Time to pregnancy in young women with high response to controlled ovarian stimulation undergoing fresh transfer vs. a freeze-all strategy after in vitro fertilization treatment—a nationwide register-based cohort study

Objective

To investigate the time to pregnancy in women ≤37 years of age with high response to controlled ovarian stimulation and undergoing an initial fresh transfer vs. those women proceeding with a freeze-all strategy.

Design

A retrospective cohort study.

Subjects

The study included 56,614 women, aged ≤37 years and those with ≥15 oocytes retrieved after their first oocyte retrieval for in vitro fertilization (IVF) between January 2014 and December 2019, with data entered in the Society of Assisted Reproductive Technology Clinical Outcomes Reporting System.

Exposure

Initial fresh autologous IVF and fresh embryo transfer cycles compared with a freeze-all strategy of embryos

Main Outcome Measures

The primary outcome was time to pregnancy resulting in live birth, defined as the start of controlled ovarian stimulation through 10 days after embryo transfer. Secondary end points included clinical pregnancy rate (CPR), miscarriage rate, live birth rate (LBR) per embryo transfer, rates of ovarian hyperstimulation syndrome, singleton birthweights, and preterm birth rate. The outcomes were assessed with proportional hazard regression analysis and adjusted for body mass index, protocol type, insemination method, days of ovarian stimulation, number of embryos transferred in the initial cycle, and reporting year of retrieval cycle. Further, a subgroup analysis was performed based on the number of oocytes retrieved (cohort A: 15–19, cohort B: 20–24, cohort C: 25–29, cohort D: 30–34, cohort E: 35–39, and cohort F: ≥40).

Results

A total of 56,614 patients were included in the analysis. A total of 35,058 women (mean [SD] age, 31 [3.28] and mean [SD] body mass index, 26.4 [6.23]) underwent fresh embryo transfers and 21,556 women (mean [SD] age, 31 [3.32] and mean [SD] body mass index, 26.3 [6.19]) underwent a freeze-all strategy. The time to pregnancy in weeks, mean (SD) in women who had a fresh embryo transfer was 12.6 (20.6) and 20.8 (21.9) in women who used the freeze-all strategy. After adjusting for multiple treatment variables there was a statistically significant shorter time to pregnancy in those who had a fresh embryo transfer than those who used a freeze-all strategy (adjusted hazard ratio, 1.66 [95% confidence interval {CI}, 1.62–1.69], adjusted mean difference, −8.1 [95% CI, −8.64 to −7.55] weeks). In the adjusted subgroup analyses, the significant reduction in time to pregnancy between groups was compromised by a statistically significant reduction in LBR and CPR in the initial transfer cycle, but not the cumulative outcomes. The adjusted relative risk, 95% CI for LBR between groups in cohort A was 0.94 (0.92–0.97) and cohort F was 0.79 (0.72–0.87). The adjusted relative risk, 95% CI for CPR between groups in cohort A was 0.91 (0.89–0.94) and cohort F was 0.80 (0.74–0.87).

Conclusion

In women ≤37 years with ≥15 oocytes retrieved after IVF, a fresh embryo transfer was associated with a statistically significant reduction in time to achieve a pregnancy, a difference of 6–8 weeks compared with a freeze-all strategy. The occurrence of ovarian hyperstimulation syndrome was <2% in women who underwent a fresh embryo transfer. Although a fresh embryo transfer is safe and effective, the benefit of reduction in time to pregnancy was compromised by a significant decline in LBRs with increasing number of oocytes retrieved.