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Is it ethical to provide IVF add-ons when there is no evidence of a benefit if the patient requests it?
  1. Mila Stefanova Zemyarska
  1. Nuffield Department of Women’s and Reproductive Health, University of Oxford, Oxford, UK
  1. Correspondence to Mila Stefanova Zemyarska, Nuffield Department of Women’s and Reproductive Health, University of Oxford, Oxford OX1 2JD, UK; mzemyarska94{at}


In vitro fertilisation (IVF) ‘add-ons’ are therapeutic or diagnostic tools developed in an endeavour to improve the success rate of infertility treatment. However, there is no conclusive evidence that these interventions are a beneficial or effective adjunct of assisted reproductive technologies. Additionally, IVF add-ons are often implemented in clinical practice before their safety can be thoroughly ascertained. Yet, patients continue to request and pay large sums for such additional IVF tools. Hence, this essay set out to examine if it is ethical to provide IVF add-ons when there is no evidence of a benefit if the patient requests it. In order to determine what is ethical—namely, morally good and righteous, the question was considered in relation to three key values of medical ethics—autonomy, beneficence and non-maleficence. It was determined that providing IVF add-ons might be morally acceptable in specific circumstances, if true informed consent can be given, there is a potential of cost-effective physiological or psychological benefit and the risk of harm is minimal, particularly with regard to the unborn child.

  • clinical ethics
  • obstetrics and gynaecology
  • in vitro fertilization and embryo transfer
  • reproductive medicine
  • interests of woman/fetus/father

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Globally, there are over 180 million people who are affected by infertility and an ever-increasing proportion of those seek treatment with assisted reproductive technologies (ART).1 In response, the field of ART has seen a notable diversification and refinement in techniques since the first successful application of in vitro fertilisation (IVF) in 1978. Presently, patients can resort to complex manipulations such as surgical sperm retrieval, uterine transplantation and intracytoplasmic sperm injection (ICSI), which bypasses the normal oocyte-sperm interactions required for fertilisation. However, ART success is still suboptimal at best: between 2014 and 2016 the average live birth rate (LBR) per cycle started in the UK was 28%,2 which is subject to clinic expertise and can vary greatly with patient age. In a quest to improve success rates, public and private bodies have been racing to develop tools, methodologies or protocols that target different aspects of the ART process—from selecting the best sperm to transferring the embryo with the highest implantation potential and even aiming to optimise the molecular and immunological receptivity of the uterine environment.3

Such efforts have generated an ever-growing list of therapeutic or diagnostic tools, also termed ‘add-ons’ and ‘adjuncts’, that can be implemented as part of an ART treatment cycle alongside the core fertilisation technique used, be it IVF or ICSI (figure 1). As a result, patients are now presented with a multitude of options regarding what will be applied to them and to their embryos in the course of their infertility treatment, which should allow for increased individual tailoring in line with the current global move towards personalised medicine. However, these add-ons might not add up, as there is no conclusive evidence that any of them is beneficial or effective.4 5 Some tools lack sound biological plausibility behind their mechanism of action, while others are brought into practice despite insufficient information regarding their safety.3 Furthermore, an overwhelming majority of these techniques are associated with controversial results and unjustified cost-effectiveness claims, based on data of poor quality or non-existence.4 5 Importantly, only a number of them have even been subjected to randomised controlled trials, which are the gold standard for assessing the impact of an intervention, and, of the ones that have, many fail to show a significant contribution to LBR, if any at all, despite thorough investigations carried out in the form of Cochrane reviews and meta-analysis studies.4 5 This has prompted experts in the field to voice concerns over the use of IVF adjuncts in clinical practice against the principles of evidence-based medicine (EBM).

Figure 1

Therapeutic or diagnostic add-ons for in vitro fertilisation (IVF) grouped by purpose. Information collated by author.

