No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Can a smaller than expected crown-rump length reliably predict the occurrence of subsequent miscarriage in a viable first trimester pregnancy?
Abstract
To elicit the diagnostic value of smaller than expected crown-rump length (CRL) to predict the occurrence of subsequent miscarriage in women with a viable first trimester pregnancy.
A cohort study was conducted in the fetal special care unit of a tertiary care maternity hospital. The recruited participants were young pregnant women at 6-13 weeks of gestation. Transvaginal ultrasonography was performed to determine pregnancy viability and measure the embryonic CRL. To compare the differences in CRL between those pregnancies that remained viable and those that subsequently miscarried, the deviation of observed and expected CRL was calculated and expressed in standard deviations (SD) as Z score. The primary outcome measure was the percentage of pregnancies with antecedent growth delay that miscarried by the end of the first trimester.
Of the pregnancies that subsequently miscarried, 79.3% (42/53) had smaller than expected CRL, and in 56.6% (30/53) the CRL was 2 SD or less from that expected for gestational age (GA). The mean Z score for CRL was significantly lower in pregnancies that subsequently miscarried compared to pregnancies that remained viable (-2.9 ± 2.6 vs -0.8 ± 2.1, respectively, P < 0.001). A CRL of 2 SD or less from that expected for GA as a cut-off point had a sensitivity of 56.6, specificity of 81.9, positive predictive value of 36.6, negative predictive value of 91.1, likelihood ratio positive of 3.1 and likelihood ratio negative of 0.5 in predicting subsequent miscarriage.
Viable first trimester pregnancies with small for GA CRL were associated with a higher probability of a subsequent miscarriage.
... Existing studies aimed to predict pregnancy loss have primarily investigated specific components of the first trimester ultrasound scan, including subchorionic hemorrhage, [1][2][3][4] fetal heart rate, [5][6][7][8] crown-rump length, [9][10][11] and yolk sac diameter. [12][13][14][15] Individually these factors have been associated with pregnancy loss. ...
... While prediction of subsequent pregnancy loss could be improved through joint examination of multiple sonographic features, most existing studies investigated individual components of the first trimester ultrasound, including subchorionic hemorrhage, 1-4 fetal heart rate, [5][6][7][8] crown-rump length, [9][10][11] and yolk sac diameter. [12][13][14][15] The current findings differ from previous studies of subchorionic hemorrhage, which reported elevated risk of pregnancy loss with hemorrhage overall 1,2 and with increasing size of hemorrhage, 3,4 although subchorionic hematoma has not been shown to be an independent risk factor for pregnancy loss once vaginal bleeding has been taken into account. ...
... This difference may be due to prior studies not having taken fetal heart rate and crown-rump length into account, which were more highly predictive of clinical loss in the current study. As expected, losses have been associated with lower heart rates [5][6][7][8]16,18,32,33 and smaller crown-rump lengths, [9][10][11]16,17,22,33 although when used, cut-points for these parameters are not based on prediction (fetal heart rate 5,7,10,33 and crown-rump length 11,33 ); rather, when data-defined, cut-points have been based on the distribution of the population examined. 10,33 One study used data to define gestational week-specific cut-points 8 and reported fetal heart rate cutpoints of ≤115 bpm for 6-7 weeks and ≤145 bpm for 7-8 weeks for elevated risk of pregnancy loss (vs ≤122 for 6 to <7 weeks and 123 for 7 to <8 weeks in our study). ...
Background
Pregnancy loss prediction based on routinely measured ultrasound characteristics is generally aimed towards distinguishing nonviability. Physicians also use ultrasound indicators for patient counseling, and in some cases to decide upon the frequency of follow-up sonograms. To improve clinical utility, allocation of cut-points should be based on clinical data for multiple sonographic characteristics, be specific to gestational week, and be determined by methods that optimize prediction.
Objectives
Identify routinely measured features of the early first trimester ultrasound and their gestational age specific cut-points that are most predictive of pregnancy loss.
Study design
A secondary analysis of 617 pregnant women enrolled in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial; all women had 1-2 previous pregnancy losses and no documented infertility. Each participant had a single ultrasound with a detectable fetal heartbeat between 6w 0d and 8w 6d. Cut-points for low fetal heart rate and small crown-rump length were separately defined for gestational weeks 6, 7, and 8 to optimize prediction. Identity and log-binomial regression models were used to estimate absolute and relative risks (RRs), respectively, and 95% confidence intervals (CI) between jointly categorized low fetal heart rate, small crown-rump length and clinical pregnancy loss. Adjusted models accounted for gestational age at ultrasound in weeks. Missing data were addressed using multiple imputation.
Results
64 women experienced a clinical pregnancy loss following the first ultrasound (10.4%), 7 were lost to follow-up (1.1%), and 546 (88.5%) women had a live birth. Low fetal heart rate and small crown-rump length (≤ 122, 123, and 158 bpm; ≤ 6.0, 8.5, and 10.9 mm for gestational weeks 6, 7, and 8, respectively) were independent predictors of clinical pregnancy loss, with greatest risks observed for pregnancies having both characteristics (RR 2.08 [95% CI: 1.24 to 2.91]). The combination of low fetal heart rate and small crown-rump length was linked to a 16% [95% CI: 9.1 to 23%] adjusted absolute increase in risk of subsequent loss, from 5.0% [1.5 to 8.5%] to 21% [15 to 27%]. Abnormal yolk sac diameter or the presence of a subchorionic hemmhorage did not improve prediction of clinical pregnancy loss.
Conclusions
Identified cut-points can be used by physicians for patient counseling, and in some cases to decide upon the frequency of follow-up sonograms. Specified criteria should not be used to diagnose non-viability.
... Early growth restriction, fetal heart rate, gestational sac diameter, and yolk sac diameter have been used as early predictors of subsequent miscarriage [9,10]. Conversely, the crown-rump length (CRL) measurement is also clinically used for predicting adverse pregnancy outcomes of threatened abortion or risk of spontaneous miscarriage in early pregnancy [11][12][13]. Most of these studies were hospital-based and conducted in developed countries with a small number of selected populations. ...
... A hospital-based study in London showed that the pregnancies with a CRL smaller than expected were more likely to be at risk for miscarriages [11]. Another hospital-based study in Egypt reported that approximately 60% of pregnancies that ended in subsequent miscarriage had smaller than expected CRL [12]. The present study shows that the risk of miscarriage increases with the advancing negative CRL z-score categories. ...
