Ovarian infertility and subfertility presenting with premature ovarian insufficiency (POI) and diminished ovarian reserve are major issues facing in the developed world due to the trend of delaying child birth. Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting 6-10% of women in reproductive age. Based on advances in whole exome sequencing, evaluation of gene copy variants, together with family-based and genome-wide association studies (GWAS), we discussed genes responsible for the POI, PCOS, and ovarian senescence. We used a gene-centric approach to sort out literature deposited in the Ovarian Kaleidoscope database (http://okdb.appliedbioinfo.net) by sub-categorizing candidate genes as ligand-receptor signaling, meiosis and DNA repair, transcriptional factors, RNA metabolism, enzymes, and others. We discussed individual gene mutations found in POI patients and verification of gene functions in gene-deleted model organisms. Decreases in the expression of some of the POI genes could be responsible for early menopause, especially those essential for DNA repair and meiosis. Although multiple individual candidate gene single nucleotide polymorphisms have been analyzed in PCOS patients, only a limited number of findings have been verified and dealing with genes with known ovarian functions. We propose to set up a panel of candidate genes for targeted sequencing in POI patients and investigate ovarian expression of a set of candidate genes in PCOS patients, together with studies on mitochondria-associated genes in middle-aged subfertile patients. Continuing studies on POI and PCOS as well as ovarian senescence genes could allow better diagnosis and formulation of treatment strategies.

Based on literature review.