High-order Multiple Pregnancies Research Articles

To be born twin: effects on long-term neurodevelopment of very preterm infants-a cohort study.

To examine the effect of twin birth on long-term neurodevelopmental outcomes in a cohort of Italian preterm infants with very low birth weight. We performed a retrospective cohort study on children born in a tertiary care centre. We included children born between 1 January 2007 and 31 December 2013 with a gestational age (GA) of ≤32 weeks and birth weight of <1,500 g. The infants born from twin pregnancies complicated by twin-to-twin transfusion syndrome and from higher-order multiple pregnancies were excluded. The children were evaluated both at 2 years corrected age and 5 years chronological age with Griffiths mental development scales revised (GMDS-R). The linear mixed effects models were used to study the effect of being a twin vs. being a singleton on GMDS-R scores, adjusting for GA, being born small for gestational age, sex, length of NICU stay, socio-economic status, and comorbidity score (CS) calculated as the sum of the weights associated with each of the major morbidities of the infants. A total of 301 children were included in the study, of which 189 (62.8%) were singletons and 112 (37.2%) were twins; 23 out of 112 twins were monochorionic (MC). No statistically significant differences were observed between twins and singletons in terms of mean general quotient and subscales at both 2 and 5 years. No effect of chorionicity was found when comparing scores of MC and dichorionic twins vs. singletons; however, after adjusting for the CS, the MC twins showed lower scores in the hearing and language and performance subscales at 5 years. Overall, in our cohort of children born very preterm, twin infants were not at higher risk of neurodevelopmental impairment compared with singletons at pre-school age.

Change in prevalence of preterm birth in Israel following publication of national guidelines recommending routine sonographic cervical-length measurement at 19-25 weeks' gestation.

To compare the prevalence of preterm birth (PTB) (delivery before 37 weeks) in Israel before and after publication of national guidelines recommending second-trimester sonographic cervical-length (CL) measurement. The Israeli Society of Obstetrics and Gynecology (ISOG) guidelines, issued on 1 January 2012, specified that CL should be measured transabdominally or, if this is not possible, transvaginally, at the 19-25-week ultrasound anomaly scan and that CL < 25 mm should indicate further work-up and treatment, although the type of treatment was unspecified. In 2000, the Israel Ministry of Health issued a legal requirement for the submission of delivery records to a national registry. These data were used to compare PTB prevalence in the period before (2000-2011) and that after (2012-2020) publication of the guidelines, as well as trends within each time period. Information was available on singleton and multiple pregnancy and maternal age and parity, as well as low birth weight (< 2500 g). During the period 2000-2020, there were 3 403 976 infants liveborn in Israel: 1 797 657 before and 1 606 319 after publication of the ISOG guidelines. There were 247 187 PTBs overall, with a prevalence of 7.64% (95% CI, 7.52-7.77%) before publication of the guidelines and 6.84% (95% CI, 6.43-7.24%) afterwards (P < 0.0002, two-tailed). The annual PTB prevalence was static in the first time period but declined by 0.18% per annum during the second period, after publication of the guidelines. The proportionate reduction in PTB prevalence after compared with before publication of the guidelines was 10% overall, 9% for PTB at 33-36 weeks, 18% for PTB at 28-32 weeks and 24% for PTB at < 28 weeks. After publication of the guidelines, reduced prevalence of PTB was observed among singletons (5.49% before vs 4.83% after, P < 0.0001), but not among infants in twin or higher-order multiple pregnancy. There was a statistically significant reduction in the rate of PTB following publication of the guidelines in both nulliparous and parous women and in the 19-39-year-old maternal-age group. Although reductions in PTB prevalence were also noted in high-risk age groups (maternal age < 19 years and ≥ 40 years), these did not reach statistical significance. Following publication of the guidelines, there was a statistically significant reduction in the prevalence of birth weight under 2500 g, of a magnitude similar to that for PTB prevalence. The publication of national guidelines recommending routine CL measurement at the time of the second-trimester anomaly scan was associated with a fall in PTB prevalence in singleton pregnancies. Whilst direct evidence linking screening with this fall in prevalence is lacking, it is likely that implementation of routine CL screening played an important role in the reduction of PTB rate. Our experience indicates that screening can be incorporated into the second-trimester anomaly scan. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Outcomes of higher-order multiple pregnancies in an Australian setting.

