Mourad Ali, Jamal Wael, Hemmings Robert, Tadevosyan Artak, Phillips Simon, Kadoch Isaac-Jacques
Department of Obstetrics and Gynecology, University of Montreal, Montreal, QC, Canada.
Ovo Clinic Montreal, Montreal, QC, Canada.
Hum Reprod. 2025 Jan 1;40(1):77-84. doi: 10.1093/humrep/deae251.
Does adjuvant growth hormone (GH) therapy in GnRH antagonist cycles improve reproductive outcomes in the general IVF population?
Empiric adjuvant GH therapy in GnRH antagonist cycles does not improve IVF stimulation results or reproductive outcomes, including implantation, miscarriage, and clinical pregnancy rates.
Previous evidence regarding the benefits of GH therapy in IVF cycles has been inconclusive due to the lack of well-designed, large-scale randomized controlled trials (RCTs) in the general IVF population.
STUDY DESIGN, SIZE, DURATION: This is a phase III open-label RCT involving 288 patients undergoing antagonist IVF cycles at the Ovo clinic in Montreal, Canada, between June 2014 and January 2020. Patients were randomly assigned at a 1:1 ratio to either the GH or control group. The intervention group received daily 2.5 mg subcutaneous injections of GH from Day 1 of ovarian stimulation until the day of oocyte retrieval, while the control group received standard ovarian stimulation without any adjuvant therapy.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were expected normal responders. All embryo transfers, both fresh and frozen, resulting from the studied IVF cycle were included in an intention-to-treat and per-protocol analyses. The primary outcome was the clinical pregnancy rate, while secondary outcomes included the number of retrieved oocytes, good-quality embryos, maturation, fertilization, implantation, and miscarriage rates.
A total of 288 patients were recruited and randomly assigned at a 1:1 ratio to either the GH or the control group. After excluding cycle cancellations and patients who did not undergo transfer, 105 patients remained in each group. The overall mean age was 38.0 years, the mean BMI was 25.11 kg/m2 and the mean anti-Müllerian hormone was 2.51 ng/ml. The cycle characteristics were similar between both groups. No differences were observed regarding the total dose of gonadotropins (4600 versus 4660 IU for the GH and control groups, respectively, P = 0.752), days of stimulation (11.4 versus 11.7 days, P = 0.118), and endometrial thickness (10.63 versus 10.94 mm, P = 0.372). Both the intention to treat (ITT) and per protocol analyses yielded similar results for stimulation outcomes. In the ITT analysis, no differences were found in the number of follicles ≥15 mm (7.8 versus 7.1, P = 0.212), retrieved oocytes (11.7 versus 11.2, P = 0.613), mature oocytes (8.5 versus 8.6, P = 0.851), maturation rate (73.8 versus 78.4%, P = 0.060), fertilization rate (64.3 versus 67.2%, P = 0.388), and good quality embryos (2.5 versus 2.6, P = 0.767). Reproductive outcomes in fresh embryo transfer showed no difference for implantation rate (38.2 versus 39.5%, P = 0.829), miscarriage rate (26.5 versus 31.1%, P = 0.653), clinical pregnancy rate (43.6 versus 50.0%, P = 0.406, rate difference, 95% CI: -0.06 [-0.22, 0.09]), and live birth rate (32.1 versus 33.3%, P = 0.860). The number of embryos needed to achieve a clinical pregnancy was 3.0 versus 2.5 in the GH and control groups, respectively. Similarly, reproductive outcomes in first frozen embryo transfer showed no difference for implantation rate (31.6 versus 45.3%, P = 0.178), miscarriage rate (28.6 versus 26.3%, P = 0.873), clinical pregnancy rate (35.1 versus 44.2%, P = 0.406, P = 0.356, rate difference, 95% CI: -0.09 [-0.28, 0.10]), and live birth rate (22.8 versus 32.6%, P = 0.277). The number of embryos needed to achieve a clinical pregnancy was 3.1 versus 2.4 in the GH and control groups, respectively.
LIMITATIONS, REASONS FOR CAUTION: The study focused on expected normal responders, limiting its applicability to other patient populations such as poor responders.
These findings suggest that adding GH therapy to ovarian stimulation in GnRH antagonist cycles may not benefit the general IVF population. Additional high-quality RCTs are warranted to identify subgroups of patients who might benefit from this treatment.
STUDY FUNDING/COMPETING INTEREST(S): EMD Serono Inc., Mississauga, Canada, supplied Saizen® for the study, free of charge. In addition, they provided funding for the statistical analysis. I-J.K. declares grants or contracts from Ferring Pharmaceuticals, consulting fees from Ferring Pharmaceuticals, honoraria from Ferring Pharmaceuticals and EMD Serono, support for attending meetings or travel from Ferring Pharmaceuticals and EMD Serono, participation on a Data Safety Monitoring Board or Advisory Board for Ferring Pharmaceuticals, and stock or stock options from The Fertility Partners; W.J. declares support for attending meetings or travel from EMD Serono; and S.P. declares stock or stock options from The Fertility Partners. All other authors have no conflicts of interest to disclose.
NCT01715324.
25 October 2012.
DATE OF FIRST PATIENT’S ENROLMENT: 25 June 2014.
在GnRH拮抗剂方案周期中，辅助使用生长激素（GH）治疗能否改善普通体外受精（IVF）人群的生殖结局？
在GnRH拮抗剂方案周期中经验性使用辅助GH治疗并不能改善IVF刺激结果或生殖结局，包括着床率、流产率及临床妊娠率。
由于在普通IVF人群中缺乏设计良好的大规模随机对照试验（RCT），先前关于GH治疗在IVF周期中的益处的证据尚无定论。
研究设计、规模、持续时间：这是一项III期开放标签RCT，于2014年6月至2020年1月期间在加拿大蒙特利尔的奥沃诊所纳入了288例接受拮抗剂IVF周期治疗的患者。患者按1:1比例随机分配至GH组或对照组。干预组从卵巢刺激第1天开始至取卵日，每天皮下注射2.5mg GH，而对照组接受标准卵巢刺激，不进行任何辅助治疗。
参与者/材料、地点、方法：患者预期为正常反应者。研究的IVF周期产生的所有新鲜及冷冻胚胎移植均纳入意向性分析和符合方案分析。主要结局为临床妊娠率，次要结局包括取卵数、优质胚胎数、成熟率、受精率、着床率及流产率。
共招募288例患者，并按1:1比例随机分配至GH组或对照组。排除周期取消及未进行移植的患者后，每组各有105例患者。总体平均年龄为38.0岁，平均BMI为25.11kg/m2，平均抗苗勒管激素为2.51ng/ml。两组的周期特征相似。在促性腺激素总剂量（GH组和对照组分别为4600IU和4660IU，P = 0.752）、刺激天数（11.4天和11.7天，P = 0.118）及子宫内膜厚度（10.63mm和10.94mm，P = 0.372）方面未观察到差异。意向性分析（ITT）和符合方案分析在刺激结局方面产生了相似的结果。在ITT分析中，卵泡≥15mm的数量（7.8个对7.1个，P = 0.212）、取卵数（11.7个对11.2个，P = 0.613）、成熟卵母细胞数（8.5个对8.6个，P = 0.851）、成熟率（73.8%对78.4%，P = 0.060）、受精率（64.3%对67.2%，P = 0.
