A Phase III, Multicentric, Randomized, Open, Comparative Study to Evaluate if the Addition of Recombinant Human Luteinising Hormone [r-hLH (Luveris®)] to Follicle Stimulating Hormone (FSH) From Day 8 of Ovarian Stimulation is Able to Decrease Total FSH Dose and to Improve Cycle Outcome in Infertile Women Undergoing Assisted Reproduction Technology (ART), Who Required High FSH Dose in a Previous Cycle
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 133
- 试验地点
- 1
- 主要终点
- Total Dose of Follicular Stimulating Hormone (FSH) for Retrieved Oocytes
研究概览
简要总结
The present study was designed to investigate, in hyporesponder subjects, that required in a previous assisted reproductive technologies (ART) cycle follicle stimulating hormone (FSH) >3500 International Unit (IU), the possibility to decrease through recombinant human luteinizing hormone (r-hLH) supplementation, the FSH amount per oocytes retrieved and in the mean time to improve the overall cycle outcome.
详细描述
Recombinant human follicle stimulating hormone (r-hFSH), which totally lacks LH activity, is widely used to induce multiple follicle development in women under pituitary desensitization, in order to submit them to treatment with assisted reproduction techniques (ART). Clinical experience from hypogonadotropic-hypogonadic women suggests that while FSH alone is sufficient to induce follicle development, LH plays a significant part in final follicle maturation, estrogen synthesis and optimal endometrium growth.
This was a phase III, multicentre, randomized, open-label comparative study to evaluate if the addition of r-hLH (Luveris) in a 2:1 ratio to FSH from day 8 of ovarian stimulation is able to decrease the total FSH dose and to improve cycle outcome in 250 infertile women undergoing ART, who required high FSH dose in a previous cycle (≥ 3500 IU). Subjects who have met all the inclusion criteria, achieved pituitary desensitization and started controlled ovarian hyperstimulation (COH) treatment with FSH, on stimulation day 8 (S8) received an identification number and will be allocated to one of the two following arms:
Arm : FSH + r-hLH (2:1 ratio of FSH:r-hLH), Arm : FSH alone. Treatment with Luveris was commenced on day 8 (S8) and continued until injection of hCG or cancellation of the treatment cycle.
Monitoring of stimulation, FSH dose escalation, criteria for injection of hCG, ovum pick up, embryo transfer and pregnancy confirmation took place according to standard management practice. The in-vitro fertilization (IVF) or intracytosolic sperm injection (ICSI) procedure, including luteal phase support, was performed according to each centres' normal procedures.
The subjects were followed up and the treatment outcome (menstruation or pregnancy) was recorded. The delivery outcome for any pregnant subjects was recorded in the Case Report Form (CRF).
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
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Pre-menopausal infertile woman, aged 18 to 40 years inclusive, who wishes to conceive
- •Regular, spontaneous menstrual cycle of 25-35 days
- •Body mass index (BMI) ≤ 28
- •FSH ≤ 10 IU/L (follicular phase, days 2-5)
- •Prolactin (PRL) within the normal ranges
- •Evidence of both ovaries by ultrasound scan
- •Women undergoing IVF-Embryo Transfer (ET) or ICSI, down regulated with Gonadotropin releasing hormone analogues (GnRHa) (daily dose) under controlled ovarian hyperstimulation (COH) with FSH
- •Washout > 90 days from last dose of clomiphene or gonadotrophin, before ongoing COH cycle
- •Only one previous IVF-ET or ICSI cycle (in the last 9 months preceding the ongoing COH cycle) resulted in a hypo-response properly documented (from 6 to 12 oocytes with a total FSH dose ≥ 4000 IU)
- •Negative pregnancy hCG test (urine or blood sample) before the ongoing COH cycles
- •Willing and able to comply with the protocol for the duration of the study
- •Written informed consent before applying any procedure related to the study protocol, which is not part of routine medical care, with the understanding that consent may be withdrawn by the subject at any time, without prejudice on their future medical care
排除标准
- •Oligo/Anovulatory cycles (World Health Organization [WHO] I and II)
- •Male partner azoospermia (assessed within the last 12 months)
- •Follicular phase (day 2-5) FSH > 10 IU/L even if only once observed in the medical history
- •Abnormal cervical cytology (assessed within the last 12 months)
- •History of unexplained gynecologic hemorrhage
- •Any contraindication to pregnancy
- •Known allergy to gonadotrophin
- •Any clinically important systemic disease (e.g. insulin-dependent diabetes mellitus, epilepsy, serious migraine, intermittent purpura, hepatic, renal or cardiovascular disease, serious corticoid-dependent asthma) which constitutes a contraindication to gonadotropin use
- •Any medical condition which, according to the investigator's judgement, may affect the absorption, distribution, metabolism or excretion of the drug. In case of doubt, inclusion of the subject in question should be discussed with the Medical Responsible of Serono
- •Known Human Immunodeficiency Virus (HIV) positivity
- •Any substance abuse or history of drugs or alcohol abuse within the past 5 years
- •Prior inclusion in the present study or simultaneous inclusion in a clinical study of another drug
- •Refusal or inability to comply with the protocol
研究组 & 干预措施
A
Subjects treated with r-hFSH and r-hLH (2:1 ratio of r-hFSH:r-hLH)
干预措施: Recombinant human Follicle Stimulating Hormone (r-hFSH) and Recombinant human Luteinizing Hormone (r-hLH) (Drug)
B
Subjects treated with r-hFSH alone
干预措施: r-hFSH (Drug)
结局指标
主要结局
Total Dose of Follicular Stimulating Hormone (FSH) for Retrieved Oocytes
时间窗: Baseline (Stimulation day 8 [S8]) until hCG day
次要结局
- Mean Total Number of Retrieved Oocytes(34-36 hours post-hCG (OPU))
- Percentage of Participants With Implantation(12-18 day post-hCG and/or Week 7)
- Number of Participants With Ovarian Hyper Stimulation Syndrome (OHSS)(Baseline (S8) until 12-18 day post-hCG and/or Week 7)
- Number of Cycles Cancelled Due to Risk of OHSS(Baseline (S8) until 12-18 day post-hCG and/or Week 7)
- Percentage of Participants With Clinical Pregnancy(12-18 day post-hCG and/or Week 7)
- Change From Baseline in Oestradiol (E2) Levels at Human Choriogonadotropin (hCG) Day(Baseline (S8) and hCG day)
- Fertilization Rate(12-18 day post-hCG and/or Week 7)
- Number of Obtained Embryos(Day 3 post-hCG (Embryo transfer [ET]))
- Number of Transferred Embryos(Day 3 post-hCG (ET))
- Percentage of Participants With Pregnancy(12-18 day post-hCG and/or Week 7)
- Mean Total Follicle Stimulating Hormone (FSH) and Recombinant Human Luteinizing Hormone (r-hLH) Dose(Baseline (S8) until hCG day)
- Mean Number of Ovarian Stimulation Days(Baseline (S8) until hCG day)
- Mean Number of Mature Oocytes (Metaphase II)(34-36 hours post-hCG (OPU))