An Exploratory, Randomized, Open-label, Controlled Study to Evaluate the Potential Benefit of r-hLH Addition in Patients Aged 35 to 40 Under Ovarian Stimulation Treatment
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Good quality embryo rate (cleavage stage)
研究概览
简要总结
This will be an exploratory, prospective, randomized, open-label and controlled trial to evaluate the potential benefit of r-hFSH:r-hLH 2:1 co-treatment starting from COS D1 versus r-hFSH alone in patients aged 35 to 40 under ovarian stimulation treatment.
After signing informed consent form (ICF), all eligible participants will be randomly assigned in a 1:1 ratio to either treatment or control group, and GnRH antagonist protocol will be used in both treatment and control groups.
详细描述
This will be an exploratory, prospective, randomized, open-label and controlled trial to evaluate the potential benefit of r-hFSH:r-hLH 2:1 co-treatment starting from COS D1 versus r-hFSH alone in patients aged 35 to 40 under ovarian stimulation treatment.
After signing informed consent form (ICF), all eligible participants will be randomly assigned in a 1:1 ratio to either treatment or control group, and GnRH antagonist protocol will be used in both treatment and control groups.
- Treatment group: The r-hFSH starting dose will be based on the patient's profile and physician's experience. r-hLH will be added at a ratio of 2:1 starting from day 1 of r-hFSH administration; the dose of r-hFSH during COS will be adjusted by the physician based on clinical experience and the patient's ovarian response, and the r-hFSH: r-hLH dose will be 2:1, continuing to 24~48 hours prior to trigger drug injection.
- Control group: r-hFSH alone will be administrated for ovarian stimulation. The r-hFSH starting dose will be based on the patient's profile and physician's experience. The dose of r-hFSH during COS will be adjusted by the physician based on clinical experience and the patient's ovarian response, continuing to 24~48 hours prior to trigger drug injection.
The estimated treatment duration is 11 days from the first day of COS until 24~48 h prior to trigger drug injection, and this may vary depending on individual circumstances.
Follicular development, serum E2 and P levels will be monitored during COS according to the investigator site's ART practice until the criteria to administer trigger drug are met to induce final oocyte maturation. Trigger drug administration is to be performed according to the site's routine clinical practice.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 35 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age 35 to 40 (including 40)
- •18.5<BMI<28 kg/m2
- •AFC up to 14
- •First or second ART cycle
- •Planned for ovarian stimulation with GnRH-antagonist for down-regulation
- •Ejaculated sperm
排除标准
- •Contraindications to ART treatment
- •History of two or more spontaneous miscarriages
- •History of two or more implantation failures after fresh or frozen-warmed embryo transfers
- •Diagnosis of severe endometriosis
- •Patients with endocrine and metabolic diseases (diabetes mellitus, hypogonadotropic amenorrhea, genital system tumors, hyperprolactinemia, etc.)
- •Confirmed chromosomal abnormalities
研究组 & 干预措施
Treatment group
The r-hFSH starting dose will be based on the patient's profile and physician's experience. r-hLH will be added at a ratio of 2:1 starting from day 1 of r-hFSH administration; the dose of r-hFSH during COS will be adjusted by the physician based on clinical experience and the patient's ovarian response, and the r-hFSH: r-hLH dose will be 2:1, continuing to 24~48 hours prior to trigger drug injection.
For both groups, daily injection of 0.25 mg of cetrorelix (Cetrotide®, Merck Serono S.A.) will be administrated subcutaneously when at least one follicle with diameter ≥ 14 mm or serum LH level exceeds 10 IU/L or LH level is 2 folder than basal LH level or P level exceeds 0.8 ng/ml, continuing until ovulation triggering day. Cetrorelix can be administrated earlier in patients with advanced age or diminished ovarian reserve according to judgment of clinicians.
干预措施: Recombinant Human Follitropin Alfa Solution for Injection (Gonal-f®) (Drug)
Treatment group
The r-hFSH starting dose will be based on the patient's profile and physician's experience. r-hLH will be added at a ratio of 2:1 starting from day 1 of r-hFSH administration; the dose of r-hFSH during COS will be adjusted by the physician based on clinical experience and the patient's ovarian response, and the r-hFSH: r-hLH dose will be 2:1, continuing to 24~48 hours prior to trigger drug injection.
For both groups, daily injection of 0.25 mg of cetrorelix (Cetrotide®, Merck Serono S.A.) will be administrated subcutaneously when at least one follicle with diameter ≥ 14 mm or serum LH level exceeds 10 IU/L or LH level is 2 folder than basal LH level or P level exceeds 0.8 ng/ml, continuing until ovulation triggering day. Cetrorelix can be administrated earlier in patients with advanced age or diminished ovarian reserve according to judgment of clinicians.
干预措施: Recombinant Human Lutropin alfa for Injection (r-hLH, Luveris®) (Drug)
Control group
r-hFSH alone will be administrated for ovarian stimulation. The r-hFSH starting dose will be based on the patient's profile and physician's experience. The dose of r-hFSH during COS will be adjusted by the physician based on clinical experience and the patient's ovarian response, continuing to 24~48 hours prior to trigger drug injection.
For both groups, daily injection of 0.25 mg of cetrorelix (Cetrotide®, Merck Serono S.A.) will be administrated subcutaneously when at least one follicle with diameter ≥ 14 mm or serum LH level exceeds 10 IU/L or LH level is 2 folder than basal LH level or P level exceeds 0.8 ng/ml, continuing until ovulation triggering day. Cetrorelix can be administrated earlier in patients with advanced age or diminished ovarian reserve according to judgment of clinicians.
干预措施: Recombinant Human Lutropin alfa for Injection (r-hLH, Luveris®) (Drug)
结局指标
主要结局
Good quality embryo rate (cleavage stage)
时间窗: Day 3 after fertilization
Cleavage stage good-quality embryos are defined as embryos derived from normally fertilized zygotes with 7\~9 cells on day 3 post-fertilization, stage-specific cell size, less than 10% fragmentation, and no multinucleation. Cleavage stage good-quality embryo rate is defined as the number of cleavage stage good-quality embryos divided by the number of normally fertilized zygotes. Embryos will be assessed by two independent experienced embryologists to minimize intra-observation variability.
次要结局
- Number of oocytes(24 hours after Oocytes pick up)
- Number of MII oocytes (analyzed in ICSI subgroup only)(24 hours after Oocytes pick up)
- Total r-hFSH dose(24 hours after ovulation triggering)
- Fertilization rate(24 hours after fertilization)
- Blastocyst development rate(5 days after fertilization, up to 7 days)
- Clinical pregnancy rate (per transfer cycle and per oocyte retrieval cycle)(At 4-6 weeks of amenorrhea after customized timing of embryo transfer)
- Ongoing pregnancy rate(At 12 weeks of amenorrhea after customized timing of embryo transfer)
- Ovarian sensitivity index (OSI)(24 hours after fertilization)
- Follicular output rate (FORT)(24 hours after fertilization)
- Follicle oocyte index (FOI)(24 hours after fertilization)
- Safety Assessments(During the COS cycle (average cycle range 11 days), Up to 12 weeks after transfer)
- Utilizable embryo rate(5 days after fertilization, up to 7 days)
- Implantation rate(At 4-6 weeks of amenorrhea after customized timing of embryo transfer)
研究者
Li-jun Ding
Director of Reproductive Medicine Department
Nanjing University