Consequences of vanishing twins in IVF/ICSI pregnancies

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

Maternal serum concentrations of pregnancy associated placental protein A and pregnancy specific {beta}-1-glycoprotein in multifetal pregnancies before and after fetal reduction

Placental function in multifetal pregnancies before and afterembryo reduction was investigated by measuring maternal serumconcentrations of pregnancy associated placental protein-A (PAPP-A)and pregnancy specific -1-glycoprotein (SP-1). Three groupsof pregnant women were studied following assisted reproduction;groups 1 and 2, were 12 singleton and 12 twin pregnancies respectively,and group 3 comprised 12 women with multifetal pregnancies undergoingembryo reduction. PAPP-A and SP-1 were measured serially at8–21 weeks gestation. In all pregnancies, maternal serumPAPP-A and SP-1 increased with gestation. In twin pregnanciesthe mean concentrations of SP-1 were significantly higher thanin singletons at all gestations, whereas for PAPP-A, concentrationswere similar between these groups. In multifetal pregnanciesbefore embryo reduction, the serum concentrations of both proteinswere significantly higher than in twin pregnancies. Followingreduction, the concentrations of PAPP-A remained significantlyhigher than for twins throughout, whereas the concentrationsof SP-1 gradually converged towards those of twins; by 19 weeksthere was no difference between the means of the two groups.These findings suggest that circulating concentrations of SP-1reflect total placenta mass, which is proportional to the numberof live fetuses, whereas the pattern of PAPP-A changes suggeststhat this protein is produced by the placenta, decidua and othertissues.     

Genetics: Genetic analysis prior to selective fetal reduction in multiple pregnancy: technical aspects and clinical outcome

Multiple pregnancies resulting from ovarian stimulation areat a higher risk of carrying at least one fetus affected byMendelian or chromosomal anomalies, the incidence of which isdirectly related to the order of multiples. Genetic analysisbefore fetal reduction was offered to both high-and low-riskpregnant women carrying two or more fetuses after ovulationinduction. Chorionic villus sampling (CVS) and fetal reductionwere achieved by transabdominal needling. The use of short-termculture, the polymerase chain reaction and fresh tissue enzymaticanalyses have made it possible for genetic diagnosis to be availablein a few days. A total of 100 patients had multifetal pregnancyreduction performed by a single operator; all of them completedpregnancy and none was lost at follow-up. The total fetal lossbefore 24 weeks was 7% and no statistically significant relationshipwas found with the final number of fetuses and CVS. Perinatallosses (3.9%) were only present in the series with a final numberof two fetuses. Pregnancy duration and birthweight were significantlyhigher in singletons than in twins, but were not related toCVS. The rate of chromosomal disorders was higher (7.2%) inthe study series than in singleton pregnancies not undergoingfetal reduction. Diagnostic error due to incorrect samplingwas reported in 1.5% of cases. These data support fetal reductionas a valuable strategy to improve the outcome of multiple pregnancy.The outcome of pregnancies reduced to singletons was significantlybetter than of those reduced to twins, and was not related toCVS. Therefore, prenatal genetic diagnosis should become anintegral part of counselling on multiple pregnancy, and is stronglyrecommended when reduction to singleton pregnancy is requested.     

Peri-implantation and late gestation maternal undernutrition differentially affect fetal sheep skeletal muscle development

