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This Committee Opinion provides practitioners with suggestions to reduce the likelihood of iatrogenic multiple gestation resulting from infertility treatment. This document replaces the document of the same name previously published in 2012 (Fertil Steril 2012;97:825-34 by the American Society for Reproductive Medicine)., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Delayed delivery is designed to allow the remaining fetus(es) to develop after premature expulsion of the first twin in the second trimester of pregnancy. This decision is aimed to allow the remaining fetus(es) to reach full fetal growth. We here report a clinical case of delayed delivery in a patient with triple pregnancy in whom the time between the expulsion of the first twin and the birth of the third twin was 10 weeks. The purpose of this study was to highlight the benefit and indications for delayed delivery., Competing Interests: Les auteurs ne déclarent aucun conflit d´intérêts., (Copyright: Mehdi El Hassani et al.)

Seasonality of demographic data has been of great interest. The seasonality depends mainly on climatic conditions, and the findings may vary from study to study. Commonly, the studies are based on monthly data. The population at risk plays a central role. For births or deaths over short periods, the population at risk is proportional to the lengths of the months. Hence, one must analyse the number of births (deaths) per day. If one studies the seasonality of multiple maternities, the population at risk is the total monthly number of confinements and the number of multiple maternities in a given month must be compared with the monthly number of all maternities. Consequently, one considers the monthly rates of multiple maternities, the monthly number of births is eliminated and one obtains an unaffected seasonality measure of the rates. In general, comparisons between the seasonality of different data sets presuppose standardization of the data to indices with common means, mainly 100. When seasonal models are applied, one must pay special attention to how well the applied model fits the data. If the goodness of fit is poor, non-significant models obtained can erroneously lead to statements that the seasonality is slight, although the observed seasonal fluctuations are marked. The estimated monthly models chosen are approximately orthogonal and they have little influence on the parameter estimates. Exact orthogonality should be obtained if the data are equidistant, that is, if the months are of equal length (e.g. 30 days), corresponding to 30 ∘ . Exactly equidistant data can be observed when circadian rhythms (24 h) are studied. In this study, we compare seasonal models with models with exact orthogonality., Competing Interests: Declaration of competing interest There are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The new West Japan Twins and Higher Order Multiple Births Registry was established by recruiting young twins and multiple births and by referrals from public health centers in the 1990s. The participants included in the survey comprised over 7800 twins and 4241 higher order multiples, and their families. Specifically, the present registry contains one of the largest triplet samples in the world. For these twins and multiples, data on year of delivery, mode of delivery, gestational age, intrapartum complications, longitudinal physical measures, motor milestones, cerebral palsy and feeding methods were obtained from records in the Maternal and Child Health Handbooks and schools. Participating mothers were asked to indicate family structure, parental educational history, maternal sleeping time, maternal health condition, maternal and paternal age at multiple delivery, complications during pregnancy, handedness of multiples and age at menarche of multiples. However, the zygosity differed among the various collaborating public health centers according to factors such as the time of investigation. Follow-up questionnaires have been mailed out every 3-4 years for longitudinal studies. This article describes the goals of this registry, recruitment of multiples and the focus of the study. The goals of this registry are not only to conduct research on human genetics and maternal and child health, but also to contribute to providing appropriate information for families with multiples.

Exclusive breastfeeding is currently recommended until at least 6 months of postnatal age, due to maternal breast milk (BM) unique composition and beneficial properties. In fact, BM modifies itself according to gestational age (GA) at birth, adapting its composition to neonatal requests during lactation. Multiple births represent about 3% of the whole pregnancies; such neonates result more vulnerable than full-term newborns, due to lower GA and birth weight (BW) and the higher incidence of perinatal complications. Although an adequate nutrition is fundamental for twins and other multiples, studies on this topic are lacking. We collected and analyzed BM from mothers of 19 twins and 5 triplets showing GA < 33 weeks and BW < 1500 g, comparing it to a control group of 28 preterm singletons. As a result, at GA ≤ 28 weeks, we observed that protein content is higher in BM for multiples (1.53 vs. 1.29 g per 100 ml), lactose concentration is greater in BM for singletons (6.72 vs. 6.34 g per 100 ml) and GA results the most relevant factor influencing BM protein composition. BM for multiples results higher in proteins and lower in lactose, if compared with singleton's samples; this could promote and sustain growth and organ development in this vulnerable category. BM from multiples shows a trophic and immunologic role, since these neonates often show lower GA and BW instead of singletons. These findings could help in optimizing nutritional strategies and improving BM individualized fortification.

Objective: The objective of this study is to evaluate if adolescence confers additional risk for preterm delivery in multifetal gestations., Methods: This is a retrospective review of all twin and triplet deliveries from 8/2008 to 12/2012 at two Detroit Hospitals. Outcomes in adolescent mothers aged 19 or younger (n = 59) were compared with adult controls aged 20-34 (n = 350)., Results: Mean gestational age at delivery in adolescents was 31.3 (SD: 5.8) weeks versus 34.2 (SD: 4.3) weeks in adults (p < .001). On multivariable analysis, adolescence was associated with preterm delivery (adjusted odds ratio [aOR], 2.3; 95% confidence intervals [95% CI], 1.1-4.7, p = .02) and early-preterm delivery (aOR, 2.2; 95% CI 1.2-4; p = .01). Adjusted rates of preterm and early-preterm delivery were markedly higher in adolescents compared with controls. Being an adolescent was also a significant risk factor for iatrogenic preterm delivery (aOR, 2.4; 95% CI 1.1-5.5; p = .04)., Conclusions: Adolescents pregnant with twins or triplets deliver 3 weeks, on average, before adults and are at markedly increased risk of preterm and early-preterm delivery.

