Special Article
The Cost of a Successful Delivery with in Vitro Fertilization
N Engl J Med 1994; 331:239-243July 28, 1994
- Abstract
Background
The use of in vitro fertilization has engendered considerable debate about who should have the procedure, whether health insurance should cover the cost, and if so, to what extent. We investigated the cost of a successful delivery with in vitro fertilization.
Methods
We calculated the cost per successful delivery with in vitro fertilization (defined as at least one live birth) for a general population of couples undergoing in vitro fertilization and for two subgroups: couples with a diagnosis of tubal disease (who have a better chance of success), and couples in which the woman is over the age of 40 years and the man has a low sperm count (who have a lower chance of success). Information on charges per cycle of in vitro fertilization was obtained from six facilities across the country; delivery rates with this procedure were estimated from the literature.
Results
On average, the cost incurred per successful delivery with in vitro fertilization increases from $66,667 for the first cycle of in vitro fertilization to $114,286 by the sixth cycle. The cost increases because with each cycle in which fertilization fails, the probability that a subsequent effort will be successful declines. Sensitivity analyses indicated that the cost per delivery ranges from $44,000 to $211,940. For couples with a better chance of successful in vitro fertilization (i.e., those with a diagnosis of tubal disease), it costs $50,000 per delivery for the first cycle and $72,727 for the sixth. For couples in which the woman is older and there is a diagnosis of male-factor infertility, the cost rises from $160,000 for the first cycle to $800,000 for the sixth.
Conclusions
The debate about insurance coverage for in vitro fertilization must take into account ethical judgments and social values. But analyses of costs and cost effectiveness help elucidate the economic implications of using in vitro fertilization and thus inform the policy discussion.
Media in This Article
Table 1
Cost Assumptions for the Base Case of in Vitro Fertilization.Table 2
Rate of Successful in Vitro Fertilization per Cycle in Selected Studies.Article Activity
- Article
The use of in vitro fertilization has engendered considerable debate about who should receive treatment, whether health insurance should cover the costs, and if so, to what extent. The debate has been fueled by conflicting and sometimes misleading claims. Conflicting statistics on in vitro fertilization reflect differences in how the rate of success associated with the procedure is defined and measured1. Moreover, success rates differ widely among programs2. When data on costs have been presented, they have sometimes been used inappropriately. For example, one group has lobbied for coverage of in vitro fertilization on the grounds that it represents an exceedingly small fraction of health care costs, accounting for only 0.03 percent of the total3.
The key question, however, is not how much we spend on in vitro fertilization but what is gained from the investment. In other words, what is the cost of a successful outcome of in vitro fertilization? Measurement of this cost was the goal of our study. In particular, we considered the cost incurred per cycle of in vitro fertilization and how it varied according to the number of cycles in which the procedure was used. We calculated overall cost estimates as well as estimates for two subgroups defined by the woman's age and the cause of infertility. Because of the uncertainty surrounding these estimates, we used sensitivity analyses to determine how the results would change when we used high-range and low-range assumptions about costs.
Methods
At the outset, we defined three terms: a cycle of in vitro fertilization, delivery after in vitro fertilization, and the marginal cost per delivery for each successive cycle of in vitro fertilization. A complete cycle of in vitro fertilization involves four steps: first, a woman takes fertility drugs intended to stimulate her eggs to develop; second, these eggs are retrieved from the woman's ovaries by an outpatient transcervical procedure; third, the eggs are fertilized in a laboratory with her husband's or partner's sperm; finally, the fertilized eggs are reimplanted in her uterus for completion of the pregnancy. Couples often proceed through several cycles of in vitro fertilization before an infant is conceived and carried to term or the effort is abandoned.
We defined delivery after in vitro fertilization as the birth of at least one live baby as a result of a cycle of in vitro fertilization. We focused on deliveries instead of births in order to avoid the potential confusion involved in considering multiple births separately. For example, two couples, each having a single baby through in vitro fertilization, should not be treated the same as one couple having twins and the other having no infants at all. We did, however, consider the important implications of the fact that many cycles of in vitro fertilization result in multiple births.
Finally, we defined the marginal cost per delivery for each successive cycle of in vitro fertilization as the cost incurred for a given cycle divided by the probability of achieving a delivery as a result of that cycle.
Cost per Cycle
In estimating the cost of a cycle of in vitro fertilization, we relied on the 1992 listings of charges from published brochures obtained from large in vitro fertilization facilities at six sites in the United States: Brigham and Women's Hospital, Boston; Cornell University Medical Center, New York; Genetics and IVF Institute, Fairfax, Virginia; IVF America, Waltham, Massachusetts; Jones Institute for Reproductive Medicine, Norfolk, Virginia; and the Vanderbilt University Center for Fertility and Reproductive Research, Nashville.
The charge for a single cycle of in vitro fertilization at these centers in 1992 ranged from $7,000 to $11,000, including the costs for initial consultations, laboratory tests, medications, ultrasonography, egg retrieval, gamete culturing, embryo transfer, and physician and nursing services. On the basis of these published charges, we assumed a base case with an average cost of $8,000 per cycle. We used a figure at the low end of the range because we relied on charges that probably overstate the economic costs. Our base case takes into account only the direct costs associated with the procedure, since in general, the measurement of other factors is more uncertain, and their inclusion more controversial among cost analysts. However, in sensitivity analyses we adjusted the cost for the base case to take into account several other factors (Table 1Table 1
Cost Assumptions for the Base Case of in Vitro Fertilization.).In vitro fertilization may involve costs associated with time and complications. Since the time that couples devote to in vitro fertilization could be spent productively in other endeavors, it should be considered a component of economic costs. The cost associated with time varies considerably among couples, from a few hours or days to extended leaves of absence from work in some cases4. In the sensitivity analyses we estimate that time away from work adds $880 to the cost of an average cycle, assuming that both partners miss one week of work per cycle and we value time at $11 per hour (average hourly earnings in 1992): 2 × (5 days/cycle) × ($11/hour) × (8 hours/day) = $880 per cycle.
Complications associated with the procedure may also add to its cost. Maternal risks from in vitro fertilization include ovarian hyperstimulation syndrome, bleeding, infection, cysts, anesthesia-related complications, and possibly an increased risk of thromboembolism, stroke, myocardial infarction, and ovarian cancer5-13. In general, as compared with in vivo fertilization, in vitro fertilization is associated with higher rates of difficult pregnancies and deliveries13-16.
The incidence of adverse outcomes is higher among babies born after in vitro fertilization, though the difference appears to be attributable to the higher incidence of multiple births and not to the procedure itself6,14,17. It is well documented that in vitro fertilization, because of the methods of ovarian stimulation used and the practice of implanting multiple embryos in a woman's uterus to improve the chance of pregnancy, increases the incidence of multiple births18,19. Twins naturally occur in about 7 deliveries per 1000, and triplets, quadruplets, and quintuplets occur in 1 in 9520, 1 in 600,000, and 1 in 15,000,000, respectively15,20. On the other hand, some 20 to 25 percent of pregnancies with in vitro fertilization result in multiple births, including triplets and higher-order multiple births in 2 to 3 percent of such pregnancies21.
Multiple births are associated with higher rates of neonatal complications and stays in neonatal intensive care units than are births of singleton infants,14,16,22-24 as well as higher costs after discharge due to chronic health problems and developmental disabilities23,25. The average hospital charge for an infant in the neonatal intensive care unit ranges from $10,000 to $100,000 (in 1992 dollars), depending on the birth-weight category,22,23,26 and lifetime costs can add another $100,000 or more25.