Poor prenatal nutrition is associated with a greater risk of adult glucose intolerance and insulin insensitivity in the offspring. Skeletal muscle is the primary tissue for glucose utilization, and insulin resistance in muscle is the earliest identifiable abnormality in the pre-diabetic patient. We investigated the effect of early and late gestation undernutrition on structure and markers of growth and glucose metabolism regulation in the fetal triceps brachii (TB, slow- and fast-twitch myofibres) and soleus (slow-twitch myofibres) muscles. Pregnant sheep were fed 100% nutrient requirements (C, n = 8) or a restricted diet peri-implantation (PI, n = 9; 40%, 1–31 days gestation (dGA) (term ∼147)) or in late gestation (L, n = 6; 50%, 104–127 dGA). At 127 ± 1 dGA we measured myofibre and capillary density in the fetal TB and soleus muscles, and mRNA levels in the TB of insulin receptor (InsR), glucose transporter-4 (GLUT-4) and type 1 insulin-like growth factor receptor (IGF-1R). Total myofibre and capillary densities were lower in the TB, but not the soleus, of PI and L fetuses. The predominant effect in the L group was on slow-twitch myofibres. In TB, InsR, GLUT-4 and IGF-1R mRNA levels were greater in L group fetuses. Our finding of reduced myofibre density is consistent with a redistribution of resources at the expense of specific peripheral tissues by early and late gestation undernutrition which may be mediated by a decrease in capillary density. The increase in key regulatory components of glucose uptake following late gestation undernutrition may constitute a short-term compensation to maintain glucose homeostasis in the face of fewer type I (insulin-sensitive) myofibres. However, together these adaptations may influence the risk of later metabolic disease and thus our findings have implications for future strategies aimed at improving maternal diet.     

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

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

Maternal serum inhibin levels in twin and singleton pregnancies conceived by assisted reproduction

BACKGROUND: To investigate whether second trimester serum inhibin levels differ in pregnancies conceived by assisted reproduction technology (ART). METHODS: In Israel, serum samples from twin pregnancies were obtained for inhibin testing from women either referred for routine ultrasound monitoring, follow up after multi-fetal reduction or amniocentesis, largely for advanced maternal age. In the UK, inhibin had been tested prospectively in singleton and twin pregnancies of women having routine Down's syndrome (DS) screening. Results were available from 207 ART pregnancies: 170 singletons and 37 twins. This includes 15 twins from Israel, known to have been reduced from triplets to twins. Comparison was made with 4384 spontaneous pregnancies: 4334 singletons and 50 twins. Results were expressed in multiples of the gestation-specific median (MoM) for normal spontaneous pregnancies. RESULTS: In ART singletons, the median maternal inhibin level was higher (1.11 MoM) than in spontaneous singletons (0.99 MoM, P < 0.001, two-tail Wilcoxon Rank Sum Test). In twins, there was no material difference between ART and spontaneous pregnancies with medians of 1.98 and 2.18 MoM, respectively (P = 0.62). There was no effect of multi-fetal reduction, with medians of 1.76 and 1.81 MoM in reduced and non-reduced twins, respectively (P = 0.46). CONCLUSION: It appears that serum inhibin levels are increased on average in ART singletons but not in ART twin pregnancies. More data will be needed before deciding whether risk calculation parameters need to be altered when using inhibin for DS screening in pregnancy.     

Obstetric and perinatal outcome of children conceived from cryopreserved embryos

The main purpose of this study was to evaluate the obstetric and neonatal outcome of children conceived from cryopreserved embryos. The medical records of 270 infants (163 singletons, 98 twins and nine triplets) were reviewed and compared with two control populations of children born after in-vitro fertilization (IVF) with fresh embryos and children born after spontaneous pregnancies. The controls were matched according to maternal age, parity, plurality and date of delivery. In the cryopreserved group the gestational age at delivery for singletons was 279 +/- 13 days with birthweight 3476 +/- 616 g; for twins gestational age was 257 +/- 19 days with birthweight 2574 +/- 560 g; for triplets gestational age was 228 +/- 3 days with birthweight 1752 +/- 183 g. The incidence of preterm birth (< 37 weeks gestation) was 5.6% for singletons, 44.9% for twins and 100% for triplets. Seven children had major malformations (2.7%) and perinatal mortality occurred in two children (8/1000). Gestational age at delivery, birthweight, the incidence of malformations and the perinatal mortality were comparable with the two control groups both for singletons and twins. Significantly more singletons in the cryopreserved group were delivered by Caesarean section compared with the spontaneous group. The number of infants with low Apgar score (< 7 at 5 min) and the number of infants admitted to neonatal intensive care units were similar in the cryopreserved and spontaneous groups. In conclusion, the cryopreservation process did not seem to adversely influence fetal development and no increased perinatal risk was found.      

