BackgroundThe development and refinement of blastocyst media in recent years has allowed embryos to be cultured in-vitro for 5 or 6 days post oocyte retrieval and has been established as an effective selection tool to aid embryo selection for IVF treatment. It is generally accepted that blastocyst culture is not an appropriate option for all patients but the criteria for patient selection varies between clinics. Our blastocyst culture programme started in February 2005; the patient criteria was set at a minimum of 4 oocytes retrieved, a minimum of 4 2PN pronuclear embryos and at least 4 8-cell embryos of any quality on Day 3 where the female patient was 34 years and under. In the female age group of 35 years and over the criteria was at least 6 oocytes retrieved, a minimum of 6 2PN pronuclear embryos and at least 6 8-cell embryos of any quality on day 3. Improvements in pregnancy rates demonstrated the effectiveness of blastocyst transfer and clinical opinion was that the criteria should be adjusted to allow this option to be available to an increased patient population. From February 2007 the blastocyst patient selection criteria was changed to at least 4 oocytes retrieved, at least 4 2PN pronuclear embryos and at least 2 8-cell and 2 6-cell or 7-cell embryos of top quality on Day 3 in women 38 years and under. For women 39 years and over the criteria was lowered to at least 5 eggs retrieved, at least 5 2PN and at least 3 8-cell embryos and 2 6-cell embryos of top quality on Day 3.Methods Retrospective statistical analysis was carried out to determine the pregnancy rates, live birth rates and twin rate for the period under the initial criteria and to examine the impact that lowering the criteria for patient selection for blastocyst culture had on these parameters. Results There was an overall fall in the ongoing pregnancy/ live birth rate from 50.9% under the old criteria to 45.0% under the new criteria. However, the patients who had blastocyst culture under the new criteria but would have had day-3 embryo transfer under the initial criteria had a significantly increased live birth/ongoing pregnancy rate from 22.7% to 40.7%. There is an increase in the number of blastocyst culture cycles from 26.4% under the old criteria to 39.1% with the refined criteria. The twin pregnancy rate was reduced from 25.2% to 17.5%. Conclusion The result of this cohort study revealed that lowering the blastocyst selection criteria may lead to a lower overall clinical live birth rate from blastocyst culture; however, it will benefit a specific group of patients to achieve a better pregnancy and live birth rate. Furthermore, it increases the number of patients who will benefit from the blastocyst culture programme and also reduces multiple pregnancy rate.
Motivation Simple tandem repeats, microsatellites in particular, have regulatory functions, links to several diseases, and applications in biotechnology. There is an immediate need for an accurate tool for detecting microsatellites in newly sequenced genomes. The current available tools are either sensitive or specific but not both; some tools require adjusting parameters manually. Results We propose Look4TRs, the first application of self-supervised hidden Markov models to discovering microsatellites. Look4TRs adapts itself to the input genomes, balancing high sensitivity and low false positive rate. It auto-calibrates itself. We evaluated Look4TRs on 26 eukaryotic genomes. Based on F measure, which combines sensitivity and false positive rate, Look4TRs outperformed TRF and MISA —the most widely-used tools—by 78% and 84%. Look4TRs outperformed the second and the third best tools, MsDetector and Tantan by 17% and 34%. On eight bacterial genomes, Look4TRs outperformed the second and the third best tools by 27% and 137%. Availability https://github.com/TulsaBioinformaticsToolsmith/Look4TRs Supplementary information Supplementary data are available at Bioinformatics online and on https://drive.google.com/open?id=1cIcS7Gvj0wj1B81-rnTU_OAG3IiNH54Y.
Simple tandem repeats, microsatellites in particular, have regulatory functions, links to several diseases, and applications in biotechnology. Sequences of thousands of species will be available soon. There is immediate need for an accurate tool for detecting microsatellites in the new genomes. The current available tools have limitations. As a remedy, we proposed Look4TRs, which is the first application of self-supervised hidden Markov models to discovering microsatellites. It adapts itself to the input genomes, balancing high sensitivity and low false positive rate. It auto-calibrates itself, freeing the user from adjusting the parameters manually, leading to consistent results across different studies. We evaluated Look4TRs on eight genomes. Based on F-measure, which combines sensitivity and false positive rate, Look4TRs outperformed TRF and MISAthe most widely-used tools -by 106% and 82%. Look4TRs outperformed the second best tool, MsDetector or Tantan, by 11%. Look4TRs represents technical advances in the annotation of microsatellites.
Purpose Total fertilisation failure (TFF), even with intracytoplasmic sperm injection (ICSI), occurs in approximately 3 % of cycles, can be recurrent and the exact cause is difficult to elucidate. Differentiation between oocyte and sperm-related cause of TFF is possible using mouse oocyteactivation techniques, but is not an option within most clinical settings. Therefore, the management of these couples is clinically driven, and the endpoint, if recurrent, is often the use of donor gametes. However, with the invariable lack of a definitive cause of TFF, any decision between the use of donor sperm or oocytes remains an emotive one. We present two case reports demonstrating the importance of appropriate investigation, activation techniques (mechanical and chemical) and clinical management options to develop a clinical algorithm prior to the use of donor gametes. Methods This study is composed of two case reports of assisted reproduction investigation and treatment within an assisted conception unit for couples with recurrent total fertilisation failure. Results Using appropriate investigation (endocrine, urological and embryological) and treatments (ICSI, IMSI, oocyteactivation techniques), a fertilisation rate of 48 % was achieved in two cycles in couples following a total of nine previous cycles (and 200 previously collected eggs) with TFF.Conclusions Oocyte activation requires the triggering of intracellular calcium oscillations by the release of a spermspecific factor (phospholipase C zeta (PLCζ)) into the oocyte cytoplasm. Although, PLCζ deficiencies have been demonstrated as putative causes of failed activation, impaired oocyte responsiveness may also be a factor. The use of donor gametes is often recommended and is often the required endpoint of treatment. However, these reports outline a clinical algorithm that potentially offers success without donation, and also offers a systematic approach to help decide whether donor oocytes or sperm should be recommended.
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