Conforti Alessandro, Carbone Luigi, Di Girolamo Raffaella, Iorio Giuseppe Gabriele, Guida Maurizio, Campitiello Maria Rosaria, Ubaldi Filippo Maria, Rienzi Laura, Vaiarelli Alberto, Cimadomo Danilo, Ronsini Carlo, Longobardi Salvatore, D'Hooghe Thomas, Esteves Sandro C, Alviggi Carlo
Department of Neuroscience, Reproductive Science and Odontostomatology, University of Naples Federico II, Naples, Italy.
Department of Neuroscience, Reproductive Science and Odontostomatology, University of Naples Federico II, Naples, Italy.
Fertil Steril. 2025 Mar;123(3):457-476. doi: 10.1016/j.fertnstert.2024.09.038. Epub 2024 Sep 26.
The clinical management of women with diminished ovarian reserve (DOR) is a challenge in the field of medically assisted reproduction. Several therapeutic strategies have been proposed, but with mixed results, mainly because the definition of DOR used was inconsistent among trials.
To investigate adjuvant treatments and protocols involving only women with DOR according to POSEIDON (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) criteria.
We conducted a systematic search using the MEDLINE (PubMed), EMBASE, and ISI Web of Knowledge databases to identify relevant studies published up to June 2024.The review protocol was registered at http://www.crd.york.ac.uk/PROSPERO/ (registration number: CRD42022346117).
After duplication removal, the titles and abstracts of 4,806 articles were scrutinized, and 124 full-text articles were assessed for eligibility. In total, 38 randomized controlled trials were included in the qualitative/quantitative analysis. The following interventions were evaluated: dehydroepiandrosterone (n = 1,336); testosterone (n = 418); high- vs. low-dose gonadotropin (n = 957); delayed-start protocol with gonadotropin hormone-releasing hormone antagonist (n = 398); letrozole (n = 612); clomiphene citrate (1,113); growth hormone (311); luteal phase stimulation (n = 57); dual triggering (n = 139); dual stimulation (168); luteinizing hormone (979); oestradiol pretreatment (n = 552); and corifollitropin alfa (n = 561).
The primary outcome was live birth rate or ongoing pregnancy if data on live birth were unavailable. Secondary outcomes were number of oocytes retrieved, number of metaphase II oocytes, clinical pregnancy rate and miscarriage rate.
Testosterone supplementation is associated with higher live birth rates compared with nonsupplemented women among all interventions evaluated (odds ratio: 2.19, 95% confidence interval [CI]: 1.11-4.32, four studies, 368 patients). Testosterone (weighted mean difference [WMD] 0.88, 95% CI: 0.03-1.72; 4 studies, n = 368 patients), dehydroepiandrosterone (WMD 0.60, 95% CI: 0.07-1.13; 4 studies, n = 418 patients), and delayed started protocol (WMD 1.32, 95% CI: 0.74 to 1.89; 3 studies, n = 398 patients) significantly improved the total number of eggs collected. Lower number of oocytes retrieved is achieved in women undergoing low dose gonadotropin regimen vs high dose (WMD: -1.57, 95% CI: -2.12 to -1.17; 2 studies, n = 905 patients), The other interventions did not produce significant improvements.
Specific interventions such as testosterone seem to correlate with a better live birth rate in women with DOR; these findings should be further explored in randomized trials.
卵巢储备功能减退(DOR)女性的临床管理是医学辅助生殖领域的一项挑战。已经提出了几种治疗策略,但结果不一,主要是因为各试验中使用的DOR定义不一致。
根据POSEIDON(涵盖个体化卵母细胞数量的以患者为导向的策略)标准,研究仅涉及DOR女性的辅助治疗方法和方案。
我们使用MEDLINE(PubMed)、EMBASE和ISI Web of Knowledge数据库进行了系统检索,以识别截至2024年6月发表的相关研究。该综述方案已在http://www.crd.york.ac.uk/PROSPERO/(注册号:CRD42022346117)注册。
在去除重复项后,对4806篇文章的标题和摘要进行了审查,并对124篇全文文章进行了资格评估。总共38项随机对照试验纳入了定性/定量分析。评估了以下干预措施:脱氢表雄酮(n = 1336);睾酮(n = 418);高剂量与低剂量促性腺激素(n = 957);使用促性腺激素释放激素拮抗剂的延迟启动方案(n = 398);来曲唑(n = 612);枸橼酸氯米芬(1113);生长激素(311);黄体期刺激(n = 57);双重触发(n = 139);双重刺激(168);促黄体生成素(979);雌二醇预处理(n = 552);以及注射用重组促卵泡素α(n = 561)。
主要结局是活产率,若没有活产数据则为持续妊娠率。次要结局是取卵数、MII期卵母细胞数、临床妊娠率和流产率。
在所有评估的干预措施中,与未补充睾酮的女性相比,补充睾酮与更高的活产率相关(优势比:2.19,95%置信区间[CI]:1.11 - 4.32,四项研究,368例患者)。睾酮(加权平均差[WMD] 0.88,95% CI:0.03 - 1.72;4项研究,n = 368例患者)、脱氢表雄酮(WMD 0.60,95% CI:0.07 - 1.13;4项研究,n = 418例患者)和延迟启动方案(WMD 1.32,95% CI:0.�4至1.89;3项研究,n = 398例患者)显著提高了收集的卵子总数。与高剂量促性腺激素方案相比,接受低剂量促性腺激素方案的女性取卵数更低(WMD: - 1.57,95% CI: - 2.12至 - 1.17;2项研究,n = 905例患者),其他干预措施未产生显著改善。
睾酮等特定干预措施似乎与DOR女性更好的活产率相关;这些发现应在随机试验中进一步探索。