A multicriteria approach to patient-friendly IVF

Despite its successes, IVF still has a bad name. After 30 years, its success rate is barely up to the level of natural conception. Moreover, patients are injected with high doses of hormones and suffer physically and mentally during treatment. It is no wonder that fertility specialists have been trying to improve the procedures from the start. Their main focus was on success rate and improving the take-home baby rate. However, this focus had considerable side effects; the most important effect is the high number of multiple pregnancies, with all the ensuing complications, both for the mother and children. The focus on success rate was so strong that, for years, these consequences were ignored. Multiple pregnancies were the price to be paid for a high chance of success. Nevertheless, after some years, discussion started on the acceptability of these iatrogenic problems. This movement, now known as ‘single-embryo transfer’, implied an important modification of the standard practice [1], which meant a major reversal of the value hierarchy used to evaluate an IVF cycle. Safety of both mother and child was reluctantly moved up as a criterion. The reluctance can be illustrated by the fact that in some countries where the embryo transfer policy is not regulated by law or enforceable guidelines, there is no sign of increased single-embryo transfers, even now [101]. Even in countries where the professionals have adopted the goal of reducing the number of multiples, the multiple pregnancy rates remain too high. Nonetheless, this movement was the first step in a process that should culminate in a ‘patient-friendly’ approach.

Patient-friendly IVF is a procedure that takes into account and simultaneously tries to maximize four criteria: cost–effectiveness, minimal harm, equal access and minimal burden [2]. These criteria incorporate the four basic principles in bioethics as defended for decades in principlism [3]. Principlism is the standard theory in bioethics and is constantly used to solve ethical problems in medicine. The four principles are beneficence, nonmaleficence, justice and respect for autonomy. There is no fixed ranking between the principles, that is, no principle has precedence over any of the others in all circumstances. Obviously, four equal principles cannot all be fully respected of all times; they will inevitably conflict with one another on several occasions. The solution is to balance the applicable principles in particular situations. The criteria are already balanced to a certain extent in clinical practice. It is not acceptable to use a highly efficacious method when there is a high risk that the woman or child will suffer serious health consequences; neither is it acceptable to apply a method that is extremely safe but has very low efficacy. Let us take a closer look at the meaning of the multicriteria approach for IVF.

The fixation on success rate has lead to an increasingly complex and costly procedure. Every practitioner knows that, for some category of patients, some procedures are as efficient as others but considerably less costly. Reports recommend that in those situations, the least costly treatment should be performed [4]; however, recommendations and guidelines are not always followed by practitioners. The overuse of intracytoplasmic sperm injection and the underuse of intrauterine insemination can serve as examples in this instance. There may be several explanations for these deviations from good clinical practice: a tendency to stick to familiar procedures, financial incentives from pharmaceutical companies and fear of declining success rates. Another explanation could be the conviction that patients have a right to the best (meaning the most effective) treatment. However, this is a mistake: patients only have a right to the most cost-effective treatment. Given the limited healthcare budget, cost-ineffective treatment harms other patients, whether they suffer from infertility or from some other disease. Put in a positive way, well-being and happiness will be maximized by using cost-effective methods.

At least as important as beneficence is the obligation to avoid causing harm to the patients. The standard hormonal stimulation holds a real danger of ovarian hyperstimulation syndrome. The current percentage of severe and moderate ovarian hyperstimulation syndrome can be reduced significantly [5]. The second risk (mentioned previously) is the multiple pregnancies. Although one has to walk the thin line between low success rates and multiple pregnancies, it seems clear that with current knowledge and technology, a balance can be reached with a much lower multiple birth rate [6]. The third criterion is equal access. Only very few countries guarantee people access to infertility treatment without excessive burden. However, to the extent that infertility is considered a part of basic healthcare, the ‘ability to pay’ should not be a criterion for access [7]. Two movements should coincide to remedy this situation: first, the cost of IVF should be decreased and second, health insurance should at least partially cover the price of a cycle.

In the last 5 years, there has been a tremendous rise in attention to the reduction of the general burden of IVF for the patient. This criterion is expressed in the advent of ‘minimal-stimulation IVF’. Alternatives such as soft, natural cycles and other nonstandard IVF procedures all illustrate the same trend. The main characteristic of these procedures is that they all attempt to reduce the amount of hormones given to patients. Flisser et al. complain that ‘patient-friendly’ IVF is now identified as ‘minimal stimulation’ IVF [8]. It would indeed be a mistake to make minimal stimulation the sole criterion, standing above all others. However, this movement is extremely important in the same sense as the single-embryo transfer movement was: it expresses an increased awareness of other values in the application of IVF. This adaptation increases the position of the patients’ experience within the ranking. There has been a remarkable discrepancy between the general respect paid to patient rights in general medicine and patient rights in assisted reproduction. Put broadly, respect for patient rights means that patients are informed regarding the options that are open to them, with the intention of enabling them to choose the option that best fits their values, plans and preferences. However, in assisted reproduction, patients are generally not informed of the fact that they can have different types of stimulation protocols. Practitioners seem to assume that patients want the treatment that offers them the highest chance of success, almost regardless of the other aspects of the procedure; however, until a few years ago, this was never verified empirically. Recent studies reveal that this was in fact a mistake. Although most patients prefer the most efficacious treatment, a considerable minority is willing to counterbalance the disadvantages of low or minimal stimulation cycles (less efficiency per cycle) against the advantages on other points (few side effects and short duration). A Dutch study showed that 30% of the patients were willing to trade off 6% success of a stimulated cycle for three natural cycles [9]. There are several indications of the importance of burden of treatment and hormonal stimulation for patients. We have known from the start that IVF is a challenging procedure that causes psychological, physical, social and emotional stress. Psychological distress is also the main reason why patients drop out [10]. The stress is, to a large extent, explained by fear of the unknown, worry concerning the injections and possible side effects of the drugs [11]. A Danish study showed that patients preferred the simplicity and short duration of a low stimulation cycle in spite of drawbacks, such as a high risk of cancelation and a corresponding necessity to do more cycles [12]. Respect for the patient’s autonomy implies that one explains the advantages and disadvantages of the different stimulation protocols. If a patient really fears the hormone injections, she should have the opportunity to opt for a natural cycle knowing the implications for the success rate.

We urgently need more studies to evaluate procedures not on one criterion but on all four criteria simultaneously. This is a serious challenge because we have to rethink some of the basic rules that we are currently using. We will, for instance, have to stop thinking in terms of success per cycle but move on to a cumulative pregnancy rate in a certain time span in combination with cost and burden; an example of a study that comes close to this has been conducted by Eijkemans et al.[13]. In this study they compared the effectiveness, cost and psychological burden of two treatment strategies that differ in ovarian stimulation protocol and embryo transfer policy. This is the way to proceed in order to reach a balanced patient-friendly approach that respects all ethical principles.

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.