Assisted Reproductive Technology Twins Research Articles

Perinatal outcome in twins. A hospital based comparative study at a single third-level care centre in Croatia

Background: The goal of our study is to explore the association of assisted reproductive technology (ART) as contributing factor for obstetric complications and perinatal outcome in twin pregnancies during a 14-year period at a single tertiary centre. Methods: We collected the data (from maternal and neonatal medical records) from 731 twin pregnancies; 192 conceived by ART and 539 twin pregnancies conceived naturally during a 14-year period. Results: Pregnancy complications in twin pregnancies mainly included preterm premature rupture of membranes, gestational diabetes mellitus, and preeclampsia. Higher occurrence of placenta praevia in the ART group was the only perinatal risk related to twin pregnancies in the ART group as compared to those conceived naturally. Over 71% of ART twins were delivered by caesarean section, which is considerably increased as compared to non-ART twins (p = 0.042). Neonatal complications in both groups mainly included low Apgar score in the 1st minute, low birth weight and admission to NICU, and the incidences of these complications were comparable between the groups. Conclusion: Our results indicated that ART procedures were not followed by adverse obstetric and perinatal outcome in twin pregnancy delivered at single tertiary centre, except for the slightly higher risk of placenta praevia.

Perinatal outcomes in vanishing twin pregnancies following assisted reproductive technology (ART) - a systematic review and meta-analysis.

Objectives To compare the fetal and maternal outcomes in surviving singletons of vanishing twin, with singletons or twins, in pregnancies following assisted reproductive technology (ART). Content We searched the PubMed, Embase, Web of Science and Cochrane databases from the time of conception of the database until Dec 2019 to identify relevant published studies. Perinatal outcomes were synthesized with random effects meta-analysis using RevMan 5.3. Summary and Outlook Fifteen studies were included. Dichorionic twin pregnancies conceived by ART wherein the vanishing twin phenomenon occurred had a risk of fetal malformation similar to that of ART singleton pregnancies (OR=1.25; 95% CI 0.87-1.79) and a higher risk of fetal malformation compared with ART twin pregnancies (OR=1.82; 95% CI 1.23-2.70). Moreover, the remaining fetus in ART vanishing twin pregnancy was at a significantly higher risk of preterm birth (<37 weeks) compared to fetuses in ART singleton pregnancies (OR=2.41; 95% CI 1.46-3.99) and a markedly lower risk of preterm birth (<37 weeks) compared to the fetuses in ART twin pregnancies (OR=0.19; 95% CI 0.16-0.22). Meanwhile, the risk of delivery of infants who were small for gestational age (SGA) was significantly higher in ART vanishing twin pregnancies compared to that in ART singleton pregnancies (OR=2.70; 95% CI 1.39-5.24) and similar to that in ART twin pregnancies (OR=0.67; 95% CI 0.27-1.65). The risks of preterm birth and of the infant being SGA is higher for the remaining fetus in an ART vanishing twin pregnancy compared to those for the fetuses in ART singleton pregnancies; the risk of fetal malformation is also higher in such cases compared with ART twin pregnancies.

The contribution of twins conceived by in vitro fertilization to preterm birth rate: observations from a quarter of century.

Objective Little information exists related to the contribution of assisted reproductive technology (ART) twins to the preterm and very preterm birth rate. We sought to examine this contribution over a period of more than two decades in a tertiary perinatal center. Methods We identified all preterm births from 1993 to 2017, born at <37 or <32 weeks' gestation, by mode of conception [in vitro fertilization (IVF) vs. non-IVF pregnancies]. We generated trend lines of the annual change of the dependent variable (% preterm birth). Results We evaluated 74,299 births, including 3934 (5.3%) preterm births at <37 and 826 (1.1%) at <32 weeks' gestation. In this period, 1019 (1.4%) twin pairs were born including 475 (46.6%) and 80 (7.8%) at <37 and <32 weeks, respectively. There were 213 (5.4%) IVF pregnancies among the preterm births at <37 weeks, including 88 (41.3%) twins. Fifteen (1.8%) births of all IVF gestations were at <32 weeks, and all were twins. Whereas the annual rate of spontaneous twins did not change, a significant increase over time exists for IVF twins (P < 0.05, R2 = 0.6). We demonstrated an increase in IVF twin births at <37 weeks but not for spontaneously conceived twins. Whereas the twin birth rate at <32 weeks did not change over time, all preterm births at <32 weeks following IVF were twins. Conclusions The risk of twins after ART increasingly contributes to preterm births at <37 weeks and ART twins are at significant risk for preterm births at <32 weeks.

