First trimester screening for Down syndrome and assisted reproduction: no basis for concern

In pregnancies obtained after assisted reproduction the false-positive rate of second trimester Down syndrome (DS) screening is increased by 1.5-3-fold. This may cause an increase in the number of amniocenteses and the fetal loss rate. The present study for the first time examined whether assisted reproductive technologies affect the results of first trimester screening. The markers PAPP-A, free beta-hCG and the nuchal translucency (NT) thickness were examined at 12-14 weeks' gestation. Screening markers in 47 in vitro fertilisation (IVF), 63 ovulation induction (OI) and 3026 spontaneously conceived singleton pregnancies were compared. The MoM (multiples of the median) value in the IVF pregnancies was 1.02 (95% CI: 0.85-1.22) for PAPP-A, 1.14 (95% CI: 0.95-1.37) for beta-hCG and 0.97 (95% CI: 0.89-1.05) for NT; the MoM value in the OI pregnancies was 0.89 (95% CI: 0.76-1.05) for PAPP-A, 1.08 (95% CI: 0.93-1.25) for beta-hCG and 1.02 (95% CI: 0.95-1.11) for NT. The first trimester marker values in assisted reproductive pregnancies and spontaneously conceived pregnancies were not significantly different. Estimated false-positive rates for a risk cut-off of 1:400 varied from 4.7% in IVF pregnancies to 5.1% in OI pregnancies. Therefore the false-positive rate in Down syndrome screening should be independent of the method of conception.     

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

Screening for trisomy 21 in twin pregnancies in the first trimester: an update of the impact of chorionicity on maternal serum markers

OBJECTIVE: To examine the distribution of first-trimester biochemical markers of aneuploidy in twin pregnancies, and to assess whether there are differences in the distributions between monochorionic and dichorionic twins. METHODS: Maternal serum-free beta-hCG and PAPP-A were measured between 11 + 0 and 13 + 6 weeks as part of a routine first-trimester screening program in conjunction with fetal nuchal translucency (NT) performed at two sites. Data from twin pregnancies were extracted from the fetal databases along with information on the chorionicty. The individual marker concentrations were expressed as weight corrected, ethnicity corrected, smoking corrected and IVF corrected MoM using data from singleton pregnancies as the reference. The overall medians were compared to those in singleton pregnancies and between monochorionic and dichorionic twins. RESULTS: Data was available from 1914 sets of twins. Of these, 1214 had information with respect to chorionicity, with 1024 being dichorionic and 190 being monochorionic. The overall median weight corrected, ethnicity corrected, smoking corrected and IVF corrected MoM amongst twin pregnancies were 2.023 for free beta-hCG (sd log(10) MoM = 0.2611 and 2.121 for PAPP-A (sd log(10) MoM = 0.2255) -- both medians were significantly greater than the medians in singleton pregnancies (1.00 MoM). In the case of monochorionic and dichorionic twins the median weight corrected, ethnicity corrected, smoking corrected and IVF corrected, free beta-hCG MoM's were not significantly different (1.983 v 2.041), however for PAPP-A the median weight corrected, ethnicity corrected, smoking corrected and IVF corrected MoM in monochorionic twins was significantly lower than in dichorionic twins (1.756 v 2.250) whilst the sd log(10) MoM's were not significantly different (0.2185 v 0.2167). CONCLUSION: Screening in twin pregnancies requires adjustment of the calculated MoM to account for the presence of two fetuses. In general, for free beta-hCG, this should be by dividing the observed corrected MoM by 2.023. For PAPP-A two different factors are required - 2.192 in dichorionic twins and 1.788 in monochorionic twins.     

Maternal risks and perinatal outcome in a Danish national cohort of 1005 twin pregnancies: the role of in vitro fertilization