Most reports have noted that the incidence of serious maternal complications is low -- 0.1 to 0.2 percent of all cases6. On the basis of a comprehensive review of the literature, Schenker and Ezra estimated that complications -- major and minor -- occur in 3 to 6 percent of cases13. If we assume that serious maternal complications occur in 0.2 percent of cases and cost $20,000 per case (for a hospital stay of several weeks), and minor complications occur in 5 percent of cases and cost $2,500 per case (for approximately a four-day hospital stay), the additional cost is (0.002 × $20,000) + (0.05 × $2,500) = $165. We further assume that 20 percent (roughly the proportion of multiple births) of pregnancies resulting from in vitro fertilization are problematic, requiring an average of four extra weeks away from work. Again, if time is valued at $11 per hour, this adds $11/hour × 8 hours × 5 days/week × 4 weeks = $1,760. But since only about 20 percent of initiated cycles result in a pregnancy (see below), this adds only another 0.20 × $1,760 = $352.
If multiple births occur in 3 percent of cases and cost as much as $200,000 per case ($66,667 per baby), the additional cost is $6,000 per case, but since the probability of a delivery is only 12 percent to begin with (see below), the added cost is $720 per case. If twins are delivered in 20 percent of cases and the cost of delivery is $20,000 per case, the additional cost is 0.20 × $20,000 × 0.12 = $480 per case. Adding these amounts together, we assume that the additional cost of all complications is $165 + $352 + $720 + $480 = $1,717 per case. These are probably generous assumptions, since a cost per case of this magnitude will occur only in the lowest birth-weight categories.
On the other hand, our base-case cost of $8,000 per cycle may overstate the actual cost for several reasons. First, our assumption of constant marginal costs may be questioned. The first cycle may cost somewhat more than subsequent cycles because of the initial consultation with a social worker and other steps of the workup that are not repeated for subsequent cycles. However, most components of the cost of in vitro fertilization are variable, including the costs of laboratory tests, medications, and physicians' and nurses' time. In sensitivity analyses we assumed that the initial cycle costs $2,000 more than subsequent cycles.
Second, only about 86 percent of cycles in which treatment is initiated result in successful egg retrieval,21 though most of the costs are still incurred, including the cost of medications and ultrasonography and much of the required physician and nursing services. The costs associated with embryo transplantation, however, are averted. If we assume that the cost is 25 percent lower (roughly equivalent to the reduction in charges in the facilities noted above) in the 14 percent of cases with unsuccessful egg retrieval, our estimate is reduced by (0.14 × $2,000) = $280.
Finally, the cost may also be lower because some cycles use embryos that have been cryopreserved from previous cycles. Cycles in which frozen embryos are used may cost less, because the steps of egg retrieval and gamete preparation are bypassed and the frozen embryos are thawed and transferred to the woman's uterus. However, any overall cost reduction is probably small. Frozen embryos are used in only a small fraction of cycles -- about 11 percent in 199021. Also, the process involves additional costs (ranging from $1,500 to $4,000 at the facilities noted above) for storage and thawing. In addition, the use of frozen embryos may result in a lower success rate, so the cost per delivery with frozen embryos may actually be higher27. For these reasons, we have not made a separate adjustment for this factor.
Delivery Rate with in Vitro Fertilization
We estimated the probability of a delivery with in vitro fertilization from reports in the literature. This probability -- which we refer to as the delivery rate with in vitro fertilization -- has a long and somewhat controversial history in the literature, in part because definitions vary among studies. Some studies report pregnancy rates, for example, whereas others report delivery rates; some report the outcome per initiated cycle, whereas others report the outcome per successful retrieval. Studies have generally reported that between 10 and 15 percent of initiated cycles result in at least one live birth5,21,28-32. In general, the rates are higher among couples in which the woman is relatively young or has tubal disease and lower among couples in which the woman is older or there is an indication of a low sperm count, severe endometriosis, or unexplained infertility.
Researchers have disputed whether and, if so, to what extent the probability of a delivery varies with the number of cycles (the cycle rank). This issue lies at the heart of a key question: What does a failed cycle reveal about a couple's ultimate chance of a successful delivery with in vitro fertilization? Put another way, if a couple is told that they have a 15 percent chance of having a baby on the first cycle, what is the revised probability on the second try, if the first one fails? What is the probability on the third attempt, given the failure of the first two?
Table 2Table 2
Rate of Successful in Vitro Fertilization per Cycle in Selected Studies. shows data from five studies on the rate of successful in vitro fertilization according to the cycle rank. Note that the rates in these studies differ because of differences in definitions. Some studies report a constant probability per cycle,33,34 whereas others report that the probability declines with the number of cycles attempted30,32,35. But a declining rate is to be expected in a heterogeneous population, because as Hershlag et al. note, for a randomly chosen woman, failure to achieve a pregnancy in each successive cycle constitutes increasing evidence of an inherently low potential for fertility30. That is, the women with the higher potential for fertility are more likely to become pregnant early, leaving those with a lower potential to continue with subsequent cycles. Thus, we should expect to observe a declining probability of success as the number of cycles increases. The fact that studies do not always bear this out is probably explained by selection bias at the point of entry or between cycles30. In other words, some programs weed out patients with a lower potential for fertility, encouraging only those candidates considered to have a higher potential to pursue additional cycles.In our analyses, we assumed a gradually declining rate of success in all cases. For simplicity, we used round numbers. Our base-case assumption was that the probability declines one percentage point per cycle, from 12 percent on the first cycle to 7 percent on the sixth. We also considered how probabilities vary for two subgroups: couples with a diagnosis of tubal disease and couples in which the woman is 40 years of age or older and there is a diagnosis of male-factor infertility (defined as a sperm concentration of less than 20 million per milliliter or motility below 40 percent)2. Assumptions for these subgroups are based on those reported in the literature32,35.
In the sensitivity analyses, we varied the probabilities by two percentage points in each direction to take into consideration several areas of uncertainty. In general, it is difficult to know the true probability of success per cycle, because after every failed attempt, many couples -- on the order of 50 percent -- discontinue their pursuit of in vitro fertilization30,32,35. All published data on the rate of successful in vitro fertilization according to the cycle rank reflect this bias. But in the hypothetical case of a sample with no dropouts, we would expect an even greater decline in the success rate, because more lower-risk couples would initiate each cycle. Thus, the assumptions used here are probably conservative.
Two other points about success rates are also important. First, among some couples seeking in vitro fertilization, pregnancy occurs without the intervention, either before its inception or after its discontinuation5. Second, since some of the embryos frozen in earlier cycles will ultimately result in live births, the true success rate per retrieval is somewhat higher than that stated above36.
Results
Table 3Table 3
Marginal Cost per Delivery with in Vitro Fertilization for the Base Case and Low- and High-Range Assumptions. shows the marginal cost per cycle of in vitro fertilization. Under the assumptions for the base case, it costs $66,667 per delivery for couples undergoing their first cycle of treatment and rises to $114,286 per delivery for couples attempting their sixth cycle. The marginal cost increases because, with each failed cycle, we revised downward the probability that the next cycle will be successful.Table 3 also shows the results of analyses with low-range (optimistic) and high-range (pessimistic) assumptions for both costs and success rates. Under the low-range assumptions, the marginal cost is $55,143 for the first cycle and $44,000 for the second, rising gradually to $63,556 for the sixth. Under the high-range assumptions, the cost per delivery increases from $105,970 for the first cycle to $211,940 for the sixth.
Table 4Table 4
Marginal Cost per Delivery with in Vitro Fertilization for Couples with Selected Fertility Problems. shows the substantial difference in cost per delivery for two groups of infertile couples. For couples in which the woman has tubal disease, the cost per delivery is $50,000 for the first cycle and $72,727 for the sixth, whereas for couples in which the woman is older and there is male-factor infertility, the cost rises from $160,000 for the first cycle to $800,000 for the sixth.Discussion
In vitro fertilization forces us to confront difficult questions: Who should have access to the procedure? Everyone? Only childless couples? Only couples with a presumably good chance of success? And who should pay for the procedure?
To be sure, some of these questions can be answered not by analyses of costs and outcomes, but only by consideration of ethical judgments and social values. However, our analyses can help elucidate the economic implications of in vitro fertilization and thus inform the debate. Even those who believe that procreation is a fundamental right would not provide unlimited resources for a couple's pursuit of a child. Inevitably, we are forced to confront trade-offs. The results here suggest that, on average, it costs approximately $67,000 to $114,000 per successful delivery with in vitro fertilization. For older couples with more difficult problems of infertility, the cost is approximately $800,000 per delivery.
An implication of these results is that more deliveries will result per dollar expended if we give priority to the couples with the best chance of success -- if, for example, couples in which the woman has tubal disease are allowed more cycles than couples in which the woman is older and there is male-factor infertility.
Of course, efficiency is not the only goal of public policy. Ideally, we would like to know not only the cost per delivery but the associated benefit or value as well. In a community survey, Neumann and Johannesson found that the amount the respondents were willing to pay for a delivery with in vitro fertilization ranged from $170,000 to $1.7 million and depended considerably on how the questions were framed37. In weighing public-policy options, it is important to consider public attitudes. Notwithstanding individual preferences, for example, the public may want to guarantee that every infertile couple has at least some access to in vitro fertilization, instead of simply maximizing the total number of deliveries.
Our analyses did not take into account several factors that will be important to explore in further research. First, our base case was calculated from charges, not economic costs, and we assumed that costs are constant among groups of couples. Second, in vitro fertilization may result in an additional benefit to the extent that it raises the economic productivity of infertile couples who are despondent over not being able to have a child. Third, we did not explore fully the social effects of multiple births.
It is also important to investigate the cost effectiveness of in vitro fertilization as compared with other interventions to correct problems of infertility, such as tubal surgery. Haan, for example, reported that the average cost per ongoing pregnancy for tubal surgery was roughly comparable to the cost per ongoing pregnancy for three attempts at in vitro fertilization38. Finally, it is important to compare the cost of in vitro fertilization with alternative uses of public funds, including current expenditures for costly life-saving technology. Such comparisons will be difficult, since they will require a comparison of the life-years of living persons and the life-years of those not yet born or even conceived.
Those who oppose the inclusion of in vitro fertilization as a health insurance benefit tend to argue that there are more important uses for society's scarce resources. Advocates counter that the benefits outweigh the costs and that treatment for infertility should be regarded in the same way as treatment for other diseases. Over the years, some insurers have covered the procedure, though many have not. Eight states have required private insurers to cover the procedure39. Recently, in vitro fertilization was one of the few procedures explicitly excluded from the standard benefit package in the Clinton administration's health plan40.
In the absence of government intervention, a private market for in vitro fertilization would still exist. The procedure would be available to those who could afford it. How the procedure is treated in the changing U.S. health care system will thus reveal something about Americans' ability to tolerate inequities in access to expensive procedures, even those that make a considerable contribution to the quality of life. As we debate this issue, the least we can do is to improve the discourse over policy by a better understanding of the costs and results involved.
Source Information
From the Project HOPE Center for Health Affairs, Bethesda, Md. (P.J.N.); the Division of General Medicine and Primary Care, Brigham and Women's Hospital and Harvard Medical School, Boston (S.D.G.); and the Department of Health Policy and Management, Harvard School of Public Health, Boston (M.C.W.).
Address reprint requests to Dr. Neumann at the Project HOPE Center for Health Affairs, Suite 600, 7500 Old Georgetown Rd., Bethesda, MD 20814.
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