Clinical trial NCT05677269: The (Cost-)Effectiveness of Surgical Excision of Colorectal Endometriosis Compared to ART Treatment Trajectory
Official title: The (Cost-)Effectiveness of Surgical Excision of Colorectal Endometriosis Compared to ART Treatment Trajectory
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Endometriosis, Rectum
Endometriosis of Colon
Subfertility, Female
Keywords: Colorectal endometriosis
Subfertility
Surgery
In vitro fertilisation
Live birth rate
Quality of life
Cost-effectiveness
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: Haaglanden Medical Centre
name: University Medical Center Groningen
name: Maastricht University Medical Center
name: Radboud University Medical Center
name: Reinier de Graaf Groep
name: Catharina Ziekenhuis Eindhoven
name: UMC Utrecht
First posted: 2023-01-10
Enrollment: 339
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 40
Standard ages: ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subfertile women between 21 and 40 years with colorectal endometriosis facing the choice (at the start of their treatment trajectory or after one or two unsuccessful IVF/ICSI cycles) between IVF/ICSI or laparoscopic excision of (colorectal) endometriosis to increase the chance to conceive (naturally)

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.

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.

Primary outcomes:
measure: Cumulative live birth rate
timeFrame: 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 outcomes:
measure: Endometriosis specific symptoms
timeFrame: At baseline (T=0: when informed consent is granted), 12, 24 and 36 months and in case of surgery, before surgery.
measure: Quality of life in general
timeFrame: 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.
measure: Bowel specific symptoms
timeFrame: At baseline (T=0: when informed consent is granted), 12, 24 and 36 months and in case of surgery, before surgery.
measure: Pain scores
timeFrame: At baseline (T=0: when informed consent is granted), 12, 24 and 36 months and in case of surgery, before surgery.
measure: Productivity costs
timeFrame: At baseline (T=6, 12, 18, 24, 30, 36 and 40 months and in case of surgery, before surgery.
measure: Medical costs per group
timeFrame: 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) )
measure: Complications
timeFrame: 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) )
Other outcomes:
Locations:
city: Den Haag
country: Netherlands
facility: Haaglanden Medical Center
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Enschede
country: Netherlands
facility: Medical Spectrum Twente
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Nijmegen
country: Netherlands
facility: Radboud university medical center
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Centre
city: Utrecht
country: Netherlands
facility: Utrecht Medical Center
city: Voorburg
country: Netherlands
facility: Nederlandse Endometriose Kliniek (Reinier de Graaf Gasthuis)
Study officials:
affiliation: Nederlandse Endometriose Kliniek (NEK), Reinier de Graaf Gasthuis
name: Mathijs D. Blikkendaal, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Leiden University Medical Center
name: Andries RH Twijnstra, MD, PhD
role: STUDY_CHAIR
affiliation: University Medical Center Groningen
name: Astrid EP Cantineau, MD, PhD
role: STUDY_CHAIR
affiliation: Maastricht University Medical Center
name: Jacques Maas, MD, PhD
role: STUDY_CHAIR
affiliation: Radboud University Medical Center
name: Annemiek Nap, MD, PhD
role: STUDY_CHAIR
affiliation: Catharina Ziekenhuis
name: Dana Huppelschoten
role: STUDY_CHAIR
affiliation: UMC Utrecht
name: Simone Broer
role: STUDY_CHAIR
affiliation: Nederlandse Endometriose Kliniek (NEK), Reinier de Graaf Gasthuis
name: Tobias Limperg
role: STUDY_CHAIR
affiliation: Erasmus Medical Center
name: Yvonne Louwers
role: STUDY_CHAIR
affiliation: Medisch Spectrum Twente
name: Marieke Verberg
role: STUDY_CHAIR
References:
citation: 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