BACKGROUND: Twin pregnancies constitute 25% of all in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) pregnancies. There is a lack of knowledge on maternal risks and perinatal outcome of IVF/ICSI twin pregnancies. METHODS: National survey by questionnaire (n = 1769). The study population consisted of all IVF/ICSI twin mothers (n = 266) and the two control groups of all IVF/ICSI singleton mothers (n = 764) and non-IVF/ICSI twin mothers (n = 739) who delivered in Denmark in 1997. The response rate was 89% among IVF twin mothers and overall 81%. RESULTS: In terms of maternal risks and perinatal outcome no significant differences were observed between IVF/ICSI twin and non-IVF/ICSI twin pregnancies after stratification for maternal age and parity. Nevertheless, IVF/ICSI twin mothers were more frequently on sick leave (OR 2.5, 95% CI 1.5-4.0) and hospitalized (OR 1.9, 95% CI 1.3-2.8) during pregnancy. Compared with IVF/ICSI singleton pregnancies, IVF/ICSI twin pregnancies were characterized by a higher incidence of preeclampsia (OR 2.4, 95% CI 1.5-4.2) and a higher frequency of sick leave (OR 6.8, 95% CI 4.4-10.5) and hospitalizations during pregnancy (OR 3.5, (95% CI 2.5-4.9); moreover, mean birthweight (p < 0.001) and gestational age (p < 0.001) were lower. No differences were observed in the incidence of pregnancy-induced hypertension and gestational diabetes between IVF/ICSI twin and singleton pregnancies. CONCLUSION: Although this population study indicates that maternal risks in IVF/ICSI twin pregnancies are comparable with non-IVF/ICSI twin pregnancies, the IVF/ICSI twin mothers were more likely to be on sick leave or hospitalized during pregnancy. Furthermore, maternal risks were higher and obstetric outcome poorer in IVF/ICSI twin vs. IVF/ICSI singleton pregnancies.     

Screening for trisomy 21 in twin pregnancies in the first trimester using free beta-hCG and PAPP-A, combined with fetal nuchal translucency thickness

In the first trimester of pregnancy the biochemical markers free beta-hCG and pregnancy associated plasma protein-A (PAPP-A) are used for the prenatal screening of trisomy 21, either alone or in combination with nuchal translucency (NT) thickness. In this study, I have analysed the distribution of these biochemical markers in 159 twin pregnancies and compared this with 3466 singleton pregnancies. On average free beta-hCG values are 2.099 times greater in twins than in singletons and PAPP-A some 1.86 times greater. The width of the analyte distribution in twins is very similar to that in singleton pregnancies. Using statistical modelling techniques I have predicted that at a 5% false positive rate the detection rate in twins discordant for trisomy 21 will be 52% and in twins concordant for trisomy 21 will be 55%, if correction for twin pregnancy is carried out using the 'pseudo risk' approach. The detection rate using biochemical parameters is less than that achievable for twins using NT (75%). However, the combination of NT and maternal serum biochemistry will give detection rates approaching 80%. These rates are some 10% less than in singleton pregnancies, but nevertheless combining NT and biochemistry will allow high rates of detection of affected twins with the benefit of ultrasound and NT being able to specifically locate the affected twin. Twin screening using both modalities should be considered when introducing first trimester screening.     

Maternal serum free-beta-chorionic gonadotrophin, pregnancy-associated plasma protein-A and fetal nuchal translucency thickness at 10-13(+6) weeks in relation to co-variables in pregnant Saudi women

OBJECTIVE: To establish normative values and distribution parameters of first-trimester screening markers, namely, fetal nuchal translucency (NT), maternal serum free beta-human chorionic gonadotrophin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A), at 10 to 13(+6) weeks of gestation in Saudi women and to evaluate the effect of co-variables including maternal body weight, gravidity, parity, fetal gender, twin pregnancy, smoking and ethnicity on these markers. METHODS: A cohort of Saudi women (first cohort n = 1616) with singleton pregnancies prospectively participated in the present study, and fetal NT together with maternal serum free beta-hCG and PAPP-A were determined at 10 to 13(+6) weeks of gestation. The distribution of gestational age-independent multiples of the median (MoM) of the parameters was defined and normative values were established, and correction for maternal body weight was made accordingly. The influence of various co-variables was examined using the data collected from the first and the second (n = 1849) cohorts of women and 62 twin pregnancies, and compared with other studies. RESULTS: All markers exhibited log-normally distributed MoMs. Gestational age-independent normative values were established. Maternal body weight was corrected, particularly for maternal free beta-hCG and PAPP-A using standard methods. Fetal NT showed a negative relationship with increasing gravidity (r = -0.296) or parity (r = -0.311), whereas both free beta-hCG and PAPP-A exhibited a significant positive relationship. There was a significant increase in the MoM of free beta-hCG in female fetuses. Smoking decreased MoM values of free beta-hCG (by 14.6%; P < 0.01) and PAPP-A (by 18.8%; P < 0.001). Twin pregnancy showed significant increases in MoM values of free beta-hCG (by 1.87-fold) and PAPP-A (by 2.24-fold), with no significant changes in fetal NT MoM values. Fetal NT MoM values were lower in Africans and Asians but higher in Orientals, as compared to Saudi women (P < 0.05; in each case). MoM values (body weight-corrected) of free beta-hCG were 25.2% higher in Africans and 19.4% higher in Orientals but 6.8% lower in other Arabian and Asian (by 5.8%) women as compared to Saudi women (P < 0.05; in each case). CONCLUSIONS: The normative values and distribution parameters for fetal NT, maternal serum free beta-hCG and PAPP-A were established in Saudi singleton pregnancies, the maternal body weight together with smoking, twin pregnancy and ethnicity being important first-trimester screening co-variables. Gravidity, parity and fetal gender are also considered to influence one or more of the first-trimester markers examined.     

