Health care costs resulting from IVF: prenatal and neonatal periods

S. Koivurova1,2,5, A.-L. Hartikainen1, M. Gissler3, E. Hemminki3, R. Klemetti3 and M.-R. Järvelin1,4

1 Department of Public Health Science and General Practice, University of Oulu, P.O.Box 5000, University of Oulu, 90014 Oulu, 2 Department of Obstetrics and Gynecology, University Hospital of Oulu, P.O.Box 220, 90024 Oulu, Finland, 3 National Research and Development Center for Welfare and Health, P.O.Box 220, 00531 Helsinki, Finland and 4 Department of Epidemiology and Public Health, Imperial College London, Norfolk Place, London W2 1PG, UK

5 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, University Hospital of Oulu, P.O.Box 24, 90024 Oulu, Finland. Email: sari.koivurova{at}oulu.fi


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
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 {euro}5780 and {euro}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 ~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.

Key words: costs/health care/IVF


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
IVF is a routine method for treating couples suffering from infertility. Due to its efficacy, IVF has been rapidly accepted in developed countries. However, negative obstetric and paediatric outcomes mainly arising from multiple births have been linked to IVF treatments. These include increased maternal morbidity (Tan et al., 1992Go; Tallo et al., 1995Go; Tanbo et al., 1995Go; Maman et al., 1998Go; Koivurova et al., 2002bGo), preterm birth, low birthweight and smallness for gestational age (Friedler et al., 1992Go; Balen et al., 1993Go; Gissler et al., 1995Go; Bergh et al., 1999Go; Klemetti et al., 2002Go; Koivurova et al., 2002aGo) and consequently increased neonatal morbidity and hospitalization (Gissler et al., 1995Go; D'Souza et al., 1997Go; Addor et al., 1998Go; Koudstaal et al., 2000Go; Koivurova et al., 2002aGo).

IVF is a costly method and due to its most prominent complication, multiple birth, the prenatal and neonatal costs are also high (Callahan et al., 1994Go). International comparisons of IVF costs are difficult due to variable prices (Mor-Yosef, 1995Go; Collins, 2001Go), cost calculations and funding policy in different countries. It has been stated, however, that costs are generally underestimated (Mor-Yosef, 1995Go), due to the complexity of the components involved. The costing structure of IVF is also dependent on the funding policy; whether there is a national health insurance (NHI) coverage involved or not. In most countries the cost of a single IVF cycle is greater than one-quarter of the gross domestic product (GDP) per capita (Collins, 2001Go). In the Nordic countries IVF accounted for 0.08–0.16% of total health care costs in 1994 (Granberg et al., 1998Go). The major contributor to the total costs has been multiple births, especially high-order multiple births (Gissler et al., 1995Go; Goldfarb et al., 1996Go).

In Finland, >7000 IVF treatments (including also ICSI and frozen embryo transfers) have been performed annually. In 2002, 20% of all IVF treatments ended in a live birth (1428 children). This equals 2.5% of all children born during that year. The multiplicity rate was reduced from 27% in 1992 to 14% in 2002 due to the increasing policy of using single embryo transfer (Stakes, 2004Go).

A number of studies on the health economics of IVF have been conducted during the past 10 years. The studies are heterogeneous with different study designs and end-points. Only a few studies have included the costs of neonatal care in the cost calculations and to our knowledge only Gissler et al. compared the cost of an IVF birth with the cost of a spontaneous birth (Garceau et al., 2002Go). There is a lack of information on the difference in the health care costs between IVF and spontaneously conceived children. In this matched population-based study, we aim to focus on the actual health care costs caused by conventional IVF treatments and their consequent phenomena using an established follow-up of a cohort of IVF mothers and children followed from pregnancy to the end of the neonatal period. We calculate the costs after the known level of utilization of health care services; that is, we compare the costs of a live neonate after IVF and spontaneous conception during 1990–1995 in Finland. Our hypothesis was that the prenatal and neonatal care of IVF pregnancies and IVF neonates is more costly than the care of spontaneous ones.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
The present study on costs after conventional IVF derives from our population-based follow-up study of a cohort of IVF pregnancies and children described previously (Koivurova et al., 2002aGo,bGo, 2003Go). In this study we used data from IVF mothers and neonates and their control cohorts to calculate the total costs of liveborn neonates from IVF and spontaneous pregnancies. The IVF treatments were performed during 1990–1995 in Oulu by two infertility clinics—the IVF outpatient clinic in the University Hospital of Oulu and the Infertility Clinic of the Family Federation of Finland in Oulu—which cover all IVF treatments in Northern Finland.

