title: Are intracytoplasmic sperm injection and high serum estradiol compounding risk factors for adverse obstetric outcomes in assisted reproductive technology?
abstract: To evaluate whether intracytoplasmic sperm injection (ICSI) use and E2 on the final day of assisted reproductive technology (ART) stimulation are associated with adverse obstetric complications related to placentation.
  
  
  
  Retrospective cohort study.
  
  
  
  Large private ART practice.
  
  
  
  A total of 383 women who underwent ART resulting in a singleton live birth.
  
  
  
  None.
  
  
  
  Adverse placental outcomes composed of placenta accreta, placental abruption, placenta previa, intrauterine growth restriction, preeclampsia, gestational hypertension, and small for gestational age infants.
  
  
  
  Patients with adverse placental outcomes had higher peak serum E2 levels and were three times more likely to have used ICSI. Adverse placental outcomes were associated with increasing E2 (odds ratio 1.36, 95% confidence interval 1.13-1.65) and ICSI (odds ratio 3.86, 95% confidence interval 1.61-9.27). Adverse outcomes increased when E2 was >3,000 pg/mL and continued to increase in a linear fashion until E2 was >5,000 pg/mL. The association of ICSI with adverse outcomes was independent of male factor infertility. Interaction testing suggested the adverse effect of E2 was primarily seen in ICSI cycles, but not in conventional IVF cycles. Estradiol >5,000 pg/mL was associated with adverse placental events in 36% of all ART cycles and 52% of ICSI cycles.
  
  
  
  ICSI and elevated E2 on the day of hCG trigger were associated with adverse obstetric outcomes related to placentation. The finding of a potential interaction of E2 and ICSI with adverse placental events is novel and warrants further investigation.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Walter Reed National Military Medical Center, Bethesda, Maryland; Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. Electronic address: DonRoysterMD@gmail.com.
authors.forename: Greene Donald
authors.initials: GD
authors.lastname: Royster
authors.affiliation: Department of Obstetrics and Gynecology, University of Miami Jackson Health System, Miami, Florida.
authors.forename: Kavitha
authors.initials: K
authors.lastname: Krishnamoorthy
authors.affiliation: Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Walter Reed National Military Medical Center, Bethesda, Maryland.
authors.forename: John M
authors.initials: JM
authors.lastname: Csokmay
authors.affiliation: Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Walter Reed National Military Medical Center, Bethesda, Maryland.
authors.forename: Belinda J
authors.initials: BJ
authors.lastname: Yauger
authors.affiliation: Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Walter Reed National Military Medical Center, Bethesda, Maryland.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Chason
authors.affiliation: Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
authors.forename: Alan H
authors.initials: AH
authors.lastname: DeCherney
authors.affiliation: Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
authors.forename: Erin F
authors.initials: EF
authors.lastname: Wolff
authors.affiliation: Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Walter Reed National Military Medical Center, Bethesda, Maryland.
authors.forename: Micah J
authors.initials: MJ
authors.lastname: Hill
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D006063:Chorionic Gonadotropin / Q000008:administration & dosage; D004958:Estradiol / Q000097:blood*; D005260:Female; D005298:Fertility; D005300:Fertility Agents, Female / Q000008:administration & dosage; D006772:Hospitals, Military; D006801:Humans; D007236:Infant, Small for Gestational Age; D007246:Infertility / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D008396:Maryland; D016017:Odds Ratio; D010062:Ovulation Induction; D010929:Placentation; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D018873:Pregnancy Rate; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D020554:Sperm Injections, Intracytoplasmic / Q000009:adverse effects*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006063:Chorionic Gonadotropin; D005300:Fertility Agents, Female; D004958:Estradiol
keywords: Elevated E(2); ICSI; IVF; adverse obstetric outcomes