Time trends in placenta-mediated pregnancy complications after assisted reproductive technology in the Nordic countries

The use of assisted reproductive technology is increasing worldwide and conception after assisted reproduction currently comprises 3%-6% of birth cohorts in the Nordic countries. The risk of placenta-mediated pregnancy complications is greater after assisted reproductive technology compared with spontaneously conceived pregnancies. Whether the excess risk of placenta-mediated pregnancy complications in pregnancies following assisted reproduction has changed over time, is unknown. To investigate whether time trends in risk of pregnancy complications (hypertensive disorders in pregnancy, placental abruption and placenta previa) differ for pregnancies after assisted reproductive technology compared with spontaneously conceived pregnancies during 3 decades of assisted reproduction treatment in the Nordic countries. In a population-based cohort study, with data from national health registries in Denmark (1994-2014), Finland (1990-2014), Norway (1988-2015) and Sweden (1988-2015), we included 6,830,578 pregnancies resulting in delivery. Among these, 146,998 (2.2%) were pregnancies after assisted reproduction (125,708 singleton pregnancies, 20,668 twin pregnancies and 622 of higher order plurality) and 6,683,132 (97.8%) pregnancies were conceived spontaneously (6,595,185 singleton pregnancies, 87,106 twin pregnancies and 1,289 of higher order plurality). We used logistic regression with post-estimation to estimate absolute risks and risk differences for each complication. We repeated analyses for singleton and twin pregnancies, separately. In subsamples with available information, we also adjusted for maternal body mass index, smoking during pregnancy, previous cesarean delivery, culture duration, and cryopreservation. The risk of each placental complication was consistently greater in pregnancies following assisted reproductive technology compared with spontaneously conceived pregnancies across the study period, except for hypertensive disorders in twin pregnancies, where risks were similar. Risk of hypertensive disorders increased over time in twin pregnancies for both conception methods, but more strongly for pregnancies following assisted reproductive technology (risk difference, 1.73 percentage points per 5 years; 95% confidence interval, 1.35-2.11) than for spontaneously conceived twins (risk difference, 0.75 percentage points; 95% confidence interval, 0.61-0.89). No clear time trends were found for hypertensive disorders in singleton pregnancies. Risk of placental abruption decreased over time in all groups. Risk differences were -0.16 percentage points (95% confidence interval, -0.19 to -0.12) and -0.06 percentage points (95% confidence interval, -0.06 to -0.05) for pregnancies after assisted reproduction and spontaneously conceived pregnancies, respectively, for singletons and multiple pregnancies combined. Over time, the risk of placenta previa increased in pregnancies after assisted reproduction among both singletons (risk difference, 0.21 percentage points; 95% confidence interval, 0.14-0.27) and twins (risk difference, 0.30 percentage points; 95% confidence interval, 0.16-0.43), but remained stable in spontaneously conceived pregnancies. When adjusting for culture duration, the temporal increase in placenta previa became weaker in all groups of assisted reproductive technology pregnancies, whereas adjustment for cryopreservation moderately attenuated trends in assisted reproductive technology twin pregnancies. The risk of placenta-mediated pregnancy complications following assisted reproductive technology remains higher compared to spontaneously conceived pregnancies, despite declining rates of multiple pregnancies. For hypertensive disorders in pregnancy and placental abruption, pregnancies after assisted reproduction follow the same time trends as the background population, whereas for placenta previa, risk has increased over time in pregnancies after assisted reproductive technology.

Maternal and Neonatal Outcomes of Monochorionic and Dichorionic Twin Pregnancies Following Assisted Reproductive Technology in Southern Iranian Women

ObjectivesThis study aimed to investigate the effect of assisted reproductive technology (ART) on both maternal and neonatal outcomes in monochorionic (MC) and dichorionic (DC) twin pregnancies.MethodsThis retrospective cohort study was conducted on women with twin pregnancies who delivered at Hafez and Hazrat Zeinab hospitals (affiliated to the Shiraz University of Medical Sciences) from March 2013 to May 2018.ResultsIn this study, 651 twin pregnancies (122 MC and 529 DC) were analyzed. Among MC twin pregnancies, the adverse maternal and neonatal outcomes were similar between the ART and the spontaneous pregnancies, except for lower 1-minute and 5-minute Apgar scores (5.3 vs. 7.2; P = 0.036 and 6.4 vs. 8.5; P = 0.039, respectively) and a higher fetal death rate in ART group (19% vs. 3.5%, P = 0.001). Among the DC twin pregnancies, the risks for pregnancy-related hypertensive disorders, gestational diabetes mellitus, emergency cesarean section and antenatal corticosteroid exposure significantly increased in the ART group (P < 0.001, P = 0.002, P = 0.014, and P = 0.001, respectively). Furthermore, DC twins showed significantly higher rates of deliveries before the 34 weeks of gestation (44.8% vs. 31.0%, P = 0.002), extremely low birth weight (11.9% vs. 4.0%, P < 0.001), intrauterine fetal growth restriction (29.3% vs. 13.5%, P < 0.001), lower 1-minute (P = 0.009 for fetus A and P = 0.003 for fetus B, respectively) and 5-minute (P < 0.001 for fetus A and P < 0.001 for fetus B, respectively) Apgar scores, perinatal mortality (14.4% vs. 6.9%, P < 0.001) and congenital anomaly (8.3% vs. 2.3%, P = 0.001) after ART treatment. These results were confirmed by multivariate analysis after adjusting for the baseline variables.ConclusionsDespite the controversial perinatal outcomes in the literature, we found that ART is associated with an increased risk of perinatal morbidity and mortality, particularly in DC twin pregnancies. Therefore, ART twin pregnancies management requires closer surveillance and advanced facilities at tertiary care centers.

