Abstract
Objective: To compare the cumulative live birth rates (cLBRs) after the first assisted reproductive technology (ART) cycle using flexible gonadotropin releasing hormone (GnRH)-antagonist protocol vs. standard long GnRH agonist protocol for controlled ovarian stimulation (COS) in infertile women with different ages and ovarian reserve.Methods: Women who underwent ART treatment at our center between June 1st, 2015 and December 31st, 2018 were screened. Among them, only women who underwent their first COS cycle with flexible GnRH antagonist protocol or standard long GnRH agonist protocol were included in this study. The main outcome measurement was cLBR.Results: A total of 4,402 patients were eligible for the analysis, of whom, 2,762 patients used the GnRH agonist protocol and 1,640 patients used the GnRH antagonist protocol. The cLBRs of women in the antagonist protocol group and long agonist protocol group were 45.3 and 50.0%, respectively. Subgroup multivariable regression analysis showed that, in patients with low ovarian reserve (AFC ≤ 7), the cLBR was significantly lower in the antagonist group than in the long agonist protocol group [OR (95% CI) 0.62 (0.41, 0.94)], which effect was more robust in younger patients (<30 y) [OR (95% CI) 0.29 (0.11, 0.74)]. The analysis also revealed remarkably lower cLBR in patients above 40 years regardless of their AFC, although the difference was not statistically significant. However, in patients with high ovarian reserve (AFC >24), the cLBR was higher in cycles with antagonist protocol than with the long agonist protocol [OR (95% CI) 1.43 (0.96, 2.12)], and the effect was of statistical significance in younger patients (< 30 y) [OR (95% CI) 1.78 (1.07, 2.96)].Conclusion: The present study suggests that the flexible GnRH antagonist protocol might not be suitable for patients with low ovarian reserve (AFC ≤ 7) or patients aged over 40 years. However, flexible GnRH antagonist protocol might be strongly recommended for patients under 30 years old and with high ovarian reserve (AFC > 24). For the rest groups of patients in the present cohort, antagonist protocol was slightly favored because it had lower OHSS in general and in patients with poly-cystic ovarian syndrome (PCOS) according to previous publications.
Highlights
In vitro fertilization and embryo transfer (IVF-ET) as the most effective treatment for infertility has been widely used worldwide
We found that compared with long protocol, flexible gonadotropin releasing hormone (GnRH) antagonist protocol might not be suitable for patients with basal antral follicle count (AFC) ≤7, especially those younger than 30 years and with low basal AFC, nor for patients over 40 years regardless of AFC, because it resulted in significantly lower cLBR in these subgroups (Tables 2, 3)
Our results showed that the GnRH antagonist protocol resulted in significantly and consistently lower cLBR with very robust effect value in younger patients with low ovarian reserve [odds ratios (ORs), 0.29 (0.11, 0.74), n = 112], indicating that the flexible GnRH antagonist protocol might not be suitable for this cLBRs of GnRH-ant vs. GnRH-a population
Summary
In vitro fertilization and embryo transfer (IVF-ET) as the most effective treatment for infertility has been widely used worldwide. The long protocol has plenty of advantages, such as maintaining stable and low LH and progesterone (P) levels throughout the stimulation phase, synchronized follicular development, good number of retrieved oocytes and short learning curve [6,7,8] This suppression is related to clear disadvantages including the initial flare-up and menopausal symptoms [9]. GnRH antagonist was developed about 40 years ago, but wasn’t widely applied in clinical practice until recently [3] It instantly blocks the pituitary LH secretion without any flare-up effect and is proved to be with shorter treatment duration, less use of gonadotropic hormones, improved patient acceptance, but with fewer follicles and oocytes when compared with standard long protocol in various clinical studies [4, 5, 10, 11]. Advantages of GnRH antagonist as mentioned above, numerous clinical trials and meta-analyses [12, 13] based on the studies comparing GnRH agonist protocol and antagonist protocol have showed a consistent conclusion that
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