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.     

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 and neonatal outcomes in dichorionic twin pregnancies following IVF treatment: a hospital-based comparative study

Aim: To compare maternal, and neonatal outcomes in IVF/ICSI and spontaneously conceived dichorionic twin pregnancy. Method: We collected data regarding dichorionic twin pregnancies following in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI, n=162) with the transfer of fresh embryos as well as data regarding spontaneously conceived pregnancies (n=213) delivered after 28 weeks of gestation at the Department of Obstetrics and Gynecology, Renmin Hospital in Wuhan in the years of 2010-2013. We then compared maternal and neonatal outcomes between IVF/ICSI and spontaneous dichorionic twin pregnancies, with a subgroup analysis separating traditional IVF from ICSI pregnancies. Odds ratios (OR) for associations between IVF/ICSI and pregnancy outcomes were adjusted for maternal factors. Results: The mean maternal age and the percentage of primiparous women were significantly higher in the IVF/ICSI group. Multivariate analysis revealed that maternal outcomes were comparable in both groups with/without adjustment for maternal age and parity. However, IVF/ICSI twins were less likely to have birth weight discordance than those spontaneously conceived (unadjusted OR=0.526, 95% CI 0.297-0.932; adjusted OR=0.486, 95% CI 0.255-0.856). In subgroup analyses, these associations were confirmed in the IVF (adjusted OR=0.496, 95% CI 0.265-0.926), but not in the ICSI group (adjusted OR=0.500, 95% CI 0.139-1.807). Conclusion: IVF/ICSI treatment was not a risk factor for adverse maternal neonatal outcomes, but the risk for birth weight discordance is lower among IVF/ICSI twins.     

Hospital care utilization of IVF/ICSI twins followed until 2-7 years of age: a controlled Danish national cohort study

BACKGROUND: IVF/ICSI twins are likely to have a higher risk of prematurity associated with higher morbidity. The aim of this study was to assess the use of hospital care resources in IVF/ICSI twins on data retrieved until 2-7 years of child age. METHODS: National controlled cohort study on hospital admissions and surgical interventions in 3393 IVF twins, 10,239 spontaneously conceived twins and 5130 IVF singletons born between 1995 and 2000 in Denmark. Cross-linkage of data from the Danish IVF Registry and the National Patient Registry enabled us to identify children who were admitted to hospital or underwent an operation. RESULTS: The frequency of hospitalized children was 69.8, 69.6 and 49.8%, and of children who underwent a surgical intervention 10.6, 11.2 and 8.5% in IVF/ICSI twins, control twins and IVF/ICSI singletons respectively. Odds ratios (OR) (95% confidence intervals) of hospitalization in IVF/ICSI twins versus control twins and IVF/ICSI singletons were 1.04 (0.96, 1.14) and 2.44 (2.22, 2.63) and OR adjusted for year of birth, maternal age and parity were 1.00 (0.91, 1.11) and 2.38 (2.17, 2.63) respectively. Also for term birth infants, IVF/ICSI twins were more likely to be hospitalized than IVF/ICSI singletons: adjusted OR 1.37 (1.22, 1.51). Similar risk of a surgical procedure was observed in IVF/ICSI versus control twins. However, IVF/ICSI twins more often underwent a surgical intervention than IVF/ICSI singletons: adjusted OR 1.26 (1.08, 1.47). This risk disappeared when restricted to term infants: adjusted OR 1.00 (0.81, 1.22). Different sex IVF/ICSI and control twins had equal risk of admissions and surgical interventions, and ICSI children had the same risk as children born after conventional IVF. CONCLUSIONS: Though the use of hospital care resources was similar in IVF/ICSI and control twins, the over-use in IVF/ICSI twins versus IVF/ICSI singletons adds to the arguments for implementing elective single embryo transfer as our standard procedure.     

