1 National Perinatal Epidemiology Unit and 2 Department of Obstetrics and Gynaecology, University of Oxford, Oxford, UK
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Abstract |
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Key words: economics/infertility/systematic review
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Introduction |
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Assisted reproductive technology (ART) covers a range of interventions [IVF, gamete intra-Fallopian transfer (GIFT) and ICSI], all of which have the ultimate aim of assisting the infertile patient to become pregnant and deliver a live infant. Predominantly, ART involves the manipulation of gametesboth at a pharmacological level (i.e. ovarian stimulation) and at an in-vitro level, sometimes using micromanipulation (e.g. ICSI). Additionally, surgical interventions may be required to treat damaged pelvic organs.
The use of ART, though often perceived to be discretionary and expensive, has important economic implications. Debate abounds regarding both the allocation of finite resources in this area and the appropriate balance of costs borne by individual patients and society (Redmayne and Klein, 1993; Lieberman and Matson, 1995
; Ledger and Skull, 2000
). Different countries pursue different policies regarding which treatments, if any, are publicly funded. For example, in France, IVF is fully reimbursed by the social security system, whilst in Belgium, Denmark and Norway the state bears most, but not all, of the cost of IVF (Redmayne and Klein, 1993
). In contrast, there are wide variations in local provision of ART via the National Health Service (NHS) in England and Walesthe so-called postcode lottery effect, which results in inequalities in access to NHS-funded ART (Brown, 1999
). According to recent estimates, only one in four IVF cycles performed in the UK is funded by the NHS (Ledger and Skull, 2000
).
Economic appraisal provides a useful approach to informing current debate in this area. Economic studies fall into three broad categories: full economic evaluations; costing studies; and economic benefit studies (Table I). Economic evaluation has been defined as the comparative analysis of alternative courses of action in terms of both their costs and consequences (Drummond et al., 1997
). Application of economic evaluation to ART may inform decision making at a variety of levels. At the national level, it may inform policy makers (such as the Department of Health and NHS); at the level of the individual clinic, it may inform clinicians or managers with budgetary responsibilities; and at the individual clinician and/or patient level, it may assist with the clinical decision-making process.
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Materials and methods |
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An initial search strategy was developed by the research team and tested extensively on Medline. The search terms (available from the authors) were then applied (with small modifications) to all electronic databases. The reference lists of all papers identified by the searches were reviewed to identify relevant additional studies. Studies were included in the literature search if they were published between January 1990 and December 2000; if they had been conducted in a developed country; if the paper was in English or French (for pragmatic reasons); and if the focus was human research. In order to keep apace of rapidly changing technology in the field of ART, an additional Medline search was conducted for the time period January 2001 to March 2001.
Categorization and assessment of studies
Each study was categorized independently by two of the investigating team on the basis of its title, medical subject heading (MeSH) and, where available, its abstract. The following initial criteria were used to determine the relevance of each study to the systematic review:
Studies in categories (A), (B) and (C) were considered relevant to this systematic review and were obtained from local and national libraries. A decision was made to sample 20% of the studies categorized as (D). If 20% of this subset had been considered relevant to the aims of this review, then the remainder would have been obtained. One of the investigators (L.D.) upgraded any (D) paper to (D*) if it warranted additional review. All (D*) papers were obtained for secondary review; (E) and (F) papers were excluded from the review.
All retrieved studies were reviewed in full by two reviewers (one of whom was a health economist) and independently allocated to one of the following categories:
At each stage, disagreements over the categorization of studies were resolved by consensus. All studies finally categorized as economic evaluations, cost studies, or economic benefit studies were included in the systematic review, i.e. studies finally classified as (A)1, (A)2, (A)3, (B)1, (B)2, (B)3, (C)1, (C)2 or (C)3. All other studies were excluded from further review.
