Currently, the optimal treatment to increase the chance of pregnancy and live births in patients with colorectal endometriosis and subfertility is unknown. Evidence suggests that that both surgery and in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) are effective in improving the live birth rate (LBR) among these women. However, the available evidence is of low quality, reports highly heterogeneous results, lacks direct comparison between both treatment options, and does not assess whether a combination strategy results in a higher LBR compared to IVF/ICSI-only treatment. Additionally, the optimal timing of surgery within the treatment trajectory remains unclear. The primary objective of the TOSCA study is to assess the effectiveness of surgical treatment (potentially combined with IVF/ICSI) compared to IVF-/ICSI-only treatment to increase the chance of an ongoing pregnancy resulting in a live birth in patients with colorectal endometriosis and subfertility, measured by cumulative LBR. Secondary objectives are to assess and compare quality of life and cost-effectiveness in both groups. Patients will be followed for 40 months after inclusion or until live birth. The TOSCA study is expected to be completed in 6 years. Trial registration number The TOSCA trial is registered as ‘Cost-Effectiveness of Surgical Excision of Colorectal Endometriosis Compared to ART Treatment Trajectory (TOSCA)’ in the Clinical Trials Register (NCT No. NCT05677269, https://clinicaltrials.gov/ct2/show/NCT05677269 ) Date of first patient enrolment The first patient was included in February 2023. Lay summary Treating bowel endometriosis in people with fertility problems is difficult, and at the moment, there is no consensus on the best way to increase the chances of pregnancy. This makes it hard for gynaecologists to advise people when to have either IVF/ICSI or surgery, particularly in patients with fewer pain symptoms, as the benefits of surgery to enhance fertility have to be balanced against the potential risk of ...