Spontaneous fetal loss rates in a non-selected population

The objective of this work was to determine the rate of spontaneous fetal loss up to 28 weeks of gestation in uncomplicated pregnancies of a low-risk population after sonographically identified intact intrauterine pregnancy during the first trimester. Transvaginal ultrasounds were given to 2,534 women at between six and 12 weeks of gestation. Inclusion criteria were a positive fetal cardiac activity and no antecedent signs of vaginal bleeding. Gestational age was confirmed by measurement of the crown-rump length and/or biparietal diameter (BIP). Patients were followed until delivery or up to a fetal loss. The mean fetal loss rate between 12 and 28 weeks was 3.86% (n = 99). Fetal loss increased with maternal age: fetal loss rate under 20 yr: 2.94% (OR 0.75; CI 0.23-2. 46), 20-24 yr: 3.20% (OR 0.77; CI 0.48-1.23), 25-29 yr: 3.39% (OR 0.77; CI 0.50-1.19), 30-34 yr: 3.89% (OR 1.01; CI 0.59-1.71), 35-39 yr: 7.82% (OR 2.13; CI 1.04-4.32), 40-45 y: 50% (OR 13.84; CI 6.67-28.72) and > 45 yr: 50% (OR 13.05; CI 1.96-86.71) respectively. The frequency of spontaneous fetal loss before 28 weeks gestation was assessed systematically in a low-risk population. There was a very clear correlation with advancing maternal age. These data now can be used as background loss rate information for evaluating the safety of invasive prenatal diagnosis, and they will be more valid for this purpose than the available data taken from selected cohorts of women, such as those from hospital clinics or from infertility programs.     

Early rapid growth,early birth: Accelerated fetal growth and spontaneous late preterm birth

The past two decades in the United States have seen a 24% rise in spontaneous late preterm delivery (34–36 weeks) of unknown etiology. This study tested the hypothesis that fetal growth was identical prior to spontaneous preterm (n = 221, median gestational age at birth 35.6 weeks) and term (n = 3706) birth among pregnancies followed longitudinally in Santiago, Chile. The hypothesis was not supported: Preterm‐delivered fetuses were significantly larger than their term‐delivered peers by mid‐second trimester in estimated fetal weight, head, limb, and abdominal dimensions, and they followed different growth trajectories. Piecewise regression assessed time‐specific differences in growth rates at 4‐week intervals from 16 weeks. Estimated fetal weight and abdominal circumference growth rates slowed at 20 weeks among the preterm‐delivered, only to match and/or exceed their term‐delivered peers at 24–28 weeks. After an abrupt growth rate decline at 28 weeks, fetuses delivered preterm did so at greater population‐specific sex and age‐adjusted birth weight percentiles than their peers from uncomplicated pregnancies (P < 0.01). Growth rates predicted birth timing: one standard score of estimated fetal weight increased the odds ratio for late preterm birth from 2.8 prior to 23 weeks, to 3.6 (95% confidence interval, 1.82–7.11, P < 0.05) between 23 and 27 weeks. After 27 weeks, increasing size was protective (OR: 0.56, 95% confidence interval, 0.38–0.82, P = 0.003). These data document, for the first time, a distinctive fetal growth pattern across gestation preceding spontaneous late preterm birth, identify the importance of mid‐gestation for alterations in fetal growth, and add perspective on human fetal biological variability. Am. J. Hum. Biol., 2009. © 2008 Wiley‐Liss, Inc.     

