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.      

Incidence of congenital malformations in children born after ICSI

The aim of this study was to determine the incidence of congenital malformations in a complete cohort of children born after intracytoplasmic sperm injection (ICSI). The medical records were retrieved for 1139 infants, 736 singletons, 200 sets of twins and one set of triplets. The total number of infants with an identified anomaly was 87 (7.6%), 40 of which were minor. The incidence of malformations in children born after ICSI was also compared with all births in Sweden using data from the Swedish Medical Birth Registry and the Registry of Congenital Malformations. For ICSI children, the odds ratio (OR) for having any major or minor malformation was 1.75 [95% confidence interval (CI) 1.19-2.58] after stratification for delivery hospital, year of birth and maternal age. If stratification for singletons/twins was also done, the OR was reduced to 1.19 (95% CI 0.79-1.81). The increased rate of congenital malformations is thus mainly a result of a high rate of multiple births. The only specific malformation which was found to occur in excess in children born after ICSI was hypospadias (relative risk 3.0, exact 95% CI 1. 09-6.50) which may be related to paternal subfertility.     

Twinning, nonrighthandedness, and fusion malformations: evidence for heritable causal elements held in common

Certain relatively common congenital malformations that are reported to be excessive in frequency among twins are also found in excess among first-degree relatives of twins. They are familially associated with each other. Like twinning, they are familially associated with nonrighthandedness (NRH). They also share the fact that they affect structures that are built by the fusion of bilateral embryonic halves and then remodeled under the influence of neural crest mesenchyme. This conjunction of associations suggests that twinning, NRH, and the fusion malformations share causal elements, some of which may be heritable. Determination of spatial relationships in embryogenesis ("embryonic body symmetry determination") and the functions of neural crest mesenchyme may be mechanisms unifying these effects.     

Sex and congenital malformations: an international perspective

The study evaluated the sex distribution of major isolated malformations and common trisomies among a large and geographically varied sample. Eighteen registries from 24 countries contributed cases, which were centrally reviewed and classified in three clinical types as isolated, associated, or syndromic. We selected cases of 26 major defects (n = 108,534); trisomy 21, 18, and 13 (n = 30,114); other syndromes (n = 2,898); and multiple congenital anomalies (n = 24,197), for a total of 165,743 cases. We observed a significant deviation of sex distribution (compared to a sex ratio of 1.06 or male proportion of 51.4%) for 24 of the 29 groups (a male excess in 16, a female excess in 8), and in 8 of such groups these estimates varied significantly across registries. A male excess was noted for two left obstructive cardiac defects (hypoplastic left heart and coarctation of the aorta) and a female excess for all the main types of neural tube defects. A male excess was seen for omphalocele but not gastroschisis. For neural tube defects the female excess tended to be stronger in areas with historically high prevalence for these defects. For 15 of the 26 birth defects the sex distribution differed among isolated, associated, and syndromic cases. Some of these epidemiologic commonalities are consistent with known or putative developmental processes. Further, the geographic variation for some defects may reflect local prevalence rates and risk factors. Finally, the findings underscore the need for clinical classification (e.g., into isolated, multiple, syndromes) in studies of birth defects.     

Danish National In-Vitro Fertilization Registry 1994 and 1995: a controlled study of births, malformations and cytogenetic findings.

This paper reports data from the Danish in-vitro fertilization (IVF) registry from 1994 to 1995 including data on treatments and the results of these (perinatal outcome, cytogenetic findings and fetal malformations) in comparison with a control group matched for maternal age, parity, multiplicity and year of birth. There were 1756 deliveries of 2245 children (24.3% twins, 1.8% triplets). The rate of prematurity among IVF children was 23.8% (NS) [singletons 7. 3% (P < 0.05), twins 41.2% and triplets 93.5%], 23.6% weighed <2500 g [singletons 7% (P < 0.05), twins 42.2% and triplets 87.1%]. The perinatal mortality rate was 21.8 in the study group compared to 17. 4 in the control group (NS). In total, 13.2% of all clinical pregnancies and 15.4% of the pregnancies that resulted in a delivery had a prenatal genetic examination. Of all examined, 3.5% had an abnormal karyotype. In total, 107 (4.8%) children in the study group and 103 (4.6%) in the control group were born with malformations (NS), compared to 2.8% in the background population. Our results indicate that it is the characteristics of the patients and multiplicity of pregnancy, rather than the assisted reproductive technology that determines the fetal risks of IVF pregnancies compared to the background population.     

