Free Access Articles
Home monitoring of ovarian stimulation: an important step towards more patient-centred IVF
Since the early 1980s there has been constant evolution in the clinical management of IVF treatments. From the patient's perspective, significant innovations have included: (i) the replacement of oocyte retrieval through laparoscopy under general anaesthesia by ultrasound-guided out-patient transvaginal puncture; (ii) the introduction of GnRH analogues to suppress a premature rise in LH (avoiding the need for frequent LH peak monitoring); (iii) calibrated pens allowing patients to inject gonadotrophins themselves and avoiding dependency on nurses or hospital facilities; (iv) the introduction of milder and less complex stimulation protocols (significantly reducing side effects and the need for intense ovarian response monitoring and frequent hospital visits) (Nargund and Fauser, 2020); and (v) the recognition of the distinct burden of treatment and psychological stress associated with IVF (resulting in significant treatment drop out and reduced cumulative pregnancy chances per started IVF treatment).Reproduction, Technology and Society - a new section in RBMO
This issue sees the launch of Reproduction, Technology and Society (RTS), a new section of RBMO fully dedicated, as the name conveys, to issues at the interfaces between reproduction, technology, and society.Meet our new editor: Professor Laura Rienzi
Laura Rienzi is a Senior Clinical Embryologist and Laboratory Director at the GENERA Centres for Reproductive Medicine in Rome, Marostica, Umbertide and Naples in Italy. Laura has academic degrees in biology from the University of Rome 'La Sapienza' and in reproductive medicine from the University of Padua. Since 2016, she has been adjunct Professor of Biotechnology at the University of Urbino, Italy.Mild ovarian stimulation for IVF is the smartest way forward
The aim of IVF treatment is to achieve a healthy full-term baby, with minimal health risks to the woman and her child, and at reasonable cost to allow this treatment option to be within financial reach for many women around the world. Ovarian stimulation – which contributes a considerable proportion of the overall cost of IVF – aims to generate multiple follicle development, allowing for the retrieval of multiple oocytes to improve success rates. Complex ovarian stimulation regimens have become an integral part of most IVF programmes.Male fertility: a window on the health of this generation and the next
In this issue of RBMO Martín-Calvo and colleagues (Martín-Calvo et al., 2019) provide clinical data showing that higher paternal pre conception folate intake was significantly associated with a longer gestation time. Previous studies in mice have shown that manipulation of paternal dietary folate was associated with increased birth defects and identified marked changes in the sperm epigenome associated with health of the offspring (Lambrot et al., 2013). Whilst the potential epigenetic mechanisms remain to be elucidated fully in animals and are, at best, unclear in humans, this study puts the focus of examination on the contribution of the male to overall health of future generations.May the colleague who truly has no conflict of interest now please stand up!
A vividly remembered conversation from quite a few years ago with someone influential in Dutch society began ‘I am sure you academics do very important scientific work, but the problem is that we as society notice so little health benefits resulting from these discoveries. Since universities are primarily paid by tax payers' money, what's our return on this investment?’ It took quite some time to get to grips with this message, but it did lead to the profound realization of how far away from mainstream society we often operate.The female post-cancer fertility-counselling clinic: looking beyond the freezer. A much needed addition to oncofertility care
The number of girls and young women surviving cancer is increasing. It has been estimated that each year 43 new cancer cases are diagnosed per 100,000 people of both sexes between the ages of 20 and 39 years. Cancer is more common in women than men (Fidler et al, 2017). The consequences of being diagnosed with a malignant disease are serious, not just for the individual but also at a societal and economic level. While treatment is often successful, the impact of the disease on the life course is significant, as multiple long-term side effects of cancer treatment, and the psychological fallout of facing such a diagnosis at a young age, continue to resonate in later life.Chief editor’s 2018 annual report
We have completed yet another exciting year at RBMO. Most importantly the broad scope of the journal's content and the close interaction between the editorial office staff and the editors and the authors remains a constant strength. In addition, we completely updated the layout of the journal: both the artwork and logo on the cover and also the layout of the papers themselves. We are very proud of the new look and feel of RBMO, which is now completely in line with the identity of the journal, the growth of the field and our level of ambition! During summer, the editorial office moved to Bourn Hall, Cambridge, UK, a most fitting location.Origins of mosaicism and criteria for the transfer of mosaic embryos
Blastocysts classified as mosaic by preimplamtation genetic testing for aneuploidy (PGT-A) [usually through array comparative genomic hybridization (aCGH) or next-generation sequencing (NGS)] have been reported to implant less frequently and miscarry more frequently than embryos classified as euploid, but still be able to produce chromosomally normal and viable pregnancies (Fragouli et al., 2017; Greco et al., 2015; Munné et al., 2017; Spinella et al., 2018). As such, the Preimplantation Genetic Diagnosis International Society (PGDIS), Controversies in Preconception, Preimplantation and Prenatal Genetic Diagnosis (CoGEN) and others (Munné et al., 2016) have recommended that care providers prioritize euploid embryos over mosaic embryos for transfer and only consider mosaics for replacement when no euploid embryos are available.Chief editor's 2017 annual report
