Endometrial Injury for Assisted Reproduction

Endometrial Injury Prior Ovulation Induction for Assisted Reproductive Techniques: a Randomized Controlled Trial

The objective of this study is to evaluate the effect of endometrial injury performed prior ovulation induction for assisted reproductive techniques main outcomes.

Study Overview

• Status: Terminated
• Conditions: Infertility
• Intervention / Treatment: Procedure: Endometrial injury; Procedure: Control group

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo
    • Ribeirao Preto, Sao Paulo, Brazil, 14049-900
      • Setor de Reproducao Humana do HC-FMRP-USP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women who will start assisted reproductive techniques with planned fresh embryo transfer.
• Age between 18 and 38 years.
• Written informed consent.

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Endometrial injury group; Endometrial biopsy was performed once with a pipelle de Cornier® in the month before initiating controlled ovarian stimulation.	Procedure: Endometrial injury; Evaluate the position and size of the uterus by transabdominal ultrasonography, with the bladder comfortably full. Identify the cervix with a disposable speculum. Open one sealed opaque envelope for allocation. Endometrial injury: Slide the Pipelle de Cornier® (Laboratoires Prodimed, Neully-En-Thelle, France) gently through the cervix up to the uterine fundus. Transbadominal ultrasound might be used to confirm position.; Draw back the piston to the end of the biopsy cannula until it locks creating a negative pressure.; Sweep the uterine fundus slowly several times up to the internal orifice of the cervix, using regular to-and-fro movements while rotating the sampler to include the whole uterine cavity in the specimen, for 30 seconds or until participant ask for stopping.
Sham Comparator: Control group; Introduction of the speculum and wiping of the cervix with gaze for 30 seconds.	Procedure: Control group; The investigator will dry the cervix with gauze and forceps for for 30 seconds or until participant ask for stopping.; Other Names: Sham procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live Birth	The complete expulsion or extraction from its mother of a product of fertilization, irrespective of the duration of the pregnancy, which, after such separation, breathes or shows any other evidence of life, such as heart beat, umbilical cord pulsation, or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is attached. Note: All allocated women will be used as denominator when assessing live birth rate.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Pregnancy	Pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It includes ectopic pregnancy. Multiple gestational sacs are counted as one clinical pregnancy. Note: All allocated women will be considered when assessing clinical pregnancy rate.	3 months
Ongoing Pregnancy	At least one fetus with heart beat after 12 weeks of gestational age. Note: All allocated women will be considered when assessing ongoing pregnancy rate.	6 months
Miscarriage	Loss of a clinical pregnancy before 20 completed weeks of gestational age (18 weeks after fertilization). Note: All allocated women will be considered when assessing miscarriage rate.	9 months
Implantation Rate	The number of gestational sacs observed divided by the number of embryos transferred.	3 months
Endometrial Thickness	The maximum distance perpendicular to the inter-endometrial interface from the endometrium-myometrium interface of the anterior to the posterior wall of the uterus assessed in the sagittal plane. This outcome will be assessed when at least one follicle ≥ 17mm is observed.	1 month
Endometrial Volume	The total volume of endometrial tissue assessed by three-dimensional ultrasonography. This outcome will be assessed when at least one follicle ≥ 17mm is observed.	1 month
Three-dimensional Doppler Indices From Endometrium (VFI)	Vascularization index (VI), flow index (FI) and vascularization-flow index (VFI) assessed from endometrium using three-dimensional Power Doppler ultrasonography. This outcome will be assessed when at least one follicle ≥ 17mm is observed. Only VFI was reported as it is a combination of VI and FI (VFI = VI*FI/100), and currently there are several concerns about the validity of these indices. Such indices have no scale.	1 month
Procedure Related Pain	Pain will be assessed using a Visual Analogue Scale (VAS). We will use a 10 cm length horizontal line, anchored by word descriptors at each end: "No Pain" = 0 cm and "Very Severe Pain" = 10 cm. This outcome will be assessed in both groups, just after endometrial injury or sham procedure.	Immediately after procedure

Collaborators and Investigators

• Sponsor: University of Sao Paulo
• Collaborators: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.; Conselho Nacional de Desenvolvimento Científico e Tecnológico; Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
• Investigators: Principal Investigator: Wellington P Martins, PhD, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo

Publications and helpful links

General Publications

• Lensen SF, Armstrong S, Gibreel A, Nastri CO, Raine-Fenning N, Martins WP. Endometrial injury in women undergoing in vitro fertilisation (IVF). Cochrane Database Syst Rev. 2021 Jun 10;6(6):CD009517. doi: 10.1002/14651858.CD009517.pub4.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: May 26, 2010
• First Submitted That Met QC Criteria: May 26, 2010
• First Posted (Estimate): May 27, 2010

Study Record Updates

• Last Update Posted (Estimate): February 17, 2014
• Last Update Submitted That Met QC Criteria: January 2, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Ultrasonography; Endometrium; Reproductive Techniques; Embryo Implantation
• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: HCRP10340/09