RBMO Insights Issue 20: January 2024
Reproductive BioMedicine Online
An international journal dedicated to biomedical research on human conception and the welfare of the human embryo
A very Happy New Year to you and a warm welcome to the first RBMO Insights issue of 2024. This is a time to look ahead and at RBMO we are pleased to see a number of new developments taking shape.
In the December issue of RBMO we launched a new journal section with associated article types, to better support our Society Partners. The section, Affiliated Society Communications, will be the new home for two new article types: Society Guidelines and Society Statements. Society Statements are short documents that describe or define the position of a Society on a specific matter, with recommendations and suggestions for practice. Society Guidelines are typically more extensive articles, based on review methodologies that may include literature and statistical analysis, discussion, concluding guidance with recommendations or prompts for future actions. The first Society Statement published in this format was the statement from ARCS, Male infertility and semen analysis: the advantages and disadvantages of turning to ‘home testing’, and the first Guideline will be from the Canadian Fertility and Andrology Society, Fertility preservation in patients undergoing gonadotoxic treatments.
We are also pleased to have accepted three of our new Viewpoint article types, all of which are available online now, and will be published in an issue very soon. The latest Viewpoint is highlighted in our Talking Points section of this issue of Insights on endometrial preparation strategies for frozen embryo transfer.
In this issue we also take a look back at all the Hot Topic paper selections from 2023, shine a spotlight on the work of our in-house editorial team, consider how social media platform use may be changing in the new year, and look towards events coming up over the next few months, including the return of ‘RBMO Live!’.
We hope you enjoy this issue, and wish you all the best for 2024.
Mediterranean diet found a ‘straightforward approach’ for improving success rates in IVF
Once again, the Mediterranean diet has been named number one in the U.S. News & World Report’s Best Diets of the year - for the sixth time in a row. Health benefits have been well documented - in the prevention of cardiovascular disease, dementia and some cancers, and even improvement in rates of all-cause mortality. Now, following a recent review in RBM Online, fertility - or at least the chance of success in IVF - may be added to the list of ever expanding benefits from following a diet dominated by fruits, vegetables, legumes, whole grains and nuts, all rich in antioxidants, vitamins, minerals and fibre.
The review, researched for RBMO by Professor Roger Hart from the University of Western Australia, Perth, analysed the evidence for many nutritional supplements and diets thought to improve outcome in IVF and concluded that adopting a Mediterranean diet during treatment would offer a single ‘straightforward approach’ with good evidence of benefit - especially in contrast to that of a Western diet.
However, while the many studies were not difficult to find, their results and methodologies proved inconsistent and of poor quality. ‘Nutritional supplements are usually not prescribed,’ explained Professor Hart, ‘but are bought online or over-the-counter. They’re self-medicated and solid data on usage is impossible to determine. Our information is largely anecdotal but it’s quite clear from online IVF discussion forums that they are widely used and of great public interest.’
However, the evidence in favour of a Mediterranean diet was much stronger and included several well designed RCTs showing benefits in both embryo development and pregnancy outcome (even from a six-week intervention programme). ‘These diets are high in B-vitamins, antioxidants, omega-3 poly-unsaturated fatty acids and fibre and are low in saturated fat, sugar and sodium,’ said Professor Hart. Evidence suggested that omega-3 fatty acids ‘may be beneficial’ in improving IVF clinical outcomes and embryo quality, although one major review in 2020 of 63 antioxidant studies described them as of low quality and was unable to demonstrate any benefit in terms of live birth rate. Studies were similarly found of poor quality in subfertile men given antioxidant supplements, with evidence of benefit described as of ‘low certainty’.
The report was featured in a press release issued by RBMO in December, which was well covered by UK, US and Australian media, as part of our programme of activities to support our publications with public news value.
