Fertility treatment options

COS is particularly indicated for women who do not ovulate, but it is also used in other conditions, including cases of unexplained infertility. Under most COS protocols, the patient initially takes an oral medication, but if this is not successful in establishing ovulation or pregnancy, patients may be prescribed injectable medications called gonadotropins. IVF is a more complex and invasive treatment than COS. Clinicians stimulate a woman’s ovaries to recruit many more mature eggs than she would produce in a normal monthly cycle, using the same medication (injectable gonadotropins) used in some COS protocols, but usually at higher doses. The eggs are then surgically retrieved and fertilized in the embryology laboratory. If fertilization is successful, the embryos are kept in culture in the laboratory incubators for between two and six days. On the day of the embryo transfer, the physician and the embryologist select one or more embryos that appear viable for transfer. Selection of embryo(s) to transfer is generally based on an empirical scoring model consisting of analysis of the embryo’s morphology, including the number of cells at specific days of in vitro development and the overall appearance of the embryo (cell symmetry, presence of fragments or vacuoles). The embryo that gets the best score is assumed to be the best quality embryo. Some embryos are tested using pre-implantation genetic diagnosis and screening to rule out chromosomal errors or genetic disorders (like cystic fibrosis), however these techniques involve embryo biopsy and are not yet recommended as a way to improve live-birth rates (American Society for Reproductive Medicine, 2014). Newer noninvasive technologies for assessing embryo viability, including analysis of by-products of the metabolism of the embryo taken from the culture medium and the use of time lapse photography to assess the lag between cell divisions, are currently being developed and evaluated for their effectiveness in many IVF clinics (Yang et al., Reference Yang, Liu, Collins, Salem, Liu, Lyle, Peck, Sills and Salem2012; Forman et al., Reference Forman, Hong and Ferry2013; Montag et al., Reference Montag, Toth and Strowitzki2013). Transfer of one embryo is known as single embryo transfer (SET) and transfer of two is called double embryo transfer (DET). Any viable embryos not transferred can be frozen for subsequent use. In 2011, American clinicians transferred an average of 2.0 embryos in patients under 35 undergoing a fresh IVF cycle using their own eggs and an average of between 2.0 and 2.7 in patients in older age brackets (CDC, 2013).

All IVF clinics in the country must annually provide the US Centers for Disease Control and Prevention (CDC) with data on all procedures they performed. CDC, in turn, is required to use that data to calculate and publish national as well as clinic-specific ‘pregnancy success rates’ (Fertility Clinic Success Rate and Certification Act). Very little, by comparison, is known about the use of COS for non-IVF treatments in the United States. In an article published in 2009, CDC researchers used historical data on multiple births combined with existing data on births resulting from IVF to estimate the number of babies, including multiples, born following COS treatments (Schieve et al., Reference Schieve, Devine, Boyle, Petrini and Warner2009). They concluded that 22.8% of all multiples born in the US in 2005 (31,902 infants) were likely conceived in COS cycles, which is more than the proportion of the nation’s multiples conceived using IVF. An earlier study asking similar questions had estimated that 36.9% of triplets and 62.4% of quadruplets or higher born in the United States result from COS (Dickey, Reference Dickey2007). Together, the data on IVF births and the research on COS births suggest that ~40,000 twins, triplets or higher are born each year in the United States as a result of IVF and COS fertility treatments combined.

Insurance coverage for fertility treatment

Coverage of fertility treatment in the United States is limited, particularly for IVF. Prior to implementation of the Affordable Care Act (ACA), over 48 million Americans had no health insurance and therefore, of course, no coverage for any fertility treatment. Medicaid, the United States’ main safety-net insurance program, provides coverage to almost 60 million Americans, including preconception care as part of family planning services, but infertility testing and treatment are rarely covered (Ranji et al., Reference Ranji, Salganicoff, Stewart, Cox and Doamekpor2009). Even among those with private insurance, coverage for COS treatment is often limited, and very few have any coverage for IVF. Those US patients with COS and IVF coverage have it largely thanks to laws passed by individual states.

State mandates enacted over the last 25 years have helped to expand coverage in 15 of the 50 US states. Yet their reach is modest and not uniform, with policies variable state by state. Further, they do not apply to patients whose insurance is provided by employers who self-insure. In the United States, many people get their insurance as a benefit of employment. Some employers purchase insurance for their employees directly from insurance companies, and these plans are subject to state laws. But large employers often choose to ‘self-insure’, which means that the company pays directly for its employees’ claims rather than purchasing plans from an insurance company (although the employer may contract with an insurance company to administer the benefits). These plans are covered by the Employee Retirement Income Security Act (ERISA) of 1973, a federal law focused primarily on pensions, which preempts state regulation meaning that state laws about insurance benefits do not apply to these plans. Self-insured plans cover about half of all employees with job-based health benefits in the United States. Court cases that have challenged ERISA have all found that state benefit mandates do not apply to self-insured plans (Solis, Reference Solis2011).

