The Outcomes of ICSI Cycles With and Without Letrozole and Its Correlation With Mid-luteal Endometrial αvβ3 Integrin and Leukemia Inhibitory Factor
试验速览
- 阶段
- 4 期
- 入组人数
- 224
- 试验地点
- 1
- 主要终点
- ongoing pregnancy rate.
研究概览
简要总结
A variety of genes working together with ovarian hormones conducts and precisely control the process of endometrial receptivity and implantation.
Leukemia inhibitory factor and αvβ3 integrin are two markers of implantation with at most importance. Reports have emphasized that these important biomarkers have a great role during the process of embryonic implantation.
αvβ3 integrin is one of the adhesion molecules which has a critical role in blastocyst apposition and attachment. Many studies have demonstrated that abnormal expression of αvβ3 integrin is associated with poor reproductive outcomes. Other studies haven't found a strong relation between αvβ3 integrin expression and reproductive outcomes Letrozole is an aromatase inhibitor which has been used in controlled ovarian stimulation especially in women with PCOS . Data suggests that letrozole addition to gonadotropins during ovarian stimulation protocols improve the response of the ovaries to FSH in low responders and increase the number of preovulatory follicles without adversely affect the outcomes.
Letrozole is used as an adjuvant therapy in ovarian stimulation protocols. So this study aims to evaluate whether the use of letrozole in combination with gonadotropins and GnRH antagonist is superior to gonadotropins and antagonist alone in women undergoing ICSI treatment.
Furthermore, both αvβ3 integrin and leukemia inhibitory factor are important markers of endometrial receptivity and implantation. Therefore, this study aims to assess the correlation between mid-luteal gene expression of both αvβ3 integrin and leukemia inhibitory factor and the clinical outcomes of antagonist cycles with or without letrozole.
详细描述
Embryo implantation depends on quality of the embryo, endometrial receptivity and embryo/endometrial interaction. It is estimated that two third of implantation failure is a result of defects in endometrial receptivity. A variety of genes working together with ovarian hormones conducts and precisely control the process of endometrial receptivity and implantation.
Leukemia inhibitory factor and αvβ3 integrin are two markers of implantation with at most importance. Reports have emphasized that these important bio-markers have a great role during the process of embryonic implantation . Both are expressed in the epithelial cells during the mid-secretory phase of the menstrual cycle in healthy fertile women and their absence is associated with infertility and recurrent pregnancy loss .
Leukemia inhibitory factor is a class of cytokines which plays a key role in the process of implantation in both human and animals . Studies suggest that absence of leukemia inhibitory factor in the endometrium has a negative impact on embryo implantation .
αvβ3 integrin is one of the adhesion molecules which has a critical role in blastocyst apposition and attachment. Many studies have demonstrated that abnormal expression of αvβ3 integrin is associated with poor reproductive outcomes . Other studies haven't found a strong relation between αvβ3 integrin expression and reproductive outcomes.
Letrozole is an aromatase inhibitor which has been used in controlled ovarian stimulation especially in women with PCOS . Data suggests that letrozole addition to gonadotropins during ovarian stimulation protocols improve the response of the ovaries to FSH in low responders and increase the number of preovulatory follicles without adversely affect the outcomes.
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 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women aged from 18 - 40 years old.
- •Regular menstrual cycle (25-35).
- •Women undergoing ICSI cycle
排除标准
- •Women younger than 18 or older than 40 years old.
- •Women who had unilateral oophorectomy.
- •Women who had uterine abnormality or pathology.
- •Women who will not meet the inclusion criteria.
- •Women who will refuse to participate in in the study.
- •ICSI cycles with fresh or frozen TESE samples.
研究组 & 干预措施
letrozole, gonadotropins and fixed GnRH antagonist
letrozole (2.5 mg) will be given from the second day of the cycle and for 5 days, gonadotropins will be given from the third day of the cycle and GnRH antagonist will be added from the six day of the cycle for controlled ovarian stimulation in IVF (interventional group). Participant will be exposed to mid luteal endometrial sample in the pretreatment cycle. couples will be asked to use condom in the pretreatment cycle.
干预措施: Letrozole 2.5Mg Tablet (Drug)
letrozole, gonadotropins and fixed GnRH antagonist
letrozole (2.5 mg) will be given from the second day of the cycle and for 5 days, gonadotropins will be given from the third day of the cycle and GnRH antagonist will be added from the six day of the cycle for controlled ovarian stimulation in IVF (interventional group). Participant will be exposed to mid luteal endometrial sample in the pretreatment cycle. couples will be asked to use condom in the pretreatment cycle.
干预措施: Gonadotropins (Drug)
letrozole, gonadotropins and fixed GnRH antagonist
letrozole (2.5 mg) will be given from the second day of the cycle and for 5 days, gonadotropins will be given from the third day of the cycle and GnRH antagonist will be added from the six day of the cycle for controlled ovarian stimulation in IVF (interventional group). Participant will be exposed to mid luteal endometrial sample in the pretreatment cycle. couples will be asked to use condom in the pretreatment cycle.
干预措施: endometrial sample in the pretreatment cycle (Procedure)
gonadotropins and fixed GnRH antagonist (control group).
gonadotropins will be given from the third day of the cycle and GnRH antagonist will be added from the six day of the cycle for controlled ovarian stimulation in IVF(control group). Participant will be exposed to mid luteal endometrial sample in the pretreatment cycle. couples will be asked to use condom in the pretreatment cycle.
干预措施: Gonadotropins (Drug)
gonadotropins and fixed GnRH antagonist (control group).
gonadotropins will be given from the third day of the cycle and GnRH antagonist will be added from the six day of the cycle for controlled ovarian stimulation in IVF(control group). Participant will be exposed to mid luteal endometrial sample in the pretreatment cycle. couples will be asked to use condom in the pretreatment cycle.
干预措施: endometrial sample in the pretreatment cycle (Procedure)
结局指标
主要结局
ongoing pregnancy rate.
时间窗: 12 weeks
Number of pregnant women with viable fetus at 12 weeks gestation per woman randomized
次要结局
- miscarriage rate(20 weeks)
- multiple pregnancy rate(12 weeks)
- Correlation between mid-luteal gene expression of both αvβ3 integrin and leukemia inhibitory factor and the clinical outcomes of antagonist cycles with or without letrozole.(8 weeks)
- endometrial thickness at day of HCG administration(9-12 days from first day of menstruation when at least three growing follicle reaches above 18 mm)
- Rate of implantation(21 days after embryo transfer)
- Rate of clinical pregnancy(5 weeks after embryo transfer)
- estrogen and progesterone levels during day of HCG,(9-12 days from first day of menstruation when at least three growing follicle reaches above 18 mm)
研究者
Ahmed Gibreel
Assistant professor
Mansoura University