Health care costs resulting from IVF: prenatal and neonatal periods

BACKGROUND: The use of expensive infertility treatments is increasing rapidly. To compare the prenatal and neonatal health care costs after IVF and spontaneous conception, we conducted a study based on a cohort of IVF and control pregnancies and neonates. METHODS: A cohort of 215 IVF mothers and 255 IVF neonates were compared with a cohort of 662 control mothers and 388 control children, randomly chosen from the Finnish Medical Birth Register and matched for sex, year of birth, area of residence, parity, maternal age, socioeconomic status and plurality. The analyses on prenatal and neonatal costs were performed by plurality. Singletons were also compared with twins. The cost calculations were based on the known level of utilization of maternal and neonatal health care services. RESULTS: The total health care costs for an IVF singleton until the end of the neonatal period were 5780 and 15 580 for an IVF twin. The health care costs were 1.3-fold for IVF singletons and 1.1-fold for IVF twins compared to control singletons and twins. The costs for twins were approximately 3-fold compared to singletons. CONCLUSIONS: The health care costs of an IVF singleton neonate were higher than those of a spontaneously conceived control neonate with similar backgrounds. For twins the health care costs were equal. Multiple births increase the health care costs and therefore the reduction of multiple pregnancies is the most effective way to reduce the health care costs resulting from IVF.     

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.     

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.     

Obstetric and neonatal outcome after single embryo transfer

BACKGROUND: Single embryo transfer (SET) pregnancies practically lack vanishing twins and may be associated with improved neonatal outcome. Our objective was to compare the obstetric and neonatal outcome of SET singletons with the outcome of singletons following double embryo transfer (DET) and spontaneous conception. METHODS: A 7-year (1997-2003) cohort of fresh SET (n = 269) and DET (n = 230, including 25 vanishing twins) cycles resulting in singleton birth at Helsinki University Central Hospital, Finland, was linked to the Finnish Medical Birth Register and the obstetric and neonatal outcome data compared with that from 15 037 spontaneously conceived singleton pregnancies. RESULTS: The obstetric and neonatal outcome of the SET group was comparable to that in the DET group. Compared with the comparison cohort, gestational hypertension (P = 0.005), placenta praevia (P < 0.001), preterm contractions (P = 0.01) and maternal hospitalization (P < 0.001) was more typical of women in the SET group. After adjusting for age, parity and socio-economic status the SET pregnancies showed increased risks of Caesarean section [odds ratio (OR) 1.54 with 95% confidence interval (CI) 1.18-2.00], preterm birth (OR 2.85; 95% CI 1.96-4.16) and low birthweight (OR 2.01; 95% CI 1.19-3.99) compared with the comparison cohort. CONCLUSIONS: Our results indicate that subject- and infertility-related mechanisms other than the number of transferred embryos influence the neonatal outcome of singleton IVF pregnancies.     

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.     

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.     

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.     

The obstetrical and neonatal outcome of babies born after single-embryo transfer in IVF/ICSI compares favourably to spontaneously conceived babies

BACKGROUND: Recently, concern has risen about poor obstetrical and neonatal outcome of singletons after IVF/ICSI. Because the population of patients receiving single-embryo transfer (SET) resulting in singleton pregnancies is different from the one that would have become pregnant (with a singleton) before SET was introduced, we wanted to investigate whether the outcome of singleton pregnancies after SET differed from spontaneously conceived singletons. METHODS: The obstetrical and early neonatal outcome of all pregnancies originating from SET after IVF/ICSI procedures between 1 January 1998 and 31 December 2003, was prospectively collected and analyzed. RESULTS: Data from 251 singleton pregnancies and births after SET were analyzed and compared to data from 59,535 spontaneously conceived singletons retrieved from the Centre for Perinatal Epidemiology. The mean birthweight of the singletons after SET was 3322 g (+/-538 SD) versus 3330 g (+/-531 SD) for the spontaneously conceived singletons (P = 0.82). The mean gestational age was 38.7 weeks (+/-1.9 SD) for SET and 38.9 weeks (+/-1.8 SD) for spontaneously conceived singletons (P = 0.06). The proportion of very preterm birth (<32 weeks) was 0.8% in each group, and the proportion of preterm birth (<37 weeks) was 10.0% for SET singletons and 6.24% for spontaneous singletons (P = 0.03). However, mean birthweight of very preterm, preterm and term SET singleton babies was similar to the mean birthweight in every category of gestational age in the spontaneous conceived control group. Stillbirth was 0.4% for both populations (P = 0.99). CONCLUSIONS: Good prognosis patients, in whom SET is applied, do not only have a higher chance of conception but do not have an unfavourable outcome of their singleton baby when compared to spontaneous singletons.     

