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

Endometriosis, Rectum Clinical Trial

— TOSCA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05677269
• Other study ID #: N22.085
• Status: Recruiting
• Start date: February 17, 2023
• Est. completion date: January 1, 2029

Study information

• Verified date: January 2024
• Source: Leiden University Medical Center
• Contact: Mathijs D. Blikkendaal, MD,PhD
• Phone: 088 979 44 89
• Email: M.Blikkendaal[@]rdgg.nl
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 339
• Est. completion date: January 1, 2029
• Est. primary completion date: July 2028
• Gender: Female
• Age group: 21 Years to 40 Years

Eligibility

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 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

• 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.

Related Conditions & MeSH terms

• Endometriosis
• Endometriosis of Colon
• Endometriosis, Rectum
• Infertility
• Infertility, Female
• Subfertility, Female

Intervention

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.
• 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.

Locations

Country	Name	City	State
Netherlands	Haaglanden Medical Center	Den Haag
Netherlands	Catharina Ziekenhuis	Eindhoven
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Maastricht University Medical Center	Maastricht
Netherlands	Radboud university medical center	Nijmegen
Netherlands	Utrecht Medical Center	Utrecht
Netherlands	Nederlandse Endometriose Kliniek (Reinier de Graaf Gasthuis)	Voorburg

Sponsors (8)

Lead Sponsor	Collaborator
Leiden University Medical Center	Catharina Ziekenhuis Eindhoven, Haaglanden Medical Centre, Maastricht University Medical Center, Radboud University Medical Center, Reinier de Graaf Groep, UMC Utrecht, University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative live birth rate	Live birth is defined as the complete expulsion or extraction from a women of a product of fertilization, after 20 weeks of gestational age; 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 of the placenta is attached. A birth weight of 350 grams or more can be used if gestational age is unknown	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	Endometriosis specific symptoms	Endometriosis Health Profile-30 (EHP-30). The overall EHP-30 score ranges from 0 to 100, with a high score indicating poorer health-related quality of life.	At baseline (T=0: when informed consent is granted), 12, 24 and 36 months and in case of surgery, before surgery.
Secondary	Quality of life in general	EuroQql five-dimensional 5 levels (EQ-5D-5L) and EuroQql Visual Analog Scale (EQ-VAS).; According to the Dutch scoring algorithm, the EQ-5D-5L score index value ranges from -0.446 (55555 worst health state) to 1 (11111, best health state).; Overall health will be represented by the EQ-VAS, ranging from 0 to 100, with higher scores indicating better health.	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.
Secondary	Bowel specific symptoms	Lower Anterior Resection Syndrome score (LARS score). The total LARS score ranges from 0, indicating no LARS to 42 points, indicating major LARS.	At baseline (T=0: when informed consent is granted), 12, 24 and 36 months and in case of surgery, before surgery.
Secondary	Pain scores	NRS score for dysmenorrhea, dysuria, dyschezia, dyspareunia and chronic pelvic pain. The NRS scale ranges from 0 (no pain) to 10 (worst pain imaginable).	At baseline (T=0: when informed consent is granted), 12, 24 and 36 months and in case of surgery, before surgery.
Secondary	Productivity costs	Productivity costs questionnaire: institute for Medical Technology Assessment (iMTA) Productivity Cost Questionnaire (iPCQ).; Productivity costs will be measured by calculating absence from paid work (absenteeism), reduced productivity at paid work (presenteeism), and productivity loss in unpaid work. Hours of productivity loss will be translated by a standard cost price of productivity per hour.	At baseline (T=6, 12, 18, 24, 30, 36 and 40 months and in case of surgery, before surgery.
Secondary	Medical costs per group	Costs surgery, costs IVF/ICSI treatment, costs extra hospital admissions / emergency room visits / visits outpatient care	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	Complications	Intraoperative and postoperative complications, IVF/ICSI associated complications, pregnancy complications	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) )