Attitudes of IVF/ICSI-twin mothers towards twins and single embryo transfer

BACKGROUND: Our aim was to study attitudes towards twins and single embryo transfer (SET) among IVF/ICSI-twin mothers with 3 to 4-year old children. METHODS: A national survey was conducted by questionnaire (n = 1769). The study population consisted of IVF/ICSI-twin mothers (n = 266), and the two control groups of IVF/ICSI-singleton mothers (n = 764) and non-IVF/ICSI-twin mothers (n = 739), all giving birth in Denmark in 1997. The overall response rate was 81%. RESULTS: More IVF/ICSI-twin mothers (84.7%) preferred twins as their first child compared with IVF/ICSI-singleton mothers (62.3%) and non-IVF twin mothers (60.0%). The IVF/ICSI-twin mothers had a significantly higher wish for twins (OR = 4.4, 95% CI 2.8-6.9) compared with the non-IVF/ICSI-twin mothers. Though relatively few IVF/ICSI-twin mothers (23.4%) and IVF/ICSI-singleton mothers (17.3%) agreed to SET, delivery of a child with very low birth weight (VLBW) (<1500 g) was predictive of high acceptance of SET (OR = 2.9, 95% CI 1.2-6.9). CONCLUSION: Our study suggests that IVF/ICSI-twin mothers have a greater wish for twins compared with non-IVF/ICSI-twin mothers. Despite the fact that only a quarter of IVF/ICSI mothers agreed to SET, delivery of a child with VLBW and hence high morbidity was predictive of high acceptance of SET. The implementation of elective SET requires extensive counselling of the infertile couples and legislation including strict selection criteria may also be used to facilitate this process.     

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.     

'Vanishing embryo syndrome' in IVF/ICSI

BACKGROUND: In a Danish population-based cohort study assessing the risk of cerebral palsy in children born after IVF, we made some interesting observations regarding 'vanishing co-embryos'. METHODS and RESULTS: All live-born children born in Denmark from 1 January 1995 to 31 December 2000 were included in this analysis. The children conceived by IVF/ICSI (9444) were identified through the IVF Register, the children conceived without IVF/ICSI (395 025) were identified through The Danish Medical Birth Register. Main outcome measure was the incidence of cerebral palsy. Within the IVF/ICSI children we found indications of an increased risk of cerebral palsy in those children resulting from pregnancies, where the number of embryos transferred was higher than the number of children born. CONCLUSIONS: The association between vanishing embryo syndrome and incidence of cerebral palsy following IVF requires further investigation in larger, adequately powered, studies.     

IVF/ICSI twin pregnancies: risks and prevention

Since the 1970s, the national twin birth rates have been increasing worldwide. Apart from the increasing childbearing age, the main cause is the use of assisted reproductive technologies (ART). To explore the overall consequences of dual embryo transfer (DET), the literature has been reviewed systematically regarding short- and long-term outcomes of IVF/ICSI twin pregnancies i.e. pregnancy complications, maternal risks, obstetric outcome and long-term morbidity including neurological sequelae, cognitive development and family implications. Another consequence of DET is vanishing twins, which seems to be a possible cause of adverse outcome in IVF singletons. The sparse literature on vanishing twins in IVF pregnancies and the influence on the surviving co-twin were also addressed. Finally, to determine the effects of implementing elective single embryo transfer (eSET), trials concerning eSET versus DET were analysed. In the light of the steadily increasing twin birth rates and the findings in this overview, where IVF/ICSI twins carry adverse outcome, it should be emphasized that the major obstacle in IVF remains the high twin birth rate. Furthermore vanishing twins account for another hazard of DET. These problems can be resolved by implementing eSET, diminishing the twin birth rate without affecting the overall goal of achieving a healthy infant.     