Convenience or safety? The pros and cons of endometrial preparation strategies for FET
In the latest RBMO Viewpoint, published online in December, clinical specialists Professor Christophe Blockeel and Barbara Lawrenz propose that the use of hormone therapy in endometrial preparation for FET ‘should now belong to the past’. Their argument? That serum levels of estradiol, which encourage endometrial proliferation, also suppress follicle growth and consequently the formation of a corpus luteum. Evidence now indicates that complications of pregnancy, such as pre-eclampsia and miscarriage, are more frequent in ‘medicated’ cycles primed with hormone therapy. And this, they add, ‘is likely due to the absence of a corpus luteum’, which denies the mother relaxin and other vasoactive substances important for her adaptation to the pregnancy.
Recognising a general move to avoid these complications, the Viewpoint notes ‘contemporary evidence’ favouring a natural cycle approach, which allows follicle growth and corpus luteum formation, described as ‘the optimal strategy’ for mitigating the hazards of the HRT approach.
But adopting the natural cycle (pure or modified), of course, puts the clinic in a dilemma about the timing of the trigger and the window of implantation. Minimise the risk of pregnancy complications, or minimise the risk of weekend working for the clinic and multiple visits for the patient? Or as a Nordic group recently put it in an RBMO commentary, ‘convenience or safety?’
The Nordic commentary described four approaches to endometrial preparation for FET: natural cycle, in which no medication is given; modified natural cycle, in which ovulation is usually triggered by timed hCG; stimulated cycle + ovulation trigger; and an ‘artificial’ programmed cycle with hormone therapy. The reviewers noted that the main reason for choosing the programmed cycle ‘is probably convenience, both for the clinic and for the patient’. One can schedule the embryo transfer according to office hours and avoid weekends. But they too cited studies in which adverse outcomes (hypertensive disorders) proved most common in these programmed FETs ‘related to the lack of corpus luteum’ - an odds ratio of 1.6 against those from stimulated cycles in one study. The reviewers thus concluded - as Blockeel and Lawrenz suggest - ‘that the FET strategy with an intact corpus luteum should be preferred’. A recent systematic review also concluded that, based on the current evidence, natural cycle should be the recommended treatment for ovulatory patients.
How to resolve the dilemma? Large population studies would be ‘ethically troublesome’, wrote the Nordic commentators, because programmed cycles might pose an added and unnecessary risk for subjects. Yet despite such risks programmed cycles are still ‘frequently used’, presumably for more convenient patient throughput, especially as FET numbers continue to rise. Indeed, the latest preliminary world IVF data (for 2019), presented at last year’s ESHRE meeting in Copenhagen, found 40% of embryos were transferred fresh and 60% were FETs, while around 38% of all aspirations were for freeze-all cycles.
Behind the RBMO Viewpoint lies a study which suggests that the ‘ideal scenario’ - the existence of a corpus luteum along with the opportunity for improved ET scheduling - may yet be possible through a modified natural cycle approach. A recent RBMO study reported by Alonso and colleagues from IVIRMA in Madrid in more than 3000 FETs found that triggering could be successfully achieved by flexible administration of hCG at a follicle size between 13 and 22 mm. No longer might triggering be dependent on a strict adherence to 17 mm.
The study stratified triggering into three follicle-size groups - 13.0–15.9 mm, 16.0–18.9 mm, and 19.0–22 mm - with few differences found in pregnancy rate between the three. While there were apparent variations in ongoing PRs, these were no longer significant when adjusted for PGT-A or egg donation. And in their conclusions the authors note that, with a follicular growth rate of 1—1.5 mm per day, this flexible triggering approach might allow a similar flexibility for FET scheduling - of five to seven days. This, they suggest, would offer a transfer window of seven days, which would of course remove any need for weekend working. In addition, cycle monitoring might be simplified and clinic visits for the patient reduced, while safety in pregnancy would remain intact with the presence of a corpus luteum. However, as the Viewpoint notes, will a corpus luteum derived from a 13 mm follicle be as protective as one derived from a true natural cycle?