Maternal and neonatal outcomes in dichorionic twin pregnancies following IVF treatment: a hospital-based comparative study

Aim: To compare maternal, and neonatal outcomes in IVF/ICSI and spontaneously conceived dichorionic twin pregnancy. Method: We collected data regarding dichorionic twin pregnancies following in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI, n=162) with the transfer of fresh embryos as well as data regarding spontaneously conceived pregnancies (n=213) delivered after 28 weeks of gestation at the Department of Obstetrics and Gynecology, Renmin Hospital in Wuhan in the years of 2010-2013. We then compared maternal and neonatal outcomes between IVF/ICSI and spontaneous dichorionic twin pregnancies, with a subgroup analysis separating traditional IVF from ICSI pregnancies. Odds ratios (OR) for associations between IVF/ICSI and pregnancy outcomes were adjusted for maternal factors. Results: The mean maternal age and the percentage of primiparous women were significantly higher in the IVF/ICSI group. Multivariate analysis revealed that maternal outcomes were comparable in both groups with/without adjustment for maternal age and parity. However, IVF/ICSI twins were less likely to have birth weight discordance than those spontaneously conceived (unadjusted OR=0.526, 95% CI 0.297-0.932; adjusted OR=0.486, 95% CI 0.255-0.856). In subgroup analyses, these associations were confirmed in the IVF (adjusted OR=0.496, 95% CI 0.265-0.926), but not in the ICSI group (adjusted OR=0.500, 95% CI 0.139-1.807). Conclusion: IVF/ICSI treatment was not a risk factor for adverse maternal neonatal outcomes, but the risk for birth weight discordance is lower among IVF/ICSI twins.     

Risk factors for spontaneous abortion: a case-control study in France.

A case-control study was conducted in seven maternity hospitals in the Paris area in 1988 to evaluate the role of several risk factors in spontaneous abortion. A total of 279 cases and 279 controls were compared for socio-demographic characteristics, reproductive history and for conditions of conception. Prior fetal losses [odds ratio (OR) = 2.30 for n greater than or equal to 2; 95% confidence interval (CI) = 1.17-4.61] and maternal age at pregnancy (greater than 30 years) appeared to be major and independent risk factors of spontaneous abortion. Other factors associated with an increased risk of fetal loss were: geographical or ethnic origin (OR = 2.85 for North African women; 95% CI = 1.58-5.10); psychological problems at the time of conception, either related to the outcome of the pregnancy (OR = 3.08; 95% CI = 0.92-10.25) or unrelated to this outcome (OR = 3.35; 95% CI = 1.41-8.00). The following factors were not associated with spontaneous abortion: gravidity, parity, prior induced abortion, prior sexually transmitted diseases and Chlamydia trachomatis serology, menstrual cycle abnormalities, induced conception cycle and in-vitro fertilization, cigarette smoking, current or past use of combined oestrogen/progestagen pill or intrauterine device. These findings confirm the importance of two risk factors for fetal loss: maternal age and number of prior spontaneous abortions. Two risk factors, ethnic origin and psychological problems at the time of conception are also identified, which require further study.     

Omphalocele, advanced maternal age, and fetal morbidity outcomes

In this study we wanted to determine if the risk for adverse neonatal outcome among omphalocele-affected fetuses is increased among older gravidas. This was a retrospective cohort study on live-born infants with omphalocele delivered in New York State from 1983 through 1999. We compared infants of older (>or=35 years) with those of younger (<35 years) mothers with respect to the following fetal morbidity indices: low birth weight and very low birth weight, preterm and very preterm, and small for gestational age. We used adjusted odds ratios to approximate relative risks. Data on a total of 1,010 infants with omphalocele were analyzed. Mean gestational age and birth weight were similar in both maternal age categories: mean+/-standard deviation (SD) for infants with omphalocele born to older mothers=37.4 weeks+/-3.9 versus 38.0 weeks+/-5.1 for those of younger mothers (P=0.2); mean birth weights+/-SD for infants with omphalocele born to older mothers=2,813+/-871.1 versus 2,958+/-809.9 for those of younger mothers (P=0.08). Also, the two maternal age sub-groups did not differ with respect to the fetal morbidity outcome: low birth weight (OR=0.95; 95% CI=0.60-1.51), very low birth weight (OR=0.78; 95% CI=0.36-1.69), preterm (OR=0.95; 95% CI=0.58-1.57), very preterm (OR=0.73; 95% CI=0.34-1.58), and SGA (OR=1.00; 95% CI=0.44-2.27). Thus, advanced maternal age does not appear to be a risk factor for fetal morbidity outcomes among omphalocele-affected fetuses. This information is potentially useful in counseling affected parents.     

