The (Cost-)Effectiveness of Surgical Excision of Colorectal Endometriosis Compared to ART Treatment Trajectory

NCT ID: NCT05677269

Last Updated: 2024-11-21

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 339 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-02-17
• Study Completion Date: 2029-01-01

Brief Summary

To goal of this study is to determine whether laparoscopic resection of colorectal endometriosis results in an increased cumulative live birth rate (CLBR) both spontaneous and after ART (including in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), and better patient reported outcome measures (PROMs) compared to an IVF/ICSI treatment trajectory.

Detailed Description

Endometriosis is characterized by extra-uterine endometrium like tissue and affects 10-15% of the women in their reproductive years and in 5-12% of these women colorectal endometriosis is present. The quality of life is lowered due to severe pain symptoms (dysmenorrhea, dyschezia, dysuria, chronic pelvic pain) and subfertility.The management of colorectal endometriosis-related subfertility is challenging. While the impact of colorectal endometriosis per se remains inconclusive as other intraperitoneal endometriosis lesions are frequently present, fertility is most likely affected by multiple mechanisms including inflammatory alterations in peritoneal fluid, alterations in estrogen and progesterone hormone levels, lowered endometrium receptivity, associated adenomyosis, a lower ovarian reserve (in case endometriomas are present) and adhesion formation that disrupts adnexal anatomy and function. Usually, surgery is preferred in case of dominant pain complaints, while IVF/ICSI is started when the wish to conceive is dominant. Recent evidence suggests a CLBR of 44.9% in patients with rectosigmoid endometriosis treated by surgery compared to 55.9% after 4 cycles of IVF/ICSI treatment without surgery. In the Netherlands, the number of reimbursed IV/ICSI attempts in limited to three. In addition, a combined strategy may result in even higher cumulative live birth rates. However, the place and optimal timing of surgery in patients with colorectal endometriosis and a desire to have children is unknown.

To provide robust evidence that can be extrapolated to the Dutch healthcare system, this study aims to determine whether surgical excision of colorectal endometriosis results in increased CLBR both spontaneous and after IVF/ICSI, and better PROMs compared to an IVF/ICSI treatment trajectory.

Conditions

Endometriosis, Rectum; Endometriosis of Colon; Subfertility, Female

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Colorectal endometriosis patients

Subfertile women between 21 and 40 years with colorectal endometriosis facing the choice between IVF/ICSI or laparoscopic resection of (colorectal) endometriosis.

Laparoscopic excision of endometriosis, including colorectal endometriosis

Intervention Type: PROCEDURE

Laparoscopic resection of deep endometriosis, including colorectal endometriosis, in a (candidate) level 2 centre of expertise. Complete resection can exist of either 'shaving' of the nodule from the bowel (leaving the lumen closed), discoid excision or segmental resection, depending on the nodule size and extent of disease.

In vitro fertilisation or intracytoplasmic sperm injection

Intervention Type: PROCEDURE

IVF/ICSI treatment trajectory (maximum of 3 cycles), according to the local protocol. Preferably preceded by 3 months downregulation with either Gonadotrophin-releasing hormone (GnRH) analogue or oral contraceptive pill. One IVF/ICSI cycle is defined as the transfer of all the embryos created after one follicle puncture until pregnancy confirmation or failure of the last embryo transfer.

Interventions

Laparoscopic excision of endometriosis, including colorectal endometriosis

Laparoscopic resection of deep endometriosis, including colorectal endometriosis, in a (candidate) level 2 centre of expertise. Complete resection can exist of either 'shaving' of the nodule from the bowel (leaving the lumen closed), discoid excision or segmental resection, depending on the nodule size and extent of disease.

Intervention Type: PROCEDURE

In vitro fertilisation or intracytoplasmic sperm injection

IVF/ICSI treatment trajectory (maximum of 3 cycles), according to the local protocol. Preferably preceded by 3 months downregulation with either Gonadotrophin-releasing hormone (GnRH) analogue or oral contraceptive pill. One IVF/ICSI cycle is defined as the transfer of all the embryos created after one follicle puncture until pregnancy confirmation or failure of the last embryo transfer.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Colorectal endometriosis defined as endometriosis involving the (colo)rectum:

#Enzian classification score C1,C2,C3 (C=rectum) or FI (F=far locations, I=sigmoid colon) detected with ultrasound or MRI;

• Women in a heterosexual or in a same-sex relationship;
• The patient has an active wish to conceive and experiences at least one of the following criteria:

• At least one year of non-conception (either spontaneous of after intra uterine inseminations)
• Inability to have timed intercourse because of pain (dyspareunia and/or chronic pelvic pain)
• Severe complaints (expectant management is not acceptable (anymore)
• The patients has an indication for IVF/ICSI according to Dutch guidelines (Werkgroep netwerkrichtlijn, december 2010);