Fetal growth restriction in early pregnancy increases the risk of adverse pregnancy outcome, which has a significant social and psychological impact on women. There is limited information related to community-based study to evaluate early indicators related to miscarriage. The aim of this study is to examine the relationship between fetal growth restriction, measured by ultrasound crown-rump length (CRL), and subsequent occurrence of miscarriage in pregnant women in rural Bangladesh. The study was conducted within the Maternal and Infant Nutrition Interventions Trial in Matlab (MINIMat study), Bangladesh. A total of 4436 pregnant women were enrolled in the study when they were at less than 14 gestational weeks. The expected CRL was determined based on an established growth curve of gestational age and CRL, and deviation from this curve of CRL was expressed as a z-score. After identifying related covariates, the multiple Poisson regression model was used to determine the independent contribution from the CRL to miscarriage. A total of 3058 singleton pregnant women were included in analyses, with 92 miscarriages and 2966 continued pregnancies. The occurrence of miscarriages was significantly higher in the smaller categories of CRL z-score after adjustments for maternal age, parity, early pregnancy BMI, gestational age at CRL measurement and socioeconomic status (adjusted relative risk [95% confidence interval]: 1.03 [1.02–1.05] for less than -2 z-score). In a rural Bangladesh population, smaller than expected CRL for the gestational age was related to subsequent miscarriage. Ultrasound biometry information together with careful clinical assessment should provide much needed attention and care for pregnant women.
... [10] Also results of Batmaz et al, 2016 in their research agreed with the current study, they found that GS readings can help to distinguish between normal and abnormal pregnancies. [11] Also Jauniaux et al 2005 proved that in pregnancies with a live fetus at 6-10-weeks' gestation the rate of subsequent fetal loss is associated to maternal age, and the ultrasound findings of small GSD and fetal bradycardia (FHR bradycardia), relative to CRL. [12] Also, the current research is in accordance with many other researches as Balsane et al, [13] 2017, Agarwal et al, [14] 2017 and Abu Elghar et al, [15] 2013, S Abdulkadhim et al, [16] 2017found that with majority of patients with embryonic heart rate <100 BPM ended up with poor outcome. Regarding the FHR, Most of the patients who had poor first trimester outcome had EHR below 100 BPM. ...
Background: In early pregnancy, it is essential to emphasize viability, and gestational age precisely.Researchers have tried to discover some useful sonographic indicators in early pregnancy so as to expect theoutcome of the ongoing pregnancy. The aim of this study is to assess first-trimester ultrasound measurementsfor the prediction of early pregnancy loss.Subjects and Method: A prospective observational cohort study done in Tikrit city in outpatient clinic ofobstetrics and gynecology department in Salah Al-Deen General Hospital from1st February-31st August 2020. A random sample of 78 pregnant women selected, 8 were lost to follow up. Thedata collection done through a designed questionnaire, physical examination and transvaginal sonographyassessment. Sonography assessment of the crown rump length (CRL), yolk sac (YS) and gestational sac(GS) diameters, & fetal heart rate (FHR) are recording.Results: Seventy pregnant women examined by using transvaginal ultrasonography at 6th,9th and 12th weekof gestation. The readings at 6th week of gestation for the (GSD, YSD, CRL, and FHR) were (14.5±1.3),(3.2±1.8), (3.1±0.8), & (105±10.6) respectively, lower among those with first trimester loss than thosecontinue pregnancy (26.1±5.2), (3.9±0.3), (5.1±0.5), and (119±3). The readings at 12th week of gestationfor the (GSD, YSD, CRL, and FHR) were as follows; [(25.1±3.5), (3.6±0.3), (13± 2.1). & (165± 1)] werelower among with first trimester loss group than those continue pregnancy [(59.2±4.1), (4.5±0.7), (50.7±5.7)& (171±5)].Conclusions: The current study found that lower GSD, YSD, CRL, and FHR may indicate early pregnancyloss.
... Balsane et al. (10), Agarwal et al. (11), and Abu Elghar et al. (12) are only a few of the studies that agree with the findings of the current study. Abdulkadhim et al. showed that individuals whose embryonic heart rates were below 100 beats per minute had a poor prognosis. ...
Background: Pregnancy loss before 20 weeks is considered a miscarriage, as is the loss of a fetus weighing less than 500 grams before viability. A medical emergency, threatened miscarriage affects 15–25% of pregnancies. Aim and objectives: The goal of this study was to assess the predictive value of maternal blood levels of Cancer Antigen 125 (CA-125) and beta-human chorionic gonadotropin (B- HCG) in individuals at risk of miscarriage during the first trimester. Subjects and methods: This study was a prospective cohort study. This study included 120 pregnant women with threatened abortion between (6-11 weeks) and followed up till end of 14th week. Results: 36(30%) of pregnant women aborted, while 84(70%) of women continued till 14th weeks of pregnancy. At a cut-off value of 45 U/ml, the CA125 test was shown to have a sensitivity of 88.9% and a specificity of 77.5%, respectively, while also having a positive predictive value of 79.8% and a negative predictive value of 87.5%. At a cut-off value of 18.501 mlIU/ml, the B-HCG test's sensitivity and specificity were determined to be 96.3 and 88.9, respectively, with a positive predictive value of 89.7% and a negative predictive value of 96%. Conclusion: Even before fetal morphology can be investigated sonographically, abnormalities in the size of the yolk sac can be utilized as a good prognostic sign of early pregnancy loss. Pregnancy viability can be estimated from first trimester serum CA 125 and Beta HCG measurements.
... In our study as regard CRL, there was a statistically significant difference between GI and GII. Our findings agreed with Abuelghar et al. (14) who found that 56.6% of women who experienced abortion had CRL below the 5 th percentile with a sensitivity of 56.6% and specificity of 81.9% and a smaller than expected CRL reliably predict the occurrence of subsequent miscarriage in first trimester threatened abortion On the other hand, our results are not in agreement with Nibras et al. (15) , who reported that a smaller than expected crown to rump length for gestational age is not a prognostic factor for prediction of abortion in women presented with threatened miscarriage Our study found that there is a significant association between abnormal yolk sac diameter (<3 or >6) and miscarriage. These results are consistent with Sanam et al. (16) who reported that yolk sac diameter less than 2 mm or greater than 5 mm are at more risk of spontaneous miscarriage. ...
... 4 Ultrasound measurements like Gestational and yolk sac, fetal heart rate, and CRLare the ultrasound parameters used to evaluate viability and development of early pregnancy.CRL measurement is usually used to predict threatened abortion or spontaneous miscarriage in early pregnancy. [5][6][7] Various studies have reported an association between smaller-than-expected CRL and increased probability of miscarriage. [7][8][9] Most studies regarding adverse pregnancy outcomes and their association with CRLin early pregnancy are conducted in developed countries. ...
... (9) Also similar to the current study results, Odeh et al., 2009 compare gestational sac volume (GSV) between normal pregnancies, missed abortion and anembryonic pregnancies they found that GSV in missed abortion and anembryonic pregnancies are considerably smaller than normal pregnancies, starting at 7-weeks of gestational age. (10) Also results of Batmaz et al., 2016 in their research agreed with the current study, they found that GS readings can help to distinguish between normal and abnormal pregnancies (11) Also Jauniaux et al., 2005 proved that in pregnancies with a live fetus at 6-10-weeks' gestation the rate of subsequent fetal loss is associated to maternal age, and the ultrasound findings of small GSD and fetal bradycardia (FHR bradycardia), relative to CRL. (12) Also, the current research is in accordance with many other researches as Balsane et al., 2017 (13) , Agarwal et al., 2017 (14) and Abu Elghar et al., [15] 2013, S Abdulkadhim et al.,, 2017 (16) found that with majority of patients with embryonic heart rate <100 BPM ended up with poor outcome. Regarding the FHR, Most of the patients who had poor first trimester outcome had EHR below 150 BPM. ...
