Abstract
The 4th International Instituto Valenciano de Infertilidad (IVI) Congress, held in Valencia (Spain) at the beginning of April, followed in the footsteps of three previous congresses organized by the IVI network of fertility clinics. Over the years the meetings have grown in size and scope, mirroring the remarkable success of the IVI itself. The 4th IVI Congress was no exception, boasting a distinguished international faculty, addressing a broad range of subjects relevant to reproductive medicine. The meeting was divided into ten sessions and this article will attempt to give a flavor of the data presented and the conclusions reached in each.
The first session aimed to provide an up-to-date review of the current status of ovarian stimulation. For the most part, the emphasis was clinical, focused on the optimization of protocols in order to maximize success rates and minimize risks. Bart Fauser (University of Utrecht, Utrecht, The Netherlands) began the session and highlighted the growing complexity of methods used for ovarian stimulation, the time-consuming nature of many modern protocols, and the level of patient discomfort they entail. He continued by describing so-called ‘mild stimulation’, involving the administration of low doses of exogenous gonadotrophins. The intention of mild stimulation is to reduce the complexity and cost of treatment, as well as limiting the risk of complications. Ideally, a relatively small number of high-quality oocytes are retrieved (<eight oocytes). However, at present, such protocols do not succeed for all patients. Cancellation rates remain high and hyper-responses still occur, albeit at a lower frequency.
Evidently, patient-specific adjustments to stimulation protocols remain important. However, as Fauser pointed out, the modifications of drug doses that most clinicians employ in order to tailor treatments to individual patients are more a matter of tradition and personal belief than the result of well-defined clinical studies. Paul Devroey (Centre for Reproductive Medicine, UZ, Brussels, Belgium) echoed this sentiment in his lecture within the same session, stating that “ovarian stimulation is a beautiful example of lack of intellectual precision.” He reminded the audience that a 3% rate of ovarian hyperstimulation syndrome (OHSS) is well documented and that various practices, likely to result in complications, remain routine in many clinics (e.g., multiple-embryo transfer). He insisted that the goal of an OHSS-free clinic was absolutely achievable by combining gonadotropin-releasing hormone antagonist and gonadotropin-releasing hormone agonist triggering. Cryopreservation of all oocytes or all embryos, with transfer performed in a subsequent natural or artificial cycle, also formed part of Devroey’s concept of the OHSS-free clinic. With the availability of well-reasoned protocols for safe stimulation and modern vitrification methods, the pressure to move towards such strategies seems likely to increase.
It is clear that prospective investigations to define the relative effects of alternative regimens and the value of different ovarian response predictors are urgently required. This is especially true given the number of variations of protocol currently practiced and the growing number of potentially predictive factors (e.g., age, ovarian follicle count, anti-Müllerian hormone level and genetic polymorphisms in hormone receptors).
Speaking in the same session, Antonio Pellicer (University of Valencia, Valencia, Spain) spoke about the importance of providing patients with an accurate assessment of their chances of successful IVF treatment. A meaningful evaluation is critical for patients, particularly those of poor prognosis, since they may wish to abandon IVF if the chances of success are perceived to be too low to warrant the potentially expensive and stressful treatment. A difficulty in the provision of an accurate estimation of IVF success is the lack of a clear definition of what this actually means. Pellicer suggested that the most appropriate measure might be the probability of achieving a single, healthy, term pregnancy per attempt. He argued that this is highly dependent on the number and quality of embryos transferred. Although it is true that, in good-prognosis patients, the transfer of a single embryo results in a similar outcome as the transfer of two embryos, this is not the case for most poor-prognosis patients. Consequently, the total number of embryos transferred must feature in models to predict outcome, considering each embryo transfer as an opportunity for achieving a viable pregnancy. Analysis of more than a decade of data from a single clinic allowed Pellicer to calculate the cumulative live-birth rates for patients of different ages, etiology and day of transfer in relation to the number of embryos transferred. Overall, the most rapid increase in cumulative birth rate was observed between one and five embryo transfers. The age of the woman was the most obvious negative influence on success, with a dramatic decrease in live births after the age of 40 years. Endometriosis was found to be the etiology with the poorest prognosis, with polycystic ovarian syndrome and tubal occlusion having better outcomes. Pellicer concluded that the association between cumulative live-birth rates and number of embryos transferred provides accurate information concerning the likelihood of IVF success and will greatly assist patient decision-making.
