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Semin Reprod Med 2021; 39(05/06): e19-e21
DOI: 10.1055/s-0041-1739169
Epilogue

Navigating Innovation, Evidence-based Practice and Patient Choice in ART: Concluding Comments on Adjuvant Therapies

Thomas Tang
1   Regional Fertility Centre, Royal Jubilee Maternity Service, Belfast HSC Trust, Belfast, United Kingdom
,
Nikoletta Panagiotopoulou
2   Department of Gynaecology, Salford Royal NHS Foundation Trust, Salford, United Kingdom
3   Manchester Fertility, Cheadle, United Kingdom
,
Ephia Yasmin
4   Reproductive Medicine Unit, University College London Hospital, London, United Kingdom
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The use of adjuvant therapies to assisted reproductive technology (ART) is a controversial topic, like In vitro fertilization (IVF) once was. Opinions can be highly polarized with some perceiving them as innovation, while others as tools for patient exploitation. Seminars in Reproductive Medicine has dedicated the last two issues on adjuvant therapies in ART and we hope that the articles selected provided the reader with a balanced overview of those commonly encountered add-ons or adjuvants from an exhaustive list. We preferred the use of adjuvants to add-ons to use a neutral term. The categorization of adjuvant therapies to ART is used to describe any additional and non-essential medicines, procedures or techniques which can be added to standard IVF protocols and have anecdotal, equivocal or emerging evidence. It is thus clear that adjuvant therapies are distinct from additional interventions that are integral to an ART cycle, such as different ovarian stimulation protocols for oocyte retrieval. They also differ from additional interventions that are necessary for the management of certain conditions, such as intracytoplasmic sperm injection (ICSI) or surgical sperm retrieval for the management of severe male factor infertility.

While IVF is heralded as one of the major achievements of the last century culminating in the Nobel prize for one of the pioneers, Sir Robert Edwards in 2010, the first live birth in 1978 followed hundreds of unsuccessful embryo transfers. IVF was an experimental process at that time. Although there has been an improvement in IVF success rates over the years, these seem to have plateaued around an overall 25% live birth rate.[1] [2] [3] The relatively low success rates and high costs of IVF act as strong incentives for interventions that offer the promise of improving the chances of success in the ART treatment attempts. As a result, ‘add-ons’ are commonly discussed in patient forums and fertility clinics; a survey of clinic users initiated by the HFEA revealed that 74% of respondents had used at least one ‘add-on’ and that their use is growing.[4]

Assisted reproductive technology is a relatively new specialty in medicine. Like with any rapidly growing scientific field, novel ideas and new technologies are being proposed and introduced in clinical practice. This is certainly propelled by a genuine need to search for better outcomes. It is worth noting that several now well-established techniques started as adjuvant therapies with intracytoplasmic sperm injection (ICSI) being a typical example.[5] However, only a handful of ART related innovations or new technologies have demonstrated evidence-based effectiveness. A recent global initiative confirms this as it highlighted the presence of several evidence and research gaps in the four main areas of reproductive medicine (male, female and unexplained infertility, medically assisted reproduction, ethics, and access and organization of care).[6]

But how much evidence is it reasonable to expect before a treatment is offered to patients? The ideal way for a new intervention or technology to be introduced in ART would involve developing a hypothesis-driven basic science idea, testing this idea using initially an animal model and then using donated human embryos prior to conducting clinical trials.[7] In practice and because of the physiological differences that would confound the effect of the intervention in humans, the ideal way to evaluate clinical effectiveness and safety of new interventions would be through randomized controlled trials.[8] In ART, practice based on randomized controlled trials (RCTs) is not very common. Some RCTs have methodological limitations that preclude a robust assessment of the clinical effectiveness of interventions. Such limitations include small sample size thereby lacking the power to detect clinically relevant differences or outcome measures that have limited clinical significance. In addition, the presence of restrictive regulation and bureaucratic interventions may discourage researchers from initiating research projects. Evidence-based medicine in ART is thus often based on meta-analyses of heterogenous and small trials or of observational studies.

Given that new adjuvant reproductive therapies often lack regulatory review, and their introduction may be influenced by financial incentives, we need to think about how to communicate these adjuvant therapies with patients so they can make informed decisions about their treatment plans. The HFEA in the UK along with industry and patient stakeholder groups propose that adjuvant therapies may be offered if information about the current state of knowledge is given to patients.[9] It is unclear how much weight such discussions have amidst the excitement of having a new treatment to use. Several global initiatives have recently emerged that aim to improve conversations between patients and healthcare professionals and could facilitate the delivery of patient-centered care. In the UK, the Choosing Wisely UK campaign encourages patients to ask four questions prior to having any test or intervention:

  • What are the benefits?

  • What are the risks?

  • What are the alternatives?

  • What if I do nothing?

These four questions could also be useful when discussing adjuvant therapies in ART.

Patient values are of course an integral part of evidence-based medical practice. In clinical practice, patient preference can guide treatment where uncertainty exists. A recent survey of women in Australia who have undergone IVF since 2017 showed a very high prevalence of adjuvant therapies use with 82% of them having used one or more ART adjuvant therapy.[10] This suggests that patient choice driven adoption of adjuvant therapies could occur, although the lines between patient initiated and clinician driven practices are not always clear to understand. Emerging data suggest that clinicians often feel under pressure to offer additional interventions in response to patient demand.[11]

The doctor-patient relationship has evolved over time. Doctors are now asked to act as a bridge between the world of medicine and the needs and wishes of patients and at times, these paradigms appear to be mutually exclusive. Patients are encouraged to take control of their own health and some of them might see themselves as consumers. Patients' perception of evidence may be different to that of clinicians, with patients giving equal weight to friends' and family's input or information available through social media. Infertility, like other medical conditions, is a biological as well as a social process. Therefore, social and cultural factors affect health-care encounters and should be acknowledged when making health-care decisions.

ART adjuvant therapies remain a contentious topic. Criticism has ranged from adjuvant therapies lacking rigorous scientific data to prove their efficacy to them being a potentially harmful practice perpetrated by increasingly privatized and corporatized fertility sector. That said, progress in science and medicine requires a curious mind where new ideas and new interventions are properly evaluated, and we would like to thank all contributing authors for aiding readers to do so. With the 3 volumes, we feel that rather than taking a binary view, it is better to look into better research and better practical applications of innovation.

We acknowledge that the range of adjuvant therapies discussed in these two special issues is not a complete list of available options as the field of ART is rapidly moving. We also acknowledge that certain adjuvant therapies have already found a place in routine clinical practice, such as the use of the embryoscope, while new ones, such as expanded carrier screening (ECS), non-invasive preimplantation genetic testing (ni-PGT) or artificial intelligence (AI) in the IVF laboratory, are emerging. Hence the discussion about the role and effectiveness of adjuvant therapies will continue as new data emerge and novel interventions are introduced in clinical practice.



Publication History

Article published online:
21 April 2022

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