RIOTC: Reducing the Impact of Ovarian Stimulation. Novel Approaches to Luteal Support in IVF - Study 2
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- Length of luteal phase (days from aspiration untill bleeding)
研究概览
简要总结
The goal of the randomised controlled study (RCT) is to identify novel strategies that can improve the luteal phase endocrinology after ovarian stimulation, with the aim of using less or no luteal support in IVF while making the endometrium thinner and more receptive to embryo implantation.
详细描述
The high estradiol levels generated in IVF by multiple dominant follicles at the follicular-luteal phase transition generate powerful negative feedback at the pituitary gland, effectively switching off gonadotropin production. Without stimulation by endogenous luteinizing hormone (LH), the corpora lutea undergo involution and menstruation follows, preventing the establishment of pregnancy.
To address these detrimental effects of ovarian stimulation, the investigators will do a RCT with the use of aromatase inhibitors, which suppress the conversion of androgens to estrogens to ameliorate the unwanted effects of high estrogens.
This study is designed to test the hypothesis that preventing supra-physiological estrogen levels during ovarian stimulation restricts pituitary suppression sufficiently to allow LH levels to rise and support the corpora lutea, leading to a normal post-ovulatory luteal phase, evidenced by a normal duration and luteal phase endocrine profile. To test this, consenting oocyte donors will be randomized to receive co-treatment with aromatase inhibitors or no co-treatment during ovarian stimulation. Following oocyte retrieval, no luteal support will be provided to donors in both Groups.
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 35 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Meet the clinical criteria for acceptance as oocyte donors (healthy women who volunteers to donate oocytes to other women).
- •Regular ovulatory cycle of 26-32 days.
- •Age: 18-35 years old.
- •Written consent.
排除标准
- •Contraindications for ovarian stimulation or aspiration of oocytes according to local guidelines
- •Polycystic Ovary Syndrome (PCOS)
- •Allergy towards study drug
- •Women who have had a hormone or copper intra-uterine device (IUD) within 3 months
- •Exclusion of patients after earlier inclusion in the study in case of
- •Patient withdrawal of consent
- •Lack of compliance with medication
- •Medical complication arising from IVF treatment that requires the cycle to be terminated
- •Serious adverse events (SAE) or serious adverse reactions (SAR) including severe allergy to study drug.
- •Specific ARs to study drug: severe degree of hot flushed, severe degree of nausea/vomiting, severe diarrhea, severe degree of muscle and joint pain.
- •In case of exclusion of a patient after earlier inclusion in the study, a new patient will be included.
研究组 & 干预措施
Intervention
recFSH and co-treatment with letrozole 5 mg/day from stimulation day 1 on cycle day 2 or 3 until the day before gonadotrophin releasing hormone(GnRH) agonist administration to trigger final oocyte maturation. GnRH antagonist 0.25 mg/day from stimulation day 5 until day of GnRH agonist administration. No luteal phase support.
干预措施: Letrozole 5 mg (Drug)
结局指标
主要结局
Length of luteal phase (days from aspiration untill bleeding)
时间窗: Up to three weeks
Difference in lengths of days until bleeding (from aspiration until first day of bleeding) of the luteal phase between intervention group and control group.
次要结局
- Phase of endometrial receptivity according to Endometrial Receptivity Array (ERA) test(ERA-test is taken 5 days after aspiration of oocytes.)
- Estradiol (E2),progesterone (P), luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels.(Blood samples are taken on 1 day of oocyte aspiration, 2 days after, 5 days after and 14 days after.)
- Endometrium thickness.(Endometrium thickness is measured on 1 day of oocyte aspiration, 2 days after and 5 days after.)
研究者
Nicholas Macklon
Professor
Zealand University Hospital