RBMO Insights Issue 31. December 2024
Reproductive BioMedicine Online
An international journal dedicated to biomedical research on human conception and the welfare of the human embryo
A warm welcome to the December edition of RBMO Insights – our monthly journal newsletter showcasing article highlights, news from the Editorial Office, our Affiliated Society partners and wider community, event previews, section profiles, and Talking Points on topics of particular note.
In this issue, our Talking Points discuss Gartner hype cycle and Dunning–Kruger effects in fertility medicine, examine evidence in the debate around alcohol and pregnancy, and look at links between antimullerian hormone levels and time to pregnancy.Elsewhere in this issue, we put a spotlight on our Clinical Assisted Reproductive Technologies Section, with Section Editor Pasquale Patrizio, and look forward to concluding the year with our tenth journal webinar, RBMO Live. This episode will be hosted by Editor Mina Alikani, Section Editors Basak Balaban and Thomas Ebner, who will be joined by a fantastic panel of speakers focusing on our Clinical Embryology section.
And finally, a quick note to say you can find us on Bluesky, should you have an account already, or be among the many thousands of scientists (and millions of people) signing up to the site recently. We added this to our Linktree, where you can quickly find links to all our social accounts, mailing list registration form, and key journal pages.
With that, we wish all the best for the festive season and hope you enjoy this issue of RBMO Insights.
Explaining the hype in IVF add-ons
Will technology deliver? Will AI liberate IVF from the vagaries of the embryologist? Can paradise lost ever be regained? Business has a term for this familiar pattern of boom to bust, from yes to no - the ‘Gartner hype cycle’ - and it will be well known, even if not by name, to readers of this journal. The term was coined two decades ago to describe the introduction and maturity of a new technology through five apparent phases of its and, with fulfilment, the plateau of productivity. Sounds familiar? Not all introductions in IVF, of course, reach the high ground of productivity, and many, like GIFT or endometrial scratch, will struggle to emerge from the trough of disillusion; others, like slow freezing or cleavage-stage transfer, will simply be superseded by improved technologies.
The Gartner hype cycle has just been raised in a new paper in RBMO on innovations in ART but now with an added equation which goes some way to explaining their often unjustified.
The authors, two of whom are bioethicists, cite endometrial scratch as an example of the combined theories, but do not confine their argument to hypotheses, additionally building a case for the potential for real clinical harm. And in a bid to protect patients from that harm they propose the development of ‘comprehensive national and international databases accessible to researchers and clinicians’ to allow fast and reliable assessment of new treatments. The system would thus imply ‘a more rigorous’ approach to defining interventions as ‘innovative’, and, once defined as such, would necessarily require their incorporation into the monitoring databases. Assessment from the data would thus define treatments as ‘effective’ (proven), ‘innovative’ (presumed safe but unproven efficacy) or ‘experimental’ (unproven).
The hypothesis, of course, does seem yet another proposal to bridge the evidence gap now lurking behind many new interventions. RCTs remain the gold standard, as ESHRE’s new guidance on IVF add-ons makes clear, but, as one of the Chief Editors of this journal argued a few years ago, ‘RCTs have become very hard to do’. Macklon and colleagues thus proposed a scheme not unlike this latest, ‘a collective enterprise’ by which regulators such as the HFEA ‘could require clinics that offer these interventions to register their use and clinical outcomes’, building a database of individual patient data that could help address the ongoing evidence gap.
OK for pregnancy planners to carry on drinking?
Recommendations to avoid alcohol during pregnancy are widespread, based on ‘clear and compelling’ evidence. Alcohol can be risky at any stage, advise the UK’s Royal College of Obstetrics & Gynaecology and the US CDC, noting that there’s no known safe limit. Even modest amounts were associated with increased risks of small-for-gestational age and preterm delivery in a recent review, while greater amounts have been unequivocally linked to pregnancy loss and fetal alcohol syndrome.
Evidence about the preconceptional effects of alcohol is, of course, more difficult to collate. But a new report, published as an RBMO article in press, from an ongoing web-based prospective cohort of couples trying to conceive has now analysed the preconception alcohol consumption data from 9400 women and 2600 men - and concluded somewhat surprisingly that consumption in either partner appears to have no effect on risk of miscarriage.
Female participants in the Pregnancy Study Online (PRESTO), who were all hoping to become naturally pregnant, provided baseline data on medical history and lifestyle factors and invited their male partners to respond also. The female participants completed follow-up questionnaires every eight weeks for up to 12 months or until they reported a pregnancy or a ‘censoring event’ (eg, start of fertility treatment). Those who did conceive completed two additional questionnaires in early (<12 weeks’ gestation) and late pregnancy (～32 weeks).
About one quarter of the females (27%) reported no alcohol use while trying to conceive, in comparison with 20% of the males. Around one in five of the pregnancies ended in miscarriage, but, after adjustment for demographic, lifestyle and reproductive variables, no appreciable association was found between preconception alcohol and risk of miscarriage, with non-significant HRs between those who did drink (modestly or more) and those who did not. There were similar findings among the men.