2017 was an exciting and rewarding year for RBM Online, as it continued to provide cutting-edge information regarding basic, translational and clinical aspects of infertility and related areas of reproductive health. Among the successes, most notably the impact factor reached a value well above 3 for the first time in the journal's history (Figure 1), placing it in the first quartile of all journals published in the categories ‘Obstetrics and Gynecology’ and ‘Reproductive Biology’.Surging ahead
2017 was a very successful year for RBMOnline, most notably with the announcement of an Impact Factor of 3.249, the highest yet achieved by the journal since its inclusion in the ranking nearly 10 years ago, and matched by improvements in other ranking metrics such as CiteScore, Article Influence and SNIP. This outcome reflects the increased quality of the papers published in the journal and places it in sixth position in the ranking of reproductive biology titles. As part of the continuing development of the journal, we welcomed Richard Anderson to the team of editors (Anderson, 2017), joining Mina Alikani, Juan Garcia Velasco and Martin Johnson, and allowing the Chief Editor more time to focus on strategic considerations.Human-animal chimeras: circumventing rather than discussing ethical concerns comes at a price
This issue of RBMOnline features a highly interesting paper on chimeras intended for human gamete production by philosopher César Palacios-González (2017). The paper breaks new ground by linking two ethically charged scientific developments. Whilst several groups are aiming to create stem cell-derived gametes through tissue culture in the laboratory (Hendriks et al., 2015), others are working on interspecies chimeras as a possible future route to obtaining human stem cell-derived organs from animals, both for research and for transplantation purposes.First birth following spindle transfer for mitochondrial replacement therapy: hope and trepidation
In this issue, Zhang et al. (2017) report the birth of a healthy boy after mitochondrial replacement therapy (MRT) by spindle transfer to prevent transmission of mitochondrial disease from mother to child. The case was first publicized in the lay press (Hamzelou, 2016; see also editorial by Johnson, 2016) and then presented during the 2016 Annual Meeting of the American Society for Assisted Reproduction (ASRM) in October 2016 (Zhang et al., 2016a). It followed an earlier report of an unsuccessful attempt at MRT by pronuclear transfer by the same group (Zhang et al., 2016b).What do we know about endometrial receptivity in women with endometriosis? A molecular perspective
Endometriosis is a relatively wide-spread benign but debilitating gynaecological disorder affecting women of reproductive age. Endometriosis develops following the implantation of endometrial tissue at ectopic locations, mainly peritoneal and on the surface of pelvic organs (Giudice, 2010). The prevalence of this disease varies from 4–50% in different populations (Cramer and Missmer, 2002; Eskenazi and Warner, 1997), and occurs in up to 50% of women with pelvic pain and/or infertility (Giudice, 2010; Meuleman et al., 2009).Meet our new Editor
Dr Mina Alikani PhD is a Clinical Embryologist, currently working as a Laboratory Director and consultant in New York, USA. Her interest in this field was piqued in 1978, with the announcement of the world's first IVF birth. Having recently immigrated to the United States, she entered university, choosing biology as her major. Mina's early enthusiasm for developmental biology and embryology led her to the laboratories of Professor Lajos Pikó at the local Veteran's Administration Hospital, in Northridge, Southern California, where, as a young volunteer, she learned how to work with mice and isolate and culture early mouse embryos.Meet our new editor
Professor Juan A Garcia-Velasco MD PhD completed his medical training at Complutense University in Madrid, Spain in 1990 and his residency training in Obstetrics and Gynecology at La Paz Hospital, Madrid, Spain in 1995. He then joined Instituto Valenciano de Infertilidad (IVI) for a year in its early days (1996), followed immediately by a Fellowship in Reproductive Endocrinology and Infertility at Yale University, USA, where he worked under the guidance of Professor Aydin Arici (1997–1998). There he became enthusiastic about the relevance of molecular biology to human reproduction, and did extensive research in the field of cell adhesion and endometriosis.Live births following karyomapping – a “key” milestone in the development of preimplantation genetic diagnosis
Twenty-five years ago, during the early days of preimplantation genetic diagnosis (PGD), the use of the polymerase chain reaction (PCR) for single-cell genetics was in its infancy. Reamplification of short fragments of DNA with a second set of internal or “nested” primers for mutation detection was possible (Coutelle et al., 1989; Holding and Monk, 1989), but plagued with the problems of contamination and allele dropout (ADO). Separate clean-room facilities for sample preparation were therefore essential.Deep impact: sequencing embryo biopsy specimens at increasing depth
Despite major advances in assisted reproductive technologies (ART), it remains the case that more than half of all IVF treatments do not ultimately result in the birth of a child. It is clear that the majority of embryos created through IVF are not capable of producing a viable pregnancy, with most failing to implant in the uterus or miscarrying soon afterwards (Fragouli et al., 2013).Is there a clinical future for GV manipulation?
