Cost-effectiveness of single euploid frozen embryo transfer in a true natural versus a hormonal replacement cycle

To evaluate the cost-effectiveness of a true natural cycle (tNC) vs. a hormonal replacement therapy (HRT) cycle in single euploid frozen embryo transfers (seFET).

Retrospective cohort study between April 2017 and September 2021.

Women who underwent seFET in a tNC or an HRT protocol prepared with oral estrogen and vaginal progesterone supplementation.

True natural cycle and HRT self-etch cycles.

Clinical outcomes and their associated treatment costs per protocol, and the incremental cost-effectiveness ratio (ICER).

This study included 1,188 women with 788 (66.3%) prepared through the HRT protocol and 400 (33.7%) using the tNC protocol. Whereas pregnancy rates were not significantly different between the groups (HRT 64.5%, tNC 63.8%), tNC resulted in a significantly lower miscarriage rate (MR) (tNC 10.3% vs. HRT 18.9%) and a higher live birth rate (LBR) (tNC 53.0% vs. HRT 44.9%). After adjusting for confounders (age, body mass index, and antimüllerian hormone), the HRT protocol was still associated with a significantly higher MR (odds ratio, 2.44; 95% confidence interval, 1.38-4.33]) and lower LBR (odds ratio, 0.41; 95% confidence interval, 0.23-0.72). The average cost-per-cycle was significantly higher for tNC (Arab Emirates Dirham [AED] 9,331 [US$2,540]) compared with HRT (AED 7,314 [US$1,991]). The ICER of tNC vs. HRT was AED 27,494 ($7,486) per additional LB. In sensitivity analyses, tNC was cost-effective in about 65% and 90% of simulations at a willingness-to-pay for a LB of at least AED 35,000 ($9,529) and AED 85,000 ($23,142), respectively. Extrapolated scenario analyses, conducted to enhance generalizability, showed an estimated ICER of AED 3,080 ($839) per additional LB for the modified NC vs. HRT, and estimated ICERs of AED 28,738 ($7,824) for tNC vs. HRT with intramuscular progesterone, and AED 19,230 ($5,236) for tNC vs. HRT combining micronized vaginal progesterone and intramuscular progesterone.

With increasing FET cycles, it is crucial to identify the best endometrial preparation protocol. This study highlights the trade-off between the increased clinical effectiveness of tNC, largely because of reduced MR, and the lower costs of HRT in endometrial preparation for seFET. To identify the option that provides the best value-for-money, payers must consider their willingness to pay for a LB.