... Most existing studies investigate the individual components of the first-trimester ultrasound for predicting miscarriage [9,25,26]. Abnormal yolk sac size and appearance have been reported to be useful markers for miscarriage prediction before the demonstration of fetal viability [27]. However, in presence of an established viable intrauterine pregnancy, its usefulness is limited. ...
Background
It is challenging to predict the outcome of the pregnancy when fetal heart activity is detected in early pregnancy. However, an accurate prediction is of importance for obstetricians as it helps to provide appropriate consultancy and determine the frequency of ultrasound examinations. The purpose of this study was to investigate the role of the convolutional neural network (CNN) in the prediction of spontaneous miscarriage risk through the analysis of early ultrasound gestational sac images.
Methods
A total of 2196 ultrasound images from 1098 women with early singleton pregnancies of gestational age between 6 and 8 weeks were used for training a CNN for the prediction of the miscarriage in the retrospective study. The patients who had positive fetal cardiac activity on their first ultrasound but then experienced a miscarriage were enrolled. The control group was randomly selected in the same database from the fetuses confirmed to be normal during follow-up. Diagnostic performance of the algorithm was validated and tested in two separate test sets of 136 patients with 272 images, respectively. Performance in prediction of the miscarriage was compared between the CNN and the manual measurement of ultrasound characteristics in the prospective study.
Results
The accuracy of the predictive model was 80.32% and 78.1% in the retrospective and prospective study, respectively. The area under the receiver operating characteristic curve (AUC) for classification was 0.857 (95% confidence interval [CI], 0.793–0.922) in the retrospective study and 0.885 (95%CI, 0.846–0.925) in the prospective study, respectively. Correspondingly, the predictive power of the CNN was higher compared with manual ultrasound characteristics, for which the AUCs of the crown-rump length combined with fetal heart rate was 0.687 (95%CI, 0.587–0.775).
Conclusions
The CNN model showed high accuracy for predicting miscarriage through the analysis of early pregnancy ultrasound images and achieved better performance than that of manual measurement.
... Abuelghar et al. 9 detailed that 56.6 % of ladies who experienced abortion had CRL beneath the 5th percentile, and this variable anticipated early abortion with a sensitivity of 56.6 %, specificity of 81.9 %, positive predictive value (PPV) of 36.6 %, negative predictive value (NPV) of 91.1 %, and likelihood ratio positive of 3.15. D'Antonio et al. 10 found that CRL below the 5th percentile was related with abortion with an odds ratio of 2.21 (P = 0.023) 10. ...
BACKGROUND
Early pregnancy failure is stated as noncompatible, intrauterine pregnancy with
either an empty gestational sac or a gestational sac that contains an embryo or
fetus which does not have any fetal cardiac activity in the initial 12 weeks of the
pregnancy. In the assessment of early pregnancy, ultrasound plays a significant
role.
METHODS
A prospective observational study was conducted in a tertiary care hospital
between May 2019 and April 2020 among 500 pregnant females fulfilling the
inclusion and exclusion criteria. Patient follow up was done by weekly telephonic
calls until completing 12 weeks gestation or reporting miscarriage. Also, all
patients were followed by the recommended routine ultrasound (US) scanning
with or without emergency visits.
RESULTS
In our study period, 500 women fulfilling the inclusion criteria were included in our
study. Out of whom, 85 (17.5 %) women had an early pregnancy failure (before
12 weeks). There was significantly lower mean gestational sac diameter (GSD),
crown to rump length (CRL), fetal heart rate (FHR), and P-value < 0.001 in women
who experienced early pregnancy failure. In pregnancies where the GSD, CRL, and
FHR were below the 5th percentile, early pregnancy failure was a more prone
outcome. All pregnancies with FHR below 75 beats per minute ended in failure in
the present study. When FHR was less than 128 beats per minute, there was
enormous rise in the frequency of pregnancy failure. By comparison, yolk sac
diameter (YSD) was a less significant predictor of early pregnancy failure.
CONCLUSIONS
First-trimester ultrasonographic estimations help in predicting early abortion. Risk
appraisal tables dependent on combinations of abnormal parameters could
significantly help in identifying abnormal pregnancy from normal pregnancy and
could improve prediction rates.
... Also Jauniaux et al 2005 confirmed that in pregnancies with a live fetus at 6-10-weeks' gestation the rate of subsequent fetal loss is related to maternal age, cigarette smoking, history of vaginal bleeding and the ultrasound findings of small GSD and fetal bradycardia, relative to CRL. 10 Also, our study is in agreement with many other studies as Balsane et al, 2017 and Abu Elghar et al, 2013 [11][12][13] In contrast to our study, Oh et al, 2002 found no significant relationship between gestational sac and normal and abnormal pregnancy outcome. 14 Also Abdallah et al, 2011 found that slow or absent gestational sac growth is not necessarily associated with miscarriage. ...
Background Ongoing technological advancements have allowed the resolution of ultrasound imaging in the first trimester to evolve to a level at which early fetal development can be assessed and monitored in detail. Objective To find a relation between first-trimester ultrasound fetal measurements and adverse pregnancy outcomes. Subjects and Methods A prospective observational cohort study conducted on 500 pregnant women at 1st trimester attending ANC clinic of obs& gyne. department of Al-Azhar university hospital (Assiut -Egypt). Ultrasound measurements of early fetal parameter GSD, CRL and YSD at 5-12 weeks of gestation were done. Results of measurements were classified into three classes, class A<10th centile, class B 10th-90th centile and Class C>90th centile. Patients were followed up throughout pregnancy to determine normal and abnormal outcomes in each class. Comparison between different classes was made to show association with abnormal pregnancy outcomes. Results Early fetal ultrasonographic parameters class A & C were significantly associated with 1st, 2nd-trimester abortions, IUFD, APH and PROM (p<0.001) with no significant association between these parameters and other pregnancy outcomes (p>0.05). Conclusion Our study emphasizes the role of early ultrasound in predicting abnormal pregnancy outcomes it could be useful to obstetricians to anticipate adverse outcomes and being warned to manage prenatal care and delivery more appropriately. Recommendation Early fetal ultrasound should be used as a tool to predict pregnancy outcome so as to manage prenatal care and delivery more efficiently
... Also Jauniaux et al 2005 confirmed that in pregnancies with a live fetus at 6-10-weeks' gestation the rate of subsequent fetal loss is related to maternal age, cigarette smoking, history of vaginal bleeding and the ultrasound findings of small GSD and fetal bradycardia, relative to CRL. 10 Also, our study is in agreement with many other studies as Balsane et al, 2017 and Abu Elghar et al, 2013 [11][12][13] In contrast to our study, Oh et al, 2002 found no significant relationship between gestational sac and normal and abnormal pregnancy outcome. 14 Also Abdallah et al, 2011 found that slow or absent gestational sac growth is not necessarily associated with miscarriage. ...
