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Comparative Study
. 2024 Jun 5;14(1):12894.
doi: 10.1038/s41598-024-63842-x.

The cumulative live birth rate and cost-effectiveness of the clomiphene and gonadotropin cotreatment protocol versus the mid-luteal GnRH agonist protocol in women over 35 years old

Yanhui Li  1 , Dan Luo  2 , Tao Li  2 , Hui Ding  2 , Yi Liu  2
Affiliations
Comparative Study

The cumulative live birth rate and cost-effectiveness of the clomiphene and gonadotropin cotreatment protocol versus the mid-luteal GnRH agonist protocol in women over 35 years old

Yanhui Li et al. Sci Rep. .

Abstract

The decrease in assisted reproductive technology success among older women, attributed to decreased oocyte quantity and quality, poses a significant challenge. Currently, no consensus on the optimal ovarian stimulation protocol for older women undergoing IVF exists. This retrospectively registered cohort study aimed to compare the cumulative live birth rate (CLBR), time to live birth (TTLB), and cost-effectiveness among women older than 35 years who were receiving either the gonadotropin-releasing hormone agonist (GnRHa) or clomiphene citrate and gonadotropin cotreatment with ovarian stimulation (CC cotreatment) protocol. To compare treatment outcomes, we performed propensity score matching (PSM) on 2871 IVF cycles in women older than 35 years who received either the GnRHa or CC cotreatment protocol, resulting in 375 cycles in each group. Additionally, a decision tree model was utilized to assess the cost-effectiveness of the two protocols. Following PSM, both groups had similar baseline characteristics. The CC cotreatment protocol resulted in a greater rate of cycle cancellation (13.07% vs. 8.00%, p = 0.032), but the groups maintained comparable fertilization rates and embryo quality. Although the TTLB was longer in the CC cotreatment group, the CLBR per initial cycle (41.07% vs. 45.33%, p = 0.269) and delivery outcomes were similar between the two groups at the 24 months follow-up. Additionally, the average cost per live birth in the CC cotreatment group was 21.27% lower than in the GnRHa group (¥32,301.42 vs. ¥39,174.22). In conclusion, for women older than 35 years undergoing IVF, the CC cotreatment protocol offered a comparable CLBR to the GnRHa protocol but with reduced costs, indicating its potential as a viable and cost-effective ovarian stimulation option.Clinical trial registration: https://www.chictr.org.cn/ , identifier [ChiCTR2300076537].

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Decision tree model based on the real-world data of this study. Note CC cotreatment, clomiphene citrate and gonadotropin cotreatment; GnRHa, gonadotropin-releasing hormone agonist; nodes within the model are marked by circles, and triangles define endpoints.
Figure 2
Figure 2
Kaplan–Meier curves of the cumulative live birth rate (CLBR) in patients receiving the CC cotreatment or GnRHa protocol. (a) CLBR of all the patients; (b) CLBR in women aged > 35 and < 40 years; (c) CLBR in women aged ≥ 40 years; (d) CLBR in women undergoing their first IVF cycle; (e) CLBR in women undergoing their second IVF cycle. CI, confidence interval; CC cotreatment, clomiphene citrate and gonadotropin cotreatment; GnRHa, gonadotropin-releasing hormone agonist; HR, hazard ratio.
Figure 3
Figure 3
One-way sensitivity analysis of the cost-effectiveness ratio between the CC cotreatment and GnRHa protocols. (a) One-way C/E sensitivity analysis. (2) One-way NMB sensitivity analysis. (3) Tornado diagram. The parameters affecting the ICER are shown. CC cotreatment, clomiphene citrate and gonadotropin cotreatment ovarian stimulation; GnRHa, gonadotropin-releasing hormone agonist; LBR, live birth rate; OS, ovarian stimulation; OPU, oocyte pick-up; ICER, incremental cost-effectiveness ratio; NMB, net monetary benefit.
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