomised controlled trial. BMJ. 2024;386:080133. doi:10.1136/bmj-2024-080133
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