重组黄体生成素补充与单独FSH对累积活产率的影响：一项对接受抗逆转录病毒治疗的卵巢不良反应者的综合观察研究

IF 6 1区医学 Q1 OBSTETRICS & GYNECOLOGY

Human reproduction Pub Date : 2025-06-28 DOI:10.1093/humrep/deaf097.908

S Abbas, H Latif Khan, S Bhatti

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引用次数: 0

摘要

研究问题：补充黄体生成素是否能提高卵巢应答不良患者的累计活产率？补充LH （LHS）可提高中度和重度卵巢反应不良（POR）患者的CLBR，且随着严重程度的增加，效果变得更加明显。已知的卵巢反应不良（POR）通常在标准控制卵巢刺激（COS）期间产生较少的卵母细胞，导致较低的活产率。各种治疗，包括高剂量促性腺激素、轻度刺激和生长激素，旨在改善卵巢反应。黄体生成素补充（LHS）作为一种潜在的解决方案已被探索，但结果仍然相互矛盾。LHS可促进卵泡成熟和卵母细胞质量，特别是在促性腺激素低下的妇女。虽然在GnRH激动剂/拮抗剂COS期间抑制LH不会对IVF结果产生负面影响，但在LH降低的患者中添加LH并不总是能提高活产率。LHS在贫困地区的潜在益处仍不确定，需要进一步研究。这项回顾性、多中心对照研究利用了巴基斯坦5个ART中心的数据，重点关注2008年至2020年期间基于意向治疗原则，使用卵泡素-α (FSH-α)治疗或不使用lutropin-α治疗的卵巢反应不良（POR）患者。根据ESHRE Bologna标准定义POR，并使用PROP评分将其分为轻度、中度或重度。主要终点是来自同一卵巢刺激周期的新鲜和冷冻胚胎的CLBR。受试者/材料、环境、方法共对12000例卵巢刺激（COS）周期进行分析，其中6658例接受促黄体生成素（LHS）治疗，5342例单独接受促卵泡刺激素（FSH-α）治疗。拟治疗的样本包括重组FSH-α单独或重组LH治疗的POR的所有COS周期。采用逻辑回归的广义线性混合模型评估累积活产率（CLBR），并根据PROsPeR评分和严重程度进行调整。随机因素包括中心和匹配子类。缺失资料（5.9%）为随机缺失。根据POR将总周期分为轻度（32.6%）、中度（54.5%）和重度（12.9%）。一个混合逻辑回归模型，调整匹配的亚类和基线严重程度，显示中度（15.7%比12.4%,OR = 1.41, [1.05, 1.40], RR = 1.29, p = 0.015）和重度(9.9%比3.3%,OR = 2.39 [1.34, 3.11], RR = 1.99, p <；0.001)运动。然而，轻度组无明显获益（16.6% vs. 20.5%, OR = 0.98 [0.68, 2.11], RR = 0.98, p = 0.05）。此外，LHS的效果似乎随着基线POR的严重程度而增加。在对照组中，轻度POR的CLBR略高，但随着严重程度的增加而显著下降，严重POR的CLBR仅为5.6%。相比之下，LHS组轻度POR的CLBR略低，中度（15.1%）和重度（10.01%）POR的CLBR下降更为缓慢。中度（[1.33,1.47],p = 0.521）和重度POR （[1.99, 3.10], p = 0.325）的LHS效应在各中心均一致。两组中有相当比例的患者（对照组80.1%，LHS组61%）在最终移植后没有可用的胚胎。补充模型显示总促性腺激素剂量无显著影响（p = 0.321）。本研究基于来自五个非随机选择的巴基斯坦抗逆转录病毒治疗中心的数据，可能会因未知的患者特征而产生偏倚。虽然在各个中心观察到活产率的显著差异，但LHS效应保持一致，确保主要发现不受中心选择的影响。研究结果的更广泛意义黄体生成素补充（LHS）对体外受精的正常应答者没有好处，但可能改善卵巢应答不良（POR）的结果。这种效果随着POR严重程度的增加而更加明显，表明LHS可以提高不同程度卵巢反应患者的累积活产率（CLBR）。试验注册号

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P-602 Impact of recombinant LH supplementation versus FSH alone on cumulative live birth rates: a comprehensive observational study in poor ovarian responders undergoing ART