The methodological robustness of the selected studies was assessed using guidelines developed by a group of leading health economists and published by the British Medical Journal (Drummond and Jefferson, 1996). The study design, data collection methods, and analysis and interpretation of results were independently assessed by at least two reviewers. This was done using the complete checklist of 35 items contained within these guidelines for any study categorized as an economic evaluation; an abbreviated checklist of 17 items for any study categorized as a cost study; and a four-item checklist (Olsen and Smith, 2001
) for any study categorized as an economic benefit study (all checklists are available from the authors). In addition, all studies finally classified as either economic evaluations or cost studies were assessed using a subset of four criteria considered by the authors to be of critical importance. Disagreements as to whether the studies met the requirements of the guidelines were resolved by discussion.
All cost data contained within the economic evaluations and cost studies were converted into UK pounds sterling using Purchasing Power Parities supplied by the Organisation for Economic Co-operation and Development (OECD, 2002). Once converted to UK pounds, the cost data were inflated to 1999/2000 prices using the NHS Hospital and Community Health Services Pay and Prices Inflation Index. Substantial methodological variations between the studies prevented a pooling of economic data akin to meta-analyses performed in the clinical literature. Therefore, the results of the studies are presented and discussed in a qualitative manner for each area of ART.
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Results |
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In the final review there were 30 studies that were finally classified as economic evaluations, 22 as cost studies and five as economic benefit studies (reported in seven papers). Further details of the stages of the review are shown in Figure 1.
Methodological limitations of included studies
A number of methodological issues were identified by the guidelines used to assess each economic study (Drummond and Jefferson, 1996). A key limitation of the economic evaluations and cost studies was the failure to provide detailed and disaggregated information on reported costs. Additionally, 19 of the 30 full economic evaluations (Goeree et al., 1992
; Peterson et al., 1994
; Daya et al., 1995
; Granberg et al., 1995
; Khare et al., 1995
; Trad et al., 1995
; Van Voorhis et al., 1995
, 1997
, 2001
; Goldfarb et al., 1996
; Kolettis and Thomas, 1997
; Pavlovich and Schlegel, 1997
; Schlegel, 1997
; Donovan et al., 1998
; Silva et al., 1998
; Fridstrom et al., 1999
; Karande et al., 1999
; Mantovani et al., 1999
; Deck and Berger, 2000
) and 12 of the 22 costing studies (Callahan et al., 1993
; Dewire et al., 1994
; Neumann et al., 1994
; Collins et al., 1995
, 1997
; Rabin et al., 1996
; Hidlebaugh and OMara, 1997
; Ficarra et al., 1998
; Ezeh et al., 1999
; Stovall et al., 1999
; Strawn et al., 2000
; Blackwell et al., 2001
) cite charges or a combination of costs and charges for ART services rather than actual costs. The remaining studies used alternative approaches based on cost accounting methods, incorporating detailed information about individual patient resource utilization or by allocating total costs by organizational workload. Finally, four of the 59 studies used primary cost data (Liao et al., 1997
; Zayed et al., 1997
; Goverde et al., 2000
; Suchartwatnachai et al., 2000
), while four used a combination of primary and secondary cost data (Goeree et al., 1992
; Peskin et al., 1996
; Rabin et al., 1996
; Granberg et al., 1998
).
The majority of studies had a short-term perspective, and long-term costs and benefits were not collected. Discounting was therefore not necessary. This is a process used by economists to weight current resources more highly than future resources. However, only one of the 18 full economic evaluations (Mol et al., 2001) and none of the six cost studies that included costs associated with future care discounted future costs. The failure to discount future costs results in an overestimation of the costs that may accrue as a result of ART interventions. The results of these studies must therefore be viewed with a measure of caution.
Sensitivity analysis is an approach used by health economists to explore the robustness of an economic appraisal and investigate the effects of uncertainty (Briggs et al., 1994). It was applied in 11 of 30 economic evaluations with varying degrees of completeness (Neumann et al., 1994
; Rabin et al., 1996
; Schlegel, 1997
; Wolner-Hanssen and Rydhstroem, 1998
; Mantovani et al., 1999
; Philips et al., 2000
; Suchartwatnachai et al., 2000
; Sykes et al., 2000
; Van Loon et al., 2000
; Mol et al., 2001
; Van Voorhis et al., 2001
). Nine of the studies stated the choice of variables used in the sensitivity analysis (Schlegel, 1997
; Wolner-Hanssen and Rydhstroem, 1998
; Mantovani et al., 1999
; Philips et al., 2000
; Suchartwatnachai et al., 2000
; Sykes et al., 2000
; Van Loon et al., 2000
; Mol et al., 2001
; Van Voorhis et al., 2001
), while three explicitly stated the type of sensitivity analysis performed (Mantovani et al., 1999
; Sykes et al., 2000
; Van Loon et al., 2000
).