Neonatal outcomes among twins following assisted reproductive technology: an Australian population-based retrospective cohort study

BackgroundWhile their incidence is on the rise, twin pregnancies are associated with risks to the mothers and their babies. This study aims to investigate the likelihood of adverse neonatal outcomes of twins following assisted reproductive technology (ART) compared to non-ART twins.MethodsA retrospective population study using the Australian National Perinatal Data Collections (NPDC) which included 19,662 twins of ≥20 weeks gestational age or ≥ 400 g birthweight in Australia. Maternal outcomes and neonatal outcomes (preterm birth, low birth weight, resuscitation and neonatal death) were compared. Generalized Estimating Equations were used to assess the likelihood of any neonatal outcomes, with adjusted odds ratio (AOR) and 95% confidence intervals (CI) presented. Weinberg’s differential rule was used to estimate monozygotic twin rate.ResultsART mothers were 3.3 years older than non-ART mothers. The rates of pregnancy-induced hypertension and gestational diabetes were significantly higher for ART mothers than non-ART mothers (12.2% vs. 8.4%, p < 0.01) and (9.7% vs. 7.5%, p < 0.01) respectively. The incidence of monozygotic twins was 2.0% for ART twins and 1.1% for non-ART twins. Compared with non-ART twins, ART twins had higher rates of preterm birth (AOR 1.13, 95% CI: 1.05–1.22), low birth weight (AOR 1.13, 95% CI: 1.05–1.22), and resuscitation (AOR 1.26, 95% CI: 1.17–1.36). Liveborn ART twins had 28% (AOR 1.28, 95% CI 1.09–1.50) increased odds of having any adverse neonatal outcome compared to liveborn non-ART twins, especially for opposite-sex ART twins (AOR 1.42, 95% CI 1.11–1.82).ConclusionAs ART twins had higher rates of adverse outcome, special prenatal care is recommended. Couples accessing ART should be fully informed of the risk of adverse outcome of twin pregnancies.

Unusual twinning: Additional findings during prenatal diagnosis of twin zygosity by single nucleotide polymorphism (SNP) array.

To evaluate the incidence and characteristics of unusual twinning by using single nucleotide polymorphism (SNP) array to identify twin zygosity. This study reviewed 386 twin pairs who were seen for prenatal or postnatal diagnosis and underwent SNP array to detect zygosity. The incidence of monozygotic (MZ) twins was 11.36% (25/220) in the assisted reproductive technology (ART)-conceived group. Monochorionic dizygotic twins represented 3 of 24 monochorionic ART-conceived twin pairs (3/24, 12.50%) but none in the spontaneous twin pairs. Among 4 single-embryo transfer twin pairs, 3 represented unusual twinning, including 2 MZ twin pairs with discordant karyotypes and 1 dizygotic twin pair of the same gender. Of the pregnancies with 2 or more embryos transferred, 7.77% (15/193) were MZ. Additionally, there was a dichorionic monozygotic twin pair with placental vascular anastomoses from a day-5 blastocyst transfer. Single nucleotide polymorphism array can provide zygosity diagnosis in addition to chromosomal copy number variation and uniparental disomy detection. ART twin pregnancies have a risk of unusual twinning, such as monochorionic dizygotic, single-embryo transfer twin pairs with discordant karyotypes or dizygotic, and dichorionic monozygotic with vascular anastomoses from day-5 transfer.

Fetal cardiac remodeling in twin pregnancy conceived by assisted reproductive technology.