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.     

Impact of a multiple, IVF birth on post-partum mental health: a composite analysis

BACKGROUND: This study explored the impact of a multiple IVF birth on maternal mental health in the early post-partum period. METHODS: A prospective study of 207 women who had conceived following IVF treatment and followed up at 6 weeks post-partum. Mothers rated their mood using the Edinburgh postnatal depression scale (EPDS) and their baby's behaviour using the Unsettled and Irregular Behaviour scale. Mothers' emotional well-being was explored using theme analysis of semi-structured telephone interviews. RESULTS: Of the 175 (84.5%) followed up post-partum, 56 (32%) had a multiple birth (7 triplets, 49 twins). Nearly 16% of mothers in the multiple group scored>12 on the EPDS indicating clinically significant symptoms, which represented a 3-fold increased risk compared to mothers of singletons (Odds ratio=3.4, Confidence Interval=1.011-11.618, P=0.048). Unsettled and irregular infant behaviour was another independent risk factor. Qualitative analysis of interviews identified 12 themes. Mothers of multiples were more likely to express negative themes including 'tiredness' (P<0.01), 'feelings of stress/depression' (P<0.05) and 'questioning parenthood' (P<0.05). Mothers of singletons were more likely to be 'feeling wonderful', reflecting their delight in parenthood (P<0.05). CONCLUSIONS: Mothers of multiples are at increased risk of poorer emotional well-being. Clinicians should focus on the psychological benefits of a singleton birth.     

Growth, psychomotor development and morbidity up to 3 years of age in children born after IVF

BACKGROUND: To examine the long-term child outcome after IVF until the age of 3 years in Northern Finland, we conducted a population-based cohort study. METHODS: First, a cohort of 299 IVF children born in 1990-1995 was compared with a cohort of 558 controls representing the general population in terms of a multiple birth rate of 1.2%, 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 (full sample analyses). Second, IVF singletons (n = 150) were compared with singleton controls (n = 280). Third, a plurality matched control cohort (n = 100) for IVF twins (n = 100) was randomly chosen, matched as above, from the FMBR and analysed separately. Infant mortality rate was compared with the national rate from the FMBR. RESULTS: Infant mortality in the IVF group was >2-fold higher compared to the national rate in the general population. The risk (OR, 95% CI) of low weight and height, below the lowest quartile, at 1 year of age (1.6, 1.1-2.2; 1.6, 1.1-2.4) and 2 years of age (1.5, 1.1-2.4; 1.7, 1.2-2.5) was significantly higher in the IVF group when compared with the general population control group. No statistically significant differences were found in the psychomotor development between the cohorts. Cumulative incidence of different diseases up to 3 years of age was significantly higher among IVF children in the full sample and singleton analyses (OR, 95% CI: 2.3, 1.7-3.2; 2.1, 1.3-3.3 respectively) especially regarding respiratory diseases (3.5, 1.9-6.5; 3.1, 1.0-9.4) and diarrhoea (3.7, 2.2-6.2; 5.7, 2.6-12.7), but not in twin comparisons. CONCLUSIONS: The growth of IVF children was behind that of control children during the first 3 years of life, but their psychomotor development was similar. Their postnatal health was worse, probably reflecting the problems in the neonatal period.     

Parenting and the psychological development of a representative sample of triplets conceived by assisted reproduction

BACKGROUND: The aim of the study was to examine the quality of parenting and the psychological development of three-year-old children in IVF/ICSI families with triplets. METHODS: Comparisons were carried out between a representative sample of 10 families with triplets and matched groups of 15 families with twins and 30 families with singletons. The families were recruited from Follow-Up, a national organization in France that was established to study children conceived by assisted reproduction. Standardized measures of the mother's psychological well-being (parenting stress, depression and quality of marriage) and standardized measures of the child's psychological development (emotional/behavioural problems and general development) were completed by the mother. RESULTS: Mothers with a multiple birth were found to experience greater difficulties in parenting than mothers of singletons, with no differences between mothers of triplets and mothers of twins. Regarding the children, there were no differences in emotional or behavioural problems between triplets, twins and singletons. However, there were indications of mild delay among triplets and twins in some aspects of language development in comparison with the singleton children. CONCLUSIONS: The birth of triplets or twins does appear to cause difficulties for parents in the early years, however, the children themselves do not seem to experience markedly raised levels of psychological or developmental problems.     

