Whole-genome Sequencing Study in Patients With Diminished Ovarian Reserve

Nanfang Hospital, Southern Medical University

Status: Unknown

Conditions: Diminished Ovarian Reserve

Treatments: Other: whole-genome sequencing

Study type: Observational

Funder types: Other; Industry

Identifiers

NCT04711772

NFEC-2020-188

Details and patient eligibility

About

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

Full 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.

Enrollment: 140 estimated patients

Sex: Female

Ages: 18 to 40 years old

Volunteers: No Healthy Volunteers

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.

Trial design

140 participants in 2 patient groups

DOR group

Description:

Genomic DNA will be extracted from peripheral blood leukocytes to perform whole-genome sequencing in participates with diminished ovarian reserve.

Treatment:

Other: whole-genome sequencing

Control group

Description:

Participants with normal ovarian reserve will be recruited as control group and peripheral blood leukocytes genomic DNA will be extracted to perform whole-genome sequencing.

Treatment:

Other: whole-genome sequencing