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From the Journals

IVF Study: Embryo Stage Transfer Timing Compared

Blastocyst vs. cleavage-stage embryo transfers yield similar live birth rates but differ in pregnancy loss and preterm birth risks, finds large Dutch IVF trial.

Conexiant

A large randomized controlled trial found no statistically significant difference in cumulative live birth rates between blastocyst-stage and cleavage-stage embryo transfers during in vitro fertilization among women. 

In the trial, published in The BMJ, researchers recruited 1,202 women aged 18 to 43 years with at least four embryos available on day 2 post-oocyte retrieval who were undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). The study was conducted across 21 centers in the Netherlands and compared outcomes between the two embryo transfer strategies.

This superiority trial was designed to prove the presence of a two-sided difference. The researchers randomly assigned the women to either blastocyst-stage transfer on day 5 (n = 603) or cleavage-stage transfer on day 3 (n = 599). The study included women in their first, second, or third IVF/ICSI cycle between August 2018 and December 2021.

The primary outcome was cumulative live birth rate per oocyte retrieval, including fresh and frozen-thawed embryo transfers, as well as natural conceptions within 1 year. Because of COVID-19 related delays, the follow-up period was extended by 5 months for some participants.

The researchers reported cumulative live birth rates of 58.9% (n = 355) for the blastocyst group and 58.4% (n = 350) for the cleavage group (risk ratio [RR] = 1.01, 95% confidence interval [CI] = 0.84–1.22) over a 12-month follow-up period.

Among the key findings were:

  • Live birth rates following fresh embryo transfer were higher in the blastocyst group (37.0% vs 29.5%, RR = 1.26, 95% CI = 1.00–1.58).
  • Cumulative pregnancy loss rates were lower in the blastocyst group (16.3% vs 24.2%, RR = 0.68, 95% CI = 0.51–0.89).
  • Fewer embryo transfers were needed to achieve live birth in the blastocyst group (mean = 1.55 vs 1.82, P < .001).
  • Moderate preterm birth (32 to < 37 weeks) in singletons was higher in the blastocyst group (8.9% vs 4.7%, RR = 1.87, 95% CI = 1.05–3.34).

No statistically significant differences were found in other obstetric or perinatal outcomes, including very preterm birth, low birth weight, or congenital anomalies.

The study provided further detailed results:

  • Mean number of aspirated oocytes: 11.45 (standard deviation [SD] = 4.9) in the blastocyst group vs 11.52 (SD = 5.2) in the cleavage group.
  • Mean number of embryos on day 2 after oocyte retrieval: 7.5 (SD = 3.2) vs 7.6 (SD = 3.6), respectively.
  • Single embryo transfer rates for fresh transfers: 82.4% in the blastocyst group and 82.5% in the cleavage group.
  • Time to conception leading to live birth was slightly shorter for the blastocyst group, with a median time of 3.1 months (95% CI = 1.9–4.2) compared with 4.7 months (95% CI = 3.6–5.8) in the cleavage group.

A planned subgroup analysis by age showed no significant interaction between age and treatment group (P = .20). However, among women ≥ 36 years (n = 431), the cumulative live birth rate was nonsignificantly higher in the blastocyst group (52.1% vs 43.1%, RR = 1.21, 95% CI = 0.99–1.48). Conversely, among women < 36 years (n = 771), the rate was lower in the blastocyst group but not significantly (62.6% vs 67.1%, RR = 0.93, 95% CI = 0.84–1.04).

The study also reported that overall embryo utilization rates were lower in the blastocyst group (55.3% vs 71.0%, P < .001).

The study's strengths included its large sample size, multicenter design, and broad inclusion criteria, enhancing generalizability. However, the trial focused on women with at least four embryos, which may limit generalizability to women with fewer embryos. Additionally, the higher-than-expected live birth rates may have reduced the study's power to detect small differences.

The per-protocol analysis was consistent with the intention-to-treat results. The investigators suggested careful interpretation of secondary outcomes, since the study wasn't specifically powered for these.

While the study found no difference in cumulative live birth rates, it highlighted potential advantages of blastocyst-stage transfers, such as lower pregnancy loss rates and fewer transfers needed to achieve live birth. However, the increased risk of moderate preterm birth raised potential safety concerns that require further research.

The authors declare no financial relationships with any organizations that might have an interest in the submitted work in the past 3 years and no other relationships or activities that could appear to have influenced the submitted work.