Umbilical cord anomalies are more frequent in twins after assisted reproduction

BACKGROUND: The objective of this study is to analyse differences in cord characteristics between naturally conceived twins and twins born after assisted reproduction. METHODS: Between 1985 and 2004, the East Flanders Prospective Twin Survey (EFPTS) registered 4159 twin pairs. We compared cord characteristics between 2119 naturally conceived dizygotic (DZ) twin members and 2243 DZ twin members originating from assisted reproductive technologies (ART). Data were adjusted for intra-twin correlation, year of birth, maternal age, gestational age, parity, sex of the child and number of placentas. RESULTS: Marginal cord insertion, velamentous cord insertion and single umbilical artery (SUA) occur more frequently in twins following infertility treatment (P < 0.001). The incidence of velamentous cord insertion increases proportionate with 'invasiveness' of reproductive techniques: 3.6% in naturally conceived twins versus 5% in twins after artificial induction of ovulation (AIO) [odds ratio (OR) 1.45; 95% confidence interval (CI) 0.99-2.11], 7.4% in twins after IVF (OR 1.49; 95% CI 1.26-1.77) and 10.4% in twins after ICSI (OR 1.31; 95% CI 1.14-1.51). SUA has the highest incidence in twins after AIO: 1.9% compared with 0.6% in naturally conceived twins (OR 3.19; 95% CI 1.66-6.11). CONCLUSIONS: Umbilical cords of twins born after ART have more pathologic characteristics when compared with cords of naturally conceived twins.     

Uterine artery Doppler velocimetry and the outcome of pregnancies resulting from ICSI.

BACKGROUND: An increased incidence of pregnancy complications following assisted reproduction has been reported. The use of uterine artery Doppler ultrasound may aid the prediction of such complications. METHODS: Doppler was performed at 18-24 weeks gestation in 114 singleton and 32 twin pregnancies after intracytoplasmic sperm injection (ICSI) and compared with a control group matched for age, parity and plurality. Outcome variables included gestational age at delivery, prematurity, preterm premature rupture of membrane (PPROM), birth weight, birth weight discordance of >20% in twins, small for gestational age (SGA), mode of delivery, development of pre-eclampsia and placental abruption. RESULTS: Compared with the controls, there were no significant differences concerning uterine Doppler parameters, pregnancy complications and the neonatal outcome, either in singleton or in twin pregnancies. According to Doppler results and/or risk factors by medical history, 42% of singleton ICSI and 39% of spontaneous singleton pregnancies were considered as high risk. In singletons, abnormal Doppler findings were associated with pre-eclampsia in 22% and SGA in 26% of ICSI patients, compared with 33 and 21% in controls; in contrast, 0 and 10% in ICSI and 3 and 6% in controls showed these complications but no risk factors respectively. No correlation was found between PPROM, prematurity, the rate of Caesarean section and pathological Doppler results. CONCLUSIONS: Uterine Doppler examination holds the potential to identify patients with an increased risk for developing pregnancy complications. According to our results, this risk is not elevated after ICSI treatment, therefore the decision of offering an intensified antenatal care should be based on the results of Doppler examination or risks by medical history rather than the mode of conception.     

Patient attitudes towards twin pregnancies and single embryo transfer - a questionnaire study

BACKGROUND: The present trend towards selective single embryo transfer (SET) calls for evaluation of patient attitudes towards twins and how the patients balance advantages and disadvantages of one or two embryos in IVF/ICSI treatment. METHODS: The study was conducted in a Danish public fertility clinic, where the common practice was double embryo transfer (DET), and the number of reimbursed treatments was limited to three. Referred patients were given oral and written information about the IVF/ICSI treatment including twin probability following DET and the risk of preterm delivery and neonatal complications associated with twins. In order to evaluate patients and partners attitudes towards twins and SET, an anonymous survey was conducted, and 588 couples were invited to participate. RESULTS: Four hundred and fourteen women (70.4%) and 404 men (68.7%) answered the questionnaire adequately for analysis. About 58.7% preferred having twins to having one child at a time (37.9%). Primary reasons for preferring twins were desire for siblings (23.3%), a positive attitude towards twins (22.5%), and a wish to minimize physical and psychological stress through having as few IVF treatments as possible (19.3%). Economic considerations were not important. CONCLUSIONS: Obligatory single embryo policy would be in conflict with patient interests and wishes. More carefully prepared information seems to be needed. The challenge consists in balancing clinical considerations with unbiased information on twin pregnancy, respecting patient autonomy and enabling informed decision-making.     