First-trimester screening for trisomy 21 in twin pregnancy: does the addition of biochemistry make an improvement?

OBJECTIVE: To evaluate the effectiveness of the addition of first-trimester biochemistry to fetal nuchal translucency (NT) measurement in the Combined Test when screening for trisomy 21 in twin pregnancies. METHODS: Maternal serum free beta-hCG and PAPP-A were determined at 8 to 12 weeks and fetal NT was measured at 11 to 14 weeks. The individual risks were estimated for each of the fetuses using both NT screening alone and the Combined Test. An invasive diagnostic procedure was offered when the risk was 1:250 or over in either one of the fetuses. In the first period, only the results of NT screening were clinically applied. After previous analysis, the Combined Test was introduced into clinical practice. RESULTS: In the two-and-a-half-year study period, a complete follow-up was obtained in 100 twin pregnancies. Three fetuses (two pregnancies) with trisomy 21 were detected by both methods. The false-positive rate achieved by NT screening (14.3% of pregnancies and 8.6% of fetuses) was substantially reduced when first-trimester biochemistry was added in the Combined Test (5.1% of pregnancies and 3.6% of fetuses). CONCLUSION: The Combined Test appears to maintain the detection rate achieved by NT screening for trisomy 21 in twin pregnancies, but false-positive rates and invasive diagnostic procedures are reduced.     

Early vaginal bleeding and first-trimester markers for Down syndrome

OBJECTIVES: To assess the effect of early vaginal bleeding on first-trimester markers for Down syndrome. METHODS: A retrospective study was conducted on 2330 normal singleton fetuses who underwent first-trimester combined screening for Down syndrome based on ultrasound and maternal serum markers. Fetal nuchal translucency (NT), maternal serum pregnancy-associated plasma protein A (PAPP-A), free beta-hCG and the false-positive rate of the test were compared between pregnancies with (n = 253) and without (n = 2077) a history of early vaginal bleeding. RESULTS: The mean +/- SD log(10) MoM for NT, PAPP-A and free beta-hCG was -0.024 +/- 0.101, 0.007 +/- 0.244, 0.047 +/- 0.273 and -0.011 +/- 0.108, -0.006 +/- 0.223, 0.008 +/- 0.264 in pregnancies with and without a history of early vaginal bleeding, with a p value of 0.07, 0.40 and 0.03 respectively. The false-positive rate was 2.4% and 3.6% (p = 0.33). CONCLUSIONS: An earlier episode of vaginal bleeding is associated with an increase in maternal serum free beta-hCG levels at first-trimester combined screening for Down syndrome. However, this phenomenon is unlikely to significantly affect the false-positive rate of the test.     

