Montoya-Botero Pedro, Drakopoulos Panagiotis, González-Foruria Iñaki, Polyzos Nikolaos P
Conceptum-Unidad de Fertilidad del Country, Bogotá 110221, Colombia.
Department of Obstetrics, Gynaecology and Reproductive Medicine, Dexeus Mujer, Dexeus University Hospital, Barcelona 08028, Spain.
Hum Reprod Open. 2021 Feb 14;2021(1):hoaa066. doi: 10.1093/hropen/hoaa066. eCollection 2021.
Are cumulative and live birth rates (LBRs) comparable in poor ovarian response women treated with different protocols of mild stimulation IVF (i.e. oral compounds, lower doses or shorter treatments) versus conventional IVF?
Mild ovarian stimulation (MOS) results in comparable outcomes to those of conventional stimulation in poor ovarian response patients with low ovarian reserve.
Several randomized trials and meta-analyses have been published evaluating the role of mild (MOS) versus conventional ovarian stimulation in poor ovarian response patients. Most report a potentially higher safety profile, patient satisfaction and lower costs, suggesting that the higher cycle cancellation rate and fewer oocytes retrieved following MOS does not affect the final reproductive outcome. Additionally, over the last few years, new publications have added data regarding MOS, and shown the possible benefit of a higher oocyte yield which may also improve prognosis in patients with poor ovarian response.
We conducted a systematic search of relevant randomized controlled trials (RCTs). We searched electronic databases, including MEDLINE, EMBASE, LILACS-BIREME, CINAHL, The Cochrane Library, CENTRAL (Cochrane Register), Web of Science, Scopus, Trip Database and Open Grey, to identify all relevant studies published up to March 2020. We examined trial registries for ongoing trials. No publication-year or language restrictions were adopted. We explored the reference list of all included studies, reviews and abstracts of major scientific meetings. The primary outcomes were cumulative and fresh LBR (CLBR and FLBR) per woman randomized.
PARTICIPANTS/MATERIALS SETTING METHODS: We included subfertile women undergoing IVF/ICSI characterized as poor responders and compared primary and secondary outcomes between the different protocols of mild stimulation IVF (i.e. oral compounds, lower doses or shorter treatments) and conventional IVF. We used the PICO (Patients, Intervention, Comparison and Outcomes) model to select our study population.
Overall, 15 RCTs were included in the meta-analysis. CLBR and FLBR were comparable between mild versus conventional stimulation (RR 1.15; 95% CI: 0.73 - 1.81; = 0%, n = 424, moderate certainty and RR 1.01; 95% CI: 0.97 - 1.04; = 0%, n = 1001, low certainty, respectively). No difference was observed either when utilizing oral compounds (i.e. letrozole and clomiphene) or lower doses. Similarly, ongoing pregnancy rate (OPR) and clinical pregnancy rate (CPR) were equivalent when comparing the two groups (RR 1.01; 95% CI: 0.98 - 1.05; = 0%, n = 1480, low certainty, and RR 1.00; 95% CI: 0.97 - 1.03; = 0%, n = 2355, low certainty, respectively). A significantly lower oocyte yield (mean differences (MD) -0.80; 95% CI: -1.28, -0.32; = 83%, n = 2516, very low certainty) and higher rate of cycle cancellation (RR 1.48; 95% CI: 1.08 - 2.02; = 62%, n = 2588, low certainty) was observed in the MOS group.
The overall quality of the included studies was low to moderate. Even though strict inclusion criteria were used, the selected studies were heterogeneous in population characteristics and treatment protocols. We found no differences in CLBR between MOS and COS (95% CI: 0.73 - 1.81.).
MOS could be considered as a treatment option in low prognosis poor responder patients, given that it results in similar fresh and CLBRs compared with COS. A milder approach is associated with a lower number of oocytes retrieved and a higher cancellation rate, although treatment cost is significantly reduced. Future research should focus on which type of ovarian stimulation may be of benefit in better prognosis women.
STUDY FUNDING/COMPETING INTERESTS: There were no sources of financial support. N.P.P. received research grants, honoraria for lectures from: Merck Serono, MSD, Ferring Pharmaceuticals, Besins International, Roche Diagnostics, IBSA, Theramex and Gedeon Richter. P.D. received unrestricted grants and honoraria from Merck Serono, MSD and Ferring Pharmaceuticals. I.G.F. received unrestricted grants and honoraria from Merck Serono, MSD, Ferring Pharmaceuticals, Gedeon-Richter and IBSA. P.M.B. reported no conflict of interest.
CRD42020167260.
对于卵巢反应不良的女性，采用不同方案的轻度刺激体外受精（即口服药物、较低剂量或较短疗程）与传统体外受精相比，累积活产率和活产率（LBRs）是否具有可比性？
对于卵巢储备低、卵巢反应不良的患者，轻度卵巢刺激（MOS）与传统刺激的结果相当。
已经发表了几项随机试验和荟萃分析，评估了轻度（MOS）与传统卵巢刺激在卵巢反应不良患者中的作用。大多数报告显示其安全性可能更高、患者满意度更高且成本更低，这表明MOS后更高的周期取消率和更少的获卵数并不影响最终的生殖结局。此外，在过去几年中，新的出版物增加了关于MOS的数据，并显示出更高的卵母细胞产量可能带来的益处，这也可能改善卵巢反应不良患者的预后。
研究设计、规模、持续时间：我们对相关随机对照试验（RCTs）进行了系统检索。我们检索了电子数据库，包括MEDLINE、EMBASE、LILACS - BIREME、CINAHL、Cochrane图书馆、CENTRAL（Cochrane注册库）、科学网、Scopus、Trip数据库和Open Grey，以识别截至2020年3月发表的所有相关研究。我们查阅了试验注册库以获取正在进行的试验。未采用出版年份或语言限制。我们查阅了所有纳入研究、综述以及主要科学会议摘要的参考文献列表。主要结局是每位随机分组女性的累积活产率和新鲜活产率（CLBR和FLBR）。
参与者/材料、设置、方法：我们纳入了接受体外受精/卵胞浆内单精子注射（IVF/ICSI）且被判定为反应不良的不育女性，并比较了不同方案的轻度刺激体外受精（即口服药物、较低剂量或较短疗程）与传统体外受精之间的主要和次要结局。我们使用PICO（患者、干预措施、对照和结局）模型来选择我们的研究人群。
总体而言，荟萃分析纳入了15项RCTs。轻度刺激与传统刺激之间的CLBR和FLBR具有可比性（RR 1.15；95% CI：0.73 - 1.81；I² = 0%，n = 424，中等确定性；以及RR 1.01；95% CI：0.97 - 1.04；I² = 0%，n = 1001，低确定性）。在使用口服药物（即来曲唑和克罗米芬）或较低剂量时，未观察到差异。同样，比较两组时，持续妊娠率（OPR）和临床妊娠率（CPR）相当（RR 1.01；95% CI：0.
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