The full economic evaluations included in the review met an average of 60% (range 3989%) of applicable items on the British Medical Journal checklist used to assess methodological robustness. The included cost studies met an average of 56.3% (range 2578%) of applicable items on the abbreviated checklist. There was no evidence that the methodological robustness of either the economic evaluations or cost studies varied by date of publication. The subsequent discussion of the study results should only be considered in light of the above methodological issues.
Results of reported studies
The results of the 57 studies included in the review are summarized in three tables according to method: economic evaluation (Table II), costing (Table III
) and economic benefit studies (Table IV
).
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Cost-effectiveness of IVF
Comparison between different populations: Two studies compared IVF treatment costs between clinically diverse patient populations (Trad et al., 1995; Suchartwatnachai et al., 2000
). Trad et al., using costs from Neumann et al.(1994)
, estimated the cost of a successful pregnancy for women aged <33 years with no male-factor infertility at £17 102, compared with £31 923 in women aged >40 years. Suchartwatnachai et al.(2000)
excluded indirect and neonatal costs but nevertheless came to the same conclusion, that the estimated cost per delivery in women aged
38 years ~3.6 times higher than for women <38 years (see Table II
).
Natural versus stimulated IVF cycles: Improvements in oocyte culture technique, sperm preparation, oocyte retrieval method, and ovarian stimulation regimens have increased pregnancy rates resulting from IVF (CDC, 1998 CDC, 1999 CDC, 2000 CDC, 2001;HFEA, 2001). However, because ovarian stimulation is expensive and not without risk, economic evaluations have been conducted to re-evaluate natural versus stimulated cycle IVF. Daya et al.(1995)
acknowledged the relatively low success rates of natural cycle IVF (4.6% pregnancy rate and 3.8% live birth rate per cycle). However, the lower costs used in their analysis make natural cycle IVF more cost-effective than stimulated cycles with costs per live birth of ~£13000 and £26000 respectively (see Table II
). Nargund et al.(2001)
also concluded, from a selected favourable population, that natural cycles offer a cost-effective alternative to stimulated cycles, calculating natural cycle IVF costs to be ~23% of the cost of a stimulated cycle. Nargund et al.(2001)
reported higher success rates than Daya et al.(1995)
of 12.7% pregnancy per cycle and 8.8% live birth per cycle. Both these studies compared their own clinical data with data from the early 1990s that related to different populations and may have also included other costs. For example, it is not clear whether staff costs (including out of hours costs) and laboratory costs were included in costs of natural cycle IVF.
The lack of control over spontaneous ovulation during natural cycle IVF results in a greater intensity of ultrasonic and endocrine monitoring. A significant proportion of this may occur outside normal working hours, potentially resulting in higher staff costs. Add to this the cost of additional time off work for the couple undergoing multiple natural cycles (due to the significantly lower success rate) compared with stimulated cycles, and the economic benefits of natural cycle IVF may well be lost.
IVF with cryopreservation of embryos: Van Voorhis et al.(1995) evaluated the efficacy and cost-effectiveness of embryo cryopreservation compared with other assisted reproductive techniques (Van Voorhis et al., 1995
). In a retrospective review of 1000 oocyte retrievals at the University of Iowa in 1992, these authors found that the transfer of cryopreserved embryos increased the ongoing pregnancy rate per oocyte retrieval by 6.6%, and was cost-effective compared with other ARTs. The cost per delivery for cryopreserved ETs was between 25% and 45% that of fresh cycles. It should be noted, however, that some obstetric and all neonatal costs were excluded.
Other IVF considerations: Various other studies have examined the effects of delayed IVF treatment versus standard timing (Goeree et al., 1992), minimal precycle testing and ongoing monitoring (Strawn et al., 2000
), shared oocytes (Peskin et al., 1996
) and recombinant versus urinary FSH (Mantovani et al., 1999
; Sykes et al., 2000
; van Loon et al., 2000
). These are included in Table II
but, for brevity, are not discussed here.
Cost-effectiveness of IVF versus other ART techniques
IVF versus ovulation induction: Karande et al.(1999) conducted a prospective, randomized controlled trial comparing the outcome and cost of a traditional treatment algorithm (ovarian stimulation with clomiphene citrate and gonadotrophins followed by IVF) with IVF as the primary treatment for women with newly diagnosed infertility (Karande et al., 1999
). For the group undergoing standard infertility treatment, pregnancy rates were found to be higher, and costs per couple were not statistically different. Whereas cost differences between the groups diminished over time, pregnancy rates remained the same. Costs were based on charges and did not include the costs associated with maternity or neonatal care. Moreover, a higher proportion of women dropped out of the early IVF group compared with the standard treatment group (41 versus 28%) and the final numbers were small (27 and 36 women respectively).
For women with clomiphene-resistant polycystic ovarian syndrome (PCOS), Fridstrom et al.(1999) compared treatment outcome and costs of ovulation induction cycles with those of IVF. More pregnancies per completed cycle were noted in the IVF group than in the ovulation induction group. The cost per pregnancy resulting from ovulation induction was about twice that of the IVF group. The cost per term pregnancy including delivery was 1.6 times higher in the ovulation induction group, indicating that for this group of women with clomiphene-resistant PCOS, IVF was a cost-effective treatment. The number of women in this study was small, and neonatal costs were not included.
IVF versus intrauterine insemination (IUI): A number of economic evaluations has been performed which focuses on the cost-effectiveness of IVF when compared with IUI (Peterson et al., 1994; Zayed et al., 1997
; Goverde et al., 2000
; Van Voorhis et al., 2001
). While population groups differed, all four studies demonstrated the cost-effectiveness of both stimulated and unstimulated IUI when compared with IVF (see Table II
). For example, Peterson et al.(1994)
conducted a cost-effectiveness analysis with a three-way comparison: IVF versus hMG + IUI versus no therapy. These authors found that one to four cycles of hMG + IUI was just as effective as one cycle of IVF in achieving pregnancy, and IVF was more expensive. Both IVF and hMG + IUI were more effective than no therapy. Again, small numbers and a selected favourable population require a cautious interpretation.
IVF versus tubal surgery in women: Three studies (Khare et al., 1995; Copperman et al., 1996
; Mol et al., 2001
) compared the costs of IVF with other treatments when a diagnosis of tubal infertility was present. Khare et al.(1995)
modelled the cost-effectiveness of six clinical pathways in the diagnosis and treatment of tubal factor infertility resulting from hydrosalpinges and pelvic adhesions. The authors found that the most cost-effective approach (£14128 per pregnancy) was diagnosis and treatment of adhesions at laparoscopy with no previous screening. The most cost-effective approach for blocked tubes (£19913 per pregnancy) was to begin with a hysterosalpingogram (HSG). All pathways for adhesions and any screening pathway using HSG for hydrosalpinges were more cost-effective than IVF.
Mol et al.(2001) modelled 13 separate pathways to compare costs and effectiveness of various strategies in the work-up of subfertile couples suspected of having tubal pathology. The most cost-effective strategies used chlamydia antibody testing or HSG to decide when laparoscopy should be performed, either immediately or postponed for 1 year if the woman was still not pregnant. The authors suggested that the diagnostic work-up to detect tubal pathology in subfertile couples should start with chlamydia antibody testing in couples with relatively good fertility prospects, and immediate HSG in couples with relatively poor fertility prospects.
Copperman et al.(1996) conducted a primary costing study of two treatment modalities for infertility caused by tubal disease under two reimbursement models (Copperman et al., 1996
). These authors demonstrated success rates (defined as ongoing pregnancy surpassing 20 weeks gestation) of 25% for IVF and 19.3% for tubal surgery, and costs per ongoing pregnancy of £18 131 and £18 601 for IVF and tubal surgery respectively. This success rate for tubal surgery was higher than in much of the literature, but patient populations may not be comparable.
Donor oocyte IVF versus donor oocyte GIFT: In women 40 years and with good ovarian reserve, donor oocyte GIFT was found to be more cost-effective than donor oocyte IVF (Silva et al., 1998
). The mean cost per delivery resulting from donor oocyte GIFT was estimated from local data at £17311. This was compared with data previously reported for donor oocyte IVF of £22300 (Legro et al., 1997
), and to the 1994 Society for Assisted Reproductive Technology (SART) data demonstrating a cost per delivery of between £17562 and £21953 for anonymous donor oocyte IVF (SART, 1996). This study was limited by the small number of women who had donor oocyte GIFT (22 women resulting in six deliveries).
ICSI versus donor insemination: Granberg et al.(1996), who performed a cost-effectiveness analysis in 19931994 comparing ICSI and donor insemination, found the costs per delivery to be greater for ICSI than for donor insemination (Granberg et al., 1996
). However, the authors stated that, given an increase of 34% in the cost-effectiveness of ICSI from 1993 to 1994, this procedure has the potential to become cost-effective when compared with other ARTs. Additionally, ICSI has the advantage of resulting in children who are genetically related to the fathera benefit that has not been captured in this cost-effectiveness analysis.
ICSI versus surgical treatment of varicocele: The development of ICSI has afforded men with severe sperm defects with an alternative to the treatment of varicocele. Schlegel (1997) conducted a modelling study using effectiveness data from controlled trials (Schlegel, 1997
). High success rates of varicocelectomy made this the more cost-effective option. However, the length of follow-up was not stated and the high success rates quoted may not be generalizable. Furthermore, surgical treatment may be necessary in some patients to relieve pain.
ICSI versus vasectomy reversal: Four studies have been conducted to address the issue of post-vasectomy infertility (Kolettis and Thomas, 1997; Pavlovich and Schlegel, 1997
; Donovan et al., 1998
; Deck and Berger, 2000
). All four studies found that vasectomy reversal was more cost-effective than ICSI. In these studies the delivery rate following vasectomy reversal ranged from 17% (female partners aged >37 years) to 47% in more favourable populations, with costs ranging from £10454 (Donovan et al., 1998
) to £19306 (Deck and Berger, 2000
) per delivery. For ICSI, the delivery rate ranged from 8% (female partners aged >37 years) to 56%, with costs ranging from £26026 (Kolettis and Thomas, 1997
) to £70372 (Deck and Berger, 2000
) per delivery. Apart from the study by Pavlovich and Schlegel (1997)
(which included 710 cycles, but the number of was subjects not stated), these studies had small numbers of subjects ranging from 27 (Donovan et al., 1998
) to 55 men (Kolettis and Thomas, 1997
).
Multiple comparisons: Philips et al.(2000) developed a series of decisionanalytical models to reflect current diagnostic and treatment pathways for the five main causes of infertility (Philips et al., 2000
). Results of the modelling study suggested that for both tubal factors and endometriosis, IVF is the most cost-effective treatment option for severe disease, with surgery the most cost-effective in the case of mild or moderate disease. The authors suggested that ovulatory factors should be treated medically, with the addition of laparoscopic ovarian diathermy in the presence of PCOS. For other causes, stimulated IUI (unexplained and moderate male factor) and stimulated donor IUI (severe male) were considered cost-effective.
Complications of ART
Impact of multiple pregnancies: The increased incidence of multiple pregnancies and low birth weight due to ART generates increased demands on antenatal and neonatal services, long-term disability services, along with family resources, and this results in important economic implications.
Three studies (Liao et al., 1997; Wolner-Hanssen and Rydhstroem, 1998
; Miller et al., 2000
) have specifically examined the costs of these practices. Liao et al.(1997)
compared neonatal outcomes in IVF programmes in Glasgow, Scotland before (1990) and after (1993) a policy change of transferring an average of two embryos had been implemented (Liao et al., 1997
). The policy change resulted in slightly lower clinical pregnancy and live birth rates, and a significant reduction in the rate of multiple pregnancy, preterm birth, and low birth weight babies in the 1993 group. The cost of neonatal intensive care in 1993 for babies born following IVF was about nine times lower than that in 1990. While the authors did not include indirect costs and wider societal costs, it may be assumed that these costs would increase in proportion to the number of multiple births. The study demonstrated that a policy of transferring two embryos to women in an IVF programme results in improved health for the women and their resulting children, decreased costs to the NHS, although a slight decrease in the live birth rate was observed.
In the UK, it is now recommended that only two embryos are transferred following IVF except in exceptional circumstances (Royal College of Obstetricians and Gynaecologists, 2001; Human Fertilisation and Embryology Authority, 2002
). It is, therefore, not surprising that the rate of twin pregnancy remains high. The routine transfer of one rather than two embryos would be expected to decrease the rate of twin pregnancies (and associated costs) at the cost of a lower live birth rate. Wolner-Hanssen and Rydhstroem (1998)
compared actual (for two-embryo transfers) and hypothetical (for one-embryo transfers) take-home baby rates, twin pregnancies rates, and costs of sick leave and hospitalization during pregnancy, costs of deliveries, neonatal intensive care, and handicap care following transfer of one or two embryos (Wolner-Hanssen and Rydhstroem, 1998
). These authors demonstrated that even when additional IVF cycles may be needed to achieve similar take-home baby rates after transfer of one compared with two embryos, the lower twin pregnancy rate of the former approach caused it to be more cost-effective than the latter. The study was limited, however, as the actual costs of single embryo transfer were not available to the authors.
Another approach taken to decrease the number of higher-order multiple births is multifetal pregnancy reduction. To address this issue, Miller et al.(2000) examined the birth outcomes and costs averted as a result of multifetal pregnancy reduction programme at one US hospital between 1986 and 1997 (Miller et al., 2000
). These authors demonstrated that rates of preterm delivery in multifetal pregnancies reduced to triplets and singletons were similar to those for unreduced triplets and singletons. The preterm delivery rate for reduced twins was lower than that for unreduced twins. The total estimated neonatal intensive care costs averted at that hospital over 11 years was £20.3 million, in contrast to the cost of £947 856 associated with the multifetal pregnancy reduction programme. The estimated hospitalization costs averted amounted to more than £19 million, or £42 654 per reduced pregnancy. This review did not find any studies relating to the intangible costs of the anguish to parents faced with the choice of pregnancy reduction or continuing with a high-order multiple pregnancy.
While higher-order multiples occur as a result of multiple embryo transfer following IVF, many multiples also result from drug-stimulated ovulation. No health economic papers were found that examined this factor, however.
Economic benefit studies
Current economic evaluations of ARTs in generaland of IVF specificallyare criticised for assuming that the only factor of importance to users is whether they leave the service with a child (Ryan, 1994). Such an approach ignores outcomes beyond a narrow medical definition of success, and the benefits that might accrue from the actual process of treatment (Ryan and Donaldson, 1996
).
Several authors have used the willingness to pay (WTP) technique to address these concerns and have attempted to value both health and non-health benefits of IVF (Neumann and Johannesson, 1994; Granberg et al., 1995
; Ryan, 1994
, 1996
, 1997
, 1998
). The respondents in these studies were generally couples receiving IVF or other ART. In the USA, a study of potential childbearers (Neumann and Johannesson, 1994
) found that the WTP to have a child ranged from £132978 to £1.3 million, clearly exceeding most published studies on actual costs. In Sweden, Granberg et al.(1995)
found that the range of WTP for a child was wide, from £0 to £30000, and 55% of the couples were willing to pay £12000 or more. In an Australian study, Ryan (1994
, 1995)
demonstrated an average WTP for IVF/GIFT services of £1399 per attempt, with a range of £237 to £11 167. Actual government expenditure per IVF cycle was £1204. A similar study by Ryan in Scotland (1997) found that a mean WTP for IVF of £5101, with a government expenditure of £2700 per cycle.
The majority of these benefit studies suffered from poor response rates. WTP suffers from the confounding influence of ability to pay and the fact that many of the respondents had already paid for infertility treatment. In addition, some respondents were, understandably, not willing to put a price on a child. A small number of studies used conjoint analysis in which respondents were asked to choose between two options with various characteristics. The relative crudeness of the attributes (e.g. attitudes of staff as good or bad) makes interpretation difficult. A further problem is the difficulty of including dominant preferences in the analysis. Dominant preference occurs when a respondent always chooses in favour one attribute, such as the highest probability of pregnancy, even when all other factors weigh against that choice. Usually, such respondents are excluded from the analysis, although they may be reported separately. Nevertheless, these alternative techniques of benefit measurement have considerable potential to elucidate the factors of importance to infertile couples.
Macroeconomic perspectives
The costs of providing infertility services to a population compared with costs for other areas of health care is of interest to the health insurance market. Several American studies calculated total costs associated with the provision of infertility services to inform the decision-making process (Collins et al., 1995; Rabin et al., 1996
; Hidlebaugh and OMara, 1997
; Griffin and Panack, 1998; Stovall et al., 1999
; Blackwell, 2000
; Blackwell et al., 2001
).
For the Massachusetts Health Maintenance Organization (HMO) an average ART cycle cost was estimated at £1.84 per member per annum, comparable with HMO costs for podiatry and nutrition, and far less than for physical therapy, organ transplants or mental health (Hidlebaugh and OMara, 1997). Collins et al.(1995)
concurred, projecting the cost of adding IVF services to a typical employer health plan in 1995 at £1.98 per annum (Collins et al., 1995
). The latter authors also demonstrated benefit costs (the payments made by third-party payers, with all bad debts recycled) and premium costs (charges for premiums to cover the benefit, including health plan administration costs) of £6.19 and £6.95 respectively for a 300% increase in utilization, and £10.31 and £11.60 respectively for a 500% increase.
Additionally, three groups (Griffin and Panack, 1998; Stovall et al., 1999; Blackwell, 2000
) estimated infertility costs in the range of £0.39 to £0.73 per member per month (£1.31 per contract month in one study), and infertility services to consume between 0.41% and 0.79% of total health care costs. It is important to note that neither indirect costs nor neonatal costs were included in these studies, and therefore the societal costs of providing infertility services were underestimated.
Rabin et al.(1996), by using financial modelling in a managed-care setting, determined break-even capitation rates to evaluate the cost impact of fertility care decisions. After determining an average cost per pregnancy of £5016 to £15757, these authors found that as utilization of infertility services increased, the cost reductions no longer existed to offset increasing break-even capitation rates.
One Canadian study (Collins et al., 1995) estimated the direct cost of infertility management; the annual cost of diagnosis and treatment was estimated at £1651 per couple, with a 26% live birth rate. The total annual cost of infertility management in Canada, approximately £247 million, would be 0.6% of the annual cost of health care.
In summary, it is important to note that although calculations for infertility costs need to include the costs for assisted reproduction procedures, the majority of couples who present for infertility care do not ultimately undergo assisted reproduction, even if an infertility policy includes cover for IVF treatment (Blackwell et al., 2001).
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Discussion |
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Key findings
The range of infertility diagnoses, population groups and ART interventions accepted for review in this study was considerable, and the variation in methods precluded quantitative analysis. However, consistent results were found in several categories, and are discussed below:
While the majority of studies accepted for this systematic review used multiple definitions of a successful outcome, including clinical pregnancy, delivery, live birth and take-home baby rates, all assumed the only factor critical to service users was whether they left with a baby. It is, presumably, this that compels individuals to seek treatment for infertility. However, to assess the costs and benefits of ART accurately, all factors that may influence utility, both positive and negative, should be considered. Five studies in this systematic review used the WTP' technique or conjoint analysis to assess (dis)benefits of ART procedures, primarily IVF. It is interesting to note that a positive association existed between WTP and respondent income level, and that factors independent of a live birth were important to couples seeking treatment. In one study, for example, attitudes of staff were more important than a 5% increase in success rates (Ryan, 1995, 1999
). Future studies would be improved by a more inclusive accounting of user benefits from infertility services.
Limitations of the included studies
The majority of included studies met between 50 and 80% of the quality requirements. For both full economic evaluations and costing studies, it is worth noting that ~75% of the studies did not include indirect costs (costs arising from lost productivity). Measuring and valuing these wider societal costs is particularly appropriate because couples seeking infertility treatment may be highly productive in the workforce, and the potential productivity loss to society may be great. When indirect costs were included, the studies generally accounted for lost productivity arising from treatment procedures alone and failed to include those arising from ART complications, especially multiple births.
Nearly half of the economic studies reviewed were conducted in the USA where charges are often used as proxies for costs and where the unique organization of health care services may make it difficult to generalize the results to other industrialized countries. Publication bias, in which studies reporting successful outcomes are more likely to be published than reports of unsuccessful interventions, also has implications for generalizability.
Less than half of the included studies included sensitivity analysis. The failure to analyse the uncertainty surrounding key economic parameters leaves the reader unable to judge the degree to which the conclusions of these studies are meaningful and robust (Briggs et al., 1994). However, reviews of economic evaluations in other areas of medicine have revealed similar levels of quality (Petrou et al., 2000
; Whitten et al., 2002
).
When interpreting economic evaluations of ART, inherent difficulties exist arising from the variability in outcome measures used, spontaneous or background pregnancy rates, and patient selection. ART effectiveness ratesreferred to as success ratesmay appear either optimistic or dismal depending on the numerators and denominators used in the analysis. To allow for comparisons, authors must clearly define the numerators and denominators of success rates. The majority of studies included in this systematic review relied on one or more of the following reproductive outcomes: biochemical pregnancy, clinical pregnancy, ongoing pregnancy, live birth rate, maternity rate and take-home baby rate. Direct comparisons are made problematic with varying definitions. For example, IVF consists of a series of stages with drop-outs possible. Success rates may be given per started cycle or per completed cycle. Using embryo transfer cycles as the denominator will appear to increase the success rate, while using all started treatments (which use the woman as the denominator) will appear to decrease the rate. Similarly, if clinical pregnancies are used as the measure of success, then spontaneous abortion, ectopic pregnancy, stillbirth and preterm birth are all considered successes. Some studies used number of live births, or take-home babies, as an outcome measure (e.g. Stern et al., 1995), but this overstates the success rate because multiple births are counted as multiple successes unless methods are used to take account of this.
One of the main problems with ART to date remains the high incidence of multiple pregnancies. These carry a higher risk of maternal and perinatal mortality and morbidity, especially as a result of preterm delivery. While several studies did include the costs associated with multiple births, the viewpoint of many of the studies was limited to that of the provider of health care, was generally short-term, and rarely went beyond the immediate postnatal period. Long-term consequences require evaluation from an economic perspective, and include, but are not limited to: costs associated with disability; day care services and respite care; adaptations to an infants home; and incremental expenditures on health and non-health goods as a result of their impaired health status. In addition, none of the included studies estimated costs associated with the intangible psychological consequences associated with multiple birth, especially higher-order multiples. These include depression, marital discord and increased stress levels and warrant inclusion in future economic studies (Henderson and Petrou, 1999).
This systematic review has shown that, despite significant methodological limitations, consistent findings have been reported in several areas. It has also revealed gaps in the literature. The main area where further research is required is in the long-term costs associated with prematurity, and whether costs and consequences are different for naturally occurring multiples compared with ART multiples.
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* The views expressed in this paper are those of the authors and do not necessarily reflect those of the Department of Health.
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Submitted on May 13, 2002; accepted on August 9, 2002.