Power calculation
To study the outcomes (prenatal, neonatal and postnatal) and costs of an IVF child, the pre-study sample size calculations were based on clinical developmental outcomes; the approximation of a frequency of, on average, 15% for developmental disorders including neurological signs (gross and fine motor, speech and other disabilities) among an unexposed population (Hadders-Algra and Touwen, 1990Go). For 80% power, 0.05 alpha-error, a risk ratio of 1.6 for the outcome between the groups and with a ratio of 1:2 (exposed:unexposed), a sample size of ≥238 exposed and ≥476 unexposed children was required for comparison between IVF and general population cohorts. For twins, corresponding sample size calculations for 80% power, 0.05 alpha-error and a risk ratio of 1.6 for the outcome between the groups with a ratio of 1:1 assuming a frequency of developmental disorders among unexposed multiples of an average 30%, a sample size of ≥125 per group was required.

Study design
The principal study design, the original population and the sample of the cost study are shown in Figure 1. The design is based on the cohort of IVF children and their controls selected first; the number of mothers is a result of the number of children (i.e. for the full sample control group of children there were more mothers than for the IVF group because the groups were not plurality-matched). In the present study the comparisons were performed by plurality.



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Figure 1. Study design and the study population. Shaded presentation for the cost study. Children are the principal cases and controls. IVF treatments were given at two centres in Oulu and the control groups (full sample control group and its derivative singleton control group and the additional twin control group) were randomly chosen from the Finnish Medical Birth Register. aRepresents children from multiple pregnancies in the same proportion as in a general population. bThirty-nine IVF children missing second control. cOne IVF singleton had no plurality-matched control. dNineteen IVF children missing second control. eEighteen IVF twins had no plurality-matched control. fAs a group, the mothers represent similar area of residence, parity, age and social class due to the study design. gTen mothers (IVF) and nine mothers (controls) with high-order multiple births excluded.

 
The present study group for the cost comparisons stratified by plurality consisted of 215 IVF mothers (153 singleton and 62 twin pregnancies) and 662 control mothers (580 singleton and 82 twin pregnancies) and 255 IVF neonates (152 singletons and 103 twins) with 388 control neonates (285 singletons and 103 twins) (Figure 1, shaded boxes). The matching for the principal full sample groups was for sex, year of birth, area of residence, maternal age, parity and socioeconomic status defined by the occupation of the mother. Due to the study design the IVF and control mothers represent a group similar by area of residence, age, parity and socioeconomic status (Koivurova et al., 2002bGo). For the cost analyses, both singletons and twins were assigned control groups matched for plurality in addition to the other matching criteria (1:2 for singletons, 1:1 for twins). All controls were randomly chosen from the Finnish Medical Birth Register (FMBR). High-order births were excluded from the cost calculations, because no controls fulfilling the matching criteria were found for them. The only ICSI child was excluded because of the different IVF technique used with ICSI (Koivurova et al., 2002bGo, 2003Go).