Recent data suggest that singleton fetuses conceived by assisted reproductive technology (ART) present cardiovascular remodeling that may persist postnatally. Twin pregnancies are more frequent in the ART population and are associated with increased adverse perinatal outcomes, such as hypertensive disorders, gestational diabetes and preterm birth. However, it is unknown whether cardiac remodeling is also present in twin pregnancies conceived by ART. Our aim was to assess the presence of fetal cardiac remodeling and dysfunction in twin pregnancies conceived by ART as compared with those conceived spontaneously (SC). This was a prospective cohort study including 50 dichorionic twin fetuses conceived by ART and 50 SC twin fetuses. The study protocol included collection of baseline/perinatal data and a fetal ultrasound examination at 28-30 weeks' gestation, including assessment of estimated fetal weight, fetoplacental Doppler and fetal echocardiography. Measurements of atrial area, atrial/heart ratio, ventricular sphericity index, free wall thickness, mitral and tricuspid annular plane systolic excursions, and systolic and early diastolic peak velocities were assessed. Multilevel analyses were used to compare perinatal and ultrasonographic parameters. Comparisons of echocardiographic variables were adjusted for parental age, paternal body mass index and incidence of pre-eclampsia. Compared with SC twins, ART twin fetuses showed significant cardiac changes, predominantly affecting the right heart, such as dilated atria (right atrial/heart area: 15.7 ± 3.1 vs 18.4 ± 3.2, P< 0.001), more globular ventricles (right ventricular sphericity index: 1.57 ± 0.25 vs 1.41 ± 0.23, P = 0.001) and thicker myocardial walls (septal wall thickness: 2.57 ± 0.45 mm vs 2.84 ± 0.41 mm, P = 0.034) together with reduced longitudinal motion (tricuspid annular plane systolic excursion: 6.36 ± 0.89 mm vs 5.18 ± 0.93 mm, P< 0.001). ART twin fetuses present signs of cardiac remodeling and dysfunction. These changes are similar to those observed in ART singletons and reinforce the concept of fetal cardiac programing in ART. These results open opportunities for early detection and intervention in infants conceived by ART. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Outcome of monochorionic-biamniotic twins conceived by assisted reproduction: a population-based study.

We compared data from a national population-based perinatal registry on perinatal outcomes of monochorionic-diamniotic twins conceived by ART with their dichorionic counterparts and with spontaneous monochorionic-diamniotic twins. We compared maternal characteristics, pregnancy complications and perinatal outcomes. Monochorionic-diamniotic twin pregnancies (n=45) comprised 5.5% of all ART twins, and 9.3% of all monochorionic twins in this dataset. ART does not appear to increase the already high risk of monochorionicity compared to spontaneous conception, with the latter having an increased incidence for birth weight <1500 g [odds ratio (OD) 2.6, 95% confidence interval (CI) 1.2-5.4]. Our results disagree with hospital-based data and suggest that monochorionic-diamniotic twins following ART are not at increased risk of adverse perinatal outcomes compared to spontaneous monochorionic-diamniotic twins as well as to dichorionc twins conceived by ART.

Congenital heart disease in twins: The contribution of type of conception and chorionicity

BackgroundIncreased incidence of congenital heart disease (CHD) has been reported in the offspring of monochorionic twin gestations. Assisted reproductive technology (ART), which is related to increased rates of twinning, has also been associated with higher risk of birth defects. We studied the incidence of CHD in a cohort of twins to clarify the contribution of type of conception and chorionicity. MethodsData concerning 874 live-born twins of which at least one was admitted in our Neonatal Unit during 1995–2012 were analysed. Forty-five % (N=197) of the gestations resulted from ART (in vitro fertilisation or intracytoplasmic sperm insertion). ResultsIn the ART group 32/389 (8.2%) had CHD compared to 21/485 (4.3%) infants conceived naturally (OR 1.90, 95%CI 1.08–3.34, p=0.024). Spontaneous-conception gestations had higher incidence of monochorionic placentation (47/245 versus 4/197, p<0.001), and included younger mothers (29.1±5.2 versus 33.9±5.5years, p<0.001) who had higher parity (median 2 [range 1–7] versus 1 Pinborg (2005), Blondel and Kaminski (2002), Knopman et al. (2014), Kyvik and Derom (2006) ; p<0.001). Multivariable logistic regression analysis showed that ART (OR 2.60, 95% CI 1.24–5.45) and monochorionicity (OR 3.49, 95% CI 1.57–7.77) were significant determinants of CHD, independently of maternal age, parity, and the gender of the offspring. ConclusionsWe confirmed that monochorionic twins have increased risk of CHD and we documented a higher incidence of CHD in ART twins independently of chorionicity. We suggest improvement of echocardiographic skills of health care professionals involved in prenatal screening and foetal cardiology referral of ART dichorionic twins with suspicious findings at screening, in addition to all monochorionic gestations.

Chorionic Villus Sampling in Assisted Versus Spontaneous Conception Twins

Purpose To compare the outcome of chorionic villus sampling (CVS) in twin pregnancies following assisted reproduction technology (ART) versus twins that have been conceived spontaneously. Materials and Methods Retrospective analysis of dichorionic twin pregnancies that underwent CVS between 1986 and 2013 at our department which is a tertiary center for fetal medicine. 32 twin pregnancies after ART and 130 spontaneously conceived twin pregnancies, which underwent CVS, were analyzed. Results No difference was observed in the pregnancy loss rate between the two groups (0 % in the ART group vs. 3 % in the spontaneous twins group). The rate of preterm delivery before 28 weeks was higher in the ART group (18.8 %) compared to the control group (1.6 %). The perinatal mortality rate was similar in the two groups. Conclusion The pregnancy loss rate following CVS is similar in ART twins and in spontaneous twins. However, the risk of prematurity before 28 weeks is significantly higher in the ART group.