• failed intra uterine insemination
• male factor subfertility (oligoasthenoteratozoospermia defined as VCM <1 million)
• bilateral tubal pathology (e.g. bilateral hydrosalpinx, bilateral tubal occlusion)
• age > 38 years and (unexplained) subfertility
• severe endometriosis in case of subfertility
• The patient is faces the choice between IVF/ICSI or laparoscopic (colorectal) endometriosis or is on the waiting list for a respective treatment at T=0 (at the beginning of the treatment trajectory), T=1 (after one unsuccessful IVF/ICSI cycle) or T=2 (after 2 unsuccessful IVF/ICSI cycles)

Exclusion Criteria

• Patients with deep endometriosis without colorectal involvement;
• Patients who conceive spontaneously prior to intervention;
• Patients requiring surgery on short notice and therefore unable to opt for IVF/ICSI (e.g. in case of unilateral or bilateral hydronephrosis, severe bowel stenosis and suspicion of an impending ileus);
• Patients with a contra-indication for IVF/ICSI (e.g. diminished ovarian reserve (premature ovarian failure) (AMH (when available) <p10 adjusted for age), untreated congenital uterine abnormalities, maltreated/untreated systemic or malignant disease or severe risk factors for oocyte aspiration);
• Patients diagnosed with other diseases causing infertility (e.g. recurrent miscarriages, antiphospholipid syndrome);
• Not able to read and understand Dutch or English.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Haaglanden Medical Centre

OTHER

Sponsor Role: collaborator

University Medical Center Groningen

OTHER

Sponsor Role: collaborator

Maastricht University Medical Center

OTHER

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: collaborator

Reinier de Graaf Groep

OTHER

Sponsor Role: collaborator

Catharina Ziekenhuis Eindhoven

OTHER

Sponsor Role: collaborator

UMC Utrecht

OTHER

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

mdblikkendaal

Principle Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mathijs D. Blikkendaal, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Nederlandse Endometriose Kliniek (NEK), Reinier de Graaf Gasthuis

Andries RH Twijnstra, MD, PhD

Role: STUDY_CHAIR

Leiden University Medical Center

Astrid EP Cantineau, MD, PhD

Role: STUDY_CHAIR

University Medical Center Groningen

Jacques Maas, MD, PhD

Role: STUDY_CHAIR

Maastricht University Medical Center

Annemiek Nap, MD, PhD

Role: STUDY_CHAIR

Radboud University Medical Center

Dana Huppelschoten

Role: STUDY_CHAIR

Catharina Ziekenhuis

Simone Broer

Role: STUDY_CHAIR

UMC Utrecht

Tobias Limperg

Role: STUDY_CHAIR

Nederlandse Endometriose Kliniek (NEK), Reinier de Graaf Gasthuis

Yvonne Louwers

Role: STUDY_CHAIR

Erasmus Medical Center

Marieke Verberg

Role: STUDY_CHAIR

Medisch Spectrum Twente

Locations

Catharina Ziekenhuis

Eindhoven, , Netherlands

Site Status: RECRUITING

Medical Spectrum Twente

Enschede, , Netherlands

Site Status: RECRUITING

University Medical Center Groningen

Groningen, , Netherlands

Site Status: RECRUITING

Leiden University Medical Center

Leiden, , Netherlands

Site Status: RECRUITING

Maastricht University Medical Center

Maastricht, , Netherlands

Site Status: RECRUITING

Radboud university medical center

Nijmegen, , Netherlands

Site Status: RECRUITING

Erasmus Medical Centre

Rotterdam, , Netherlands

Site Status: RECRUITING

Haaglanden Medical Center

The Hague, , Netherlands

Site Status: RECRUITING

Utrecht Medical Center

Utrecht, , Netherlands

Site Status: RECRUITING

Nederlandse Endometriose Kliniek (Reinier de Graaf Gasthuis)

Voorburg, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Mathijs D. Blikkendaal, MD,PhD

Role: CONTACT

M.Blikkendaal@rdgg.nl

088 979 44 89

Rozemarijn de Koning, MD

Role: CONTACT

r.de_koning@lumc.nl

Facility Contacts

Dana Huppelschoten

Role: primary

Marieke Verberg

Role: primary

Astrid Cantineau

Role: primary

Dries Twijnstra

Role: primary

Jacques Maas

Role: primary

Annemiek Nap

Role: primary

Yvonne Louwers

Role: primary

Moniek van der Zanden

Role: primary

Simone Broer

Role: primary

Tobias Limperg

Role: primary

References

F Barra, C Scala, S Bogliolo, N Di Donato, M Ceccaroni, S Ferrero, O-309 Surgery versus IVF/ICSI in infertile women with rectosigmoid endometriosis: the FERTILITY-RECTOSIGMOID study, Human Reproduction, Volume 37, Issue Supplement_1, July 2022

Reference Type: RESULT

Other Identifiers

N22.085

Identifier Type: -

Identifier Source: org_study_id