Background: We describe two cases of dichorionic triplet pregnancy after a frozen-thawed poor-stage embryo transfer. A 39-year-old and a 41-year-old woman underwent ART treatment. The first patient underwent intracytoplasmic sperm injection (ICSI) at 34 years of age, and two frozen-thawed poor-stage embryos were transferred at 39 years of age with assisted hatching, resulting in a trichorionic triamniotic triplet pregnancy. The second patient underwent ICSI, and two poor-grade blastocysts were transferred followed by assisted hatching, resulting in a dichorionic triamniotic triplet pregnancy. In the first case, the heartbeat of one monozygotic twin fetus had stopped on day 48 post-transfer (9 weeks 2 days), resulting in a dichorionic diamniotic twin pregnancy. A healthy boy and girl were delivered by elective caesarean section at 36 weeks, 5-days gestation. In the second case, the patient underwent selective reduction of the monochorionic twins, resulting in a single pregnancy that was vaginally delivered without any problems at 38 weeks 0-days gestation., Short Conclusions: Numerous factors may be associated with the development of a monochorionic pregnancy; however, controversies still remain. The present morphological grading for embryos is insufficient for inhibiting the development of a monochorionic pregnancy.

The current systematic review and meta-analysis evaluate the perinatal outcomes in twin pregnancies following multifetal pregnancy reduction (MPR) compared with non-reduced triplet pregnancies. All studies comparing perinatal outcome of twin pregnancies following MPR to non-reduced triplet pregnancies were considered. MEDLINE, non-indexed MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science were searched for relevant published articles up to August 2016. The search yielded 653 publications of which 92 were assessed for eligibility. A total of 24 studies met the inclusion criteria. Overall, the outcomes of pregnancies following MPR were better compared with expectantly managed triplets. The MPR group delivered at a later gestational age and was less likely to be delivered before 32 or 28 weeks' gestation. Newborns in the MPR group had significantly higher birthweight at delivery (mean difference 500 g [95% CI 439.95, 560.04]). Rates of pregnancy loss before 24 weeks' gestation and overall infant survival were comparable between the groups. This meta-analysis suggests that MPR of triplet pregnancies to twins is associated with improved perinatal outcome compared with non-reduced triplets. Should primary prevention of high order multiple pregnancy fail, MPR is an appropriate alternative to minimize the perinatal morbidity and mortality of triplet pregnancies., (Copyright © 2017 Reproductive Healthcare Ltd. All rights reserved.)

Background: Little attention has been placed on the unique iron demands that may exist in women with multiple gestations. This merits attention because iron deficiency (ID) during pregnancy is associated with adverse pregnancy outcomes that are known to be more prevalent in multiple births., Objective: We characterized longitudinal changes in iron status across pregnancy in a cohort of healthy women with multiple gestations and identified determinants of maternal ID and anemia., Design: A group of 83 women carrying twins, triplets, or quadruplets (aged 20-46 y) was recruited from 2011 to 2014. Blood samples obtained during pregnancy (∼24 wk; n = 73) and at delivery (∼35 wk; n = 61) were used to assess hemoglobin, serum ferritin (SF), soluble transferrin receptor (sTfR), hepcidin, serum iron, erythropoietin, serum folate, vitamin B-12, C-reactive protein, and interleukin-6., Results: The prevalence of tissue ID (sTfR >8.5 mg/L) increased significantly from pregnancy to delivery (9.6% compared with 23%, P = 0.03). Women with depleted iron stores (SF <12 μg/L, n = 20) during pregnancy had a 2-fold greater risk of anemia at delivery, and 25% (n = 5) developed iron deficiency anemia (IDA). Overall, 44.6% of women studied (n = 37/83) were anemic at delivery, and 18% of women (n = 11/61) had IDA. Erythropoietin during pregnancy was significantly negatively associated with hemoglobin at delivery. Women with erythropoietin >75th percentile during pregnancy exhibited a 3-fold greater risk of anemia, suggesting that erythropoietin is a sensitive predictor of anemia at delivery. Inflammation was present at delivery, which limited the utility of ferritin or hepcidin as iron-status indicators at delivery., Conclusions: ID and anemia are highly prevalent in women with multiple gestations. Additional screening and iron supplementation may be warranted in this high-risk population given the known associations between ID anemia and adverse maternal and neonatal outcomes. This trial was registered at clinicaltrials.gov as NCT01582802., (© 2016 American Society for Nutrition.)

Multinational data on assisted reproduction techniques undertaken in 2013 were collected from 158 institutions in 15 Latin American countries. Individualized cycle-based data included 57,456 initiated cycles. Treatments included autologous IVF and intracytoplasmic sperm injection (ICSI), frozen embryo transfers, oocyte donations. In autologous reproduction, 29.22% of women were younger than 35 years, 40.1% were 35-39 years and 30.6% were 40 years or older. Overall delivery rate per oocyte retrieval was 20.6% for ICSI and 25.4% for IVF. Multiple births included 20.7% for twins and 1.1% for triplets and over. In oocyte donations, twins reached 30% and triplets 1.4%. In singletons, pre-term births were 7.5%: 36.58% in twins and 65.52% in triplets. The relative risk for prematurity was 4.9 (95% CI 4.5 to 5.3) in twins and 8.7 (95% CI 7.6 to 10.0) in triplets and above. Perinatal mortality was 29.4 per 1000 in singletons, 39.9 per 1000 in twins and 71.6 per 1000 in high order multiples. Elective single embryo transfer represented only 2% of cycles, with delivery rate of 39.1% in women aged 34 years or less. Given the effect of multiple births and prematurity, it is mandatory to reduce the number of embryos transferred in the region., (Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Aim: It is unknown whether weekly maternal weight gain differs between Japanese women with singleton, twin, and triplet pregnancies., Methods: Gestational weight gain defined as net weight gain during pregnancy was analyzed in 135,036 pregnant Japanese women, including 128,838 with singletons, 5573 with twins, and 132 with triplets, who gave birth at ≥22 weeks of gestation between 2007 and 2009. Weekly weight gain was defined as follows: gestational weight gain÷[gestational week (GW) at Delivery-2]., Results: Length of gestation (weeks, mean±SD) decreased significantly (38.2±2.6, 35.3±3.0, and 32.7±2.8) with increasing number of fetuses, while overall gestational weight gain (kg) was significantly smaller in women with singletons than in those with either twins or triplets (9.6±4.4 vs. 10.9±4.8 or 10.9±5.2, respectively). Thus, weekly maternal weight gain (kg/week) increased significantly with increasing number of fetuses (0.26±0.12, 0.33±0.13, and 0.35±0.16). Among women with delivery at or after GW 34, difference in gestational weight gain (kg) was prominent between the three groups (9.8±4.4, 11.4±4.7, and 13.0±5.1 for singleton, twin, and triplet pregnancies, respectively, P<0.001 between any two groups)., Conclusions: Weekly maternal weight gain increases with increasing number of fetuses. Our figures may be useful for advising Japanese women with multifetal pregnancies regarding gestational weight gain.