Citation: Al Darwish AG, Fouad M, Nasr AAM, Mohammed AE, Selim SA, Elsabour HA. Early ultrasound fetal parameters as a predictor for pregnancy outcome: A prospective observational cohort study. Gyne and Obste Open A Open J. 2019; I(1): 7-12 Background Ongoing technological advancements have allowed the resolution of ultrasound imaging in the first trimester to evolve to a level at which early fetal development can be assessed and monitored in detail. Objective To find a relation between first-trimester ultrasound fetal measurements and adverse pregnancy outcomes. Subjects and Methods A prospective observational cohort study conducted on 500 pregnant women at 1st trimester attending ANC clinic of obs& gyne. department of Al-Azhar university hospital (Assiut-Egypt). Ultrasound measurements of early fetal parameter GSD, CRL and YSD at 5-12 weeks of gestation were done. Results of measurements were classified into three classes, class A<10 th centile, class B 10th-90th centile and Class C>90 th centile. Patients were followed up throughout pregnancy to determine normal and abnormal outcomes in each class. Comparison between different classes was made to show association with abnormal pregnancy outcomes. Results Early fetal ultrasonographic parameters class A & C were significantly associated with 1 st , 2 nd-trimester abortions, IUFD, APH and PROM (p<0.001) with no significant association between these parameters and other pregnancy outcomes (p>0.05). Conclusion Our study emphasizes the role of early ultrasound in predicting abnormal pregnancy outcomes it could be useful to obstetricians to anticipate adverse outcomes and being warned to manage prenatal care and delivery more appropriately. Recommendation Early fetal ultrasound should be used as a tool to predict pregnancy outcome so as to manage prenatal care and delivery more efficient.
... In the current study, the CRL cutoff value of 22 mm was obtained with a sensitivity of and specificity of 46.9% and 42.3%, respectively. On the other hand, Abuelghar et al. [28] found that 56.6% of women who experienced abortion had CRL below the 5th percentile with a sensitivity of 56.6% and specificity of 81.9%. ...
Aim: To evaluate the role of ultrasound (US) as a predictor of pregnancy outcome in cases with threatened miscarriage.Introduction: First trimester bleeding is a common anxious medical disorder. It may end with pregnancy loss or lead to adverse maternal and fetal outcomes. Certain sonographic parameters like (GSD, YSD, CRL, and FHR) could predict these outcomes.Material and methods: A prospective study involving 500 women in their first trimester was divided into three groups: group I (130 women) in whom threatened abortion ended in abortion, group II (170 women) with threatened abortion and completed their pregnancy and group III (200 women) with normal pregnancy. US indicators included Gestational Sac Diameter (GSD), Yolk Sac Diameter (YSD), Crown-Rump Length (CRL), and Fetal Heart Rate (FHR). These patients were evaluated for the pregnancy outcomes.Results: A significant difference was found between group I and the other two groups regarding FHR and CRL (P<0.05), while no significant difference was observed among the three groups regarding GSD or YSD. Compared to control group, the cases of group II had a higher incidence of premature rupture of membrane PROM (OR=9.9, P<0.05), gestational hypertension (OR=5.4, P<0.05), and placental abruption (OR=4.8, P<0.05).Conclusion: FHR and CRL are good sonographic markers to predict pregnancy outcome in women with threatened miscarriage. FHR at 115 beat/minute yields the best predictivity and CRL at 22 mm yields the least predictive accuracy.
... It is well known that first-trimester growth is associated with pregnancy outcome [7][8][9][10] and that several factors like maternal factors and dietary pattern influence first-trimester growth [11][12][13]. Traditionally, first-trimester fetal growth has been documented by two-dimensional (2D) crown-rump length (CRL) measurements. ...
Background. With the introduction of three-dimensional (3D) ultrasound it has become possible to measure volumes. The relative increase in embryonic volume (EV) is much larger than that of the crown-rump length (CRL) over the same time period. We examined whether EV is a better parameter to determine growth restriction in fetuses with structural congenital abnormalities. Study Design, Subjects, and Outcome Measures. CRL and EV were measured using a Virtual Reality (VR) system in prospectively collected 3D ultrasound volumes of 56 fetuses diagnosed with structural congenital abnormalities in the first trimester of pregnancy (gestational age 7 ⁺⁵ to 14 ⁺⁵ weeks). Measured CRL and EV were converted to z -scores and to percentages of the expected mean using previously published reference curves of euploid fetuses. The one-sample t -test was performed to test significance. Results. The EV was smaller than expected for GA in fetuses with structural congenital abnormalities (−35% p<0.001 , z -score −1.44 p<0.001 ), whereas CRL was not (−6.43% p=0.118 , z -score −0.43 p=0.605 ). Conclusions. CRL is a less reliable parameter to determine growth restriction in fetuses with structural congenital abnormalities as compared with EV. By measuring EV, growth restriction in first-trimester fetuses with structural congenital abnormalities becomes more evident and enables an earlier detection of these cases.
... It is not surprising that embryonic growth is related to fetal growth in the second and third trimester of pregnancy and to newborn birthweight (Mook-Kanamori et al. 2010;van Uitert et al. 2013b). Moreover, when an embryo is relatively small, it has an increased risk of complications during pregnancy, such as fetal chromosomal abnormalities, miscarriage, low birthweight, fetal growth restriction and prematurity (Smith et al. 1998;Bukowski et al. 2007;Mook-Kanamori et al. 2010;Salomon et al. 2011;Abuelghar et al. 2013;Baken et al. 2013;van Uitert et al. 2013avan Uitert et al. , 2013b. In future, it would be interesting to see whether not only embryonic size, but also embryonic developmental stages are affected by environmental exposures. ...
The worldwide epidemic of non-communicable diseases (NCD), including obesity, is a burden to which poor lifestyles contribute significantly. Events in early life may enhance susceptibility to NCD, with transmission into succeeding generations. This may also explain, in part, why interventions in adulthood are less effective to reduce NCD risk. New insights reveal that the early embryo, in particular, is extremely sensitive to signals from gametes, trophoblastic tissue and periconception maternal lifestyles. Embryonic size and growth as determinants of embryonic health seem to impact future health. A relatively small embryo for gestational age is associated with pregnancy complications, as well as with the risk of early features of NCD in childhood. Although personal lifestyles are modifiable, they are extremely difficult to change. Therefore, adopting a life course approach from the periconception period onwards and integrated into patient care with short-term reproductive health benefits may have important implications for future prevention of NCD. The current reproductive population is used to Internet and social media. Therefore, they can be reached via mobile phone (mHealth) platforms that provide personalised lifestyle (pre)pregnancy programs. This will offer opportunities and possibly great benefits for the health of current and succeeding generations.
Background
Symptoms like vaginal bleeding or abdominal pain in early pregnancy can create anxiety about potential miscarriage. Previous studies have demonstrated ultrasonographic variables at the first trimester transvaginal scan (TVS) which can assist in predicting outcomes by 12 weeks gestation.
Aim
To validate the miscarriage risk prediction model (MRP) in women who present with a viable intrauterine pregnancy (IUP) at the primary ultrasound.
Materials and Methods
A multi‐centre diagnostic study of 1490 patients was performed between 2011 and 2019 for retrospective external and 2017–2019 for prospective temporal validation. The reference standard was a viable pregnancy at 12 + 6 weeks. The MRP model is a multinomial logistic regression model based on maternal age, embryonic heart rate, logarithm (gestational sac volume/crown‐rump length (CRL)) ratio, CRL and presence or absence of clots.
