The Effectiveness of Intracytoplasmic Sperm Injection Versus Conventional in Vitro Fertilization in Couples With Non-male Factor Infertility: a Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 1,064
- 试验地点
- 1
- 主要终点
- Ongoing pregnancy resulting in live birth after the first embryo transfer of the started treatment cycle.
研究概览
简要总结
Conventionally, ICSI was initially developed and has been shown to be an effective treatment for male factor infertility. It is increasingly being used for patients without a male factor diagnosis, despite the lack of clinical evidence to support its use. Moreover, ICSI is an invasive and expensive procedure. This multi-center, randomized, controlled, parallel-group trial will be conducted to compare the effectiveness of ICSI versus conventional IVF in infertile couples scheduled for IVF treatment, in whom the male partner has normal sperm.
详细描述
All patients undergoing IVF/ICSI will be treated with a GnRH antagonist protocol. Recombinant FSH (Puregon, MSD) will be given on day 2 or day 3 of menstrual cycle for 5 days. The starting dose is individualized for each patient based on the following criteria: AMH <0.7 ng/mL, dose 300 IU/day; AMH 0.7-2.1 ng/mL, dose 200 IU/day; AMH >2.1 ng/mL, dose 150 IU/day. After that, investigators can titrate the dose based on their clinical judgment. Follicular development will be monitored by ultrasound scanning and measurement of estradiol and progesterone levels, starting on day 5 of stimulation. Scanning and hormonal measurement will be repeated every 2 to 3 days, depending on the size of follicles. An antagonist is routinely used on day 5 until the day of triggering. Criteria for triggering, by hCG (Ovitrelle 250 mg, Merck, Germany) will be the presence of at least three leading follicles of 17 mm. In women with excessive follicular response (≥15 follicles ≥12 mm), 0,2 mg Triptorelin (Diphereline, Ipsen Beaufour, France) will be used when there are at least two leading follicles of 17 mm. Oocyte retrieval will be performed 36 hours after triggering.
Randomization and allocation of participants to study groups will be performed on the day of egg pick up, after having obtained the semen from the husband. Eligible participants that have provided informed consent will be randomised to either ICSI or conventional IVF.
In ICSI group, insemination will be performed by using ICSI, 3 - 4 hours after oocyte retrieval. OCCs will be stripped by using hyaluronidase. Only matured oocytes will be inseminated.
In conventional IVF group, insemination will be performed by conventional IVF. Two hours after retrieval, collected OCCs will be inseminated for another 2 hours, at a concentration of 100,000 motile sperm/ml. Inseminated OCCs will be cultured overnight in culture medium.
In both groups, fertilization check will be performed under inverted microscope at period of 16-18 hours after insemination. On day 3, embryo evaluation will be performed at fixed time point 66±2 hours after fertilization, using the Istanbul consensus. Embryo transfer will be performed on day 3 under ultrasound guidance. A maximum of 2 embryos will be transferred into the uterus. The remaining grade 1 and 2 embryos will be frozen. Luteal-phase support will be done with estradiol (Valiera 2mg) 8mg/day and vaginal progesterone 800mg/day (Cyclogest 400mg) until 7th week of gestation.
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Having ≤ 2 IVF/ICSI cycles
- •Total sperm count and motility are normal (WHO, 2010)
- •Antagonist protocol
- •Agree to have ≤ 2 embryos transferred
- •Not participating in another IVF study at the same time
排除标准
- •In-vitro maturation (IVM) cycles
- •Using frozen semen
- •Poor fertilization in previous cycle (≤ 25%)
结局指标
主要结局
Ongoing pregnancy resulting in live birth after the first embryo transfer of the started treatment cycle.
时间窗: At 12 weeks of gestation
Live birth is defined as the birth of at least one newborn after 24 weeks' gestation that exhibits any sign of life (twin will be a single count). For the timing of this occur, ongoing pregnancy will be used, conditional on the fact that this ongoing pregnancy results in live birth.
次要结局
- Positive pregnancy test(14 days after embryo transfer)
- Clinical pregnancy(At 7 weeks' gestation)
- Multiple pregnancy(7 weeks' gestation at 12 months after randomization)
- Fertilization rate per oocyte retrieved(At 16-18 hours after injected or 17-19 hours after inseminated)
- Number of good quality embryo on day 3(3 days after oocytes pick-up day in IVF/ICSI)
- Fertilization rate per oocyte inseminated/injected(At 16-18 hours after injected or 17-19 hours after inseminated)
- Birth weight(At birth, at 12 months after randomization)
- Implantation rate(At 3 weeks after embryo transferred)
- Time from randomization to ongoing pregnancy(12 weeks of gestation after the completion of first transfer)
- Hypertensive disorders of pregnancy(From 20 weeks of gestation up to at birth at 12 months after randomization)
- Antepartum haemorrhage(From 20 weeks of gestation up to at birth, at 12 months after randomization)
- High birth weight(At birth, at 12 months after randomization)
- Number of embryo freezing on day 3(3 days after oocytes pick-up day in IVF/ICSI)
- Ongoing pregnancy resulting in live birth obtained from all embryos from the first started treatment cycle(12 weeks of gestation at 12 months after randomization)
- Ovarian hyperstimulation syndrome (OHSS)(At 10 days after hCG injection and 14 days after embryo transfer)
- Abnormal fertilization rate(At 16-18 hours after injected or 17-19 hours after inseminated)
- Total fertilization failure rate(At 16-18 hours after injected or 17-19 hours after inseminated)
- Number of embryos on day 3(3 days after oocytes pick-up day in IVF/ICSI)
- Ongoing pregnancy(At 12 weeks' gestation)
- Cumulative ongoing pregnancy(At 12 weeks' gestation at 12 months after randomization. After 12 months, most patients doing IVF have finished all their frozen embryos; therefore, we consider this time point for analyzing the cumulative ongoing pregnancy rate.)
- Ectopic pregnancy(At 12 weeks of gestation at 12 months after randomization.)
- Miscarriage(At 24 weeks of gestation at 12 months after the randomization.)
- Gestational age at delivery(At birth, at 12 months after randomization)
- Iatrogenic preterm birth(At birth, at 12 months after randomization)
- Multiple delivery(At birth at 12 months after randomization)
- Small for gestational age(At birth, at 12 months after randomization)
- Gestational diabetes mellitus(At 24 weeks of gestation at 12 months after randomization)
- Preterm delivery(At birth, at 12 months after randomization)
- Low birth weight(At birth, at 12 months after randomization)
- Very low birth weight(At birth, at 12 months after randomization)
- Admission to NICU(7 days after delivery, at 12 months after randomization)
- Cost-effectiveness(Two year after randomization)
- Spontaneous preterm birth(At birth, at 12 months after randomization)
- Very high birth weight(At birth, at 12 months after randomization)
- Congenital anomaly diagnosed at birth(At birth, at 12 months after randomization)
- Genetic and epigenetic analysis of newborn(1 day (Prior to the initiation of IVF/IVM) and 1 day ( at the time of delivery))
- Large for gestational age(At birth, at 12 months after randomization)