title: C-reactive protein response is higher in early than in late ovarian hyperstimulation syndrome.
abstract: OBJECTIVE
  Many in vitro fertilization (IVF) complications are inflammatory by nature, some of which are even life-threatening. We evaluated the response of C-reactive protein (CRP) in IVF complications, especially in early and late ovarian hyperstimulation syndrome (OHSS), to support clinical decision making in gynecological emergency policlinics.
  
  
  METHODS
  In a prospective two-year study at Helsinki University Hospital, Finland, we recruited patients with IVF complications including moderate or severe OHSS (n=47 patients: 36 early and 14 late OHSS cases), or other IVF complications (n=13). As controls, we recruited women in an uncomplicated IVF cycle (n=27). Serial blood samples (CRP, blood count, platelets, albumin, estradiol, creatinine, and electrolytes) were collected from patients upon admission to the emergency polyclinic and during and after treatment on the ward, and from the controls prior, during, and after the IVF protocol. All samples were categorized according to oocyte pick-up (OPU). The statistics included comparisons between and within the study groups, and receiver-operating characteristic (ROC) curve analysis for diagnostic accuracy of CRP for early OHSS at emergency polyclinics.
  
  
  RESULTS
  On admission, CRP did not differentiate OHSS from other IVF complications, but CRP was higher in early (median 21; IQR 8-33mg/L) than in late (6; 3-9mg/L, p=0.001) OHSS. In ROC analysis for CRP (12mg/L), the area under the curve (AUC) was 0.74 (p=0.001) with sensitivity of 69% and specificity of 71% for early OHSS. CRP was significantly higher (28; 10-46mg/L) in patients with early OHSS two days after oocyte pick-up (OPU) than in the controls (5; <3-9mg/L, p<0.001). The level normalized by 12 days, similarly to the controls. On the ward, the peak CRP was higher if early OHSS was complicated with infection (108; 49-166mg/L) than without infection (20; 8-32mg/L, p=0.001). Late OHSS was associated with hypoalbuminemia (19.6; 16.2-23.1g/L, p<0.001) and thrombocytosis (494; 427-561 E9/L, p=0.004; comparisons to early OHSS).
  
  
  CONCLUSIONS
  Early OHSS associates with a distinct rise in CRP level beyond that induced by uncomplicated oocyte pick-up, whereas the CRP levels in late OHSS are comparable to those in the control cycles. CRP identifies, but cannot distinguish IVF complications.
authors.affiliation: Obstetrics and Gynecology, University of Helsinki, and Helsinki University Hospital, 00290 Helsinki, Finland. Electronic address: kati.korhonen@fimnet.fi.
authors.forename: Kati V M
authors.initials: KV
authors.lastname: Korhonen
authors.affiliation: Obstetrics and Gynecology, University of Helsinki, and Helsinki University Hospital, 00290 Helsinki, Finland; Folkhälsan Research Center, Biomedicum Helsinki, 00290 Helsinki, Finland.
authors.forename: Hanna M
authors.initials: HM
authors.lastname: Savolainen-Peltonen
authors.affiliation: Obstetrics and Gynecology, University of Helsinki, and Helsinki University Hospital, 00290 Helsinki, Finland; Folkhälsan Research Center, Biomedicum Helsinki, 00290 Helsinki, Finland.
authors.forename: Tomi S
authors.initials: TS
authors.lastname: Mikkola
authors.affiliation: Obstetrics and Gynecology, University of Helsinki, and Helsinki University Hospital, 00290 Helsinki, Finland.
authors.forename: Aila E
authors.initials: AE
authors.lastname: Tiitinen
authors.affiliation: Obstetrics and Gynecology, University of Helsinki, and Helsinki University Hospital, 00290 Helsinki, Finland.
authors.forename: Leila S
authors.initials: LS
authors.lastname: Unkila-Kallio
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D015331:Cohort Studies; D018450:Disease Progression; D004636:Emergency Service, Hospital; D005260:Female; D005307:Fertilization in Vitro; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D006785:Hospitals, University; D006801:Humans; D016471:Ovarian Hyperstimulation Syndrome / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology; D010062:Ovulation Induction / Q000009:adverse effects*; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein
keywords: Acute-phase proteins; Infection; Infertility; Inflammation; Reproductive techniques