Risk factors for asthma in young adults: a co-twin control study

Background: The liability to asthma is influenced both by genetic and environmental factors. The objective of this study was to identify risk factors for asthma in young adult twin pairs during an 8‐year period. Methods: From the birth cohorts 1953–1982 of the Danish Twin Registry, 6090 twin pairs who were initially unaffected with respect to asthma at a nationwide questionnaire‐based study in 1994 participated in a similar follow‐up study in 2002. Subjects were regarded incident asthma cases when responding affirmatively to the question ‘Do you have, or have you ever had asthma'? in 2002. Pairs in which only one twin developed asthma – discordant pairs – were identified and conditional logistic regression was applied to detect effects of risk factors. Results: A total of 126 monozygotic (MZ) and 273 dizygotic (DZ) discordant twin pairs were identified. In MZ twins hay fever (OR = 3.16, 95% CI: 1.29–7.73, P = 0.007) and exercise (OR for inactivity = 0.35, 95% CI: 0.13–0.91, P = 0.023) were significantly associated with asthma, whereas in DZ twins, hay fever (OR = 2.44, 95% CI: 1.44–4.13, P = 0.001), eczema (OR = 1.96, 95% CI: 1.02–3.78, P = 0.040), female sex (OR between males and females = 0.54, 95% CI: 0.36–0.80, P = 0.002), and increasing levels of body mass index (BMI; OR per unit = 1.11, 95% CI: 1.02–1.20, P = 0.009) were significant predictors of asthma. Conclusions: Hay fever, eczema, female sex, exercise and increasing levels of BMI were risk factors for asthma in young adults. The different risk profile observed in MZ twins compared with DZ twins may reflect an underlying genetic vulnerability shared between those risk factors and asthma.     

Hospital care utilization of infants born after IVF

BACKGROUND: Infants born after IVF are often twins, and singleton IVF babies have an increased risk for preterm birth. Both conditions are likely to increase morbidity. We examined the frequency and duration of hospitalization required by babies born after IVF, and compared this information with all infants born in Sweden during the same time period. METHODS: We used a nationwide registration of IVF pregnancies from 1984 to 1997 and a nationwide register of all in-patient care up to the end of 1998. We identified 9056 live born infants after IVF treatment and compared them with 1 417 166 non-IVF live born infants. RESULTS: The highest odds ratio (OR approximately 3) was seen for neonatal hospitalization, but an increased OR (1.2-1.3) was noted for children up to 6 years of age. The OR for being hospitalized after IVF was 1.8, but when the analysis was restricted to term infants it was 1.3 and this excess was then explainable by maternal subfertility. Statistically significant increased ORs were seen for hospitalization for cerebral palsy (1.7), epilepsy (1.5), congenital malformation (1.8) or tumour (1.6), but also for asthma (1.4) or any infection (1.4). When information from the Swedish Cancer Registry was used, no excess risk for childhood cancer was found. The average number of days spent in hospital by IVF and non-IVF children was 9.5 and 3.6 respectively. CONCLUSIONS: The increased hospitalization of IVF children is, to a large extent, due to the increased incidence of multiple births. Therefore, the increased costs associated with this may be reduced by the use of single embryo transfers, with the savings in health care costs being offset against the increased number of embryo transfer cycles required to maintain the pregnancy rate.     