Where state mandates do apply, they vary, often requiring very little coverage and leaving insurance companies with great flexibility about the different benefit packages they will offer. IVF is a mandated part of insurance plans in only a handful of states: Arkansas, Connecticut, Hawaii, Illinois, Maryland, Massachusetts, New Jersey and Rhode Island. And even in these states, the total value of the benefit may be capped at as low as $15,000 or the minimum number of cycles that must be covered may be very low. Under these laws, a ‘cycle’ is often considered complete with each embryo transfer procedure, without taking into account number of embryos transferred or whether is a fresh or a frozen cycle. The problem with this definition is that a patient who chose SET followed by a frozen SET would have undergone two cycles, whereas a patient who chose DET would have undergone one cycle. In this way, the state law can encourage patients to opt for treatment plans associated with high rates of multiple births.

When insurance plans include COS and IVF benefits, the benefits may be structured in similarly problematic ways, requiring patients to undertake many cycles of COS, including using injectable drugs, before moving to IVF, or limiting the number of IVF cycles that are covered, or offering a fixed dollar limit regardless of whether it covers the costs of the treatment.

The Affordable Care Act is not expected to immediately change the situation in the United States with respect to insurance coverage for fertility treatments. Health plans sold through the new insurance exchanges created by the ACA have to cover ‘essential health benefits’, but our review of the ‘benchmark’ plans that are used to define the meaning of essential health benefits reveals that IVF treatment has not been required to be included in plans, except in those states that had IVF coverage mandates before December 2011 (http://www.cms.gov/cciio/resources/data-resources/ehb.html; accessed on February 26, 2014). The lack of insurance coverage for IVF in particular, creates significant financial pressure on patients to maximize their pregnancy chances at each step. Because COS costs less than IVF – and is more often covered by insurance – patients have a strong financial incentive to try to avoid IVF by agreeing to use more aggressive COS protocols, which can be difficult to monitor and control for multiples. Once patients begin IVF, financial pressure mounts. When deciding how many embryos to transfer, patients learn that transferring two simultaneously is associated with higher pregnancy rates than transferring one, but carries the same price tag (a full IVF cycle is priced at over $10,000). Transferring one embryo followed by a frozen transfer if the first does not succeed is associated with almost the same pregnancy rate as a transfer of two embryos, but virtually eliminates the chance of twins (McLernon et al., Reference McLernon, Harrild, Bergh, Davies, De Neubourg, Dumoulin and Bhattacharya2010). However, this more prudent approach costs an additional $3000–$4000 and another four to six weeks of time.

One might think that the additional fee for a frozen transfer would provide clinics with a financial incentive to encourage single embryo transfer, but in the United States their stronger incentive comes from how the CDC calculates success rates, which in turn influence clinics’ popularity with patients. Rates are calculated both per cycle started and per transfer. The latter metric, pregnancy rate per transfer can involve transfer of one or more embryos, fresh or frozen. Because single embryo transfers currently result in fewer pregnancies than double embryo transfers, clinics performing many single embryo transfers will appear less ‘successful’, even if they have very low rates of multiples and even if their patients’ cumulative pregnancy rates (i.e. with subsequent transfer cycles of additional frozen embryos) equal those of clinics favoring double or even triple embryo transfers.

Lessons from other jurisdictions: how regulations and incentives can reduce multiple births

Policy makers and leaders in fertility medicine in other countries have recognized the need for SET in reducing the multiple birth rates and have used a combination of regulations and financial incentives to encourage the use of SET and to reduce the rate of multiple births. Belgium has a policy designed to encourage the use of SET by providing a strong economic incentive. In 2003, the Belgian government adopted a policy that pays the laboratory costs for up to six IVF cycles for women younger than age 43 if they agree to single embryo transfer. The policy has significantly increased the percentage of single embryo transfers and increased the number of singleton births without reducing the overall pregnancy rate (Gordts, Reference Gordts, Campo, Puttemans, Brosens, Valkenburg, Norre, Renier and Coeman2005; Ombelet et al., Reference Ombelet, De Sutter, Van der Elst and Martens2005; Van Landuyt et al., Reference Van Landuyt, Verheyen, Tournaye, Camus, Devroey and Van Steirteghem2006).

In contrast to the incentive approach adopted by Belgium, Sweden has relied on a combination of professional guidelines and flexible regulations (Karlström and Bergh, Reference Karlström and Bergh2007). In 2003, the National Board of Health and Welfare issued guidelines. Single embryo transfer is recommended for women up to age 38 for the first two treatment cycles and regulations call for these guidelines to be followed unless there are exceptional circumstances (Karlström and Bergh, Reference Karlström and Bergh2007). Between 2000 and 2004, the rate of multiple births decreased dramatically without a subsequent drop in the live birth rate. Among women under the age of 30, for example, the rate of multiple births fell from 25.3% in 2000 to 4% in 2004, but the live birth rate only dropped from 32.3% to 31% (Karlström and Bergh, Reference Karlström and Bergh2007).

Despite the success of Sweden’s regulatory approach, Jennings and Callahan object that a strict regulation of the number of embryos transferred does not adequately respect the autonomy and that women should be the ‘final arbiters of how many embryos will be transplanted into their reproductive tracts in any given cycle’ (Jennings and Callahan, Reference Jennings and Callahan2001). In contrast, Orentlicher argues that if restrictions like those imposed by Sweden ‘were coupled with insurance coverage of IVF they would not limit reproductive rights’ (Orentlicher, Reference Orentlicher2013).

Recently, the Canadian province of Quebec elected to both extend its citizens’ health coverage for fertility treatments and restrict how those treatments are practiced. Under the program, which is the first of its kind in Canada, the province covers all costs related to medical procedures and medication for ovarian stimulation, artificial insemination and three cycles of in vitro fertilization for all women of childbearing age. The plan covers three full cycles of IVF and ‘implantation of each embryo, one at a time, is covered, for as many times as there are embryos’ or ‘up to 6 cycles for natural or modified in vitro fertilization cycles’ (which generally produce a single embryo). The benefit limit is reset after the birth of a child. The plan does make provision for transfer of two and even three embryos, but these cases must be justified (Gouvernement du Québec, 2013). The Quebec program has been in place since August 2010. Data on the program’s first three months showed that of the almost 1300 cycles performed, just 50% were SET (despite the ‘exceptional circumstances’ language). Importantly, however, SET was used 79% of the time in patients under 35 years of age. The overall clinical pregnancy rate was 32% (40% in patients under 35 years of age). The multiple birth pregnancy rate was just 3.7% (all multiples were twins resulting from double embryo transfer) (Bissonnette et al., Reference Bissonnette, Phillips, Gunby, Holzer, Mahutte, St-Michel and Kadoch2011).

If financial incentives in the United States can be realigned so that COS use is limited and single embryo transfer is performed in more IVF patients, multiple birth rates will go down. The best way to do this is to expand insurance coverage for fertility treatment. Expanded coverage could be achieved by more states passing mandates. Another option, in light of recent health reform, would be to include fertility treatments in the definition of ‘essential health benefits’ for plans meeting the requirements of the Affordable Care Act. This suggestion – like the suggestion that employers voluntarily expand the coverage they purchase for their employees to include fertility treatments – is on the face of it unlikely to be taken up due to the current financial climate in the United States. Policy makers are looking to define essential health benefits in a way that results in the availability of plans affordable to consumers paying out of pocket, just as employers are looking to reduce their spending on health insurance. However, if it could be shown that the additional cost of including coverage for fertility treatments will be offset by a reduction in spending on multiple pregnancies and births that follow from out-of-pocket use of fertility treatments, then policy makers and employers may be persuaded to expand coverage. That coverage would almost certainly need to be subject to certain restrictions, for instance, on the numbers of cycles that can be undertaken and, in IVF, on the number of embryos that should be transferred. Recently, preliminary data from Quebec was published showing a reduction in overall spending under the new IVF program (Vélez et al., 2014).

If the constraints on patient decision-making can be eased, there will still be some patients who opt for protocols likely to lead to twins. These requests will be far more autonomous, however, and some may reasonably be honored depending on the patient’s circumstances. Of course, once a woman is pregnant with multiples, she and her resultant babies should receive care and support regardless of how she conceived. But until US fertility patients are free to weigh treatment options without so much financial pressure to maximize their chances of pregnancy at each step, we should expect to see continued high rates of twins and other multiples, and correspondingly high rates of expensive pregnancy and birth complications.