尽管在IVF(体外受精)和ICSI(卵胞浆内单精子注射)周期的新周期中,各种黄体期支持方案(LPS)优于安慰剂,关于具体的LPS方案选择存在争议,剂量,和持续时间。本研究的目的是在ART成功的六个核心方面确定最佳LPS,临床妊娠,作为主要结局的活产和生化妊娠,流产,多胎妊娠,卵巢过度刺激综合征(OHSS)事件作为次要结局。十二个数据库,即Embase(OVID),MEDLINE(R)(OVID),GlobalHealth(存档),GlobalHealth,健康和社会心理工具,妇幼保健数据库(MIDIRS),APA心理测验,ClinicalTrials.gov,HMIC健康管理信息联盟,中部,WebofScience,Scopus和两个潜在的登记册,MedRxiv,从成立到8月1日,对研究广场进行了搜索,2023年(PROSPERO注册:CRD42022358986)。仅包括随机对照试验(RCTs)。采用贝叶斯网络荟萃分析(NMA)模型进行结果分析,呈现固定效果,具有95%可信度区间(CrIs)的赔率比(OR)。鉴于其临床相关性,阴道孕酮(VP)被认为是参考LPS。七十六项RCT,比较22种干预措施,目前的NMA包括26,536名参与者。总体上,CiNeMa偏差风险被认为是中等的,每个结果的网络不一致性被认为较低(多胎妊娠χ2:0.11,OHSSχ2:0.26),中度(临床妊娠:χ2:7.02,活产χ2:10.95,生化妊娠:χ2:6.60,流产:χ2:11.305)。组合方案,阴道孕酮基础上皮下GnRH-a(SCGnRH-a)和口服雌激素(OE)似乎总体上改善了临床妊娠事件;VP+OE+SCGnRH-a[OR1.57(95%CrI1.11至2.22)],VP+SCGnRH-a[OR1.28(95%CrI1.05至1.55)]以及实时妊娠事件,VP+OE+SCGnRH-a[OR8.81(95%CrI2.35至39.1)],VP+SCGnRH-a[OR1.76(95%CrI1.45至2.15)]。同样,孕酮游离LPS,肌内人绒毛膜促性腺激素,还发现[OR9.67(95%CrI2.34,73.2)]增加了活产事件,然而,也与卵巢过度刺激的可能性增加有关,[OR1.64(95%CrI0.75,3.71)]。肌内和阴道孕酮的组合与较高的多胎妊娠事件相关,[或7.09(95%CrI2.49,31。)].在所有LPS方案中,发现VP+SCGnRH-a显著减少流产事件,或0.54(95%CrI0.37至0.80)。根据卵巢刺激(OS)方案进行的亚组分析显示,长OS和短OS的最佳LPS,考虑到活产的增加和流产的减少以及OHSS事件,是VP+SCGnRH-a,分别为2.89[95%CrI1.08,2.96]和2.84[95%CrI1.35,6.26]。总的来说,NMA数据表明,组合治疗,在VP基础上添加SCGnRH-a后,GnRH激动剂和拮抗剂卵巢刺激方案的临床妊娠和活产事件均得到改善.
Despite the proven superiority of various luteal phase support protocols (LPS) over placebo in view of improved pregnancy rates in fresh cycles of IVF (in vitro fertilization) and ICSI (intracytoplasmic sperm injection) cycles, there is ongoing controversy over specific LPS protocol selection, dosage, and duration. The aim of the present study was to identify the optimal LPS under six core aspects of ART success, clinical pregnancy, live birth as primary outcomes and biochemical pregnancy, miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome (OHSS) events as secondary outcomes. Twelve databases, namely Embase (OVID), MEDLINE (R) (OVID), GlobalHealth (Archive), GlobalHealth, Health and Psychosocial Instruments, Maternity & Infant Care Database (MIDIRS), APA PsycTests, ClinicalTrials.gov, HMIC Health Management Information Consortium, CENTRAL, Web of Science, Scopus and two prospective registers, MedRxiv, Research Square were searched from inception to Aug.1st, 2023, (PROSPERO Registration: CRD42022358986). Only Randomised Controlled Trials (RCTs) were included. Bayesian network meta-analysis (NMA) model was employed for outcome analysis, presenting fixed effects, odds ratios (ORs) with 95% credibility intervals (CrIs). Vaginal Progesterone (VP) was considered the reference LPS given its\' clinical relevance. Seventy-six RCTs, comparing 22 interventions, and including 26,536 participants were included in the present NMA. Overall CiNeMa risk of bias was deemed moderate, and network inconsistency per outcome was deemed low (Multiple pregnancy χ2: 0.11, OHSS χ2: 0.26), moderate (Clinical Pregnancy: χ2: 7.02, Live birth χ2: 10.95, Biochemical pregnancy: χ2: 6.60, Miscarriage: χ2: 11.305). Combinatorial regimens, with subcutaneous GnRH-a (SCGnRH-a) on a vaginal progesterone base and oral oestrogen (OE) appeared to overall improve clinical pregnancy events; VP + OE + SCGnRH-a [OR 1.57 (95% CrI 1.11 to 2.22)], VP + SCGnRH-a [OR 1.28 (95% CrI 1.05 to 1.55)] as well as live pregnancy events, VP + OE + SCGnRH-a [OR 8.81 (95% CrI 2.35 to 39.1)], VP + SCGnRH-a [OR 1.76 (95% CrI 1.45 to 2.15)]. Equally, the progesterone free LPS, intramuscular human chorionic gonadotrophin, [OR 9.67 (95% CrI 2.34, 73.2)] was also found to increase live birth events, however was also associated with an increased probability of ovarian hyperstimulation, [OR 1.64 (95% CrI 0.75, 3.71)]. The combination of intramuscular and vaginal progesterone was associated with higher multiple pregnancy events, [OR 7.09 (95% CrI 2.49, 31.)]. Of all LPS protocols, VP + SC GnRH-a was found to significantly reduce miscarriage events, OR 0.54 (95% CrI 0.37 to 0.80). Subgroup analysis according to ovarian stimulation (OS) protocol revealed that the optimal LPS across both long and short OS, taking into account increase in live birth and reduction in miscarriage as well as OHSS events, was VP + SCGnRH-a, with an OR 2.89 [95% CrI 1.08, 2.96] and OR 2.84 [95% CrI 1.35, 6.26] respectively. Overall, NMA data suggest that combinatorial treatments, with the addition of SCGnRH-a on a VP base result in improved clinical pregnancy and live birth events in both GnRH-agonist and antagonist ovarian stimulation protocols.