At least two pharmacologic approaches have been developed to prevent a premature LH surge during controlled ovarian stimulation in assisted reproduction. One technique is the long protocol of gonadotrophin-releasing hormone agonist (GnRH-a), which involves initiation of GnRH-a either in the mid-luteal or early-follicular phase of the cycle prior to ovarian stimulation. Follicular recruitment via gonadotropins is delayed until pituitary desensitization has been achieved, usually requiring 2-3wks [9
]. A more recent method utilizes gonadotrophin-releasing hormone antagonists (GnRH-antagonists), which can achieve complete pituitary suppression within 4-6
h of administration [10
]. Accordingly, administration of GnRH-antagonists can follow gonadotrophin administration bringing a dramatic reduction in duration of the IVF treatment cycle [11
]. This substantially lowers the number of injections required during IVF, and may improve drug compliance and/or prevent errors during drug administration [12
]. The use of GnRH-a and GnRH-antagonists in assisted fertility treatments has been the focus of considerable comparative research [1
]. Reproductive outcomes, as well as safety and efficacy, between these two treatment approaches are thought to be similar [8
] and GnRH-antagonists have joined alongside GnRH-a as mainstream therapeutic agents used widely at infertility units worldwide.
Interestingly, direct comparisons of traditional GnRH-a and newer GnRH-antagonist IVF protocols have rarely included pricing [21
], and none have specifically evaluated patient opinion concerning the non-reimbursed cost for these medications. One multi-center study reported that the medicines needed for IVF account for more than half of the total treatment cost [6
]. In California (and throughout the United States), GnRH-antagonists are protected by patent and command a significantly higher price compared to older GnRH-a preparations which are now available as generic substitutes. Particularly for patients whose first priority is to lower the absolute cost of IVF, if the two approaches have the same efficacy, the additional expense of a newer medication must be carefully scrutinized.
Economics is the study of scarcity, where a choice in one direction necessarily comes at the expense of what might otherwise be available in another direction. Once an IVF patient has made her choice to begin treatment, many will have already made the decision to forego services or goods that they could otherwise have afforded prior to starting IVF. Although IVF patients do, in general, prefer fewer injections, our investigation reveals that patients can sometimes make a trade-off in favor of lower out-of-pocket costs but in ways which run counter to this “fewest possible shots” axiom. This research is believed to be the first to explore this equilibrium, and while larger studies are needed, several noteworthy observations warrant discussion. First, our data align with previous studies where IVF patients responded positively to the concept of simplified IVF treatment enabled by a GnRH-antagonist [12
]. Just over half of our study patients (50.7%) indicated a definite preference for GnRH-antagonist, if their ‘out-of-pocket’ cost difference between this and GnRH-a was zero. The value of this preference among IVF patients still needs refinement, but we were able to show that if the cost gap is relatively small (e.g
., up to $100) as compared to total treatment cost, most patients (70.4%) will pay the extra expense to obtain the GnRH-antagonist associated with fewer injections. However, this study shows that when the ‘out-of-pocket’ cost difference increases, patient preference reverts to the less expensive GnRH-a product in most (77.5%) cases. Our data suggest that although most IVF patients associate greater comfort with GnRH-antagonists [25
], this effect is not unlimited and will be lost when the GnRH-antagonist is perceived as too expensive.
An unexpected finding from this research was the influence of age on treatment preference if there were no differences in treatment costs, such that younger IVF patients tended not to know which treatment they would prefer compared to older IVF patients (p
0.016). It could be speculated that less experienced, younger IVF patients might wish to avoid unnecessary injections and thus strongly favor GnRH-antagonist, yet this association was not supported by our study data. Because questionnaire data were stratified on the basis of IVF patients having previous or current experience working in a healthcare setting, we were able to measure differences across groups depending on this parameter. In this investigation, 11.5% of patients reported a health-related occupation where familiarity with injection techniques and equipment would be different compared to the general population. Indeed, evidence from this study suggests that IVF patients who have a health occupation background tend not to have a preference between GnRH-agonist vs. GnRH-antagonist, if there is no difference in treatment cost (p
0.036). Our data also revealed that patient education level influenced treatment preference in the setting of no difference in cost, with more highly educated IVF patients tending to prefer GnRH-antagonist (p
0.003). Length of time trying to conceive (infertility duration) was not associated with a preference for GnRH-antagonist in this study of IVF patients (p
Several limitations of this study should be acknowledged. Patient income was not sampled by our questionnaire, so it was impossible to stratify protocol preference by this parameter. Also, patient opinion and actual clinical decisions for IVF protocol may be quite different. Just because a patient may “dislike” a particular medication because it costs too much does not necessarily mean that it will disappear from her IVF calendar. In the context of an elective medical service like IVF, the role of patient choice is not irrelevant, however. It should be noted that the total expense of IVF represents an aggregate of numerous cost centers, and the contribution of either GnRH-a or GnRH-antagonist to overall expense might be nominal for some IVF patients. For other patients, the total quantity of gonadotropins required to complete IVF may be less when GnRH-antagonist is used [26
], although precisely quantifying this effect was beyond the scope of our investigation. The established practice of pharmaceutical manufacturers giving away incentives such as free samples, rebates, coupon offers etc. for various IVF medications (including GnRH-antagonist) seems to recognize the hardships encountered by IVF patients who are struggling financially. Additionally, because our calculation of non-reimbursed medication costs was based on data from retail pharmacies serving patients in southern California, generalizing our findings to other locations should be done with caution. This investigation was not designed to follow patients through their IVF cycles to verify which protocol was actually used, or if their actual out-of-pocket cost agreed with the pre-treatment estimate. However, because our sample captured cost data from all establishments in our immediate service area plus mail-order specialty pharmacies, the ‘price to patient’ is considered accurate and the difference between actual and predicted IVF patient costs for this treatment component was probably marginal.