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.     

Pregnancy loss in mothers of multiple births and in mothers of singletons only

We compared pregnancy loss in mothers of multiple births and in mothers of singletons only. The index of pregnancy loss used for purposes of the present analysis is: the ratio of total pregnancies to total maternities consisting of live births. Mothers of one set of like-sexed twins and mothers of one set of unlike-sexed twins had greater pregnancy loss than did mothers of singletons only. Women who had higher-order multiple births comprised only 5% of our sample; in terms of their pregnancy loss these women were similar to mothers of singletons only. Data on whether women ever had difficulty becoming pregnant, and the type of therapy received to aid in conception showed that mothers of twins had greater difficulty becoming pregnant than did mothers of singletons. Among women with difficulty becoming pregnant, pregnancy loss was greater than among those who reported no difficulty. In our sample, 4.3% of mothers of multiple births and 3.4% of mothers of singletons only received hormonal therapy, some of which included FSH or clomiphene citrate.     

An Examination of the Representativeness Assumption for Twin Studies of Eating Pathology and Internalizing Symptoms

Little research has investigated whether the twin representativeness assumption (that results from twin research generalize to singletons) holds for eating pathology and internalizing symptoms. This study compared disordered eating, depression, and anxiety among young adult female twins versus singletons. Participants included 292 twins and 997 singletons in three samples. Questionnaires included the Minnesota Eating Behavior Survey, Eating Disorder Examination Questionnaire, Beck Depression Inventory, and State-Trait Anxiety Inventory. We examined mean differences between twins’ and singletons’ scores, after adjusting for age, body mass index, and ethnicity. We found statistically significant mean differences on psychopathology, with twins reporting less disordered eating and internalizing symptoms compared with singletons. Effect sizes of these mean differences were small to moderate. Our results suggest that twins report less disordered eating and internalizing symptoms than singletons, which, combined with the generally small effect sizes, indicate that results from twin samples generalize to singletons.     

Differential increases in AFP,hCG, and uE3 in twin pregnancies: Impact on attempts to quantify Down syndrome screening calculations

Since the advent of multiple marker screening (MMS) for Down syndrome (DS) risk calculations, limitations for twins have been apparent. Recent attempts have been made to extrapolate mathematically singleton risks to twins. Here we investigate the pattern of levels among AFP, hCG, and uE3 in twins. MMS screening data from 4,443 twin pregnancies were compared to those from 258,885 singletons from 14–21 weeks of gestational age during a 3-year period (1992–1994) in our laboratory. Medians were determined for singletons and twins, and the ratios of twins to singletons were derived. Median AFP levels for twins are approximately double those of singletons, but median increases for hCG and uE3 are less than double. The data were divided further by ethnic groups (white, African American, Asian, and Hispanic), among which there were significant variations in medians, but not in the ratios of twins to singletons. The increased serum levels of different markers in twins are not consistent across analytes, possibly reflecting independent development of different compartments. Such differences mean that a mere mathematical conversion of singleton DS risks would be imbalanced among the analytes and cannot be applied reasonably to twins. Ethnic-specific databases are as important in twins as they are in singletons. Am. J. Med. Genet. 73:109–112, 1997. © 1997 Wiley-Liss, Inc.     

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.     

Comparison of pregnancy outcome after intracytoplasmic sperm injection and in-vitro fertilization

The aim of this study was to compare pregnancy characteristics and perinatal outcome of intracytoplasmic sperm injection (ICSI) pregnancies with pregnancies obtained after in-vitro fertilization (IVF). Retrospectively, 145 ICSI pregnancies were matched with 145 IVF pregnancies using the last menstruation data. The main outcome measures were preclinical and clinical abortions, ectopic pregnancies, multiple gestations, prenatal morbidity, prematurity, Caesarean section, birthweight, perinatal mortality and malformations for singletons, twins and triplets. Although patients were significantly younger (P < 0.001) in ICSI (31 years) than in IVF (33 years), their infertility duration (5 years) was similar. The mean number of transferred embryos (2.7 embryos per transfer) was similar in IVF and ICSI. The rates of preclinical (15%) and clinical abortions (11% in ICSI versus 15% in IVF) were not different. Four ectopic pregnancies were observed in the IVF group and none in the ICSI group. In ICSI, two minor malformations were detected and two therapeutic abortions were performed respectively for polymalformations and suspicion of cystic fibrosis. The rate of congenital malformation was 2.8% in ICSI and 2.2% in IVF. In this last group, one therapeutic abortion for malformation of neural tube was performed and two minor malformations were detected. The rate of aborted embryonic sacs before 16 weeks of gestation was not significantly lower in ICSI compared with IVF (13.7% versus 20%). The rate of multiple gestations was similar in both groups (31% in IVF and 35% in ICSI). The number of Caesarean sections was similar in IVF and in ICSI and was twice as frequent for twins versus singletons. The number of singletons born by Caesarean section was 21% after ICSI and 17% after IVF. Mean birthweights and gestational ages at birth for twins were significantly higher (P < 0.05) in ICSI than in IVF (2488 versus 2281 g and 36.5 versus 35.5 weeks). This difference was not observed for singletons. In conclusion, pregnancy characteristics and perinatal outcome after ICSI showed no increase in the number of pathologies in comparison with IVF.      

