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McMaster University Health Sciences Center, Hamilton, Ontario, Canada
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most commonly affects individuals from menarche through menopause, though it can also affect adolescents and postmenopausal women. It is a common cause of pain and infertility but also negatively impacts quality of life, intimate relationships
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Department of Paediatric Oncology and Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
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M 2017 Short term culture of vitrified human ovarian cortical tissue to assess the cryopreservation outcome: molecular and morphological analysis . Journal of Reproduction and Infertility 18 162 – 171 . 28377895 Rosendahl M Greve T
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Infertility is estimated to affect more than 50 million couples around the world, with male factor accounting for half of these cases, yet there is a notable absence of effective treatment options for men, other than in-vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). This review considers unlicensed and empirical treatments used for male subfertility, including hormonal therapy, phosphodiesterase inhibitors, and antioxidants. Compounds generally demonstrate variable improvements in sperm function but benefits for fertility are less clear.
There is a pressing need for effective treatment options for subfertile men, however, our knowledge of sperm function is limited, restricting the identification of precise treatment targets. The traditional drug discovery pathway is also notorious for its extensive resource and time requirements, often extending over decades and demanding significant financial investment. Unfortunately, a substantial number of potential therapies fail before reaching the marketplace. Furthermore, reliance on mammalian models is not possible in the drug development process for male subfertility, due to significant variability between animals and man.
We review recent breakthroughs and highlight novel methods aimed at improving the effectiveness and efficiency of drug discovery for male subfertility. High-throughput screening, combinatorial chemistry, and the repurposing of established medications have great potential. These strategies offer the promise of accelerating the pace of drug development, curbing the extensive demand for resources, and, in the case of drug repurposing, diminish the demand for comprehensive pharmacokinetic and pharmacodynamic studies. As these innovative approaches are adopted, the feasibility of addressing male subfertility through scientific advancements appears to be increasingly attainable.
Robinson Research Institute, The University of Adelaide, Adelaide, South Australia
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Robinson Research Institute, The University of Adelaide, Adelaide, South Australia
Freemasons Centre for Male Health and Wellbeing, The University of Adelaide, Adelaide, South Australia
Genea Pty Ltd, Sydney, New South Wales, Australia
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Robinson Research Institute, The University of Adelaide, Adelaide, South Australia
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The present study determined whether adding granulocyte–macrophage colony-stimulating factor (GM-CSF) during in vitro oocyte maturation (IVM) could improve oocyte developmental competence by examining embryo development and implantation and birth rates following embryo transfer in mice. In an initial dose-response experiment, we demonstrated that the addition of 2 and 10 ng/mL GM-CSF during IVM increased cumulus expansion (P < 0.05) but did not affect fertilisation rate compared with the control group. The addition of 10 ng/mL increased blastocyst rate (17.0%; P < 0.05) and tended to increase the number of good quality blastocysts present at 96 h of culture (+19.4%; P = 0.06) and increased blastocyst inner cell mass (+25.2%; P < 0.001), trophectoderm (+29.9%; P < 0.01), and total cell numbers (+28.6%; P < 0.05). GM-CSF also reduced the incidence of DNA damage in blastocysts in the 10 ng/mL group (−16.2%) compared with the control group. These improvements translated into increases in implantation rate (+21.0%; P < 0.05) and birth rate (+17.0%; P < 0.001) following the transfer of vitrified blastocysts. GM-CSF treatment did not alter any fetal and placental parameters. Together these results suggest that the addition of GM-CSF during IVM may improve livestock in vitro embryo production and human IVM.
Lay summary
The ability to collect immature eggs from the ovaries and mature these in the laboratory is an important technology for treating certain types of infertility in women as well as for preserving their fertility, for example prior to cancer treatment. This technique is called in vitro oocyte maturation or IVM and is also used in animal breeding. However, pregnancy and birth rates in humans and animals using this technique are lower than that which can be achieved using natural mating. We have shown that adding GM-CSF, a molecule found in the ovary, during IVM can increase the number and quality of embryos produced in mice. We have also found that when these embryos are transferred to surrogate mothers, implantation and birth rates are increased. These results suggest that the addition of GM-CSF during IVM may improve pregnancy and birth rates in humans as well as animals.