Secular trends in congenital anomaly‐related fetal and infant mortality in Canada, 1985–1996

Prenatal diagnosis of major congenital anomalies and subsequent termination of affected pregnancies has been widely available as part of routine obstetric care in recent years. In this study, vital statistical data on stillbirths, live births, and infant deaths were used to examine secular trends in gestational age‐specific and category‐specific fetal and infant mortality due to congenital anomalies in Canada (excluding Ontario and Newfoundland) from 1985–1996. Comparisons of the rates between 1985–1987 and 1994–1996 were made using relative risks and 95% confidence intervals (CI). The overall fetal mortality rate due to congenital anomalies increased significantly, from 68.0 per 100,000 total births in 1985–1987 to 78.6 per 100,000 total births in 1994–1996, while the overall infant mortality rate due to congenital anomalies decreased significantly over the same period, from 2.47 to 1.79 per 1,000 live births. The fetal death rate due to congenital anomalies at 20–21 weeks of gestation increased approximately five‐fold (relative risk [RR] = 4.83, 95% CI = 3.28–7.11) from 4.5 to 21.5 per 100,000 fetuses at risk, while the rate at 37–41 weeks decreased by 30% (RR = 0.70, 95% CI = 0.50–0.97). Fetal death rates among pregnancies at 20–25 weeks of gestation increased in all categories of congenital anomaly except anencephaly and respiratory system anomalies. Congenital anomaly‐related fetal and infant deaths have increased at early gestation but declined at later gestation in Canada. These changes suggest an increase in prenatal diagnosis and selective termination of pregnancies with congenital anomalies in recent years. © 2001 Wiley‐Liss, Inc.     

Early transvaginal embryo aspiration: a safer method for selective reduction in high order multiple gestations.

Assisted reproduction technologies and ovulation induction for treatment of infertility continue to cause high order multiple gestations. Increased perinatal morbidity and mortality, as well as maternal morbidity, may complicate these pregnancies. Selective fetal reduction, an acceptable therapeutic approach in these cases, is usually performed at or after the ninth week of gestation, with KCl injected in the vicinity of the fetal heart, and is associated with a total pregnancy loss rate of 11.7%. We report our experience with 90 women who underwent early (mean 7.5 weeks gestation, range 7. 0-8.0 weeks) transvaginal selective embryo aspiration. The mean number of viable embryos before and after reduction was 3.5 and 2.1 respectively. Six (6.7%) pregnancies were lost before 24 gestational weeks. One miscarriage occurred at the tenth gestational week. The other five pregnancies were aborted at 17.3-21.6 weeks gestation. Additional interventions were performed in three of these pregnancies: genetic amniocentesis in two cases and cervical suture in one case. In the subset of 39 patients with>/=4 embryos, only one (2.6%) pregnancy loss was recorded. This loss rate is significantly lower (P < 0.05) than the 15.3% loss rate in patients with >/=4 fetuses calculated from other work. Four (4.4%) other pregnancies were complicated by premature delivery (25-28 weeks gestation). Mean gestational age of delivered pregnancies in our series was 35.7 weeks. In conclusion, early transvaginal embryo aspiration is a simple and relatively safe method for multiple pregnancy reduction. The overall pregnancy loss rate associated with early embryo aspiration is similar to that of procedures performed at later gestational age, but is significantly lower when the initial number of embryos is four or greater.     

