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Efficacy of the delayed start antagonist protocol for controlled ovarian stimulation in Bologna poor ovarian responders: a systematic review and meta-analysis

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Abstract

Background

Patients with a poor ovarian response (POR) represent the most difficult group of population to deal with in the clinical fertility practice. Bologna criteria are the first uniform definition of POR. Choosing a suitable controlled ovarian stimulation (COS) protocol which could give adequate oocytes to maximize the chance of obtaining at least one euploid blastocyst is crucial in the management for such patients. The delayed start antagonist protocol is a novel COS protocol designed for POR patients, however, its real efficacy is controversial compared to conventional protocols. The present study aims to summarize all available studies on this topic and perform a meta-analysis to explore the real treatment effect of this novel protocol in terms of reproductive outcomes.

Study design

PubMed, EMBASE, Google Scholar, and the Cochrane Library from database establishment to June 2019 were searched. Randomized controlled trials (RCTs), which compared delayed start antagonist protocol (Del) to conventional controlled ovarian stimulation (COS) protocols (Con) in terms of reproductive outcomes, were included. The RevMan 5.3 was used to perform statistical analysis. The primary outcomes were the cycle cancellation rate, the clinical pregnancy rate and the miscarriage rate.

Results

5 RCTs yielding 514 patients were eligible, of which 5, 5, 4 studies were included in analyzing the cycle cancellation rate, the clinical pregnancy rate, and the miscarriage rate respectively. Synthesized data of meta-analysis showed: delayed start antagonist protocol introduced a lower risk of cycle cancellation [risk ratio (RR) = 0.63, 95% confidence interval (CI) (0.45, 0.90), P = 0.01; 5 RCTs, 514 women (Del:Con = 256:258); I2 = 0%; with rates of 16.02% (Del) vs. 26.36% (Con)], an increased chance to get clinical pregnancy [RR = 2.30, 95% CI (1.38, 3.82), P = 0.001; 5 RCTs, 514 women (Del:Con = 256:258); I2 = 0%; with rates of 16.80% (Del) vs. 7.36% (Con)], and a comparable miscarriage rate [RR = 0.55, 95% CI (0.24, 1.23), P = 0.15; 4 RCTs, 58 women (Del:Con = 41:17) I2 = 17%; with rates of 19.51% (Del) vs. 35.29% (Con)] compared to conventional COS protocols.

Conclusions

Delayed start antagonist protocol was a potentially valuable alternation for poor ovarian responders. However, future RCTs with large sample size and more scientific design are needed to verify its validity and draw a sound conclusion.

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Availability of data and materials

All data generated or analysed during this study are included in this published article.

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Funding

The authors was funded by the National Natural Science Foundation of China (http://www.nsfc.gov.cn/) (Grant no. 81571441).

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Authors and Affiliations

  1. Reproductive Medicine Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China

    Shuang Yang, Nenghui Liu, Yanping Li, Lei Zhang & Rongya Yue

  2. Clinical Research Center For Women’s Reproductive Health In Hunan Province, 87 Xiangya Road, Changsha, 410008, Hunan, China

    Shuang Yang, Nenghui Liu, Yanping Li, Lei Zhang & Rongya Yue

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  1. Shuang Yang
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Contributions

YS contributed to the study design and acquisition of data, article drafting and revising as well as organization of the final approval of the version to be published. ZL contributed substantially to the interpretation of the data and helped with drafting and revision of the article. LNH and LYP contributed to conception and design, acquisition of data and analysis and interpretation of data. ZL and YRX contributed significantly to the acquisition, analysis and interpretation of the data. LNH and LYP helped with revision of the article. All authors read and approved the final manuscript.

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Correspondence to Nenghui Liu.

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Yang, S., Liu, N., Li, Y. et al. Efficacy of the delayed start antagonist protocol for controlled ovarian stimulation in Bologna poor ovarian responders: a systematic review and meta-analysis. Arch Gynecol Obstet 303, 347–362 (2021). https://doi.org/10.1007/s00404-020-05894-8

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