EMBRYO IMPLANTATIONPhase 4NCT04159649
The Outcomes of ICSI Cycles With and Without Letrozole
A Phase 4 study testing Letrozole 2.5Mg Tablet, Gonadotropins and endometrial sample in the pretreatment cycle in people with EMBRYO IMPLANTATION, run by Mansoura University at 1 site in Egypt.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- EMBRYO IMPLANTATION
- What is being tested?
- Letrozole 2.5Mg Tablet, Gonadotropins and endometrial sample in the pretreatment cycle
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 224 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Dec 2019to 30 Dec 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Women aged from 18 - 40 years old.
- Regular menstrual cycle (25-35).
- Women undergoing ICSI cycle
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Egypt1 site, 1 recruiting
- Recruiting
Mansoura University
Al Mansurah, 53111
Ahmed Gibreel, 0020104045733, ahmedfathgi@yahoo.com
Ahmed Gibree, MD
About this study
Official title: The Outcomes of ICSI Cycles With and Without Letrozole and Its Correlation With Mid-luteal Endometrial αvβ3 Integrin and Leukemia Inhibitory Factor
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.
Read more
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.
Read the 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 .
- Conditions
- EMBRYO IMPLANTATION
- Being tested
- Letrozole 2.5Mg Tablet, Gonadotropins, endometrial sample in the pretreatment cycle
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Letrozole 2.5Mg TabletDrug
Also called Femara
Gonadotropins with or letrozol in fixed Gn RH antagonist IVF protocol
GonadotropinsDrug
Gonadotropins without letrozol in fixed Gn RH antagonist IVF protocol
endometrial sample in the pretreatment cycleProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| letrozole, gonadotropins and fixed GnRH antagonist | Experimental | 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. Receives: Drug: Letrozole 2.5Mg Tablet; Drug: Gonadotropins; Procedure: endometrial sample in the pretreatment cycle |
| gonadotropins and fixed GnRH antagonist (control group). | Active comparator | 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. Receives: Drug: Gonadotropins; Procedure: endometrial sample in the pretreatment cycle |
What is being measured
The primary outcome is the main question the study is designed to answer.
ongoing pregnancy rate.
Number of pregnant women with viable fetus at 12 weeks gestation per woman randomized
Measured: 12 weeks
Secondary outcomes (7)
endometrial thickness at day of HCG administration
Thickness of endometrium
Measured: 9-12 days from first day of menstruation when at least three growing follicle reaches above 18 mm
estrogen and progesterone levels during day of HCG,
estrogen and progesterone serum levels
Measured: 9-12 days from first day of menstruation when at least three growing follicle reaches above 18 mm
Rate of implantation
Number of gestational sac recognized by ultrasound in uterus 3 weeks after embryo transfer
Measured: 21 days after embryo transfer
Rate of clinical pregnancy
Number of gestational sacs with evident fetal pulsations per woman randomized
Measured: 5 weeks after embryo transfer
miscarriage rate
Number of miscarriages per woman with positive pregnancy tests
Measured: 20 weeks
multiple pregnancy rate
Number of multiple pregnancies per pregnant women with evident fetal pulsations
Measured: 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.
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.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2019
- Study start1 Dec 2019
- Primary completion30 Dec 2020 (estimated)
- Study completion30 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EMBRYO IMPLANTATIONStudies of the same condition, open and under way.
- More trials run by Mansoura UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 224 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mansoura University
- Sponsor type
- University, hospital or other
- Collaborators
- Zagazig University
- Responsible party
- Principal investigator, Ahmed Gibreel, Mansoura University
- Investigators
- Eman ElGindy, MD, PhD, Principal investigator, Zagazig
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04159649
- Sponsor's protocol ID
- ZU-IRB
- Status last verified
- Nov 2019
- First submitted
- 15 Jul 2019
- Last updated
- 16 Dec 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Outcomes of ICSI Cycles With and Without Letrozole and Its Correlation With Mid-luteal Endometrial αvβ3 Integrin and Leukemia Inhibitory Factor
- ClinicalTrials.gov ID
- NCT04159649
- Acronym / sponsor ID
- ZU-IRB
- Conditions
- EMBRYO IMPLANTATION
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 224 participants (estimated)
- Lead sponsor
- Mansoura UniversityUniversity, hospital or other
- Collaborators
- Zagazig University
- Study start
- 1 Dec 2019 (actual)
- Primary completion
- 30 Dec 2020 (estimated)
- Study completion
- 30 Dec 2020 (estimated)
- First posted
- 12 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 .
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| letrozole, gonadotropins and fixed GnRH antagonist | Experimental | Drug: Letrozole 2.5Mg Tablet, Drug: Gonadotropins, Procedure: endometrial sample in the pretreatment cycleletrozole (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. |
| gonadotropins and fixed GnRH antagonist (control group). | Active comparator | Drug: Gonadotropins, Procedure: endometrial sample in the pretreatment cyclegonadotropins 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. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Women aged from 18 - 40 years old.
- Regular menstrual cycle (25-35).
- Women undergoing ICSI cycle
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Letrozole 2.5Mg TabletAlso: FemaraGonadotropins with or letrozol in fixed Gn RH antagonist IVF protocol | Drug | letrozole, gonadotropins and fixed GnRH antagonist |
| GonadotropinsGonadotropins without letrozol in fixed Gn RH antagonist IVF protocol | Drug | gonadotropins and fixed GnRH antagonist (control group)., letrozole, gonadotropins and fixed GnRH antagonist |
| endometrial sample in the pretreatment cycleAll participant will be exposed to mid luteal endometrial sample in the pretreatment cycle. couples will be asked to use condom in the pretreatment cycle. | Procedure or surgery | gonadotropins and fixed GnRH antagonist (control group)., letrozole, gonadotropins and fixed GnRH antagonist |
Primary outcome
ongoing pregnancy rate.
Time frame: 12 weeks
Number of pregnant women with viable fetus at 12 weeks gestation per woman randomized
7 secondary outcomes
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
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
Rate of implantation
Time frame: 21 days after embryo transfer
Rate of clinical pregnancy
Time frame: 5 weeks after embryo transfer
miscarriage rate
Time frame: 20 weeks
multiple pregnancy rate
Time frame: 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.
Time frame: 8 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eman ElGindy, MD, PhD principal investigator
Zagazig
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Letrozole 2.5Mg Tablet, Gonadotropins and endometrial sample in the pretreatment cycle in people with EMBRYO IMPLANTATION, run by Mansoura University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Eman ElGindy, MD, PhD (01227491143, eman_elgindy2013@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ongoing pregnancy rate. (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2019.