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.     

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.     

Babies born after ART treatment cost more than non-ART babies: a cost analysis of inpatient birth-admission costs of singleton and multiple gestation pregnancies

BACKGROUND: Currently, about one-third of infants born after assisted reproductive technology (ART) worldwide are twins or triplets. This study compared the inpatient birth-admission costs of singleton and multiple gestation ART deliveries to non-ART deliveries. METHODS: A cohort of 5005 mothers and 5886 infants conceived following ART treatment were compared to 245 249 mothers and 248 539 infants in the general population. Birth-admission costs were calculated using Australian Refined Diagnosis Related Groups and weighted national average costs (2003-2004 euro). RESULTS: ART infants were 4.4 times more likely to be low birthweight (LBW) compared with non-ART infants, translating into 89% higher birth-admission costs (euro2,832 and euro1,502, respectively). ART singletons were also more likely to be LBW compared with non-ART singletons, translating into 31% higher birth-admission costs (euro1,849 and euro1,415, respectively). After combining infant and maternal admission costs, the average cost of an ART singleton delivery was euro4,818 compared with euro13 890 for ART twins and euro54 294 for ART higher order multiples. Findings were not sensitive to changes in casemix. CONCLUSIONS: The poorer neonatal outcomes of ART singletons compared with non-ART singletons are significant enough to impact healthcare resource consumption. The high costs associated with ART multiple births add to the overwhelming clinical and economic evidence in support of single embryo transfer.     

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

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

Outcome of pregnancies complicated by severe ovarian hyperstimulation syndrome (OHSS): a follow-up beyond the second trimester

The main aim of this study was to assess the obstetric complications for those pregnancies that are complicated by ovarian hyperstimulation syndrome (OHSS) and continue beyond the first trimester. We checked also for other related serious events that occurred during the first trimester. METHODS: We included only patients whose pregnancies continued beyond the first trimester and compared them with IVF-treated patients displaying moderate ovarian response. RESULTS: We studied 165 patients with OHSS (101 singletons and 64 twins) and 156 IVF control patients (85 singletons and 71 twins). Two serious complications, gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH), were noted in both groups. However, the incidence of these two complications did not differ significantly between the groups. In the OHSS group, GDM presented with an incidence of 9.9% for singletons and 9.4% for twins, and 12.9% and 7.0%, respectively, for the control group. PIH presented as 6.9% for singletons and 10.9% for twins in the OHSS group, and 8.2% and 7.0%, respectively, for the control groups. During the first trimester laparoscopies for suspected ovarian torsion were performed in 13 patients, and in 10 patients the diagnosis were confirmed. CONCLUSIONS: Although patients with OHSS-complicated pregnancies previously reported a relatively high risk of GDM and PIH, the occurrence rates do not differ from a matched control group of normally responding patients who conceived after IVF.     

A pilot study of attachment patterns in adult twins

The hypothesis that attachment in adults is influenced by genetic factors was investigated. The within-pair differences in attachment representation in same-sex monozygotic and dizygotic twins were compared using the Adult Attachment Interview (AAI). The results showed a clear tendency toward monozygotic twins (n = 28) being more concordant than dizygotic twins (n = 13), but the within-pair similarity was also high in both zygosity groups. The results suggest, in behavior genetic terms, that heredity and shared environment may contribute to attachment status in adulthood. This differs from studies of attachment in infancy and early childhood, which report attachment to be explained mainly by shared environment, with minimal influence from genetic factors. Furthermore, the results showed that the distribution of the attachment pattern in twins had the same percentage distribution as reported for singletons. Consequently, there was no tendency toward more insecure attachment in twins than in singletons.     

