RBMO Insights Issue 21: February 2024
Reproductive BioMedicine Online
An international journal dedicated to biomedical research on human conception and the welfare of the human embryo
Welcome to February’s RBMO Insights; our monthly newsletter of journal related news, updates and community activity. We hope the first month of 2024 has been treating you well, and to all our Chinese colleagues, we wish you the best for the Lunar New Year.
March 12 will see the return of RBMO Live, our quarterly webinar event held in collaboration with the International IVF Initiative (I3). The seventh edition of this webinar will feature Marga Esbert Algam on chromosome segregation, Cermisoni Greta discussing ejaculatory abstinence and fertilisation success, and RBMO Development Editor, Duncan Nicholas with the first part of a publishing tips series.
To mark this webinar, and as a notable occasion in itself, we have launched our official journal YouTube channel, with all six episodes of RBMO Live that are well worth catching up on if you missed them the first time round. The channel also features an interview with leading authors and members of Alpha and I3 giving behind-the-scenes details of their recent review paper, Sustainability in the IVF Lab, and videos of recent Hot Topic papers. Be sure to subscribe to the channel as we have many more insightful, inspiring and informative videos lined up for the coming months.
On a similar note, our recently launched Instagram profile has been picking up followers as we increase our activity on that platform, so please do follow us there if Instagram is one of your favoured sites.
Our Chief Editors, Nick Macklon and Juan A. García Velasco , and founding Editor and Chair of Reproductive Healthcare Ltd. Dr Kamal Ahuja , have published an Editorial that reflects on some of these recent activities, as well as the editorial services our in-house team at the journal have been providing since its launch in 2000, in 25 years of ‘making good papers better’.
The Editorial includes testimonials from authors in recognition of the work our Science Editors provide to enhance the quality of papers published in RBMO. as our Chief Editors put it in their article, ‘Those contemplating RBMO as a journal for their research should be reassured that this editing stage is likely to enhance the quality of their manuscript – or as one author said, ‘make papers better’.’
With that, we will leave you to enjoy this packed issue of Insights, with Talking Points tackling recent papers on platelet-rich plasma, DNA fragmentation, and heart disease, plus article highlights, news from our community and Partner Societies, and a profile highlighting our Female Reproduction, Health and Fertility section.
Platelet-rich plasma treatment in fertility remains dependent on standardised protocols, despite signs of benefit
Platelet-rich plasma, an autologous concentrate of growth factors and other bioactive cytokines, first hit the headlines more than 20 years ago as a tentative adjunct in wound healing and joint pain, especially in sports medicine. Although the evidence seemed mixed - even controversial - the theoretical basis of PRP, that its concentration of growth factors would encourage cell proliferation, seemed not surprisingly applicable in reproductive medicine, notably in endometrial cell proliferation for the improvement of endometrial thickness, and thus of implantation in ART.
A new review of PRP in female fertility, just published in RBM Online, finds PRP the subject of multiple studies in endometrial thickness, poor ovarian response, primary ovarian insufficiency, recurrent implantation failure and chronic endometritis. The majority of them (12/35), according to the authors of this narrative review, were to ‘enhance the endometrial environment’ for successful embryo transfer, and overall there’s a suggestion that PRP ‘might improve implantation rates’. However, as with most systematic reviews today, the studies are dogged by heterogeneity in methodology, small numbers and low grade evidence. The studies which did show a notably increased growth in endometrial thickness following intrauterine PRP infusion were observational.
The same variation in design, study populations and methodology hindered any firm conclusions in ‘ovarian rejuvenation’, nor in the prevention of recurrent implantation failure, despite several promising results ‘suggesting a potential role for PRP’.
One of the variables mentioned by the authors was the protocol for the application of PRP, both in its blood collection, centrifugation (to enhance platelet concentration) and injection. Several of the studies, the authors report, used commercially available kits for PRP preparation, which may potentially lead to greater standardisation in protocol. However, validation studies on these kits still revealed variations in blood components, including platelets. Separate studies, apparently, using the same commercial kits have also shown significantly differing results.
So where does that leave PRP for boosting endometrial receptivity or ovarian rejuvenation? Inconsistency and heterogeneity mark the studies according to this review, with discrepancies and unrecorded practice ‘conspicuous’ in the studies. And given the potential for PRP to offer some benefit in implantation or POI, the absence of a standard protocol is, say the authors, ‘unexpected’. The urgency for such a protocol is ‘palpable’, at last enabling the way for meaningful RCTs.