Higher-order multiple (HOM) pregnancies are associated with significant maternal and neonatal morbidity, especially consequent to preterm birth. Multi-fetal pregnancy reduction (MFPR) may be provided, though its benefits in prolonging gestation and improving neonatal outcomes must be weighed against its risks. The aim was to compare outcomes of HOM pregnancies where expectant management was chosen (EM) with those where MFPR was provided. The method involved a retrospective study of HOM pregnancies referred to a single quaternary hospital between 2007 and 2016. The primary outcome was gestational age. Secondary outcomes included miscarriage, nursery admission, hospital stay, Apgar scores, early fetal loss, stillbirth, neonatal death and composite fetal loss. Fifty-seven pregnancies were eligible for inclusion. Median gestation at birth (weeks) was significantly higher for MFPR (35.3 vs 33.1, P < 0.01). Pregnancies after MFPR were less likely to lead to preterm birth (63.2 vs 100.0%, P < 0.001), half as likely to birth before 34 weeks (31.6 vs 60.0%, P=0.09) but similarly likely to extremely preterm birth (<28 weeks, 8.6 vs 10.5%, P=0.58). Miscarriage was more likely after MFPR (13.6 vs 0%, P=0.05). EM neonates were more likely to be admitted to the nursery (P < 0.01) and have longer hospital stay (29.6 vs 20.2 days, P=0.05); however, they had similar Apgar scores. Our study demonstrates that MFPR is associated with an increase in gestational age, with a reduction by almost half of births before 34 weeks, but no difference in extremely preterm births; the latter represents the highest risk group. This should be used to guide management counselling for HOM pregnancies.

Quadruplet pregnancy with widespread Tenney-Parker changes: A case report

Introduction: The incidence of multiple pregnancies has increased tremendously over the last 3–4 decades due to the advent of assisted reproductive technology treatment. Generally, multifetal pregnancy is associated with increase in maternal and perinatal morbidity and mortality, which are directly proportional with increasing numbers of fetuses in higher order multiple pregnancies. Case Report: We present a case of a 26-year-old G1P0104 female with a 3-year history of anovulatory infertility. After the third cycle of ovarian stimulation with clomiphene citrate, she became pregnant with quadruplets. She had no significant past medical or surgical history. The pregnancy was a tetrachorionictetraamniotic quadruplet and it was relatively uncomplicated during the first and second trimesters. However, the patient had prolonged antepartum admission from 25w6d due to symptomatic preterm uterine contractions. At 31w3d, the patient underwent primary cesarean section due to non-reassuring fetal heart tracing and biophysical profile of quadruplet A. Four viable neonates were delivered, three females and one male. All four quadruplets were admitted to the Neonatal Intensive Care Unit (NICU) with varying degrees of neonatal complications due to prematurity, but they were discharged home between 8 and 9 weeks of life. The placental pathology showed Tenney-Parker changes, but it did not adversely affect the outcome of these infants. Conclusion: Higher-order multifetal pregnancies can pose serious management challenges because of increased preterm delivery. Hence, management should be in a tertiary medical center with a multi-disciplinary team that includes an Obstetrician, Perinatologist, and Neonatologist.

Impact of the COVID-19 pandemic on preterm birth and stillbirth: A nationwide, population-based retrospective cohort study

ObjectiveThis study aimed to establish whether there was a decrease in the rate of prematurity in France after the beginning of lockdown (March 17, 2020) and whether there was an increase in the rate of stillbirths compared with 2017 to 2019.Study designWe included all births from January to September of each year from 2017 to 2020 from the national Programme de Médicalisation des Systèmes d’Information database: 496,171 newborns from women with singleton pregnancies and 15,441 newborns from women with multiple pregnancies were included for 2020. Concerning the 2017 to 2019 period, we included a mean of 518,798 newborns from women with singleton pregnancies and 16,441 newborns from women with multiple pregnancies per year.ResultsBetween April to May 2017 to 2019 and April to May 2020, there was a decrease of - 7.53% in the rate of prematurity (from 5.31% to 4.91%; P < 0.01) for singleton pregnancies. Between these 2 periods, the rate of change was −12.90% between 22 and 27 WG (P = 0.03), +1.96% between 28 and 31 WG (P = 0.69), and −8.24% between 32 and 36 WG (P < 0.01). The decrease in the rate of prematurity was still observed after the end of lockdown (from June to September 2020). For multiple births, there was no decrease in prematurity between January to September 2017 to 2019 and January to September 2020: 50.14% vs. 50.36% (P = 0.63), respectively, for twins and 95.51% vs. 94.9% (P = 0.62), respectively, for high-order multiple pregnancies. In January to September, there were 363 stillbirths among singleton pregnancies in 2017 to 2019 and 114 in 2020 (0.00% change rate). Among the 1752 women with a diagnosis of SARS-CoV-2 infection with singleton pregnancies, the rate of prematurity was higher in 2020 than in 2017 to 2019 (9.93% vs. 5.32%; P < 0.01), regardless of the severity of prematurity (P < 0.05 for all).ConclusionLarge-scale socioenvironmental modifications like the lockdown in spring 2020 may be associated with beneficial effects on perinatal morbidity. We did not find an increase in the rate of stillbirth since the beginning of the pandemic. At this stage, the practical consequences are not obvious, but our results encourage further reflection regarding behaviors that could modify the risk of prematurity outside of the context of an epidemic.