Results
Temporal validation data from 290 viable IUPs were collected: 225 were viable at the end of the first trimester, 31 had miscarried and 34 were lost to follow‐up. External validation data from 1203 viable IUPs were collected at two other ultrasound units: 1062 were viable, 69 had miscarried and 72 were lost to follow‐up. Temporal validation with a cut‐off of 0.1 demonstrated: area under the curve (AUC) of 0.8 (0.7–0.9), sensitivity 66.7%, specificity 83.9%, positive predictive value (PPV) 35.7%, negative predictive value (NPV) 94.9%, positive likelihood ration (LR+) 4.1 and negative LR (LR−) 0.4. External validation demonstrated: AUC 0.7 (0.7–0.8), sensitivity 44.9%, specificity 90.4%, PPV 23.3%, NPV 96.2%, LR+ 4.6 and LR− 0.6 (0.4–0.7).
Conclusion
The MRP model is not able to be used in real time for counselling, and management should be individualised.
Objective:
To evaluate the relationship between endometrial thickness measured before embryo transfer, and pregnancy outcomes in frozen-thawed embryo transfer (FET).
Methods:
We retrospectively analyzed outcomes of all consecutive FET cycles, from January 2012 to August 2018. Based on ROC analysis for endometrial thickness, we found 8 mm was a reliable cutoff point to predict pregnancy prior to embryo transfer. Accordingly, the cycles were divided into Group A: cycles with endometrial thickness ≤ 8 mm and Group B: > 8 mm.
Results:
Group A included 485 FET cycles and group B included 626 cycles. Compared with group A, Group B had significantly higher chemical and clinical pregnancy rates (30.3 vs. 24.6%; p = .046, and 24.0 vs. 18.6%; p = .036), respectively. In multivariate analysis, endometrial thickness and the protocols used were the only parameters influencing the chance to achieve pregnancy, with odds ratio 1.54 (95%CI 1.07-2.22, p = .019) for the endometrium and odds ratio 1.95 (95%CI 1.31-2.9; p = .001) to the protocol used. Endometrial thickness might predict crown-rump length (CRL) discordancy with odds ratio 4.61 (p = .001; 95% CI 1.42-14.92). Compared with group B, Group A had more cases of overt discordancy (13.3 vs. 4%; p = .016).
Conclusions:
For patients undergoing FET cycles, endometrial thickness and treatment protocol may predict the chemical and clinical pregnancy rates, as well as CRL discordancy.
Summary:
Endometrial thickness and preparation improved pregnancy rate in FET cycles and significantly greater crown-rump length discordancy was observed with thinner endometria.
Research question:
This study aimed to evaluate the association between discordance in crown-rump length (CRL) and adverse pregnancy and perinatal outcomes in dichorionic twin pregnancies.
Design:
This was a retrospective cohort study of dichorionic twin pregnancies after IVF that showed two live fetuses at the first ultrasound scan between 6 +5 and 8 weeks gestational age from 1 January 2015 to 31 December 2016. Study groups were defined by the presence or absence of 20% or more discordance in CRL. The primary outcomes were early fetal loss of one or both fetuses before 12 weeks and birthweight discordance. Secondary outcomes included fetal anomalies, fetal loss between 12 and 28 weeks, stillbirth, small for gestational age (SGA) at birth, low birthweight (LBW), very low birthweight (VLBW), admission to the neonatal intensive care unit (NICU) and preterm delivery (PTD).
Results:
CRL-discordant twin pregnancies were more likely to end in the loss of one fetus before 12 weeks' gestation (odds ratio [OR] 15.877, 95% confidence interval [CI] 10.495-24.019). Discordant twin pregnancies with twin deliveries had a significantly higher risk of birthweight discordance (OR 1.943, 95% CI 1.032-3.989). There was no significant difference in perinatal outcomes including fetal anomalies, PTD, LBW, VLBW, SGA, neonatal death and admission to NICU between singleton or twin deliveries.
Conclusions:
Discordant twin pregnancies were at increased risk of one fetal loss prior to 12 weeks' gestation. Except for birthweight discordance, there was no significant difference between CRL discordance and other adverse perinatal outcomes.
Both ultrasound and biochemical markers either alone or in combination have been described in the literature for the prediction of miscarriage. We performed this systematic review and meta-analysis to determine the best combination of biochemical, ultrasound and demographic markers to predict miscarriage in women with viable intrauterine pregnancy. The electronic database search included Medline (1946-June 2017), Embase (1980-June 2017), CINAHL (1981-June 2017) and Cochrane library. Key MESH and Boolean terms were used for the search. Data extraction and collection was performed based on the eligibility criteria by two authors independently. Quality assessment of the individual studies was done using QUADAS 2 (Quality Assessment for Diagnostic Accuracy Studies-2: A Revised Tool) and statistical analysis performed using the Cochrane systematic review manager 5.3 and STATA vs.13.0. Due to the diversity of the combinations used for prediction in the included papers it was not possible to perform a meta-analysis on combination markers. Therefore, we proceeded to perform a meta-analysis on ultrasound markers alone to determine the best marker that can help to improve the diagnostic accuracy of predicting miscarriage in women with viable intrauterine pregnancy. The systematic review identified 18 eligible studies for the quantitative meta-analysis with a total of 5584 women. Among the ultrasound scan markers, fetal bradycardia (n=10 studies, n=1762 women) on hierarchical summary receiver operating characteristic showed sensitivity of 68.41%, specificity of 97.84%, positive likelihood ratio of 31.73 (indicating a large effect on increasing the probability of predicting miscarriage) and negative likelihood ratio of 0.32. In studies for women with threatened miscarriage (n=5 studies, n=771 women) fetal bradycardia showed further increase in sensitivity (84.18%) for miscarriage prediction. Although there is gestational age dependent variation in the fetal heart rate, a plot of fetal heart rate cut off level versus log diagnostic odds ratio showed that at ≤110 beat per minutes the diagnostic power to predict miscarriage is higher. Other markers of intra uterine hematoma, crown rump length and yolk sac had significantly decreased predictive value. Therefore in women with threatened miscarriage and presence of fetal bradycardia on ultrasound scan, there is a role for offering repeat ultrasound scan in a week to ten days interval.
Objective(s):
To determine whether an association exists between small crown-rump length (CRL) and adverse obstetrical outcomes in pregnancies conceived by IVF and to compare a CRL reference based on IVF pregnancies to a reference based on spontaneous pregnancies.
Design:
Retrospective cohort study. CRL was classified as small by comparing it with the local university hospital maternal fetal medicine standard and the Monash IVF reference chart.
Setting:
University-affiliated fertility center.
Patient(s):
Singleton pregnancies conceived by IVF with ultrasounds performed between 7+0 and 8+6 weeks of gestational age.
Intervention(s):
None.
Main outcome measure(s):
Pregnancy loss, preterm birth, and low birth weight.
