TOSCA: The (Cost-)Effectiveness of Surgical Excision of Colorectal Endometriosis Compared to IVF Treatment Trajectory
Study Details
Study Description
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 in vitro fertilization (IVF), and better patient reported outcome measures (PROMs) compared to an IVF treatment trajectory.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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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 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 IVF 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, and better PROMs compared to an IVF treatment trajectory.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Colorectal endometriosis patients Subfertile women between 18 and 43 years with colorectal endometriosis facing the choice between IVF or laparoscopic resection of (colorectal) endometriosis. |
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
IVF 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 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.
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Outcome Measures
Primary Outcome Measures
- Cumulative live birth rate [At the end of the study period (live birth or after 3 IVF attempts and/or surgery in the follow-up period (40 months) )]
Live birth rate is defined as a pregnancy ending after 24 weeks and resulting in a live born child. Cumulative live birth rate is the number of patients who achieve a live birth rate after surgery, surgery combined with IVF or IVF alone, divided by the number of patients who initially started the respective treatment.
Secondary Outcome Measures
- Endometriosis specific symptoms [At baseline (T=0: when informed consent is granted), 12, 24 and 36 months and in case of surgery, before surgery.]
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.
- Quality of life in general [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.]
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.
- Bowel specific symptoms [At baseline (T=0: when informed consent is granted), 12, 24 and 36 months and in case of surgery, before surgery.]
Lower Anterior Resection Syndrome score (LARS score). The total LARS score ranges from 0, indicating no LARS to 42 points, indicating major LARS.
- Pain scores [At baseline (T=0: when informed consent is granted), 12, 24 and 36 months and in case of surgery, before surgery.]
NRS score for dysmenorrhea, dysuria, dyschezia, dyspareunia and chronic pelvic pain. The NRS scale ranges from 0 (no pain) to 10 (worst pain imaginable).
- Productivity costs [At baseline (T=0: when informed consent is granted), 6, 12, 18, 24, 30, 36 and 40 and in case of surgery, before surgery.]
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.
- Medical costs per group [At the end of the study period (live birth or after 3 IVF attempts and/or surgery in the follow-up period (40 months) )]
Costs surgery, costs IVF treatment, costs extra hospital admissions / emergency room visits / visits outpatient care
- Complications [At the end of the study period (live birth or after 3 IVF attempts and/or surgery in the follow-up period (40 months) )]
Intraoperative and postoperative complications, IVF associated complications, pregnancy complications
Eligibility Criteria
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, small bowel) detected with ultrasound, MRI or diagnostic laparoscopy.
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The patient an active wish to conceive and experience at least one of the following criteria:
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At least one year of non-conception
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Inability to have timed intercourse because of pain (dyspareunia and/or chronic pelvic pain)
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Severe complaints (expectant management is not acceptable (anymore)
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The patient is at the beginning of her fertility treatment and faces the choice between IVF or laparoscopic colorectal endometriosis excision surgery or is on the waiting list for a respective treatment
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Patients undergoing intracytoplasmic sperm injection (ICSI), not due to male factor infertility, but for example in case of multiple cancelled embryo transfers due to no fertilization.
Exclusion Criteria:
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Deep endometriosis without bowel involvement
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Unilateral of bilateral hydronephrosis
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Severe bowel stenosis with high risk of problems during pregnancy
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Contra-indication for IVF (e.g. partner with severe male infertility (<1x10^16 motility count in semen analysis, untreated uterine factor infertility, maltreated/untreated systemic or malignant disease or severe risk factors for oocyte aspiration, anti-Mullerian hormone or antral follicle count <p10 (adjusted for age))
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Not able to read, write and understand Dutch
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Haaglanden Medical Centre
- Leiden University Medical Center
- University Medical Center Groningen
- Maastricht University Medical Center
- Radboud University Medical Center
Investigators
- Principal Investigator: Mathijs D. Blikkendaal, MD, PhD, Endometriosis in Balance expertise centre (HMC)
- Study Chair: Andries RH Twijnstra, MD, PhD, Leiden University Medical Center
- Study Chair: Astrid EP Cantineau, MD, PhD, University Medical Center Groningen
- Study Chair: Jacques Maas, MD, PhD, Maastricht University Medical Center
- Study Chair: Annemiek Nap, MD, PhD, Radboud University Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- N22.085