Back to resultsEffect of Danazol on Endometrial αvβ3 Integrin Expression in Patients With Unexplained Recurrent Implantation Failure
Primary Purpose
Unexplained Infertility
Status
Completed
Phase
Phase 3
Locations
Egypt
Study Type
Interventional
Intervention
Pre-treatment endometrial biopsy
Danazol
Post-treatment endometrial biopsy
Sponsored by
About this trial
This is an interventional treatment trial for Unexplained Infertility
Eligibility Criteria
Inclusion Criteria:
- Age: 20-38 yrs
- Unexplained recurrent implantation failure (RIF), defined as failure to achieve an intrauterine gestational sac recognized by ultrasonography after transfer of at least four good-quality embryos (defined as those with four or five blastomeres on day 2, seven or more cells on day 3, ≤ 20% anucleated fragments and absence multinucleated blastomeres) in a minimum of three fresh or frozen IVF cycles after exclusion of other causes of RIF (as depicted by normal transvaginal ultrasonography, hysteroscopy, hysterosalpingography, laparoscopic findings, male and female karyotypic examination, endocrinological profile during ovarian stimulation and negative anti-cardiolipin antibody IgM/IgG, lupus anticoagulant, thrombophilia screening (including protein C, protein S, anti thrombin III and factor V leiden) and normal male semen analysis as depicted by 2010 WHO criteria for semen analysis and sperm DNA fragmentation testing).
Exclusion Criteria:
- Anovulation
- Contraindications to treatment with danazol (including chronic liver disease, congestive heart failure, dyslipidemia or history/current thrombo-embolic disease)
- Medical comorbidities (e.g. autoimmune disorders, diabetes mellitus, etc)
- Patients who underwent induction of ovulation / received hormonal treatment during the previous three months
Sites / Locations
- Ain SHams Maternity Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Study group
Arm Description
38 ovulatory patients with unexplained recurrent implantation failure were recruited. Pre-treatment endometrial biopsy and immunohistochemical examination for endometrial αvβ3 integrin expression (using immunohistochemically stained endometrial biopsy) was done. After treatment with danazol (Danol® 200mg capsules, Sanofi, Guildford, UK) in daily dosage of 400 mg for 12 weeks, post-treatment endometrial biopsy and immunohistochemical examination was repeated and compared with previous results.
Outcomes
Primary Outcome Measures
H-score
Stained sections were evaluated by the same pathologist for the intensity of brownish cytoplasmic and membranous staining of the endometrial components using the semi-quantitative scoring system originally described by Budwit-Novotny et al., H-score [6], calculated using the formula H-score=∑▒〖P_i (i+1)〗 where i is the staining intensity valued as 0, absent; 1+, weak, but detectable above control; 2+, moderate and 3+, strong; and Pi is the percentage of epithelial cells stained with each intensity (varying from 0 to 100%)
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03563664
Brief Title
Effect of Danazol on Endometrial αvβ3 Integrin Expression in Patients With Unexplained Recurrent Implantation Failure
Official Title
Effect of Danazol on Endometrial αvβ3 Integrin Expression in Patients With Unexplained Recurrent Implantation Failure - A Self-controlled Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
August 1, 2015 (Actual)
Primary Completion Date
August 15, 2017 (Actual)
Study Completion Date
August 15, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ain Shams University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study investigates the presence of a possible link between treatment with danazol and expression of endometrial αvβ3 integrin which might allow tailoring of danazol treatment to the subset of repeated IVF/ET failure that might benefit most from it.
38 eligible ovulatory women were recruited aged 20 - 38 years with unexplained recurrent implantation failure (RIF). Timed suction endometrial biopsy was obtained from participants during the implantation window of the pretreatment cycle, followed by immunohistochemical staining for endometrial αvβ3 integrin expression, scored using H-score.