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.     

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.     

Perinatal outcome after in-vitro fertilization-surrogacy

The perinatal outcome of pregnancies (both single and multiple) established after in-vitro fertilization (IVF)-surrogacy was evaluated and compared to the outcome of pregnancies that resulted from standard IVF. Analysis of medical records and a telephone interview with physicians, IVF-surrogates, and commissioning mothers were conducted to assess prenatal follow up and delivery care in several hospitals. 95 IVF-surrogates delivered 128 liveborn (65 singletons, 27 sets of twins and two sets of triplets). The commissioning mothers and the IVF-surrogates average ages were 37.7 +/- 5.0 and 30.4 +/- 4.7 years old respectively. IVF-surrogates carrying twin and triplet gestations delivered substantially earlier than those who gestated singleton pregnancies (36.2 +/- 0.4 versus 35.5 versus 38.7 +/- 0.3 weeks gestation respectively; P < 0.001). Twin newborns were significantly lighter than singleton infants born through IVF-surrogacy (2.7 +/- 0.06 versus 3.5 +/- 0.07 kg; P < 0.001). The incidence of low birth weight infants rose from 3.3% in the single births to 29.6% (P < 0.01) in the twins and to 33.3% in the triplets born through IVF-surrogacy. The incidence of prematurity was significantly greater in both twins delivered by IVF-surrogates (20.4%) and infertile IVF patients (58%). The occurrence of pregnancy-induced hypertension and bleeding in the third trimester was four to five times lower in the IVF-surrogates, independently of whether they were carrying multiples. The incidence of Caesarean section was 21.3% for singleton gestations, while two times higher in the IVF-surrogates carrying multiples (56.3%). Postpartum complications occurred in 6.3% of patients and the incidence of malformation was similar to those reported for the general population. The results provide general reassurance regarding perinatal outcome to couples who wish to pursue IVF-surrogacy.     

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.     

A health-economic decision-analytic model comparing double with single embryo transfer in IVF/ICSI

BACKGROUND: Single embryo transfer (SET) is the sole strategy with which to reduce the incidence of twins following assisted reproductive technology (ART), but SET may increase the number of ART cycles needed per live-born child. Its cost-effectiveness compared with double embryo transfer (DET) is therefore unknown. METHODS: A decision-analytic model comparing SET with DET was developed. Estimates were obtained from literature, national pregnancy registers and local hospital records. A sensitivity analysis was performed, using pregnancy rates from four published studies. The outcome measure was the cost per child born, calculated from IVF procedure-related, pregnancy-related and neonatal care costs. Neonatal mortality and long-term morbidity costs were not taken into account. RESULTS: Independently of the pregnancy rates used, the SET cost per child born was in all instances the same as with DET, varying from EURO= 9520 (SET) versus EURO= 9511 (DET) to EURO= 12254 (SET) versus EURO= 12934 (DET). CONCLUSIONS: More ART cycles are required to obtain the same numbers of children born following SET compared with DET. Because SET allows the avoidance of twins and thus diminishes pregnancy-related and neonatal care costs, there is no difference in the cost per child born between SET and DET. The real advantage of SET is the avoidance of the very high long-term costs resulting from the increased morbidity of twins after birth.     

A real-life prospective health economic study of elective single embryo transfer versus two-embryo transfer in first IVF/ICSI cycles