Data collection
The data regarding pregnancy (spontaneous abortions, ectopic pregnancies, number of visits to maternal health care centres (MHC) and outpatient clinics, number of days in hospital during pregnancy and after delivery, mode of delivery) and neonatal period (number of days in neonatal wards or intensive care units) were collected by a resident physician (S.K.) from hospital records. The neonatal period was defined as 0–27 days from birth, so the maximum number of hospitalization days was 27. The mean unit prices (year 2001) of these health care services during pregnancy and neonatal period were collected from the data of National Research and Development Center for Welfare and Health (Stakes) (Hujanen, 2003Go; Tables II and III). The costs of IVF treatments during 2003 (oocyte retrieval, embryo transfer, related visits to the infertility clinic) were collected from the Infertility Clinic of Oulu University Hospital (Table I, unpublished data). The costs of medication for ovulation induction (years 1996–1998) were received from research data from the Social Insurance Institution of Finland (KELA). Mean costs of sickness allowance due to IVF treatment were received from age- and sex-stratified statistics of KELA (Lindroos and Kuusisto, 1994Go). The costs of unsuccessful cycles were estimated using statistics compiled by Stakes which showed one successful cycle out of 5.26 cycles in total in Finland in 1996–1998, and selected parts of the IVF costs listed in Table I (i.e. those repeated in succeeding treatments: medication, IVF treatment and 3 day sick leave) were multiplied by 4.26 to estimate the costs of unsuccessful cycles (for Table IV). Data on sickness allowances during pregnancy or travelling costs were not available, and therefore not included in the cost calculations.


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Table II. The unit prices in euros of different health care services in Finland in 2001, the mean numbers of utilization of maternal and neonatal health care services, the percentage of the mode of delivery and resulting total costs in the singleton comparison

 

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Table III. The unit prices in euros of different health care services in Finland in 2001, the mean numbers of utilization of maternal and neonatal health care services, the percentage of the mode of delivery and resulting total costs in the twin comparison

 

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Table I. The cost of one successful IVF treatment in Oulu University Hospital in 2003 in euros

 

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Table IV. Total costs in euros with the costs of IVF and additional costs from the unsuccessful cycles and 1st trimester pregnancy loss added.

 
Analysis
We calculated the mean numbers of visits to maternal health care centres and hospital outpatient clinics, and the mean number of days of hospitalization during pregnancy and after birth for mothers. The percentages of the different delivery types were calculated. (Tables II and III). Children were divided into five categories according to their neonatal status: (1) healthy full-term neonates; (2) full-term neonates with neonatal morbidity [excluding respiratory distress syndrome (RDS)]; (3) healthy preterm neonates (born < 37 weeks of gestation); (4) preterm neonates with neonatal morbidity (born <37 weeks of gestation, excluding RDS); (5) neonates with RDS. This DRG-based (Diagnosis-Related Groups) categorization was made to follow the national categorization of the costs resulting from neonatal hospitalization by Stakes (Hujanen, 2003Go). The percentages of children in different categories were calculated. For children the mean numbers of days of hospitalization in neonatal wards and intensive care units were calculated in these categories (Tables II and III). The cost calculations were performed using the known mean unit prices for one hospitalization of different health services in Finland shown in Tables II and III (Hujanen, 2003Go) to calculate the actual cost for 1 day, and then multiplying them by the mean number of visits to MHC and outpatient clinics or days at the hospital. To simplify the MCH cost calculations, all mothers were regarded as primiparas though a minority were giving subsequent births. This assumption had no effect on the conclusions. The statistical significance tests were computed for the differences between the means or proportions (Tables II and III) but not for the total costs between IVF and control groups because the total prices constituted of the sum of the means of all available cases. We used all available mothers in the prenatal comparisons (mothers of singletons and twins in the full sample control group and the additional control group of mothers of twins) and hence the matching proportions 1:2 and 1:1 for the children cannot be seen in the number of mothers. The costs were inflated to correspond to the prices during 2003 using the consumer price index. Sensitivity analysis was performed by calculating the health care costs at 25th and 75th percentiles for IVF and control groups to indicate the interquartile range of the health care costs in these groups and also by calculating the health care costs applying 10.0% frequency of multiple births among the IVF population as recommended by the ESHRE Campus Course Report (2001)Go in comparison with: (i) the multiple birth frequency of 46.2% in our IVF population from 1990 to 1995; and (ii) 12.0% as it was in 2002 in the population of IVF children in Northern Finland.


