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

Unexplained Infertility Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03563664
• Other study ID #: RIF-Danazol
• Status: Completed
• Phase: Phase 3
• Start date: August 1, 2015
• Est. completion date: August 15, 2017

Study information

• Verified date: June 2018
• Source: Ain Shams University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: August 15, 2017
• Est. primary completion date: August 15, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 38 Years

Eligibility

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

Related Conditions & MeSH terms

• Infertility
• Unexplained Infertility

Intervention

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.

Locations

Country	Name	City	State
Egypt	Ain SHams Maternity Hospital	Cairo	Abbaseya

Sponsors (1)

Lead Sponsor	Collaborator
Ain Shams University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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