Pregnancy and obstetric outcomes of dichorionic and trichorionic triamniotic triplet pregnancy with multifetal pregnancy reduction: a retrospective analysis study

BackgroundIt is generally beneficial for triplet gestation or high-order multiple pregnancies to operate multifetal pregnancy reduction (MFPR) after assisted reproductive techniques. However, data on pregnancy outcomes is lacking regarding dichorionic triamniotic (DCTA) and trichorionic triplets (TCTA) pregnancy.MethodThis research analyzes the difference between 128 DCTA and 179 TCTA pregnancies with or without MFPR after in vitro fertilization/intracytoplasmic sperm injection cycles between January 2015 and June 2020. The subdivided subgroups of the two groups are reduction to singleton, reduction to dichorionic twins, and expectant management groups. We also compare the pregnancy and obstetric outcomes between 2104 dichorionic twins and 122 monochorionic twins.ResultThe research subgroups were DCTA to monochorionic singleton pregnancies (n = 76), DCTA to dichorionic twin pregnancies (n = 18), DCTA-expectant management (n = 34), TCTA to monochorionic singleton pregnancies (n = 31), TCTA to dichorionic twin pregnancies (n = 130), and TCTA-expectant management (n = 18). In DCTA-expectant management group, the complete miscarriage rate is dramatically higher, and the survival rate and the rate of take-home babies are lower. However, there was no difference between the rates of complete miscarriages, survival rates, and take-home babies in TCTA-expectant management group. But the complete miscarriage rate of DCTA-expectant management was obviously higher than that of TCTA-expectant management group (29.41 vs. 5.56%, p = 0.044). For obstetric outcomes, MFPR to singleton group had higher gestational week and average birth weight, but lower premature delivery, gestational hypertension rates and low birth weight in both DCTA and TCTA pregnancy groups (all p < 0.05). DCTA to monochorionic singleton had the lowest incidence of gestational diabetes, whereas The subdivided subgroups of TCTA had no significant difference in the incidence of gestational diabetes. Monochorionic twins have higher rates of complete, early, and late miscarriage, premature delivery, and late premature delivery, and lower survival rate (p < 0.05).ConclusionMFPR could improve gestational week and average birth weight, reducing premature delivery, LBW, and gestational hypertension rates in DCTA and TCTA pregnancies. Monochorionic twins have worse pregnancy and obstetric outcomes. MFPR to singleton is preferable recommended in the pregnancy and obstetric management of complex triplets with monochorionic pair.

Obstetric and Perinatal Outcomes of Dichorionic-Diamniotic Twin Pregnancies Conceived by IVF/ICSI Compared with Those Conceived Spontaneously.

This study aimed to investigate differences in mater-nal and perinatal outcomes between dichorionic-diamniotic (DCDA) twin pregnancies between those conceived spontaneously and those conceived through in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). This study was a single-center, retrospective cohort study. All women with DCDA twin pregnancies were considered for inclusion. Monochorionic twins and higher-order multiple pre-gnancies were excluded. All data related to maternal and perinatal outcomes were extracted from the hospital database and compared between spontaneously conceived DCDA twin pregnancies and those conceived by IVF/ICSI. Multivariable logistic regression was used to adjust for confounders to determine factors associated with maternal and perinatal outcomes. Of 739 identified DCDA twin pregnancies, 483 (65.4%) were conceived through IVF/ICSI treatment (IVF/ICSI group), and 256 (34.6%) were spontaneously conceived (SC group). Women in the IVF/ICSI group were older and had fewer previous live births than women in the SC group. The women in the IVF/ICSI group had significantly higher risks of preeclampsia (adjusted odds ratio [aOR]: 2.50; 95% confidence interval [CI]: 1.12-5.55), cesarean delivery (aOR: 2.0; 95% CI: 1.27-3.17), an postpartum hemorrhage following cesarean section (aOR: 3.15; 95% CI: 1.53-6.45). The DCDA twins in the IVF/ICSI group were delivered at an earlier gestational age (36.2 vs. 36.7 weeks, p < 0.001), had slightly lower mean birth weights (2298 vs. 2367 g, p = 0.005), and required more respiratory support (aOR: 0.69; 95% Cl: 0.48-0.98) than those in the SC group. Our study demonstrated that women with DCDA twin pregnancies conceived through IVF/ICSI experienced more complications than those with SC DCDA twin pregnancies. Newborns in the IVF/ICSI group had a slightly lower mean birth weight and required respiratory support more frequently, but no other significant differences in perinatal outcomes or perinatal mortality were observed between the two groups.

