Silver Russell Syndrome, Parental Fertility and Assisted Reproductive Technology (SRS-AMP)

Official Title : Silver Russell Syndrome, Parental Fertility and Assisted Reproductive Technology 600 caractères Maximum

Silver Russell Syndrome (SRS) is a rare imprinting disorder (about 1/16000). Parental imprinting is an epigenetic regulation phenomenon leading to the monoallelic expression of some genes. Its establishment takes place in the gametes and its maintenance is important at the early embryonic stage. Increase in the prevalence of conception by assisted reproductive technology (ART) has already been found in patients with imprinted disorder such as Angelman, Beckwith-Wiedemann or Prader Willi Syndromes, and more recently with SRS; ART is associated with an increase in the frequency of SRS. Several hypotheses are formulated to explain this increase. The first one is the involvement of the infertility etiology in the imprinting disorder genesis. The second one is the involvement of ART technics in the genesis of abnormal gamete imprinting during their manipulation or during imprinting maintenance at early embryonic stages.

Our main objective is to estimate ART conceptions prevalence in children followed for a SRS. The secondary objectives are to estimate infertility prevalence among parents of patients with SRS, to estimate factors frequency possibly responsible for the genesis of imprinting anomalies among parents of patients with SRS, to describe the infertility causes and to detail ART technics used (stimulation protocols, type of fertilization used, modality of embryonic culture and transfer, embryonic characteristics).

A transversal pilote study will be firstly conducted in parents of patients followed in Silver Russell Syndrome Reference Center (Pediatric Endocrine department, in Trousseau Hospital, Paris).

Data collection will be done by phone, after collecting the non-opposition of the parents, in order to complete a questionnaire concerning their fertility and conception mode of their child. If ART was used to conceive, a questionnaire concerning the details of the ART technics used will be sent to the doctor and:or the ART biologist, who performed the ART. The data will be anonymized and collected on a REDCap database.

Study Overview

• Status: Not yet recruiting
• Conditions: Syndrome, Russell Silver

Detailed Description

There is no planned follow-up, and the parents' participation is limited to the telephone interview.

The aim is to conduct / carry out a single-centre observational cross-sectional study, on the one hand by collecting data from the centre's patient files (molecular anomaly leading to the diagnosis of Silver Russell syndrome) and on the other hand by conducting a 30-minute telephone questionnaire to collect additional data. The first part of this questionnaire will be carried out with the parents of these patients in order to specify their age, height, weight, drug consumption and profession at the time of the start of pregnancy, as well as the time required for conception and recourse to ART.

In the event of recourse to ART, with the authorisation of the parent(s), a questionnaire will be sent to the clinical doctor and/or the biologist at the ART centre.

• Study Type: Observational
• Enrollment (Estimated): 125

Contacts and Locations

• Study Contact: Name: Marie-Pierre LUTON, PhD; Phone Number: +33(0) 1 87 89 26 00; Email: mariepierre.luton@aphp.fr
• Study Contact Backup: Name: Irène Netchine, PUPH, MD, PhD; Phone Number: 0033 1 44 73 66 31; Email: irene.netchine@aphp.fr

Study Locations

• France
  • Paris, France, 75012
    • Pediatric Endocrine department - Trousseau Hospital
    • Contact: Marie-Pierre LUTON, PhD; Phone Number: +33(0) 1 87 89 26 00; Email: mariepierre.luton@aphp.fr
    • Contact: Irène Netchine, PUPH - MD, PhD; Phone Number: 00 33 1 44 73 66 31; Email: irene.netchine@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Parents of children being followed for Silver-Russell syndrome at the Silver-Russell Syndrome Reference Centre at Trousseau Hospital in the Endocrine Functional Investigation Unit.

Description

Inclusion Criteria:

• ≥ 18 years old
• parents from patients followed in the department " Unité Fonctionnelle Endocrinienne du Pr Netchine " for un Silver Russell syndrome

Exclusion Criteria:

• parent's objection
• patient under State Medical Aid

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of SRS patients whose mode of conception was ART	To estimate ART conceptions prevalence in children followed for a SRS	Day 0, visit inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimate infertility prevalence among parents of patients with SRS (defined as a delay to conception of more than 12 months)	The time required for conception is defined by the time between stopping contraception and the start of pregnancy	Day 0, visit inclusion
Estimate frequency of maternal and paternal BMI at the time of conception		Day 0, visit inclusion
Estimate frequency of consumption of tobacco and alcohol at the time of conception	At the time of conception maternal and paternal BMI, consumption of tobacco and alcohol and both parents' occupations	Day 0, visit inclusion
Estimate frequency of parents's profession at the time of conception		Day 0, visit inclusion
The etiology of infertility in detail	Study infertility causes in detail this will be do through a questionnaire send to the fertility doctor who treated the parents.	3 years, end of the study
Describe the ART techniques used from the point of view of ovarian stimulation but also oocyte, sperm and embryo manipulations	Details of ART techniques used this will be do through a questionnaire send to the fertility doctor who treated the parents.	3 years, end of the study

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Irène Netchine, PUPH, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: February 21, 2025
• First Submitted That Met QC Criteria: March 10, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Infertility; Assisted Reproductive Technology; In vitro fertilization; Imprinting disorders; - Silver Russell syndrome
• Additional Relevant MeSH Terms: Imprinting Disorders; Musculoskeletal Diseases; Pathologic Processes; Genetic Diseases, Inborn; Disease; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Congenital Abnormalities; Abnormalities, Multiple; Chromosome Disorders; Dwarfism; Syndrome; Silver-Russell Syndrome
• Other Study ID Numbers: APHP240670; IDRCB 2021-A02781-40 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No