Study question Does luteinizing hormone supplementation improve cumulative live birth rates in poor ovarian responders. Summary answer LH supplementation (LHS) enhances CLBR in moderate and severe poor ovarian responders (POR), with the effect becoming more pronounced as severity increases. What is known already Poor ovarian responders (POR) typically produce fewer oocytes during standard controlled ovarian stimulation (COS), leading to lower live birth rates. Various treatments, including high-dose gonadotropins, mild stimulation, and growth hormones, aim to improve ovarian response. LH supplementation (LHS) has been explored as a potential solution, but results remain conflicting. LHS may enhance follicular maturation and oocyte quality, particularly in hypogonadotropic women. While suppressed LH during GnRH agonist/antagonist COS does not negatively impact IVF outcomes, adding LH in patients with reduced LH does not always improve live birth rates. The potential benefits of LHS in POR remain uncertain and require investigation. Study design, size, duration This retrospective, multicenter controlled study utilized data from 5 ART centers in Pakistan, focusing on poor ovarian responders (POR) treated with follitropin-alfa (FSH-α), with or without lutropin-α, based on an intention-to-treat principle during 2008 to 2020. POR was defined per the ESHRE Bologna criteria and categorized as mild, moderate, or severe using the PROP score. The primary endpoint was CLBR from fresh and frozen embryos derived from the same ovarian stimulation cycle. Participants/materials, setting, methods A total of 12,000 controlled ovarian stimulation (COS) cycles were analyzed, with 6,658 receiving luteinizing hormone supplementation (LHS) and 5,342 receiving FSH-α alone. The intent-to-treat sample included all COS cycles for POR treated with recombinant FSH-α alone or with recombinant LH. A generalized linear mixed model with logistic regression assessed cumulative live birth rate (CLBR), adjusted for PROsPeR score and severity. Random factors included center and matched sub-classes. Missing data (5.9%) were missing at random. Main results and the role of chance The total cycles were classified into Mild (32.6%), Moderate (54.5%), and Severe (12.9%) categories based on POR. A mixed logistic regression model, adjusted for matched sub-classes and baseline severity, revealed a significant improvement in CLBR with luteinizing hormone supplementation (LHS) in patients with moderate (15.7% vs. 12.4%, OR = 1.41, [1.05, 1.40], RR = 1.29, p = 0.015) and severe (9.9% vs. 3.3%, OR = 2.39 [1.34, 3.11], RR = 1.99, p < 0.001) POR. However, no significant benefit was observed in the mild category (16.6% vs. 20.5%, OR = 0.98 [0.68, 2.11], RR = 0.98, p = 0.05). Additionally, the effect of LHS appeared to increase with the severity of baseline POR. In the control group, CLBR was slightly higher for mild POR but declined significantly with increasing severity, reaching just 5.6% for severe POR. In contrast, the LHS group showed a slightly lower CLBR for mild POR, with a more gradual decline observed for moderate (15.1%) and severe (10.01%) POR. The LHS effect was consistent across centers for both moderate ([1.33, 1.47], p = 0.521) and severe POR ([1.99, 3.10], p = 0.325). A substantial proportion of patients in both groups (80.1% in control and 61% in LHS) had no available embryos after the final transfer. A supplementary model showed no significant effect of total gonadotropin dose (p = 0.321). Limitations, reasons for caution This study, based on data from five non-randomly selected Pakistani ART centers, may be subject to bias from unknown patient characteristics. While significant differences in live birth rates were observed across centers, the LHS effect remained consistent, ensuring that the main findings were not influenced by center selection. Wider implications of the findings Luteinizing hormone supplementation (LHS) does not benefit normal responders in IVF but may improve outcomes for poor ovarian responders (POR). This effect appears more pronounced with increasing severity of POR, suggesting LHS could enhance cumulative live birth rates (CLBR) in patients with varying degrees of ovarian response. Trial registration number No

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来源期刊

Human reproduction 医学-妇产科学

CiteScore

10.90

自引率

6.60%

发文量

1369

审稿时长

1 months

期刊介绍： Human Reproduction features full-length, peer-reviewed papers reporting original research, concise clinical case reports, as well as opinions and debates on topical issues. Papers published cover the clinical science and medical aspects of reproductive physiology, pathology and endocrinology; including andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, early pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues.