title: Cardiovascular dysfunction in offspring of ovarian-hyperstimulated women and effects of estradiol and progesterone: a retrospective cohort study and proteomics analysis.
abstract: BACKGROUND
  The cardiovascular dysfunction in children born with assisted reproductive technologies has been of great concern. However, the association of ovarian hyperstimulation syndrome (OHSS), a complication of assisted reproductive technologies, with worse cardiovascular functions and underlying mechanism remains unknown.
  
  
  OBJECTIVE
  The objective of the study was to assess the cardiovascular functions of children born to mothers with OHSS and investigate the underlying regulator(s).
  
  
  METHODS
  This was a retrospective cohort recruited in a university hospital.
  
  
  METHODS
  We assessed the cardiovascular functions by Doppler echography in 42 children born to OHSS women, 34 children of mothers with non-OHSS in vitro fertilization, and 48 spontaneously conceived (SC) children (mean age ∼ 4.5 y). Groups were matched for gestational age at delivery and birth weight. An isobaric tag for relative and absolute quantitation-labeled proteomics analysis was performed with another set of umbilical arteries from OHSS and SC pregnancies (n = 3 for both groups).
  
  
  RESULTS
  Children of OHSS mothers showed a significantly decreased mitral ratio of early to late mitral peak velocities, reduced systolic and diastolic diameters of common carotid arteries, and impaired flow-mediated dilation compared with non-OHSS in vitro fertilization and SC children. Intima-media thickness and arterial stiffness indices were similar in the three groups. In the proteomics study, 1640 proteins were identified from OHSS and SC umbilical arteries, and 40 differentially expressed proteins were selected for further analysis. Estradiol and progesterone were identified as activated upstream regulators.
  
  
  CONCLUSIONS
  Children born to ovarian-hyperstimulated women displayed cardiovascular dysfunctions. The underlying mechanisms may involve the effects of supraphysiological estradiol and progesterone levels.
authors.affiliation: Key Laboratory of Reproductive Genetics (G.-F.X., S.T., M.-E.L., T.-T.Y., J.-Y.L., X.-H.L., J.-X.P., Y.L., C.-L.Z., D.Z., X.-M.L., H.-F.H.) and Bio-X Institutes (J.-Y.Z., H.-F.H.), Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Department of Pathology and Pathophysiology (H.-T.P., J.-Z.S.), School of Medicine, and Departments of Reproductive Endocrinology (G.-F.X., S.T., M.-E.L., T.-T.Y., J.-Y.L., X.-H.L., Y.L., W.-W.S., X.-Q.Y., F.-H.Z., J.-X.P., Y.L., C.-L.Z., D.Z.,, Y.-M.Z.) and Ultrasound (W.-W.Y., W.-M.Y.), Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China; and International Peace Maternal and Child Health Hospital (J.-Y.Z., H.-F.H.), Shanghai Jiao Tong University, School of Medicine, Shanghai 200030, China.
authors.forename: Gu-Feng
authors.initials: GF
authors.lastname: Xu
authors.forename: Jun-Yu
authors.initials: JY
authors.lastname: Zhang
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Pan
authors.forename: Shen
authors.initials: S
authors.lastname: Tian
authors.forename: Miao-E
authors.initials: ME
authors.lastname: Liu
authors.forename: Tian-Tian
authors.initials: TT
authors.lastname: Yu
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Li
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Ying
authors.forename: Wei-Miao
authors.initials: WM
authors.lastname: Yao
authors.forename: Xian-Hua
authors.initials: XH
authors.lastname: Lin
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lv
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Su
authors.forename: Xiao-Qun
authors.initials: XQ
authors.lastname: Ye
authors.forename: Fang-Hong
authors.initials: FH
authors.lastname: Zhang
authors.forename: Jie-Xue
authors.initials: JX
authors.lastname: Pan
authors.forename: Ye
authors.initials: Y
authors.lastname: Liu
authors.forename: Cheng-Liang
authors.initials: CL
authors.lastname: Zhou
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.forename: Xin-Mei
authors.initials: XM
authors.lastname: Liu
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Zhu
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Sheng
authors.forename: He-Feng
authors.initials: HF
authors.lastname: Huang
mesh_terms: D002318:Cardiovascular Diseases / Q000209:etiology* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004452:Echocardiography; D004958:Estradiol / Q000097:blood*; D005260:Female; D006334:Heart Function Tests; D006801:Humans; D008297:Male; D016471:Ovarian Hyperstimulation Syndrome / Q000150:complications* / Q000235:genetics; D011374:Progesterone / Q000097:blood*; D040901:Proteomics; D012189:Retrospective Studies; D014469:Umbilical Arteries / Q000737:chemistry
chemical_list: D011374:Progesterone; D004958:Estradiol