Result(s):
Included were 940 clinical pregnancies. The overall and CRL-discrepant miscarriage rates were 12.7% and 41%, respectively. When CRL was small, the maternal age-adjusted odds of miscarriage were 13.8 times higher (95% confidence interval [CI], 8.9-21.6). At age 30, small CRL was associated with a 30% risk of miscarriage, versus 61% at age 45. There was no association between small CRL and preterm birth or low birth weight. The sensitivity and specificity for predicting miscarriage from the optimal Monash cut point were 0.69 (95% CI, 0.61-0.77) and 0.84 (95% CI, 0.82-0.87), which were similar to those of the CRL reference based on spontaneous pregnancies.
Conclusion(s):
Small CRL in IVF pregnancy was strongly associated with miscarriage, especially in the context of advanced maternal age. Small CRL was not associated with preterm birth or low birth weight. A CRL reference based on IVF pregnancies was equivalent to the standard reference for predicting miscarriage.
Objective:
To assess first-trimester ultrasound measurements for the prediction of early spontaneous abortion.
Methods:
In a prospective observational study in Jamshedpur, India, women with a singleton pregnancy of 42-76 days were enrolled between November 2014 and April 2016. Inclusion criteria were spontaneous conception, embryonic cardiac activity, and regular menstrual cycle. Fetal crown-to-rump length (CRL), gestational sac diameter (GSD), yolk sac diameter (YSD), and fetal heart rate (FHR) were measured by transvaginal ultrasonography. Ultrasonography was repeated at 12 weeks and beyond to determine pregnancy continuation.
Results:
Among 800 women, 140 (17.5%) experienced early spontaneous abortion. CRL, GSD, and FHR values below the 5th percentile (odds ratio [OR] 26.48, 26.94, and 100.63, respectively), and YSD above the 95th percentile (OR 1.04) were predictors of early abortion. Normal YSD did not reduce the risk of abortion if the other three parameters were below the 5th percentile (OR 34.27). For every 10-bpm decrease in FHR below 130, there was 26.7% increased risk of abortion. GSD-CRL difference of less than 5 mm was associated with a higher likelihood of abortion (OR 4.88).
Conclusion:
First-trimester ultrasound measurements are predictors of early abortion. Risk assessment tables based on combinations of abnormal measures might improve prediction rates. This article is protected by copyright. All rights reserved.
Embryonic growth and development differ between pregnancies. Constitutional maternal characteristics and environmental influences affect embryonic size. Slowed embryonic growth is associated with an increased risk of gestational complications such as foetal growth restriction. A child who was small when an embryo is also at more risk of having an adverse cardiovascular risk profile at 6 years of age. The importance of embryonic health means that preconception care needs to be generally available.
Functional linear discriminant analysis (FLDA) is a new growth assessment technique using serial measurements to discriminate between normal and abnormal fetal growth. We used FLDA to assess and compare growth in live pregnancies destined to miscarry with those remaining viable.
This was a prospective cohort study of women with ultrasound scans on at least two separate occasions showing live pregnancies. Serial crown-rump length (CRL), mean gestational sac diameter and mean yolk sac diameter measurements were recorded. The ability of FLDA to predict subsequent miscarriage was compared with that of a single CRL measurement.
Of 521 included pregnancies, 493 (94.6%) remained viable at 14 weeks and 28 (5.4%) miscarried. The CRL growth rate was significantly lower in those that miscarried (one-sample t-test, P = 2.638E-22). The sensitivity of FLDA in predicting miscarriage from serial CRL measurements was 60.7% and specificity was 93.1% [positive predictive value (PPV) 33.3%, negative predictive value (NPV) 97.7%]. This was significantly better for predicting miscarriage than a single CRL observation of more than 2SD below that expected (sensitivity 53.6%, specificity 72.2%, PPV 9.9%, NPV 96.5%).
FLDA discriminates between normal and abnormal growth to predict miscarriage with high specificity. FLDA predicts miscarriage better than a single observation of a small CRL.
Measurement of embryonic or foetal size using the greatest length of the embryo or foetal crown rump length can be used to accurately determine the gestational age of a normal first trimester pregnancy to within three to five days. Transvaginal ultrasound scan can be used to measure the size of an embryo and gestation sac earlier than transabdominal ultrasound. The original Robinson curve used for dating pregnancies is still valid in most cases. Ultrasound dating in the first trimester is now recommended for all women with spontaneous pregnancies, even those with certain menstrual dates. First trimester growth in normal pregnancy is not uniform and is influenced by both maternal and foetal factors. Early foetal growth restriction is demonstrated in many pregnancies that subsequently end in first trimester miscarriage and is also demonstrated in fetuses with triploidy, trisomy 18 and possibly trisomy 13. Pregnancies which are small at the 11-14 week ultrasound scan appear to be at risk of later intrauterine growth restriction, preeclampsia and preterm delivery. Cross-sectional and serial measurement of foetal growth in the first trimester may be helpful in predicting both miscarriage and adverse late pregnancy outcomes.
To examine whether viable early pregnancies that subsequently end in miscarriage exhibit evidence of first-trimester growth restriction.
Prospective cohort study.
Early pregnancy unit (EPU) of a teaching hospital.
Women attending EPU between 5 and 10 weeks of gestation.
Women with spontaneously conceived intrauterine, viable singleton pregnancies with certain last menstrual period and regular cycles were included. The deviation between the observed and expected crown-rump length (CRL) for gestation was calculated and expressed as a z score. Pregnancies were followed up until the 11-14 week scan, and the deviation between those that remained viable and miscarried subsequently was calculated.
Viability at 11-14 week scan.
Over 6 months, 316 women met the inclusion criteria. Twenty-four (7.4%) women were excluded. Of the remaining 292, the pregnancy remained viable in 251 (86%) and 41 (14%) suffered a miscarriage. At the first transvaginal ultrasound, the z score of the mean measured CRL for pregnancies that remained viable was -0.82, SD 1.46, while in pregnancies that subsequently miscarried the z score was -2.42 and the CRL was significantly smaller, SD 1.31 (P < 0.0001). In the latter group, the initial CRL was below the expected mean for gestational age in all women, while in 61% (25/41), the CRL was at least 2 SDs below the expected mean.
CRL was significantly smaller in pregnancies that subsequently ended in miscarriage. This suggests that early first-trimester growth restriction is associated with subsequent intrauterine death.
In a study to evaluate the reproducibility and accuracy of the sonar technique of measurement of the in vivo fetal crown-rump length (Robinson, 1973), a series of in vivo and in vitro experiments was performed in which the random and systematic errors inherent in the technique were assessed. The potential sources of random error were those of operator judgement, movement of the fetus and mother, machine sensitivity settings and measurement from the photograph; while the sources of systematic error were those of oscilloscope scale factor, and velocity calibration inaccuracies, and the effect of beam width. The overall effect of the random errors, that is, the reproducibility of the technique, was assessed in an in vivo blind trial in which three independent measurements were made of the fetus. In a series of 30 experiments the average standard deviation of the three readings was found to be 1.2 mm. Evaluation of the systematic errors by in vivo experimentation, on the other hand, showed that the basic sonar measurements were in error by an overestimate of 1 mm for the beam width effect and 3.7 per cent for the scale factor and velocity calibration errors. A weighted non-linear regression analysis of 334 measurements was performed in order to obtain a "curve of best fit" for the period covering 6 to 14 weeks of menstrual age. The values obtained were corrected for the systematic errors and compared with widely quoted anatomical figures. In the second part of this investigation the original data was further analyzed to determine on a statistical basis the accuracy of the technique as a method of estimating maturity. It was shown that such an estimate could be made to within 4.7 days with a 95 per cent probability on the basic of a single measurement, and to within 2.7 days if three independent measurements were made.
