Freeze-all is no better than fresh embryo transfer in women undergoing IVF, study says

UK: In IVF treatment, freeze-all is not better than fresh-embryo transfer with respect to efficacy, safety, and costs, states trial data published in the Health Technology Assessment. The data do not support an elective freeze in preference to fresh embryo transfer as a routine policy to improve IVF effectiveness in obtaining a healthy baby.

Globally, infertility affects an estimated 15% of couples.IVF treatment is recommended for those with prolonged unresolved infertility. Overall, the live birth rate resulting from the first fresh IVF cycle is 33.0%. Electively freezing all suitable embryos (elective freeze) is now possible due to advances in freezing techniques.

It has been suggested that the transfer of frozen-thawed embryos in a non-stimulated cycle is more conducive to early placentation and embryogenesis when compared with fresh IVF cycles. Initial research suggested that this strategy reduces the chance of ovarian hyperstimulation syndrome (OHSS), decreases maternal and perinatal risks, and improves pregnancy rates. Data was promising but since it came from small studies, was not enough to change practice and policy.

Maheshwari A, NHS Grampian and the University of Aberdeen, UK and colleague tried to evaluate if the policy of freeze-all, results in a higher healthy baby rate than the current policy of transferring fresh embryos.

The study was a pragmatic two-arm parallel randomized controlled trial (E-Freeze) conducted across 18 clinics in the UK. A total of 619 couples (the female partner aged < 42 years) undergoing their first, second, or third cycle of in vitro fertilization treatment were randomized (309 to elective freeze/310 to fresh). The primary outcome was a healthy baby after the first embryo transfer (term, singleton live birth with appropriate weight for gestation); secondary outcomes included OHSS, live birth, clinical pregnancy, pregnancy complications, cost-effectiveness, and State-Trait Anxiety Inventory scores

Key findings of the data,

• The intention-to-treat analysis showed a healthy baby rate of 20.3% in the freeze-all arm and 24.4% in the fresh-embryo transfer arm. Complier-average causal effect analysis, per-protocol analysis, and as-treated analysis showed similar results

• The risk of OHSS was 3.6% in the freeze-all arm and 8.1% in the fresh-embryo transfer arm.

• There were no statistically significant differences in the live birth rates and clinical pregnancy rates between both arms.

• Anxiety scores for male participants and female participants between the arms showed no statistically significant difference

• The economic analysis showed that freeze-all had a low probability of being cost-effective in terms of the incremental cost per healthy baby and incremental cost per live birth.

The authors conclude that freezing all did not lead to a higher chance of having a healthy baby when compared to fresh embryo transfer. Strategies did not show differences in the rate of live births, the miscarriage, and the pregnancy complications.

Although the results were limited by not reaching the estimated full sample size as well as non-adherence, the study findings do not support a shift to a universal elective freeze policy on grounds of clinical or cost-effectiveness. It should only be adopted if there is a definite clinical indication, the authors wrote.

Reference:

Maheshwari A, Bari V, Bell J L, Bhattacharya S, Bhide P, Bowler U, et al. Transfer of thawed frozen embryo versus fresh embryo to improve the healthy baby rate in women undergoing IVF: the E-Freeze RCT. Health Technol Assess 2022;26(25). https://doi.org/10.3310/AEFU1104