Effect of Danazol on Endometrial αvβ3 Integrin Expression in Patients With Unexplained Recurrent Implantation Failure

NCT ID: NCT03563664

Last Updated: 2018-06-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-01
• Study Completion Date: 2017-08-15

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.

Conditions

Unexplained Infertility

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Study group

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.

Group Type: EXPERIMENTAL

Pre-treatment endometrial biopsy

Intervention Type: PROCEDURE

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.

Danazol

Intervention Type: DRUG

Participants were treated with danazol (Danol® 200mg capsules, Sanofi, Guildford, UK) in daily dosage of 400 mg for 12 weeks.

Post-treatment endometrial biopsy

Intervention Type: PROCEDURE

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.

Interventions

Pre-treatment endometrial biopsy

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: PROCEDURE

Danazol

Participants were treated with danazol (Danol® 200mg capsules, Sanofi, Guildford, UK) in daily dosage of 400 mg for 12 weeks.

Intervention Type: DRUG

Post-treatment endometrial biopsy

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.

Intervention Type: PROCEDURE

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 38 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Ain Shams University

OTHER

Sponsor Role: lead

Responsible Party

mohammed mahmoud samy

Lecturer in Obstetrics and Gynecology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mohamed Samy, MD

Role: PRINCIPAL_INVESTIGATOR

M Samy

Locations

Ain SHams Maternity Hospital

Cairo, Abbaseya, Egypt

Countries

Egypt

Other Identifiers

RIF-Danazol

Identifier Type: -

Identifier Source: org_study_id