Clinical trial NCT04159649: The Outcomes of ICSI Cycles With and Without Letrozole
Official title: The Outcomes of ICSI Cycles With and Without Letrozole and Its Correlation With Mid-luteal Endometrial αvβ3 Integrin and Leukemia Inhibitory Factor
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: EMBRYO IMPLANTATION
Lead sponsor: Mansoura University
Sponsor class: OTHER
Collaborators: name: Zagazig University
First posted: 2019-11-12
Enrollment: 224
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

The study by Miller and his colleagues suggested that letrozole might improve αvβ3 integrin expression with possible increase in pregnancy and implantation rate. They suggested that, this drug may be a useful adjunct therapy during IVF protocols .

Eligibility criteria: Inclusion Criteria:

Women aged from 18 - 40 years old.

* Regular menstrual cycle (25-35).
* Women undergoing ICSI cycle

Exclusion Criteria:

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.

Primary outcomes:
measure: ongoing pregnancy rate.
timeFrame: 12 weeks
Secondary outcomes:
measure: endometrial thickness at day of HCG administration
timeFrame: 9-12 days from first day of menstruation when at least three growing follicle reaches above 18 mm
measure: estrogen and progesterone levels during day of HCG,
timeFrame: 9-12 days from first day of menstruation when at least three growing follicle reaches above 18 mm
measure: Rate of implantation
timeFrame: 21 days after embryo transfer
measure: Rate of clinical pregnancy
timeFrame: 5 weeks after embryo transfer
measure: miscarriage rate
timeFrame: 20 weeks
measure: multiple pregnancy rate
timeFrame: 12 weeks
measure: 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.
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Mansoura
country: Egypt
facility: Mansoura University
Study officials:
affiliation: Zagazig
name: Eman ElGindy, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: