Iron metabolism in monochorionic twin pregnancies in relation to twin--twin transfusion syndrome

Fetal iron metabolism was investigated in monochorionic (MC) twin pregnancies in relation to twin-twin transfusion syndrome (TTTS). Matched maternal and fetal blood samples were obtained both in utero and at birth from MC twins with TTTS (n = 23) and without TTTS (n = 18). In a second group of 30 twin pairs (15 with and 15 without TTTS), liver iron content was assessed by using archived paraffin wax-embedded blocks. Serum ferritin was determined by radioimmunoassay and values are given as gestation independent Z-scores and expressed as mean with 95% confidence intervals. Ferritin concentrations in the recipients were higher than in the donors both in utero (P < 0.01) and at birth (P < 0.01). Fetal serum ferritin in non-TTTS twins were similar to the recipient twins but higher than the donor twins (P < 0.05). A significant association was found between ferritin concentrations, the total red blood cell count and haemoglobin in the TTTS twin pairs (P < 0.01) and the non-TTTS twins as a group (P < 0.01). The total stainable liver iron was comparable between twin pairs in the TTTS and non-TTTS groups. This study fails to provide evidence of iron overload in the recipient and depletion in the donor twins and, thereby, questions the validity of the conventional theory of inter-twin transfusion as the cause of TTTS.     

Endothelin concentrations in monochorionic twins with severe twin-twin transfusion syndrome.

The objective of this study was to determine endothelin (ET-1) concentrations in monochorionic twin fetuses with and without twin-twin transfusion syndrome (TTTS). Fourteen monochorionic twin pregnancies complicated by TTTS and six without TTTS were studied. Matched maternal and fetal blood samples were obtained both in utero and at birth. Amniotic fluid samples were also collected from twin pairs. ET-1 concentrations were measured by radio-immunoassay. ET-1 concentrations in recipient fetuses were higher than in the donors both in utero(P < 0.001) and at birth (P < 0.01). Fetal concentrations of ET-1 in donors were similar to non-TTTS twins. Plasma ET-1 concentrations were significantly higher (P < 0.01) in recipient fetuses with severe hydrops than those with mild/no hydrops. Maternal concentrations of ET-1 were comparable in the two groups. Endothelin concentrations in recipient twins were 2(1/2) times higher than in their co-twins and this was related to the severity of hydrops.     

Outcome of twin pregnancies complicated by single intrauterine death in relation to vascular anatomy of the monochorionic placenta.

The objective of this study was to determine the relationship between the type of placentation, vascular anatomy of the monochorionic (MC) placenta and the perinatal outcome of the surviving twin following a single intrauterine fetal death (IUFD). In this retrospective study, 92 twin pregnancies complicated by a single intrauterine death were identified from three tertiary referral centres [50 MC and 42 dichorionic (DC)]. Antenatal and neonatal data as well as information on the chorionicity, vascular anastomoses, and autopsy findings were also obtained. The percentage risk of IUFD (26 versus 2.4; P < 0.001), anaemia (51.4 versus 0; P < 0.001) and intracranial lesions at birth (46 versus 0; P < 0.001) was greater in MC than in DC twins. In MC twins without twin-twin transfusion syndrome (TTTS), perinatal mortality was higher in the group with superficial arterioarterial (AA)/venovenous (VV) channels than those with only multiple bidirectional arteriovenous (AV) anastomoses (12/15 versus 0/8; P < 0.001). However, in the TTTS pregnancies (n = 26), perinatal outcome of the surviving twin was dependent on whether the recipient (n = 16) or the donor twin (n = 10) died first. Incidence of IUFD (9/16 versus 0/10; P < 0.001), severe anaemia (7/7 versus 1/10; P < 0.001) and intracranial lesions at birth (6/7 versus 2/10; P < 0.001) was common in pregnancies where the recipient twin died first. In the TTTS group, unidirectional AV anastomotic channels were found in all but two placentae. In conclusion, this study suggests that the outcome of twin pregnancies complicated by IUFD is dependent on the type of vascular anastomoses and TTTS.     

Genes or placenta as modulator of fetal growth: evidence from the insulin-like growth factor axis in twins with discordant growth

To determine whether fetal growth is regulated by placental and/or fetal factors, we measured maternal and fetal concentrations of insulin-like growth factor-I (IGF-I), IGF-II and insulin-like growth factor binding protein-1 (IGFBP-1) (total and non-phosphorylated) in dichorionic (DC) and monochorionic (MC) twins with (DC, n = 13; MC, n = 12) or without (DC, n = 13; MC, n = 12) discordant birth weight. In the discordant MC pregnancy, growth-restricted (IUGR) twins had lower IGF-II concentrations (P < 0.001) but similar IGF-I concentrations compared to the appropriate for gestational age(AGA) co-twin. The differences in IGF-II concentrations showed a positive association with percentage birth weight discordance (r = 0.60; P < 0.05) in MC twins. In contrast, IUGR DC twins had lower IGF-I concentrations (P < 0.05) but similar IGF-II concentrations compared to the AGA co-twins. There was a positive correlation between IGF-I concentrations and birth weight (r = 0.47; P < 0.05) in DC twins. Total IGFBP-1 concentrations were higher in both MC and DC IUGR twins (P < 0.05) compared to AGA twins. A negative association was found between total IGFBP-1 concentrations and birthweight of both MC (r = 0.47; P < 0.05) and DC (r = 0.58; P < 0.01) twins. No such differences in IGF concentrations were found between concordant MC and DC twin pairs. The maternal IGF concentrations were comparable between the MC and DC groups. These data suggest that growth discordances of twins exposed to the same maternal environment may be due to variations in either IGF-I or IGF-II/IGFBP-1, depending upon the functioning of the placenta.     

X-chromosome inactivation patterns do not implicate asymmetric splitting of the inner cell mass in the aetiology of twin-twin transfusion syndrome

The aetiology of twin-twin transfusion syndrome (TTTS) is unclear. We investigated the hypothesis that monochorionic (MC) pregnancies with TTTS are associated with differences in the timing and symmetry of twinning compared to MC twin pregnancies without TTTS. DNA was extracted from the umbilical cord vessels of 26 female MC twins, 14 with and 12 without TTTS on serial antenatal ultrasound. X-inactivation patterns were determined by DNA digestion with Hhal and Hpall followed by polymerase chain reaction for a polymorphic trinucleotide repeat in the androgen receptor gene. Products were quantified by densitometry and results compared to those in peripheral blood samples of adult female controls. The median degree of non-random inactivation was similar in MC twins with TTTS, in MC twins without TTTS, and in adult controls. The percentage of individuals with skewed (> or =30/70%) inactivation patterns was no different in MC twins with TTTS compared to those without TTTS, and was similar to adult controls using either enzyme technique. In conclusion we found no difference in the degree or frequency of non-random X-inactivation patterns in TTTS. X-inactivation patterns do not appear to be a useful tool for studying the symmetry of inner cell mass splitting in monochorionic twins.     

Arterio-venous flow between monochorionic twins determined during intra-uterine transfusion

Twin-twin transfusion syndrome (TTTS) is a severe complication of monozygotic (identical) twin fetuses sharing one single (monochorionic) placenta. TTTS is caused by a net inter-twin transfusion of blood through placental anastomoses, from one twin (the donor) to the other (the recipient), which link the two feto-placental circulations. Currently, the only reliable method to measure the net inter-twin transfusion clinically is when incomplete laser therapy of TTTS occurs and one of the twins becomes anemic and requires an intra-uterine transfusion of adult red blood cells. Then, differences between adult hemoglobin concentrations measured during the transfusion and at birth relate not only to the net inter-twin transfusion but also to the finite lifetime of the adult red blood cells. We have analyzed this situation, derived the differential equations of adult hemoglobin in the donor and recipient twins, given the solutions and given expressions relating the net inter-twin flow with clinically measured parameters. We have included single and multiple intra-uterine transfusions. In conclusion, because incomplete laser therapy occurs frequently, and some cases require an intra-uterine transfusion, this method may allow collecting a wealth of net inter-twin flow data from clinicians involved in laser therapy of TTTS. To aid to the widespread use of this method, we have presented the equations as clearly as possible in tables for easy use by others.     

Maternal vascular endothelial growth factor receptor and interleukin levels in pregnant women with twin-twin transfusion syndrome

Twin-twin transfusion syndrome (TTTS) is an unusual and serious condition that occurs in twin pregnancies when identical twins share a placenta but develop discordant amniotic fluid volumes. TTTS is associated with an increased risk of fetal death and birth defects if untreated. This study investigated the soluble levels of biomarkers including growth factors and interleukins in pregnant women with and without TTTS during pregnancy. We quantified plasma levels of VEGF-R1, VEGF-R2, IL-1β, IL-6 and IL-8 in twin pregnant women with (n=53) and without TTTS (n=72) and in women with single pregnancy (n=30) by ELISA and analyzed the association of maternal circulating biomarker levels with TTTS. Our results showed that maternal VEGF-R1 levels were significantly higher in twins compared to single pregnancy (P<0.05) and were decreased in the second trimester compared to the first trimester (P = 0.065, 0.019 and 0.072 for twins with and without TTTS and single pregnancy, respectively). VEGF-R2 levels had a trend to be lower in twins compared to single pregnancy. In addition, soluble VEGF-R1 and VEGF-R2 levels were significantly decreased while IL-6 levels were increased after surgical treatment with laser in twin pregnant women with TTTS (P = 0.016, 0.041 and 0.04, respectively). These results suggest that IL-6, VEGF-R1 and VEGF-R2 are involved in vascular regulation and stabilization in twin pregnancies and may contribute to the pathogenesis of TTTS and thus play a prognostic role in the surgical treatment of TTTS.     

Early demise of twins in a cohort of stillbirths and second trimester miscarriages

Twins, particularly monochorionic (MC) pairs, are at increased risk for fetal death. Whereas previous work has sought to understand the mechanisms for this increased mortality, most studies analyze viable twin pregnancies or liveborn twin cohorts. In the Wisconsin Stillbirth Service Program cohort of 3,137 stillbirths and second trimester miscarriages, we identified 175 twin pregnancies for a twinning rate of 56/1,000, which is approximately double the general population. The excess of twins among miscarriages and stillbirths was attributable to MC pairs as the incidence of dizygotic (DZ) twinning was not increased compared to livebirth data. The leading causes of fetal demise among twins were twin–twin transfusion, acardia, and twin–twin disruption. Maternal causes of death, primarily premature rupture of membranes, were moderately increased in both MC and DZ twins relative to singletons. Although deceased twins were smaller than expected for viable twins at comparable gestational ages, placenta weights of deceased MC pairs were large compared to combined fetal weight, which indicates placental inefficiency likely due to vascular shunting. Co‐twin survival was much lower for MC than for DZ pairs. Therefore, earlier diagnosis and treatment of MC twinning complications may decrease prenatal mortality.     

Doppler detection of arterio-arterial anastomoses in monochorionic twins: feasibility and clinical application

The accuracy of in-vivo detection of arterio-arterial anastomoses (AAA) in monochorionic (MC) twins and its predictive value for twin-twin transfusion syndrome (TTTS) was assessed in 105 consecutive MC twins scanned at fortnightly intervals. AAA were sought using spectral and colour energy Doppler and ultrasound findings were compared with placental injection studies. AAA were identified in vivo in 59 (56%) pregnancies and at injection study in 68 (65%). The overall sensitivity and specificity was 85 and 97.3% respectively for the detection of AAA. Detection rates were higher at later gestations, with anterior placentae and with larger diameter AAA. The median insonation time to detect an AAA was 10 min (range 1-30). Where an AAA was identified, 15% of pregnancies (nine of 59) developed TTTS compared to 61% (28 of 46) when no AAA was seen (odds ratio 8.6). We conclude that AAA can be detected in vivo with high sensitivity and specificity without undue prolongation of scanning times and have a role in risk stratification in the antenatal assessment of MC twins.     