Consequences of vanishing twins in IVF/ICSI pregnancies

BACKGROUND: Spontaneous reductions are a possible cause of the increased morbidity in IVF singletons. The aim of this study was to assess incidence rates of spontaneous reductions in IVF/ICSI twin pregnancies and to compare short- and long-term morbidity in survivors of a vanishing co-twin with singletons and born twins. METHODS: We identified 642 survivors of a vanishing co-twin, 5237 singletons from single gestations and 3678 twins from twin gestations. All children originated from pregnancies detected by transvaginal sonography in gestational week 8. By cross-linkage with the national registries the main endpoints were prematurity, birth weight, neurological sequelae and mortality. RESULTS: Of all IVF singletons born, 10.4% originated from a twin gestation in early pregnancy. Multiple logistic regression analyses adjusted for maternal age, parity and ICSI treatment showed for birth weight <2500 g an odds ratio (OR) of 1.7 [95% confidence interval (CI) 1.2-2.2] and for birth weight <1500 g OR 2.1 (95% CI 1.3-3.6) in singleton survivors of a vanishing twin versus singletons from single gestations; corresponding figures were seen for preterm birth. This increased risk was almost entirely due to reductions that occurred at >8 weeks gestation. We found no excess risk of neurological sequelae in survivors of a vanishing co-twin versus the singleton cohort; however, OR of cerebral palsy was 1.9 (95% CI 0.7-5.2). Furthermore, we observed a correlation between onset of spontaneous reduction, i.e. the later in pregnancy the higher the risk of neurological sequelae (r = -0.09; P = 0.02). Adjusted OR of child death within the follow-up period was 3.6 (95% CI 1.7-7.6) in the survivor versus the singleton cohort. CONCLUSIONS: One in 10 IVF singletons originates from a twin gestation. Spontaneous reductions that occur at >8 weeks gestation are one of the causes for the higher risk of adverse obstetric outcome in IVF singletons.     

Does confined placental mosaicism account for adverse perinatal outcomes in IVF pregnancies?

BACKGROUND: IVF singletons have poorer perinatal outcomes than singletons from spontaneous conceptions. This may be due to the influence of ovarian stimulation on the chromosomal constitution of the embryos which could be translated into localized chromosomal anomalies in the placenta. The aim of this study was to compare the incidence of confined placental mosaicism (CPM) in IVF/ICSI pregnancies and spontaneous conceptions. METHODS: We conducted a multi-centre retrospective analysis of karyotype results obtained by chorionic villus sampling (CVS), performed due to advanced maternal age (>or=36 years at 18 weeks of gestation), in the Netherlands between 1995 and 2005. RESULTS: From a total of 322 246 pregnancies, 20 885 CVS results were analysed: 235 in the IVF/ICSI group and 20 650 in the control group. The mean age of women in both groups was 38.4 years (mean difference -0.08, 95% CI -0.35 to 0.18). Data relating to the fetal karyotype were missing in 143 cases in the control group. When taking into account missing data, the incidence of CPM was lower in the IVF-ICSI group than in the control group, 1.3% versus 2.2% (odds ratio 0.59, 95% CI 0.19-1.85), whereas the incidence of fetal chromosomal anomalies was increased 4.3% versus 2.4% (odds ratio 1.81, 95% CI 0.95-3.42). Neither differences were statistically significant. CONCLUSIONS: The incidence of CPM is not increased in IVF/ICSI pregnancies compared with spontaneous conceptions. CPM probably does not account for the adverse perinatal outcomes following IVF/ICSI.     