Integrated ultrasound and biochemical screening for trisomy 21 using fetal nuchal translucency,absent fetal nasal bone,free beta-hCG and PAPP-A at 11 to 14 weeks

BACKGROUND: Screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) thickness and maternal serum free beta-hCG and pregnancy-associated plasma protein-A (PAPP-A) at 11 to 14 weeks of gestation is associated with a detection rate of 90% for a false-positive rate of 5%. Recent evidence suggests that in about 70% of fetuses with trisomy 21, the nasal bone is not visible at the 11th- to 14th-week scan (Cicero et al., 2001). The aim of this study was to examine whether fetal NT thickness and the level of maternal serum biochemical markers is independent of the presence or absence of the nasal bone, and to estimate the performance of a screening test that integrates the two sonographic and the two biochemical markers. METHODS: This was a retrospective case-control study comprising 100 trisomy 21 and 400 chromosomally normal singleton pregnancies at 11 to 14 weeks of gestation. Ultrasound examination was carried out for measurement of fetal NT and assessment of the presence or absence of the fetal nasal bone. Maternal serum free beta-hCG and PAPP-A were measured using the Kryptor rapid random-access immunoassay analyser (Brahms Diagnostica GmbH, Berlin). The distribution of fetal NT, maternal serum free beta-hCG and PAPP-A in trisomy 21 fetuses with absent and present nasal bone was examined. RESULTS: The nasal bone was absent in 69 and present in 31 of the trisomy 21 fetuses. There were no significant differences in median maternal age, median gestational age, NT delta, free beta-hCG MoM and PAPP-A MoM in trisomy 21 fetuses with and without a visible nasal bone. For a false-positive rate of 5%, it was estimated that screening with the four markers in combination with maternal age would be associated with a detection rate of 97%. For a false-positive rate of 0.5%, the detection rate was 90.5%. CONCLUSIONS: An integrated sonographic and biochemical test at 11 to 14 weeks can potentially identify about 90% of trisomy 21 fetuses for a false-positive rate of 0.5%.     

Maternal midtrimester serum AFP and free beta-hCG levels in in vitro fertilization twin pregnancies

We aimed to compare the levels of alpha-fetoprotein (AFP) and free beta-human chorionic gonadotrophin (beta-hCG) levels as multiples of the median (MoM) values between spontaneous and in vitro fertilized (IVF) twin pregnancies. The control group of spontaneous singleton pregnancies was used for calculating the gestational age specific median levels of the values. Within a cohort of 19 310 pregnancies, 145 twin pregnancies were identified. The data were collected from Down syndrome (DS) screening programmes in four University catchment areas in Finland between 1994-98. Maternal midtrimester serum marker levels were measured across gestational weeks 14-18. There were no fetal chromosome anomalies in either of the twin groups or the singleton group. Serum AFP of 145 and beta-hCG values of 39 spontaneous twin pregnancies were compared to the values of 6548 singleton pregnancies. In IVF twins 30 AFP and 29 beta-hCG values were compared to the levels of the control group. Both AFP and beta-hCG values were twice as high in the spontaneous twin pregnancies (medians 2.18 and 1.83 MoM respectively) as in the singleton group (medians 1.00 and 1.00 MoM respectively). In IVF twin pregnancies beta-hCG levels were higher (median 2.20 MoM) than in spontaneous twins (p=0.08), whereas no significant difference was found in AFP levels (2.30 MoM). In conclusion, the higher levels of beta-hCG levels in IVF twin pregnancies should be considered in DS screening to avoid high false positive rates.     

Combined measurement of fetal nuchal translucency, maternal serum free beta-hCG, and pregnancy-associated plasma protein A for first-trimester Down's syndrome screening.

PURPOSE: It has been proposed that first-trimester Down's syndrome screening has a higher detection rate compared to second-trimester biochemical screening. This study investigated the accuracy of Down's syndrome screening during gestational weeks 10 to 13 using the combination of fetal nuchal translucency (NT) measurement with maternal serum concentrations of free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A). METHODS: A total of 1,514 women with singleton pregnancies were enrolled in this study. Fetal NT was measured using the criteria published by the Fetal Medicine Foundation. Maternal serum concentrations of free beta-hCG and PAPP-A were determined by microtiter-plate ELISA. Down's syndrome risk was calculated using multivariate Gaussian distribution and Alpha software. RESULTS: Seventeen (1.12%) of the 1514 screened pregnancies had a fetal NT of at least 3 mm, and 41.2% of these had a poor pregnancy outcome, including four fetal aneuploidies. The odds of a fetal aneuploidy when the NT was greater than 2.0 multiples of median (MoM) was 90, when serum PAPP-A concentration was less than 0.45 MoM, it was 8.6, and when serum free beta-hCG concentration was greater than 2.2 MoM, it was 4.7. Using a risk cut-off level of 1 in 400, nine of 10 fetal aneuploidies were identified with a 4.7% false-positive rate, including two with trisomy 21, one with trisomy 18, and three with Turner's syndrome. CONCLUSIONS: This study demonstrated that Down's syndrome screening using the combined test in the first trimester had a higher detection rate than that of serum screening in the second trimester. Implementation of NT measurement in the first trimester provides substantial advantages for Down's syndrome detection and early diagnosis of fetal structural abnormalities.     