The second session concerned the treatment of women of advanced reproductive age, a challenging patient group, exhibiting declining prognosis with increasing years. The changing population dynamics in industrialized countries have led to growing numbers of women postponing childbearing, resulting in an expansion in the number of patients seeking fertility treatment in their late thirties or forties. Again, the issue of obtaining accurate prognostic information and the desire to optimize stimulation protocols for individual patients were important themes of this session. Frank Broekmans (University Medical Center Utrecht, Utrecht, The Netherlands) initiated the session, emphasizing that maternal age is the single most consistent factor influencing the success of fertility treatments, principally owing to the decline in oocyte quality. He iterated the desire of clinicians to be able to accurately assess the ovarian reserve in order to adapt treatment regimens and provide appropriate counseling concerning the probability of different outcomes. Data suggest that tests used for the assessment of ovarian reserve (e.g., anti-Müllerian hormone and antral follicle count) allow prediction of poor- or hyper-response independently of age, which may have important implications for treatment. However, Broekmans cautioned that such approaches are unreliable for the prediction of pregnancy unless female age is also taken into account. Older patients with a test result indicating diminished ovarian reserve should be counseled that their prospects are poor and consider discontinuing treatment. However, a test result indicating poor ovarian reserve in younger patients is not necessarily indicative of low oocyte quality.
Juan Garcia-Velasco (Instituto Valenciano de Infertilidad [IVI], Madrid, Spain) considered which strategies might be available to improve reproductive outcomes for women of advanced reproductive age. He highlighted the importance of understanding the underlying biological basis of ovarian aging in order to develop treatment strategies for this patient population. Among Garcia-Velasco’s conclusions were that IVF treatment is superior to intrauterine insemination in terms of live-birth rate, suggesting that for patients who are rapidly running out of time owing to advancing age, spending excessive time on intrauterine insemination attempts is inadvisable. He also discussed the controversial topic of androgen priming. It is certainly the case that age sees a marked decline in testosterone, androstendione and dehydroepiandrosterone sulfate, and therefore a supplementation approach seems to make biological sense. Androgen priming should lead to increased FSH receptor expression and better response to stimulation, although this remains to be proven. Garcia-Velasco also considered the possibility of oocyte banking, which, since the advent of vitrification, appears to be an increasingly valid approach provided oocytes are cryopreserved while their potential is still high. Unfortunately, it is often the case that the patients requesting banking of oocytes are already in their late thirties and are considered to have reduced oocyte quality.
Finally, the possibility of using preimplantation genetic screening (PGS) was discussed. This has been yet another controversial area, but recent technical innovations appear to have addressed many of the difficulties of earlier methods, leading to improved outcomes. Carmen Rubio (Instituto Universitario IVI, Valencia, Spain) spoke about the application of chromosome-analysis methods to embryos, beginning with traditional FISH approaches before moving on to new microarray-comparative genomic hybridization (microarray-CGH) techniques. Most FISH protocols only allow detection of approximately 85% of the aneuploidies present in embryos, whereas microarray-CGH permits a comprehensive evaluation of the chromosomal content of the oocyte or embryo tested. While debate continues over the efficacy of screening using FISH, particularly if applied to cleavage-stage embryos, data from microarray-CGH are, thus far, entirely positive. Analysis of different embryological stages may also improve the efficacy of PGS, with increasing interest being shown in analyzing oocytes (via polar body biopsy) and blastocysts (discussed in greater detail later). On the subject of PGS, Garcia-Velasco reported that chromosome screening provided a twofold improvement in IVF success rates for women over 40 years of age, provided that they had at least six mature meiosis II oocytes. While there data were not from a randomized trial, they are nonetheless encouraging.
In the morning of the second day, the conference comprised parallel sessions. One series of lectures concerned the role of the endometrium as a fertility factor, featuring talks on intramural fibroids and infertility by Mohamed Aboulghar (Cairo University, Cairo, Egypt), the effect of a thin endometrium by Rene Frydman (University Paris XI, Paris, France), and the importance of high progesterone levels in the follicular phase by Ernesto Bosch (University of Valencia, Valencia, Spain). This was followed by a session on recurrent miscarriage, which included presentations on uterine abnormalities by Rudi Campo (Leuven Institute for Fertility and Embryology, Leuven, Belgium), inherited thrombophilia by Benjamin Brenner (Israel Institute of Technology, Haifa, Israel), and alloimmune factors by Raj Rai (Imperial College London, London, UK). The parallel session covered methods for the selection of the most competent gamete and preceded a session on innovative strategies for preimplantation and prenatal genetic diagnosis. The rest of this article will focus on the latter two of these sessions.