‘Drifting back to nature’ was the subtext of a RBMO Countercurrent, also from IVIRMA, which too considered strategies to minimise the perceived risks of artificial and natural cycle transfer (notably cycle cancellation). This opinion also recognised that a modified natural cycle would allow the purely natural cycle to become ‘more practical’, and that a more flexible hCG triggering protocol, as proposed by Alonso et al, ‘may balance workload organization in IVF centres and lead to optimal pregnancy outcomes’
To start the year, we round up of all the Hot Topic papers selected by Mina Alikani and Richard Anderson last year to look back at some of the most progressive papers published in RBMO, and give a snapshot of the areas of groundbreaking reproductive medicine research in 2023.
Maria Cristina Magli et al.
Distinguishing viable from non-viable sperm in asthenozoospermic samples presents a challenge during ICSI. Using polarized light microscopy, the authors identified and used differences in the birefringence of the sperm head, with good clinical results. There is an element of subjectivity in the methodology, and confirmation by other groups will be critical.
Nathalie Sermondade et al.
This thought-provoking study based on analysis of a large dataset from the French National Health System confirms the impact of ART on fetal growth disorders, also concluding that these are independent of maternal-fetal morbidities.
Nardin Aslih et al.
Although very preliminary, this intriguing study?uses non-invasive spectrometric technology and machine learning to assess metabolites in culture media for better embryo selection.
Sapthami Nadesapillai et al.
The indications for fertility preservation are expanding, but particularly for ovarian tissue cryopreservation when the pathology lies within the ovary, there is a lot of uncertainty about its value. This paper explores the views of young women with Turner syndrome and their parents on this challenging topic.
Shari Mackens et al.
An observational study suggesting the value of testing and adding progestogen when required. As the authors point out, there is a real need for RCTs to address this, before it becomes accepted but inadequately tested practice.
Yidong Chen et al.
Conjoined twinning is rare and its pathogenesis poorly understood. This study combines DNA methylation, gene expression and exome mutation analysis to reveal epigenomic similarities and differences between conjoined fetuses. The findings shed light on the mechanisms underlying this enigma of early development.
Kilian Vomstein et al.
Immune function in the endometrium continues to be of interest in the investigation of RPL and infertility but getting samples has challenges. Here the noninvasive collection and analysis of menstrual blood is shown to match traditional endometrial biopsies. Easier sampling paves the way for bigger, better studies in this controversial field.
Nuno Costa Borges et al.
This paper by Nuno Costa-Borges and colleagues reports two healthy live births from a semi-automated sperm injection procedure performed via a robotic arm. This is a milestone that undoubtedly will hasten development of more (and fully) automated technologies in the IVF laboratory, in turn (and in time) increasing consistency and improving efficacy of laboratory procedures.
Juan Giles et al.
Progestogen suppression in ovarian stimulation is gaining traction, with a substantial cost saving. This observational analysis considers its used in elective fertility preservation and PGT-A cycles, when there is no possibility of fresh embryo transfer. Results were very positive: will this be another example of a treatment becoming standard without rigorous RCT evaluation, or is that unnecessary?
Radhika Kakulavarapu et al
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Cell exclusion during and following compaction is a well-known phenomenon in early embryo development. In this paper, the authors get into a deeper analysis of the events surrounding exclusion and its downstream effects. Another example of the value of timelapse technologies in expanding our understanding of human embryo development in vitro.
Giles Palmer et al.
Clinical embryology is entering a new era where IoT, automation, AI and standard procedures will be increasingly intersecting and merging. To understand how and why, you need to read this comprehensive and important review!
Cermisoni Greta et al.
Some concepts in assisted reproduction remain oddly persistent over time: what is the impact of requiring 2-7 days of abstinence when it’s for a sample to use in ICSI? This paper puts the concept to test and shows the importance of challenging long-established practice.
Jaime Guerrero et al.
Random start ovarian stimulation is increasingly widely used, since its origins as a way to minimise delays in fertility preservation. This analysis of its use in the context of oocyte donation supports its efficacy with no difference in LBR between follicular and luteal phase starts, as well as its convenience when there is no need to consider endometrial synchrony.
Nicole McPherson et al.
