Higher Risk Of Pregnancy Loss Research Articles

Prenatal Genetic Diagnosis through Chorionic Villus Sampling

Chorionic villus sampling (CVS) is a technique for prenatal diagnosis of the fetal karyotype through cytogenetic analysis, and of Mendelian inherited diseases through molecular or biochemical analysis. Because the sampling technique can be performed in the first-trimester of pregnancy and diagnostic results can be obtained earlier than with amniocentesis, it has been utilized by clinicians in Europe and the US since 1982. CVS includes two methods: a transcervical approach and a transabdominal approach. Both are performed in the 10th week of pregnancy under careful ultrasound guidance to prevent adverse effects, but in comparison with amniocentesis, a slightly higher risk of pregnancy loss has been reported. Moreover, diagnostic accuracy is often disturbed by maternal cell contamination and chromosomal mosaicism of the placenta. Therefore, clinicians must give patients sufficient information on such technical and diagnostic trouble through counseling in order to obtain fully informed consent.

Reproductive outcomes in patients with recurrent pregnancy loss associated with a structural chromosome abnormality

Objectives: Recurrent pregnancy loss (RPL), defined as two or more pregnancy losses, affects up to 5% of couples trying to establish a family. A structural chromosome abnormality is found in association with RPL in 3.5% of couples (Stephenson, 1996). The objectives of this study are: 1)to summarize the reproductive outcomes of RPL couples with an identified structural chromosome abnormality.2)to describe the cytogenetic findings of pregnancy losses in this cohort.3)to compare these results to published controls.Study Design: This study is a retrospective cohort-control study.Methods and Materials: Couples were identified using the BC Women’s RPL Database (ACCESS 2000) created by one of the authors (MDS). Inclusion criteria were: 1) a history of at least 2 miscarriages <20 weeks of gestation; and 2) either the maternal or paternal partner was identified as a carrier of a balanced structural chromosome abnormality. Descriptive analyses were done using EpiInfo (CDC, 2002).Results: 34 couples with 183 pregnancies were identified. Mean maternal age at the time of pregnancy loss or delivery was 30 years (SD 5). The distribution of the structural chromosome abnormalities in the RPL carriers is shown below.Of these 183 pregnancies, 102 (56%) resulted in miscarriage under 10 weeks’ gestation, and 27 (15%) resulted in an intrauterine fetal demise of 10 or more gestational weeks. Four of the pregnancies were terminated electively. The remaining 50 pregnancies resulted in livebirths (27%). An amniocentesis was performed in 9 of these 50 pregnancies; the results were diploid (46, XX or 46, XY) in 4 of the 9 pregnancies; the other 5 consisted of a balanced structural chromosome abnormality similar to the parental carrier.34 of the 129 (26%) pregnancy losses were sent for cytogenetic analysis; 9 did not grow in culture for a failure rate of 26%. The cytogenetic findings and comparisons to historic controls are shown below. Tabled 1 Tabled 1Conclusions: RPL couples who have a structural chromosome abnormality have a high risk of pregnancy loss (70%), of which approximately one-third can be attributed to an unbalanced translocation or inversion. This incidence is higher than that seen in published controls (4–6%). Since 44% of the pregnancy losses are not due to a structural or numeric chromosome abnormality, other factors associated with RPL should be evaluated. Ongoing pregnancies appear to be at low risk of having an unbalanced structural chromosome abnormality in carriers of a balanced structural chromosome abnormality ascertained by a history of RPL. Objectives: Recurrent pregnancy loss (RPL), defined as two or more pregnancy losses, affects up to 5% of couples trying to establish a family. A structural chromosome abnormality is found in association with RPL in 3.5% of couples (Stephenson, 1996). The objectives of this study are: 1)to summarize the reproductive outcomes of RPL couples with an identified structural chromosome abnormality.2)to describe the cytogenetic findings of pregnancy losses in this cohort.3)to compare these results to published controls. Study Design: This study is a retrospective cohort-control study. Methods and Materials: Couples were identified using the BC Women’s RPL Database (ACCESS 2000) created by one of the authors (MDS). Inclusion criteria were: 1) a history of at least 2 miscarriages <20 weeks of gestation; and 2) either the maternal or paternal partner was identified as a carrier of a balanced structural chromosome abnormality. Descriptive analyses were done using EpiInfo (CDC, 2002). Results: 34 couples with 183 pregnancies were identified. Mean maternal age at the time of pregnancy loss or delivery was 30 years (SD 5). The distribution of the structural chromosome abnormalities in the RPL carriers is shown below. Of these 183 pregnancies, 102 (56%) resulted in miscarriage under 10 weeks’ gestation, and 27 (15%) resulted in an intrauterine fetal demise of 10 or more gestational weeks. Four of the pregnancies were terminated electively. The remaining 50 pregnancies resulted in livebirths (27%). An amniocentesis was performed in 9 of these 50 pregnancies; the results were diploid (46, XX or 46, XY) in 4 of the 9 pregnancies; the other 5 consisted of a balanced structural chromosome abnormality similar to the parental carrier. 34 of the 129 (26%) pregnancy losses were sent for cytogenetic analysis; 9 did not grow in culture for a failure rate of 26%. The cytogenetic findings and comparisons to historic controls are shown below. Tabled 1 Tabled 1 Conclusions: RPL couples who have a structural chromosome abnormality have a high risk of pregnancy loss (70%), of which approximately one-third can be attributed to an unbalanced translocation or inversion. This incidence is higher than that seen in published controls (4–6%). Since 44% of the pregnancy losses are not due to a structural or numeric chromosome abnormality, other factors associated with RPL should be evaluated. Ongoing pregnancies appear to be at low risk of having an unbalanced structural chromosome abnormality in carriers of a balanced structural chromosome abnormality ascertained by a history of RPL.