A comparison of the early growth of twins and singletons

BACKGROUND: It is well known that the birth weight of twins is less than that of singletons, but there is less information about how birth lengths compare and how twins grow in the postnatal and early childhood period. The implications of the shorter duration of gestation of twins in comparing their postnatal progress with that of singletons are seldom taken into consideration. AIMS: The study aimed to compare the growth of healthy twins and singletons over the first 4 years of life. SUBJECTS AND METHODS: Birth length data on English twins born between 1990 and 1997 were used to produce reference values for gestational ages from 33 to 40 weeks. Follow-up data of weights and lengths up to the equivalent of 40 weeks' gestation are reported on some of these infants who were born pre-term. On the basis of questionnaires, the growth of twins in terms of weight, length/height and head circumference has been followed up to 4 years of age. RESULTS: Mean birth length of twins showed a fall-off when compared with singletons at comparable gestational ages, which was more marked in boys than girls and evident earlier. Extrauterine growth of twins born pre-term was comparable to that of adequately nourished twins remaining in utero until term. Much of the smallness of twins at birth was because of their shorter gestation. Subsequently singletons gained weight faster. Lengths/heights showed no deficit compared with singletons. Head circumferences of twins were, however, smaller than singletons throughout. CONCLUSIONS: The early growth of normal twins differs markedly from that of singletons. It is important to recognize that singleton reference values do not correctly reflect the growth of twins.     

Multiple gestation pregnancy. The ESHRE Capri Workshop Group

Multiple gestation pregnancy rates are high in assisted reproductivetreatment cycles because of the perceived need to stimulateexcess follicles and transfer excess embryos in order to achievereasonable pregnancy rates. Perinatal mortality rates are, however,4-fold higher for twins and 6-fold higher for triplets thanfor singletons. Since the goal of infertility therapy is a healthychild, and multiple gestation puts that goal at risk, multiplepregnancy must be regarded as a serious complication of assistedreproductive treatment cycles. The 1999 ESHRE Capri Workshopaddressed the psychological, medical, social and financial implicationsof multiple pregnancy and discussed how it might be prevented.Multiple gestations are high risk pregnancies which may be complicatedby prematurity, low birthweight, pre-eclampsia, anaemia, postpartumhaemorrhage, intrauterine growth restriction, neonatal morbidityand high neonatal and infant mortality. Multiple gestation childrenmay suffer long-term consequences of perinatal complications,including cerebral palsy and learning disabilities. Even whenthe babies are healthy they must share their parents' attentionand may experience slow language development and behaviouralproblems. Current data indicate that the average hospital costper multiple gestation delivery is greater than the averagecost of in-vitro fertilization (IVF) and intracytoplasmic sperminjection (ICSI) cycles. Prevention is the most important meansof decreasing multiple gestation rates. Multiple gestation ratesin ovulation induction and superovulation cycles can be reducedby using lower dosage gonadotrophin regimens. If there are morethan three mature follicles, the cycle should be converted toan IVF cycle, or it should be cancelled and intercourse shouldbe avoided. In IVF cycles two embryos can be transferred withoutreducing birth rates in most circumstances. Embryo reductioninvolves extremely difficult decisions for infertile couplesand should be used only as a last resort. Assisted reproductivetreatment centres and registries should express cycle resultsas the proportion of singleton live births; twin and tripletrates should be reported separately as complications of theprocedures. Reducing the multiple gestation pregnancy rate shouldbe a high priority for assisted reproductive treatment programmes,despite the pressure from some patients to transfer more embryosin order to improve success. If nothing is done, public concernmay lead to legislation in many countries, a step that wouldbe unnecessary if assisted reproductive treatment programmesand registries took suitable steps to reduce multiple pregnancyrates.     