Vascular anatomy of monochorionic placenta in relation to discordant growth and amniotic fluid volume

The objective of this study was to determine the chorionic platevascular anatomy of the monochorionic (MC) placenta in relationto the discordance in fetal growth with or without disparityin amniotic fluid volume. In 58 MC placentae, anastomoses weredelineated by dye-contrast injection under optimal physiologicalconditions. Thirty-two pregnancies were complicated by twin-twintransfusion syndrome (TTTS) (n = 32), of which 16 placentaewere from severe disease. Ten pregnancies with fetal growthdiscordance of >20% and with a normal amniotic fluid index(AFI) were also studied. Sixteen uncomplicated MC pregnancieswere used as controls. Severe TTTS placentae (median, m 1; range,r 0 to 2) had significantly fewer anastomoses than those frommild disease (m 2; r 1 to 4; P < 0.01), discordant growth(m 3; r 2 to 6; P < 0.001) and controls (m 5; r 2 to 8; P< 0.001). Placentae from severe TTTS had a single unidirectionaldeep arteriovenous anastomosis, while milder cases, in addition,had a 1 mm bidirectional superficial arterioarterial (n = 9)or venovenous (n = 6) -type shunts. Multiple arteriovenous anastomoseswith a paucity of superficial anastomoses were detected in discordantgrowth placenta. In contrast, control placentae had multipleshunts which were symmetrical in number, type and size bothoverall and per placenta. The subchorionic distance in severeTTTS and discordant growth placenta were comparable (m 3.5 cm;r 1.6 to 5.8 cm versus m 3.6 cm; r 2.5 to 5.7 cm), but weregreater than the mild disease (m 2.5 cm; r 1.2 to 3.8 cm; P< 0.01) and control groups (m 1 cm; r 0.5 to 2.4 cm; P <0.001). The perinatal mortality in severe TTTS (57%) was higherthan that in the mild TTTS (17%) and growth discordant groups(15%). The paucity of superficial anastomoses with presenceof solitary or multiple arteriovenous anastomoses is likelyto be associated with severe TTTS and fetal growth discordanceof >20% respectively. In contrast, in mild TTTS additionalsuperficial arterioarterial or venovenous channels are presentalong with single deep arteriovenous anastomoses.     

Chimerism involving a RB1 pathogenic variant in monochorionic dizygotic twins with twin–twin transfusion syndrome

We report the first case of blood chimerism involving a pathogenic RB1 variant in naturally conceived monochorionic‐dizygotic twins (MC/DZ) with the twin–twin‐transfusion syndrome (TTTS), presumably caused by the exchange of stem‐cells. Twin A developed bilateral retinoblastoma at 7 months of age. Initial genetic testing identified a de novo RB1 pathogenic variant, with a 20% allelic ratio in both twins' blood. Subsequent genotyping of blood and skin confirmed dizygosity, with the affected twin harboring the RB1 pathogenic variant in skin and blood, and the unaffected twin carrying the variant only in blood.     

Kinetic aspects of monoamine oxidase activity in twins with psychoses

Monoamine oxidase activity was assayed in platelets from 22 (8 monozygotic and 14 dizygotic) twin pairs. At least one twin of each pair had a serious psychiatric disorder (proband). Phenethylamine was used as substrate and the assay was performed at two different oxygen concentrations (0.06 and 0.12 mM). Apparent K_m and V_max values were estimated from double reciprocal plots. The correlation between proband and control twins was high for both apparent K_m (r=0.83) and V_max (r = 0.69) when the enzyme was assayed at the higher concentration of oxygen. The monozygotic twins pairs showed very high correlations (K_m r=0.93; V_max, r = 0.86)as compared to dizygotic twins (K_m r = 0.81, V_max r = 0.50) and apparently healthy subjects (K_m r = 0.46, V_max r = 0.33). No difference in kinetic properties was found between schizophrenic and non-schizophrenic twins.     