    Results
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
The costs of IVF
The cost of an IVF procedure in this study consists of the costs of one preliminary visit to the infertility outpatient clinic prior to IVF treatment; IVF treatment consisting of oocyte retrieval, embryo transfer, three visits to the outpatient clinic and the costs of equipment and trained staff; the cost of one visit to the outpatient clinic after pregnancy detection at gestational week 7; medication for ovulation induction and a 3 day sick leave during oocyte retrieval and embryo transfer. This results in a total sum of {euro}3291 per successful IVF treatment (Table I).

The costs of prenatal and neonatal care
The mean numbers of the utilization of prenatal and neonatal health care services, on which the cost calculations are based, are given in Tables II and III. There were no differences in the mean number of visits to the MHC or days in hospital after delivery between the groups, but hospital outpatient and ward services were utilized more often during pregnancy in the IVF groups than in the control groups. No major differences were found in the mode of delivery between IVF and control groups, although the Caesarean section rate was somewhat higher in the twin IVF group than in the twin control group and a few more vacuum or breech deliveries occurred in control groups than in IVF groups. In singleton comparisons, IVF neonates were treated for RDS more often than controls. In twin comparisons, control twins had more days in the hospital than IVF twins, mostly in the RDS group. Apart from prenatal hospital outpatient and ward service utilization, no significant differences were found in the utilization of other health care services.

An example of the health care calculations (IVF neonates with RDS in Table II): divide the unit price ({euro}) 24 405.8 by 22.55 (to obtain the cost of 1 day treatment), multiply this by 27.0 (to obtain the cost of 27 day treatment) and multiply this result by 0.0204 (proportion of neonates in the IVF RDS group, see footnote ‘c’ in Table II) to obtain the cost of RDS treatment in the IVF group ({euro}596.1)

Figure 2 and Tables II and III show that prenatal costs were higher in IVF groups compared to control groups; 1.2-fold in the singleton comparisons and 1.3-fold in the twin comparisons. The neonatal costs for IVF singletons were 1.5-fold those for control singletons, but for twins the situation was reversed; 1.4-fold for controls compared to IVF twins. When the prenatal and neonatal costs were calculated together, the costs were 1.3-fold in the singleton comparisons and 1.1-fold in the twin comparisons for IVF groups compared to controls. Prenatal costs were 2.4–2.5-fold, neonatal costs 3.7–7.8-fold and total health care costs 2.7–3.2-fold for twins compared to singletons (Tables IIIII).



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Figure 2. Prenatal and neonatal costs in euros among the IVF and control groups. MHC = maternal healthcare centre.

 
Sensitivity analysis
Sensitivity analysis at 25th and 75th percentiles of the resource use showed that the interquartile range of the total health care costs would be {euro}3230–{euro}6790 for IVF singletons, {euro}1950–{euro}5280 for control singletons, {euro}6360–{euro}18 180 for IVF twins and {euro}7000–{euro}17 380 for control twins. The total prenatal and neonatal costs for the whole IVF population (n=303, Figure 1, 46.2% multiple births) were ~{euro}3 100 000. By decreasing the frequency of multiple births to 10.0%, the costs would be reduced to {euro}2 000 000. With a frequency of 12.0% of multiple births in 2002 among the IVF population in Northern Finland (Stakes, unpublished data), the costs would be {euro}2 100 000.

Additional costs of IVF technology and 1st trimester pregnancy loss
Table IV summarizes the health care costs and other additional costs. After adding the costs of a successful IVF treatment to the health care costs, the costs were 2.0-fold for singletons and 1.3-fold for twins compared to controls respectively. The costs of unsuccessful cycles were estimated to be between {euro}5740 and {euro}12 306 per IVF pregnancy—the lower limit including only the costs of medication, and the upper limit also including the costs of IVF treatment and a 3 day sickness allowance. Furthermore there were on average 0.3 spontaneous abortions and ectopic pregnancies in the obstetric history of IVF women, with control women having had on average 0.1–0.2 spontaneous abortions and 0.01–0.02 ectopic pregnancies. After adding the costs of unsuccessful cycles and 1st trimester pregnancy loss, the costs of IVF neonates were 4.7–4.8-fold in the singleton comparison and 2.2-fold in the twin comparison (Table IV).


    Discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
Infertility is a problem for every sixth couple in their fertile age (Speroff et al., 1999Go). IVF as an effective infertility treatment method is costly, requiring specialized expertise, equipment and heavy medication; it also has severe side-effects and complications, which have been claimed to account for the major part of the societal IVF costs (Callahan et al., 1994Go; Gissler et al., 1995Go; Goldfarb et al., 1996Go). In this population-based study we investigated the accurate costs of IVF and its consequences during the neonatal period, as well as the additional costs resulting from multiple births compared to the costs from spontaneously conceived pregnancies and children of women with similar age and parity. It was found that the health care costs were higher for IVF singleton neonates compared to control singleton neonates, but for twins the costs were equal. Multiple births increased the health care costs markedly.

In Northern Finland, our catchment area, treatments are given in two clinics of which one is a public clinic and the other a private non-profitable clinic. IVF treatments in Finland are partly covered by national health insurance, both in the public and private sectors. It has been estimated that 1500 couples per 106 population per annum would need IVF/ICSI services globally. In 1995, 663 IVF/ICSI cycles per 106 population were given in Finland indicating an under-utilization of IVF services by infertile Finnish couples. However, international comparisons indicate that the availability of IVF services in Finland was reasonably high and similar to that of the other Nordic countries: only Israel reported >1500 IVF/ICSI cycles per 106 population per annum (Collins, 2001Go). The reasonably high number of cycles in Finland (Nygren and Nyboe Andersen, 2002Go) could be due to the fact that NHI covers part of private treatments.

As expected, the prenatal costs in IVF groups exceeded those of control groups in the present study. This may be partly explained by increased maternal morbidity (uterine bleeding, threatened preterm birth, intrahepatic cholestasis of pregnancy) during pregnancy among the IVF mothers presented earlier (Koivurova et al., 2002bGo). Delivery costs were equally high in both IVF and control groups due to the high Caesarean section rate in both groups, reflecting the high age and primiparity of the mothers also in the control group due to the strict matching criteria. The costs originating from the neonatal period showed more variation. The neonatal care for the control twins was more expensive than the care of the IVF twins, while the situation was reversed in the singletons. This could possibly be explained by the fact that the IVF mothers were more often treated in the hospital which may have led to more frequent prophylactic corticosteroid treatment for fetal lung maturation. The zygosity–chorionicity rate as a prognostic factor may also play some role, since IVF is known to alter the rate of zygosity in twin pregnancies. The increased health care costs of IVF singletons in this study may reflect the maternal characteristics of infertile women, since infertility itself has been linked to adverse birth outcomes even without infertility treatments (Ghazi et al., 1991Go; Basso and Baird, 2003Go).

When the prenatal costs for singleton and twin pregnancies were compared (IVF singletons versus IVF twins; control singletons versus control twins) the costs were >2-fold in both twin groups, indicating the high price of multiple pregnancies as has been reported earlier (Callahan et al., 1994Go; Goldfarb et al., 1996Go). The costs of neonatal care for twins were understandably also higher than those for singletons (3.8- and 7.7-fold respectively). Similar results on neonatal costs have been recently published by a Belgian study group (Gerris et al., 2004Go). A study from Scotland showed that the reduction of multiple pregnancies by reducing the number of embryos transferred reduced the costs for neonatal intensive care attributable to IVF to one-ninth in 3 years (Liao et al., 1997Go). In ongoing IVF/ICSI pregnancies in our catchment area the twin rate is ~7% (Martikainen et al., 2004Go) indicating that economic savings have already been gained, referring to our sensitivity analysis. In our data there was a slightly greater variation in interquartile costs among the IVF cases than the controls.

The cost of an IVF child also includes the costs resulting from IVF technology and from probable unsuccessful cycles. In the present study, IVF technology increased the costs 2–5-fold. This is consistent with another Finnish study where the health care costs for one IVF newborn from induction of pregnancy until the age of 7 days were 5.4-fold compared to other newborns (Gissler et al., 1995Go). Similarly, unsuccessful first trimester pregnancies that commonly characterize the obstetric history of infertile women tend to increase costs. In this maternal study population, ectopic pregnancies especially were more common among IVF mothers than among control mothers (21–24 versus 1–2%) (Koivurova et al., 2002bGo).