Fetal signaling through placental structure and endocrine function: Illustrations and implications from a nonhuman primate model

The placenta is a transmitter of fetal need and fetal quality, interfacing directly with maternal physiology and ecology. Plasticity of placental structure and function across the developmental timeframe of gestation may serve as an important tool by which a fetus calibrates its growth to shifting maternal ecology and resource availability, and thereby signals its quality and adaptability to a changing environment. Signals of this quality may be conveyed by the size of the placental interface, an important marker of fetal access to maternal resources, or by production of placental insulin‐like growth factor‐II, a driver of fetoplacental growth. Litter size variation in the common marmoset monkey offers the opportunity to explore intrauterine resource allocation and placental plasticity in an important nonhuman primate model. Triplet marmosets are born at lower birth weights and have poorer postnatal outcomes and survivorship than do twins; triplet placentas differ in placental efficiency, microscopic morphology, and endocrine function. Through placental plasticity, triplet fetuses are able to adjust functional access to maternal resources in a way that allows pregnancy to proceed. However, the costs of such mechanisms may relate to reduced fetal growth and altered postnatal outcomes, with the potential to lead to adverse adult health consequences, suggesting an important link between the placenta itself and the developmental origins of health and disease. Am. J. Hum. Biol. 2009. © 2009 Wiley‐Liss, Inc.     

Effect of nutritional restriction in early pregnancy on isolated femoral artery function in mid-gestation fetal sheep

Unbalanced maternal nutrition affects fetal endocrine and cardiovascular systems, sometimes accompanied by changes in growth, although this is usually in late gestation. We determined the effect of moderate restriction for the first half of gestation of maternal dietary protein, or of total calorific intake on isolated resistance artery function of mid-gestation fetal sheep. Welsh Mountain ewes were nutritionally restricted by 30 % of the recommended nutrient intake (globally restricted) or 30 % of the recommended protein intake (protein-restricted), compared to control ewes fed 100 % of recommended nutrient intake, for ~12 days prior to conception and for the subsequent 70 days of gestation. At mid-gestation, fetal and placental weights were similar in all dietary groups. In isolated femoral arteries, the response curve to noradrenaline was reduced in protein-restricted group fetuses (   P < 0.05  ). Maximal relaxation (   P < 0.01  ) and sensitivity (   P < 0.05  ) to acetylcholine were markedly reduced in protein-restricted group fetuses, and to a smaller extent in globally restricted group fetuses (response curve,   P < 0.05  ). The dilator response (   P < 0.05  ) and sensitivity (   P < 0.05  ) to the α₂ agonist UK14304 was lower in protein-, but not in globally restricted group fetuses. The response (   P < 0.05  ) and sensitivity (   P < 0.05  ) to the nitric oxide donor sodium nitroprusside were reduced in protein-restricted group fetuses compared to controls. Our data show that dietary imbalance, in particular restricted protein, of the ewe can produce blunting of endothelial-dependent and -independent relaxation in systemic arteries from the mid-gestation fetus. These changes may precede perturbed late-gestation fetal and postnatal cardiovascular control.     

Relationship between maternal serum vascular endothelial growth factor concentration in early pregnancy and fetal and placental growth.

Vascular endothelial growth factor (VEGF) has important effects on endothelial cells increasing cell proliferation, permeability and nitric oxide production; concentrations of VEGF in the maternal serum increase during the first 10 weeks of pregnancy. In this study, the relationship of maternal serum VEGF with maternal health during pregnancy and with fetal and placental size at mid-pregnancy and at term was investigated. Serum was obtained from 539 Caucasian women with singleton pregnancies between 8 and 20 weeks of pregnancy (mean 14 weeks). Total serum VEGF concentrations were measured by direct competitive radioimmunoassay. Fetal size and placental volume were measured by ultrasound between 16 and 20 weeks gestation. Birthweight, placental weight and anthropometric measurements of the baby were obtained after delivery. Serum VEGF concentrations were found to be higher in women with a lower weight before pregnancy (P = 0.01) and in those carrying a female fetus (P = 0.002). VEGF concentrations were positively correlated with placental volume (r = 0.17, P = 0.0001) but not with fetal size between 16 and 20 weeks gestation. Serum VEGF concentrations were positively correlated with both birthweight (r = 0.10, P = 0.02) and placental weight at delivery (r = 0.13, P = 0.003). The data presented support the view that VEGF may be one of the factors involved in mediating the maternal cardiovascular adaptation to pregnancy.     

