Molecular Evaluation of Endometrium After Endometrial Injury

Molecular Evaluation of Endometrium Obtained From Women With Repeated Implantation Failure (RIF) After Endometrial Injury in Compare to Women Without Endometrial Injury; Phase 3 Clinical Trial

Repeated implantation failure (RIF) is determined when failure of implantation occurred during at least three consecutive IVF attempts while at least one high-grade embryo was transferred in each cycle. Several methods have been suggested to improve the implantation rate in RIF patients. One of the most promising methods is local injury to the endometrium. It has been reported that the rates of implantation, clinical pregnancy, and live birth reach more than double in RIF patients with local endometrial injury than patients without it. The population of this study included all infertile couples attending the Royan Institute, who have at least three consecutive cycles of ART failure. Also this study is phase 3 randomized clinical trial. Based on the average menstrual cycle 30-28 days, endometrial and blood samples were collected from two groups of patients on day 21 of luteal phase of their spontaneous menstrual cycle. The intervention, but not the control group underwent prior biopsy treatment in follicular phase on days 8 or/and 11 to 13 of that same cycle but in these days blood sample in both groups were collected. To investigate the impact of local endometrial injury in increasing the rate of pregnancy in ART - treated RIF patients, the investigators will examine the changes of immunological factors involved in the implantation including some cytokines, growth factors ( in serum and endometrial biopsies) and the expression of TLRs and HOX genes ( in endometrial biopsies) obtained from both groups.

Study Overview

• Status: Completed
• Conditions: Endometrial Injury
• Intervention / Treatment: Procedure: PIPELLE Endometrial injury

Detailed Description

This study is phase 3 randomized clinical trial that the 20 infertile women with the following conditions will be studied in 2 groups. In the intervention group, Endometrial sampling is obtained twice by Pipelle [one in the follicular phase (during 8-9 or 11- 13 day in the beginning of buserelin cycle) and the last in the luteal phase (during 19-21 or 20-23 day) preceding the embryo transfer cycle preceding the embryo transfer cycle]. In the control group endometrial sampling will be done only in the luteal phase of the cycle preceding the embryo transfer cycle. Blood samples (5- 10 cc) are taken in the both groups twice (one on the 9-8 or 11- 13 day and 19-21 or 20-23 day preceding the embryo transfer cycle).

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Royan Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• < 40 years old
• Patients had history of 3 failed consecutive cycles of IVF / ICSI.
• Patients were good responders in prior ovulation induction cycle.
• There were at least two embryos with grade A in each embryo transfer cycle.
• Normal uterus in Hysterosalpingography (HSG) or ultrasound or hysteroscopy scans.
• The minimum thickness of the endometrium is 7 mm in injection day.

Exclusion Criteria:

• Submucosal myoma.
• Intramural and sub serousal myoma greater than 5 cm.
• Endometrioma equal to or greater than 3 cm or Hydrosalpinx.
• The number of available embryos is less than 2 in the current cycle.
• Patients with endometrial tuberculosis and persons who are treated for tuberculosis.
• Patients with any specific drug consumption.
• Patients with a history of thyroid disease, diabetes and other endocrine disorders.
• Lost to follow up or sampling.
• Impossibility of prepare endometrial sampling because of severe pain or probability infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Endometrial injury; In the intervention group, endometrial sampling is obtained twice by Pipelle [one in the follicular phase (during 8-9 or 11- 13 day in the beginning of buserelin cycle) and the last in the luteal phase (during 19-21 or 20-23 day) preceding the embryo transfer cycle preceding the embryo transfer cycle]. Blood samples (5- 10 cc) are taken in the both groups twice (one on the 9-8 or 11- 13 day and 19-21 or 20-23 day preceding the embryo transfer cycle).	Procedure: PIPELLE Endometrial injury; The endometrial injury which is induced with pipelle.
No Intervention: Control; In the control group endometrial sampling will be done only in the luteal phase of the cycle preceding the embryo transfer cycle. Blood samples (5- 10 cc) are taken twice (one on the 9-8 or 11- 13 day and 19-21 or 20-23 day preceding the embryo transfer cycle).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cytokine	Measurement of cytokines in endometrial sample in both group.	1month
growth factor	Measurement of growth factors in endometrial sample in both groups.	1month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expression of TLRs	Evaluation of TLRs expression in endometrial sample in both groups.	1month
Expression of HOX	Evaluation of HOX expression in endometrial sample in both groups.	1month
pregnancy rate	Evaluation of pregnancy rate in both groups.	6months

Collaborators and Investigators

• Sponsor: Royan Institute
• Investigators: Study Director: Reza Aflatoonian, PhD, Department of Endocrinology and Female Infertility at Reproductive Biomedicine Research Centre, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.; Study Director: Mahnaz Ashrafi, MD, Department of Endocrinology and Female Infertility at Reproductive Biomedicine Research Centre, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.; Principal Investigator: Samaneh Aghajanpour, M.S.c, Department of Endocrinology and Female Infertility at Reproductive Biomedicine Research Centre, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.; Principal Investigator: Elham Amirchaghmaghi, MD,PhD, Department of Endocrinology and Female Infertility at Reproductive Biomedicine Research Centre, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2014
• Primary Completion (Actual): November 1, 2018
• Study Completion (Actual): March 1, 2020

Study Registration Dates

• First Submitted: June 7, 2015
• First Submitted That Met QC Criteria: June 19, 2015
• First Posted (Estimate): June 24, 2015

Study Record Updates

• Last Update Posted (Actual): September 9, 2020
• Last Update Submitted That Met QC Criteria: September 7, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries
• Other Study ID Numbers: royan-Emb-021