Does addition of progesterone to sperm preparation media help bridge the gap in fertilisation rates between ICSI and standard IVF? This seems feasible, based on extensive testing in animal models in this paper. Clinically translatable? Perhaps – but RCTs are needed.
Testimonials for our Editorial team
This year we are shining a light on the work that goes on behind the scenes at the journal in the peer review process, and acceptance stages, prior to final publication - and the dedicated colleagues who ensure that your accepted papers reach publication quickly and in fine fettle.
A hidden secret of RBMO, as anyone with an accepted paper will tell you, is our expert in-house science editors, Catherine Field and Fiona Warrander , who work closely with our authors on final edits of their papers to make them as accurate and effective in conveying the value of their findings as possible.
Don’t just take our word for it. Here are some recent testimonials of our Editors’ work from our authors
‘I'd like to express my gratitude for the meticulous review of our manuscript. Your comprehensive feedback has been instrumental in enhancing the quality of our work. Thank you once again for your dedicated attention to our manuscript.’
- Dr Luca Pagliardini, Ospedale San Raffaele, Italy
‘Thank you very much for further editing the manuscript and going deeply into the details. Your work is very important, and the editing has improved the quality and presentation of the final published article even further.’
- Prof. Thomas Hviid, Zealand University Hospital, University of Copenhagen, Denmark
‘I am writing to express my heartfelt gratitude for the time and effort you devoted to carefully editing our manuscript. We have carefully considered and implemented all of the changes you suggested, and we are confident that your scientific editing has greatly improved the quality of our work. Thank you once again for your invaluable contribution to our research.’
- Dr Sunita Sharma, Institute of Reproductive Medicine, India
Social media platforms in 20242023 was a time of some disruption in the social media landscape, with enthusiasm for Twitter falling, and several alternatives vying for our attention as a replacement.
The Society for Scholarly Publishing ’s (SSP’s) Marketing and Communications team undertook a survey to understand more about the direction that online discussion is heading among the academic community. The group have now published a discussion of their findings on industry blog, The Scholarly Kitchen .
At RBMO, we have been wondering similar questions. Through which channels did you find this newsletter; social media or direct email? Did you know you can find RBMO on LinkedIn, Twitter/X and Instagram? Have you already investigated the newer platforms of Mastodon or Twitter sibling, Bluesky? Should we set up a channel on one of those too?
What are your preferences for social media, and will you be making any changes to your habits this year? Let us know your thoughts in the comments below.
Real-time image analysis for Piezo-intracytoplasmic sperm injection infographic
Diana Tain has created an illustration for recent RBMO article by Morimoto et al, demonstrating that a real-time image analysis during Piezo-ICSI markedly reduced oocyte degeneration by avoiding areas associated with a high risk of unintentional membrane rupture.
Thanks to Diana for her support of the journal and her illustrations. Follow her work on Instagram and LinkedIn, and future issues of Insights!
RBMO Live
Tuesday 12 March, 3pm EST / 8pm UK / 9pm CET
Our quarterly webinar series with the International IVF Initiative will return this year, starting Tuesday 12 March. Stay tuned, as we unveil more details in next month’s issue of Insights.
Fertility 2024, Edinburgh, UK
10 - 13?January
The annual conference of our partner society The Association of Reproductive and Clinical Scientists (ARCS), organised in collaboration with the British Fertility Society (BFS) and the Society for Reproduction and Fertility (SRF). Sessions will feature RBMO Editors Nick Macklon, Richard Anderson and Christopher Barrett, plus several of our Section Editors and Editorial Board members.
14th ALPHA Biennial Conference, Lisbon, Portugal
30 May - 02 June
This progressive conference will feature renowned plenary speakers Jacques Cohen (founding RBMO Chief Editor) discussing The Next Big Thing In IVF, RBMO Editor David Gardner reflecting on The Future Of Human Embryo Culture, and the announcement of our 2023 Robert G. Edwards Prize Paper Award winners.
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 send us an email.
The RBMO Editorial Team
Professor and Medical Director, London Women's Clinic, London UK
10 个月Recommended and a great way to start the year!