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

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.

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.

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