Outcome of monochorionic twins conceived by assisted reproduction

To evaluate monochorionic twins conceived by assisted reproductive technology (ART). We compared perinatal outcomes of monochorionic twins conceived by ART with their dichorionic counterparts and with spontaneous monochorionic twins. Referral center. Mothers to monochorionic and dichorionic twins conceived by ART and spontaneous monochorionic twins. None. Maternal characteristics, pregnancy complications, and perinatal outcomes. Monochorionic twin pregnancies (n = 25) comprise 7.2% of all ART twins and 4.9% of all monochorionic twins in this data set. Monochorionic pairs have a significantly worse outcome compared with dichorionic sets in terms of lower gestational age and birth weight. ART appears to increase the already high risk of monochorionicity compared with spontaneous conception: odds ratio (OR), 2.9 (1.1-7.3) for preterm birth at <32 weeks and OR, 5.9 (2.5-1.49) for birth weight <1,500g. Monochorionic twins after ART are at increased risk of adverse perinatal outcomes compared with spontaneous monochorionic twins and with dichorionic twins conceived by ART.

Risk of hypertensive disorders in pregnancies following assisted reproductive technology: a cohort study from the CoNARTaS group.

Is the risk of hypertensive disorders in pregnancies conceived following specific assisted reproductive technology (ART) procedures different from the risk in spontaneously conceived (SC) pregnancies? ART pregnancies had a higher risk of hypertensive disorders, in particular following cryopreservation, with the highest risk seen in twin pregnancies following frozen-thawed cycles. The risk of hypertensive disorders is higher in ART pregnancies than in SC pregnancies. The increased risk may be partly explained by multiple pregnancies and underlying infertility, but a contribution from specific ART procedures has not been excluded. Population-based cohort study, including sibling design with nationwide data from health registers in Sweden, Denmark and Norway. All registered ART pregnancies and a sample of SC pregnancies with gestational age ≥22 weeks from 1988 to 2007 were included. ART singleton pregnancies (n = 47 088) were compared with SC singleton pregnancies (n = 268 599), matched on parity and birth year. ART twin pregnancies (n = 10 918) were compared with SC twin pregnancies (46 674). We used logistic regression to estimate adjusted odds ratios and risk differences for hypertensive disorders in pregnancies following IVF, ICSI and fresh or frozen-thawed cycles. We also compared fresh and frozen-thawed cycles within mothers who had conceived following both procedures using conditional logistic regression (sibling analysis). Hypertensive disorders were reported in 5.9% of ART singleton and 12.6% of ART twin pregnancies. Comparing singleton pregnancies, the risk of hypertensive disorders was higher after all ART procedures. The highest risk in singleton pregnancies was seen after frozen-thawed cycles [risk 7.0%, risk difference 1.8%, 95% confidence interval (CI) 1.2-2.8]. Comparing twin pregnancies, the risk was higher after frozen-thawed cycles (risk 19.6%, risk difference 5.1%, 95% CI 3.0-7.1), but not after fresh cycles. In siblings, the risk was higher after frozen-thawed cycles compared with fresh cycles within the same mother (odds ratio 2.63, 95% CI 1.73-3.99). There were no clear differences in risk for IVF and ICSI. The number of ART siblings in the study was limited. Residual confounding cannot be excluded. In addition, we did not have information on all SC pregnancies in each woman's history, and could therefore not compare risk in ART versus SC pregnancies in the same mother. Pregnancies following frozen-thawed cycles have a higher risk of hypertensive disorders, also when compared with fresh cycle pregnancies by the same mother. The safety aspects in frozen-thawed cycles merit further attention. Funding was received from the European Society for Human Reproduction and Embryology, the University of Copenhagen, the Danish Agency for Science, Technology and Innovation, the Nordic Federation of Societies of Obstetrics and Gynecology and the Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology. None of the authors has any competing interests to declare.

Assisted reproductive technology and risk of congenital malformations: a meta-analysis based on cohort studies.