The authors note that few studies have investigated the effect of preconception drinking, but add that their results, though at variance with those in pregnancy, are consistent with ‘several’, though not all, other studies. A Cochrane review of preconception lifestyle advice, which included alcohol in both partners, described their evidence as low quality and failed to find any meaningful association.
However, it’s worth noting that a recent report in this journal from another prospective cohort (the Rotterdam periconception cohort, Predict) did find that moderate maternal alcohol consumption was negatively associated with fetal growth parameters when assessed by 3-D transvaginal ultrasound from week 7 to 12 of gestation. Based on their results and the evidence that alcohol is a proven teratogen, the Rotterdam authors did recommend that its consumption before and during pregnancy should be discouraged in both women and men.?
The PRESTO investigators, despite their neutral results, would also seem to agree, concluding: ‘While alcohol consumption is quite common among pregnancy planners and is not appreciably associated with an increased risk of miscarriage in most studies, alcohol moderation still appears a reasonable recommendation.’
More evidence favours link between AMH and pregnancy outcome
The prognostic value of AMH as a predictor of live birth in IVF continues to be a matter of heated debate. A recent report from a US cohort study concluded that a low AMH level (<1 ng/ml) is ‘associated with a reduced chance of conceiving at all ages’, while a commentary in the same journal dismissed the results as ‘biased’ and ‘inaccurate’ - and subject to conflicts of interest. ‘We have had good evidence that AMH does not predict natural fertility,’ insisted Anne Steiner. ‘Using AMH as a fertility test has the potential to induce unnecessary anxiety in women with low AMH and false reassurance to those women with high AMH.’
Now, a small piece has been added to the AMH puzzle in results from a large retrospective study from China just published as an article in press in RBMO. This comprehensive study, from a single centre in Zhengzhou, cross-referenced patients with and without PCOS according to three different thresholds of AMH, and found a clinical predictive value of AMH levels in both patient groups. Thus, in the non-PCOS group, when AMH levels were ≤2.98 ng/ml, there was a positive correlation between AMH and LBR: for every 1 ng/ml increase in AMH, the likelihood of LBR rose by 29%. However, in those with PCOS, the LBR decreased by 5% per unit increase in AMH when AMH level >7.13 ng/ml. This latter pattern, the authors proposed, ‘may be indirectly related to the hyperandrogenic environment caused by increased AMH levels’.
There were 4631 patients in this study, all aged below 35 years and all having their first FET. Most studies linking AMH to LBR, write the authors, have been in fresh cycles and with inconsistent results, but the few in FET cycles have also produced inconsistencies. The results of this study, however, would suggest a positive association.
The known association between oocyte yield in IVF and outcome would suggest that a similar correlation exists with LBR, yet systematic reviews have failed to show that. Nevertheless, a recent analysis of SART data (34,000 cycles) found that AMH was indeed strongly associated with cumulative LBR independent of age and is considered ‘a robust predictor of quantitative ART outcomes’ correlating with oocyte yield following ovarian stimulation.
Lucie Delaroche , Lucile Besnard, Nino Guy Cassuto, Sébastien Bristeau, Anne Togola
Bisphenols A and S are released in small quantities from some disposable devices used in IVF procedures, but do not appear to accumulate with sequential use or when used in combination. The inclusion of these bisphenol-releasing devices could lead to contamination throughout the entire procedure. While considerations such as cost-effectiveness and compatibility with existing procedures need to be addressed, exploring alternatives is important to identify safer materials for ART, and understanding impacts human health and reproduction to minimize their negative effects.?
Lead author Lucie Delaroche will be talking about this paper in our forthcoming RBMO Live event, December 10 – see more details in the Events section of this issue.
Nina Gidel-Dissler, Thais Roque, Guillaume CANAT , Benjamin Angelard, Jessica Vandame , Alexandra Boussommier-Calleja
The AI-powered annotation of 11 biological events revealed that embryos with too fast cleavage and too slow blastulation are the most likely to lead to an early pregnancy loss. The results of the present study demonstrate that automatic, AI-annotated kinetic parameters can be used to differentiate embryos that lead to an early pregnancy or not but also between embryos that will likely lead to an early pregnancy loss or to a clinical pregnancy.
Rita Lobo, M.D., ObGyn , Ali Falahati , Kelle Moley , Anja Pinborg , Samuel Santos Ribeiro , Nick Macklon , Ida Engberg Jepsen
The results of this meta-analysis suggest an optimum ovarian response in the range of 8-14 oocytes retrieved to achieve a live birth in the fresh cycle following ovarian stimulation with individualised follitropin delta. The analysis also demonstrates a marked increase in OHSS rate from 15 oocytes retrieved, further supporting the follitropin delta dosing algorithm.
Celine Frank, Claire Laeven, Deidre Meulenbroeks , Edith Coonen , Christine de Die-Smulders, Ron van Golde , Lonne Mallens, Aimee Paulussen , Juliette Schuurmans , Liesbeth van Osch
In this survey, patients seeking IVF/ICSI treatment generally reported positive attitudes towards preconception carrier screening (PCS), valuing the opportunity to make informed reproductive choices. However, specific concerns and misconceptions about PCS arose in the IVF/ICSI population, emphasizing the need for tailored information and counselling.
