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Objectives: To measure maternal serum and amniotic fluid levels of macrophage inhibitory cytokine-1 (MIC-1) in Down syndrome and normal pregnancies, assessing the utility of MIC-1 as a prenatal marker of Down syndrome. Method(s): Stored serum from 64 Down syndrome and 399 control pregnancies, collected at 8 to 17 weeks of pregnancy, and stored amniotic fluid from 17 Down syndrome and 53 controls, collected at 15 to 19 weeks of pregnancy, were retrieved for analysis. MIC-1 was measured using an established in-house ELISA, blinded to sample type. Result(s): In maternal serum, MIC-1 levels are not altered in Down syndrome in either the first or second trimester. Levels, expressed as median (95% CI) multiples of the median (MoM), in the Down syndrome cases and controls were 1.07 (0.9-1.1) MoM and 1.0 (0.95-1.03) MoM respectively. In amniotic fluid, MIC-1 levels were significantly decreased compared to controls, 0.52 (0.44-0.64) MoM versus 1.0 (0.85-1.08) MoM (p < 0.0001). Conclusion(s): MIC-1 is decreased in amniotic fluid but not in maternal serum in Down syndrome pregnancies. MIC-1 will not be useful as a prenatal marker of Down syndrome. Copyright © 2004 John Wiley & Sons, Ltd.

Macrophage inhibitory cytokine 1 (MIC 1) is thought to have immunomodulatory actions favouring fetal viability. We measured serum concentrations of MIC 1 in asymptomatic women at 6-13 weeks' gestation who subsequently miscarried or who had already miscarried. MIC 1 concentrations in the miscarriage cohort (n=100), were a third of those who had ongoing pregnancies (n=197). Multiples of the median for miscarriage was 0.32 (95% CI 0.23-0.32) versus 1.00 (0.93-1.06) for ongoing pregnancies; p<0.0001. Concentrations were just as low 3 weeks before diagnosis as on the day of diagnosis. That MIC 1 serum concentrations seem to be low weeks before miscarriage suggests possible predictive and causative roles, as well as therapeutic potential.

OBJECTIVE: Miscarriage is the commonest complication of human pregnancy. We undertook this study to assess whether inhibin A, pro-alphaC inhibin and/or activin A, products of the corpus luteum and placenta, might be useful in either the prediction or diagnosis of miscarriage. DESIGN: Case-control study. PATIENTS: Ninety-eight asymptomatic women at 6-13 weeks gestation who subsequently had a miscarriage and 198 gestation-matched women with a normal singleton pregnancy. MEASUREMENTS: Maternal serum levels of inhibin A, pro-alphaC inhibin, activin A and human chorionic gonadotrophin (hCG) were measured. RESULT(S): Inhibin A, pro-alphaC and hCG, expressed as multiples of the normal median (MoM; +/-95% confidence intervals) in the miscarriage cases were significantly lower than in the viable controls, 0.56 (0.48-0.69) MoM vs. 1.00 (0.98-1.13) MoM, 0.55 (0.51-0.84) MoM vs. 1.0 (0.86-1.22) MoM and 0.34 (0.23-0.36) MoM vs. 1.00 (0.94-1.08) MoM, respectively (P < 0.0001 for all). Of the three analytes, hCG was the most discriminating between cases and controls. Levels of activin A in the miscarriage cases were not significantly different from controls, 0.96 (0.86-1.07) vs. 1.0 (0.95-1.08). CONCLUSION(S): These data suggest that inhibin A, pro-alphaC inhibin and activin A will not be useful in either the prediction or diagnosis of early pregnancy miscarriage.

In early pregnancy, serum levels of the luteal-derived hormone pro-alphaC inhibin peak by the second week after conception. Whether this early rise is biologically important and a consistent feature of only successful pregnancy is unknown. We undertook a prospective cross-sectional study to determine whether serum pro-alphaC inhibin levels at d 15-17 are predictive of a successful clinical in vitro fertilization pregnancy and compared levels between fresh embryo transfer (ET) and frozen-thawed ET. Median (95% confidence interval) pro-alphaC inhibin levels were 68 (57-76) pg/ml in 204 women who did not become clinically pregnant after ET, significantly lower than in either 90 women who became clinically pregnant after fresh ET and who had 3139 (1684-4220) pg/ml or in 39 women with a successful frozen ET who had 877 (678-1111) pg/ml. Pro-alphaC was highly sensitive and specific in predicting clinical pregnancy success but did not improve on the performance of human chorionic gonadotropin. Pro-alphaC inhibin levels were not correlated with progesterone or human chorionic gonadotropin. Levels were no higher in singleton compared with multiple pregnancies and did not increase across gestation, suggestive of a luteal source. The increase in circulating pro-alphaC inhibin in very early pregnancy is highly specific to clinical pregnancy, suggesting a possible biological role in early gestation.

Background: Pro-alphaC inhibins are luteal derived analytes peaking in the maternal serum as early as Day 16 after conception. We set out to verify a previous post hoc analysis which suggested that pro-alphaC levels measured this early are extremely sensitive in predicting clinical pregnancy success after unstimulated IVF with ovulatory cycles. Method(s): Prospective observational study of 246 women undergoing frozenembryo transfer with ovulatory cycles. Serum pro-alphaC and beta-HCG levels at 14-17 days after conception were measured by enzyme-linked immunosorbent assay and grouped according to whether a clinical pregnancy occurred (demonstrable cardiac activity at >=6 weeks' gestation). Result(s): Of 34 (13.8%) women who achieved a clinical pregnancy, median (25th-75th centile) Days 14-17 pro-alphaC levels were 995 pg/ml (758-1463), 6- to 7-fold higher than levels observed in the remainder who did not fall pregnant (112.8 pg/ml (104-121); P < 0.0001). At a fixed 95% specificity, pro-alphaC was 100% sensitive in predicting clinical pregnancy. The best specificities achieved at 100% sensitivity were; 94.8% for pro-alphaC, 96.7% for beta-HCG and 98.1% when both analytes were combined. Conclusion(s): Clinical pregnancy is always associated with a release of luteal derived pro-alphaC 14-17 days after conception. Pro-alphaC may play a possible biological role and be a useful clinical biomarker of luteal health. © The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

In an asymptomatic cohort, serum pregnancy-associated protein-A (PAPP-A) levels among women destined to miscarry were 14% of those seen with ongoing pregnancies. Levels were as low 3 weeks before diagnosis as on the day of diagnosis, suggesting that PAPP-A levels might predict future miscarriage. © 2004 by American Society for Reproductive Medicine.