Is the risk of bipolar disorder in twins equal to the risk in singletons? A nationwide register-based study

BACKGROUND: A previous study demonstrated a higher rate of schizophrenia in dizygotic twins than in the general population, and a higher rate of schizophrenia in siblings of dizygotic twins than in siblings of monozygotic twins and singletons, pointing to a common genetic predisposition for dizygotic twinning and schizophrenia. The aim of the present study was to investigate whether these findings also apply to bipolar disorder. METHODS: Through record linkage between The Danish Twin Register, The Danish Psychiatric Central Register and The Danish Civil Registration System, the rate of bipolar disorder (diagnosed for the first time during admission to hospital) in dizygotic and monozygotic twins was compared with the rate in singletons, and the rate in siblings and parents of twins was compared with the rate in siblings and parents of singletons. RESULTS: The rate of bipolar disorder was the same in dizygotic twins, monozygotic twins and singletons as well as for parents and siblings of dizygotic twins, monozygotic twins and singletons. LIMITATIONS: The study is a register-based study, only including hospitalized patients. CONCLUSION: This study shows that there is an equal rate of bipolar disorder in twins and in singletons. Assuming that DZ twinning is under some genetic influence, a differential relationship between schizophrenia and DZ twinning on one hand and bipolar disorder and DZ twinning on the other hand may suggest differences in the genetic basis of the two diseases. The finding that the rate of bipolar disorder in monozygotic twins is the same as the rate of bipolar disorder in singletons supports studies finding no association between bipolar disorder and obstetric complications.     

Attenuation of ductus arteriosus intimal thickening in preterm sheep twins compared with singletons

Preterm twins have a higher morbidity rate of patent ductus arteriosus (PDA) than do singletons. However, the effect of multiple births on maturation of the ductus arteriosus (DA) has not been reported. Because intimal thickening (IT) is required for DA anatomical closure, we examined IT development in the DA of preterm twins and singletons. Sheep DA tissues obtained from preterm fetuses were subjected to elastica van Gieson staining to evaluate IT. The total IT score in each DA was the sum of the IT scores obtained from six evenly divided parts of the DA, which was positively correlated with gestational ages in singletons. Total IT scores were smaller in preterm twins than in singletons, although no difference in gestational age, birth weight, or gender ratio was observed. These data suggest that IT development of the DA is attenuated in sheep preterm twins, which may affect the higher morbidity of PDA.     

Seven years of intracytoplasmic sperm injection and follow-up of 1987 subsequent children

Intracytoplasmic sperm injection (ICSI) with ejaculated, epididymal or testicular spermatozoa was first successful in 1992 and has since become the widely accepted treatment for couples with severe male-factor infertility. The outcome of several thousands of ICSI cycles in terms of fertilization, embryo cleavage and implantation is similar to that for conventional in-vitro fertilization in couples with tubal or idiopathic infertility. To evaluate the important issue of safety of the new technique of ICSI, a prospective follow-up study of 1987 children born after ICSI was carried out. The aim was to compile data on karyotypes, congenital malformations, growth parameters and developmental milestones. Parents' agreement to genetic counselling was obtained as well as prenatal diagnosis, followed by a physical examination of the children at 2 months, 1 year and 2 years. Between April 1991 and August 1997, 1699, 91 and 118 children were born after ICSI with ejaculated, epididymal and testicular spermatozoa respectively; 79 children were born from cryopreserved ICSI embryos. In all, 1082 karyotypes were determined by prenatal diagnosis, 18 of which were abnormal and de novo (1.66%) (nine each of autosomal and sex chromosomal aberrations), and 10 karyotypes (0.92%) were inherited structural aberrations. Of these, nine (eight balanced structural aberrations and one unbalanced trisomy 21) were transmitted from the father. Ten pregnancies were terminated after prenatal karyotyping or DNA testing. Forty-six major malformations (2.3%) were observed at birth. Seven malformations, observed by prenatal ultrasound, were terminated. Twenty-one (1.1 %) stillbirths, including four with major malformations, occurred later than 20 weeks of pregnancy. Mean gestational age at birth was 38.7 weeks for singletons, 36.0 weeks for twins and 32.0 weeks for triplets. No specifically higher incidence of malformations was found in any given subgroup.