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

Sponsor

Ain Shams University (Other)

Overall Status

Completed

CT.gov ID

NCT03563664

Collaborator

(none)

Enrollment

Location

Arm

24.5

Actual Duration (Months)

1.6

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Unexplained Infertility	Procedure: Pre-treatment endometrial biopsy Drug: Danazol Procedure: Post-treatment endometrial biopsy	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

38 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention 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.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)

Primary Purpose:

Treatment

Official Title:

Effect of Danazol on Endometrial αvβ3 Integrin Expression in Patients With Unexplained Recurrent Implantation Failure - A Self-controlled Clinical Trial

Actual Study Start Date :

Aug 1, 2015

Actual Primary Completion Date :

Aug 15, 2017

Actual Study Completion Date :

Aug 15, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Procedure: 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. Drug: Danazol Participants were treated with danazol (Danol® 200mg capsules, Sanofi, Guildford, UK) in daily dosage of 400 mg for 12 weeks. Procedure: 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.

Arm

Intervention/Treatment

Experimental: 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.

Procedure: 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.

Drug: Danazol

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

Procedure: 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.

Outcome Measures

Primary Outcome Measures

H-score [12 weeks]
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%)

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 38 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ain SHams Maternity Hospital	Cairo	Abbaseya	Egypt	002

Sponsors and Collaborators

Ain Shams University

Investigators

Principal Investigator: Mohamed Samy, MD, M Samy

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

mohammed mahmoud samy, Lecturer in Obstetrics and Gynecology, Ain Shams University

ClinicalTrials.gov Identifier:

NCT03563664

Other Study ID Numbers:

RIF-Danazol

First Posted:

Jun 20, 2018

Last Update Posted:

Jun 21, 2018

Last Verified:

Jun 1, 2018

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Infertility

Danazol

Study Results

No Results Posted as of Jun 21, 2018