An additional cost is related to absence from work. Finnish women are characterized by a high level of education and employment. Fifty-nine per cent of Finnish women aged >15 years have an educational qualification beyond basic education, 42% of them at a tertiary level of education (Statistics Finland, 2002Go). Seventy-six per cent of Finnish women of childbearing age are daily workers (Hartikainen-Sorri and Sorri, 1989Go). Unfortunately, in this study we do not have data on the extent of the loss of working days, apart from the 3 days during IVF treatment or travelling costs. Therefore the total costs presented in our study are underestimated in this respect. It is probable that IVF mothers have spent more days on sickness allowance during pregnancy than control mothers, since their maternal morbidity and hospitalization during pregnancy were at a higher level in comparison to control mothers (Koivurova et al., 2002bGo). All IVF treatments were performed in Oulu, but patients came from all around Northern Finland which is a large geographical area, ~160 500 km2 with 645 000 inhabitants. Taking into account the fact that the IVF treatment protocol includes up to five visits to the infertility clinic in Oulu, there have been significant travelling costs for the patients living outside Oulu. Furthermore, if our control mothers had represented mothers at normal childbearing age rather than older primiparas, the cost differences would have been even greater for the IVF group compared to the controls. The increasing age of the mother has been found to increase the costs per delivery after IVF (Suchartwatnachai et al., 2000Go).

During the 3 year follow-up of this cohort of IVF children we have noted that they have significantly more chronic illnesses diagnosed at paediatric clinics during early childhood than their controls (Koivurova et al., 2003Go). Unfortunately, we do not have data on the utilization of health care services during that time, but it can be assumed that these IVF children have used more health care services than the controls. Thus, it is probable that the health care costs of IVF children continue to be higher also in later childhood. It has been noted earlier in a large series of IVF children that the increased utilization of hospital care of IVF children continued to the age of 6 years (Ericson et al., 2002Go), although, according to a smaller Australian study on 95 IVF children, they were less likely to visit general practitioners or other health care workers during infancy (Leslie et al., 1998Go).

In conclusion, our study showed that the health care of an IVF child is more expensive than the health care of a spontaneously conceived child, with most of the additional expenses arising from multiple births. We were not able to calculate the additional costs resulting from sickness allowances during pregnancy or travelling, making our total cost smaller than it actually is. The goal of assisted reproduction should be the birth of a healthy child without excess problems during pregnancy, birth or childhood, rather than achieving as high a pregnancy rate as possible. To achieve this goal, and to lower the total costs after IVF, the technology of assisted reproduction should be continuously improved, and the right couples should be chosen for single embryo transfer, making single embryo transfer the future gold standard of IVF treatments.


    Acknowledgements
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
We gratefully acknowledge the financial support from The Alma and K.A.Snellman Foundation, Oulu and from the National Social Insurance Institute, Finland, Academy of Finland and the University Hospital of Oulu, Finland.


    References
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
Addor V, Santos-Eggiman B, Fawer CL, Paccaud F and Calame A (1998) Impact of infertility treatments on the health of newborns. Fertil Steril 69, 210–215.[CrossRef][ISI][Medline]

Balen AH, MacDougall J and Tan SL (1993) The influence of the number of embryos transferred in 1060 in-vitro fertilization pregnancies on miscarriage rates and pregnancy outcome. Hum Reprod 8, 1324–1328.[Abstract]

Basso O and Baird DD (2003) Infertility and preterm delivery, birthweight, and Caesarean section: a study within the Danish National Birth Cohort. Hum Reprod 18, 2478–2484.[Abstract/Free Full Text]

Bergh T, Ericson A, Hillensjö T, Nygren K-G and Wennerholm U-B (1999) Deliveries and children born after in-vitro fertilization in Sweden 1982-95: a retrospective cohort study. Lancet 354, 1579–1585.[CrossRef][ISI][Medline]

Callahan TL, Hall JE, Ettner SL, Christiansen CL, Greene MF and Crowley WF (1994) The economic impact of multiple-gestation pregnancies and the contribution of assisted-reproduction techniques to their incidence. N Engl J Med 331, 244–249.[Abstract/Free Full Text]

