Local Endometrial Injury in Fresh Embryo Transfer Cycles

NCT01844453 | Unknown Phase 3

• 1 other identifier: 3216
• Study Type: interventional
• Target: 360
• Locations: 1 country
• Sites: 1

Brief Summary

The application of in-vitro fertilization (IVF) has provided remarkable opportunities for infertile couple to conceive in the last four decades. Historically IVF was performed for patients with bilateral tubal obstruction, but its use is presently widespread. Although the efficacy of assisted reproductive technology continues to improve, endometrial implantation remains the limiting step towards a successful pregnancy. Reduced endometrial receptivity and embryonic defects are the probable primary causes of implantation failure during IVF(1). Patients with repeated implantation failure despite transferring good-quality embryos continue to be a major dilemma for clinicians and are a topic of great research interest. Barash et al. unintentionally discovered and initially reported that an endometrial biopsy prior to IVF in women who have had one or more implantation failures was associated with an increased clinical pregnancy (66.7% vs 30.3%, p\<0.01) and live birth rates 48.9% vs 22.5%, p=0.02) compared to a control group(2). The mechanism by which a local endometrial injury (LEI) may increase the pregnancy rate is still not fully clear. Possible etiologies include its role in promoting a beneficial local inflammatory response, inducing endometrial decidualization, or improving endometrial maturation synchrony (3-6). Following Barash et al's publication, several randomized controlled studies confirmed their findings (7-11). However, there has been extensive heterogeneity among studies, including the number of biopsies, how the biopsy is performed and the selected patient population. On the other hand all the studies have in common that the endometrial biopsy was performed prior to the start of the IVF cycle. The optimal timing of an endometrial biopsy with respect to an IVF cycle is unknown. There is reason to suspect that an endometrial biopsy during the follicular phase of an IVF stimulation cycle may improve pregnancy outcomes, although this has not been directly examined. We therefore propose a randomized controlled study to evaluate the impact of an endometrial biopsy on the implantation and pregnancy rate in both the luteal phase prior to the IVF cycle as well as the follicular phase of the concurrent IVF cycles.

Conditions

Infertility

Keywords

Subfertility; Recurrent Implantation Failure

Outcome Measures

Primary Outcomes (1)

• Implantation Rate

  Implantation rate is defined as the number of intrauterine gestational sacs seen on transvaginal ultrasound (clinical pregnancy) divided by the number of embryos transferred \[implantation rate = number of gestational sacs noted on the viability ultrasound / number of embryos transferred\].

  4-5 weeks after embryo transfer

Secondary Outcomes (4)

• biochemical pregnancy rate

  2 weeks after embryo transfer

• clinical pregnancy rate

  4-6 weeks after embryo transfer

• Live birth rate

  within 1 year of embryo transfer

• Miscarriage Rates

  Within 5 months of embryo transfer

Study Arms (3)

Luteal Phase Arm

EXPERIMENTAL

Local Endometrial Injury in mid-luteal phase (cycle day 21-26) prior to the treatment cycle.

Procedure: Endometrial Biopsy

Proliferative Phase Arm

EXPERIMENTAL

Local Endometrial Injury in early proliferative phase of current treatment cycle (cycle day 2-3).

Procedure: Endometrial Biopsy

Control Arm

NO INTERVENTION

No Local Endometrial Injury will be performed. Patients will undergo a routine fresh IVF treatment cycle.

Interventions

Endometrial Biopsy PROCEDURE

The Local Endometrial Injury will be performed using the standard technique using a Pipelle sampling catheter in the outpatient department. After a speculum examination is performed and the cervix is well visualized, the Pipelle will be inserted gently through the cervical canal into the uterine cavity and advanced slowly until resistance is noted. At this point the internal piston is withdrawn to create negative suction and the Pipelle is gently maneuvered up and down alongside the uterine cavity wall. The Pipelle catheter is then withdrawn gently and any obtained specimen (uterine lining) will be sent for histopathological examination.

Also known as: Local Endometrial Injury

Luteal Phase Arm; Proliferative Phase Arm

Eligibility Criteria

• Age: 36 Years - 44 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Infertile patients age ≥36 years old.
• Patients who are planned to undergo a second fresh IVF cycle
• Patients who have previously had a fresh IVF-ET and ≥1 frozen - thawed ET in the past and did not achieve a clinical pregnancy \[two or more failed embryo transfers\].
• Ovarian stimulation with a "microdose flare" protocol
• Patients who are scheduled to undergo a single embryo transfer
• Consent in writing to participate in the study.

You may not qualify if:

• Age of \<36 years old.
• Known or suspected intrauterine factor on ultrasound imaging (submucosal fibroid, endometrial polyp, intrauterine adhesions or intramural fibroids causing uterine distortion).
• Endometriosis (documented by laparoscopy or known endometriomas by ultrasound)
• Previous hysteroscopy (since the start of their 1st IVF cycle)
• Patients who does not speak English or French.
• Patients who will be transferred more than one embryo.

Sponsors & Collaborators

• McGill University: lead

Study Sites (1)

McGill University Health Centre

Montreal, Quebec, H3A1A1, Canada

Location

MeSH Terms

Conditions

Infertility

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Study Officials

• Dan Nayot, BSc; MSc; MD

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  STUDY DIRECTOR

• Togas Tulandi, MD, MHCM

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

• Hananel Holzer, MD

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dan Nayot, MD

CONTACT

4166163334; dan.nayot@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: B.Sc.; M.Sc.; M.D.

Study Record Dates

• First Submitted: April 29, 2013
• First Posted: May 1, 2013
• Study Start: August 1, 2013
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: May 1, 2013

Record last verified: 2013-04

Locations

CA (1)