Effectiveness of an anti-inflammatory diet before in vitro fertilisation in women with endometriosis: protocol for a randomised controlled trial.

introductionEndometriosis is a common, benign, chronic inflammatory disease with multiple consequences, from chronic pain to systemic comorbidities and poor quality of life. As it usually affects people of reproductive age, one of the most distressing consequences is infertility, which can be only partly overcome by medically assisted reproduction. Poor outcomes are, in fact, frequent adverse events. As no definitive therapy exists for endometriosis-related infertility, affected women often tend to try either complementary and alternative medicine or self-management strategies to improve their quality of life, with the hope of also enhancing their fertility. Among available options, dietary interventions are commonly explored, even if no robust evidence is available on the optimal type of diet and its effects on reproductive outcomes. This trial will investigate whether an anti-inflammatory dietary intervention can improve fertility outcomes in women affected by endometriosis undergoing in vitro fertilisation (IVF). METHODS AND ANALYSIS: The DietAry interveNtion in ameliorating fertiliTy parameters in women with Endometriosis undergoing IVF (DANTE) study is a single-centre, randomised, controlled, non-pharmacological interventional trial in patients living with endometriosis who are infertile and require IVF. Participants will be allocated to either a 12-week intervention based on an anti-inflammatory diet or no diet before the beginning of controlled ovarian stimulation. Following baseline assessment, 438 participants aged <40 years with a diagnosis of infertility according to WHO criteria (ie, not conceiving after 12 months or more of regular unprotected intercourse) and a normal ovarian reserve will be randomly allocated to one of the two groups (1:1 ratio). In both groups, the dietary habits of participants will be assessed at baseline, and adherence to the intervention will be monitored throughout the study period via 24-hour recalls and food diaries. Participants will provide biological samples (peripheral blood, vaginal swabs and faeces) before and after the intervention to evaluate potential differences in inflammatory markers and microbiome composition between the two groups and across timepoints (before and after diet in the intervention group). Follicular fluid will be collected at the time of oocyte retrieval to describe potential difference in sex steroid levels. Patients will also complete questionnaires on quality of life, sexual function and symptom severity before and after the intervention to assess differences between the two groups and across time points. The primary outcome will be the rate of inadequate ovarian response (defined as the retrieval of ≤3 oocytes according to the Poseidon 2016 criteria) at the time of oocyte retrieval in the treatment versus the no-treatment groups. Secondary outcomes will include clinical pregnancy and live birth rates, IVF-related embryological outcomes, inflammatory marker levels in peripheral blood, vaginal and bowel microbiota features, steroid composition of follicular fluid, life quality and pain symptoms variation. ETHICS AND DISSEMINATION: The study has received ethics approval from Comitato Etico Territoriale Lombardia 3 (#5587_18.12.2024). Results will be presented in peer-reviewed journals and at international conferences. TRIAL REGISTRATION NUMBER: NCT06885125.