Impact of Operation on Fertility for Women With Severe Endometriosis (EFFORT)

Comparing Impact of Operation and Fertility Treatment on Fertility for Women With Deep Infiltrating Endometriosis: A Multicenter Randomized Controlled Trial

The EFFORT study compares the impact on fertility of operation or fertility treatment (IVF, in vitro fertilization) in a multicenter randomized controlled trial. The study population consists of women with colorectal deep infiltrating endometriosis and a pregnancy intention. These women will be randomized to either of the two treatment groups: Group A = Operation or Group B = fertility treatment (IVF). Group A will be further divided postoperatively into spontaneous conception or IVF depending on the Endometriosis Fertility Index score.

Study Overview

• Status: Recruiting
• Conditions: Infertility, Female; Deep Endometriosis
• Intervention / Treatment: Procedure: Operation; Procedure: Fertility treatment

• Study Type: Interventional
• Enrollment (Anticipated): 352
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ulla B Knudsen, Professor; Phone Number: +45 78426592; Email: ubk@dadlnet.dk
• Study Contact Backup: Name: Maja Raos; Email: majaraos@clin.au.dk

Study Locations

• Denmark
  • Central Region
    • Aarhus N, Central Region, Denmark, 8200
      • Recruiting
      • Aarhus University Hospital
      • Contact: Mikkel Seyer-Hansen, MD
    • Horsens, Central Region, Denmark, 8700
      • Recruiting
      • Horsens Regional Hospital
      • Contact: Ulla B Knudsen, Professor; Phone Number: +45 7842 6592; Email: ubk@dadlnet.dk
• France
  • Bordeaux, France
    • Recruiting
    • The Endometriosis Center, Clinique Tivoli-Ducos
    • Contact: Horace Roman, MD

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:

• Rectosigmoid endometriosis and wish for surgery
• Pregnancy intention for at least 6 months
• AMH above 5 pmol/ml
• Maximum of 2 previous IVF treatments
• Male partner

Exclusion Criteria:

• Endometriosis involving the ureter unilaterally or bilaterally (randomization unethical)
• BMI above 32
• Contraindication for IVF (untreated uterine factor infertility, untreated/maltreated systemic or malignant disease, oocyte aspiration severely riskful (e.g. severe abdominal adhesions)
• No wish for randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Operation; Operation for severe endometriosis	Procedure: Operation; Operation for deep infiltrating endometriosis
Active Comparator: Fertility treatment; Fertility treatment for women with severe endometriosis.	Procedure: Fertility treatment; In vitro fertilisation (IVF) and IVF-intracytoplasmic injection (ICSI)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative pregnancy rate (CPR)	Rate of cumulative pregnancies defined as a fetal heartbeat by ultrasound at gestational week 6 to 8	18 months
Live birth rate (LBR)	Rate of live births	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-viable pregnancies	Number of biochemical pregnancies, miscarriages, missed abortions, extrauterine pregnancies and pregnancies of unknown location (PUL)	18 months
Ovarian potential	Concentration of Anti-Müllerian hormone (AMH)	Baseline and 9-18 months
Time to pregnancy	Shortest time from intervention date to date of visualisation of the first ongoing pregnancy	18 months
Postoperative complications	Rate of complications in accordance to Clavien-Dindo Classification, including anastomotic leakage or stenosis, ureteral lesion or obstruction, pelvic abscess, fistula, bladder or bowel perforation and urinary retention	18 months
Fertility treatment complications	Rate of hospital admissions, bleeding, superinfection, worsening of pain or having ovarian hyperstimulation syndrome (OHSS)	18 months
Pain score	Numeric Rating Scale (NRS) score from 0 to 10, where 10 implies the worst pain	Baseline, 9 and 18 months
Quality of Life (QoL)	Development in Endometriosis Health Profile (EHP-30+23), including section C (sexual function QoL questions) and section F (fertility QoL questions)	Baseline, 9 and 18 months
Delayed bowel function	Development in bowel function rated by Low Anterior Resection Syndrome (LARS) score	Baseline, 9 and 18 months
Delayed bladder function	Development in urinary tract function rated by International Consultation on Incontinence Questionnaire (ICIQ- FLUTS)	Baseline, 9 and 18 months
Endometriosis hormonal and inflammatory status	Concentrations of hormonal and inflammatory markers in blood samples	Baseline and 9-18 months
Follicles, oocytes, fertilized oocytes, blastocysts, and frozen embryos	Number of follicles as measured at last scan prior to oocyte pick-up (OPU), number of oocytes at OPU, fertilized oocytes, blastocysts and frozen embryos	18 months
Blastocyst morphology score	Gardner scoring system, Steer grading system, Veecks criteria, or other scoring systems of blastocyst morphology	18 months

Collaborators and Investigators

• Sponsor: Horsens Hospital
• Collaborators: Aarhus University Hospital; Clinique Tivoli Ducos

Publications and helpful links

General Publications

• Raos M, Roman H, Seyer-Hansen M, Kesmodel US, Knudsen UB. EFFORT study: Comparing impact of operation and assisted reproductive technologies on fertility for women with deep infiltrating endometriosis - study protocol for a multicentre randomised trial. BMJ Open. 2022 Apr 11;12(4):e052877. doi: 10.1136/bmjopen-2021-052877.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Anticipated): January 31, 2025
• Study Completion (Anticipated): July 31, 2026

Study Registration Dates

• First Submitted: October 22, 2020
• First Submitted That Met QC Criteria: October 29, 2020
• First Posted (Actual): October 30, 2020

Study Record Updates

• Last Update Posted (Estimate): March 6, 2023
• Last Update Submitted That Met QC Criteria: March 2, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility; Endometriosis; Infertility, Female
• Other Study ID Numbers: Horsens MR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No