Measurement of inhibin and activin in early human pregnancy: demonstration of fetoplacental origin and role in prediction of early-pregnancy outcome.
To determine the source of the dimeric glycoproteins inhibin A (alpha-betaA) and activin A (betaA-betaA) in early pregnancy, we analyzed serial blood samples from women who became pregnant following in vitro fertilization (IVF) with fresh embryo transfer (ET; n = 52) and from women who achieved pregnancy with frozen-thawed embryos (n = 8). Elevated serum levels of inhibin A were detected in ongoing pregnancies from 4 wk gestation (13 days following ET) and increased to an initial peak at 9-10 wk gestation. Significantly higher levels (p < 0.05) were found in the multiple pregnancies, and nonviable clinical pregnancies had very low levels of inhibin A. Total activin A was detectable 14 days after ET (positive pregnancy test), and higher levels were associated with multiple gestations while rapidly falling levels heralded embryonic demise. The fetoplacental unit is thus confirmed as the major source of these glycoproteins. Inhibin pro-alphaC, which circulates in great excess as a functionally inactive monomer and as part of high molecular weight functional dimers, was detectable at levels above normal late-luteal values in singleton and multiple IVF arising from fresh ETs. With frozen-thawed embryo pregnancies, the levels of pro-alphaC-containing inhibins were extremely low, confirming that the corpus luteum of pregnancy is the major source of the alpha monomer. 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.
Lockwood
G M
GM
Nuffield Department of Obstetrics and Gynaecology, University of Oxford, United Kingdom. gillian.lockwood@obstetrics-gynaecology.oxford.ac.uk
Ledger
W L
WL
Barlow
D H
DH
Groome
N P
NP
Muttukrishna
S
S
D028341:Activins; D006063:Chorionic Gonadotropin / Q000097:blood; D015925:Cryopreservation; D004624:Embryo Transfer; D005260:Female; D005307:Fertilization in Vitro; D005313:Fetal Death; D005333:Fetus / Q000378:metabolism*; D005865:Gestational Age; D006801:Humans; D007265:Inhibins / Q000097:blood*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011498:Protein Precursors / Q000097:blood
D006063:Chorionic Gonadotropin; D011498:Protein Precursors; C095971:inhibin-alpha subunit precursor; D028341:Activins; D007265:Inhibins