To assess the association between assisted reproductive technology (ART) and risk of congenital malformations (CM) by conducting a meta-analysis of cohort studies. PubMed, Google Scholar, Cochrane Libraries and Chinese database were searched through August 2014 to identify studies that met pre-stated inclusion criteria. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analysis was performed to explore potential heterogeneity moderators. Fifty-seven studies involving 119,874 infants conceived following ART and 1,212,320 infants conceived naturally were included in the analysis. The ART-conceived infants were associated with a higher risk of CM [relative risk (RR)=1.33; 95% confidence interval (CI) 1.24-1.43] when compared with those conceived naturally. When data were restricted to singleton births (RR=1.38; 95% CI 1.30-1.47), major CM (RR=1.47; 95% CI 1.29-1.68), matched/adjusted studies (RR=1.37; 95% CI 1.27-1.47) or high quality studies (RR=1.40; 95% CI 1.27-1.55), the increased risk of CM still existed in ART pregnancies. Additionally, an increased risk of CM was also found when the ART twin (RR=1.18; 95% CI 1.06-1.32) or multiple births (RR=1.16; 95% CI 1.05-1.27) were separately compared with spontaneously conceived twin or multiple births. Substantial heterogeneity was observed across studies (I (2)=68, 44, 39, and 33% for all infants, singletons, twins and multiples, respectively). Whether confounding factors were matched or adjusted, study quality and sample size as the first three of the most relevant heterogeneity moderators have been identified. No evidence of publication bias was observed (P>0.10). The ART-conceived infants have a higher risk of CM compared with those conceived naturally. However, these estimates have to be viewed with caution because of heterogeneity.

İkiz gebeliklerde koryon ve amniyon tiplerinin dağılımı

Objective: Our aim was to determine the distribution of chorion and amnion sac types in twin pregnancies during the routine screening procedures during the first trimester, and to investigate their relevance with pregnancy being natural or by assisted reproductive technology. Methods: Twin pregnancies analyzed during routine first trimester screening were evaluated retrospectively. The twins were grouped according to their conception types which are natural birth and by assisted reproductive technologies (ART). The cases which have missing or suspicious information about chorion-amnion types and with unknown conditions for pregnancies whether they were by ART or naturally were excluded from the study. In the sonographic chorionicity distinction, the presence of classic lambda and T signs was considered. The unavailability of amniotic membrane among fetuses was defined as monoamniotic twin. Results: During 14 years, 286 twin pregnancies were considered as appropriate cases to analyze. Mean maternal age was 30.47±5.07 years, and mean week of gestation during sonography was 12.23±0.70. Double placentas were found in 83.2% of all pregnant women, and single placenta in 16.7% of all pregnant women. While 54.5% (n=156) of twin pregnancies were ART pregnancies, 45.5% of them were natural pregnancies. It was determined that 67.7% of natural twins were diamniotic dichorionic, 27.7% of them were diamniotic monochorionic and 4.6% of them were monoamniotic monochorionic while 96.2% of ART pregnancies were diamniotic dichorionic, 3.2% of them were diamniotic monochorionic and 0.6% of them were monoamniotic monochorionic. There was statistically significant difference between ART twins and natural twins in terms of chorionicity distributions (p<0.05). Conclusion: Monochorionic structure is observed more frequently in natural twins. In the follow-up of these pregnancies, early and accurate diagnosis may be the basis of early and accurate approach for the issues related with monochorionic placentation.

Hospital Costs of Multiple-Birth and Singleton-Birth Children During the First 5 Years of Life and the Role of Assisted Reproductive Technology

The unprecedented increase in multiple births during the past 3 decades is a major public health concern and parallels the uptake of medically assisted conception. The economic implications of such births are not well understood. To conduct a comprehensive economic and health services assessment of the frequency, duration, and cost of hospital admissions during the first 5 years of life for singleton, twin, and higher-order multiple (HOM) children and to examine the contribution of assisted reproductive technology (ART) to the incidence and cost of multiple births. A retrospective population cohort study using individually linked birth, hospital, and death records among 233,850 infants born in Western Australia between October 1993 and September 2003, and followed up to September 2008. Multiple-gestation delivery and ART conception. Odds of stillbirth, prematurity and low birth weight, frequency and length of hospital admissions, the mean costs by plurality, and the independent effect of prematurity on childhood costs. Of 226,624 singleton, 6941 twin, and 285 HOM infants, 1.0% of singletons, 15.4% of twins, and 34.7% of HOM children were conceived following ART. Compared with singletons, twins and HOMs were 3.4 and 9.6 times, respectively, more likely to be stillborn and were 6.4 and 36.7 times, respectively, more likely to die during the neonatal period. Twins and HOMs were 18.7 and 525.1 times, respectively, more likely to be preterm, and 3.6 and 2.8 times, respectively, more likely to be small for gestational age. The mean hospital costs of a singleton, twin, and HOM child to age 5 years were $2730, $8993, and $24,411 (in 2009-2010 US dollars), respectively, with cost differences concentrated in the neonatal period and during the first year of life. Almost 15% of inpatient costs for multiple births could have been avoided if ART twins and HOMs had been born as singletons. Compared with singletons, multiple-birth infants consume significantly more hospital resources, particularly during the neonatal period and first year of life. A significant proportion of the clinical and economic burden associated with multiple births can be prevented through single-embryo transfer. Increasing ART use worldwide and persistently high ART multiple-birth rates in several countries highlight the need for strategies that encourage single-embryo transfer. The costs from this study can be generalized to other settings.