Fetal and maternal outcome of higher-order multiple pregnancies in a tertiary hospital: A 5-year single-center observational study from Nigeria.

Objective:The aim of this study was to determine the pattern and outcomes of higher-order multiple pregnancies in a tertiary hospital in NigeriaMethods:This is a retrospective review of all cases of higher-order multiple pregnancies that were managed between 1 January 2012 and 31 December 2016 in Alex Ekwueme Federal University Teaching Hospital Abakaliki, Nigeria. Data obtained were represented with frequency tables, percentages, bar charts, and odds ratio.Results:There were 22 higher-order multiple pregnancies over the study period and 12,002 deliveries, giving a higher-order multiple prevalence rate of 0.2%. Five of the mothers (four triplets and one quadruplet) had in vitro fertilization (0.4 per 1000 deliveries), while other mothers conceived naturally. Many of the women (12, 54.6%) were in the 30–34 years age group, and more than half (16, 72.7%) were multiparas. More than half of the neonates were delivered preterm (13, 59.1%). Being booked is associated with better neonatal outcomes although not significant (odds ratio = 3.06. 95% confidence interval: 0.55–16.83, p = 0.197). Anemia was common in the antepartum and postpartum periods. Half of the women (11, 50%) were delivered by elective cesarean section and 7 (31.8%) by emergency cesarean section (C/S), while 4 (18.2%) had a spontaneous vaginal delivery. The neonates had a mean birth weight of 2.14 ± 0.35 kg. Overall, 61 neonates (91.0%) were born alive and 6 (9.0%) suffered perinatal deaths, giving a perinatal mortality rate of 89.8 neonates per 1000 live births.Conclusion:Our study shows that higher-order multiple pregnancies are high-risk pregnancies that are associated with fetal and maternal complications. Anemia is the commonest complication seen in our study. The majority had preterm delivery. Proper antenatal care and close feto-maternal monitoring are important in reducing adverse outcomes associated with these pregnancies.

Clinical outcomes in higher-order multiples reduced to dichorionic diamniotic (DCDA) twins compared with primary twins and singletons: A prospective observational study.

To compare outcomes in higher-order multiple pregnancies reduced to dichorionic diamniotic (DCDA) twins with primary DCDA twins and singleton pregnancies. This prospective observational study included all higher-order multiple pregnancies that underwent ultrasound-guided transabdominal fetal reduction at 11-13weeks of gestation from January 2018 to June 2020. Outcomes were compared with 100 primary DCDA twins and 1078singletons. Sixty-four higher-order multiples underwent reduction at mean gestational age of 11.46weeks. Of the reduced pregnancies, 3.12% resulted in miscarriage before 24weeks compared with 2% (2/100) of primary twins and 0.74% of singletons (P=0.09). The mean gestational age at delivery was 33.48weeks for reduced twins, 34.52weeks for primary twins (P=0.10) and 38.14weeks for singletons (P<0.001). Compared with primary twins, the adjusted odds of preterm delivery before 34weeks and before 36weeks for reduced twins were 0.56 (95% confidence interval [CI] 0.48-3.54, P=0.62) and 0.84 (95% CI 0.78-8.85, P=0.08), respectively. There was no significant difference in rates of pre-eclampsia, Cesarean delivery, birth weight below the 10th and 3rd centiles, and perinatal mortality among primary and reduced twins. All risks were significantly lower in singleton pregnancies. Reduced twins have similar obstetric and perinatal outcomes as primary twins, but adverse outcomes are significantly higher in both groups when compared with singleton pregnancies.