Increased nuchal translucency in trisomy 13 fetuses at 10–14 weeks of gestation

In a multicenter screening study for trisomy 21 involving ultrasonographic measurement of fetal nuchal translucency thickness (NT) at 10–14 weeks of gestation, 100,311 singleton pregnancies with a live fetus were examined. There were 46 cases of trisomy 13, and in 33 (72%) of these, the NT was above the 95th centile. The estimated risk for trisomy 21, based on maternal age-related risk for this chromosomal abnormality and fetal NT, was above 1 in 300 in 37 (80.1%) of the trisomy 13 fetuses. The fetal crown-rump length was significantly reduced, but the fetal heart rate was increased, being above the 95th centile in 64% of cases. Additionally, 24% of trisomy 13 fetuses had holoprosencephaly and 10% had exomphalos. This study has demonstrated that at 10–14 weeks of gestation, about 80% of fetuses with trisomy 13 can be identified in a screening program for trisomy 21, based on a combination of maternal age and fetal NT. Am. J. Med. Genet. 86:205–207, 1999. © 1999 Wiley-Liss, Inc.     

Fetal growth and gestational factors as predictors of schizophrenia in 22q11.2 deletion syndrome

PurposeSchizophrenia occurs in 20–25% of adults with 22q11.2 deletion syndrome (22q11.2DS). General population studies of schizophrenia report associations with perinatal complications, although effect sizes are generally low. We aimed to determine whether such factors are associated with expression of schizophrenia in individuals with 22q11.2DS.MethodsWe investigated the relationship of small for gestational age (SGA) birth weight (<3rd percentile for sex and gestational age) and prematurity (<37 weeks gestation) to expression of schizophrenia in a well-characterized cohort of 123 adults with 22q11.2DS. Outcome measures included adjusted odds ratios and positive and negative predictive values (PPV and NPV) for schizophrenia.ResultsSGA birth weight (OR = 3.52, 95% CI = 1.34–9.22) and prematurity (OR = 5.38, 95% CI = 1.63–17.75), but not maternal factors, were significant risk factors for schizophrenia in 22q11.2DS. Being born SGA or premature resulted in a PPV of 46% for schizophrenia; NPV in the absence of both features was 83%. Post hoc analyses suggested these perinatal complications were also associated with factors indicative of increased severity of schizophrenia.ConclusionIn 22q11.2DS, fetal growth and gestation may have a clinically significant impact on future risk for schizophrenia. These data advance our understanding of determinants of disease-specific expression in 22q11.2DS, with implications for other genomic disorders.     

Maternal Prepregnancy Underweight and Risk of Early and Late Stillbirth in Black and White Gravidas

ObjectiveThe association between underweight and stillbirth remains poorly defined, especially across racial/ethnic sub-populations. We investigate the association of pre-pregnancy underweight on the risk for early and late stillbirth among black and white mothers.MethodsWe conducted analysis on the Missouri maternally linked data files covering the period 1989-1997 inclusive. Using body mass index (BMI), we categorized mothers as underweight (BMI >18.5) and normal weight (BMI = 18.5-24.9). By applying logistic regression modeling with adjustment for intracluster correlation, we estimated the risk for total, early (≤28 weeks of gestation), and late stillbirth (>28 weeks of gestation) among black and white mothers.ResultsA total of 1808 cases of stillbirth were registered. The rate of stillbirth among white mothers was 3.7 per 1000, while the rate among blacks was 7.1 per 1000. Underweight black mothers had comparable risk for total (OR, 0.9; 95% CI, 0.7-1.2), early (OR, 1.1; 95% CI, 0.8-1.5), and late stillbirth (OR, 0.8; 95% CI, 0.5-1.2) as compared to their normal-weight counterparts. By contrast, underweight white gravidas had a 30% reduced likelihood (OR, 0.7; 95% CI, 0.6-0.9) for late stillbirth as compared to normal-weight white mothers. However, the risks for total and early stillbirth among underweight white mothers were similar to those of normal-weight white mothers.ConclusionLow prepregnancy BMI has similar effects on fetal survival in both blacks and whites except for late stillbirth. The underweight white survival advantage over blacks in late pregnancy could probably be due to greater access for identified white at-risk groups to effective obstetrical interventions as previously reported.     