Objective: To determine the contribution of monozygotic twining to in vitro fertilization multiple births., Study Design: We performed a retrospective analysis of the incidence of monozygotic twining in multiple births resulting from fresh embryo transfers using 2006-2010 data from the Society for Reproductive Technology Clinic Outcome Reporting System., Results: The number of embryos transferred were fewer than the number of births in 0.5% (223/40950) of twin, 29% (659/2289) of triplet, and 64% (43/67) of quadruplet births resulting from transfer of fresh embryos from 2006 to 2010. In 2010, 37% of triplets and 100% of quadruplet births occurred when fewer than 3 and fewer than 4 embryos respectively were transferred., Conclusion: Monozygotic twinning plays a key role in the development of triplet and quadruplet pregnancies achieved through in vitro fertilization., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Objective: The purpose of this study was to document cost that is associated with multiple births vs singleton births in the United States., Study Design: This was a retrospective cohort study that used a claims database. Women 19-45 years old with live-born infants from 2005-2010 were identified. Infant deliveries were identified by International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes. The cost entailed all payment made by insurers and patients. For mothers, the cost included expenses from 27 weeks before delivery to 1 month after delivery. For infants, the cost contained all expenses until their first birthday. Adjusted cost was estimated by generalized linear models after adjustment for the potential confounding variables with a gamma distribution and a log link., Results: The analysis included 437,924 eligible deliveries. Of them, 97.02% were singletons; 2.85% were twins, and 0.13% was triplets or more. Women with multiple pregnancies had higher systemic and localized comorbidities compared with women with singleton pregnancies (P < .0001). Twins and triplets or more were more likely to have stayed in a neonatal intensive care unit than were singletons (P < .0001). On average, adjusted total all-cause health care cost was $21,458 (95% confidence interval [CI], $21,302-21,614) per delivery with singletons, $104,831 (95% CI, $103,402-106,280) with twins, and $407,199 (95% CI, $384,984-430,695) with triplets or more., Conclusion: Pregnancies with the delivery of twins cost approximately 5 times as much when compared with singleton pregnancies; pregnancies with delivery of triplets or more cost nearly 20 times as much., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: Fetal reduction (FR) in multiples dramatically improves outcomes. We prioritize FR decisions for health and historically declined to factor gender. As male preferences apparently diminished, our bioethicist encouraged a re-evaluation., Methods: Three hundred ninety-six patients reducing triplets or twins were categorized as 3➔2, 3➔1, and 2➔1, Major (M) anomaly or minor (m) anomaly, same gender (SG), and those for whom gender preference (GP) was possible. Higher order and non chorionic villus sampling were excluded. FR decisions were prioritized by M anomaly, Suspicious, or m anomaly. If neither, we considered GP., Results: Of 319, 214 (67%) had either M/m or SG. Of those, 3➔2 with gender option: 71/79 chose male and female or had no preferences, one chose male/male, and seven chose female/female. We reduced monochorionic twins in 33/35 3➔1 cases. Of 20 with GP choice, 10 chose male and 10 chose female. Of 162 2➔1, 54 had M or m, 50 were SG, but of the 44 M/F twins, 20 chose male and 24 chose female., Conclusions: There has been a cultural shift mostly preferring one of each or having no preference. When reducing to one, >50% prefer a girl. In addition to identifying abnormalities, chorionic villus sampling before FR expands patient autonomy., (© 2013 John Wiley & Sons, Ltd.)

We present a case of spontaneously conceived monochorionic triamniotic triplet pregnancy with no fetal anomaly or feto-fetal transfusion. The mother developed gestational diabetes at 20 weeks gestation, and at 20 weeks and 4 days gestation triplet 2 was found to have selective growth restriction and absent end diastolic flow. Although laser treatment and clamping of the umbilical cord of the growth-restricted baby was considered, the management was conservative with regular ultrasound scans and antenatal corticosteroids at 24 weeks gestation, and the umbilical artery Doppler reverted to normal at 26 weeks and 4 days and growth velocity was maintained. An elective caesarean section was performed at 33 weeks gestation to deliver three boys in excellent condition who only required feeding support.

A 27-year-old Ghanaian primigravida with a known triamniotic trichorionic triplet pregnancy presented at 17 weeks gestation following a miscarriage of one triplet at home. Examination and investigation revealed no signs of imminent delivery or infection. After careful counselling with regard to prognosis and options available for management, the couple opted for intervention including rescue cerclage. The patient received antibiotic prophylaxis for five days and daily progesterone suppositories until delivery. An ultrasound scan was performed every three weeks to monitor fetal growth and cervical length. At 24 weeks corticosteroids for fetal lung maturity were given. At 31 weeks gestation she experienced spontaneous rupture of membranes followed by active labour and forceps delivery. There were no maternal complications. Both babies were born in a good condition, but required ventilatory support for 72 h.

Heterotopic pregnancy is a rare event that occurs in less than 1% of pregnancies following in vitro fertilization and embryo transfer, especially when complicated with ovarian hyperstimulation syndrome. We report a case of a 31-year-old woman in the 6th gestational week of pregnancy achieved after in vitro fertilization, who was complaining of acute lower abdominal pain and distension, breathing difficulties and vaginal spotting. Transvaginal ultrasound examination and laboratory tests confirmed the ovarian hyperstimulation syndrome in the presence of two viable gestational sacs. The patient's condition worsened five days later with sudden onset of sharp abdominal pain, nausea and vomiting, along with impaired laboratory test values. Laparoscopy was attempted, but enlarged ovaries and adhesions prevented further procedure, which was then converted to mini-laparotomy. Operative removal of the right tubal pregnancy resulted in uncomplicated course of the intrauterine twin pregnancy and delivery of two healthy neonates by cesarean section at 37 weeks of gestation. Clinicians need to be aware of this rare complication where ovarian hyperstimulation syndrome coexists with heterotopic pregnancy after in vitro fertilization and embryo transfer procedure. Enlarged ovaries may mask accurate ultrasound diagnosis, but timely surgical intervention can prevent fatal consequences and result in normal course and outcome of intrauterine pregnancy.