Developmental outcome at 2 years of age for children born after ICSI compared with children born after IVF

BACKGROUND: Since the introduction of ICSI in 1991, medical outcome studies on ICSI children have been performed, but few have addressed developmental outcome. Hence, this outcome was assessed by performing a standard developmental test on children born after ICSI as compared with children born after IVF, at the age of 2 years. METHODS: In a prospective study, the medical and developmental outcome of 439 children born after ICSI (378 singletons, 61 twins) were compared with those of 207 children born after IVF (138 singletons, 69 twins), at the age of 24-28 months. These children were part of a cohort of children followed since birth. Of children reaching the age of 24-28 months between May 1995 and March 2002, 44.3% (2375/5356) were examined by a paediatrician who was unaware of the type of treatment used for each couple. Of all the children born, 12.2% (439/3618) in the ICSI group and 11.9% (207/1738) in the IVF group underwent a formal developmental assessment using the Bayley Scale of Infant Development (mental scale) by a paediatrician blinded to the type of treatment. RESULTS: There was no significant difference in maternal educational level, maternal age, gestational age, parity, birthweight, neonatal complication rate or malformation rate at 2 years between ICSI and IVF singletons, or between ICSI and IVF twins. No significant difference was observed in the developmental outcome using the Bayley scale at the age of 24-28 months (raw scores or test age) between ICSI children or IVF children. A multivariate regression analysis for the singleton children indicated that parity, sex (boys had lower scores than girls) and age had a significant influence on the test result, but that the fertility procedure (ICSI versus IVF) did not influence the test result. ICSI children from fathers with low sperm concentration, low sperm motility or poor morphology had a similar developmental outcome to that of children from fathers with normal sperm parameters. There were no significant differences between the initial cohort and the group lost to follow-up, nor between the psychologically tested and the non-tested group for a number of variables such as maternal educational level, birthweight in singletons and neonatal malformation rate. Although only some of the cohort of ICSI children were evaluated, a representative sample of both ICSI and IVF children was compared. CONCLUSIONS: There is no indication that ICSI children have a lower psychomotor development than IVF children. Paternal risk factors associated with male-factor infertility were found not to play a role in developmental outcome.     

Impact of overweight and underweight on assisted reproduction treatment

BACKGROUND: Underweight and overweight may affect reproduction and interfere with treatment of infertility. The purpose of this report is to describe the independent effect of body weight on treatment with IVF and ICSI. METHODS: Records of 5019 IVF or ICSI treatments in 2660 couples were reviewed. The influence of body mass index (BMI) on treatment outcome was examined, after accounting for differences in age and infertility diagnosis. RESULTS: The cumulative live birth rate within three treatment cycles was 41.4% [95% confidence interval (CI) 32.1-50.7] in obese women with BMI > or =30 kg/m2 and 50.3 (95% CI 47.0-53.7) in normal weight women with BMI 18.5-24.9 kg/m2. Obesity was associated with an increased risk of early pregnancy loss occurring before 6 weeks gestation. Positive correlation between BMI and gonadotrophin requirement during stimulation and negative correlation between BMI and number of collected oocytes were observed. Underweight (BMI <18.5 kg/m2) was not related to an impaired outcome of IVF or ICSI. CONCLUSIONS: Obesity is associated with lower chances for live birth after IVF and ICSI and with an impaired response to ovarian stimulation.     

Number of embryos for transfer after IVF and ICSI: a Cochrane review

BACKGROUND: The most common complication of IVF is multiple pregnancy, which occurs in 25% of pregnancies following the transfer of two embryos. Single embryo transfer can minimize twin pregnancies but could also lower live birth rates. Our aim was to perform a systematic review of randomized trials to determine the effectiveness of single versus double embryo transfer. METHODS: Cochrane Collaboration review methods were followed. Randomized controlled trials comparing single and double embryo transfers were identified by searching Medline, EMBASE and the Cochrane register of controlled trials. Contents of specialist journals and proceedings from meetings of relevant societies were hand searched. Data were pooled with Rev Man software using the Peto-modified Mantel-Hanzel method. RESULTS: Pooled results from four trials indicate that although double embryo transfer leads to a higher live birth rate per woman [odds ratio (OR) 1.94, 95% confidence interval (CI) 1.47-2.55] in a fresh IVF cycle, comparable results are obtained by subsequent transfer of a frozen embryo (OR 1.19, 95% CI 0.87-1.62). The multiple pregnancy rate is significantly higher (OR 62.83, 95% CI 8.52-463.57) after double embryo transfer. CONCLUSIONS: Single embryo transfer significantly reduces the risk of multiple pregnancy, but also decreases the chance of live birth in a fresh IVF cycle. Subsequent replacement of a single frozen embryo achieves a live birth rate comparable with double embryo transfer.     