Outcome of monochorionic twin pregnancy complicated by Type-III selective intrauterine growth restriction.

Type-III selective intrauterine growth restriction (sIUGR) is associated with a high and unpredictable risk of fetal death and fetal brain injury. The objective of this study was to describe the prospective risk of fetal death and the risk of adverse neonatal outcome in a cohort of twin pregnancies complicated by Type-III sIUGR and treated according to up-to-date guidelines. We reviewed retrospectively all monochorionic diamniotic twin pregnancies complicated by Type-III sIUGR managed at nine fetal centers over a 12-year period. Higher-order multiple gestations and pregnancies with major fetal anomalies or other monochorionicity-related complications at initial presentation were excluded. Data on fetal and neonatal outcomes were collected and management strategies reviewed. Composite adverse neonatal outcome was defined as neonatal death, invasive ventilation beyond the resuscitation period, culture-proven sepsis, necrotizing enterocolitis requiring treatment, intraventricular hemorrhage Grade > I, retinopathy of prematurity Stage > II or cystic periventricular leukomalacia. The prospective risk of intrauterine death (IUD) and the risk of neonatal complications according to gestational age were evaluated. We collected data on 328 pregnancies (656 fetuses). After exclusion of pregnancies that underwent selective reduction (n=18 (5.5%)), there were 51/620 (8.2%) non-iatrogenic IUDs in 35/310 (11.3%) pregnancies. Single IUD occurred in 19/328 (5.8%) pregnancies and double IUD in 16/328 (4.9%). The prospective risk of non-iatrogenic IUD per fetus declined from 8.1% (95% CI, 5.95-10.26%) at 16 weeks, to less than 2% (95% CI, 0.59-2.79%) after 28.4 weeks and to less than 1% (95% CI, -0.30 to 1.89%) beyond 32.6 weeks. In otherwise uncomplicated pregnancies with Type-III sIUGR, delivery was generally planned at 32 weeks, at which time the risk of composite adverse neonatal outcome was 29.0% (31/107 neonates). In twin pregnancies that continued to 34 weeks, there was a very low risk of IUD (0.7%) and a low risk of composite adverse neonatal outcome (11%). In this cohort of twin pregnancies complicated by Type-III sIUGR and treated at several tertiary fetal centers, the risk of fetal death was lower than that reported previously. Further efforts should be directed at identifying predictors of fetal death and optimal antenatal surveillance strategies to select a cohort of pregnancies that can continue safely beyond 33 weeks' gestation. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Reduction of multiple pregnancy: Counselling and techniques.

The incidence of multiple births has risen in the last few decades. This rise is mainly due to the widespread use of assisted reproduction techniques mainly as a result of increasing maternal age at conception. Twin and higher-order multiple pregnancies are associated with increased risk of perinatal, as well as maternal, mortality and morbidity compared to singleton pregnancies. There can also be psychosocial and socioeconomic implications for women and their families. In this chapter, we aim to discuss the risks associated with multiple pregnancies, the pros and cons of fetal reduction, the current techniques used in clinical practice, and how to approach counselling parents, enabling them to make informed decisions.

Delayed interval delivery of preterm multiples: experience from a large specialized twin center

Objective Preterm delivery is a recognized complication of twins and higher order multiple pregnancies. Delayed interval delivery is a rarely used management option for pre- or peri-viable preterm labor in these pregnancies. We describe the management and outcomes of 7 delayed interval deliveries over an 8-year period in a large specialized twin center. Study design A retrospective cohort study of all delayed interval deliveries of preterm multiples from 2009 to 2016, defined as >24 h between deliveries of twins 1 and 2. Results During the study period there were 68,845 deliveries with 1377 multiple pregnancies comprising 1331 sets of twins and 46 sets of higher-order multiples. 7 of these were identified as being delayed interval deliveries – 6 twin pregnancies and 1 triplet pregnancy. The mean gestation of delivery of the first infant was 23 + 4 weeks (range 22 + 3 to 30 + 0 weeks) with a mean interval of 10 days (range 1.5–39 days). Outcomes for the first infant delivered were poor, with 5 out of 7 (71%) dying from extreme prematurity. However, out of the remaining twins or triplets, 5/8 (62%) survived. The mean gestation of delivery of the remaining infant (or infants in the triplets) was 25 + 0 weeks (range 23 + 0 to 30 + 2 weeks). Only one mother (16%) developed clinical chorioamnionitis requiring iatrogenic delivery of the remaining infant with subsequent neonatal death due to extreme prematurity. There were no cases of severe maternal morbidity – however, there was one maternal death in the cohort due to an amniotic fluid embolism. The neonatal follow up of the surviving infants to date is mostly normal. Conclusion Delayed interval deliveries can offer hope for survival for the remaining infant(s) with an acceptable risk profile to the mother. Close clinical and laboratory monitoring is essential to reduce the risk of severe maternal morbidity.