Erythropoietin concentrations are elevated in the peritoneal fluid of women with endometriosis

Erythropoietin (Epo) is an important regulator of erythropoiesis and stimulates the proliferation of early erythroid precursors as well as the differentiation of late erythroid precursors of the erythroid lineage. However, recent studies have indicated that Epo also has angiogenic properties and plays an important role in the oestrogen-dependent cyclical angiogenesis within the mouse uterus. It was therefore postulated that Epo may be an important angiogenic factor in endometriosis. In order to address this hypothesis the concentration of Epo in peritoneal fluid (PF) was determined in patients with or without endometriosis. PF was collected from patients with endometriosis (n = 42) or without endometriosis (n = 18). Detectable concentrations of Epo were found in all PF samples analysed. The concentration of Epo in PF from patients with endometriosis was significantly higher than that in the control group (13.1 +/- 1.2 mIU/ml versus 7.2 +/- 0.7 mIU/ml, mean +/- SE respectively, P < 0.01). Furthermore, in patients with endometriosis the Epo concentrations in PF from patients with stage I disease (n = 17, 16.6 +/- 3.0 mIU/ml) were significantly higher than those with stage II (n = 8, 10.7 +/- 1.2 mIU/ml, P < 0.03), III (n = 13, 8.4 +/- 1.0 mIU/ml, P < 0.01), IV disease (n = 7, 7.5 +/- 1.0 mIU/ml, P < 0.01). These data suggest that Epo may play a role in the pathogenesis of endometriosis particularly in the initiation of the disease.     

产前超声检查对双胎输血综合征的价值

目的评价产前超声检查对双胎输血综合征(TTTS)的价值。方法对2005年1月-2010年6月在我院孕早期就判断为单绒毛膜性的12例TTTS患者进行分期、宫内监测等。结果在超声协助下,胎儿存活率为44.4%。结论超声对TTTS可作出早期诊断,并指导临床进行有效的宫内治疗、适时终止妊娠,提高围产儿存活率。     

Birth weight and age at menopause in Australian female twin pairs: exploration of the fetal origin hypothesis

In a twin sample where duration of gestation can be controlled, a specific example of the fetal origins hypothesis concerning association between low birth weight and early age at menopause is explored. The hypothesis is based on the physiologically plausible path from intrauterine growth retardation and reduced numbers of primary follicles to an earlier menopause. The sample comprised 323 Australian female twin pairs where both co-twins had reached menopause naturally and reported on their weight at birth. Regression analysis showed no linear association between the two variables (P = 0.371, r(2) = 0.0009). Intra-pair differences in age at menopause were investigated in the context of relative birth weight of co-twins. In 265 pairs an intra-pair birth weight difference was reported. In monozygotic (MZ) pairs (n = 168) this allowed for control of genetic effects as well as gestation duration. No significant differences dependent on birth weight relative to co-twin were found for age at natural menopause in either MZ or dizygotic (DZ) twin pairs, even in pairs whose birth weights differed markedly. There was some indication that twins with premature ovarian failure were heavier at birth than twins with normal or later menopausal age. We conclude that the hypothesis that lower birth weight is associated with earlier menopause is not supported by our data.     