Objective: To present an unusual case of hyperreactio luteinalis and a comprehensive review of the recent literature. Hyperreactio luteinalis is a benign ovarian condition of pregnancy that at times becomes life threatening. The medical literature provides only case reports., Design: Case report and systematic review of the literature., Setting: University Center., Patient(s): A multiparous woman with polycystic ovary syndrome who underwent ovarian stimulation with oral and injectable medications and conceived triplets. She presented at 10 weeks of pregnancy with hyperreactio luteinalis., Intervention(s): Fetal reduction to singleton., Main Outcome Measure(s): Resolution of condition., Result(s): The condition resolved 6 weeks after fetal reduction. The patient delivered at term without further complications., Conclusion(s): Our review showed that many unnecessary surgeries are performed to treat hyperreactio luteinalis. When feasible, fetal reduction may improve outcome and represents an effective approach that does not compromise maternal well-being or future fertility., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine the proportion of infants admitted to our neonatal intensive care unit (NICU) from multiple gestations resulting from artificial reproductive technology (ART), the complications experienced and interventions required by these infants, and the estimated effect of a mandatory policy of single embryo transfer on admissions and complication rates in our hospital and across Canada., Study Design: We conducted a review of a prospectively maintained database and of hospital records and calculated excess complications compared with either universal single embryo transfer or a policy allowing transfer of two embryos in as many as 33% of women., Results: Of our NICU admissions, 17% are infants from multiple gestations after ART, a significant increase in 10 years. In a 2-year period, the excess NICU use that would have been saved by mandatory single embryo transfer included 3082 patient days and 270 patient ventilator days. Extrapolated across Canada, a policy of single embryo transfer would prevent 30 to 40 deaths, 34 to 46 severe intracranial haemorrhages, and 13 to 19 retinal surgeries annually. Savings in NICU resources would be 5424 to 7299 patient-days of assisted ventilation and 35 219 to 42 488 patient-days of NICU care., Conclusions: A mandatory policy of single embryo transfer would be of substantial benefit to the health of Canadian babies while still benefiting infertile couples., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objective: Assisted human reproduction has been associated with increased rates of multiple births. Data suggest that twins and higher order multiple pregnancies are at risk for pre- and postnatal health complications that contribute to stress on both the family and the Canadian health care system. No published Canadian data estimate the contribution of assisted human reproduction to multiple birth rates. This study was designed to determine the contributions of age and assisted human reproduction to multiple birth rates in Canada., Methods: We performed analyses of existing Canadian databases, using a mathematical model from the Centers for Disease Control and Prevention. More specifically, data from the Canadian Vital Statistics: Births and Stillbirths database were combined with data from the Canadian Assisted Reproductive Technologies Register collected by the Canadian Fertility and Andrology Society. Datasets were standardized to age distributions of mothers in 1978., Results: RESULTS suggest that in vitro fertilization, ovulation induction, and age each contribute more to the rates of triplets than to twins. As expected, the contribution of natural factors was higher to twins than to triplets., Conclusion: These are the first Canadian data analyzed to separate and measure the contributions of age and assisted reproductive technologies to multiple birth rates. Our findings are important for guiding physician and patient education and informing the development of treatment protocols that will result in lower-risk pregnancies and improved long-term health for women and their offspring.

Introduction: Higher-order multiple births have implications for perinatal and maternal morbidity and mortality. This study aimed to determine the incidence and outcomes of higher-order multiple pregnancies in a rural area in Southeast Nigeria., Methods: The study reviewed the data on all higher-order multiple deliveries conducted in two tertiary health institutions in Abakaliki over a seven-year period from January 2000 to December 2006., Results: Higher-order multiple births constituted 0.13 percent of the 16,968 deliveries at the two institutions. There were 21 triplet births and one quadruplet delivery. Mothers with higher-order multiple pregnancies had more antenatal admissions for preterm uterine contractions and had more preterm deliveries. The vaginal route was the preferred method of delivery. Stillbirth was recorded in 12.7 percent of the triplets, with 25.5 percent involving triplets I, II and III, who suffered birth asphyxia. The perinatal mortality rate was 276 per 1,000., Conclusion: The Igbo women of Ebonyi State, Nigeria, have a high rate of higher-order multiple births. These are attended by increased obstetric and perinatal complications. Abdominal delivery is therefore recommended in order to reduce the rate of intrapartum stillbirth and birth asphyxia among triplets.

Objective: To study the impact on pregnant outcome of reducing the number of embryos transferred from three to two in women at age less than 35 who received frozen-thawed embryo transfer (FET)., Methods: The analysis was performed on 90 FET cycles (77 infertile couples, less than 35 years old) with slow-freezing/rapid-thawing method, including 48 cycles with two embryos transferred and 42 cycles with three embryos transferred. The embryo survival rate, high quality embryo rate, clinical pregnancy rate, implantation rate and multiple pregnancies rate were analyzed., Results: No significant differences in embryo survival rate (88.9% versus 88.1%), high quality embryo rate (89.6% versus 81.0%), clinical pregnancy rate (37.5% versus 42.9%), implantation rate (26.0% versus 18.3%) and multiple pregnancy rate (38.9% versus 16.7%) were observed between two and three embryos transferred group (all P > 0.05). However, there were 2 triple pregnancies in three embryos transferred group while none in two embryos transferred group., Conclusion: Reducing the number of high quality embryos transferred from three to two in women at age of less than 35 years old who received FET, could decrease the incidence of triple pregnancy and keep the similar clinical pregnancy rate.