Farming environment and prevalence of atopy at age 31: prospective birth cohort study in Finland

Background Cross‐sectional studies have shown an association between the farming environment and a decreased risk of atopic sensitization, mainly related to contact with farm animals in the childhood. Objective Investigate the association of a farming environment, especially farm animal contact, during infancy, with atopic sensitization and allergic diseases at the age of 31. Methods In a prospective birth cohort study, 5509 subjects born in northern Finland in 1966 were followed up at the age of 31. Prenatal exposure to the farming environment was documented before or at birth. At age 31, information on health status and childhood exposure to pets was collected by a questionnaire and skin prick tests were performed. Results Being born to a family having farm animals decreased the risk of atopic sensitization [odds ratio (OR) 0.67; 95% confidence interval (CI) 0.56–0.80], atopic eczema ever (OR 0.77; 95% CI 0.66–0.91), doctor‐diagnosed asthma ever (OR 0.74; 95% CI 0.55–1.00), allergic rhinitis at age 31 (OR 0.87; 95% CI 0.73–1.03) and allergic conjunctivitis (OR 0.86; 95% CI 0.72–1.02) at age 31. There was a suggestion that the reduced risk of allergic sensitization was particularly evident among the subjects whose mothers worked with farm animals during pregnancy, and that the reduced risk of the above diseases by farm animal exposure was largely explained by the reduced risk of atopy. Having cats and dogs in childhood revealed similar associations as farm animals with atopic sensitization. Conclusion and Clinical Relevance Contact with farm animals in early childhood reduces the risk of atopic sensitization, doctor‐diagnosed asthma and allergic diseases at age 31. Cite this as: J. Lampi, D. Canoy, D. Jarvis, A.‐L. Hartikainen, L. Keski‐Nisula, M.‐R. Järvelin and J. Pekkanen, Clinical & Experimental Allergy, 2011 (41) 987–993.     

Maternal HLA panel-reactive antibodies in early gestation positively correlate with chronic chorioamnionitis: evidence in support of the chronic nature of maternal anti-fetal rejection

Citation Lee J, Romero R, Xu Y, Kim J‐S, Park JY, Kusanovic JP, Chaiworapongsa T, Hassan SS, Kim CJ. Maternal HLA panel‐reactive antibodies in early gestation positively correlate with chronic chorioamnionitis: evidence in support of the chronic nature of maternal anti‐fetal rejection. Am J Reprod Immunol 2011; 66: 510–526 Problem Maternal tolerance of the fetus is essential for viviparity, yet anti‐fetal rejection occurs in several pregnancy complications. Chronic chorioamnionitis is a feature of anti‐fetal cellular rejection. There is a robust association between chronic chorioamnionitis and maternal seropositivity for anti‐human leukocyte antigen (HLA) panel‐reactive antibodies (PRA) at the time of delivery. This longitudinal study was performed to assess maternal HLA PRA status in early gestation and the temporal evolution of maternal HLA PRA in the context of chronic chorioamnionitis and, thereby, to determine whether HLA PRA during the course of pregnancy is useful for the detection of anti‐fetal rejection. Method of study Maternal sera obtained before 16 weeks of gestation and at delivery were analyzed for HLA PRA in cases with (N = 100) and without (N = 150) chronic chorioamnionitis. Results IgG (but not IgM) HLA class I and II PRA positivity at delivery was higher in cases with chronic chorioamnionitis than in those without chronic chorioamnionitis. IgG HLA class I PRA positivity before 16 weeks of gestation was higher in cases with chronic chorioamnionitis than in those without (30.3 versus 13.3%; P = 0.001). Positive conversion (negative HLA PRA before 16 weeks of gestation but positive at delivery) of IgG HLA class I and II PRA was significantly associated with chronic chorioamnionitis. Fetal HLA class I antigen‐specific antibodies were confirmed in 12 of 16 mothers tested who were sensitized to HLA class I antigens before 16 weeks of gestation. Conclusion Positive maternal HLA PRA before 16 weeks of gestation and the temporal evolution of maternal HLA PRA are associated with the presence of chronic chorioamnionitis at the time of delivery. Maternal IgG HLA PRA has the potential to be a monitoring tool of anti‐fetal rejection. Furthermore, the findings herein indicate that subsets of fetuses are exposed to alloimmune HLA antibodies for months, especially in cases with chronic chorioamnionitis.     