Neonatal outcome and congenital malformations in children born after in-vitro fertilization

BACKGROUND: To evaluate the neonatal outcome and the prevalence of congenital malformations in children born after IVF in northern Finland we carried out a population-based study with matched controls. METHODS: Firstly, 304 IVF children born in 1990-1995 were compared with 569 controls, representing the general population in proportion of multiple births, randomly chosen from the Finnish Medical Birth Register (FMBR) and matched for sex, year of birth, area of residence, parity, maternal age and social class. Secondly, plurality matched controls (n = 103) for IVF twins (n =103) were randomly chosen from the FMBR and analysed separately. Additionally, IVF singletons (n = 153) were compared with singleton controls (n = 287). Mortality rates were compared with national figures from FMBR. RESULTS: Most mortality rates were twice as high as national figures in the general population. When compared with the control group representing the general population, the incidences of preterm birth [odds ratio (OR) 5.6, 95% confidence interval (CI) 3.7-8.6], very low birth weight (OR 6.2, 95% CI 2.0-19.0), low birth weight (OR 9.8, 95% CI 5.6-17.3), neonatal morbidity (OR 2.4, 95% CI 1.7-3.4) and hospitalization (OR 3.2, 95% CI 2.2-4.6) were significantly higher in the IVF group. The prevalence of heart malformations was four-fold in the IVF population than in the controls representing the general population (OR 4.0, 95% CI 1.4-11.7). CONCLUSIONS: Neonatal outcome after IVF is worse than in the general population with similar maternal age, parity and social standing, mainly due to the large proportion of multifetal births after IVF. The higher prevalence of heart malformations does not solely arise from multiplicity but from other causes. In order to improve neonatal outcome after IVF, the number of embryos transferred should be limited to a minimum.     

Imprinting diseases and IVF: Danish National IVF cohort study

BACKGROUND: The aim of this study was to compare the frequency of imprinting diseases in children born after IVF with the incidence in naturally conceived children. METHODS: All singleton children born in Denmark from January 1, 1995 through December 31, 2001 were stratified into children born without and after IVF, and were followed from birth until the end of 2002 in the National Register of Patients and the Central Register of Psychiatric Diseases, which include all discharge diagnoses from somatic and psychiatric hospitals/clinics, respectively. Included in the study were malignancies, mental, behavioural and neurological diseases, congenital syndromes, and developmental disturbances. Only diagnosis codes potentially relevant for imprinting diseases were included. RESULTS: During the 7-year study period, 442,349 singleton non-IVF and 6052 IVF children were born. Mean follow-up time was 4.5 and 4.1 years for the two groups, respectively, corresponding to 2 million and 25 000 follow-up years. In the IVF/non-IVF cohort, we detected 0/72 children with cancer, 47/3766 with mental diseases, 72/3654 neurological diseases, 4/287 congenital syndromes and 96/6727 developmental disturbances, in a total of 219/14,506 clinical outcomes. The number of children with specific imprinting diseases in the non-IVF group was 54: 44 kidney cancers, five retinoblastoma, three Prader-Willi syndrome and two Russel-Silver syndrome. Anticipating the same occurrence in IVF children, the total expected number was calculated to be 0.74. The observed number in the IVF group was 0. We found a significantly increased risk of cerebral palsy in the IVF group, with a rate ratio (RR) (IVF:non-IVF) of 1.8 [95% confidence interval (CI) 1.2-2.8; P < 0.01], and of sleeping disturbances, with an RR 2.0 (95% CI 1.2-3.3). The incidence rate of childhood cancers, mental diseases, congenital syndromes and developmental disturbances was equal in the two groups. CONCLUSIONS: We found no indication of an increased risk of imprinting diseases after IVF, but an 80% increased risk of cerebral palsy. We observed equal frequencies of childhood cancers, mental diseases, congenital syndromes and developmental disturbances in the two groups. Danish register data do not support reports of an increased risk of imprinting diseases after IVF.     

