An observational study in Primary Ovarian Insufficiency, sponsored by Ospedale Policlinico San Martino. Recruiting at 1 site in Italy. Open to female participants aged 15 Years to 38 Years. Per ClinicalTrials.gov, last updated 2022-04-25.
Sponsored by Ospedale Policlinico San Martino · Observational
Primary ovarian insufficiency (POI), also known as premature ovarian failure, is an ovarian defect characterized by the premature (before the age of 40 years) depletion of ovarian follicles. POI affects about 1% of women, reaching 30% in some familial cases.
This heterogeneous disorder is characterized by progressive cessation of the ovarian function with temporary or intermittent amenorrhea associated with elevated serum FSH concentration and low AMH dosage. Low serum AMH dosage is able to detect a diminished ovarian pool occurring before the onset of FSH elevation and the ultimate deficiency leading to amenorrhea.
POI causes infertility and a poor ovarian response in IVF stimulations, and it has important health consequences for affected patients, including psychological distress, infertility, osteoporosis, autoimmune disorders, ischaemic heart disease.
Although the cause of POI remains unknown in about 80% of the cases, several mechanisms have been proposed to explain ovarian dysfunction. Currently, a wide spectrum of causes has been linked to POI, including genetic, autoimmune, infectious, or iatrogenic ones.
Genetic causes are highly heterogeneous and might explain at least some of the sporadic idiopathic cases, which comprise 50-90% of cases. Ten to fifteen percent of cases are X-linked abnormalities, mainly Turner Syndrome (45,X) or X structural abnormalities such as X deletions, X inversions, isochromosomes or X-autosome translocations. Also fragile X mental retardation 1 (FMR1) gene permutation (defined as having 55 to 200 CGG repeats in the 5' untranslated region of the gene) is another frequent genetic etiology.
Irrespectively, the majority of cases remains idiopathic, and identifying precise causative genes for POI has been challenging.
Although in the last decades an increasing number of aberrant genes involved in POI were identified, currently only a minority of affected women can be explained at gene level. Elucidating the biology of the premature declining ovarian function is paramount to develop better testing and treatment strategies for affected women in the future.
Importantly, two clinical features remain unexplained: i) the overall sporadic nature of POI, and ii) observations of patients harboring the identical mutation yet developing POI either early in life (puberty) or later (\< 40 years old). Therefore, the investigators postulate that defects affecting more than one gene might explain this variability. Based on investigators' preliminary data and literature reports, it is likely that a synergistic effect of several variant/gene abnormalities may underlie the idiopathic POI phenotype.
The investigators hypothesize that different genome-wide strategies (namely, high resolution array-CGH and WES) may discover genetic variants without the limitation of a single candidate or a panel of candidates, and thus are more promising for explanation of the genetic heterogeneity of POI and elucidating the pathogenic mechanisms.
172 studies on the registry are indexed under Primary Ovarian Insufficiency; 45 are open to participants now.
This study's planned enrollment of 100 is close to the median of 100 across 59 observational studies indexed under Primary Ovarian Insufficiency.
Browse Primary Ovarian Insufficiency studies →Ospedale Policlinico San Martino is the lead sponsor of 30 studies on the registry; 11 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Idiopathic, sporadic and familial POI cases.
at least one marker of ovarian reserve not age-appropriate:
Exclusion Criteria:
Idiopathic, sporadic POI Caucasian cases. The inclusion criteria will be: * age at diagnosis \<38 years; * a normal 46,XX karyotype (no FRM1 premutation); * at least one marker of ovarian reserve not age-appropriate: * baseline FSH levels \> cut-off \[1\] and/or * age-specific AMH \< cut-off \[2\] and/or * AFC \< 5; and/or * cancellation of a PMA cycle because of poor response (\<3 follicles) to high-dose gonadotrophins (250 U/die) and/or * retrieval of \< 4 oocytes in response to high-dose stimulation protocols (3000 U of gonadotrophins).
Familial POI cases and not-affected members of pedigrees.
Identification of putative POI-related genes.
Genomic imbalances (\<5 Mb in size: copy number variations (CNVs) as micro-deletions and micro-duplications) will be detected in sporadic idiopathic POI patients with the purpose to clarify the role of CNVs in POI pathogenesis and to better unveil both novel candidate genes and pathogenic mechanisms
Time frame: Year 1-20
Identification of genetic variants co-segregated with phenotype.
Novel genetic variants not previously anticipated will be found: given the variants co-segregate with phenotype, whole-exome sequencing approach in consanguineous and POI pedigrees will identify the causative gene and variants that cause the phenotype.
Time frame: Year 1-20
To combine array-CGH and WES data mining.
The cumulative effect of different genes/variants will be considered in support of the polygenicity of POI and its heterogeneous phenotype (primarily, the sporadic and familial ones).
Time frame: Year 1-20
Plan to share: Undecided
No publications or documents are linked to this record.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Primary Ovarian Insufficiency→
Ospedale Policlinico San Martino