Collins J (2001) Cost-effectiveness of in vitro fertilization. Semin Reprod Med 19, 279–289.[CrossRef][ISI][Medline]

D'Souza SW, Rivlin E, Cadman J, Richards B, Buck P and Lieberman A (1997) Children conceived by in vitro fertilization after fresh embryo transfer. Arch Dis Child 76, F70–F74.[ISI]

Ericson A, Nygren KG, Olausson PO and Källén B (2002) Hospital care utilization of infants born after IVF. Hum Reprod 17, 929–932.[Abstract/Free Full Text]

ESHRE Campus Course Report (2001) Prevention of twin pregnancies after IVF/ICSI by single embryo transfer. Hum Reprod 16, 790–800.[Abstract/Free Full Text]

Friedler S, Mashiach S and Laufer N (1992) Births in Israel resulting from in-vitro fertilization/embryo transfer, 1982-1989: National Registry of the Israeli Association for Fertility Research. Hum Reprod 7, 1159–1163.[Abstract]

Garceau L, Henderson J, Davis LJ, Petrou S, Henderson LR, McVeigh E, Barlow DH and Davidson LL (2002) Economic implications of assisted reproductive techniques: a systematic review. Hum Reprod 17, 3090–3109.[Abstract/Free Full Text]

Gerris J, De Sutter P, De Neubourg D, Van Royen E, Vander Elst J, Mangelschots K, Vercruyssen M, Kok P, Elseviers M, Annemans L et al. (2004) A real-life prospective health economic study of elective single embryo transfer versus two-embryo transfer in first IVF/ICSI cycles. Hum Reprod 19, 917–923.[Abstract/Free Full Text]

Ghazi HA, Spielberger C and Källén B (1991) Delivery outcome after infertility—a registry study. Fertil Steril 55, 726–732.[ISI][Medline]

Gissler M, Malin Silverio M and Hemminki E (1995) In-vitro fertilization pregnancies and perinatal health in Finland 1991-1993. Hum Reprod 10, 1856–1861.[Abstract]

Goldfarb JM, Austin C, Lisbona H, Peskin B and Clapp M (1996) Cost-effectiveness of in vitro fertilization. Obstet Gynecol 87, 18–21.[Abstract/Free Full Text]

Granberg M, Wikland M and Hamberger L (1998) Financing of IVF/ET in the Nordic countries. Acta Obstet Gynecol. Scand 77, 63–67.[CrossRef][ISI][Medline]

Hadders-Algra M and Touwen BCL (1990) Body measurements, neurological and behavioural development in six-year-old children born preterm and/or small-for-gestational-age. Early Hum Dev 22, 1–13.[ISI][Medline]

Hartikainen-Sorri A-L and Sorri M (1989) Occupational and socio-medical factors in preterm birth. Obstet Gynecol 74, 13–16.[Abstract]

Hujanen, T (2003) Terveydenhuollon yksikkökustannukset Suomessa vuonna 2001. Stakes. Aiheita 1/2003. Helsinki. http://www.stakes.fi/verkkojulk/pdf/Aiheita1-2003.pdf.

Klemetti R, Gissler M and Hemminki E (2002) Comparison of perinatal health of children born from IVF in Finland in the early and late 1990s. Hum Reprod 17, 2192–2198.[Abstract/Free Full Text]

Koivurova S, Hartikainen A-L, Gissler M, Hemminki E, Sovio U and Järvelin M-R (2002a) Neonatal outcome and congenital malformations in children born after in-vitro fertilization. Hum Reprod 17, 1391–1398.[Abstract/Free Full Text]

Koivurova S, Hartikainen A-L, Karinen L, Gissler M, Hemminki E, Martikainen H, Tuomivaara L and Järvelin M-R (2002b) The course of pregnancy and delivery and the use of maternal healthcare services after standard IVF in Northern Finland 1990-1995. Hum Reprod 17, 2897–2903.[Abstract/Free Full Text]