Cribado de aneuploidía en gestación gemelar: resultados de la aplicación del test combinado

Objective

To evaluate the effectiveness of the Combined Test for trisomy 21 screening in twin pregnancies. To assess the performance of biochemical markers and nuchal translucency (NT) measurement in pregnancies with euploid fetuses and in twin pregnancies with one or two affected fetuses. To compare the value of markers according to chorionicity and the mode of conception.

Material and methods

Retrospective study including 161 twin pregnancies. Maternal serum fß-hCG and PAPP-A were determined at 8 to 12 weeks and fetal NT was measured at 11 to 14 weeks. The individual risk of trisomy 21 was calculated in each fetus using the Combined Test. In monochorionic pregnancies, the single risk for the pregnancy was obtained with the largest NT. An invasive diagnostic procedure was offered when the risk was 1:250 or more in one or both of the fetuses.

Results

All trisomy 21 pregnancies were identified (three pregnancies and four fetuses) by the combined testfor a false-positive rate of 6.4% of pregnancies and 3.5% of fetuses. The median fß-hCG level, expressed in MoM, was 1.72 and the median PAPP-A level was 2.01. The median NT was 1.05 MoM. Both fß-hCG and PAPP-A levels were significantly decreased in monochorionic pregnancies and PAPP-A was significantly decreased in pregnancies resulting from assisted reproduction. No significant differences were observed in NT measurement between monochorionic and dichorionic fetuses or between those conceived naturally or by assisted reproduction.

Conclusions

The combined test shows high sensitivity and specificity in screening for trisomy 21 in twin pregnancies. The differences obtained in the biochemical markers according to chorionicity or the mode of conception require confirmation in further studies with a larger number or cases.     

Early pregnancy screening for fetal aneuploidy with serum markers and nuchal translucency.

We determined the aneuploidy detection rate achievable by early pregnancy screening with pregnancy associated plasma protein (PAPP)-A, free beta human chorionic gonadotrophin (hCG) and ultrasound nuchal translucency (NT) measurement. Women having prenatal diagnosis were scanned, and a blood sample was taken and stored. Stored samples were tested and a total of 37 were found to have Down syndrome, 8 to have Edwards syndrome and 255 were controls. Results were expressed in multiples of the gestation-specific median (MOM) value in the controls after regression and, for the serum markers, maternal weight adjustment. In Down syndrome the medians were for PAPP-A 0.63 MOM (95 per cent confidence interval (CI) 0.45-0.87); free beta-hCG 1.88 MOM (1.33-2.66); and NT 2.34 MOM (1.70-3.22). Using these parameters the expected detection rate for a 5 per cent false-positive rate for different marker combinations were: 55.3 per cent for PAPP-A and free beta-hCG; 68.4 per cent for NT alone; and 84.6 per cent for PAPP-A, free beta-hCG and NT. The median values for Edwards syndrome were: 0.17 MOM for PAPP-A; 0.18 MOM for free beta-hCG; and 2.64 MOM for NT. Early pregnancy screening with the combined measurement of maternal serum PAPP-A and free beta-hCG and fetal nuchal translucency could achieve a high Down syndrome detection rate.     