The objective of this study is to evaluate neonatal and maternal outcomes of multiple gestations undergoing delayed-interval delivery at a single institution. A 10-year retrospective review of medical records of patients followed by a Maternal-Fetal Medicine practice in a university-based setting was performed. Patients met criteria for inclusion if a single fetus was delivered spontaneously between 16 and 28 weeks of gestation and a planned attempt was made to prolong the gestation for the remaining fetus(es). Nineteen pregnancies met criteria for inclusion. The median gestational age at delivery of the first fetus was 20 (2)/(7) weeks and the last fetus was 25 (1)/(7) weeks. The median latency was 16 days (range 0 to 152 days). Three patients (15.8%) delivered within 24 hours. There was a 15.8% survival rate for the firstborn fetus and a 53.8% survival rate for all retained fetuses (p = 0.01). There was a 31.6% incidence of serious maternal morbidity related to the procedure. One patient required a postpartum hysterectomy due to massive hemorrhage and uterine atony. Delayed-interval delivery is associated with a higher neonatal survival rate when retained fetuses are compared with firstborn fetuses. However, the procedure is associated with a significant risk of serious maternal morbidity., (© Thieme Medical Publishers.)

Objectives: The aim of this research was to find out the frequency and tendency of multiple pregnancy. Study design. There are used retrospective and prospective comparative analysis. The study includes 51162 births, 960 twins, 39 triplets and 1 quadruplets., Results: The number of multiple pregnancy in 1994 was 44, but in 2009 it was 152. The frequency of twins increased from 1.18% in the beginning of the observed period to 3.62% in the end of the period. The frequency of triplets chanced from 0.06% to 0.34%. We determined that the number of twins increased 3 times and the number of triplets - 6 times. In the beginning of the researched period in 2005, the frequency of twin pregnancy shows a tendency of smooth increase, while form 2006 there is a significant and rapid increase. The frequency of the triplet's births shows relative stability from 1996 till 2006, while from 2007 till now there is a progressive increase in it too., Conclusions: There is a significant increase in the frequency of the multiple preganancies, observed in twins as well as in triplets. There is a stable tendency of increasing, which has the following characteristics smooth growth in the beginning of the period and rapid expand in the last years. The problem of the increasing frequency of the multiple pregnancies and the following up complications must be the aim of our future research and discussion.

Objective: To evaluate the accuracy of amnionicity and chorionicity (A/C) diagnosis of referral physicians and a tertiary care center as compared to histopathologic diagnosis., Method: A retrospective study of 289 multi-fetal gestations was performed comparing A/C diagnoses of referring physicians, a tertiary care center, and histopathology., Results: Two hundred and eighty-nine multi-fetal pregnancies were referred for evaluation; only 43.6% (126/289) carried an accurate diagnosis of A/C before tertiary care center evaluation. The tertiary care center accurately identified A/C in 94.8% (274/289) overall and 100% in first trimester twins and triplets. Referrals with an unspecified A/C diagnosis included 46.1% (113/245) twins and 64.1% (25/39) triplets., Conclusion: Accurate diagnosis of A/C can be obtained by the early assessment of key sonographic findings. Referral providers are less accurate at determining A/C of multifetal gestation when compared to a tertiary center, suggesting that an emphasis should be placed on enhancing these diagnostic skills in the general community or encouraging referral when diagnosis is ambiguous., (Copyright © 2011 John Wiley & Sons, Ltd.)

Objective: To describe a case of successful triplet pregnancy after testicular sperm extraction (TESE) from a man with AZFc deletion and intracytoplasmic sperm injection (ICSI)., Design: Case report., Setting: University hospital., Patient(s): A 38-year-old man affected by complete AZFc deletion and azoospermia., Intervention(s): Spermiogram, Y-chromosome microdeletion screening, TESE for sperm recovery from testicular tissue on the same day as ICSI, transfer of frozen-thawed embryos, vaginal ultrasound examination., Main Outcome Measure(s): The Y chromosome genetic status of an azoospermic patient who underwent TESE and ICSI, the fertilization and pregnancy outcome., Result(s): The patient was found to be azoospermic, and the deletion screening showed complete AZFc deletion. After TESE, the recovered testicular sperm were selected for ICSI. Three good quality embryos were obtained and were frozen due to ovarian hyperstimulation syndrome in the female partner. After transfer of the thawed embryos, a triplet pregnancy was diagnosed by vaginal ultrasonography at the seventh week of gestation. Two male and one female healthy babies were born., Conclusion(s): This is the first report of a successful triplet pregnancy after the transfer of frozen-thawed embryos in a couple in whom the male partner was azoospermic and a carrier of complete AZFc deletion. This deletion should not adversely affect a man's TESE retrieval prognosis or the fertilization, cleavage, and implantation of embryos. The offspring were healthy, although the two sons inherited the AZFc deletion., (Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Monochorionic pregnancies present unique challenges for selective fetal reduction, as vaso-occlusive procedures are required to ablate blood flow, usually in the umbilical cord, to achieve asystole in the selected fetus. We describe a case series of 35 monochorionic pregnancies (27 twins and eight triplets) undergoing selective fetal reduction using radiofrequency ablation. All procedures were performed under local anaesthesia. The procedure was technically successful in all cases. The live born rate was 88.6%. One (2.9%) woman miscarried within 2 weeks of the procedure, and two (5.7%) babies were stillborn. The median gestation at delivery was 36 weeks of gestation (range 24-41 weeks). There were no maternal complications. The median gestational age at procedure was 17 + 3 weeks (range from 12 + 5 to 27 + 4 weeks). All women had antenatal magnetic resonance imaging (MRI) post procedure. There were two (5.7%) cases of abnormal brain imaging. Our experience suggests that radiofrequency ablation is a safe and effective procedure for fetal reduction in complicated monochorionic pregnancies.

