Cohen_Jacques by emad mohamed

Reproductive BioMedicine Online (2011) 23, 269– 270

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EDITORIAL

Publish or perish: a maxim relevant to authors, readers and editors alike ‘Less is more’ has become the catch-cry of progressive applications of western medicine. Nowhere is this more evident than in assisted reproduction technology, where laboratory developments have sometimes been applied without rigorous investigation. In this issue of Reproductive BioMedicine Online, Gleicher et al. (2011) argue that the trend to apply minimal ovarian stimulation in combination with freezing all oocytes or embryos for later fertilization or transfer has been rushed into routine clinical usage without the checks and balances normally required and rigorously applied to other medical advances. Ovulation induction, now mini-stimulation; multiple embryo transfer, now single embryo transfer; non-invasive tests of pelvic anatomy, rather than endoscopic surgery as a preamble to assisted reproduction treatment; the list lengthens. No sooner does a technology appear online (or is promulgated ahead of that through simple marketing) than it is pressed into clinical usage by the enthusiasm of the clinician or pressure from patients who wish to have a treatment strategy different from the last one. ‘Mini-IVF minimal stim’, ‘physiological IVF-lite’, ‘mild stim’ strategies have the attraction of lower medication costs and reduction of risk of ovarian hyperstimulation syndrome (Verberg et al., 2009). Other benefits claimed, such as a reduction in aneuploidy, are still to be proven. Whether these real and presumed benefits translate into superior live-birth rates as well as into safer outcome and substantial cost reduction per treatment cycle, and more significantly per live birth, remains to be demonstrated. Despite the fact that this approach is practised vigorously in Japan and is now being exported, actual proof of concept is missing. Yet there is something intriguing about the approach to transferring embryos in a natural cycle, as Shapiro et al. (2009, 2010) have shown using regular ovarian stimulation by freezing entire cohorts of zygotes routinely. If that concept can stand up to scrutiny, then it may not be much of a leap to replace standard ovarian stimulation with a more modest approach. One should evaluate carefully why such modest approaches were abandoned in the 1980s and conduct simple

yet constructive randomized trials before applying an entirely new approach. Thus, is a reduction in the cost of medication absorbed by the need for more cycle monitoring to avoid cancellation/postponement? How should new strategies be assessed? Cost per embryo transfer? Intention-toembryo-transfer interval lengths? Live births per number of oocyte retrievals? These are some of the suggested outcomes that perhaps should be measured. There is no doubt that the future in assisted reproduction treatment is and will continue to be influenced by cryobiology and its advances. Cryobiology, in particular oocyte vitrification, is typically not well done in the majority of the centres in the European Union, a view based on the dearth of peer-reviewed publications, but with some notable exceptions such as in Spain, Germany and Italy. This observation begs the question whether it is the apparent simplicity of the technique, matched with low/no capitalisation cost, which has encouraged practitioners to consider employing it widely and often without regard to the critical quality issues. As it is not entirely clear where the explanations lie for these cross-border differences, it would be naive to suggest solutions, but it is self-evident that any obstruction or disincentive to learn these important techniques should be removed, or should we look across borders to determine which incentives have resulted in higher standards of cryobiology practices. Faced with claims of improved birth-weight and reduced rates of premature labour when the time of embryo transfer is shortened from the time of oocyte retrieval and, separately, from ovulation induction (and so indirectly exposure to exogenous hormones), the benefits of cryobiology become more persuasive (Pinborg et al., 2010). Non-stimulation/minimal-stimulation oocyte retrieval is argued to be safer, cheaper, and as cost-effective, when used together with first-class vitrification. However, arguments about cost-effectiveness and safety abound. Zhang et al. (2010) have advocated this approach, joining Teramoto and Kato (2007) in their retrospective observations on many thousands of women. But as the basis of the observational data is at times not robust, so the credibility is low. We chose to

270 publish Zhang et al. (2010) given the interest in reducing the cost of medications and, more importantly, the relevance of cryobiology today in assisted reproduction treatment. Gleicher and colleagues have challenged the claimed implications of the data, drawing attention to the weaknesses evident when rigorous scientific methodology is applied. For this we are grateful and trust that their Commentary provokes the thorough scientific discussion this subject deserves – not only concerning this technology, but for all advances in the assisted reproduction arena.

References Gleicher, N., Weghofer, A., Barad, D.H., 2011. Low-intensity IVF: real progress? Reprod. Biomed. Online 23, 342–346. Pinborg, A., Loft, A., Aaris Henningsen, A.K., Rasmussen, S., Andersen, A.N., 2010. Infant outcome of 957 singletons born after frozen embryo replacement: the Danish National Cohort Study 1995–2006. Fertil. Steril. 94 (4), 1320–1327. Shapiro, B.S., Daneshmand, S.T., Garner, F.C., Aguirre, M., Hudson, C., Thomas, S., 2009. High ongoing pregnancy rates after deferred transfer through bipronuclear oocyte cryopreservation and post-thaw extended culture. Fertil. Steril. 92, 1594–1599.

Editorial Shapiro, B.S., Daneshmand, S.T., Garner, F.C., Aguirre, M., Hudson, C., Thomas, S., 2010. Similar ongoing pregnancy rates after blastocyst transfer in fresh donor cycles and autologous cycles using cryopreserved bipronuclear oocytes suggest similar viability of transferred blastocysts. Fertil. Steril. 93, 319–321. Teramoto, S., Kato, O., 2007. Minimal ovarian stimulation with clomiphene citrate: a large-scale retrospective study. Reprod. Biomed. Online 15, 134–148. Verberg, M.F., Macklon, N.S., Nargund, G., Frydman, R., Devroey, P., Broekmans, F.J., Fauser, B.C., 2009. Mild ovarian stimulation for IVF. Hum. Reprod. Update 15, 13–29. Zhang, J., Chang, L., Sone, Y., Silber, S., 2010. Minimal ovarian stimulation (mini-IVF) for IVF utilizing vitrification and cryopreserved embryo transfer. Reprod. Biomed. Online 21, 485–495.

Jacques Cohen Gedis Grudzinskas Martin Johnson E-mail address: office@rbmonline.com