Adjuncts in the IVF laboratory: where is the evidence for ‘add-on’ interventions?

Globally, IVF patients are routinely offered and charged for a selection of adjunct treatments and tests or ‘add-ons’ that they are told may improve their chance of a live birth, despite there being no clinical evidence supporting the efficacy of the add on. Any new IVF technology claiming to improve live birth rates (LBR) should, in most cases, first be tested in an appropriate animal model, then in clinical trials, to ensure safety, and finally in a randomized controlled trial (RCT) to provide high quality evidence that the procedure is safe and effective. Only then should the technique be considered as ‘routine’ and only when applied to the similar patient population as those studied in the RCT. Even then, further paediatric and long-term follow up studies will need to be undertaken to examine the long-term safety of the procedure. Alarmingly, there are currently numerous examples where adjunct treatments are used in the absence of evidence-based medicine and often at an additional fee. In some cases, when RCTs have shown the technique to be ineffective, it is eventually withdrawn from the clinic. In this paper, we discuss some of the adjunct treatments currently being offered globally in IVF laboratories including embryo glue and adherence compounds, sperm DNA fragmentation, time lapse imaging, preimplantation genetic screening, mitochondria DNA load measurement and assisted hatching and examine the evidence for their safety and efficacy in increasing LBRs. We conclude that robust studies are needed to confirm the safety and efficacy of any adjunct treatment or test before they are offered routinely to IVF patients

Studies on in vitro fertilised human preembryos. Morphological and chromosomal aspects

The success rate of in vitro fertilisation (IVF) has gradually increased due to basic research in preembryonic biology and the introduction of new methods, both technical and medical. However, further research is needed to establish which preembryos are developmentally most competent in order to be able to maintain the pregnancy rate while only a single preembryo is being transferred.In this thesis human gametes and preembryos were studied from the oocyte to the blastocyst stage with emphasis on both morphology and chromosomal status. The main purpose was to increase our understanding of the specific conditions for gametes and preembryos produced by IVF, and use this knowledge to improve our possibilities to select the preembryo with the highest chance of implanting in the uterus and develop into a healthy child.Four different developmental stages were studied:Oocyte stage: By using immunohistochemical methods it was found that the second metaphase spindle which is produced during the second meiotic division (meiosis II) is not - as previously believed - always positioned directly under the first polar body (PB). These findings can have important implications for the safety of both IVF techniques such as intracytoplasmic sperm injectons (ICSI) and other related techniques.First cleavage stage: We compared early cleaved preembryos to late cleaving preembryos in regard to pregnancy, implantation and birth rates. It was found that early cleaved preembryos had a higher biological competence than preembryos that cleaved late. Furthermore, we found that this parameter could be used to select the most optimal preembryo for embryo transfer after ICSI.Early cleavage stage: Cleavage stage preembryos with cells of uneven size versus even size were compared in regard to pregnancy/implantation rates as well as the occurrence of chromosomal aberrations. It was found that preembryos with uneven sized cells had significantly lower pregnancy/implantation rates and that this could partially be explained by a higher degree of chromosomal abnormalities. Blastocyst stage: Preembryos considered morphologically suboptimal at the four to eight cell stage, were cultured to the blastocyst stage. The aim was to study the chromosomal status of these blastocysts. As a control group we used preembryos of good morphological quality that had been frozen-stored and were not intended for transfer to the patient. It was found that blastocysts from suboptimal preembryos were of lower quality, both morphologically and chromosomally, than blastocysts from preembryos of good quality. These findings indicate that morphological scoring is of great importance but furthermore that many of the morphologically suboptimal preembryos have the potential to reach the blastocyst stage.In conclusion, this thesis shows that basic research that goes hand in hand with clinical work can lead to valuable findings which can rapidly be implemented into clinical practice. At the same time, it demonstrates the need for further studies to increase our understanding of the many, still unknown, factors in early human preembryonic development

Artists of the company, in Symphonie fantastique, Second movement, A ball, Original Ballet Russe, Australian tour, His Majesty's Theatre, Melbourne, April 1940 (1) [picture] /

From: Symphonie fantastique, an episode in the life of an artist : choreographic symphony / by Leonide Massine ; music and book by Hector Berlioz.; Inscription: "4I/17".; Part of the collection: Hugh P. Hall collection of photographs, 1938-1940.; Choreography by Leonide Massine ; scenery and costumes by Christian Bernard ; scenery executed by Prince A. Schervachidze.; Also available in an electronic version via the Internet at: http://nla.gov.au/nla.pic-vn3963537. One of a collection of photographs taken by Hugh P. Hall of 28 ballet productions performed by the Covent Garden Russian Ballet (toured Australia 1938-1939) and the Original Ballet Russe (toured Australia 1939-1940). These are the second and third of the three Ballets Russes companies which toured Australasia between 1936 and 1940. The photographs were taken from the auditorium during a live performance in His Majesty's Theatre, Melbourne and mounted on cardboard for display purposes. For conservation and storage, the photographs have been demounted. The original arrangement of the photographs has been recorded, and details are available from the Pictures Branch of the National Library

Comprehensive analysis of soluble RNAs in human embryo culture media and blastocoel fluid

PURPOSE: miRNAs have been suggested as biomarkers of embryo viability; however, findings from preliminary studies are divergent. Furthermore, the presence of other types of small RNA molecules remains to be investigated. The purpose of this study was to perform a comprehensive analysis of small non-coding RNA levels in spent and unconditioned embryo culture media, along with miRNA levels in blastocoelic fluid samples from human embryos. METHODS: miRNAs in unconditioned culture medium from 3 different manufacturers, along with miRNA from day 5 conditioned culture medium, control medium, and corresponding blastocoel fluid from 10 human blastocysts were analyzed with array-based q-PCR analysis. Subsequently, deep sequencing of total and small RNA in day 5 spent culture medium from 5 human blastocysts and corresponding controls was performed. RESULTS: In spite of using state-of-the-art sensitive detection methods, no miRNAs were found to be reliably present in the spent culture medium or the blastocoel fluid. C(t) values were above the recommended limit for detection in the array-based analysis, a finding that was confirmed by deep sequencing. The majority of miRNAs identified by deep sequencing were expressed in all samples including control media and seem to originate from sources other than conditioned IVF media. CONCLUSIONS: Our findings question the use of miRNAs as a reliable biomarker and highlight the need for a critical methodological approach in miRNA studies. Interestingly, tiRNA fragments appear to be overexpressed in conditioned IVF media samples and could potentially be a novel biomarker worthy of investigation

A noninferiority, prospective, randomized, controlled trial comparing embryo development using media developed for sequential or undisturbed culture in a time-lapse setup.

To study whether a culture medium that allows undisturbed culture supports human embryo development to the blastocyst stage equivalently to a well-established sequential media

The Istanbul consensus workshop on embryo assessment: Proceedings of an expert meeting

Background: Many variations in oocyte and embryo grading make inter-laboratory comparisons extremely difficult. This paper reports the proceedings of an international consensus meeting on oocyte and embryo morphology assessment. Methods: Background presentations about current practice were given. Results: The expert panel developed a set of consensus points to define the minimumcriteria for oocyte and embryomorphology assessment. Conclusions: It is expected that the definition of common terminology and standardization of laboratory practice related to embryo morphology assessment will result in more effective comparisons of treatment outcomes. This document is intended to be referenced as a global consensus to allow standardized reporting of the minimum data set required for the accurate description of embryo development