Cervical conization doubles the risk of preterm and very preterm birth in assisted reproductive technology twin pregnancies

Does cervical conization add an additional risk of preterm birth (PTB) in assisted reproduction technology (ART) singleton and twin pregnancies? Cervical conization doubles the risk of preterm and very PTB in ART twin pregnancies. ART and cervical conization are both risk factors for PTB. In this national population-based controlled cohort study, we included all ART singletons and twin deliveries from 1995 to 2009 in Denmark by cross-linkage of maternal and child data from the National IVF register and the Medical Birth register. Furthermore, control groups of naturally conceived (NC) singletons and twins were extracted. Cervical diagnoses were obtained from the Danish Pathology register. Cervical conization included both cold knife cone and LEEP (loop electrosurgical excision procedure) but not cervical biopsies. The main outcomes measures were PTB (PTB ≤ 37 + 0 gestational weeks), very preterm birth (VPTB ≤ 32 + 0 gestational weeks) and preterm premature rupture of membranes (PPROM). In all 16 923 ART singletons and 4829 ART twin deliveries were included. A random sample of NC singletons, 2-fold the size of the ART singleton group matched by date and year of birth (n = 33 835) and all NC twin deliveries (n = 15 112), was also extracted. Multiple logistic regression analyses were performed to adjust for the following confounders: maternal age, parity, year of child birth and sex of child. Cervical morbidity (dysplasia and conization) was more often observed in ART pregnancies (6.2% of ART singletons and 5.4% ART twins) than in NC pregnancies (4.2% for NC singletons and 4.5% for NC twins), both for singletons and twins. In ART singleton deliveries, the PTB rate was 13.1 versus 8.2% in women with and without conization, respectively, with an adjusted odds ratio (aOR) of 1.56 [95% confidence interval (CI) 1.21-2.01]. In ART twin deliveries, the prevalence of PTB was 58.2 versus 41.3% in women with and without conization, respectively, with an aOR 1.94 (95% CI 1.36-2.77), and the risk of VPTB was also doubled. Furthermore, previous dysplasia (without conization) increased the risk of VPTB in ART twins (aOR 1.74, 95% CI 1.04-2.94). Cervical dysplasia did not increase the risk of any of the other adverse outcomes in ART singletons or twins. The risk of PPROM was increased in both in ART and NC singleton deliveries with conization versus no conization; however, this increased risk of PPROM after conization was not observed in either ART or NC twin pregnancies. We were not able to adjust for the height of the cervical cone or the severity of the cervical intraepithelial neoplasia (CIN) or the time window between diagnosis of CIN and ART treatment. The finding on an increased risk of VPTB in ART twin pregnancies after dysplasia without conization may be random as we found no other increased risk after dysplasia alone either in singletons or in twins. After ART and prior conization, 58% of twin pregnancies versus 13% of ART singleton pregnancies result in PTB. There is a doubled risk of preterm delivery in ART twins with conization versus ART twins with no prior conization. Single-embryo transfer should always be recommended in women with prior conization irrespective of female age, embryo quality and prior number of ART attempts. No external funding was achieved for this project.

Twins conceived using assisted reproduction: parent mental health, family relationships and child adjustment at middle childhood.

Compared with singletons, what is the parent mental health, parent-child and couple relationship satisfaction, and child adjustment of 6- to 12-year-old assisted reproduction technology (ART) twins and their families? There are no differences between 6- and 12-year-old ART twin and singleton families in parent mental health or family relationships; however, twins had significantly fewer behavior and attention problems than singletons in middle childhood. When ART twins are younger than 5 years old, parents have more mental health difficulties and poorer parent-child relationship quality, and no differences have been found in ART twin and singletons' psychosocial adjustment. However, studies have only examined the implications of ART twin status in families with infant and toddler aged children. A cross-sectional study of 300 6-12-year-old ART children (n = 124 twins and n = 176 singletons) from 206 families at a reproductive endocrinology clinic in the USA. Patients from one clinic with a child born between 1998 and 2004 were invited to participate in an online survey (82% recruitment rate). Participants provided information on each 6- to 12-year-old ART child in the family, and responded to questions on parent mental health, family relationships and child adjustment. There were no differences in parent mental health or family relationships in families with 6- to 12-year-old ART twins versus singletons. However, twins (M = 2.40, SE = 0.35) had significantly fewer behavior problems than singletons (M = 3.47, SE = 0.36; F(1, 201) = 4.54, b = 1.08, P < 0.05). Twins (M = 1.86, SD = 0.23) also had fewer attention problems than singletons (M = 2.64, SD = 0.23; F(1, 156) = 5.75, b = 0.78, P < 0.05). Results also suggest that full-term twins had significantly fewer attention problems (M = 1.37, SE = 0.33; F(1, 222) = 2.65, P = 0.05) than premature twins (M = 2.32, SE = 0.32, b = 0.95, P < 0.05), full-term singletons (M = 2.25, SE = 0.21, b = 0.88, P < 0.05) and premature singletons (M = 2.84, SE = 0.49, b = 1.47, P = 0.01). There were no significant differences between the other groups. Although the response rate is high (82%) and family demographics are representative of US ART patients, patients are from one US clinic. Responses also are from one family member and may be subject to social desirability biases. Additionally, our data did not include identification of monozygotic and dizygotic twins. Studies on infant and toddler ART twins suggest these families have parents with more mental health difficulties and lower parent-child relationship quality than singleton families. This study indicates the negative effects of twin status may have ameliorated by middle childhood, and twins may even have more optimum psychosocial adjustment than singletons in this developmental period. This research is based on a collaborative research effort supported by University of Minnesota Agriculture Experiment Station Project Number MN-52-107, a University of Minnesota Grant-in-Aid of Research, Artistry and Scholarship grant, a University of Minnesota College of Education and Human Development Research Development Investment Grant and the M. Janice Hogan Fellowship. The authors of this article have no commercial or corporate interests to declare.