Influence of the HCV subtype on the virological response to pegylated interferon and ribavirin therapy

The hepatitis C virus genotype is considered to be the most important baseline predictor of a sustained virological response in patients with chronic hepatitis C treated with pegylated interferon and ribavirin. The influence of the subtype on the sustained virological response was investigated in patients infected with genotypes 1, 4, 5, or 6. This study was done on 597 patients with chronic hepatitis C who were given pegylated interferon and ribavirin for 48 weeks. The overall rate of sustained virological response in the 597 patients was 37.8%. Univariate analysis indicated that the sustained virological response of patients infected with subtype 1b (39%) tended to be higher than that of patients infected with subtype 1a (30.6%; P = 0.06) and it was similar to those patients infected with subtypes 4a (51.3%; P = 0.12) or 4d (51.7%; P = 0.16). Multivariate analysis indicated that five factors were independently associated with sustained virological response: the age (OR 0.97; 95% CI = 0.95–0.99), absence of cirrhosis (OR: 2.92; 95% CI = 1.7–5.0; P < 0.01), absence of HIV co‐infection (OR: 2.08; 95% CI = 1.2–3.5; P < 0.01), low baseline plasma HCV RNA concentration (OR: 1.74; 95% CI = 1.2–2.6; P < 0.01), and the subtype 1b (OR: 1.61; 95% CI = 1.0–2.5; P = 0.04) or subtypes 4a and 4d (OR: 2.03; 95% CI = 1.1–3.8; P = 0.03). In conclusion, among difficult‐to‐treat genotypes, the subtype 1a is associated with a lower response to anti‐HCV therapy than subtypes 1b, 4a, and 4d. J. Med. Virol. 81:2029–2035, 2009. © 2009 Wiley‐Liss, Inc.     

Regulation of costimulatory signal in maternal-fetal immune tolerance

Citation
Jin L‐P, Fan D‐X, Li D‐J. Regulation of costimulatory signal in maternal‐fetal immune tolerance. Am J Reprod Immunol 2011; 66: 76–83 A pregnancy is associated with modifications in the immune status of the mother, but the mechanisms are not well understood. Several observations have indicated that CD28/CTLA‐4 and B7‐1/B7‐2 are involved in the maternal–fetal immune regulation. This review aims to recapitulate our current knowledge concerning the role of CD28/CTLA‐4 and B7‐1/B7‐2 in maternal–fetal immune regulation. Several studies suggest that up‐regulation of B7‐2 and/or CD28 and/or down‐regulation of CTLA‐4 are correlated with the occurrence of pregnancy loss. Therefore, an accurate expression of costimulatory molecules at the maternal–fetal interface may ensure that the decidual cells do not elicit a ‘danger’ signal to the maternal immune system, perhaps instead contributing to the establishment of immune tolerance in vivo. It is showed that costimulation blockade with anti‐B7 mAbs results in altered allogeneic T‐cell response and overcomes increased maternal rejection to the fetus, which improves fetus growth in the abortion‐prone system. These findings suggest that the anti‐B7‐treated T cells not only function as potent suppresser cells but also exert immunoregulatory effect on the maternal T cells. This procedure might be potentially useful to immunotherapy for human recurrent spontaneous abortion.     