Guideline No. 398: Progesterone for Prevention of Spontaneous Preterm Birth.

To assess the benefits and risks of progesterone therapy for women at increased risk of spontaneous preterm birth (SPB) and to make recommendations for the use of progesterone to reduce the risk of SPB and improve postnatal outcomes. To administer or withhold progesterone therapy for women deemed to be at high risk of SPB. Preterm birth, neonatal morbidity and mortality, and postnatal outcomes including neurodevelopmental outcomes. Maternity care providers, including midwives, family physicians, and obstetricians. Pregnant women at increased risk of SPB. Medline, PubMed, EMBASE, and the Cochrane Library were searched from inception to October 2018 for medical subject heading (MeSH) terms and keywords related to pregnancy, preterm birth, previous preterm birth, short cervix, uterine anomalies, cervical conization, neonatal morbidity and mortality, and postnatal outcomes. This document represents an abstraction of the evidence rather than a methodological review. This guideline was reviewed by the Maternal-Fetal Medicine Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) and approved by the SOGC Board of Directors. Therapy with progesterone significantly reduces the risk of SPB in a subpopulation of women at increased risk. Although this therapy entails a cost to the woman in addition to the discomfort associated with its use, no other adverse effects to the mother or the baby have been identified. RECOMMENDATIONS (GRADE RATINGS IN PARENTHESES).

Adverse Maternal Outcomes in High-Order Multiple Pregnancies in a Private Health Facility in Nigeria: A 10-Year Experience

Background: Naturally occurring high-order multiple (HOM) pregnancies are rare (1 - 7 per 10,000) even in Nigeria noted to have the highest twinning rates. Worldwide multiple pregnancies are increasing and are associated with increased adverse maternal outcomes. Materials and Methods: This was a retrospective study of all patients with HOM pregnancy in Prime Medical Consultants between Jan 2004 to Dec 2013. We identified all the patients with high-order multiple pregnancy and extracted relevant data from the ante-natal and labour ward records, theatre records, and patients case notes. Demographic characteristics, gestational age at delivery, preterm rupture of membranes, preterm labour, hypertensive disease in pregnancy, proteinuria, anaemia, and postpartum haemorrhage were data extracted from the records. Results: The incidence of HOM pregnancy in this hospital was 0.24%. The mean maternal age was 35.7 ± 1.81 years. Over 85% of all the high-order multiple pregnancies in this hospital were from in-vitro fertilization and embryo transfer treatments for infertility. About 11% of the HOM pregnancy ended as spontaneous miscarriages. The mean gestational age at birth was 31 ± 1.5 weeks, and primary postpartum haemorrhage (22.2%) was the most common maternal adverse outcome from birth. Conclusion: The high incidence of HOM pregnancy in this hospital was mainly from in-vitro fertilization and embryo transfer. The HOM pregnancies are associated with high occurrence of preterm labour, caesarean sections and primary postpartum haemorrhage.

Validation of fetal DNA fraction estimation and its application in noninvasive prenatal testing for aneuploidy detection in multiple pregnancies.

To analyze the fetal fraction, fetal sex, and chromosomal aneuploidy in multiple pregnancies using noninvasive prenatal testing (NIPT). A total of 362 pregnant women including 203 singleton pregnancies, 69 twins, and 90 higher-order multiple pregnancies were recruited. Fetal fractions estimated by size ratio-based and Y chromosome-based approaches in singleton pregnancies with male fetus were used as source data to establish the model. The model was then applied to multiple pregnancies for fetal fraction estimation. By comparing the fetal fractions estimated by size ratio to those estimated by Y chromosome or autosomal chromosomes, fetal sex and chromosomal aneuploidy can be analyzed. The size ratio-based approach has been well established in estimating fetal fractions for twin and higher-order multiple pregnancies. Fetal fraction had a positive correlation with gestational age in twin and triplet pregnancies. Fetal sex was determined with accuracies of 98.6% (95% CI, 92.19%-99.96%) in twins and 97.6% (95% CI, 91.76%-99.71%) in triplet pregnancies. Four trisomy 21, one trisomy 18, and one trisomy 13 cases were detected by NIPT. Two trisomy 21 singleton pregnancies and one trisomy 21 twin pregnancy were confirmed by karyotyping. Fetal sex and chromosomal aneuploidy in multiple pregnancies can be determined using NIPT.

