Effectiveness of mild ovarian stimulation versus GnRH agonist protocol in women undergoing assisted reproductive technology: a meta-analysis

Abstract

Objective: our meta-analysis was conducted to evaluate the effectiveness of the mild ovulation induction protocol using CC/gonadotropin/GnRH antagonist compared to the conventional GnRH agonist protocol in women undergoing ART. Method: Six electronic databases were searched from their date of establishment until August 2016. Outcomes in our analysis were calculated in terms of relative risk (RR) and weighted mean differences (WMD) and standard mean differences (SMD) with 95% confidence intervals (CI) using random effect models or fixed effect models.

Results: Six prospective controlled clinical trials with 1543 women comparing the clinical impacts of the two protocols were included. The synthesized results suggested a significant reduction in the quantity of gonadotropins (SMD: −1.96, 95% CI: −2.28 to 1.64, I² = 78.5%), the incidence of OHSS (RR: 0.16, 95% CI 0.03–0.86, I² = 0%) and an increase in the cycle cancelation rate (RR: 1.46, 95% CI 1.05–2.03, I² = 89.4%). While no evidence of statistically significant differences between the groups existed in the other clinical outcomes.

Conclusion: This study suggested that the probable benefits of the mild protocol, including its less costs and safer process without reducing the overall IVF treatment success rates, seemed to make it a better treatment option. Larger sample prospective trials evaluating live birth, clinical pregnancy, OHSS, multiple pregnancy incidence and so on were desired to establish.

Chinese abstract

目的：进行meta分析以对比用CC/促性腺激素/GnRH拮抗剂进行温和诱导排卵和常规GnRH激动剂方案对ART治疗妇女的有效性。

方法：搜索了六个电子数据库从建立日期开始至2016年8月的数据。使用随机效应模型或固定效应模型, 以相对危险度（RR）, 加权均数差（WMD）以及95%置信区间（CI）的标准化均数差（SMD）对搜索结果进行分析。

结果：纳入了6项包括1543名妇女在内的比较两种方案临床影响的前瞻性对照实验。综合结果表明了促性腺激素量(SMD:-1.96, 95% CI:-2.28 to 1.64,I²=78.5%)和OHSS发生率(RR: 0.16, 95% CI 0.03–0.86, I²=0%)的显著降低以及循环消除率的升高(RR: 1.46, 95% CI 1.05–2.03, I²=89.4%)。然而, 其他临床研究结果没有证据表明组间存在统计学显著差异。

结论：研究结果表明了卵巢微刺激方案的可能收益, 在满足更低成本和更安全过程的同时并不降低IVF治疗的总体成功率, 似乎微刺激可成为一种较好的临床方案。但需要设计更大的样本量来评估活产率, 临床妊娠率, OHSS发生率和多胎妊娠率等。

Keywords:

• Clomiphene citrate
• CC
• GnRH antagonists
• meta-analysis
• mild ovarian stimulation

Acknowledgements

Yuan Fan made substantial contributions to the acquisition of data, analysis and interpretation of data and drafting the manuscript. Li Tian initiated the project and revised the manuscript critically. All other listed authors also contributed to preparation of the manuscript. All authors read and approved the final manuscript.

Declaration of interest

This work was supported by funding from The Chinese Ministry of Health Special Fund for Public Welfare Industry Research (No. 201302013), which is received by Li Tian. There are no conflicts of interest to declare.