Objective: To test whether 17 alpha-hydroxyprogesterone caproate (17P) will reduce neonatal morbidity by increasing gestational age at delivery in triplet pregnancies., Study Design: Double-blind, randomized clinical trial. Mothers carrying trichorionic-triamniotic triplets were randomly assigned (in a 2:1 ratio) to weekly injections of 250 mg of 17P or placebo, starting at 16-22 weeks and continued until 34 weeks. Primary outcome was composite neonatal morbidity., Results: Fifty-six women were randomized to 17P and 25 to placebo. Composite neonatal morbidity occurred with similar frequency in the 17P and placebo groups (38% vs 41%, respectively; P = .71). Mean gestational age at delivery was not affected by 17P (31.9 vs 31.8 weeks; P = .36). There were 13 midtrimester fetal losses with 17P vs none with placebo (P < .02)., Conclusion: In triplet pregnancy, prophylactic treatment with 17P did not reduce neonatal morbidity or prolong gestation but was associated with increased midtrimester fetal loss., (Copyright 2010 Mosby, Inc. All rights reserved.)

Developments in assisted reproductive technology have allowed us to decrease the numbers of transferred embryos and thereby reduce the risk of multifetal pregnancies. However, even when the numbers of transferred embryos are restricted, the incidence of monozygotic multiple pregnancies is not reduced, and can be significantly higher than normal. We report two cases of monochorionic triamniotic triplet pregnancies after applying assisted reproductive technology. Three male babies were born in one pregnancy and the other pregnancy aborted at 10 weeks of gestation. Several factors, such as manipulation of the zona pellucida or extended blastocyst culture, might increase the risk of such monozygotic multiple gestations in this setting, but the actual causes remain unknown. Besides detecting predictive factors for monozygotic pregnancies, any manipulation of the zona pellucida in combination with blastocyst culture must be done cautiously to minimize the likelihood of monochorionic multiple pregnancies.

Objective: To assess changes in incidence rates and outcomes of triplets over 40 years with a particular focus on the influence of assisted reproductive technology (ART)., Design: Population-based cohort study., Setting: The Medical Birth Registry of Norway., Population: 2.18 million pregnancies, including 448 sets of triplets and 27,575 twin pairs, covering the years 1967-2006. Since 1988, pregnancies from ART have been available through a separate registry and linked with the birth record., Methods: Incidence rates and outcomes for triplets were analysed and compared with those for singletons and twins. Relative risks were estimated between time periods and between ART and non-ART pregnancies., Main Outcome Measures: Incidence rates, birthweight, gestational age and perinatal mortality., Results: The total triplet rate per 10,000 pregnancies increased from 1.0 during 1967-71 to 3.5 during 1987-92, followed by a decline to 2.7 during 2002-06. After excluding ART pregnancies, the incidence was more than doubled at the end of the study period. The mean gestational age and birthweight of triplets were significantly lower during 1988-2006 than 1967-87, but similar for ART and non-ART triplets in the last period. The caesarean rate in triplets increased from 47 to 92%. The relative risk of perinatal death in triplets relative to singletons did not change after the introduction of ART [before: relative risk, 8.9 (95% confidence interval, 6.8-11.7); after: relative risk, 10.4 (95% confidence interval, 8.3-13.0)]., Conclusions: The triplet incidence rate in Norway has more than doubled during the last 40 years, even after excluding ART pregnancies. The risk of perinatal death in triplets is ten times higher relative to singletons and has not changed during this 40-year period, independent of the introduction of ART.

Background: Monozygotic monochorionic triplet pregnancies in which triplets share an amniotic cavity (di- or monoamniotic) are very rare. In addition to the other risks of high-order multiple pregnancy, such triplets are at risk for cord entanglement and therefore cord accident and intrauterine demise., Case: A 32-year-old primigravid woman was found on ultrasound at 25 to 26 weeks' gestation to have a monochorionic diamniotic triplet pregnancy, a short dilated cervix, one fetus with biometry < 10th centile, and cord entanglement. The woman was hospitalized, ultrasound assessment was performed three times per week, and elective Caesarean section was performed at 30 weeks. The triplets subsequently did well., Conclusion: Monochorionic diamniotic triplet pregnancy with cord entanglement can be successfully managed by admission, close inpatient monitoring, and elective delivery.

Uterine malformations and spontaneous triplet pregnancy are rare situations separately, and both are related to worse perinatal outcomes. In the 3 cases of combined triplet pregnancy and uterus didelphys previously published, at least 2 of the 3 fetuses died. Morbidity rates are also high. We report the case of a 24-year-old Caucasian woman with a uterus didelphys and two previous caesarean sections who carried a spontaneous triplet pregnancy. To our knowledge, this is the first case of a spontaneous triplet pregnancy in a uterus didelphys ever reported and the only one with uneventful perinatal outcome for all fetuses. Expectant management may be an alternative to embryo reduction to manage triplet pregnancies in a didelphys uterus, especially when this option is not considered. Nevertheless, there is not enough evidence to confirm which is the optimal management strategy, and more studies are needed., (Copyright 2010 S. Karger AG, Basel.)

The purpose of our study was to evaluate perinatal and neonatal outcomes in triplet gestations in relation to placental chorionicity. We hypothesized that triplets containing a monochorionic pair (dichorionic triamniotic) would have increased morbidity compared with triplets without a monochorionic pair (trichorionic triamniotic). We retrospectively analyzed all triplet sets > or =20 weeks delivering at our institutions from January 1995 through April 2007. Data were collected via perinatal and neonatal databases, chart review, and placental pathology. Individuals in dichorionic triamniotic triplet sets (N = 75), when compared with trichorionic triamniotic triplets (N = 309), were more likely to have a lower mean birth weight (P < 0.001) and lower gestational age at delivery (P < 0.001), spend more days in the neonatal intensive care unit (P = 0.045), have culture-proven sepsis (P = 0.02), and require intubation (P = 0.05). Multivariate analysis demonstrated that dichorionicity is not an independent cause of morbidity, but results in earlier delivery and lower birth weight. Dichorionic triamniotic triplets are at increased risk for earlier deliveries and lower birth weight at delivery compared with trichorionic triamniotic triplets., (Thieme Medical Publishers.)