Is it worth reducing twins to singletons after IVF-ET? A retrospective cohort study using propensity score matching.

Many studies have shown that multifetal reduction of high-order multiple pregnancies results in improved pregnancy outcomes. However, whether conducting elective fetal reduction from dichorionic twins after in vitro fertilization (IVF) is worthwhile remains controversial. This study aimed to determine whether elective fetal reduction of dichorionic twins after IVF and embryo transfer (IVF-ET) is associated with increased take-home baby rate. This was a retrospective cohort study of 3600 dichorionic twin pregnancies after IVF-ET. The reduced group included 71 women with transvaginal elective fetal reduction between 7 and 8weeks of gestation. The control group (n=3529) comprised women who were managed expectantly. Propensity score matching was conducted before pregnancy outcomes were compared. The take-home baby rate was significantly lower in the reduced group (83.1% vs 92.8%, P=0.004). The total miscarriage rate was significantly higher in the reduced group (12.7% vs 6.2%, P=0.04). Although preterm delivery rate was lower in the reduced group (P<0.001), over 90% were over 32weeks, whereas the proportions were equal in the reduced group. In dichorionic twin pregnancies after IVF-ET, elective fetal reduction to singleton significantly decreased the chance of taking home live babies.

Comparing pregnancy outcomes and loss rates in elective twin pregnancy reduction with ongoing twin gestations in a large contemporary cohort

As compared with singleton gestations, twin pregnancies are associated with a significantly higher risk of preterm birth and maternal complications as well as fetal and neonatal morbidity and mortality. Multifetal pregnancy reduction is a technique developed in the 1980s to reduce the fetal number in higher-order multiple pregnancies to reduce the risk of adverse pregnancy outcomes, most importantly preterm birth. The objective of the study was to compare pregnancy outcomes and loss rates in elective twin pregnancy reduction to ongoing twin gestations in a large contemporary cohort. This was a retrospective review of dichorionic diamniotic twin gestations that underwent first-trimester ultrasound at our institution from January 2008 to September 2016. Planned elective 2-to-1 multifetal pregnancy reductions at less than 15 weeks' gestation were compared with ongoing dichorionic diamniotic twin gestations. Data were collected via chart review. Demographics between 2-to-1 reduced singletons and ongoing twins were assessed using a Student t test or a Wilcoxon rank-sum test, as appropriate, for continuous variables and χ2 or Fisher exact tests, as appropriate, for categorical variables. Univariable and multivariable logistic regressions were used to compare pregnancy outcomes between ongoing twins and reduced singletons adjusting for maternal age, body mass index, race, invitro fertilization, use of chorionic villus sampling, prior term birth, and prior preterm birth. Of 1070 dichorionic diamniotic twin pregnancies identified, completed follow-up data were available and analyzed for 855 patients (79.9%). Among those, 250 (29.2%) were 2-to-1 singletons and 605 (70.8%) were ongoing twins. Reduced singleton patients were slightly older, more likely white, and had lower body mass index. They were also more likely to have undergone invitro fertilization (63.6% vs 48.8%), had chorionic villus sampling (92% vs 37.5%), and had prior term births (54% vs 35.7%). Compared with 2-to-1 singletons, the adjusted odds of having preterm delivery at 37 weeks for ongoing twins were 5.62 times (95% confidence interval, 3.67-8.61; P < .001) and 2.22 times (95% confidence interval, 1.20-4.11; P < .001) at 34 weeks. While intrauterine growth restriction, placental abruption, and gestational diabetes were not significant, ongoing twins were more likely to have a cesarean delivery (odds ratio, 5.53, 95% confidence interval, 3.60-8.49; P < .001) and preeclampsia (odds ratio, 3.33, 95% confidence interval, 1.60-6.96; P < .001) after adjusting for maternal characteristics. There were also significant differences between groups for preterm premature rupture of membranes and low birthweight at less than the fifth and 10th percentiles. Total pregnancy loss (at 24 and 20 weeks) was similar between singleton and ongoing twins (4% vs 2.5%, P= .23, and 3.6% vs 1.7%, P= .09 for respective weeks). There were no significant differences in the rate of unintended pregnancy loss (2.4% vs 2.3%; P= .94) and the rate of intrauterine fetal death greater than 24 weeks (1.2% vs 0.7%; P= .43) in reduced singleton versus ongoing twin group, respectively. In our study, patients who elected to reduce to a singleton pregnancy had a higher gestational age of delivery and lower rates of preterm birth and pregnancy complications without an increased risk of pregnancy loss.