Koivurova S, Hartikainen A-L, Sovio U, Gissler M, Hemminki E and Järvelin M-R (2003) Growth, psychomotor development and morbidity up to 3 years of age in children born after IVF. Hum Reprod 18, 2328–2336.[Abstract/Free Full Text]

Koudstaal J, Braat DDM, Bruinse HW, Naaktgeboren N, Vermeiden JPW and Visser GHA (2000) Obstetric outcome of singleton pregnancies after IVF: a matched control study in four Dutch university hospitals. Hum Reprod 15, 1819–1825.[Abstract/Free Full Text]

Leslie GI, Gibson FL, McMahon C, Tennant C and Saunders DM (1998) Infants conceived using in-vitro fertilization do not over-utilize health care resources after the neonatal period. Hum Reprod 13, 2055–2059.[Abstract]

Liao X-H, de Caestecker L, Gemmel J, Lees A, McIlwaine G and Yates R (1997) The neonatal consequenses and neonatal cost of reducing the number of embryos transferred following IVF. Scot Med J 42, 76–78.[ISI][Medline]

Lindroos K and Kuusisto S (1994) Sairausvakuutus. In Lindroos K and Kuusisto S (eds) Statistical Yearbook of the Social Insurance Institution, Finland 1993. Vammalan Kirjapaino Oy, Vammala, Finland, pp 123 and 138.

Maman E, Lunenfeld E, Levy A, Vardi H and Potashnik G (1998) Obstetric outcome of singleton pregnancies conceived by in vitro fertilization and ovulation induction compared with those conceived spontaneously. Fertil Steril 70, 240–245.[CrossRef][ISI][Medline]

Martikainen H, Orava M, Lakkakorpi J and Tuomivaara L (2004) Day 2 elective single embryo transfer in clinical practice: better outcome in ICSI cycles. Hum Reprod 19, 1364–1366.[Abstract/Free Full Text]

Mor-Yosef S (1995) Cost effectiveness of in vitro fertilization. J Assist Reprod Genet 12, 524–530.[ISI][Medline]

Nygren KG and Nyboe Andersen A (2002) Assisted reproductive technology in Europe, 1999. Results generated from European registers by ESHRE. Hum Reprod 17, 3260–3274.[Abstract/Free Full Text]

Speroff L, Glass RH and Kase NG (1999) Female infertility. In Mitchell C, Reter R, and Magee RD (eds) Clinical Gynecologic Endocrinology and Infertility. Lippincott, Williams & Wilkins, Baltimore, USA, pp. 1013–1042.

Stakes (2004) IVF-tilastot 2002 (ennakko2003). IVF-statistik 2002 (preliminär 2003). IVF statistics 2002 (preliminary 2003). Tilastotiedote 9. (http://www.stakes.info/files/pdf/Tilastotiedotteet/Tt09_04.pdf.).

Suchartwatnachai C, Wongkularb A, Srisombut C, Choktanasiri W, Chinsomboon S and Rojanasakul A (2000) Cost-effectiveness of IVF in women 38 years and older. Int J Gynecol Obstet 69, 143–148.[CrossRef][ISI][Medline]

Statistics Finland (2002) Statistical Yearbook of Finland. Karisto Oy, Hämeenlinna, Finland, 488 pp.

Tallo CP, Vohr B, Oh W, Rubin LP, Seifer DB and Haning RV, Jr (1995) Maternal and neonatal morbidity associated with in vitro fertilization. J Pediatr 127, 794–800.[ISI][Medline]

Tan SL, Doyle P, Cambell S, Beral V, Rizk B, Brinsden B, Mason B and Edwards RG (1992) Obstetric outcome of in vitro fertilization pregnancies compared with normally conceived pregnancies. Am J Obstet Gynecol 167, 778–784.[ISI][Medline]

Tanbo T, Dale PO, Lunde O, Moe N and Åbyholm T (1995) Obstetric outcome in singleton pregnancies after assisted reproduction. Obstet Gynecol 86, 188–192.[Abstract/Free Full Text]

Submitted on December 23, 2003; resubmitted on June 14, 2004; accepted on August 26, 2004.