Since most IVF cycles result in the generation of a surplus of embryos (i.e., more than the one to two embryos that would be typically transferred to the uterus), the identification of the oocyte or embryo most likely to produce a viable pregnancy is of great importance. The first presentation in the session on ‘Methods for the selection of the most competent gamete’ was delivered by Marcos Meseguer (Insitituto Universitario IVI, Valencia, Spain). He highlighted the deficiencies of current methods used for embryo selection, including the arbitrary timing and subjective nature of routine morphological evaluations. Meseguer went on to discuss the use of oxygen microsensors to monitor the respiration of individual oocytes and embryos, an approach that may complement standard morphological analysis, providing additional information concerning metabolic performance. He also described a system for real-time, continuous observation of embryos. Surveillance of this type avoids the need to remove the embryo from the optimal environment of the incubator and allows time-lapse analysis and precise measurement of the timing of cell division. The idea of metabolic analysis and continuous embryo observation were also the subject of presentations later in the conference, discussed later.
Despite all of its well-known deficiencies, morphological examination remains the principal method of embryo evaluation. Improved microscopy, computer-aided evaluation and time- lapse analysis have breathed new life into morphological analysis. Furthermore, recent advances in optical capabilities have provided an opportunity to enhance morphological analysis of sperm. High-resolution evaluations (>6000× magnification) of spermatozoa, using inverted microscopes with Nomarski phase-contrast objectives, are employed to identify those that are morphologically normal. These spermatozoa can then be used for intracytoplasmic sperm injection (ICSI). This process, known as intracytoplasmic morphology-selected sperm injection (IMSI), was described in a presentation by Juan Felipe Velez de la Calle (IVF Unit Clinique Pasteur, France). Various aspects of sperm morphology can be assessed, including the acrosome, postacrosomal lamina, neck, tail and nucleus. However, the presence/absence of nuclear vacuoles has been shown to be of particular importance. While many clinics remain to be convinced of the value of IMSI, Velez de la Calle summarized some encouraging data, showing improved pregnancy rates in IMSI versus ICSI cycles (50 vs 25%). Further work is still needed to define the true extent of the benefit conferred by IMSI and the patient groups that may benefit the most from sperm selection based on this method; however, initial data are promising.
Sergio Oehninger (Jones Institute for Reproductive Medicine, VA, USA) also spoke at the session, highlighting the range of characteristics that determine sperm quality, including: competence for acquisition and maintenance of capacitation; progressive motility; recognition, binding and penetration of the zona pellucida; acrosomal exocytosis; oocyte fusion and activation; and formation of the male pronucleus. He also reminded the audience that the role of the spermatozoon extends beyond the simple delivery of genetic material, providing a putative oocyte activation factor, a centriole (essential for organizing the mitotic spindle), and a variety of paternal mRNA transcripts, some of which may be essential for subsequent embryo development. Many of the key features associated with sperm competence and functionality are difficult to assess with existing technology. However, one aspect that has become increasingly accessible in recent years has been DNA integrity. This can now be evaluated using a variety of methods. Sperm samples with high levels of DNA fragmentation have been shown to have a significant negative impact on the outcomes of fertility treatments. Oehninger reported that even morphologically normal, motile sperm of the type typically selected for fertilization using ICSI may be affected by DNA fragmentation. Indeed, in men with severe teratozoospermia, 20–60% of apparently normal sperm had damaged DNA. Increased proportions of ‘normal’ sperm with fragmented DNA were negatively correlated with embryo quality and pregnancy rate following ICSI. On this basis, Oehninger suggested that evaluation of DNA integrity in morphologically normal spermatozoa (rather than the entire sperm population) might provide the most useful insight into the likely impact of DNA damage on ICSI outcomes.
Nicolas Garrido (IVI, Valencia, Spain) continued the theme of sperm selection, considering what else could be done to identify sperm with the greatest potential for producing a viable embryo, above and beyond the routine swim-up or density gradient centrifugation approaches. There has been increasing interest in analysis of DNA damage, but this is just one of a range of alternative targets of possible prognostic relevance, including ubiquitin, hyaluronic acid receptors and transcripts and gene products identified by analysis using gene-expression microarrays. Garrido described the concept of magnetic-activated cell sorting, a technology involving the exposure of a sperm sample to molecules or antibodies that recognize membrane epitopes of diagnostic relevance. The molecules/antibodies are linked to magnetic microspheres, allowing any sperm that they bind to be purified by passage through a filter under a magnetic field. A variety of molecules on the outer sperm membrane could serve as valuable targets for such an approach.
The afternoon of the second day saw a session devoted to the long-term consequences of assisted reproduction. Jose Bellver (University of Valencia, Valencia, Spain) spoke on the controversial subject of cancer risk following assisted reproductive treatments, concluding that more well-controlled research was needed, but that existing information is generally reassuring. Bernhard Horsthemke (University of Duisburg-Essen, Essen, Germany) gave a lecture on chromatin- and RNA-based epigenetic inheritance, a subject of great relevance to the control of the ‘developmental trajectory’ of the embryo, potentially influencing problems associated with assisted reproduction, such as the increased incidences of low birthweight, congenital malformations and (possibly) imprinting disorders. It remains unclear whether these increased risks are associated with assisted reproductive techniques or are related to the underlying infertility problem of the patients.
Nick Macklon (University of Southampton, Southampton, UK) discussed periconceptional determinants of health, highlighting some of the factors that complicate infertility treatment, such as increasing incidence of obesity and treatment of women of advanced reproductive age. He also described the so-called ‘Barker hypothesis’, which states that the nutritional environment of the embryo and fetus affects its risk of developing health problems later in life (e.g., cardiovascular disease). The concern is that the periconceptional environment, including embryo culture systems used during IVF, may induce long-term perturbations of processes essential for fetal growth and development. It is known that the dietary environment at the time of conception and during pregnancy is linked to altered birthweight and various aspects influencing long-term health, so this speculation is not without basis.
Finally, Karen Middleburg (Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands) gave a lecture on neuromotor, cognitive and behavioral outcomes in children born using assisted reproductive technologies. There are relatively few ‘high-quality’ studies, and most that exist only examine children in infancy, precluding the evaluation of fine motor skills and problems such as dyslexia. From the data available, it seems that IVF and ICSI per se do not increase the risk of severe cognitive or neuromotor impairments, although additional factors associated with treatment, such as multiple pregnancy and preterm birth, may lead to elevated rates of some problems (e.g., cerebral palsy). More well-designed studies with long-term follow-up are clearly needed.
The parallel afternoon session was dedicated to innovative strategies for preimplantation and prenatal diagnosis. Dagan Wells (University of Oxford, UK) began by providing an overview of the new generation of chromosome-screening techniques, which provide comprehensive data on the chromosomal complement of the oocyte or embryo tested. Although a relatively new innovation, these methods have already been employed in hundreds of IVF cycles, and data concerning technical accuracy and clinical efficacy are beginning to emerge. Data were reported on 1276 blastocysts derived from 195 patients (mean female age: 38.2 years; mean 2.0 previous failed cycles). In total, 65.5% of embryos were found to be aneuploid using microarray-CGH, emphasizing that lethal chromosome abnormalities remain common even during the final stages of preimplantation development. An implantation rate of 75.0% and a birth rate per cycle of 69.9% was observed; significantly higher than seen in a well-matched contemporary control group. These data suggest that microarray-CGH applied at the blastocyst stage represents an extremely promising supplement to traditional methods of embryo evaluation. Promising results concerning the technical accuracy of microarray-CGH applied to polar bodies was also presented. However, thus far there is relatively little data on the clinical outcome of polar body-microarray-CGH cycles, and consequently, efficacy is difficult to judge. Randomized trials are now needed to define the extent of benefits conveyed and the patient groups that benefit the most from this type of screening.
Samir Hamamah (University Hospital of Montpellier, Montpellier, France) provided an update on the use of cumulus cells for oocyte/embryo selection. The cumulus cells are intimately associated with the oocyte they surround, and share the same follicular microenvironment. For this reason, it has been suggested that biological processes occurring in cumulus cells might reveal much concerning the status of the corresponding oocyte. Hamamah’s team has previously assessed the expression of thousands of genes in cumulus cells using microarrays and attempted to correlate variation in expression with pregnancy outcome. This has resulted in the identification of a putative transcriptomic signature predictive of pregnancy, which will be utilized in a prospective trial to assess efficacy. Novel noninvasive forms of oocyte or embryo assessment, such as transcriptomic and metabolomic profiling, provide information that may supplement standard morphological testing. Although the data provided are indicative (such as morphological analysis) rather than definitive (such as chromosomal analysis), the fact that it can be gathered without having to subject the oocyte/embryo to micromanipulation is highly attractive.