Two of the authors, Sofia Makieva PhD (pictured) from the University Hospital in Zurich, and Georgios Liparis from Westmead Fertility Centre in Sydney, told RBMO’s Talking Points that they have ‘a keen interest in the efficacy of PRP for the benefit of our patients’, but still any confidence in its application ‘remains contingent upon the establishment of standardized practices’. To witness the unequivocal benefits of PRP, they add, ‘a concerted effort to refine and implement these standardized practices is imperative’.
Recurrent pregnancy loss: Baseline measurement of sperm parameters at referral, including DNA fragmentation, fails to identify risk of further loss
The latest European guidelines on recurrent pregnancy loss, updated in 2022 from the 2017 version, failed to find a clear evidence-based definition of RPL, nor a clear indication of when most treatments might be started. Indeed, says the guideline, even an evidence-based practice in RPL is not yet feasible, as studies are lacking. However, the guidelines did accept the prevalent definition that a diagnosis might be made after the loss of two or more pregnancies.
Most of the guidelines’ risks, investigations and treatments concentrate on the female partner, while for the male only lifestyle factors (paternal age, smoking, alcohol consumption, exercise and body weight) merit a strong recommendation. Sperm DNA fragmentation testing is recommended as ‘conditional’ and ‘for diagnostic purposes’ only. This conclusion now seems justified in the conclusions of a new prospective cohort study of 95 couples diagnosed with RPL (with three or more unexplained losses) at four specialist centres in Denmark. The study by Maria Christine Krog (pictured) and colleagues, published online by RBM Online, assessed the effects of sperm parameters (including DNA fragmentation) on live birth outcomes in the RPL couples referred for investigation and treatment.
Baseline DNA fragmentation measurements at referral showed no differences between the male partners of couples who had a further pregnancy loss (DNA fragmentation index 11.7) and those who had a live birth (index 12.5). These findings in a ‘fertile population’, the authors point out, seem different from those in an infertile population, where high levels of sperm DNA fragmentation in IVF/ICSI patients have been associated with pregnancy loss. Yet in this latest study men with increasing levels of sperm DNA fragmentation referred with their partners for RPL had no increased risk of a further pregnancy loss. The authors thus conclude that our results ‘may imply that a high [sperm DNA fragmentation index] does not play a role in the pathogenesis of most pregnancy losses in RPL couples who are able to conceive’
What about other sperm parameters? Again, pregnancy outcome after referral was not associated with median sperm concentration, with median levels recorded above the WHO’s lower reference limit of 15 million/ml, nor with sperm cells of normal morphology. The authors did report that results of previous studies investigating the association of sperm concentration and morphology with RPL have been mixed. Here in this study, however, with high levels of sperm DNA fragmentation not associated with an increased risk of further pregnancy loss and with sperm concentration and morphology often in the normal range, the authors suggested that some ‘unrecognized male factor’ is contributing to reproductive failure - in addition to lifestyle factors.
Cross-linkage cohort study finds no association of CVD with ART
Fertility treatment is not associated with any increased risk of hospitalisation for cardiovascular disease, according to a large retrospective cohort analysis from Australia. The results, say the authors (Dunya Tomic, pictured), ‘provide reassurance that fertility therapy is a safe option for many women’. The conclusion, which echoes those of other recent studies, is based on results of a cross-linkage study just published in RBM Online in which all women registered for treatment at Monash IVF clinics between 1998 and 2014 were linked to hospital admission records. There was a total of 27,262 women registered for treatment, of whom 24,131 went ahead and 3131 did not.
Anxieties about ART and CVD risk have persisted for many years, despite no strong evidence of an association. The link between ovarian stimulation and thrombosis, say the authors of this report, ‘remains unclear’, while metabolic pregnancy complications following ART, particularly FET, have been well described.
Yet despite such possibilities of how ART might increase the risk of CVD, large-scale safety studies have failed to make the association. Last year, for example, a study from the Nordic CoNARTaS registry collaboration, which included almost 2.5 million subjects with 100,000 ART patients, reported that women who gave birth after ART were at no greater risk of CVD over a median follow-up of 11 years than women who had conceived without ART.
In this latest study, after a median follow-up time of 11.8 years, there was no significant difference in CVD hospitalisation rates between the treated and non-treated women, nor was any difference found in admission rates for five specific CVD sub-types. However, the study did stratify for area of residence and found that the relative risk of CVD admissions between treated and untreated women was lowest in the two lowest socially disadvantaged fifths (reflecting the lowest area-based social disadvantage), and reaching statistical significance in the second fifth. The relative risk increased toward the highest levels of social advantage - though the authors were cautious about any strict interpretation.
The study, of course, was retrospective and observational, and was unable to include potentially confounding information on lifestyle or other risks for CVD (smoking, PCOS). Similarly excluded was any distinction between successful and unsuccessful treatment - thus the only ‘control’ was a relatively small component of women registered for treatment at Monash who did not go ahead with it. Successful of unsuccessful treatment was not followed up, leaving this as a major confounder, especially with pregnancy complications a well-established known risk factor for CVD.
Jullin Fjeldstad , Weikai Qi , Natalie Mercuri , Nadia S. , Jim Meriano, B.Sc, M.Sc, PhD , Alex K. , Dan Nayot
This paper reports on the development of an artificial intelligence image analysis model to evaluate the developmental potential, as defined by blastocyst development outcomes (formation and quality), of metaphase II oocytes – which may facilitate greater consideration of the oocyte in clinical practice and assist with scientific research on the oocyte.
Carla Olmedo, Ernesto Veiga, Lourdes Sánchez, Empar Ferrer, Nereida Ortiz, Alba Mauri, María Fernández, Luis Martínez, María Luisa López Regalado, Miriam Iglesias
Assisted human reproduction has undergone rapid advances since its inception 45 years ago. To keep pace with these advances, assisted reproduction laboratories should adhere to a quality management system that addresses staffing and training, physical space and air quality, equipment maintenance and other operational matters, and ensures gamete and embryos handling in accordance with the latest quality and safety standards.
This review from the ASEBIR Quality Special Interest Group serves as a reference document highlighting critical aspects to consider when establishing and operating an ART laboratory.
The authors, CARLA OLMEDO , Ernesto Veiga, Lourdes Sánchez, Empar Ferrer Robles , @Nereida Ortiz, Alba Mauri López , María Fernández, Luis Martínez, María Luisa López Regalado, and Miriam Iglesias, collate and expand upon published consensus documents, national and international guidelines, providing easier access to this large body of important information.
This paper collates already published guidelines, recommendations and standards related to operation of a human IVF laboratory into a comprehensive reference document, addressing:
Altogether, the key aspects covered aim to help IVF laboratories minimize risk and ensure safety of gametes and embryos.
In healthcare, leadership plays a crucial role in determining the quality of care and overall clinical performance, however, the pivotal role of leadership in the effective functioning and success of in IVF laboratories is often overlooked. This commentary from Alessandra Alteri and George Koustas addresses this disconnect, and suggests that by enhancing leadership skills, IVF laboratories can improve their efficiency, team morale, and patient outcomes. The authors also emphasise the necessity for formal leadership training for IVF laboratory directors, urging the involvement of IVF centres, scientific societies, and professional bodies.
Elkin Mu?oz , Fernando Bronet , Belen Lledo, Gabriela Palacios Verdu , Lorena Martinez-Rocca, Signe Altm?e , Josep Pla
This narrative review summarizes current knowledge about mosaic embryos in the field of assisted reproduction techniques. The authors conducted a literature search and this review is intended to serve as reference material for practitioners in reproductive medicine who must manage a mosaic embryo result after PGT-A. The review covers the aetiology, classification and diagnosis of human embryonic mosaicism, as well as clinical outcomes and genetic counselling when transferring mosaic embryos. It is intended to serve as a reference for practitioners in assisted reproduction.
领英推荐
Sustainability in the IVF Lab Interview
We spoke to Dr Mina Alikani , Prof. Jacques Cohen , Giles Palmer and Francesca Farlie about the background and goals of their recent collaborative review Sustainability in the IVF laboratory: recommendations of an expert panel.
This paper is the result of work between members of Alpha Scientists, International IVF Initiative and a network of experts from the fields of environmental science, architecture, biorepository, and law, who came together with the aim of understanding the key issues, and developing a framework that helps IVF labs take the first steps towards a greener, more ecologically sustainable industry.
