Investigating maternal genes and reproductive risks in Beckwith-Wiedemann syndrome

Role of Maternal Effect Genes and Epimutations in Beckwith-Wiedemann Syndrome and Adverse Reproductive Outcomes

This study is trying to see if certain genetic changes in mothers are linked to reproductive issues in women with infertility or those who have children with Beckwith-Wiedemann syndrome.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 208 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico (other)
• Locations: 2 sites (Milan and 1 other locations)
• Trial ID: NCT06346418 on ClinicalTrials.gov

What this trial studies

This project aims to explore the role of pathogenic variants in maternal genes, specifically those in the subcortical maternal complex (SCMC), in relation to reproductive outcomes in women with a history of infertility and those with children affected by Beckwith-Wiedemann syndrome (BWS). The study will recruit three cohorts: healthy women with BWS offspring, women under 35 undergoing assisted reproductive technology (ART) for infertility, and women under 35 with recurrent pregnancy loss (RPL). Whole-exome sequencing (WES) and whole-genome methylation analysis will be utilized to identify genetic variants and methylation changes that may contribute to reproductive challenges. The findings could provide insights into the molecular mechanisms underlying female infertility and imprinting disorders associated with SCMC variants.

Who should consider this trial

Good fit: Ideal candidates include women under 35 with a history of infertility, recurrent pregnancy loss, or those with children affected by Beckwith-Wiedemann syndrome.

Not a fit: Patients with known causes of infertility or recurrent pregnancy loss, such as hormonal disorders or male infertility, may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding and management of reproductive risks in women with a history of infertility and BWS.

How similar studies have performed: While the specific approach of this study is novel, similar studies investigating maternal genetic factors in reproductive outcomes have shown promise.

Eligibility criteria

Inclusion Criteria:

* Cohort 1: healthy women with offspring affected by BWS and peculiar reproductive history from our population of clinically and molecularly diagnosed BWS families;
* Cohort 2: women under 35 undergoing ART for infertility (defined as failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourses) and unable to obtain a live birth after three completed cycles or after the transfer of at least 6 blastocysts;
* Cohort 3: women under 35, with RPL (defined as the loss of two or more pregnancies before 24 weeks of gestation).

Exclusion Criteria:

* presence of conventional and molecular karyotype alterations
* occurrence of known causes that can lead to decreased fertility or recurrent abortions: disorders of the ovaries, such as polycystic ovarian syndrome and other follicular disorders, disorders of the endocrine system causing imbalances of reproductive hormones levels, autoimmune conditions, male infertility, uterine or tubal dysfunctions and malformations, thrombophilic or noncorrected thyroid dysfunctions.

Where this trial is running

Milan and 1 other locations

• Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico — Milan, Italy (RECRUITING)
• Istituto Auxologico Italiano — Milan, Italy (RECRUITING)

Study contacts

• Principal investigator: Edgardo Somigliana, PhD — Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Study coordinator: Edgardo Somigliana, PhD

Conditions: Beckwith-Wiedemann Syndrome