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The Outcomes of ICSI Cycles With and Without Letrozole

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04159649
Recruitment Status : Recruiting
First Posted : November 12, 2019
Last Update Posted : December 16, 2019
Sponsor:
Collaborator:
Zagazig University
Information provided by (Responsible Party):
Ahmed Gibreel, Mansoura University

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.


Condition or disease Intervention/treatment Phase
EMBRYO IMPLANTATION Drug: Letrozole 2.5Mg Tablet Drug: Gonadotropins Procedure: endometrial sample in the pretreatment cycle Phase 4

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 .

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 224 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Outcomes of ICSI Cycles With and Without Letrozole and Its Correlation With Mid-luteal Endometrial αvβ3 Integrin and Leukemia Inhibitory Factor
Actual Study Start Date : December 1, 2019
Estimated Primary Completion Date : December 30, 2020
Estimated Study Completion Date : December 30, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Letrozole

Arm Intervention/treatment
Experimental: 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.
Drug: Letrozole 2.5Mg Tablet
Gonadotropins with or letrozol in fixed Gn RH antagonist IVF protocol
Other Name: Femara

Drug: Gonadotropins
Gonadotropins without letrozol in fixed Gn RH antagonist IVF protocol

Procedure: endometrial sample in the pretreatment cycle
All participant will be exposed to mid luteal endometrial sample in the pretreatment cycle. couples will be asked to use condom in the pretreatment cycle.

Active Comparator: 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.
Drug: Gonadotropins
Gonadotropins without letrozol in fixed Gn RH antagonist IVF protocol

Procedure: endometrial sample in the pretreatment cycle
All participant will be exposed to mid luteal endometrial sample in the pretreatment cycle. couples will be asked to use condom in the pretreatment cycle.




Primary Outcome Measures :
  1. ongoing pregnancy rate. [ Time Frame: 12 weeks ]
    Number of pregnant women with viable fetus at 12 weeks gestation per woman randomized


Secondary Outcome Measures :
  1. endometrial thickness at day of HCG administration [ Time Frame: 9-12 days from first day of menstruation when at least three growing follicle reaches above 18 mm ]
    Thickness of endometrium

  2. estrogen and progesterone levels during day of HCG, [ Time Frame: 9-12 days from first day of menstruation when at least three growing follicle reaches above 18 mm ]
    estrogen and progesterone serum levels

  3. Rate of implantation [ Time Frame: 21 days after embryo transfer ]
    Number of gestational sac recognized by ultrasound in uterus 3 weeks after embryo transfer

  4. Rate of clinical pregnancy [ Time Frame: 5 weeks after embryo transfer ]
    Number of gestational sacs with evident fetal pulsations per woman randomized

  5. miscarriage rate [ Time Frame: 20 weeks ]
    Number of miscarriages per woman with positive pregnancy tests

  6. multiple pregnancy rate [ Time Frame: 12 weeks ]
    Number of multiple pregnancies per pregnant women with evident fetal pulsations

  7. 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. [ Time Frame: 8 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04159649


Contacts
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Contact: Eman ElGindy, MD, PhD 01227491143 eman_elgindy2013@hotmail.com

Locations
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Egypt
Mansoura University Recruiting
Mansoura, Egypt, 53111
Contact: Ahmed Gibreel    0020104045733    ahmedfathgi@yahoo.com   
Principal Investigator: Ahmed Gibree, MD         
Sponsors and Collaborators
Mansoura University
Zagazig University
Investigators
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Principal Investigator: Eman ElGindy, MD, PhD Zagazig
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Responsible Party: Ahmed Gibreel, Assistant professor, Mansoura University
ClinicalTrials.gov Identifier: NCT04159649    
Other Study ID Numbers: ZU-IRB
First Posted: November 12, 2019    Key Record Dates
Last Update Posted: December 16, 2019
Last Verified: November 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Letrozole
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs