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
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Abstract |
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Key words: costs/health care/IVF
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Introduction |
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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., 1994). International comparisons of IVF costs are difficult due to variable prices (Mor-Yosef, 1995
; Collins, 2001
), cost calculations and funding policy in different countries. It has been stated, however, that costs are generally underestimated (Mor-Yosef, 1995
), 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, 2001
). In the Nordic countries IVF accounted for 0.080.16% of total health care costs in 1994 (Granberg et al., 1998
). The major contributor to the total costs has been multiple births, especially high-order multiple births (Gissler et al., 1995
; Goldfarb et al., 1996
).
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, 2004).
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., 2002). 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 19901995 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.
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Materials and methods |
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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, 1990). 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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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 027 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, 2003; 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 19961998) 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, 1994
). 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 19961998, 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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Results |
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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 () 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 (
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 2.42.5-fold, neonatal costs 3.77.8-fold and total health care costs 2.73.2-fold for twins compared to singletons (Tables IIIII).
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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 5740 and
12 306 per IVF pregnancythe 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 0.10.2 spontaneous abortions and 0.010.02 ectopic pregnancies. After adding the costs of unsuccessful cycles and 1st trimester pregnancy loss, the costs of IVF neonates were 4.74.8-fold in the singleton comparison and 2.2-fold in the twin comparison (Table IV).
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Discussion |
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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, 2001). The reasonably high number of cycles in Finland (Nygren and Nyboe Andersen, 2002
) 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., 2002b). 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 zygositychorionicity 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., 1991
; Basso and Baird, 2003
).
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., 1994; Goldfarb et al., 1996
). 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., 2004
). 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., 1997
). In ongoing IVF/ICSI pregnancies in our catchment area the twin rate is
7% (Martikainen et al., 2004
) 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 25-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., 1995). 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 (2124 versus 12%) (Koivurova et al., 2002b
).
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, 2002). Seventy-six per cent of Finnish women of childbearing age are daily workers (Hartikainen-Sorri and Sorri, 1989
). 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., 2002b
). 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., 2000
).
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., 2003). 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., 2002
), 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., 1998
).
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.
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Acknowledgements |
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Submitted on December 23, 2003; resubmitted on June 14, 2004; accepted on August 26, 2004.