Nuchal translucency in twins according to mode of assisted conception and chorionicity

The impact of nuchal translucency (NT) screening in twins conceived after use of assisted reproduction technology (ART) has not been addressed properly in the literature. The aim of the current study was to assess, in a large cohort from a single center, NT in twins following various modes of ART as compared with NT in spontaneously-conceived twins and to differentiate results with regard to chorionicity. Retrospective data from 825 twin pregnancies were available for this study. All pregnant women underwent NT screening and chorionicity determination between 11 + 0 and 13 + 6 weeks' gestation in our center. Information about mode of conception and pregnancy outcome was obtained from hospital records and by telephone interviews. Twins were classified as having been conceived after in-vitro fertilization (IVF) with the woman's own or a donated embryo, after non-IVF ART or spontaneously. NT distribution in subgroups of fetuses was compared on the basis of the multiple of the normal median (MoM), SD of log10 MoM estimated by the 90(th) -10(th) centile range divided by 2.563 and the proportion of NT values exceeding the normal 95(th) centile which was 1.641 MoM in the singletons. NT values were statistically significantly higher in ART pregnancies as compared with spontaneously-conceived pregnancies (Wilcoxon rank-sum test, P < 0.05) with medians of 1.073 and 1.038 MoM, respectively, but the proportion with values above the normal 95(th) percentile did not differ (chi-square test, P = 0.89). Among the ART twins, NT values were significantly higher for those conceived using IVF methods (P < 0.005), with a median of 1.082 MoM, compared with a median of 1.022 MoM using other methods. However, although a greater proportion exceeded the 95(th) centile (7.3% compared with 4.8%) this difference did not reach statistical significance (P = 0.17). There were no differences in NT values according to chorionicity (Wilcoxon rank-sum test, P = 0.75). The standard deviation of log10 NT was similar for all subgroups of twins. The correlation coefficient between fetuses in ART pregnancies was statistically significantly lower than that in spontaneously-conceived pregnancies (P < 0.05) but no significant differences were found between types of ART or according to chorionicity. There was a small but significant increase in NT levels among ART pregnancies, which appeared to be confined to those conceived using IVF, and a small reduction in the correlation between fetuses. These effects probably have little impact on the estimated risk based on algorithms in use today.

Assisted reproductive technology and birth defects: a systematic review and meta-analysis

It has been 10 years since we carried out a systematic search of the literature on birth defect risk in infants born following assisted reproductive technology (ART) compared with non-ART infants. Because of changes to ART practice since that review and the publication of more studies the objective of this review was to include these more recent studies to estimate birth defect risk after ART and to examine birth defect risk separately in ART singletons and multiples. We searched Medline, Embase and Current Contents databases (1978-2012). We used the same data extraction sheet and questionnaire we had used previously with the addition of a quality score to the questionnaire. Pooled relative risk (RR) estimates were calculated using a random effects model. All data were analysed using Comprehensive Meta-Analysis V2. There were 45 cohort studies included in this review. ART infants (n = 92 671) had a higher risk of birth defects [RR 1.32, 95% confidence interval (CI) 1.24-1.42] compared with naturally conceived infants (n = 3 870 760). The risk further increased when data were restricted to major birth defects (RR 1.42, 95% CI 1.29-1.56) or singletons only (RR 1.36, 95% CI 1.30-1.43). The results for ART multiples were less clear. When all data for multiples were pooled the RR estimate was 1.11 (95% CI 0.98-1.26) but this increased to 1.26 (0.99-1.60) when the analysis was restricted to studies of ART twins where some adjustment was made for differences in zygosity distribution between ART and non-ART multiples. Birth defects remain more common in ART infants. Further research is required to examine risks for important subgroups of ART exposure.