Participants were treated with danazol (Danol® 200mg capsules, Sanofi, Guildford, UK) in daily dosage of 400 mg for 12 weeks. Post-treatment suction endometrial biopsy was obtained during the implantation window following the first ovulation after danazol treatment and endometrial αvβ3 integrin expression was compared to the pretreatment cycle.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Unexplained Infertility
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Model Description
38 ovulatory patients with unexplained recurrent implantation failure were recruited. Endometrial αvβ3 integrin expression (using immunohistochemically stained endometrial biopsy) was compared before and after treatment with danazol.
Masking
None (Open Label)
Allocation
N/A
Enrollment
38 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Study group
Arm Type
Experimental
Arm Description
38 ovulatory patients with unexplained recurrent implantation failure were recruited. Pre-treatment endometrial biopsy and immunohistochemical examination for endometrial αvβ3 integrin expression (using immunohistochemically stained endometrial biopsy) was done. After treatment with danazol (Danol® 200mg capsules, Sanofi, Guildford, UK) in daily dosage of 400 mg for 12 weeks, post-treatment endometrial biopsy and immunohistochemical examination was repeated and compared with previous results.
Intervention Type
Procedure
Intervention Name(s)
Pre-treatment endometrial biopsy
Intervention Description
Timed suction endometrial biopsy was obtained from participants via Wallach Endocell® 908014A endometrial cell sampler timed during the implantation window of the pretreatment cycle; followed by immunohistochemical staining using immunoperoxidase staining incorporating avidin-biotin complex (ABC) method.
Intervention Type
Drug
Intervention Name(s)
Danazol
Intervention Description
Participants were treated with danazol (Danol® 200mg capsules, Sanofi, Guildford, UK) in daily dosage of 400 mg for 12 weeks.
Intervention Type
Procedure
Intervention Name(s)
Post-treatment endometrial biopsy
Intervention Description
Post-treatment suction endometrial biopsy was obtained during the implantation window following the first ovulation after danazol treatment, timed, processed and stained as described previously.
Primary Outcome Measure Information:
Title
H-score
Description
Stained sections were evaluated by the same pathologist for the intensity of brownish cytoplasmic and membranous staining of the endometrial components using the semi-quantitative scoring system originally described by Budwit-Novotny et al., H-score [6], calculated using the formula H-score=∑▒〖P_i (i+1)〗 where i is the staining intensity valued as 0, absent; 1+, weak, but detectable above control; 2+, moderate and 3+, strong; and Pi is the percentage of epithelial cells stained with each intensity (varying from 0 to 100%)
Time Frame
12 weeks
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
38 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age: 20-38 yrs
Unexplained recurrent implantation failure (RIF), defined as failure to achieve an intrauterine gestational sac recognized by ultrasonography after transfer of at least four good-quality embryos (defined as those with four or five blastomeres on day 2, seven or more cells on day 3, ≤ 20% anucleated fragments and absence multinucleated blastomeres) in a minimum of three fresh or frozen IVF cycles after exclusion of other causes of RIF (as depicted by normal transvaginal ultrasonography, hysteroscopy, hysterosalpingography, laparoscopic findings, male and female karyotypic examination, endocrinological profile during ovarian stimulation and negative anti-cardiolipin antibody IgM/IgG, lupus anticoagulant, thrombophilia screening (including protein C, protein S, anti thrombin III and factor V leiden) and normal male semen analysis as depicted by 2010 WHO criteria for semen analysis and sperm DNA fragmentation testing).
Exclusion Criteria:
Anovulation
Contraindications to treatment with danazol (including chronic liver disease, congestive heart failure, dyslipidemia or history/current thrombo-embolic disease)
Medical comorbidities (e.g. autoimmune disorders, diabetes mellitus, etc)
Patients who underwent induction of ovulation / received hormonal treatment during the previous three months
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mohamed Samy, MD
Organizational Affiliation
M Samy
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ain SHams Maternity Hospital
City
Cairo
State/Province
Abbaseya
ZIP/Postal Code
002
Country
Egypt
12. IPD Sharing Statement
Learn more about this trial
Effect of Danazol on Endometrial αvβ3 Integrin Expression in Patients With Unexplained Recurrent Implantation Failure
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