Obstetrical outcomes of embryo reduction and fetal reduction compared to non-reduced twin pregnancies

To prevent perinatal morbidity and mortality of high-order multiple pregnancy (HOMP), multifetal pregnancy reduction (MPR) is offered to some patients. In this study, we investigated whether twin pregnancies derived from MPRs carry a higher adverse obstetrical outcome compared to non-reduced control group of twins. We retrospectively analyzed the data from HOMPs on which transvaginal ER (n = 153) at a mean gestational age of 7.6weeks or transabdominal FR (n = 59) at a mean gestational age of 12.4weeks was performed between December 2006 and January 2018. The risk of each procedure was evaluated by comparing obstetrical outcome with that of a control population of 157 non-reduced twins conceived by infertility treatment. The mean gestational ages at delivery were 35.2weeks in the ER group, 35.7weeks in the FR group, and 34.1weeks in the control group (P = NS). Compared with those in the control group, the ER group had higher miscarriage (1.3% vs. 6.5%; P = 0.047; OR 0.21; 95% CI 0.45-0.898) and higher overall fetal loss (3.8% vs. 14.4%; P = 0.003; OR 0.24; 95% CI 0.09-0.60) rates. Differently compared with those in the control group, the FR group had no statistical difference in miscarriage (2.5% vs. 1.7%; P=NS) and overall fetal loss (3.8% vs. 6.8%; P=NS) rates. Compared with the control group, ER in twins had a higher miscarriage and fetal loss rate, whereas FR in twins was similar to the control group. So, the FR procedure is overall a better and safer approach of MPR in reducing morbidity and mortality in HOMPs.

Characterization of embryonic cells obtained from multifetal reduction.

The multifetal reduction (MFR) procedure is usually reserved for high-order multiple pregnancies, and aspirated tissues are typically discarded. In this study, cells obtained from MFR tissue (termed multifetal reduction embryonic cells (MFR-ECs)), were characterized in vitro by genotypic and phenotypic analyses and tested in vivo by injection under the kidney capsule of nude mice. MFR-ECs were highly proliferative in culture and showed a normal karyotype by microarray CGH. Immunohistochemical analysis at day zero showed positive focal staining for desmin, S-100 protein, synaptophysin and chromogranin. Histology examination showed a mixture of cells from the three germ layers at different stages of differentiation. Markers of these stages included important developmental transcription factors, such as beta three-tubulin (ectoderm), paired box 6 (ectoderm) and alpha-smooth muscle actin (mesoderm). Quantitative polymerase chain reaction (qPCR) showed down-regulation of the mRNAs of cancer-related genes such as TP53. In vivo transplantation in nude mice showed a typical hyaline cartilage plate and no teratoma formation. Thus, MFR-ECs represent a rich, unique source for studying stem cell development, embryogenesis and cell differentiation.

Small-sized follicles could contribute to high-order multiple pregnancies: outcomes of 6552 intrauterine insemination cycles.

Can predictors of twin and high-order multiple pregnancy among women with multiple cycles of ovarian stimulation intrauterine insemination (IUI) be identified? Retrospective cohort study of IUI cycles carried out between January 2014 and December 2015 in a private clinic in Spain. The 4879 women and 6552 cycles analysed in this study include single IUI with ovarian stimulation using recombinant FSH. Number of follicles and follicle size were the only factors with a significant effect (P < 0.001) on the likelihood of achieving a twin or multifetal pregnancy. Follicles 12 mm or wider greatly increase the chances of achieving a twin or multifetal pregnancy. A total of 73 out of 127 (57.5%) twin pregnancies occurred in cycles with at least one additional follicle measuring 12 mm or wider, and 102 out of 127 twin pregnancies (80.3%) occurred in cycles with at least one additional follicle measuring 14 mm or wider. Cancellation criteria should consider the presence of follicles 12 mm or wider. Follicles measuring 12 mm or wider increase the risk of having a twin or a high-order multiple pregnancy rate. These data may help clinicians balance decision-making between cancelling and performing the cycle within an IUI procedure.