Second-trimester levels of pregnancy-associated plasma protein-A and free beta-hCG in pregnancies with trisomy 13

OBJECTIVE: To examine the levels of free beta-human chorionic gonadotrophin (free beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in second-trimester maternal serum from pregnancies affected by trisomy 13 and compare these with the known reduced levels of these markers in first-trimester cases in an attempt to better understand the pathophysiology of changes in marker levels in chromosomally abnormal pregnancies between the first and second trimester. METHODS: Using the Kryptor immunoassay system, we measured free beta-hCG and PAPP-A in 32 singleton pregnancies affected by trisomy 13 between 14 and 20 weeks of gestation. Using medians established in a previous study, these results were compared against 450 normal singleton pregnancies over the same gestational range. The data were combined with data from 82 cases of trisomy 13 previously examined in the first trimester (11-13 weeks) and an analysis of analyte trend was performed. RESULTS: The median free beta-hCG in multiples of the appropriate gestational median (MoM) in the second-trimester samples was not significantly different from the controls (1.15 (95% CI 0.827-1.651) vs 1.00). The median PAPP-A MoM in the second-trimester samples was significantly lower (p<0.001) than in controls (0.25 (95% CI 0.164-0.373) vs 1.00). Seventy-eight percent of cases were below the 5th centile of normal for PAPP-A. The combined cases in the first trimester had a median free beta-hCG MoM of 0.58 (95% CI 0.454-0.668) and a median PAPP-A MoM of 0.26 (95% CI 0.218-0.320). For PAPP-A, there was no significant change in median across the gestational period of 11 to 20 weeks, whilst for free beta-hCG, there was a significant increase with gestation (r=0.458, p<0.001). CONCLUSIONS: Although PAPP-A levels are reduced in trisomy 13 pregnancies in the second trimester, this isolated lower marker value is unlikely to be of value in screening for trisomy 13 in the second trimester. The aetiology of reduced levels of PAPP-A in cases with trisomy 13 may be similar to that in cases with trisomy 18, but different from that in cases with trisomy 21 since the temporal pattern in trisomies 13 and 18 are different from that in trisomy 21.     

Medically assisted reproduction and second-trimester maternal serum marker screening for Down syndrome

OBJECTIVES: To evaluate the effect of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) on total hCG, free ss-hCG, AFP and unconjugated estriol (uE3) used as markers for second-trimester Down syndrome maternal serum screening. METHODS: Second-trimester maternal sera from 1515 singleton pregnancies (970 by IVF, 545 by ICSI) were compared with control sera (21 014 cases). Free ss-hCG, total hCG, AFP and uE3 were compared between the control group and the medically assisted reproduction groups. The percentages of at-risk patients (>/=1/250) were also compared. RESULTS: No differences in values of the maternal serum markers were observed between the medically assisted and control groups. When maternal age was taken into account, the screen-positive rate for Down syndrome screening did not differ between the two groups. CONCLUSION: Patients undergoing assisted reproduction techniques can be counseled for maternal serum Down syndrome screening with the same efficacy as patients with naturally conceived pregnancies.     

First trimester screening for Down's syndrome after assisted reproductive technology: non-male factor infertility is associated with elevated free beta-human chorionic gonadotropin levels at 10-14 weeks of gestation

We retrospectively compared the first trimester Down's syndrome serum screening markers free beta-hCG (fbetahCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11-14 weeks of gestation in 4,088 women with naturally conceived pregnancies and in women pregnant after ICSI (n = 163), IVF (n = 59) and frozen-thawed embryo transfer (n = 31), and we searched for a potential relationship between infertility cause and marker levels. We found lower serum PAPP-A levels in pregnancies after IVF and ICSI compared with spontaneously conceived pregnancies and non-male factor infertility was associated with elevated serum fbetahCG levels at 11-14 weeks of gestation.     

A comparison between maternal serum free beta-human chorionic gonadotrophin and pregnancy-associated plasma protein A levels in first-trimester twin and singleton pregnancies

OBJECTIVES: To determine the levels of first-trimester free beta-human chorionic gonadotrophin (free betahCG), pregnancy-associated plasma protein A (PAPP-A) and nuchal translucency (NT) in twin pregnancies. METHODS: The study included 93 patients with twin pregnancy and 4,977 with singletons who underwent first-trimester testing using free betahCG, PAPP-A and NT at 10-13 weeks of gestational age. RESULTS: In twin pregnancies, the maternal serum free betahCG level was 2.18 higher and the PAPP-A level was 2.38 higher than in singleton pregnancies. These marker levels were significantly higher than the expected 2.0 multiples of the median (MoM). In contrast, NT values did not differ between twins and singletons. CONCLUSION: These data may be used to establish first-trimester combined screening for twin pregnancies.     