Modelling the influence of amnionicity on the severity of twin-twin transfusion syndrome in monochorionic twin pregnancies

Clinical treatment for diamniotic-monochorionic twin-twin transfusion syndrome (TTTS) may include conversion of diamniotic pregnancies to a monoamniotic-monochorionic state by disrupting the amnion septum. We sought to test the underlying hypothesis, i.e. that a monoamniotic state reduces the severity of TTTS. With use of our previously developed mathematical model of two equal fetoplacental circulatory units connected by various sizes and types of placental anastomoses, we compared the haemodynamic and amniotic fluid dynamics of monoamniotic and diamniotic twins that develop TTTS. We used three anastomotic patterns that produce severe, moderate or mild forms of TTTS, respectively, in our diamniotic-monochorionic twin model. Monoamnionicity was modelled by adding the two amniotic fluid volumes and using the volume-averaged amniotic fluid osmolality. The results were as follows: for severe TTTS, small differences develop between diamniotic and monoamniotic donor twins in fetal urine production, swallowed volume, blood volume, blood pressures, net fetofetal transfusion, and blood and amniotic fluid osmolality. However, the circulatory imbalance between the monoamniotic twins deteriorates similar to that of diamniotic twins. The pathophysiological differences tend to disappear for milder TTTS. In conclusion, our model suggests that the uncommon finding of TTTS in monoamniotic twins is not due to the presence of a single amniotic sac. Rather, clinically significant differences in anastomotic patterns and the delayed or lack of identification of manifestations in monoamniotic twins account for the reduced rate of TTTS diagnosis. Based on these results we expect the clinical disruption of the amnion septum in diamniotic-monochorionic TTTS pregnancies to have only minimal benefits.     

The feto-placental unit stimulates the pregnancy-associated increase in maternal bone metabolism

The aim of the study was to investigate role of the feto-placental unit in the pregnancy-induced increase in maternal bone metabolism. To achieve this, circulating concentrations of carboxy terminal pro-peptide of type I pro-collagen (PICP, a marker of bone formation) and cross-linked carboxy terminal telopeptide of type I collagen (ICTP, a marker of bone resorption) were measured in three groups of pregnant women. Group 1 comprised 12 women with singleton pregnancies; group 2, nine women with twin pregnancies; and group 3, 19 women with multifetal pregnancies (> or =3 fetuses) before and after selective fetal reduction to twin pregnancies. Blood samples were obtained at 10-12 weeks gestation (groups 1-3, pre-fetal reduction in group 3) and 4 weeks and 8 weeks later (groups 2 and 3). Before fetal reduction there was a significant correlation between the number of fetuses and the concentrations of both PICP and ICTP (r = 0.503 and P = 0.001 and r = 0.573 and P < 0.001 respectively). The circulating concentrations of PICP and ICTP were significantly higher in the pre-reduction multifetal pregnancies than in the twin pregnancies (P < 0.001 and P = 0.0013 respectively). The circulating concentrations of ICTP in multifetal pregnancies fell by 4 weeks after fetal reduction to those observed in control twins. Concentrations of PICP were unaltered after fetal reduction. Higher order multiple pregnancies had the greatest decline in ICTP concentrations. These data suggest that the increased bone turnover observed in the multifetal pregnancies is due to a factor derived from the feto-placental unit and that this factor acts primarily to stimulate bone resorption.     

Morbidity in a Danish national cohort of 472 IVF/ICSI twins, 1132 non-IVF/ICSI twins and 634 IVF/ICSI singletons: health-related and social implications for the children and their families

BACKGROUND: There is a lack of knowledge on child health as well as family well-being in IVF/ICSI twins. METHODS: These data originated from questionnaires completed by mothers taking part in a national cohort study of twin and singleton births occurring in Denmark in 1997. The overall response rate was 83%. The three cohorts consisted of all IVF/ICSI twin children (n = 472), all IVF/ICSI singletons (n = 634) and all non-IVF/ICSI twin children (n = 1132) born in Denmark in 1997. RESULTS: No major differences in physical health were observed between IVF/ICSI twins and non-IVF/ICSI twins. Compared with IVF/ICSI singletons, more IVF/ICSI twins were admitted to a neonatal intensive care unit (NICU) (P < 0.01) and more had surgical interventions (P = 0.03) and special needs (P = 0.02), moreover they had poorer speech development (P < 0.01). Correspondingly, IVF/ICSI twin mothers rated their infant's general health poorer than IVF/ICSI singleton mothers did. All discrepancies between IVF/ICSI twins and singletons disappeared after stratification for birthweight except for NICU admissions and speech development. Multiple logistic regression analyses showed that both IVF/ICSI and non-IVF/ICSI twin parents experienced more marital stress [odds ratio (OR) 2.9, 95% CI 2.2-3.8] and that twins had more impact on the mother's life (OR 1.7, 95% CI 1.2-2.4) compared with singletons. Nevertheless, the only predictor of low divorce/separation risk was IVF/ICSI treatment. CONCLUSION: Our study indicates that physical health of IVF/ICSI twins is comparable with that of non-IVF/ICSI twins. However, physical health of IVF/ICSI twins is poorer and the implications for the families stronger compared with IVF/ICSI singletons.     