BACKGROUND: We analysed the difference in maternal, neonatal and total costs after single (SET) versus double day 3 embryo transfer (DET). METHODS: We performed a two-centre prospective study of women in their first IVF/ICSI cycle choosing between SET or DET. Infertility treatment data were gathered from a database; maternal and neonatal outcome data from a case report form (CRF); health economic data from medical acts registered in the CRF for the outpatient part and from hospital bills. SET was performed in 206/367 (56.1%) and DET in 161/367 (43.9%) women. RESULTS: In all, 367 transfers yielded 186 positive pregnancy tests, 148 ongoing pregnancies and 136 live deliveries (50.7, 40.3 and 37.1% per embryo transfer) of which 15 (11.0%) were twins. Live birth rate was 37.4% for SET, 36.6% for DET. Intention-to-treat analysis showed differences for: duration of pregnancy (SET: 39.0 +/- 1.4 versus DET: 38.3 +/- 2.2 weeks; P = 0.055), percentage prematurity (8.5 versus 23.8%; P = 0.033), percentage of neonates hospitalized (5.7 versus 17.9%; P = 0.121) and duration of neonatal hospitalization (6.3 +/- 2.2 versus 10.3 +/- 10.1 days; P = 0.01). Total cost after DET was higher (SET: 4700 +/- 3239 versus DET: 8613 +/- 10 105; P = 0.105), due to significantly higher neonatal costs (451 +/- 957 versus 3453 +/- 8154; P < 0.001) and not to differences in maternal costs (4250 +/- 2882 versus 5160 +/- 4106; P = 0.152). CONCLUSIONS: This prospective health economic study shows that transfer of a single top quality embryo is equally effective as, but substantially cheaper than, double embryo transfer in women <38 years of age in their first IVF/ICSI cycle.     

Matched follow-up study of 5 8-year-old ICSI singletons: child behaviour, parenting stress and child (health-related) quality of life

BACKGROUND: Psychosocial follow-up of ICSI children is scarce. We compared child behaviour, parenting stress and quality of life for singletons aged 5-8 years born after ICSI, IVF and natural conception (NC). METHODS: All singletons born between June 1996 and December 1999 after ICSI in the Leiden University Medical Center were invited (n = 110). Matched singletons born after IVF and NC were recruited. Parents completed the Child Behaviour Checklist (measures problem behaviour), the Parenting Stress Index (Nijmeegse Ouderlijke Stress Index) and two quality of life questionnaires (Dux25 and TACQOL). Children completed the Dux25 Child form. RESULTS: Eighty-seven ICSI children (79%), 92 IVF children (73%) and 85 NC children enrolled. Prevalence of behavioural disorders-as reported by the parents-was comparable in the three groups. Three of 87 ICSI children had autism or an autistic spectrum disorder (ASD). Problem behaviour scores were similar for ICSI and NC children; IVF children (mainly girls) scored less problem behaviour (P < 0.05) and their scores were less often in the (borderline) clinical range. Parenting stress was similar for ICSI and IVF, but lower for NC than ICSI parents, mainly on the child scale. Quality of life scores were similar in the three conception groups. CONCLUSIONS: Prevalence of autism/ASD seemed higher after ICSI, but this unexpected finding should be confirmed by future studies with larger group sizes. ICSI parents experienced more stress than NC parents, although selection bias cannot be ruled out. The majority of ICSI singletons assessed at age 5-8 years showed a normal psychosocial well-being.     

A multi-centre cohort study of the physical health of 5-year-old children conceived after intracytoplasmic sperm injection, in vitro fertilization and natural conception

BACKGROUND: Over a million children have been born from assisted conception worldwide. Newer techniques being introduced appear less and less 'natural', such as intracytoplasmic sperm injection (ICSI), but there is little information on these children beyond the neonatal period. METHODS: 540 ICSI conceived 5-year-old children from five European countries were comprehensively assessed, along with 538 matched naturally conceived children and 437 children conceived with standard IVF. RESULTS: Of the 540 ICSI children examined, 63 (4.2%) had experienced a major congenital malformation. Compared with naturally conceived children, the odds of a major malformation were 2.77 (95% CI 1.41-5.46) for ICSI children and 1.80 (95% CI 0.85-3.81) for IVF children; these estimates were little affected by adjustment for socio-demographic factors. The higher rate observed in the ICSI group was due partially to an excess of malformations in the (boys') urogenital system. In addition, ICSI and IVF children were more likely than naturally conceived children to have had a significant childhood illness, to have had a surgical operation, to require medical therapy and to be admitted to hospital. A detailed physical examination revealed no further substantial differences between the groups, however. CONCLUSIONS: Singleton ICSI and IVF 5-year-olds are more likely to need health care resources than naturally conceived children. Assessment of singleton ICSI and IVF children at 5 years of age was generally reassuring, however, we found that ICSI children presented with more major congenital malformations and both ICSI and IVF children were more likely to need health care resources than naturally conceived children. Ongoing monitoring of these children is therefore required.