In this issue of RBMOnline, Zhang and Liu present their latest work involving mammalian germinal vesicle (GV) transfer (Zhang and Liu, 2015). This study extends the prior work of these authors and others in examining this technique (Liu et al., 2003; Takeuchi et al., 2001; Zhang et al., 1999). One finding of developmental interest is the observation that when reciprocal GV transfers between human and mouse oocytes were performed, the maturation process and spindle formation followed the expected form of the species donating the ooplast.A plea for caution and more research in the ‘experimental’ use of ionophores in ICSI
Other than the fear of a negative pregnancy outcome, fear of fertilization failure is probably one of the foremost motives for the growing practice of using ICSI, rather than conventional insemination, for all couples undergoing IVF. However, even with the insertion of a morphologically normal sperm from an individual of known fertility, there are instances, albeit relatively rare, where no fertilization occurs, as indicated by absent pronuclear formation. Artificial oocyte activation, aimed at obtaining at least one zygote, is considered when all mature oocytes are supposedly affected.Oocyte donor information – how much is enough?
One of the most contested debates in the field of reproductive donation concerns the question of how much information about gamete donors should be provided to gamete recipients. Part of what makes this question challenging is that there is only a limited pool of empirical research to draw from when making evidence-based arguments in favour of one policy or practice of information provision over another. Analysis of this evidence is further complicated by the fact that more evidence exists about recipients of sperm donation than recipients of oocyte donation.Regulation of assisted reproduction in the USA – a just target or a target of unfair criticism?
Soon after the first IVF clinics opened their doors, sensible voices within this emerging field contemplated the many facets and complexities of manipulating reproduction. The new reproductive options were often debated publicly, and ethical and safety guidelines were proposed by IVF pioneers, interest groups and legislators. Several decades have passed, yet there has been no uniformity in this international effort. Some countries, most notably Australia, Belgium and the UK, have had effective regulatory systems in place for some time.Therapy for mitochondrial genetic disease: are we at the thin end of the wedge?
This issue contains a commentary by Tetsuya Ishii (Ishii, 2014) which raises a number of important ethical issues, some of which were also raised last year by Francoise Baylis in Reproductive Biomedicine Online (Baylis, 2013), and to which we responded then with a critical editorial (Johnson, 2013). Three letters, also in this issue, are likewise critical of Ishii's stand (Flinter, 2014; Norcross, 2014; Pennings, 2014). However, whilst we agree with all of the points made in these letters, on two of the issues raised by Ishii we do share some concerns that are not addressed in the letters.Biomarkers for infertility and recurrent pregnancy loss
Impairment of placental vascularization is often caused by thrombophilias, which in turn can lead to recurrent pregnancy loss (RPL) and IVF failure (Ivanov et al., 2012). Impaired placental vasculature has been associated with individual maternal factors such as factor V Leiden and factor II prothrombin. A set of four variants in the annexin5 (ANXA5) gene, the M2 haplotype, has been shown to increase the risk of RPL (Bogdanova et al., 2007; Chinni et al., 2010). The protein encoded by ANXA5 is an anticoagulant that is found at the boundary between the maternal and foetal circulations and thus may affect placental vasculature.Is there a new future for poor-quality embryos?
The use of human embryos in research will always provoke controversy and discussion, and rightly so, as it raises complex moral and ethical questions. This was recognised by the government of the UK in 1989 when, whilst drafting legislation to regulate the practice of IVF, it allowed a free vote in Parliament on whether to permit, or to ban outright, embryo research. The legislation that was introduced later in other countries was in some cases permissive, in others less so, and in others prohibitive.