Amniocentesis and chorionic villus sampling for prenatal diagnosis.

A major disadvantage of second trimester amniocentesis is that the result is usually available only after 18 weeks' gestation. Chorionic villus sampling (CVS) and early amniocentesis can be done between 9 and 14 weeks and offer an earlier alternative. The objective was to assess comparative safety and accuracy of second trimester amniocentesis, early amniocentesis, transcervical and transabdominal CVS. We searched the Cochrane Pregnancy and Childbirth Group trials register (March 2003) and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2002). All randomised trials comparing amniocentesis and CVS. Two reviewers assessed eligibility and trial quality and performed data extraction. We analysed the data using RevMan software. A total of 14 randomised studies have been included. In a low risk population with a background pregnancy loss of around 2%, a second trimester amniocentesis will increase this risk by another 1%. This difference did not reach statistical significance, but the increase in spontaneous miscarriages following second trimester amniocentesis compared with controls (no amniocentesis) did (2.1% versus 1.3%; relative risk (RR) 1.02 to 2.52). Early amniocentesis is not a safe early alternative to second trimester amniocentesis because of increased pregnancy loss (7.6% versus 5.9%; RR 1.29, 95% CI 1.03 to 1.61) and higher incidence of talipes compared to CVS (1.8% versus 0.2%; RR 6.43, 95% CI 1.68 to 24.64).Compared with second trimester amniocentesis, transcervical CVS carries a significantly higher risk of pregnancy loss (14.5% versus 11%; RR 1.40, 95% CI 1.09 to 1.81) and spontaneous miscarriage (12.9% versus 9.4%; RR 1.50, 95% CI 1.07 to 2.11). One study compared transabdominal CVS with second trimester amniocentesis and found no significant difference in the total pregnancy loss between the two procedures (6.3% versus 7%). Transcervical CVS is more technically demanding than transabdominal CVS with more failures to obtain sample and more multiple insertions. Second trimester amniocentesis is safer than transcervical CVS and early amniocentesis. If earlier diagnosis is required, transabdominal CVS is preferable to early amniocentesis or transcervical CVS. In circumstances where transabdominal CVS may be technically difficult the preferred options are transcervical CVS in the first trimester or second trimester amniocentesis.

Genetic amniocentesis in multifetal pregnancies reduced to twins compared with nonreduced twin gestations

Reduction of the number of fetuses in a multifetal pregnancy has been recommended in an attempt to improve perinatal outcome. Women carrying multifetal pregnancies are also at higher risk of having a chromosomally abnormal fetus than are women carrying singletons, and this risk is even higher in infertility patients because of advanced maternal age. Therefore, it is not unusual for patients with twin pregnancies who have undergone multifetal pregnancy reduction (MFPR) to also seek prenatal diagnosis. In such cases, amniocentesis is the method of choice at most centers. We investigated whether genetic amniocentesis entails higher risk of pregnancy loss in twin pregnancies that are the result of MFPR than in nonreduced twin pregnancies.