Genetic analysis in the form of preimplantation genetic diagnosis (PGD) and prenatal diagnosis was also discussed in this session, with Julio Martin (IVI, Valencia, Spain), providing an insight into PGD for cancer predisposition. Testing of cancer genes in embryos has sometimes been considered controversial owing to the relatively late onset and incomplete penetrance displayed by many cancer syndromes, and the legal status of such diagnoses varies considerably from country to country. However, there is considerable demand from patients for this reproductive option.
Prenatal diagnostic techniques, such as amniocentesis and chorionic villus sampling, are well established, but nonetheless have limitations. One of the greatest concerns for patients utilizing prenatal testing is the risk of miscarriage induced by the procedure, which may be as high as 1%. This has led to a desire to develop less-invasive forms of prenatal testing. Approaches based on the analysis of fetal cells isolated from the maternal bloodstream and, more recently, circulating cell-free fetal DNA (ccffDNA) have been developed, although reported detection rates for abnormalities have been variable. Ana Bustamante-Aragones (Fundación Jiménez Diáz, Madrid, Spain) provided an update on the current status of the use of ccffDNA, a highly promising strategy for noninvasive diagnosis. Although fetal DNA represents only a small fraction of the cell-free circulating DNA in the maternal bloodstream (<20%), the technique has been successfully clinically applied to the determination of fetal sex and fetal Rhesus D assignment. The main limitation faced by prenatal testing based upon ccffDNA is that the large background of maternal DNA makes it impossible to assess maternally derived anomalies, meaning that only mutations unique to the father can be targeted for diagnosis. However, as Bustamante-Aragones described, research into the diagnosis of paternally derived dominant mutations is advancing and the introduction of next-generation sequencing approaches shows promise for the detection of fetal aneuploidies. This looks to be an extremely promising prospect for the future.
The final day of the conference continued the theme of noninvasive diagnostics, with an entire session dedicated to this subject. Henry Leese (Hull York Medical School, York, UK) presented data on the measurement of amino acid turnover to assist identification of viable embryos. Leese and his collaborators had previously demonstrated that human embryos that display a lesser rate of amino acid turnover have a greater probability of forming blastocysts. Similar findings have been reported in some other mammalian species. These findings are consistent with the ‘quiet embryo’ hypothesis, which suggests that embryos that are less metabolically active have the greatest potential for further development. Leese speculated that the design of algorithms that combine traditional morphological analysis and noninvasive measurement of amino acids in embryo culture medium could lead to improved embryo selection, helping to achieve high implantation rates in single embryo transfer cycles.
Metabolomic profiling of embryos was also the subject of the presentation by Francesco Dominguez (Embryomics, Bilbao, Spain), who is aiming to identify novel biomarkers of aneuploidy. Given the lethality and high prevalence of chromosome anomalies in human oocytes and embryos, this is an appealing possibility. Mass spectroscopy and nuclear magnetic resonance were applied to spent medium and the results obtained for individual embryos compared with corresponding cytogenetic data from the same embryos obtained using FISH. Initial findings appear promising, although it is clear that additional validation, ideally using comprehensive chromosome screening approaches, will be necessary to verify the results.
Shehua Shen (Auxogyn, CA, USA) moved the subject from chemical analysis back to morphological evaluation, focusing on the introduction of time-lapse analysis of embryo behavior, which permits precise assessment of the timing of key developmental milestones, such as each cleavage division. It has been demonstrated that such measurements are highly predictive of blastocyst formation. This approach offers the hope that embryos capable of forming blastocysts could be revealed without having to subject them to extended culture. The argument is that culture to the blastocyst stage may subject embryos to unnecessary stresses that may ultimately affect outcome. This is still a matter of debate, but there is evidence of an increased risk of monozygotic twinning, preterm delivery, low birthweight, low Apgar score, and possible epigenetic alterations associated with blastocyst culture. It now seems that the failure of traditional morphological analyses to provide an accurate prediction of blastocyst formation may have been due to the static images and very limited number of time points upon which evaluation was based. Time-lapse analysis overcomes these restrictions.
