title: Premature Ovarian Insufficiency: Phenotypic Characterization Within Different Etiologies.
abstract: Premature ovarian insufficiency (POI) is highly heterogeneous, both in phenotype and etiology. They are not yet clearly stated and correlated.
  
  
  
  To characterize clinical presentations of a large, well-phenotyped cohort of women with POI, and correlate phenotypes with etiologies to draw a comprehensive clinical picture of POI.
  
  
  
  In this retrospective study, a total of 955 Chinese women with overt POI between 2006 and 2015 were systemically evaluated and analyzed. The phenotypic features, including menstrual characteristics, hormone profiles, ovarian ultrasonography/biopsy, pregnancy/family history, and genetic/autoimmune/iatrogenic etiologies were assessed and further compared within different subgroups.
  
  
  
  Among 955 women with POI, 85.97% presented with secondary amenorrhea (SA) and 14.03% with primary amenorrhea (PA). PA represented the most severe ovarian dysfunction and more chromosomal aberrations than SA. The decline of ovarian function in patients with SA progressed quickly. They had shortened reproductive periods (approximately 10 years) and developed amenorrhea within 1 to 2 years after menstrual irregularity. The ovaries were invisible or small, and the presence of follicles (28.43%) was correlated with other good reproductive indicators. Familial patients (12.25%) manifested better ovarian status and fewer chromosomal aberrations than sporadic patients. The etiologies consisted of genetic (13.15%), autoimmune (12.04%), and iatrogenic (7.29%), approximately 68% remaining idiopathic. There were significant differences among different etiologies, with the genetic group representing the most severe phenotype.
  
  
  
  Our results regarding distinct phenotypic characteristics and association with different etiologies further confirmed the high heterogeneity of POI. Additional longitudinal clinical studies and pathogenesis research are warranted.
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated with Shandong University, Jinan, 250001, Shandong, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250001, Shandong, China.|The Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, Jinan, 250001, Shandong, China.|Suzhou Institute of Shandong University, Suzhou, 215123, Jiangsu, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Jiao
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated with Shandong University, Jinan, 250001, Shandong, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250001, Shandong, China.|The Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, Jinan, 250001, Shandong, China.|Center for Reproductive Medicine, Linyi People's Hospital, Linyi, 276003, Shandong, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated with Shandong University, Jinan, 250001, Shandong, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250001, Shandong, China.|The Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, Jinan, 250001, Shandong, China.
authors.forename: Hanni
authors.initials: H
authors.lastname: Ke
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated with Shandong University, Jinan, 250001, Shandong, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250001, Shandong, China.|The Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, Jinan, 250001, Shandong, China.
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated with Shandong University, Jinan, 250001, Shandong, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250001, Shandong, China.|The Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, Jinan, 250001, Shandong, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Yixun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated with Shandong University, Jinan, 250001, Shandong, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250001, Shandong, China.|The Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, Jinan, 250001, Shandong, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated with Shandong University, Jinan, 250001, Shandong, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250001, Shandong, China.|The Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, Jinan, 250001, Shandong, China.|Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200135, China.|Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, 200135, China.
authors.forename: Zi-Jiang
authors.initials: ZJ
authors.lastname: Chen
mesh_terms: D000328:Adult; D000367:Age Factors; D000568:Amenorrhea / Q000209:etiology / Q000235:genetics; D001323:Autoantibodies / Q000097:blood; D001706:Biopsy; D002869:Chromosome Aberrations; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D059785:Karyotype; D009154:Mutation; D010053:Ovary / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D010298:Parity; D010641:Phenotype; D016649:Primary Ovarian Insufficiency / Q000000981:diagnostic imaging / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D017584:Reproductive History; D012189:Retrospective Studies; D014463:Ultrasonography / Q000379:methods
chemical_list: D001323:Autoantibodies