The effect of ICSI, maternal age, and embryonic stage on early clinical loss rate of twin versus singleton pregnancies

OBJECTIVES: To compare early loss rates between twin and singleton pregnancies following ART. STUDY DESIGN: First-trimester sonography counted the number of embryos with positive heartbeat in women undergoing IVF/ICSI and transfer of one to three embryos. The number of lost pregnancies was calculated from a second-trimester sonogram. Loss rates of the entire pregnancy were related to maternal age <38 or > or = 38 years, IVF or ICSI, and cleavage or blastocyst stage embryo transfers (in ICSI cases). RESULTS: Patients underwent IVF with (n = 672) and without (n = 189) ICSI. The overall odds of miscarrying the entire singleton pregnancy were 2.6 times that of a twin gestation (95% CI 1.5, 4.5). The disadvantage for singletons compared to twins seems more apparent in pregnancy after ICSI in the subgroup of patients <38 years (OR 2.9, 95% CI 1.5, 5.8). In this subgroup, the disadvantage conferred to singletons appeared only among days 2-3 embryo transfers (OR 3.0, 95% CI 1.3, 7.2). CONCLUSION: A significantly lower early spontaneous loss rate of twin pregnancies seems related to ICSI followed by cleavage stage embryo transfer in patients <38 years.     

Obstetric and neonatal risk of pregnancies after assisted reproductive technology: a matched control study

BACKGROUND: The aim of the study was to evaluate the obstetric and neonatal outcome of pregnancies after assisted reproduction technology (ART) in comparison with matched controls from spontaneous pregnancies. METHODS: A total of 12 920 deliveries at the Department of Obstetrics and Gynecology, University of Szeged, from 1 January 1995 to 31 December 2001 were subjected to retrospective analysis. Two hundred and eighty-four singleton, 75 twin and 17 triplet pregnancies after ovulation induction (n = 114; 30.3%), intrauterine insemination (n = 33; 8.8%) and in vitro fertilization (n = 229; 60.9%) were evaluated. The pregnancy outcome of the singleton and twin pregnancies was compared with that for controls matched with regard to age, gravidity and parity and previous obstetric outcome after spontaneous pregnancies. RESULTS: Twenty-four percent of the assisted reproductive pregnancies were multiple pregnancies. The incidences of singleton intrauterine growth retardation (IUGR) and preterm birth were reasonably similar to those among the controls (IUGR: 6.3% vs. 4.2%; preterm births: 13.0% vs. 9.9%, for the cases and the controls, respectively). As compared with the controls, there was an increased incidence of cesarean section among the singleton (41.2% vs. 34.5%, p = 0.12; OR 1.33; 95% CI 0.95-1.87) and twin assisted reproduction pregnancies (66.7% vs. 60.0%), but without significant differences. CONCLUSIONS: Increased obstetric risk could be observed concerning threatened preterm delivery and cesarean section rate in the study group. The perinatal outcome of singleton and twin pregnancies following assisted reproductive techniques is comparable with that of spontaneously conceived, matched pregnancies.     

First-trimester nuchal translucency and maternal serum free beta-hCG and PAPP-A can detect triploidy and determine the parental origin

OBJECTIVE: To evaluate the levels of first-trimester screening markers in triploid pregnancies and to determine the parental origin of triploidy. STUDY DESIGN: During the five-year study period, 12322 patients with singleton pregnancies underwent combined first-trimester screening using nuchal translucency (NT) and maternal serum free beta-human chorionic gonadotrophin (free beta-hCG) and pregnancy associated plasma protein-A (PAPP-A) at 10 to 14 weeks' gestation. Maternal serum markers and NT were evaluated in cases of triploidy. Molecular analysis was performed using polymorphic markers to establish the parental source of triploidy. RESULTS: Eight cases of triploidy were detected at a rate of at least 1 in 1540. All cases were electively terminated early in gestation or resulted in spontaneous miscarriage. Two patterns of first-trimester markers emerged: type I, characterized by extremely high levels of free beta-hCG and elevated NT; and type II, characterized by very low levels of PAPP-A and free beta-hCG with normal NT. Molecular analysis demonstrated that type I triploidy is of paternal origin (diandric) and type II is of maternal origin (digynic). CONCLUSIONS: On the basis of these results, it may be possible to detect triploid pregnancies in the first trimester and determine their origin using combined first-trimester screening.