Fetal body weight and the development of the control of the cardiovascular system in fetal sheep

Reduced birth weight predisposes to cardiovascular diseases in later life. We examined in fetal sheep at 0.76 ( n = 18) and 0.87 ( n = 17) gestation whether spontaneously occurring variations in fetal weight affect maturation of autonomic control of cardiovascular function. Fetal weights at both gestational ages were grouped statistically in low (LW) and normal weights (NW) ( P < 0.01). LW fetuses were within the normal weight span showing minor growth dysproportionality at 0.76 gestation favouring heart and brain, with a primary growth of carcass between 0.76 and 0.87 gestation ( P < 0.05). While twins largely contributed to LW fetuses, weight differences between singletons and twins were absent at 0.76 and modest at 0.87 gestation, underscoring the fact that twins belong to normality in fetal sheep not constituting a major malnutritive condition. Mean fetal blood pressure (FBP) of all fetuses was negatively correlated to fetal weight at 0.76 but not 0.87 gestation ( P < 0.05). At this age, FBP and baroreceptor reflex sensitivity were increased in LW fetuses ( P < 0.05), suggesting increased sympathetic activity and immaturity of circulatory control. Development of vagal modulation of fetal heart rate depended on fetal weight ( P < 0.01). These functional associations were largely independent of twin pregnancies. We conclude, low fetal weight within the normal weight span is accompanied by a different trajectory of development of sympathetic blood pressure and vagal heart rate control. This may contribute to the development of elevated blood pressure in later life. Examination of the underlying mechanisms and consequences may contribute to the understanding of programming of cardiovascular diseases.     

The growth, development and education of Finnish twins: a longitudinal follow-up study in a birth cohort from pregnancy to nineteen years of age

The growth, development and vocation of 289 twins in a one year birth cohort beginning during pregnancy and followed up to the age of 19 years was compared with that of 11,623 singletons and two sets of controls matched either by maternal factors only or by these and perinatal morbidity, all from the same cohort. The twins were more often pre-term and small for their gestational age, and had more often suffered from perinatal asphyxia, neonatal hyperbilirubinaemia and hypoglycemia. They had learned to walk without support later than the singletons and the controls matched only by maternal factors, but this difference did not exist between the twins and the controls also matched by perinatal morbidity. The same kind of result was found when studying the number of words spoken at the age of one year and physical growth at the ages of 1 and 14 years. The twins did not differ significantly from the singletons during their compulsory nine years of primary and secondary schooling. According to the national registers of vocational choices, the twins had applied for admission to further education courses less often than the singletons or their controls matched only by maternal factors, but not when compared with the controls also matched by perinatal morbidity. Logistic regression analysis revealed numerous perinatal or environmental factors having an adverse effect on educational achievements, but the twin situation itself was not shown to have adverse effects. About half of the same-sex twin pairs and one seventh of the opposite-sex pairs had chosen the same vocation, compared with just over 10% similarity between the twins and their controls.     

双胎妊娠-胎宫内死亡20例临床分析

目的探讨双胎妊娠-胎宫内死亡的原因、临床处理及预后。方法回顾性分析1994年3月至2008年2月北京大学第三医院双胎妊娠-胎宫内死亡的病例共20例。结果双胎-胎宫内死亡的发生率为3．2％,其中双卵双胎17例,单卵双胎3例。28w前发现-胎宫内死亡者6例,平均期待治疗95．8天,平均分娩孕周为34．4w（32^＋4-39w）;28w后发现-胎宫内死亡者14例,平均期待治疗10．1天,平均分娩孕周为34．6w（29^＋4-39^＋2w）;仅2例新生儿发生轻度窒息。无一例孕妇发生凝血功能障碍。追踪新生儿6月至14年,1例新生儿因合并隐性脊柱裂及早产原因早期死亡,1例患儿3岁时发生运动障碍性脑瘫（分娩孕周为29^＋6w）,4例失访,其余均健康存活。结论双胎妊娠-胎宫内死亡后可采取期待治疗,严密监测存活胎儿宫内状况,尽量延长孕周,可提高存活胎儿的生存质量。     