A method is reported by which the "in utero" crown-rump length of the fetus may be determined by sonar in the first trimester of pregnancy. The accuracy of the technique was assessed by comparing the sonar and the direct postabortum measurements of fetuses in cases of missed abortion. A normal curve of fetal crown-rump length was derived from 214 examinations on 80 patients and by using these values in a further "blind" series it was found possible to predict the maturity of pregnancy to within three days, between the sixth and the 14th weeks of pregnancy.
Out of 255 patients with threatened abortion 67 gave a regular menstrual history and at ultrasound examination had a live fetus with a crown-rump length (CRL) of 10-65 mm, equivalent to a gestational age of 7-13 weeks. The CRL of these fetuses was smaller than expected from their menstrual age (P less than 0.01). For this phenomenon we suggest the term early fetal growth delay. Seven patients aborted and one experienced intrauterine fetal death. These eight fetuses had on average smaller CRL than the remainder 59 fetuses (P less than 0.05). Fetal growth delay may therefore be considered a risk factor in threatened abortion.
Our purpose was to investigate whether fetuses with aneuploidies demonstrate evidence of growth retardation during the first trimester.
This was a retrospective, cross-sectional study of singleton pregnancies undergoing fetal karyotyping at 10 to 13 weeks' gestation. Measurements of crown-rump length in 135 chromosomally abnormal fetuses were compared with those in 700 chromosomally normal fetuses.
The median crown-rump length of fetuses with trisomy 18 (n = 32) was significantly reduced. In contrast, in fetuses with trisomy 21 (n = 72), trisomy 13 (n = 11), 47,XXX (n = 6), 47,XXY (n = 6), 45,X (n = 5), and triploidy (n = 3) the crown-rump length was not lower than normal.
At 10 to 13 weeks' gestation fetuses with trisomy 18 are growth retarded, whereas in trisomy 21, trisomy 13, and sex chromosome aneuploidy growth is normal.
The objective of this study was to determine if measurement of initial crown--rump length (CRL) is helpful in predicting low birth weight, newborn length, spontaneous abortions, or abortus karyotype. We measured CRL prospectively in 837 consecutive singleton pregnancies at the time a heart rate was first detectable with transvaginal ultrasonography and compared these measurements to normal values for the 10th through 90th centiles determined from 227 transvaginal ultrasound measurements in in-vitro fertilization and gamete intra-Fallopian transfer pregnancies with known ovulation dates. The relationship of initial CRL to birth weight and length and to abortion and abortus karyotype was analysed after all pregnancies had delivered. Initial CRL measured after the 28th post-ovulation day was predictive of subsequent abortion, but not of low birth weight or length. The abortion rate was 3.3% [95% confidence interval (CI) 1.5%, 5.1%] when initial CRL > or = 50th centile, compared to 19.4% (95% CI 15.4%, 23.4%) when < 50th centile. Initial CRL was < 50th centile in 13 out of 14 trisomic and in eight out of 10 other karyotypically abnormal aborti. These results indicate that initial CRL measured after the 28th post-ovulation day may help to identify pregnancies at increased risk of abortion due to abnormal karyotypes.
A retrospective comparison of cytogenetic and ultrasound findings in first trimester spontaneous fetal loss after demonstration of cardiac activity was made. The crown-rump length (CRL) was measured twice for each fetus resulting in spontaneous abortion: (i) CRL was measured in the viable state while demonstrating cardiac activity, and the growth deviation was expressed as the measured/expected CRL ratio (M/E CRL ratio); (ii) in the same fetus, CRL was measured after confirmation of fetal death, and designated as the post-mortem CRL. The chorionic tissues of these abortuses were karyotyped. The CRL of fetuses which resulted in normal deliveries were also measured as controls. As a result, 16 of 24 abortuses displayed an abnormal chromosomal analysis (67%). The mean M/E CRL ratio of still-viable fetuses was smaller than that of control fetuses (0.74 +/- 0.20 versus 0.98 +/- 0.13 respectively, P < 0.01). The differences in ratio between karyotypically normal and abnormal abortuses were not statistically significant. The post-mortem CRL of dead fetuses was > 20 mm in four of five monosomy X, two of three 21-trisomy, one of three triploidy and none of eight embryos with normal karyotype and five other trisomies. In conclusion, our study demonstrated that the M/E CRL ratio could be used as a predictor of spontaneous abortions, although it does not discriminate abnormal karyotypes from normal ones. The embryos with a post-mortem CRL more than 20 mm have a higher likelihood of suffering monosomy X or 21-trisomy. The ultrasonographic findings might offer a cytogenetic clue as to a possible cause to the developmental arrest.
The objective of our study was to investigate the relationship between sonographic findings and the occurrence of abortion in pregnancies complicated by first-trimester bleeding in which fetal cardiac activity was documented upon admission.
A prospective study of transvaginal sonography was performed in 270 pregnant patients with bleeding between 5 and 12 weeks' gestation. The study group included 149 cases in which a singleton fetus with cardiac activity was initially documented. The outcome variable was pregnancy loss prior to 20 weeks. The influence of sonographic findings on admission was studied by univariate analysis and logistic regression.
The prevalence of abortion was 23/149 (15%). A significant relationship (p < 0.05) was found between the occurrence of abortion and the following: fetal bradycardia (heart rate less than −1.2 SD from the mean), a discrepancy between the diameter of the gestational sac and crown-rump length less than −0.5 SD from the mean, and a discrepancy between menstrual and sonographic age of more than 1 week. According to the logistic regression equation that was obtained, the probability of abortion in first-trimester bleeding with documented fetal cardiac activity upon admission varied between a minimum of 6% when none of the above risk factors were present and a maximum of 84% when all were present. The presence of any of the above factors identified 84% of all subsequent abortions. Copyright © 1996 International Society of Ultrasound in Obstetrics and Gynecology
To determine if in women with threatened miscarriage the measurement of fetal crown-rump length (CRL) is a useful predictor of spontaneous miscarriage and small for gestational age (SGA) infants.
Fetal CRL was measured in 310 singleton pregnancies with live fetuses, presenting with threatened miscarriage before 13 weeks of gestation. The relationship between fetal CRL and pregnancy outcome was investigated.
In fetuses with CRL < 18 mm there was a significant positive association between the deficit in CRL for gestation and the incidence of subsequent spontaneous miscarriage. In those cases with CRL deficit more than 2 standard deviations (SDs) the incidence of miscarriage was 13.7%, whereas if the CRL was between the mean and -2 SDs the incidence of miscarriage was 8.3%. In fetuses with CRL > or = 18 mm there was a significant positive association between the deficit in CRL for gestation and the incidence of SGA. In those cases with CRL deficit of more than 2 SD the incidence of SGA was 27.3%, whereas if the CRL was between the mean and -2 SDs the incidence of SGA was 18.9%.