Risk of spontaneous abortion in singleton and twin pregnancies after IVF/ICSI

BACKGROUND: The risk of spontaneous first trimester abortion is estimated to be between 10 and 20%. Although it is common knowledge that the incidence of abortion decreases as pregnancy progresses, exact data in relation to the duration of pregnancy are scarce. METHODS: We reviewed 1597 clinical IVF/ICSI pregnancies with known outcome and tabulated the number of miscarriages or fetal demise per intervals of 2 weeks. We furthermore compared the outcome in terms of fetal survival of 1200 singleton pregnancies with that of 397 twin pregnancies. RESULTS: The overall incidence of non-ongoing singleton pregnancies was 21.7%. Fetal death, after positive heart activity had been recorded, occurred in 12.2% of singleton pregnancies. The overall incidence of spontaneous abortion in twin pregnancies was 17.1% (12.1% vanishing twins and 5.0% complete miscarriages). The incidence of miscarriage in the twin pregnancies, expressed per gestational sac, was 11.1%. Once fetal heart activity was present, the risk of abortion (per gestational sac) was 7.3%, which is significantly lower than that in singleton pregnancies. CONCLUSIONS: Our data give an estimate of the probability of miscarriage or fetal demise at any given period of the first trimester both for singleton and twin pregnancies. Twin pregnancies after IVF have a better potential for survival than singleton pregnancies.     

Predicting ongoing pregnancy chances after IVF and ICSI: a national prospective study

BACKGROUND: The Dutch IVF guideline suggests triage of patients for IVF based on diagnostic category, duration of infertility and female age. There is no evidence for the effectiveness of these criteria. We evaluated the predictive value of patient characteristics that are used in the Dutch IVF guideline and developed a model that predicts the IVF ongoing pregnancy chance within 12 months. METHODS: In a national prospective cohort study, pregnancy chances after IVF and ICSI treatment were assessed. Couples eligible for IVF or ICSI were followed during 12 months, using the databases of 11 IVF centres and 20 transport IVF clinics. Kaplan-Meier analysis was performed to estimate the cumulative probability of an ongoing pregnancy, and Cox regression was used for assessing the effects of predictors of pregnancy. RESULTS: 4928 couples starting IVF/ICSI treatment were prospectively followed. On average, couples had 1.8 cycles in 12 months for both IVF and ICSI. The 1-year probability of ongoing pregnancy was 44.8% (95% CI 42.1-47.5%). ICSI for severe oligospermia had a significantly higher ongoing pregnancy rate than IVF indicated treatments, with a multivariate Hazard ratio (HR) of 1.22 (95% CI 1.07-1.39). The success rates were comparable for all diagnostic categories of IVF. The highest success rate is at age 30, with a slight decline towards younger women and women up to 35 and a sharp drop after 35. Primary subfertility with a HR of 0.90 (95% CI 0.83-0.99) and duration of subfertility with a HR of 0.97 (95% CI 0.95-0.99) per year significantly affected the pregnancy chance. CONCLUSIONS: The most important predictors of the pregnancy chance after IVF and ICSI are women's age and ICSI. The diagnostic category is of no consequence. Duration of subfertility and pregnancy history are of limited prognostic value.