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- beta A) and activin A (beta A-beta A) 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). Eleva ted serum levels of inhibin A were detected in ongoing pregnancies fro m 4 wk gestation (13 days following ET) and increased to an initial pe ak at 9-10 wk gestation. Significantly higher levels (p < 0.05) were f ound in the multiple pregnancies, and nonviable clinical pregnancies h ad very low levels of inhibin A. Total activin A was detectable 14 day s after ET (positive pregnancy test), and higher levels were associate d with multiple gestations while rapidly falling levels heralded embry onic demise. The fetoplacental unit is thus confirmed as the major sou rce of these glycoproteins. Inhibin pro-alpha C which circulates in gr eat excess as a functionally inactive monomer and as part of high mole cular weight functional dimers, was detectable at levels above normal late-luteal values in singleton and multiple IVF arising from fresh ET s. With frozen-thawed embryo pregnancies, the levels of pro-alpha C-co ntaining inhibins were extremely low, confirming that the corpus luteu m of pregnancy is the major source of the alpha monomer. The initially low levels and very rapid decline in inhibin A in pregnancies with em bryonic failure suggest a role for this glycoprotein as a monitor of e arly-pregnancy viability.