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

Overview

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.

Interventions

• Procedure 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.
• 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.

Primary outcome measures

• Cumulative live birth rate [Time frame: At the end of the study period (live birth or after 3 IVF/ICSI attempts and/or surgery in the follow-up period (40 months) )]

Secondary outcome measures (7)

• Endometriosis specific symptoms [Time frame: At baseline (T=0: when informed consent is granted), 12, 24 and 36 months and in case of surgery, before surgery.]
• Quality of life in general [Time frame: At baseline (T=0: when informed consent is granted), 6, 12, 18, 24, 30, 36 and 40 months and in case of surgery, before surgery.]
• Bowel specific symptoms [Time frame: At baseline (T=0: when informed consent is granted), 12, 24 and 36 months and in case of surgery, before surgery.]
• Pain scores [Time frame: At baseline (T=0: when informed consent is granted), 12, 24 and 36 months and in case of surgery, before surgery.]
• Productivity costs [Time frame: At baseline (T=6, 12, 18, 24, 30, 36 and 40 months and in case of surgery, before surgery.]
• Medical costs per group [Time frame: At the end of the study period (live birth or after 3 IVF/ICSI attempts and/or surgery in the follow-up period (40 months) )]
• Complications [Time frame: At the end of the study period (live birth or after 3 IVF/ICSI attempts and/or surgery in the follow-up period (40 months) )]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Study design

Observational model

Cohort

Study locations

Netherlands · 10 centers

• Catharina Ziekenhuis — Eindhoven
• Medical Spectrum Twente — Enschede
• University Medical Center Groningen — Groningen
• Leiden University Medical Center — Leiden
• Maastricht University Medical Center — Maastricht
• Radboud university medical center — Nijmegen
• Erasmus Medical Centre — Rotterdam
• Haaglanden Medical Center — The Hague
• … and 2 more centers

Publications

• 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

Identifiers

NCT: NCT05677269 · N22.085

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