Watch the teaser video and the full interview on our YouTube channel now.
SCOPUS AI
Our publisher, Elsevier has announced the official launch of its SCOPUS AI platform following its trials from August 2023, in a blog post titled ‘Trusted content. Powered by responsible AI’.
The platform is a bibliographic summary tool, providing text summaries and relationship networks of related articles from within the Scopus database in response to prompts. The blog post references feedback provided by users during the alpha phases of the project, addressing concerns around accuracy, reliability, trustworthiness, transparency and accountability that have limited the value of outputs from most generative AI tools up to this point, but the post goes as far as including the disclaimer that ‘Although it's currently impossible to entirely eliminate inaccurate responses, these steps greatly reduce the risk of them appearing, and we continue to work on developments to limit that risk.’
The post describes the purposes and outputs of the tool, including its ability to provide researchers with summary overviews of key topics that can provide contextual detail and sometimes even highlighting gaps in literature, as well as highlight foundational papers and prominent researchers.
We have seen this platform and its features in use ourselves, and it does look to have some interesting and worthwhile potential. Scientific references have not been one of the more successful features of the outputs of AI generated text, but this tool does appear to have been carefully modelled and managed, and may mark another step in the right direction.
You can learn more about Scopus AI, view a short demo and register your interest here.
Alpha Scientists have updated the dedicated RBMO page of their website with the latest Hot Topics from Volume 48 of the journal, including papers on clinical use of progesterone in human sperm preparation media, random start ovarian stimulation, and two papers that highlight the impact of metabolic and immune changes on reproductive potential.
Registration is open now for the 14th ALPHA Biennial Conference, in Lisbon, Portugal
30 May - 02 June. The Organizing Committee has put together an exciting program of international speakers, which covers many facets of human IVF and ART. As always, the program is designed to provoke thought and inspire debate and discussion of the hottest topics, including the announcement and presentations from our 2023 Robert G. Edwards Prize Paper Award winners.
Register on the conference webpage.
Affiliated Society Communications
We have published two papers in our new formats for partner society guidelines and statements.
Society Guideline from the Canadian Fertility & Andrology Society
Fertility preservation in patients undergoing gonadotoxic treatments: a Canadian Fertility and Andrology Society clinical practice guideline
Jeffrey E Roberts, Janie Benoit, Shu Foong, Julio Saumet, Ann Korkidakis, Kristin Marr, Sarah McQuillan, Nicole Todd
Society Statement from Association of Reproductive and Clinical Scientists
Male infertility and semen analysis: the advantages and disadvantages of turning to ‘home testing’ – a statement from ARCS
Chief Editors Nick Macklon and Juan Garcia Velasco introduce a new episode of RBMO Live, our quarterly webinar series in collaboration with the International IVF Initiative. Register now, to join us at 3pm Eastern/8pm UK, Tuesday 12 March for 90 minutes of presentations from RBMO authors, behind the scenes insights into the journal, panel discussion and audience questions.
Marga Esbert will present on her recent paper on chromosome segregation and IVF, investigating the effect of rescue-in vitro maturation in presence or absence of cumulus cells on meiosis I progress. From a cytogenetic perspective, this study's results argue that immature oocytes should not be discarded, particularly when few metaphase II oocytes have been retrieved, and we look forward to Marga unpacking the implications of this interesting work.
Greta Cermisoni will discuss her group’s paper on the effect of ejaculatory abstinence period on fertilisation and clinical outcomes from an analysis of 6,919 cycles. This paper put concepts around abstinence time-frames to the test, and shows the importance of challenging long-established practices.
RBMO Development Editor, Duncan Nicholas will deliver the first in a publishing tips series for RBMO Live that will cover topics such as submission, peer review and revision, open science, post-acceptance and post-publication skills for newer (and more experienced!) researchers. Our first set of tips will start with manuscript preparation and requirements for submission and acceptance at a high impact journal.
This issue we put a spotlight on our Female Reproductive Health and Fertility section.
Selected papers from our Female Reproductive Health and Fertility section
That brings us to the end of another Insights newsletter.
If you have any thoughts or ideas you’d like to share with us about the newsletter, please do comment below this posty, or send us an email. We will be happy to hear from you.
The RBMO Editorial Team