Does Time From Ovulation Trigger To Oocyte Pick-Up Affect Intracytoplasmic Sperm Injection Outcomes? A Multi-Center Single-Blinded Randomized Controlled Trial Comparing 36 and 38 Hour Intervals
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 850
- 试验地点
- 7
- 主要终点
- Ratio of metaphase-2 oocytes to total number of follicles
研究概览
简要总结
Women who undergo assisted reproduction technology (ART) treatment will be eligible for this study. The goal of this randomized clinical trial is to compare the outcomes of ART treatment between women who have 36 and 38 hours interval between the administration of ovulation trigger (ovulation trigger medication initiates oocyte maturation and makes it possible for the egg to be collected by aspiration, during a procedure called oocyte pick-up, OPU) and OPU. The main questions it aims to answer are, does prolonging the trigger-OPU interval to 38-hours improve:
- Primarily:
•Ratio of metaphase-2 oocytes to total number of follicles 2. Secondarily:
- Maturation rate
- Fertilization rate
- Blastulation rate
- Premature ovulation rate
- Positive pregnancy test rate
- Clinical pregnancy rate
- Live birth rate
compared to 36-hours interval?
详细描述
1.0 STUDY POPULATION AND PATIENT SELECTION Women undergoing ART treatment at the participating centers will be invited to enroll in the study. Each patient will be able to participate only once with a single oocyte pick-up (OPU) cycle and embryos obtained from this cycle. Details of inclusion and exclusion criteria are described in the ''Eligibility'' section.
2.0 RANDOMIZATION METHOD AND ALLOCATION CONCEALMENT Couples who meet the study criteria will be informed about the study when they start treatment and will be given time to decide. On the day of ovulation trigger administration, patients who give written informed consent will be enrolled and randomized to one of the study groups (36 or 38 hours) by the nurse-in-charge. The patient will be instructed about the administration time by the nurse. Randomization information will not be shared with clinicians, laboratory team or other employees in the clinic throughout the study. The patient will also be asked not to share this information with anyone from the staff.
Randomization will be performed online in real time by a professional third-party company whose services meet international regulatory guidelines. The randomization sequence will be stratified by treatment center, female age group (18-27, 28-34, 35-37, 38-40, 41-42), anticipated embryo transfer day (day 3 and day 5), and plan to utilize preimplantation genetic testing for the embryos. Randomized blocks of varying size (4,6, or 8) will be created to ensure a similar number of patients among the study groups in each stratum during and at the end of the study.
3.0. TREATMENT PROTOCOLS The intervention in this study is the time between the ovulation trigger and the OPU procedure. Therefore, each clinic will apply their own routine treatments and make their own choices regarding the protocols/drugs/materials and/or procedures to be used.
3.1. Controlled Ovarian Hyperstimulation(COH) and Triggering of Oocyte maturation One of three protocols for COH can be applied according to the preference of the clinician: Antagonist protocol, progestin-primed ovarian stimulation, or agonist protocol.
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
- Triple (Care Provider, Investigator, Outcomes Assessor)
盲法说明
Only the head-nurse and the patient will not be masked, since one will randomize the patient to a group and give her instructions on how to use the medication, and the other will apply the injection herself.
However, allocation will be concealed from the the laboratory team, treating physicians, outcome assessors and investigators. They will not be given information about when the patient applied the injection, and the patient will be instructed not to reveal information regarding her use.
入排标准
- 年龄范围
- 18 Years 至 42 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •To undergo assisted reproductive technology (ART) treatment and planning to undergo embryo transfer procedure within 6 months of oocyte collection
- •Female partner to be between 18-42 years old at the time of informed consent
- •Both partners to consent to participate in the study and be legally eligible to give consent.
排除标准
- •Female partner to have participated in the study previously.
- •Female partner to have a body mass index of 35 kg/m2 or above.
- •Female partner to have a systemic disease that may affect ART or pregnancy outcomes (e.g. antiphospholipid syndrome, severe liver dysfunction, diabetes mellitus, history of venous thrombosis, advanced renal or cardiac diseases).
- •Presence of congenital uterine anomaly (1-Women whose uterine anomalies are surgically corrected are not excluded; 2- Arcuate uterus is not accepted as a congenital uterine anomaly).
- •Presence of submucous or intramural fibroid that distorts the endometrial cavity.
- •Diagnosis of stage 3 or 4 endometriosis in the female partner.
- •Female partner planned to undergo double ovarian stimulation.
- •Known karyotype anomaly in at least one of the partners.
- •Diagnosis of azoospermia (no sperm cells in the ejaculate) in the male partner.
- •History of recurrent implantation failure [defined according to the scoring system by Ata et al in 2021 available at https://bit.ly/3huVLOn (Ata B, Kalafat E, Somigliana E. A new definition of recurrent implantation failure on the basis of anticipated blastocyst aneuploidy rates across female age. Fertil Steril. 2021;116(5):1320-
- •doi:10.1016/j.fertnstert.2021.06.045].
- •History of recurrent pregnancy loss [defined as a history of 2 or more biochemical/clinical pregnancy losses, in accordance with the European Society of Human Reproduction and Embryology(ESHRE) Guideline on the management of recurrent pregnancy loss issued on 1 February 2023, available at https://www.eshre.eu/Guidelines-and-Legal/Guidelines/Recurrent-pregnancy-loss.aspx].
研究组 & 干预措施
36-Hour Group
The women randomized to this group will undergo oocyte pick-up procedure 36 hours after the injection of the ovulation triggering agent.
The choice for ovulation trigger agent is at the discretion of the treating physician. The intervention is not the drug but the interval.
干预措施: 36-hour duration between ovulation triggering and oocyte pick-up procedure (Other)
38-Hour Group
The women randomized to this group will undergo oocyte pick-up procedure 38 hours after the injection of the ovulation triggering agent.
The choice for ovulation trigger agent is at the discretion of the treating physician. The intervention is not the drug but the interval.
干预措施: 38-hour duration between ovulation triggering and oocyte pick-up procedure (Other)
结局指标
主要结局
Ratio of metaphase-2 oocytes to total number of follicles
时间窗: 1 day
Number of metaphase-2 oocytes / total number of follicles \>10mm prior to oocyte pick-up procedure
次要结局
- Biochemical pregnancy rate(1 year)
- Blastulation rate(7 days)
- Positive Beta Human chorionic gonadotropin(Beta-hCG) test rate(8 months)
- Fertilization rate(2 days)
- Premature ovulation rate(1 day)
- Live birth rate(17 months)
- Ectopic pregnancy rate(1 year)
- Cleavage rate(4 days)
- Ongoing pregnancy rate(8 months)
- Maturation rate(2 days)
- Miscarriage rate(1 year)
- Clinical pregnancy rate(8 months)