title: Identification of the source of inhibins at the time of conception provides a diagnostic role for them in very early pregnancy.
abstract: OBJECTIVE
  Early diagnosis of a complicated or poor pregnancy outcome in patients undergoing assisted reproductive technique (ART) fertility treatment could aid their counseling and management. A possible role for the inhibin superfamily as markers of early pregnancy viability was investigated.
  
  
  METHODS
  To determine the source of the dimeric glycoproteins inhibin A (alpha-beta A) in early pregnancy, serial blood samples from women who became pregnant following in vitro fertilization (IVF) with fresh embryo transfer (n = 50), from women who achieved pregnancy with frozen-thawed embryos (n = 8), and from a control group of women with spontaneous conceptions (n = 7) were analyzed using a two-site enzyme-linked immunosorbent assay (ELISA). Gonadotropin-releasing hormone (GnRH) analogues are routinely used in ART treatment cycles and are recognized to be luteolytic, and hence, periconceptual administration may be deleterious to pregnancy outcome. Serum samples were obtained from 8 IVF patients who conceived during the cycle in which they had inadvertent luteal phase exposure to GnRH analogues.
  
  
  RESULTS
  Elevated serum levels of inhibin A were detected in ongoing pregnancies from 4 weeks' gestation and increased to an initial peak at 9-10 weeks' gestation. Significantly higher levels (P < 0.05) were found in the multiple pregnancies, and nonviable clinical pregnancies had very low levels of inhibin A. Inhibin pro-alpha C was detectable at levels above normal late luteal values in singleton and multiple pregnancies arising from IVF with fresh embryo transfer. In pregnancies established without corpus luteum activity, frozen-thaw embryo replacement, the levels of pro-alpha C containing inhibins were extremely low, suggesting that the corpus luteum is the major source of the alpha monomer. In pregnancies following inadvertent periconceptual exposure to GnRH analogue, the levels of pro-alpha C were statistically significantly higher in successful pregnancies than in early pregnancy failures.
  
  
  CONCLUSIONS
  The feto-placental unit is confirmed as the major source of inhibin A in early pregnancy, and the initially low levels and very rapid decline in inhibin A in pregnancies with embryonic failure suggest a role for this glycoprotein as a monitor of early pregnancy viability. The corpus luteum is demonstrated to be the major source of inhibin pro-alpha C in early pregnancy, and very low levels in patients with peri-implantational exposure are indicative of lytic damage and herald pregnancy failure despite luteal supplementation with progesterone.
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, United Kingdom.
authors.forename: G M
authors.initials: GM
authors.lastname: Lockwood
authors.forename: W L
authors.initials: WL
authors.lastname: Ledger
authors.forename: D H
authors.initials: DH
authors.lastname: Barlow
authors.forename: N P
authors.initials: NP
authors.lastname: Groome
authors.forename: S
authors.initials: S
authors.lastname: Muttukrishna
mesh_terms: D003338:Corpus Luteum / Q000502:physiology; D004624:Embryo Transfer; D005260:Female; D005306:Fertilization / Q000502:physiology*; D005307:Fertilization in Vitro; D006801:Humans; D007265:Inhibins / Q000097:blood*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000175:diagnosis*; D011256:Pregnancy Outcome; D011446:Prospective Studies
chemical_list: D007265:Inhibins