Maternal serum pregnancy-associated plasma protein-A and free beta-human chorionic gonadotrophin in pregnancies conceived with fresh and frozen-thawed embryos from in vitro fertilization and intracytoplasmic sperm injection.

Maternal serum pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotrophin (beta-hCG) are useful markers in the screening of Down syndrome in the first trimester. We investigated the effect of intracytoplasmic sperm injection (ICSI), freezing and thawing of embryos on the levels of these two analytes in assisted reproduction pregnancies. We recruited 149 women who conceived after assisted reproduction with fresh embryos (92 from conventional IVF and 57 from ICSI), 85 women who conceived with frozen-thawed embryos (54 from conventional IVF and 31 from ICSI) and 401 women with spontaneous conceptions as controls. The concentrations of PAPP-A and free beta-hCG were measured between 10 and 14 weeks and were converted to multiples of medians (MoM) for comparisons. Median PAPP-A MoMs were significantly reduced in ICSI pregnancies in the fresh and frozen-thawed embryo subgroups (0.70 and 0.66 MoM respectively) and in the IVF fresh embryo subgroups (0.83 MoM), as compared to controls (1.00 MoM). Free beta-hCG MoM was significantly reduced in the IVF fresh embryos subgroup (0.87 MoM), but not in the other three subgroups. Further studies for exploring the underlying pathophysiology and adjustment in the marker levels for screening of Down syndrome are warranted in pregnancies conceived after assisted reproduction.

Hui PW ，Lam YH ，Tang MH ，NG EH ，Yeung WS ，Ho PC ... -  《PRENATAL DIAGNOSIS》

First-trimester screening markers are altered in pregnancies conceived after IVF/ICSI.

To determine the levels of first-trimester screening markers and to assess the false-positive rate for first-trimester combined screening for Down syndrome in a large national population of women pregnant after assisted reproductive technology (ART), in order to decide whether or not to correct risk calculation for mode of conception. A national prospective cohort study of 1000 pregnancies achieved after ART was compared with a control group of 2543 pregnancies conceived spontaneously. All women completed a first-trimester combined screening program. Risk calculation was performed retrospectively based on the screening parameters to avoid bias due to the use of different algorithms of risk calculation. In chromosomally normal pregnancies conceived after in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), the pregnancy-associated plasma protein-A multiples of the median value was significantly decreased when compared with that of pregnancies conceived spontaneously (0.78 and 0.79 vs. 0.98), while there was no difference in the group treated by frozen embryo replacement. There was no difference in the level of free beta-human chorionic gonadotropin between groups. The median nuchal translucency thickness was smaller in the overall ART group compared with controls. The false-positive rate of first-trimester combined screening in the overall ART group, adjusted for maternal age, was significantly higher when compared with controls (9.0% vs. 6.0%). It seems advisable to use a population of IVF/ICSI pregnancies to establish median curves for the first-trimester serum screening parameters and perhaps also for nuchal translucency thickness. However, care must be taken, as different ART treatment methods and aspects of medical history seem to alter the screening parameters in different ways.

Gjerris AC ，Loft A ，Pinborg A ，Christiansen M ，Tabor A ... -  《-》

First-trimester screening for trisomy 21 by free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A: impact of maternal and pregnancy characteristics.

