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

NCT03563664 | Completed Phase 3

• 1 other identifier: RIF-Danazol
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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%)

  12 weeks

Study Arms (1)

Study group

EXPERIMENTAL

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.

Procedure: Pre-treatment endometrial biopsy; Drug: Danazol; Procedure: Post-treatment endometrial biopsy

Interventions

Pre-treatment endometrial biopsy 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.

Study group

Danazol DRUG

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

Study group

Post-treatment endometrial biopsy 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.

Study group

Eligibility Criteria

• Age: 20 Years - 38 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age: 20-38 yrs

You may not qualify if:

• 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

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Ain SHams Maternity Hospital

Cairo, Abbaseya, 002, Egypt

Location

MeSH Terms

Interventions

Danazol

Intervention Hierarchy (Ancestors)

Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Mohamed Samy, MD

  M Samy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer in Obstetrics and Gynecology

Model Details: 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.

Study Record Dates

• First Submitted: June 10, 2018
• First Posted: June 20, 2018
• Study Start: August 1, 2015
• Primary Completion: August 15, 2017
• Study Completion: August 15, 2017
• Last Updated: June 21, 2018

Record last verified: 2018-06

Locations

EG (1)