Macklon gave a second presentation, this time speaking about secretomic analysis of endometrial fluid for noninvasive assessment of endometrial receptivity, reviewing various strategies for the analysis of components of endometrial secretions. Work of this type hopes to provide an insight into the intrauterine environment, shedding light on the window of optimal endometrial receptivity with the hope of ultimately improving implantation rates.
The final session of the meeting provided an additional evaluation of new technologies that may soon begin to impact clinical practice. Daniel Ramon Vidal (Lifesequencing SL, Valencia, Spain) provided an insight into the use of second-generation massive sequencing technologies, discussing the different platforms available. The vast amount of relatively low-cost DNA sequence data generated by these approaches is already revolutionizing studies aimed at uncovering genetic components of common diseases. In the field of reproductive medicine, there are likely to be multiple applications of this technology. Prenatal testing of cell-free fetal DNA in the maternal bloodstream, as discussed previously, is one of the first potential clinical applications of second-generation massive sequencing, but potential application in other areas, such as PGS, could also be envisaged.
A further discussion of epigenetic mechanisms was provided by Manel Esteller (Cancer Epigenetics and Biology Program, Barcelona, Spain). He described how two genomes, identical at the level of the DNA sequence, can result in animals with differing phenotypes, via epigenetic modification. One of the clearest examples of these effects are the differences seen when cloned animals (which frequently display epigenetic deviations from normality) are compared with the original donor. The apparent plasticity and fragility of the epigenome during preimplantation development continues to raise questions for the practice of IVF, although at the current time risks of serious disease as a consequence of epigenetic change still appear to be low.
One of the greatest problems facing the treatment of infertility, particularly that associated with advanced maternal age, ovarian failure and poor oocyte/sperm quality, is the lack of a good understanding of human germ cell development. This is, at least in part, due to the inaccessibility of these cells for analysis. Rene Reijo Pera (Stanford University Medical School, CA, USA), presented data on the production of primordial germ cells from human induced pluripotent stem cells (i.e., stem cells created by reprogramming adult cells, nonembryonic in origin). The cells produced displayed meiotic capabilities, suggesting that they may provide researchers with a useful model system, leading to new insights into gamete formation, and perhaps eventually to novel therapeutics or even artificial gametes.
The use of stem cells was also the subject of the final lecture, given by Carlos Simon (University of Valencia, Valencia, Spain), who described work to identify and characterize the stem cell population responsible for the remarkable regenerative capacity of the endometrium. The human endometrium undergoes approximately 500 cycles of proliferation, breakdown and regeneration during a woman’s lifetime and dysfunction of this process may underlie a variety of pathological disorders. Simon’s team evaluated the hypothesis that human endometrial side-population cells represent somatic stem cells in this tissue. Side-population cells from stromal and epithelial compartments were isolated and tested using a battery of molecular, genetic and histological techniques, providing strong evidence for the role of this class of cells as endometrial stem cells. These findings may have implications for the future treatment of pathologies related to endometrial turnover and may lead to a readily available source of cells suitable for modeling the normal endometrial environment as well as that experienced in certain disease states.
Overall, the Scientific Committee of the 4th International IVI Congress did an excellent job of scanning the horizon for emerging technologies, and had invited experts involved in a variety of translational research projects to review their fields and present data. Some of the new methodologies discussed are already starting to be used in clinics for the purposes of gamete and/or embryo selection, while others are yet to be applied clinically, but show significant promise for the future. The former group of techniques includes microarray-CGH, IMSI and morphometric (time-lapse) analysis of embryos. These approaches have generated considerable interest and excitement within the reproductive medicine community and are increasing in utilization, although clinical utility remains to be conclusively proven in all of these cases. The latter group includes noninvasive methods of embryo evaluation using transcriptomic (cumulus cells) or metabolomic (culture medium) strategies, which are yet to be widely applied outside of a research setting. Other promising methods in development, discussed at the meeting, were the assessment of endometrial receptivity using secretomics and the use of next-generation sequencing for prenatal diagnosis and PGD. Some of these techniques will probably fail to live up to expectations and will be abandoned over the next few years, but it is likely that others will fulfil their potential and eventually become routine. It will be interesting to see which of these exciting advances ultimately make the grade.
Financial & competing interests disclosure
Dagan Wells is funded by the NIHR Biomedical Research Centre Programme. Dagan Wells also wishes to disclose a financial interest in Reprogenetics, a company providing genetic testing services for fertility clinics. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.