Despite the rising trend and greater acceptability of transgender parents, the number of parents who had children following their gender transition remains relatively small. This paper presents a case study demonstrating that family formation is possible for a wholly transgender couple within the current UK legal framework with the application of several reproductive technologies. With sufficient determination by the patients, and the ongoing encouragement of the medical team in the clinic, building a family in this challenging context is an achievable route to parenthood for transgender couples.
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RBMO Editorial meeting in London
November saw us gather for our annual Editorial strategy meeting, with our editorial office team, senior Editors and publisher, Elsevier.? We look forward to these occasions each year, enjoy much discussion of developments in our scientific field and research publishing industry, and come away with many new ideas and plans for the coming year.
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RBMO LIVE 10: the Clinical Embryology session
Tuesday 10 December, 3pm ET, 8pm UK
Join us Tuesday 10 December, 3pm ET (8pm UK time) for The Clinical Embryology Session of RBMO LIVE, with four expert speakers showcasing recent papers published in the journal.
Our hosts for the event will be Editor Mina Alikani, and Clinical Embryology Section Editors Thomas Ebner and Basak Balaban highlighting some progressive papers for clinical practices in the IVF lab.
The session will feature talks from
Registration is open on the International IVF Initiative platform – our partners in bringing you our quarterly webinar series.
We look forward to seeing you on the 10th!
11th International IVIRMA Congress, Barcelona, Spain
24 - 26 April, 2025
The IVI RMA GLOBAL congress promises to be an exceptional gathering of professionals, researchers, and academics from around the world, dedicated to advancing the field of reproductive medicine. The theme, assisted reproductive medicine, will be explored through a dynamic program of keynote presentations, hands-on workshops, and interactive sessions, including the announcement and presentations of the RBMO 2024 Robert G. Edwards Prize Paper Award.
Early bird registrations for the event are open now from the conference website.
Turkish Society of Reproductive Medicine
Following a very successful and enjoyable meeting at the Palazzo Hotel, Antalya, in November, we are pleased to publish the Abstracts of the 12th Scientific Meeting of The Turkish Society of Reproductive Medicine.
This issue we showcase our Clinical Assisted Reproductive Technology section, with comments from one of our Section Editors, Prof. Pasquale Patrizio and selected papers.
The CART section of the journal focuses on clinical aspects of assisted reproductive treatments, encompassing ovarian stimulation, prediction models, and clinical trials, including IVF, ICSI, and PGT, as well as fertility preservation and gamete donation and surrogacy.
Pasquale Patrizio, M.D., MBE, HCLD, FACOG , University of Miami, Miller School of Medicine
Clinical Assisted Reproductive Technology Section Editor
‘Clinical and laboratory innovations are at the forefront of Assisted Reproductive Treatments. The field of fertility preservation is constantly brewing new ideas, expanding the indications to include transgender individuals, non-oncological patients and elective procedures. The next frontiers are implementation of artificial intelligence and machine learning into CART, and RBMO is ready!’
A selection of papers from the Clinical Assisted Reproductive Technology Section
Stefano Canosa et al. - Cryostorage management of reproductive cells and tissues in ART: status, needs, opportunities, and potential new challenges
Fatih Aktoz et al. - IVF with reception of oocytes from partner in lesbian couples: a systematic review and swot analysis
Alexandra Bielfeld et al. - Effectiveness of recombinant human follicle-stimulating hormone (r-hFSH):recombinant human luteinizing hormone versus r-hFSH alone in assisted reproductive technology treatment cycles among women aged 35–40 years: a German database study
Allessandra Gallo et al. - Assessing ovarian stimulation with letrozole and levonorgestrel intrauterine system after combined fertility-sparing approach for atypical endometrial lesions: a retrospective case-control study
Sònia Gayete Lafuente. M.D., Ph.D., OBGYN, REI, Clinical Researcher. - Indirect markers of oocyte quality in patients with ovarian endometriosis undergoing IVF/ICSI: a systematic review and meta-analysis
Alessandra Alteri et al. - Are you completely aware of your citations? A cross-sectional survey study on improper citations of retracted articles in medically assisted reproduction
Yuvak Fouks et al. - Looking into the future: a machine learning powered prediction model for oocyte return rates following cryopreservation ?
Dr. Francisco Ruiz et al. - Impact of overweight and obesity on live birth rate in single euploid frozen embryo transfers: the key is in the preparation protocol!
Birgit Alsbjerg & Peter Humaidan - What to expect from a “standard vaginal progesterone regimen” in Hormone Replacement Therapy Frozen Embryo Transfer (HRT-FET) – a PRISMA review and meta-analysis ?
Kelton Kelton Tremellen et al. - Effect of a novel copper chloride gel on endometrial growth and function in healthy volunteers
That brings us to the end of another Insights Newsletter.
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The RBMO Editorial Team
Embryology lab Director, Neural network development for IVF data analytics
3 个月Oh! Yes, Dunning–Kruger effect is the main effect in our reproductive society that should be overcome (