Antiphospholipid, anti-beta 2-glycoprotein-I and anti-oxidized-low-density-lipoprotein antibodies in antiphospholipid syndrome.

Antiphospholipid antibodies (aPL), anti-beta 2-glycoprotein I (anti-beta 2-GPI) and anti-oxidized-low-density lipoprotein (LDL) antibodies are all implicated in the pathogenesis of antiphospholipid syndrome. To investigate whether different autoantibodies or combinations thereof produced distinct effects related to their antigenic specificities, we examined the frequencies of antiphospholipid syndrome (APS)-related features in the presence of different antibodies [aPL, beta 2-GPI, anti-oxidized low density lipoprotein (LDL)] in 125 patients with APS. Median follow-up was 72 months: 58 patients were diagnosed as primary APS and 67 as APS plus systemic lupus erythematosus (SLE). Anticardiolipin antibodies (aCL), anti-beta 2-GPI and anti-oxidized LDL antibodies were determined by ELISA; lupus anticoagulant (LA) by standard coagulometric methods. Univariate analysis showed that patients positive for anti-beta 2-GPI had a higher risk of recurrent thrombotic events (OR = 3.64, 95% CI, p = 0.01) and pregnancy loss (OR = 2.99, 95% CI, p = 0.004). Patients positive for anti-oxidized LDL antibodies had a 2.24-fold increase in the risk of arterial thrombosis (2.24, 95% CI, p = 0.03) and lower risk of thrombocytopenia (OR = 0.41 95% CI, p = 0.04). Patients positive for aCL antibodies had a higher risk of pregnancy loss (OR = 4.62 95% CI, p = 0.001). When these data were tested by multivariate logistic regression, the association between anti-beta 2-GPI and pregnancy loss and the negative association between anti-oxidized LDL antibodies and thrombocytopenia disappeared.

Obstetric outcome in antiphospholipid syndrome.

The presence of lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) are associated with recurring pregnancy loss. Of 387 consecutive patients investigated at a Recurring Miscarriage Clinic over a three year period, 63 (16%) were positive for LA and ACA or both. Fifty-nine patients by definition were classified as having antiphospholipid syndrome and four also had systemic lupus erythematosus (SLE). Fifty-three subsequent pregnancies occurred in 63 patients and of these 37 ended in a live birth giving an overall livebirth rate of 70%. Treatment included low dose aspirin alone in 37 pregnancies and low dose aspirin and low molecular weight heparin (LMWH) in 16 pregnancies. The decision for treatment was made empirically on past obstetric history and level of LA and ACA, and past history of venous thromboembolic disease. Obstetric outcome was worst in the group who were positive for both LA and ACA, with a success rate of 53%, compared to 72 or 81% in the single parameter groups. Complications in the 37 successful pregnancies included eight Caesarean sections, four cases of intra-uterine growth restriction, one case of pregnancy induced proteinuric hypertension, one deep vein thrombosis and one pulmonary embolism. Patients with antiphospholipid syndrome are at high risk of pregnancy loss as well as maternal morbidity, especially thrombo-embolic disease. A randomised prospective controlled trial is necessary to determine the optimum therapy for pregnancy conservation and thrombprophylaxis.

Cytogenetic diagnosis using midtrimester fetal blood samples: Application to suspected mosaicism and other diagnostic problems

Cytogenetic studies on fetal blood cells obtained at 18-25 weeks gestation have provided information for decision making in 25 cases identified as being at high risk of having an abnormal fetus. In particular, in the 21 cases studied to consider the possibility of true mosaicism, confirmation in fetal blood was obtained in three, one of which presented as a pseudomosaic on the original amniotic fluid cell study. Fetal blood was also informative in two cases (one positive and the other negative) in which a diagnosis of the fragile X syndrome was being considered. Furthermore, when high risk pregnancies presented late in gestation (21-24 weeks), these methods allowed for a rapid cytogenetic diagnosis. The procedure has proved useful in most of these cases since the couples involved had indicated that they would probably have terminated the pregnancy without the reassurance of normal fetal lymphocyte studies. Since the technique carries a much higher risk of pregnancy loss than does amniocentesis, its use should only be considered when there are compelling indications.