Nevertheless, these tools continue to be offered to patients, biological and financial implications notwithstanding. In fact, two studies by Spencer et al 6 and Heneghan et al 7 unveiled that making unsupported or unjustified claims of benefit is a predominant marketing strategy for add-ons employed by UK fertility clinics. This controversy was brought to public attention by an associated TV programme for investigative journalism—BBC One’s Panorama: Inside Britain’s Fertility Business, which portrayed the field of ART as a profit-oriented business, creating a sense of credibility gap between patients and their physicians. Despite the fact that the studies were not well accepted among leading specialists in the field,8 they raised valid concerns regarding the need to protect patients, who are particularly vulnerable during their struggle with infertility.9 In the UK, this has started a discussion about the need for new legislation to regulate adjunct IVF tools and the Human Fertilisation and Embryology Authority has been prompted to release official guidelines on the effectiveness and safety of commonly offered add-ons. In response, nine treatments have been graded using a ‘traffic light system’, but no intervention has been given the ‘green light’.

Against evidence and rationale, desperate patients request and pay large sums for such additional IVF tools. This has become an issue of public concern, amidst fears that infertility sufferers are being exploited and taken advantage of, financially and emotionally. Are add-ons providing false hope? Are patients misinformed? In such a predicament, complex clinical, emotional and financial aspects, alongside subjectivity, have the potential to obscure reasoning and judgement. Hence why, this essay set out to examine if it is ethical to provide therapeutic or diagnostic IVF add-ons when there is no evidence of a benefit if the patient requests it. In order to determine what is ethical—namely, morally good and righteous, the question was considered in relation to three key values of medical ethics—autonomy, beneficence and non-maleficence.


The principle of autonomy requires to respect an individual’s right to make decisions and develop their own purpose in life10 (p 101).

Reproductive autonomy

Persons from the general population have an inherent right to determine and complete their reproductive goals—an entitlement which becomes a privilege for infertile patients , who must rely on a team of professionals and the options offered at their discretion. However, infertility treatment must be considered apropos of the existential goals of patients, which often fall outwith the scope of simply resolving a medical issue. Childlessness has a profound negative impact on the quality of life of individuals due to the emotional disappointment faced privately, and due to the associated stigma endured socially.11 Furthermore, the benefit of adjunct IVF tools is not yet supported by evidence, but neither is it refuted. In this context, it could be argued that it is, in fact, unethical to withhold providing a potentially helpful intervention based solely on the lack of proof to its effectiveness at that given moment in time. Is it at all feasible and fair to wait for conclusive evidence on the beneficialness of an add-on, considering that the reproductive goals of couples will likely change after 5 or 10 years of infertility? Studies aiming to assess the effect of using time-lapse imaging on LBRs were first initiated over a decade ago and yet there is still controversial evidence published on the matter.4 5 If time-lapse proves to be beneficial, fertility treatment providers who were withholding its implementation into clinical practice would have a moral obligation to all patients treated during that time period. Additionally, this could provide grounds for a medicolegal quandary of significance for couples that never managed to achieve a live birth and were prevented from using a beneficial add-on. Hence, patients should not be denied the autonomy to, within reason, endeavour to maximise their chances of success.

Medical responsibility

A receptive standpoint assumed by fertility treatment providers is in line with their duty to uphold the reproductive autonomy of the patient during IVF. However, this comes secondary to the ethical and legal obligation of clinicians to care for the health of the individuals they treat10 (p 202), as well as the well-being of any potential children which might be born as a result.12 Importantly, patient requests cannot be granted medical or scientific validity and the intensely emotional aspect of infertility can obscure the physiological impacts of an intervention and any associated risks. This is particularly relevant to cases where infertility treatment is futile, but desperate patients, having undergone numerous unsuccessful ART cycles, cannot discern it is time to stop and consider alternative options.13 It is, therefore, a clinician’s right and responsibility to prioritise their professional judgment over the patient’s autonomy and reject requests which exceed what is potentially beneficial or can be deemed sensibly permissible. Particularly vulnerable patients must be additionally protected against making irrational or unfavourable decisions, as their autonomy might be compromised. Patient pressure and competition between IVF clinics contribute to the coercion to offer such therapeutic or diagnostic add-ons due to concerns of diminished clientele and financial losses.14 Clinicians and units alike should remember, however, that their primary aim is to treat, not to profit, so providing adjunct IVF treatments against medical and moral rationale must be refused, even at the risk of losing a patient.

Informed consent

The ethical value of autonomy rests on the principle of informed consent, specifically that the patient has a thorough and true understanding of the potential benefits and risks of any intervention carried out10 (p 121). This is particularly challenging in ART, as add-ons are the subject of much debate and controversy. Patients who request such adjunct IVF tools have a clear motivation—to have their dream child, and they hold a conviction that the sought intervention will improve their chances of success, despite the lack of solid scientific evidence to support the notion. This is, in part, due to the multitude of sources which perpetuate incomplete or incorrect information, from clinic websites6 7 to the media. Even reasonable patients can be misled by the marketing campaigns of some IVF adjuncts and it is of concern that fertility treatment providers too might be contributing to the information chaos, although inadvertently, by recounting anecdotal evidence against the principles of EBM.5 This raises the question: Is there autonomy where there is misinformation? How can true informed consent be achieved when patients cannot be realistically expected to read the primary research literature? In this context, it is paramount that professionals endeavour to be a reliable source of insight, providing advice principally based on examination of the data, as opposed to intuition, reviews or other secondary sources. Patients, in turn, must be critical of the information they are exposed to, in an effort to guard against misconceptions propagated by freedom of speech on the internet. Medical authority should be used to engage in a comprehensive discussion of add-ons, focusing on unbiased, factual and evidence-oriented guidance.


The principle of beneficence requires to do good, or what will benefit the patient10 (p 202).

Primary benefit and impact

The primary purpose of add-ons is to benefit the patient by increasing their chances of IVF success. Nevertheless, the majority of interventions have not reliably shown a significant positive effect on LBR.4 5 In fact, retrospective analysis has revealed that some adjuncts, such as preimplantation genetic screening, could even decrease the cumulative LBR when applied under inadequate methodology.14 Additional IVF tools should not be universally dismissed yet, because some interventions might only be beneficial to a specific patient group, as has been suggested by data on endometrial scratching in women with recurrent implantation failure.4 However, offering add-ons to the benefit of the general patient is still the subject of much controversy and, even if a statistically significant increase in LBR is reported, infertility treatment providers should be scrutinous of the size of the reported effect and the number needed to treat (NNT) for one added live birth. An illustrative example of the significance of NNT in infertility treatment was the proposition that clinics should only employ ICSI as the method of fertilisation in order to minimise cases of total fertilisation failure. The effectiveness of such an intervention was discredited by Bhattacharya et al 15 who reported that a total of 33 ICSI cycles would have to be carried out to prevent one case of total fertilisation failure. Considering the financial burden of some IVF adjuncts14 and the physiological risks of others,3 it is difficult to justify implementing them in clinical practice to patient advantage, while something as simple as adherence to a healthy Mediterranean diet might have the potential to double their chances of IVF success.16 Thus, if the main aim of treatment is to truly benefit the patient, then clinicians should prioritise what is most impactful and beneficial, even if that may be dietary advice and not a sophisticated IVF tool. Additional interventions for IVF can be considered as an available option, but certainly not the only one.

Secondary outcomes of gain

The primary most important measure of the effectiveness of an add-on is LBR, but success rates are not the sole aspect of potential gain for the patient. Secondary outcomes of treatment can also have a significant impact on the patient experience during an IVF cycle. This is particularly relevant to miscarriage rates among ART pregnancies, which have a profound devastating effect on expectant parents. Importantly, one study reported that opting for physiological intracytoplasmic sperm injection can reduce the rates of early pregnancy loss by 50% compared with conventional ICSI.17 The relationship between sperm DNA fragmentation and miscarriage rates has further prompted a timely re-evaluation of the diagnostic potential of adjunct sperm DNA testing tools such as SpermComet and HALO beyond their effect on LBR.18 In the context of miscarriage, women often suffer feelings of intense self-blame, shame and guilt, but between 30% and 60% of embryos have been reported to be aneuploid and, thus, inherently unable to result in a live birth.19 Consequently, there might be a role for preimplantation genetic testing for aneuploidy as an IVF add-on, although current evidence is highly contradictory.4 5 Nevertheless, it is imperative that additional IVF tools be studied as part of an altogether more complex reproductive process, in which the birth of a child is only the conclusion. Ultimately, there is room for both quantitative and qualitative improvements in ART.

Emotional and psychological aspects

Beyond a direct physiological impact, IVF adjuncts might also be of emotional and psychological benefit to patients during a time of intense vulnerability and desperation.9 Time-lapse imaging has revealed that embryos which undergo direct cleavage from one to three cells have a mere 1% chance of implanting, despite appearing morphologically normal at the blastocyst stage.20 Hence, using this add-on technology can protect patients from the false hope and disappointment associated with undergoing an ineffective embryo transfer. Furthermore, providing individuals with time-lapse images of their embryos has been reported to enable early bonding with the prospective child, as well as increased satisfaction and sense of involvement with the treatment.21 Using a combination of IVF tools can also enable individuals to gain emotional closure and inner assurance that they have exhausted all possible treatment options. Such psychological benefits are of particular importance to cases of futile infertility treatment and, remarkably, continue to hold true even when the patient is aware that treatment success is unlikely.13 Hence, providing additional IVF tools can be of service to patients even if it does not directly contribute to their chances of a live birth, provided that true informed consent is in place. However, it should be noted that any potential emotional gains of IVF adjuncts do not actually further the patient interest to have a child, so they should be considered within reason during the process of clinical decision-making.


The principle of non-maleficence requires to do no harm to the patient or hinder the patient’s interest10 (p 150).

Primary harm

The primary and most important duty of medical professionals is to prevent harm to the health and well-being of the patient. However, no medical intervention is without risk and IVF adjuncts are no exception. Reassuringly, procedures such as endometrial scratching and endometrial receptivity array are minimally invasive and, despite reports of increased pain, pose little danger of procedural complications.22 It is, therefore, in the interest of patient safety to provide such additional tools in a controlled environment with high-grade hygiene and operator competence, rather than encourage reproductive tourism to destinations of unknown or questionable standards. Conversely, the substances administered as part of common adjunct regimes such as quad therapy and reproductive immunology treatment have some adverse side effects (table 1), the risks of which are not inconsequential.3 Furthermore, harm to the patient can occur even in the absence of acute events, as both adjuncts and standard IVF stimulation protocols coalesce onto the female patient. Thus, even the more common side effects of adjunct therapy can exacerbate the decrease in health-related quality of life in women undergoing IVF.23 In standard practice, similar risks are justified by the benefit of the treatment—unburdening an individual from illness or, in the case of ART, childlessness. Nevertheless, it is challenging to apply such rationale to IVF add-ons, as there might be minimal or no gain for the patient and intention to treat is unwarranted. In such uncertainty, ethics dictates that it is acceptable to provide a treatment only if the potential benefit is equal to or greater than the potential harm10 (p 230). Hence, unless and until there is evidence that would warrant their use, IVF add-ons with above minimal risk of adverse side effects, acute or long-term health damage, as well as those with untested safety, should not be provided.

Table 1

Cost and health risks of five substances used for adjunct reproductive immunology treatment (Adapted from Moffett and Shreeve [3])

Hindrance of patient interest

Beyond primary harm, the principle of non-maleficence also encompasses a duty to the patient interest—namely, to have a child. In that regard, it is sensible to offer add-ons, in an attempt to maximise the chance of a live birth within the current IVF treatment cycle and prevent the need from consecutive procedures. However, the benefit of adjunct interventions is solely putative.4 5 Furthermore, no likely combination of therapeutic and diagnostic tools will increase the LBR by 30%—that of an additional IVF cycle, although it might match the cost (table 1). In a private healthcare setting, this can directly hinder the interest of the patient, as a significant proportion of couples who fund their ART treatment themselves will only be able to afford one or two IVF cycles and will stop before they have a child.24 In a public healthcare setting, this can hinder the interest of other patients, by exhausting available funds in a non-cost-effective manner. It is, therefore, possible that the financial burden imposed by adjunct IVF treatments robs present and future patients of their chance to access treatment and achieve their goal. Consequently, there is an unambiguous need to protect both individuals who might be vulnerable to emotional and financial exploitation,9 as well as entire patient groups and communities from unjust distribution of resources. It is paramount that conflicting financial interests, which might be tainting the infertility treatment industry,14 are abandoned in favour of rationally seeking out the most cost-effective option for different treatment circumstances and patient allowance. Additionally, an effort should be made to bridge the gap between the true cost of an add-on and what patients are charged for it. It is ethically unacceptable for that difference to be as large as 10-fold, which is, occasionally, the case for endometrial scratching.

A duty to the embryo

A unique characteristic in the field of ART is a simultaneous responsibility for three individuals—the mother, the father and the potential child. It could be argued that the principle of non-maleficence applies most strongly to the embryo, as no informed consent, benefit or interest can be ascertained at the time of intervention. Additionally, potential harm could occur at different stages of the ART process and with varying severity. Recent systematic reviews have confirmed previously reported findings that both assisted hatching and the addition of EmbryoGlue significantly increase the incidence of multiple gestation,4 5 thus exposing any resulting children to a 10-fold surge in the risk of preterm birth and, consequently, an array of associated health complications. Importantly, the period of preimplantation embryo development, during which add-ons are applied, is a time of extreme fragility and epigenetic plasticity. Hence, exposure of the embryo to any atypical factors in its environment or culture media could have the potential to programme the long-term health of the resulting child, as well as a number of late-onset diseases, data of which may only start emerging 50 years after the IVF adjunct was carried out.25 However, desperate patients are inclined to requesting highly controversial techniques with little consideration of the potential lasting implications for their future child. In this context, clinicians must be vigilant of unreasonable or unsafe patient pressure, always striving to balance the potential gain for the parents against any risk of harm to the resulting children.12 After all, the professionals who are involved in creating the embryos have a duty to them to protect them.


In conclusion, providing additional tools for IVF that lack evidence of a benefit might be morally acceptable if there is true informed consent, a potential of cost-effective physiological or psychological benefit and a minimal risk of harm. Ethical principles must always be considered in conjunction, with non-maleficence prioritised over beneficence and autonomy, particularly with regard to the future of the embryos that have been created and any potential children which might be born as a result. Additionally, it is imperative that desperate and vulnerable patients be protected against financial and emotional exploitation, as well as harm and disinformation, during the course of their infertility treatment. Although the patient might be seen as purchasing such IVF add-ons, it is the principle of primum non nocere (first do no harm) that infertility treatment providers should adhere to and not that of caveat emptor (let the buyer beware). Scientific efforts should continue to assess the effectiveness, safety and clinical relevance of both novel and pre-existing adjunct IVF therapies and interventions, in an endeavour to single out the tools which have a genuine potential to impact LBR and, consequently, help patients in their quest for a child. Meanwhile, add-ons can presumably be both beneficial and non-beneficial, as there is absence of evidence to either.


Professor Christian Becker and Dr Kevin Coward.



  • Contributors MSZ: creation and review of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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