Hormonal Replacement Therapy Plus Letrozole Incorporation Versus Letrozole Mild Ovarian Stimulation in Endometrial Preparation for Frozen Embryo Transfer: A Randomised Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 210
- 试验地点
- 1
- 主要终点
- ongoing pregnancy rate (OPR)
研究概览
简要总结
In order to get optimal pregnancy rates after frozen embryo transfer (FET), the embryo stage and endometrium should be synchronized. Endometrial preparation is done by either natural, artificial (Hormonal replacement therapy HRT) , modified natural methods or mild ovarian stimulation. HRT cycle has a better schedualization however, there are some reports about higher rates of miscarriage, pregnancy induced hypertension (PIH) and preeclampsia (PET) in HRT cycles. A recent study has found that incorporation of the aromatase inhibitor (letrozole) to HRT cycles was associated with better FET outcomes in comparison to hormonal replacement therapy cycles alone. Meanwhile, mild ovarian stimulation protocol can be done either by oral drugs like letrozole or by letrozole plus gonadotropins . So this study aims to compare the reproductive outcomes in two endometrial preparation protocols for frozen embryo transfer cycles; letrozole mild ovarian stimulation versus HRT plus letrozole incorporation.
详细描述
In order to get optimal pregnancy rates after frozen embryo transfer (FET), the embryo stage and endometrium should be synchronized. This can be done by hormonal replacement therapy (HRT), natural cycles (NC), modified natural cycles or mild ovarian stimulation. In hormonal replacement therapy cycle, estrogen and progesterone are sequentially given to resemble the hormonal course of the natural cycle . Hormonal replacement therapy cycle has a better schedualization and is used for patients with irregular cycles as polycystic ovary syndrome ( PCOS). However, there are some reports about higher rates of miscarriage, pregnancy induced hypertension (PIH) and preeclampsia (PET) in HRT cycles.
A recent study has found that incorporation of the aromatase inhibitor (letrozole) to HRT cycles was associated with better FET outcomes in comparison to HRT cycles alone. Ongoing pregnancy rate (OPR) was higher in HRT plus letrozole group than HRT only group.
Letrozole is a third-generation aromatase inhibitor that leads to mono-ovulatory cycles with short half-life . Miller and his colleagues found that letrozole increased Integrin expression and improved pregnancy and implantation rates among women with endometrial receptivity defects . Another study found that ovarian stimulation with letrozole was associated with increase in the expression of uterine receptivity markers including integrin, leukemia inhibitory factor, and L-selectin.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 37 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women aged between 18 and 37 years with either regular cycles or oligomenorrhoea or amenorrhoea.
- •Women undergoing FET cycles.
- •Participants should have at least one good-quality blastocyst available for vitrification and also for transfer after warming.
- •Participants having optimal endometrium before starting luteal phase support
排除标准
- •Women who will refuse to participate in in the study.
- •Women who will not reach the optimal endometrium.
- •Participants that don't have at least one good-quality blastocyst for transfer after warming.
- •PGT embryos will be excluded.
研究组 & 干预措施
Group A (HRT plus letrozole incorporation)
Exogenous oestradiol in the form of 2 mg oral oestradiol valerate , three times daily will be started on the 2nd or 3rd day of the cycle. Tri-laminar endometrium of ≥ 9 mm will be the targeted cut-off. If the endometrium does not yet reach the target, oestradiol supplementation will be continued with serial US assessment until the targeted cut-off will be reached. Upon reaching the target endometrium, oral letrozole tablets 2.5 mg will be started twice daily for 5 days only with continuation of 6 mg daily oestradiol supplementation. Then, daily intramuscular progesterone in oil (100 mg intramuscular progesterone) will be started once per day with continuation of 6 mg oestradiol
interventions:
Drug:estradiol valertae
Drug :letrozole 2.5 mg tablet
干预措施: estradiol valerate and letrozole (Drug)
Group B (Letrozole mild ovarian stimulation)
Oral letrozole 2.5-5 mg daily on cycle day(3-7) will be added . TVS will be performed from cycle day 8-10 to make sure that a dominant follicle has been recruited with the endometrium thickness ≥ 7 mm . Upon reaching the dominant follicle (18-20mm) , endometrial thickness will be measured on the day of ovulation trigger and blood sample will be withdrawn from each patient for assessment of E2 , P4 and LH levels. Patients with low LH level , high E2 level , low P4 level (<1 ng/ml) will continue in the RCT; 10,000unit HCG will be injected as ovulation trigger
intervention :
Drug :letrozole 2.5mg tablet
procedure: on the day of ovulation trigger blood sample will be withdrawn from each patient for assessment of E2 , P4 and LH levels.
干预措施: letrozole 2,5 mg tablet (Drug)
结局指标
主要结局
ongoing pregnancy rate (OPR)
时间窗: 12 weeks
Number of pregnant women with viable fetus at 12 weeks gestation per woman randomized
次要结局
- Clinical pregnancy rate (CPR)(5 weeks after embryo transfer)
- Implantation rate(21 days after embryo transfer)
- Ectopic pregnancy(7 week)
- Miscarriage rate(12 weeks)
- Number of participants with Hypertensive disorders of pregnancy(20 weeks gestation till postpartum)
- Number of participants with Large for gestational age(from gestation till delivery)
- live birth rate(22 completed weeks of gestational age)
研究者
Eman Elgindy
doctor
Rahem Fertility Center