Information on feto-fetal transfusion syndrome (FFTS) in higher-order multifetal gestation is limited. We report outcomes of 10 triplet pregnancies treated by fetoscopic laser occlusion of the chorioangiopagous vessels (FLOC). The study period was August 1992 to August 2008. Inclusion criteria were gestational age < or =25 weeks and ultrasound confirmation of monochorionicity in at least one twin set and FFTS. Treatment included FLOC, exit amnioreduction, and cerclage when indicated. Hospital records, placental pathology, neonatal course, and long term follow-up of the mother and infants were reviewed. There were eight triamnionic dichorionic and two triamnionic monochorionic triplets. Mean maternal age was 29.8 years, and five conceived following in vitro fertilization. FFTS stage at treatment was > or =II in all cases, at a mean gestational age 20.9 +/- 2.2 weeks. Two patients required immediate rescue cerclage, and all 10 had hypoproteinemia and anemia. Mean age at delivery was 31.2 +/- 3.4 weeks, with a mean birth weight 1568.4 +/- 498 g for the live-born fetuses. Twenty-three (77%) fetuses survived, with at least one fetus surviving in 9 (90%) cases. Cerebral ultrasound imaging and neurological examination were normal in all neonates, and clinical follow-up has remained normal at 67.5 +/- 56 months for the group. FLOC is feasible in dichorionic and monochorionic triplet pregnancy complicated by FFTS. Outcomes are comparable to our experience with twins, namely improved perinatal survival and neonatal morbidity when compared with alternative treatments., (Thieme Medical Publishers.)

Aim: There were two aims to the study: (1) to provide local outcome data that would be useful in counselling prospective parents of triplets; and (2) to address the deficit in accurate contemporary data on neurodevelopmental outcome and neonatal morbidity for those infants weighing less than 1500 g at birth., Methods: We reviewed the outcome of triplet pregnancies born at National Women's Hospital / Auckland City Hospital (Auckland, New Zealand) for 1995-2005 inclusive. For this study triplet pregnancy was defined as a pregnancy beyond 20 weeks leading to registration of at least one birth., Results: For the study period, 55 triplet pregnancies were identified. Forty-five percent of the pregnancies were reported as spontaneously conceived and 60% had no major complications other than premature delivery. One pregnancy spontaneously aborted; three fetuses from one pregnancy were stillborn, and four infants died in delivery suite. The median gestational age at birth was 32 (23-37) weeks and birth weight 1620 (530-2780) g. The median (range) Apgar score, for liveborns, was 8 (2-10) and 10 (4-10) for 1 and 5 minutes respectively. There were five neonatal deaths. Fifty-three infants, <1500g at birth, underwent formal developmental assessment. Three had cerebral palsy (2 hemiplegia and 1 spastic diplegia); one had marked motor delay and one hearing impairment requiring aids. The median Bayley II MDI was 95 (71-105) and PDI 94 (65-110). Outcomes were categorised in surviving triplets <1500 g as normal in 66%, mild abnormality in 17%, moderate abnormality in 15% and severely abnormal in only 2%., Conclusion: Although triplets represent a significant burden on the regional NICUs the outcome, including those <1500 g at birth, compares favourably with that reported.

Renal failure generally accompanies an alteration in reproduction function. Even though a renal transplantation does in fact improve this function, there are few cases described in medical literature of multiple pregnancies in transplant patients that ended in a successful manner. In addition, there is a greater incidence of complications such as hypertension, preeclampsia, and premature delivery. This article describes a 31-year-old patient who became pregnant with triplets at 3 years and 6 months after receiving a renal transplant from a cadaver. The patient received treatment with cyclosporine, azathioprine, and prednisolone. During the pregnancy, there was a increase in hypertension, proteinuria, cholestasia gravidic symptoms, and premature delivery. Pregnancy control included evaluation of the fetoplacental unit together with hypertensive management and adjustment of immunosuppressant treatment, especially the cyclosporine dose, seeking to facilitate greater fetal maturity. Three newborns of 840, 860, and 1020 were delivered by cesarean section. The newborns spent 6 to 8 weeks in the neonatal unit and were released without complications. The newborns have presented adequate psychomotor and physical development to date. The triplets are now 4 years old. The transplant recipient has a creatinine clearance of 81 mL/min at 7 years after transplantation.

Objective: To review some of the aspects of multiple pregnancies., Design: A retrospective review of multiple pregnancy deliveries., Setting: Pumwani Maternity Hospital- Nairobi Kenya, between 1st January and 31st December 2006., Subjects: Three hundred and twenty eight mothers with twins and two sets of triplet deliveries., Results: The total annual deliveries were 15,642. The twinning rate was one in 48 deliveries and the triplet rate was one in 7,821 deliveries. Most of the mothers were of low parity and in the lower age group. Majority had no previous history of twins and were married. The sex differences in both the first and second twins were as of the normal population with males being delivered more than females. Most of the twins were delivered alive through spontaneous vertex delivery (SVD). Majority of first twins had no complications while in second twins the majority had more complications. Most of the deliveries had no obvious congenital malformations. Most of the twins were of low birth weight and were of the same sex (monozygotic). The most common complications in both first and second twins were prematurity and asphyxia. The majority of the twins were diagnosed during the prenatal period and the most common method of diagnosis was by ultrasonography. The majority of the mothers had no complications. The most common maternal complications being preeclampia (PET) and anaemia., Conclusion: Most of the mothers with multiple pregnancies were of low parity and in the lower age group. Diagnosis was mainly done by ultrasonography therefore emphasis should be done to improve clinical diagnosis especially in resource constrained facilities. A more detailed study should be undertaken especially the events in the pre-pregnancy and during the antenatal period. The present study assumes that same sex twins are the same as monozygotic twins. A more detailed study on the types of placentation would be useful. As PET, anaemia, prematurity and asphyxia are the most common maternal and neonatal complications medical workers need to be made aware of the appropriate management of the conditions. These babies will need long-term follow-up.

