Dietary Intervention to Improve Fertility in Women With Endometriosis Undergoing IVF

Not Applicable

Recruiting

• Conditions: Endometriosis

• Registration Number: NCT06885125
• Lead Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Brief Summary

The goal of this randomized controlled trial is to assess whether a 12-week anti-inflammatory diet can improve fertility outcomes in women with endometriosis undergoing In Vitro Fertilization (IVF).

The main questions are:

* Does the anti-inflammatory diet reduce the rate of inadequate ovarian response to hormonal stimulation (retrieval of ≤3 oocytes)?

* Does it improve secondary outcomes such as embryo quality, pregnancy rates, inflammation markers, and quality of life?

Researchers will compare two groups:

* Women receiving standard IVF protocols.

* Women undergoing the same IVF protocol plus the anti-inflammatory diet.

Participants will:

* Be randomized into one of the two groups.

* Follow dietary counseling sessions and complete dietary assessments (diet group).

* Provide biological samples (e.g., plasma, vaginal and fecal swabs, and follicular fluid) before and after the dietary intervention to evaluate potential differences in inflammation, hormonal levels, and microbiome composition between the two groups and across timepoints (pre- and post-diet).

* Complete questionnaires on quality of life, sexual function, and symptomatology severity before and after the intervention to assess differences between the two groups and across timepoints.

Detailed Description

Women who agree to participate in the study will be randomized into two groups: one group will receive standard IVF protocols, and the other will undergo a 12-week anti-inflammatory diet followed by the standard IVF protocol. In both groups, participants' dietary habits will be monitored throughout the study period to detect any variations. The primary outcome will be to compare the rate of inadequate ovarian response to hormonal stimulation (defined as the retrieval of ≤3 oocytes according to the Poseidon 2016 criteria) in infertile women with endometriosis.

Study Timeline

• Status Verified: 2025-01
• Study First Submitted: 2025-02-05
• Study First Submitted QC: 2025-03-17
• Study Start: 2025-03-24
• Study First Posted: 2025-03-25
• Last Update Submitted: 2025-03-26
• Last Update Posted: 2025-03-27
• Primary Completion: 2029-06-30
• Study Completion: 2029-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 438

Inclusion Criteria

• Age < 40 years
• Pregnancy seeking for more than 12 months
• Regular menstrual cycle, i.e. mean cycle interval between 21 and 35 days
• Ultrasonographic diagnosis of ovarian endometriomas or deep peritoneal endometriosis.
• Antral Follicle Counts (AFC) ≥ 5 (no other cause of reduced ovarian reserve).
• Absence of ureteral stenosis or intestinal subocclusive symptoms

Exclusion Criteria

• Contraindication to pregnancy
• Hydrosalpinx
• Endometriomas with a mean diameter > 4 cm
• Submucosal fibroids or large intramural or subserosal fibroids (≥ 5 cm).
• Doubtful sonographic findings that do not allow to reliably rule out malignancy.
• severe male factor (<1 million sperm/ml)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Inadequate ovarian response	During the oocyte retrieval procedure	Rate of inadequate ovarian response to hormonal stimulation (defined as the retrieval of ≤3 oocytes according to the Poseidon 2016 criteria) in infertile women with endometriosis who follow an anti-inflammatory diet compared to those who do not follow any specific diet.

Secondary Outcome Measures

Name	Time	Method
Adherence to the intervention	3 months	Adherence to the intervention using 24 hour recall.
Fertilisation rate	The day after oocyte retrieval	Fertilisation rate per aspirated oocyte retrieved. Defined as the appearance of 2 pronuclei (PN)
Embryo quality	Up to six days after oocyte pick-up	Good quality blastocysts according to Gardner classification
Cumulative pregnancy rates	12 months	All clinical pregnancies achieved by IVF, including the transfer of fresh embryos and all cryopreserved-thawed embryos from the stimulation cycle.
Miscarriage rate	24 months	Spontaneous or planned abortions.
Cumulative Live Birth Rate	24 months	All live birth achieved by IVF, including the transfer of fresh embryos and all cryopreserved-thawed embryos from the stimulation cycle.
Microbiome composition	4 months	The difference in microorganism species distribution according to 16S RNA sequencing analysis between the control group and the study group, as well as before and after the diet in the study group. Both the vaginal and gut microbiome will be analyzed.
Concentration of Steroid Hormones	4 months	The difference between the steroid cascade in follicular fluids of women following the diet and those not following the diet, specifically focusing on the following hormones: Aldosterone, Cortisol, Cortisone, 11-DeoxyCortisol, 21-DeoxyCortisol, Corticosterone, 11-Deoxycorticosterone, DHEAS, DHEA, Estradiol, Androstenedione, Testosterone, DHT, 17-OHProgesterone, and Progesterone.
Inflammation Index	4 months	The difference in the inflammation index between the control group and the study group, as well as pre- and post-diet changes within the study group, will be evaluated using a composite blood-based inflammation index called the INFLA-score. This index is based on four circulating biomarkers-C-reactive protein (CRP) levels, blood platelet count (Plt), white blood cell count (WBC), and granulocyte-to-lymphocyte ratio (GLR)-and captures both serum and cellular-circulating inflammation.
Quality of life (using 30-item Endometriosis Health Profile)	4 months	Quality of life differences between the control group and the study group, as well as pre- and post-diet changes within the study group, will be evaluated using the Endometriosis Health Profile-30 (EHP-30) questionnaire. The EHP-30 consists of 30 items divided into five subscales: 'pain,' 'control and powerlessness,' 'social support,' 'emotional well-being,' and 'self-image.' Each subscale is standardized on a scale from 0 to 100, where lower scores indicate better quality of life.
Sexual function (using Female Sexual Function Index)	4 months	Sexual function differences between the control group and the study group, as well as pre- and post-diet changes within the study group, will be evaluated using the Female Sexual Function Index (FSFI), a questionnaire with a score range from 2 to 36, where higher scores indicate better sexual function.
Symptomatology severity (using Numeric Rating Scale)	4 months	Symptomatology severity differences between the control group and the study group, as well as pre- and post-diet changes within the study group, will be evaluated using Numeric Rating Scale (NRS, min 0-max 10), where higher scores indicate worse symptom severity.

Trial Locations

Locations (1)

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; 🇮🇹 Milan, Italy