Do monochorionic dizygotic twins increase after pregnancy by assisted reproductive technology?

Although monochorionic (MC) dizygotic twins (DZT) are extremely rare in natural pregnancy, six pairs of such twins have successively been reported in a recent short period. All six cases of MC DZT were the products of pregnancy by assisted reproductive technology (ART). In this overview, we summarize these six cases and discuss possible mechanisms of this twinning and clinical implications of confined blood cell chimerism (CBC). The placental MC membrane was diagnosed ultrasonographically in all cases and pathologically in four. The presence of CBC was confirmed in four cases by haplotyping at polymorphic marker loci in peripheral blood leukocytes, karyotyping of lymphocytes and skin fibroblasts, and/or ABO blood group typing. As CBC is attributable to placental vessel anastomosis between DZT, it may become a risk factor for twin–twin transfusion syndrome (TTTS), mortality, and for other complications in twins. MC DZT may produce psychological trauma, especially in a girl/woman when she grows up and is known to be chimeric for a male karyotype and vice versa, although genital organs are generally normal—unlike freemartin in cattle. In addition, CBC in twins may mislead physicians when genotyping for a disease-susceptibility test is performed in medical practice in the near future. Blood group chimera may also cause confusion if a blood transfusion is necessary. Therefore, sufficient informed consent prior to ART and genetic counseling before/after birth are absolutely necessary for improved quality of life. It is most likely that all six cases are the consequence of fusion between two outer cell masses from two zygotes. The ART used in the six MC DZT included in vitro fertilization-embryonic transfer (IVF-ET) into the uterus, FSH-induced superovulation followed by intrauterine insemination, and/or intracytoplasmic sperm injection (ICSI). The use of an ovulation-inducing agent and implantation of several fertilized eggs at close sites are probably the events common among these cases. Assisted hatching, simultaneous ET, the use of eggs that have developed to the blastcyst stage, and cell culture procedures that lead to changes of the nature of cell surface, all may increase the chance of a cell fusion. This chance hypothesis can simply explain why MC DZT are very rare in natural pregnancy. Large-scale research on the prevalence of ART-associated MC DZT and long-term follow-up of the twins are essential.     

单绒毛膜性双胎行射频消融减胎术后结局英文文献的Meta分析

目的 通过对文献进行荟萃分析评估双胎输血综合症（TTTS）与其他单绒毛膜性双胎妊娠并发症患者行射频消融减胎术后预后。方法 检索1990年12月~2019年2月行射频消融减胎术的单绒毛膜性双胎妊娠的英文文献,检索数据库PubMed以及Web of Science。结果 共纳入9篇回顾性研究,包括104例TTTS患者,341例其他手术指征患者。TTTS组术后保留胎儿存活率（62.23%）低于其他手术指征组（80.35%）,差异具有统计学意义（RR=0.85,95%CI:0.74~0.98,P=0.03）。两组胎膜早破发生率分别为3.36%和3.23%,差异具有统计学意义（RR=6.10,95%CI:1.05~35.44,P=0.04）。其余早产率、胎死宫内率均无统计学差异。结论 射频消融术治疗单绒毛膜性双胎具有一定安全性和有效性,TTTS患者术后保留胎儿存活率较低,胎膜早破风险略高,应根据临床条件选择合适的治疗方案。