The findings of this study suggest that the measurement of fetal CRL may be a useful predictor of spontaneous miscarriage and SGA in pregnancies with threatened miscarriage.
An accurate method to predict subsequent miscarriage in live embryos has not yet been established. This pilot study aimed to determine the most discriminatory ultrasound-based model for predicting spontaneous miscarriage after embryonic life was first detected in assisted conceptions. A method for estimating individual risk of miscarriage was developed.
This was a prospective cross-sectional survey of 322 live singleton embryos in women from an assisted reproductive technology program. Mean sac diameter (MSD), crown-rump length (CRL), embryonic heart rate (EHR), maternal age and gestational age at the first transvaginal scan detecting embryonic life (between 42 and 62 days) were observed. These variables were included in a multivariate model for predicting spontaneous miscarriage occurring prior to 20 weeks. MSD, CRL and MSD minus CRL were assessed in univariate logistic regression analyses. The global diagnostic accuracy of each model was compared directly using receiver-operating characteristics (ROC) curves.
The multivariate model demonstrated the best ROC curve for predicting miscarriage (ROC area 0.87; 95% CI, 0.80-0.95). The separate univariate analyses had less diagnostic accuracy. In particular, MSD - CRL had a significantly smaller ROC area (0.65) than did the multivariate model (P < 0.01).
The most discriminatory test for predicting spontaneous miscarriage in live embryos was a multivariate model, which allows estimation of individual risk levels.
The timing of factors that lead to disorders of fetal growth have been studied for many years. Previous studies have focused on disorders of the "second wave" of trophoblast invasion of myometrial arterioles and on fetal weight gain in the third trimester. Over the last 5 years, clinical studies have shown associations between first trimester ultrasound and biochemical parameters and the risk of later adverse perinatal outcome. First trimester growth restriction is associated with an increased risk of low birth weight, low birth weight percentile for gestational age and extremely preterm birth. This may reflect a defect in early pregnancy placentation and later adverse outcome. Consistent with this hypothesis, low first trimester circulating maternal concentrations of pregnancy-associated plasma protein A, a trophoblast-derived regulator of the insulin-like growth factor system, are associated with an increased risk of later stillbirth, growth restriction, pre-term birth and pre-eclampsia. Even among healthy women having normal pregnancies, first trimester circulating concentrations of pregnancy-associated plasma protein A correlate with the timing of spontaneous labor and the eventual birth weight. These analyses suggest that in some women complications of late pregnancy have their origins in the very earliest weeks of gestation and precede first attendance for prenatal care.
An early pregnancy loss (EPL) or first-trimester miscarriage is the most common complication of human reproduction, with an incidence ranging between 50 and 70% of all conceptions. Two-thirds of EPL cases present with a thinner and fragmented trophoblastic shell, and reduced cytotrophoblast invasion of the tips of the spiral arteries. This leads to incomplete plugging during early pregnancy, and premature onset of the maternal circulation throughout the placenta. The excessive entry of maternal blood into the intervillous space has a direct mechanical effect on the villous tissue, and an indirect oxidative stress effect that contributes to cellular dysfunction and/or damage. Correlation of in vivo and in vitro data suggests that overwhelming oxidative stress of the placental tissues represents a common pathophysiological mechanism for the different etiologies of EPL. Autosomal trisomies are the most frequent karyotypic abnormalities found in EPL, but the comparison of data from different cytogenetic studies is difficult because of the lack of clinical information in many cases on maternal age, gestational age, time of fetal demise and the cytogenetic methodology employed. The majority of authors did find a weak association between villous morphologic features and chromosomal abnormalities, with the exception of partial mole triploidy. The comparison of ultrasound findings and placental histological data indicates that villous changes following fetal demise in utero could explain the overall low predictive value of placental histology alone in identifying an aneuploidy or another non-chromosomal etiology. By contrast, the histological features of complete and partial hydatidiform molar EPL are so distinctive that most cases of molar EPL are correctly diagnosed by histological examination alone. Overall, histopathology when correlated with in vivo ultrasound/Doppler has provided novel clues to the pathophysiology of EPL. Prospective studies are needed to evaluate the impact of these findings on routine histopathologic examination in first-trimester miscarriages.
The advent of high-resolution transvaginal ultrasound (TVS) has revolutionized our understanding of the pathophysiology and the management of early pregnancy failure. Knowledge of the ultrasound appearances of normal early pregnancy development and a good understanding of its pitfalls are essential for the diagnosis and management of early pregnancy failure. Ultrasound imaging has rapidly replaced all other techniques used to study normal human development in the first trimester, and ultrasound features of the early gestational sac have corroborated anatomical studies showing that the first structures to appear are the celomic cavity and the secondary yolk sac. No single ultrasound measurement of the different anatomical features in the first trimester has been shown to have a high predictive value for determining early pregnancy outcome. Similarly, Doppler studies have failed to demonstrate abnormal blood flow indices in the first-trimester uteroplacental circulation of pregnancies that subsequently end in miscarriage. Ultrasound parameters combined with maternal serum hormone levels, maternal age, smoking habits, obstetric history and the occurrence of vaginal bleeding have all been combined in multivariate analyses, with mixed results. Combined ultrasound and in-vitro experiments have demonstrated that the maternal circulation inside the placenta starts at the periphery at around 9 weeks of gestation and that this is associated with a physiological oxidative stress which could be the trigger for the formation of the placental membranes. Abnormal development of these membranes can result in subchorionic hemorrhage and threatened miscarriage with subsequent long-term consequences such as preterm rupture of the membranes and preterm labor, irrespective of the finding of a hematoma on ultrasound. In both euploid and aneuploid missed miscarriages there is clear ultrasound evidence for excessive entry of maternal blood at a very early stage inside the developing placenta resulting in oxidative stress and subsequent degeneration of villous tissue. The finding of blood flow in the intervillous space in cases of first-trimester miscarriage using color Doppler also appears to be useful in the prediction of success of expectant management. Miscarriages with blood flow within the intervillous space are up to four times more likely to complete with expectant management. TVS is considered the gold standard in the diagnosis and management of incomplete miscarriage. Expectant management of miscarriage, using ultrasound parameters to determine eligibility, could significantly reduce the number of unnecessary evacuations of the retained products of conception, depending on the criteria used.
The demand for ultrasound in early pregnancy has been increasing steadily, and is now a routine investigation for most women within the first trimester of their pregnancy. It is a safe investigation which provides reassurance, charts normal development, and identifies women with abnormal or high risk pregnancies. Transvaginal ultrasound has revolutionized the diagnosis of early pregnancy as it can detect a pregnancy at an earlier stage, whether it is normal and therefore reassuring, or abnormal and require intervention. Ultrasound is also a useful tool to aid decisions regarding management of abnormal pregnancy, such as ectopic pregnancy or miscarriage. This chapter looks at the important role ultrasound plays in the diagnosis and management of abnormal pregnancy.