Preterm delivery and growth restriction in multifetal pregnancies reduced to twins

Gestation at delivery, birthweight and pregnancy outcome of surviving fetuses from 127 multifetal pregnancies undergoing embryo reduction to twins were compared to 354 chromosomally normal non-reduced dichorionic twin pregnancies. First-trimester embryo reduction was carried out by intracardiac injection of KCl. In 16 (12.6%) of the 127 multifetal pregnancies reduced to twins, there was miscarriage of both fetuses before 24 weeks of gestation. The median interval between reduction and fetal loss was 5 weeks (range 1-12). In livebirths, the median gestation at delivery was 36 weeks (range 24-41) and the median difference in birthweight from the appropriate mean was -0.94 SD (range -3.89-1.73 SD). Both fetal loss before 24 weeks and the interval between embryo reduction and delivery were significantly associated with the gestation at reduction (r = 0.40, P < 0.001 and r = -0.57, P < 0.001 respectively). In the pregnancies reduced to twins compared to the non-reduced twins, the percentage of miscarriages was higher (12.6 compared to 2.5%; chi 2 = 19.2, P < 0.001), the median gestation at delivery was lower (36 compared to 37 weeks; t = -1.74, P < 0.05), and the median birthweight deficit was greater (-0.94 compared to -0.65 SD: t = -4.1, P < 0.001).      

Restriction of placental growth in sheep impairs insulin secretion but not sensitivity before birth

Restricted growth before birth is associated with impaired insulin secretion but with initially enhanced insulin sensitivity in early postnatal life, which then progresses to insulin resistance and impaired glucose homeostasis by adulthood. This suggests that prenatal restraint impairs insulin secretion, but increases insulin sensitivity, before birth. Poor placental growth and function are major causes of restricted fetal growth in humans. We have therefore investigated the effects of restricted placental growth and function on plasma glucose, α-amino nitrogen and insulin concentrations and glucose- and arginine-stimulated insulin secretion in the fetal sheep at 120 and 140 days gestational age, and on insulin sensitivity, measured by hyperinsulinaemic euglycaemic clamp, at 130 days gestational age. Placental restriction decreased fetal blood pH and oxygen content, and weight in late gestation by ∼20%. Reduced fetal and placental weights and indices of poor placental function, in particular fetal hypoxia and hypoglycaemia, were associated with impaired glucose- and arginine-stimulated insulin secretion, but not with changes in insulin sensitivity in the fetal sheep. We conclude that the impaired insulin secretion capacity reported in children and adults after intrauterine growth restriction, and in the neonatal and young adult sheep which is small at birth, is present in utero and persists. Whether this reflects the actions of the adverse intrauterine environment or changes to intrinsic capacity is unclear, but in utero interventions may be necessary to improve postnatal insulin secretion in the infant who is growth-restricted before birth.     

Pregnancy: The influence of the number of embryos transferred in 1060 in-vitro fertilization pregnancies on miscarriage rates and pregnancy outcome