超声引导下的羊膜腔穿刺术和脐静脉穿刺术在产前诊断中的应用

目的 探讨介入超声技术在产前诊断中的应用效果。方法 对北京妇产医院2004年1月-2005年12月超声引导下的羊膜腔穿刺术和脐静脉穿刺术进行总结。结果 羊膜腔穿刺术一次穿刺成功率100％；脐静脉穿刺术：18^＋1-20w手术时间平均为8．1min，穿刺次数2．2，穿刺成功率89．3％；20^＋1-24w手术时间平均为2min，穿刺次数1．3，穿刺成功率97％；24^＋1-28w手术时间平均为1．3min，穿刺次数1．1，穿刺成功率100％；28^＋1-32w手术时间平均为1．6min，穿刺次数1．4，穿刺成功率98％；32^＋1-38w手术时间平均为5．7min，穿刺次数2．0，穿刺成功率90．3％。手术并发症：胎盘或脐带出血，羊膜腔穿刺术的发生率为1．7％，脐静脉穿刺术为12．2％；心动过缓的发生率，脐静脉穿刺术为6％，羊膜腔穿刺术为0；羊膜腔穿刺术仅1例孕妇发生流产，胎儿丢失率为0．11％，脐静脉穿刺术尚未发生胎儿丢失的病例。结论 高分辨实时超声技术使得羊膜腔穿刺术和脐静脉穿刺术变得更加安全，操作更加简单。     

Factors determining early pregnancy loss in singleton and multiple implantations

BACKGROUND: The incidence of first trimester pregnancy loss is much lower in IVF twin pregnancies than in IVF singleton pregnancies. The objective of this study was to determine which embryonic and maternal factors contribute to this finding. METHODS: Retrospective data analysis of the outcome of 1593 pregnancies after day 3 double-embryo transfer (DET) after IVF or ICSI treatment. RESULTS: Of 1148 single implantations at 6 weeks, 936 (81.5%) were ongoing pregnancies. Of 445 multiple implantations at 6 weeks, 354 (79.6%) were ongoing multiple pregnancies, 80 (17.9%) were ongoing singleton pregnancies and 11 (2.5%) ended in a spontaneous abortion. Total pregnancy loss was 18.5 and 2.5% (P < 0.001) in singleton and twin gestations, respectively. Loss per gestational sac was 18.5 and 11.46% (P < 0.001), respectively. Determinants contributing to the continuation of gestation beyond 6 weeks were young maternal age, possibility to cryopreserve embryos and short GnRH agonist flare-up stimulation protocol. Whereas factors promoting multiple implantation at 6 weeks of gestation were young maternal age, high cumulative embryo score (CES), male infertility, long stimulation protocol and thick endometrium. CONCLUSIONS: Although multiple implantation at 6 weeks is predominantly determined by (morphological) embryo quality, the continuation of pregnancy beyond 6 weeks becomes more dependent on the combination of genetic and developmental potential of the embryo(s) and an optimal uterine milieu.     

Triple marker screening for fetal chromosomal abnormalities in Korean women of advanced maternal age

The purpose of this article is to assess the value of maternal serum triple marker screening of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) for the prenatal diagnosis of fetal chromosomal abnormalities in Korean women of advanced maternal age. Maternal sera were collected from 458 pregnant Korean women aged 35 between 15 and 20 weeks gestation before amniocentesis. A patient- specific second trimester risk for fetal Down's syndrome was calculated using the median values for AFP, hCG, uE3 and maternal age. Twelve fetal chromosomal abnormalities were identified. These included six cases of trisomy 21, one case of 46,XY/47,XY,+21, two cases of trisomy 18, one case of trisomy 13, and two cases of 45, X. A cutoff level of 1:200 detected 85.7% (6/7) of the cases of Down's syndrome and 20% (1/5) of the other aneuploidies, with a 27.3% false positive rate. However, a cutoff level of 1:270 did not result in any gains in detecting Down's syndrome or other aneuploidies at the expense of a false positive rate of 34.3%. Second trimester triple marker testing is an effective screening tool for detecting fetal Down's syndrome in Korean women > or = 35 years old. However, it is not an effective screening tool for non-Down's chromosomal abnormalities.