Clinical trial NCT04711772: Whole-genome Sequencing Study in Patients With Diminished Ovarian Reserve
Official title: A Whole-genome Sequencing Base Study on Genetic Pathogenesis of Diminished Ovarian Reserve
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Diminished Ovarian Reserve
Keywords: Diminished Ovarian Reserve
Whole-genome Sequencing
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
Collaborators: name: Ferring Pharmaceuticals
First posted: 2021-01-15
Enrollment: 140
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The two groups of this study consist of DOR patients and women with normal ovarian reserve.

Brief summary: The study aims to explore the genetic pathogenesis of diminished ovarian reserve via whole-genome sequencing technology in Chinese women.

Detailed description: Diminished ovarian reserve (DOR), a pathological condition of reduced quantity and quality of oocytes, has severe impairment on women fertility. Some women experience DOR may develop into premature ovarian insufficiency (POI), which defined as a cessation of function of ovaries in women younger than 40 years old. The pathogenesis of DOR is multiple and the etiology of most DOR remains obscure. Genetic factors, including chromosome abnormality, genetic variation, and non-coding RNA abnormal regulation are considered the major mechanisms of DOR. More than 12 gene mutations, detected by whole-exome sequencing (WES), have been implicated as potential causes of DOR. However, we have found that coding gene mutation detected by WES may only account for a small part of DOR. Whole-genome sequencing (WGS) has been developing into an important strategy for identifying exons, introns and mitochondrial DNA mutation. However, the application of WGS is still lacking in detecting pathogenic genes of DOR. Therefore, this study intends to explore the possible pathogenic genes by WGS in order to deeply and comprehensively understand the pathogenic mechanism of DOR.

Eligibility criteria: Inclusion Criteria:

DOR group:

1. age between 18 and 40 years;
2. number of oocytes obtained in previous ovarian stimulation cycles ≤3;
3. bilateral ovarian antral follicle count (AFC) \< 5-7;
4. serum anti-Mullerian hormone (AMH) \<0.5-1.1ng/ml.

Control group:

1. age between 18 and 40 years;
2. bilateral AFC ≥8;
3. serum AMH ≥1.2ng/ml;
4. regular menstrual cycles occurring every 25-35 days.

Exclusion Criteria:

The exclusion criteria of the two groups were:

1. an abnormal karyotype;
2. a history of other endocrine diseases such as polycystic ovary syndrome, hyperprolactinemia and hyperthyroidism;
3. a history of radiotherapy, chemotherapy and ovarian surgery.

Primary outcomes:
measure: Genotype
timeFrame: 1/9/2020-31/12/2022
Secondary outcomes:
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University
state: Guangdong
Study officials:
affiliation: Nanfang Hospital, Southern Medical University
name: Shi-ling Chen, M.D, Ph.D
role: STUDY_DIRECTOR
References: