Adjuncts in the IVF laboratory: where is the evidence for ‘add-on’ interventions?

Abstract

Globally, IVF patients are routinely offered and charged for a selection of adjunct treatments and tests or 'add-ons' that they are told may improve their chance of a live birth, despite there being no clinical evidence supporting the efficacy of the add on. Any new IVF technology claiming to improve live birth rates (LBR) should, in most cases, first be tested in an appropriate animal model, then in clinical trials, to ensure safety, and finally in a randomized controlled trial (RCT) to provide high quality evidence that the procedure is safe and effective. Only then should the technique be considered as 'routine' and only when applied to the similar patient population as those studied in the RCT. Even then, further paediatric and long-term follow up studies will need to be undertaken to examine the long-term safety of the procedure. Alarmingly, there are currently numerous examples where adjunct treatments are used in the absence of evidence-based medicine and often at an additional fee. In some cases, when RCTs have shown the technique to be ineffective, it is eventually withdrawn from the clinic. In this paper, we discuss some of the adjunct treatments currently being offered globally in IVF laboratories including embryo glue and adherence compounds, sperm DNA fragmentation, time lapse imaging, preimplantation genetic screening, mitochondria DNA load measurement and assisted hatching and examine the evidence for their safety and efficacy in increasing LBRs. We conclude that robust studies are needed to confirm the safety and efficacy of any adjunct treatment or test before they are offered routinely to IVF patients.

Towards a better understanding of preimplantation genetic screening for aneuploidy: insights from a virtual trial for women under the age of 40 when transferring embryos one at a time

“…Selecting embryos with the highest potential for implantation offers the potential to transfer one embryo at a time in the fewest possible number of transfer procedures to optimise a woman’s chance of achieving a healthy singleton live birth event and reduce the risk of miscarriage due to chromosome aneuploidy. Appropriately powered, well-designed, peer-reviewed randomised control trials, with a live birth outcome measure which goes on to report on child health, are recommended to be the gold standard for evidenced-based IVF medicine [4]. Although, others have argued for a more pragmatic approach to circumnavigate protracted delay in introducing the highest quality treatment for patients [5].…”

Is it ethical to provide IVF add-ons when there is no evidence of a benefit if the patient requests it?

“…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?…”

Reproductive medicine: still more ART than science?

“…Contrary to guidelines, assisted reproductive technology is frequently initiated early for couples who still have a reasonable chance of conception, promoting overtreatment, increasing avoidable harm, and increasing healthcare costs . A plethora of essentially unproven add‐on interventions are offered to couples in a technological arms race between fertility clinics . As financial considerations often influence treatment policies, the novelty and apparent sophistication of these new technologies take precedence over proof of effectiveness and safety.…”