Objective: To report on a patient with a quintuplet pregnancy consisting of a monochorionic triamnionic triplet pregnancy and one case of monoamniotic twins after intracytoplasmic sperm injection (ICSI), laser-assisted hatching, and day 4 embryo transfer., Case Report: A 34-year-old woman who underwent ICSI due to male infertility. She underwent standard controlled ovarian hyperstimulation. Retrieved oocytes were fertilized in vitro, and 3 embryos were transferred on day 4 after laser-assisted hatching. Transvaginal ultrasound revealed a monoamniotic twin pregnancy and a monochorionic-triamniotic triplet pregnancy. A second ultrasound, 1 week later, showed three distinct foci of cardiac motion in one sac, while the sac of the monoamniotic twins had one embryo with heart beat. After extensive counseling with perinatologists about pregnancy complications, the patient elected to performed fetal reduction on the third sac. A healthy male infant was delivered by Caesarean section at 38 weeks of gestation., Conclusions: The exact mechanism of monozygotic multiple gestation is still poorly characterized. Procedures that modify the zona pellucida (e.g. ICSI and assisted embryo hatching) have been suggested as important in the monozygotic multiple gestation hypothesis, yet a definitive relationship between any clinical intervention during in vitro fertilization and the subsequent development of multiple monozygotic gestation remains speculative., ((c) 2009 S. Karger AG, Basel.)

Objectives: To examine birth weight in dichorionic and monochorionic twins and trichorionic triplets, and to estimate the relative independent importance on growth of fetal number, chorionicity and gestational age., Methods: Four groups of pregnancies were examined: 12,816 singleton pregnancies, 302 monochorionic twin pregnancies, 569 dichorionic twin pregnancies, and 97 trichorionic triplet pregnancies. Chorionicity was determined at 10-14 weeks on the basis of the presence or absence of the lambda sign in twins, and by examining the ipsilon zone in triplets. The relationship between birth weight and gestational age in singletons was established, and using this equation the expected mean birth weights for all gestational ages were calculated. For each case in all groups, the difference between the observed birth weight for each fetus and the appropriate normal mean for gestation in singletons was calculated (Z-score). Multiple regression analysis was used to examine the independent contribution of gestational age, number of fetuses and chorionicity in the prediction of actual birth weight and birth weight Z-score., Results: Birth weight Z-score was significantly lower than the expected mean in singletons for dichorionic twins, monochorionic twins and trichorionic triplets (t = 15.4, P < 0.0001, t = 21.7, P < 0.0001 and t = 19.9, P < 0.0001, respectively). Furthermore, the reduction in expected birth weight was significantly greater for monochorionic twins and trichorionic triplets compared with dichorionic twins (t = 6.3, P < 0.0001 and t = 7.8, P < 0.0001, respectively). Multiple regression analysis demonstrated that number of fetuses, presence of a monochorionic placenta and gestational age were independently associated with birth weight Z-score, the strongest effect being fetal number, followed by monochorionicity (t = - 23.4, P < 0.0001, t = - 8.3, P < 0.0001 and t = - 4.9, P < 0.0001, respectively)., Conclusions: The finding that monochorionic twins were of lower adjusted birth weight than dichorionic twins, and the significant independent effect of chorionicity on birth weight suggest that monochorionic placentation in itself has an effect on intrauterine growth. The effect of fetal number independent of chorionicity is demonstrated by the lower birth weight of trichorionic triplets compared with dichorionic twins., ((c) 2008 ISUOG.)

Objective: To present a case report of a unilateral triplet ectopic pregnancy (EP) conceived by IVF-embryo transfer., Design: Case report., Setting: University Hospital, Budapest, Hungary., Patient(s): A 26-year-old infertile woman with a history of right salpingectomy, hyperprolactinemia, and male factor infertility underwent IVF-embryo transfer of three embryos. Early transvaginal sonography revealed a triplet pregnancy in the left fallopian tube (two at interstitial and one at ampullary location)., Intervention(s): Multiple dose methotrexate (MTX) therapy was applied., Main Outcome Measure(s): Follow-up pelvic ultrasounds and laboratory testing confirmed fetal cardiac activity cessation and decreasing beta-hCG levels., Result(s): In spite of the decreasing beta-hCG levels the tube's diameter increased, the patient's symptoms escalated, and finally, the level of hemoglobin and hematocrit decreased. Laparotomy was performed with the removal of the left tube and cornual part of the uterus., Conclusion(s): Our case represents a very rare condition, a unilateral triplet EP after IVF-embryo transfer-the first one ever reported in the literature. After IVF-embryo transfer early ultrasound examinations are important to identify EPs at an early stage when medical management can still be taken into consideration. Strict monitoring is necessary to identify the success of medical intervention or the need for surgery.

We report a case in which a patient received IVF treatment due to massive pelvic endometriosis. The tubal patency and sperm parameters were normal. After e-SET (elective single embryo transfer) ultrasonography showed a triplet pregnancy with thick dividing membranes and lambda sign between all sacs. Two monozygotic and one dizygotic girl were delivered by Caesarean section at 28 weeks gestation. The couple had intercourse 2 days prior to the oocyte pick up (OPU) and the triplet pregnancy was attributed to a combination of assisted and spontaneous conception.

Objective: The purpose of this study was to calculate nationally representative, population-based estimates of maternal and neonatal risks in triplet and quadruplet pregnancies compared with twin pregnancies., Study Design: The study population included 316,696 twin, 12,193 triplet, and 778 quadruplet pregnancies from the 1995-2000 Matched Multiple Birth Data Set. Adjusted odds ratios (AORs) and 95% CIs estimated the risk of complications and were controlled for maternal age, race, parity, and smoking status., Results: Compared with mothers of twins, mothers of triplets and quadruplets were more likely to be diagnosed with preterm premature rupture of membranes (AORs, 1.53, 1.74, respectively), pregnancy-associated hypertension (AORs, 1.22, 1.27), and excessive bleeding (AORs, 1.50, 2.22), to require tocolysis (AORs, 2.85, 5.03), and to be delivered by cesarean (AORs, 6.55, 7.38) at < 29 weeks of gestation (AORs, 3.76, 7.96), and to have > or = 1 infants die (AORs, 3.02, 4.07)., Conclusion: Triplet and quadruplet pregnancies have significantly higher risks than twin pregnancies for most maternal and neonatal complications. Maternal anthropometric, nutritional, and previous reproductive factors may be particularly important in the reduction of these excess risks and improvement of outcomes in multiple births.