To assess the incidence of miscarriage, multiple pregnancy andoutcome of pregnancy in relation to the number of embryos transferredduring in-vitro fertilization (IVF), an analysis was performedof 1060 pregnancies conceived in a tertiary-referral IVF clinic.There was no difference in the miscarriage rate after transferof one or two embryos (37.7% and 34.6%), or after three or fourembryos (22.5% and 25.2%). The miscarriage rate was, however,higher when one or two embryos were transferred compared withthree (P < 0.01) or four embryos (P < 0.02). Of the 724ongoing pregnancies, 524 (72.3%) were singleton, 164 (22.7%)twin, 33 (4.6%) triplet and three (0.4%) quadruplet. The mean(±SD) ages of women with singleton, twin, triplet andquadruplet pregnancies were 32.5 (±3.8), 32.0 (±3.5),29.76 (±4.3) and 29.67 (±2.5) years respectively.The mean age of women with singleton and twin pregnancies wassimilar and both were greater than that of triplet pregnancies(P < 0.007). The overall perinatal mortality rate (PNMR)was 39.7/1000. The PNMR for singletons was 17.2/1000, for twins80.0/1000 and for triplets 30.6/1000. All of the babies fromthe three quadruplet pregnancies survived. There were more babieslost in the twin pregnancies than any other group, althoughthis only reached significance for singletons versus twins (P< 0.00005). We conclude that the incidence of miscarriageis increased in women in whom one or two embryos are transferred.Multiple pregnancies are more likely to occur in younger womenand are associated with a significantly higher rate of perinatalmortality.     

Early weight gain in pregnant adolescents and fetal outcome

While the contribution of total maternal gain to birthweight is well described, less is known about whether there are specific effects of early weight gain. Early weight gain adequacy may be a particular problem among teenage gravidas who are more likely to have low prepregnant weight and in developing countries where chronic undernutrition is endemic. We studied the effects of early weight gain adequacy on infant birthweight in a geographical cohort of 1,790 adolescents from Camden County, New Jersey. Weight gain was calculated for prepregnant weight to 24 weeks' gestation and 24 weeks to delivery. Inadequate early weight gain was defined as gains less than 4.3 kg and inadequate late gains as averaging less than 400 gm/week from 24 weeks' gestation to delivery. In regressions predicting birthweight outcome, we found significant independent effects of timing of weight gain inadequacy. Early inadequate gains were associated with a ?186.6 ± 31.6 gm decrement in birthweight that was not diminished even when later weight gains were compensatory. Late inadequate (?154.4 ± 29.3 gm) and inadequate gains both early and later (?298.6 ± 49.1 gm) were also associated with birthweight decrements. However, overweight (body mass index >24.5) appeared to buffer some of the effects of inadequate weight gains, reducing the decrement to about ?100 gm. Protocols that seek to improve infant outcomes should focus on early weight gain during pregnancy. Affecting weight gain only late in pregnancy may not be able to substantially reduce the risk of fetal growth retardation.     

Obstetric outcome among women with unexplained infertility after IVF: a matched case-control study

BACKGROUND: Infertility itself and also assisted reproductive treatment increase the incidence of some obstetric complications. Women with unexplained infertility are reported to be at an increased risk of intrauterine growth restriction during pregnancy, but not for other perinatal complications. METHODS: A matched case-control study was performed on care during pregnancy and delivery, obstetric complications and infant perinatal outcomes of 107 women with unexplained infertility, with 118 clinical pregnancies after IVF or ICSI treatment. These resulted in 90 deliveries; of these, 69 were singleton, 20 twin and one triplet. Two control groups were chosen from the Finnish Medical Birth Register, one group for spontaneous pregnancies (including 445 women and 545 children), matched according to maternal age, parity, year of birth, mother's residence and number of children at birth, and the other group for all pregnancies after IVF, ICSI or frozen embryo transfer treatment (FET) during the study period (including 2377 women and 2853 children). RESULTS: Among singletons, no difference was found in the mean birthweight, and the incidence of low birthweight (<2500 g) was comparable with that of the control groups. No differences were found in gestational duration, major congenital malformations or perinatal mortality among the groups studied. Among singletons in the study group, there were more term breech presentations (10.1%) compared with both spontaneously conceiving women and all IVF women (P < 0.01). The rate of pregnancy-induced hypertension was significantly lower among singletons in the study group (P < 0.05) compared with other IVF singletons. The multiple pregnancy rate was 23.3% in the study group. The obstetric outcome of the IVF twins was similar to both control groups. CONCLUSIONS: The overall obstetric outcome among couples with unexplained infertility treated with IVF was good, with similar outcome compared with spontaneous pregnancies and IVF pregnancies generally.