Adjuncts in the IVF laboratory: where is the evidence for 'add-on' interventions?
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 pediatric 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 In some cases, when RCTs have shown the technique to be ineffective, it is eventually withdrawn from the clinic.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. We 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.
Embryology, IVF and Reproductive Genetics, Institute for Women's Health, University College London, London, UK.
Joyce
J
Harper
Law Department, London School of Economics and Political Science, London, UK.
Emily
E
Jackson
Research Group Reproduction and Genetics, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.
Karen
K
Sermon
Priority Research Centre for Reproductive Science, University of Newcastle, NSW, Australia.
Robert John
RJ
Aitken
Cambridge IVF, Cambridge University Hospitals NHS Trust, Cambridge, UK.
Stephen
S
Harbottle
Rotunda Hospital and RCSI, Parnell Square, Dublin 1, Ireland.
Edgar
E
Mocanu
Fertilitetscentrum, Carlanders Hospital, 402 29Gothenburg, Sweden.
Thorir
T
Hardarson
Department of Reproductive Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK.
Raj
R
Mathur
Institut de Parasitologie et Pathologie Tropicale, EA 7292, three rue Koeberlé, 67000 Strasbourg, France and Laboratoire de diagnostic génétique, UF3472-génétique de l'infertilité, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France.
Stephane
S
Viville
Centre for Biostatistics, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PL, UK.
Andy
A
Vail
Reproductive Medicine, Sahlgrenska University Hospital, Goteborg, Sweden.
Kersti
K
Lundin
D053938:DNA Fragmentation; D019317:Evidence-Based Medicine; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods / Q000592:standards* / Q000639:trends; D006801:Humans; D050498:Live Birth; D008297:Male; D011247:Pregnancy; D018873:Pregnancy Rate; D027724:Reproductive Techniques, Assisted / Q000592:standards / Q000639:trends*; D013094:Spermatozoa; D059008:Time-Lapse Imaging
IVF adjuncts; PGS; RCT; adherence compounds; assisted hatching; embryo glue; live-birth rate; mitochondria load; sperm DNA fragmentation; time-lapse imaging