To use multiple regression analysis to define the contribution of maternal variables that influence the measured concentration of free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A), and the interaction between these covariates, in first-trimester biochemical screening for trisomy 21. This was a multicenter study of prospective screening for trisomy 21 by a combination of fetal nuchal translucency thickness, and maternal serum free beta-hCG and PAPP-A at 11 + 0 to 13 + 6 weeks of gestation. In the pregnancies subsequently found to have trisomy 21 and in those with no obvious chromosomal abnormality, we used multiple regression analysis to account for pregnancy characteristics that influence the measured concentrations of free beta-hCG and PAPP-A. We fitted Gaussian distributions to the distribution of log multiples of the median (MoM) values in trisomy 21 and in unaffected pregnancies. There were 491 cases of trisomy 21 and 96 803 chromosomally normal pregnancies. Compared with values in Caucasian women, those who were parous, non-smokers and those who conceived spontaneously, PAPP-A was 57% higher in women of Afro-Caribbean origin, 3% higher in South Asians, 9% higher in East Asians, 2% higher in nulliparous women, 17% lower in smokers and 10% lower in those conceiving by in-vitro fertilization (IVF). Free beta-hCG was 12% higher in women of Afro-Caribbean origin, 9% lower in South Asians, 8% higher in East Asians, 2% higher in nulliparous women, 4% lower in smokers and 9% higher in those conceiving by IVF. In screening for trisomy 21 by maternal age and serum free beta-hCG and PAPP-A the estimated detection rate was 65% for a false-positive rate of 5%. In first-trimester biochemical screening for trisomy 21 it is essential to adjust the measured values of free beta-hCG and PAPP-A for maternal and pregnancy characteristics.

Kagan KO ，Wright D ，Spencer K ，Molina FS ，Nicolaides KH ... -  《-》

Serum PAPP-A levels at 10-14 weeks of gestation are altered in women after assisted conception.

Increased screen-positive rate was observed in the first-trimester screening for trisomy 21 (T21) among women after assisted conception. The aim of this study was to identify the trends of changes in serum marker levels after different modes of assisted conception. Retrospectively, we analyzed the levels of free beta human chorionic gonadotrophin (f beta HCG), pregnancy-associated plasma protein-A (PAPP-A) and inhibin A in maternal serum, and fetal nuchal translucency (NT) thickness at 10-14 gestational weeks in 1098 women with singleton pregnancies: 130 after IVF-ET, 54 after ICSI and 914 after spontaneous conception. In women after IVF-ET and ICSI, PAPP-A was decreased (0.94 MoM and 0.82 MoM, respectively) and inhibin A increased (1.11 MoM and 1.48 MoM, respectively) in comparison to the women after spontaneous conception. With increasing number of oocytes retrieved PAPP-A decreased and inhibin A increased. In women pregnant after assisted conception without ovarian stimulation (transfer of frozen-thawed embryo or in spontaneous cycle) the marker levels were not significantly different from those in women after spontaneous conception. The presence of multiple corpora lutea may be responsible for the changes in marker levels. In spite of the differences in marker levels, the screen-positive rate for T21 is not significantly increased in women after assisted conception.

Tul N ，Novak-Antolic Z 《-》

First-trimester serum marker distribution in singleton pregnancies conceived with assisted reproduction.

To evaluate marker distribution of free beta-human chorionic gonadotrophin (fbeta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in singleton pregnancies conceived by assisted reproduction techniques (ART). In vitro fertilization (IVF) (n = 203) and intracytoplasmic sperm injection (ICSI) (n = 192) cases from a database of 14 645 first-trimester combined tests (overall study group) were selected and matched to 1164 controls for gestational age at sample date and maternal age. In the IVF group and ICSI group, lnPAPP-A was lower (IVF 6.74 vs 7.08; P = 0.0001; ICSI 6.59 vs 7.07; P = 0.0001) compared with the matched controls. Lnfbeta-hCG was lower in the IVF group (3.75 vs 3.90; P = 0.005) but not significantly different in the ICSI group (3.87 vs 3.93; P = 0.27). The computed correction factors for PAPP-A and fbeta-hCG were 1.42 and 1.17 for the IVF group and 1.56 and 1.05 for the ICSI group.The false-positive rate (FPR) in the IVF and ICSI group compared with the matched controls was higher (IVF 10.3% vs 8.6% and ICSI 10.9% vs 7.5%). In the overall age-biased [maternal age significantly lower compared with all ART and control groups] study group the FPR was 6.8%. The increase in FPR in the ART groups can be explained by decreased PAPP-A values. Therefore, an adjustment in risk analysis for Down syndrome is suggested.

Engels MA ，Kooij M ，Schats R ，Twisk JW ，Blankenstein MA ，van Vugt JM ... -  《-》