There are personal economic considerations with infertility treatments. Costs vary significantly for different procedures (i.e. IUI; Intra-Uterine Insemination, IVF; In Vitro Fertilization), even in a given community. Lack of insurance coverage often plays a role with utilization. IVF may not covered by insurance and can cost more than $10,000 per treatment cycle. The outcome is highly dependent upon age and ovarian function, with older patients having a lower chance to get pregnant. New technical advances, especially the ability to biopsy embryos safely and identify chromosome abnormalities via a procedure called Pre-implantation Genetic Screening (PGS) have been shown to improve implantation and pregnancy rates, primarily by eliminating the transfer of embryos that are chromosomally abnormal. The data look promising, but to date large randomized clinical trails have not proved the efficacy for all patient subgroups. From an economic standpoint, it may make sense to consider PGS as a part of IVF treatment as the opportunity cost to the patient is favorable. If doing IVF with PGS ultimately leads to more pregnancies and fewer treatment cycles, it is something to consider as a treatment option. On this page we review some of the economic issues.
Infertility affects about 15% of couples. Unfortunately, only 15 states have some sort of insurance mandate for treatment coverage. Most Americans are self-pay. The cost of these services can be substantial, especially for younger couples in the 25 to 45 year old age group, the primary patient demographic. IVF has the highest pregnancy rate as a treatment, but the total cost nationally per treatment cycle is about $19,000 (Reuters, 9/17/2013). Prices vary considerably and may not correlate with the quality of the program. Many patients may need multiple cycles to ‘take home a baby.’ In theory, any method to improve the pregnancy rates should lead to fewer cycles and less cost. This page will examine the economics of adding PGS to standard IVF as a method to improve the chance to ‘take home a baby’ and the difficult financial choices couples with infertility often make.
Overview of IVF
The 1st IVF baby born was Louise Brown in 1978, conceived with the assistance of Drs. Patrick Steptoe and Bob Edwards. Dr. Edwards received the Nobel Prize in 2010. Millions of patients have had children worldwide as a result of their monumental work. The pregnancy rates have steadily increased over the decades, but still not everyone gets pregnant. Technology has improved embryo culture techniques, cryo-preservation of embryos, and micro-manipulation of embryos. From the early days the effect of the ‘Biological Clock’ has been evident, with the chances of conceiving inversely correlated with age. There are a finite number of eggs in the ovaries with approximately 1,000,000 at birth, 200,000 at the age of 12, and 25,000 at the age of 37. There is a marked decline in pregnancy rates, and corresponding increase in miscarriage rates after the age of 37, which seems to follow this trend. Most miscarriages and IVF failures are due to embryos with aneuploidy (i.e. abnormal numbers of chromosomes, normal being 46, XX and 46 XY, respectively). The ability of the pre-implantation embryo to be biopsied and screened for aneuploidy (i.e. Down’s Syndrome, trisomy 21) shows a remarkable effect with age, and this seems to correlate with the decreased pregnancy rates seen in the older patients (Table 1).
Table 1. Age and Aneuploidy (ref. Natera, Inc) from Pre-Implantation Genetic Screening (PGS). (http://www.natera.com/preimplantation-genetic-screening-providers)
Pre-Implantation Screening (PGS) has evolved as a potential method to evaluate the health of embryos. Biopsy is done on the 5th day of embryonic growth when the embryo consists of the inner cell mass (future baby), blastocoel cavity (fluid filled in center) and the trophectoderm (TE) cells (future placenta cells). The embryo is called a blastocyst at this stage. A laser incorporated into the microscope objective opens up the zona pellucida (shell surrounding the embryo) which allows some TE cells to herniate and be excised for analysis in the DNA laboratory. Figure 1 shows how we do the biopsy in our laboratory. Figure 2 shows an embryo that was biopsied the following day. It is clearly viable as it hatches out of the zona pellucida, but unfortunately was found the have trisomy 7 (47, XX, +7), which means that in spite of being morphologically normal, it would never have resulted in a viable pregnancy and most likely would have been an early pregnancy loss. By not transferring abnormal embryos, the chance of pregnancy goes up significantly, in theory.
Figure 1. Picture of actual embryo biopsy performed in our laboratory
Figure 2. Picture of embryo biopsied in photo above the following day
In Vitro Fertilization accounts for about 2% of all births in the United States. In 2012, there were 165,172 procedures done (SART, Society of Assisted Reproductive Technology Annual Assisted Reproductive Technology Report 2012). These procedures include ‘fresh’ IVF cycles where eggs are obtained and the embryos transferred a few days later into the female, ‘frozen’ or ‘thawed’ IVF cycles where embryos are placed back in the women that produced the eggs, as well as patients that use donor eggs and donor embryos.
The following graphs (Figures 3 and 4, respectively) show the number of ‘Fresh” IVF procedures and Live Birth Rates relative to the age of the patient from SART, 2012. A substantial number of procedures are done in women less than 40 years of age. In 2012, the most recent year that data is available, there were 93,062 procedures done in the US. I have chose to present these, as these are the ‘gateway’ into the medical treatment process. The marked effect of age and aneuploidy is evident below.
Figure 3. Live Birth Rate versus Age (SART, 2012)
Figure 4. Number of ‘fresh’ procedures by age, USA, 2012 (SART)
Our infertility practice in Indianapolis is Family Beginnings, PC. The nature of the practice has changed over the past several years, as we have included significantly more PGS and embryo freezing. Studies have shown that PGS of the embryos improves the pregnancy rates, essentially by removing chromosomally abnormal embryos from the pool to be transferred (i.e. lower denominator). A randomized controlled trial by Scott, et al, (2013) showed clinical pregnancy rates of 84% in patients that had screened embryos versus 67% in patients that did not have embryo screening. It should be noted that this study included only good prognosis patients with an average age of 32 years and undoubtedly good ovarian function, unlike many of the patients that we see in our clinic. Also, these are clinical pregnancy rates (i.e. heart beat seen at 6 weeks) and not delivery rates as noted in CDC data. Delivery rates are lower due to miscarriage. Nonetheless, it makes intuitive sense that if we identify embryos that are chromosomally abnormal we should only transfer normal embryos and the pregnancy rates should be higher and the costs ultimately less.
In order to get some economic sense of PGS and IVF, we will make some assumptions. Using data from the SART (2012) regarding the national pregnancy statistics for women less than 35 years of age, we will estimate the number of patients that ‘take a baby home’ using IVF (40% per cycle) and PGS (84%, Scott et al, 2013) to develop our model for the economic viability of adding PGS to the IVF laboratory armamentarium (Figures 5 and 6, respectively). We have not included ‘frozen’ embryo transfer cycles as not all patients will have enough embryos to cryo-preserve.
Figure 5. Estimated Frequency of Pregnancy with IVF (SART, 2012).
Estimated Delivered Pregnancy and Not Pregnant from 100 Cases < 35 year Old assuming 40 % Delivery Rate (P=Pregnant and Delivered, NP=Not Pregnant).
Figure 6. Cumulative pregnancies for 100 patients undergoing 3 cycles of fresh IVF compared to a single cycle with PGS and FET of normal embryos.
From three fresh IVF cycles, we would expect that 79 % of the patients would take a baby home. The average cost of IVF in the US, including medications is $19, 000 (Reuters, 9/17/2013) , thus 79% of the 100 patients that have a baby will have spent $57,000, and unfortunately the 21 patients that did not conceive will have spent the same amount. The cost of IVF is substantially less in Indiana, and in our practice, in particular. With medications, the total cost is about $11,000 per completed cycle. We have had our infertility practice in Indianapolis since 1997 and we have had an in-office IVF lab since 2001. Hospital based procedures are typically more expensive. We have done a number of things to keep the price down for patients. For instance, Dr. Donahue is certified as a high complexity laboratory director, which is required by regulatory agencies. Because he fulfills this role as well as medical director of the program, we were able to pass the savings on to the patients. 80% of the patients are self-pay, so cost is a major issue. We are very cost conscious as a medical practice.
The total cost of a standard IVF treatment cycle is $10,895 in our clinic. Three cycles would cost $32,685 if no frozen embryo transfer cycles were included.
Proposed Addition of PGS to Standard IVF; Economic Issues
Cost PGS with Subsequent Frozen Embryo Transfer (FET) of Chromosomally Normal Embryos
Total Fresh IVF with Embryo Biopsy, PGS, and FET: $18,815
Economic Analysis for Patients
The Opportunity Cost for the patients is favorable. If one cycle of IVF with PGS costs $18,815 with us, and three cycles costs $32,685 (3 x $10,895) the opportunity cost would be $13,870. This would be even more marked when we consider the national cost for three cycles of $57,000 (3 x $19,000), or $38,185. Three fresh IVF cycles or one with PGS have a cumulative pregnancy rate of 80%. Possibly we should consider PGS more frequently?
Pooled Cycle with PGS Economics
Patients in the 38 through 40 year age group have a particularly difficult time getting pregnant with IVF. The national statistics (CDC, 2012,) show that only 22% have a child from IVF. From the above, it is clear that aneuploidy in the age group averages 50% of embryos that develop to the blastocyst stage that could be transferred. Because of our ability to freeze the fertilized egg well, and the blastocyst stage embryo, some have considered pooling IVF cycles together and only doing one culture and biopsy followed by a FET of normal embryos. Pooling would make sense as a mechanism to get more eggs from a treatment cycle. In a pooled cycle, we stimulate the ovaries to produce as many eggs as possible, retrieve, fertilize the eggs and freeze the fertilized eggs on day 1. We then do another stimulation in a month or so, collect the eggs, fertilize, and thaw the 1st batch, growing all out to day 5 and 6 for eventual biopsy. The normal embryos will eventually be transferred to the patient on a standard FET cycle.
Let’s run through an example in a 38 year old patient with a low chance to get pregnant:
Assume 10 eggs collected, 80% fertilize, 50% develop to the blastocyst stage, and 50% of these are aneuploid. Thus only 2 of 10 would be normal. This is consistent with the 22% delivery rate seen in this population. If we obtained 10 eggs, fertilized them and froze them the next day, we could come back a month later, do another stimulation, get 10 eggs, and then thaw the 10 eggs from the 1st cycle, and pool them together for culture. We would expect 16 of the pooled eggs to be fertilized, 8 grow to the blastocyst stage and 4 be chromosomally normal. Presumably they should have a better chance to get pregnant having 4 normal embryos. There are at present no controlled economic studies on this topic. This should benefit the patient with a higher chance to get pregnant. Still, it is clear that patients with borderline ovarian function had significant difficulties.
The numbers below are estimated costs from our website.
For two cycles
PGS of pooled cycles with transfer of normal embryos
Two cycles in our clinic without PGS would cost $10,895 x 2= $21,790. The addition of PGS and subsequent FET adds another $7920 to the cost. For patients in this category, is the opportunity cost favoring the pooled cycle? They could find that all embryos are abnormal (i.e. aneuploid) from both retrievals, devastating, but they may find some closure and consider egg donation. They could have a number of normal embryos and have a better chance to get pregnant than any given single cycle. I think that this example shows the difficulty in making choices for patients with age related infertility and all of the issues that come with it, especially with respect to economics. Additionally, some patients may have benefits for all or part of an IVF cycle which could play a significant role in decision process.
Does changing the cost of IVF influence utilization? We know from our own practice that when we moved from a hospital setting to an office-based setting our cost went down and the volume of cases went up. While it was 15 years ago, we went from 50 cycles to 150 cycles when the cost went down about 40%. Nowadays it is very difficult to get data on the costs of procedures at different programs in a community for a competitive comparison. There is very little transparency of prices. Few programs list their prices publicly. In order to examine the effect of price, I estimated that a 25 % decrease in price would lead to a 25 unit increase in IVF cycles over the course of a year, assuming the practice did 100 egg retrievals a year. The graph below in the spreadsheet indicates this relationship.
Figure 7. Marginal Analysis.
I found that the Elasticity of Price was =-1. This is unit elasticity. Percent change in quantity is equal to the percent change in price. The relationships in the real world would be a little easier to figure out if we were selling ‘widgets,’ rather than complex and expensive medical services with respect to the relationship between price and quantity. Elasticity may be affected by available substitutes, however many states only have a few providers, and timing and the significant expenditures that are required for treatment make it is difficult to analyze. Also, some states mandate IVF coverage, so there is no ability to do this analysis when patients do not pay for the service. The census of 2010 indicted that people of reproductive age have significantly less available free money to spend. The median net worth of families < 35 years of age excluding home equity, according to the US census was about $12,000. It is easy to see how difficult it is to pay for these procedures. It is of interest that states with insurance mandates to cover IVF have many times the number ART procedures performed in a given year compared to similar sized states. (i.e. Total cases Massachusetts vs. Indiana, SART 2012). Clearly, the ability to pay ultimately affects the price elasticity and treatment. Could we improve access by considering this price issue?
Aneuploidy screening adds significant benefits to the patient. There is much discussion regarding the utility of PGS in IVF, while in theory it would seem to be beneficial. In younger patients it may be cost effective. In patients that are older who produce fewer eggs it may be more difficult to show a clear economic benefit, but the information obtained may help guide the patient decision to continue treatment.
CDC, 2012, Annual Assisted Repro
Scott RT Jr1, Upham KM, Forman EJ, Hong KH, Scott KL, Taylor D, Tao X, Treff NR. Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro fertilization implantation and delivery rates: a randomized controlled trial. Fertil Steril. 2013 Sep;100(3):697-703.