Whole-genome Sequencing Study in Patients With Diminished Ovarian Reserve

A Whole-genome Sequencing Base Study on Genetic Pathogenesis of Diminished Ovarian Reserve

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

Study Overview

• Status: Unknown
• Conditions: Diminished Ovarian Reserve
• Intervention / Treatment: Other: whole-genome sequencing

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.

• Study Type: Observational
• Enrollment (Anticipated): 140

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University
      • Contact: Chen Shi-Ling, M.D., Ph.D; Phone Number: +86-20-62787604; Email: chensl_92@163.com
      • Principal Investigator: Chen Shi-Ling, M.D., Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

The two groups of this study consist of DOR patients and women with normal ovarian reserve.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
DOR group; Genomic DNA will be extracted from peripheral blood leukocytes to perform whole-genome sequencing in participates with diminished ovarian reserve.	Other: whole-genome sequencing; Whole-genome sequencing will be preformed for each participate to explore the potential disease-causing genes of DOR.
Control group; 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.	Other: whole-genome sequencing; Whole-genome sequencing will be preformed for each participate to explore the potential disease-causing genes of DOR.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genotype	Measure the genotype by whole-genome sequencing in all participates.	1/9/2020-31/12/2022

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University
• Collaborators: Ferring Pharmaceuticals
• Investigators: Study Director: Shi-ling Chen, M.D, Ph.D, Nanfang Hospital of Southern Medical University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Anticipated): June 30, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: January 13, 2021
• First Submitted That Met QC Criteria: January 14, 2021
• First Posted (Actual): January 15, 2021

Study Record Updates

• Last Update Posted (Actual): January 15, 2021
• Last Update Submitted That Met QC Criteria: January 14, 2021
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Diminished Ovarian Reserve; Whole-genome Sequencing
• Other Study ID Numbers: NFEC-2020-188

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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