Department of Obstetrics and Gynecology, Chinese PLA General Hospital, Beijing, China
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Department of Obstetrics and Gynecology, Chinese PLA General Hospital, Beijing, China
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Department of Obstetrics and Gynecology, Chinese PLA General Hospital, Beijing, China
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Department of Obstetrics and Gynecology, Chinese PLA General Hospital, Beijing, China
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Graphical Abstract
Abstract
The transition of maternal to zygotic gene expression regulation is critical for human preimplantation embryo development. In recent years, single-cell RNA sequencing (scRNA-seq) had been applied to detect the factors that regulate human oocyte maturation and early embryo development. Here, the evaluation of transcriptomes in single blastomere from the embryo collected from patients by scRNA-seq was performed. There were 20 blastomeres biopsied from 8-cell embryos of seven patients who received more than two ART cycles due to low embryo competence. Meanwhile, ten cells were collected from 8-cell embryos of four patients who received ART treatment due to male or tubal factors. The blastomeres were then evaluated using the previously established scRNA-seq method to determine the associations between their gene expression and developmental competence. The total number of genes detected in 8-cell embryos that failed to form blastocyst including maternal and zygotic mRNAs was reduced. There were 324 differently expressed genes detected among the 8-cell embryos including 65 genes that were significantly suppressed in the 8-cell embryos that failed to form blastocyst. Further analysis found these 8-cell embryos arrested at the cleavage stage due to the dysfunction of the cell cycle, DNA transcription activity, histone methylation, and cell division-related genes such as SMCO-1, ZNF271P,ZNF679, ASF1b, BEX3, DPPA2, and ORC4. The alterations of gene expression detected in human 8-cell embryos are tightly associated with its developmental competence and could be used as targets to enhance embryo development or parameters to predict the embryo’s development outcomes.
Lay summary
Many females are suffering infertility due to the failure of embryonic development at early stages due to unknown causes. At the very beginning of human embryo development, the embryos start to express its own genes, which should be achieved at 8-cell stage. In current research, we isolated one cell from 8-cell embryos and detected the gene expression at single-cell level. Then the remaining cells of these embryos were cultured to form blastocyst. Meanwhile, the data was analyzed according to the outcomes of embryo development. We detected 324 differently expressed genes between the 8-cell embryos that succeeded and failed to form blastocyst. Our research showed the association between the gene expression and the developmental competence of 8-cell embryos. The findings could be used to predict the embryo quality and potential therapy target to improve the efficiency of assisted reproductive techniques.
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Complete Fertility, Princess Anne Hospital, Southampton, UK
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number of oocytes retrieved is the primary predictor for any treatment cycle, but the patient’s age is an additional independent predictive factor. After optimizing the performance, a three-feature model (age, number of oocytes collected, and infertility
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the semen characteristics before and after the administration of the Covishield™ vaccine. Materials and methods This pilot study included 53 patients undergoing semen analysis as a part of infertility work-up at the university infertility
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Introduction About 30% of infertile couples are diagnosed with idiopathic infertility due to lack of any evident pathology ( Sadeghi 2015 ). In many such cases, though, ART failures can be attributed to the so-called ‘hidden’ male factor
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NIHR Applied Research Collaboration Wessex, Southampton, UK
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NIHR Applied Research Collaboration Wessex, Southampton, UK
NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
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Complete Fertility, Princess Anne Hospital, Southampton, UK
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woman is now emerging. The commencement of menarche, which can herald a plethora of deleterious symptoms, can affect the adolescent all the way through adulthood to menopause; the debilitating influence on fecundity can precipitate infertility and the
Australian Research Council Centre of Excellence for Nanoscale Biophotonics, The University of Adelaide, Adelaide, Australia
Institute for Photonics and Advanced Sensing, The University of Adelaide, Adelaide, Australia
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SUPA, School of Physics and Astronomy, University of St Andrews, North Haugh, St Andrews, Fife, United Kingdom
School of Biological Sciences, The University of Adelaide, Adelaide, Australia
Department of Physics, College of Science, Yonsei University, Seoul, South Korea
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Australian Research Council Centre of Excellence for Nanoscale Biophotonics, The University of Adelaide, Adelaide, Australia
Institute for Photonics and Advanced Sensing, The University of Adelaide, Adelaide, Australia
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at physiological oxygen, and a move to single embryo transfer. However, for many infertile patients, the journey to parenthood via IVF is a lengthy and emotionally and financially challenging process. For some patients, IVF will not lead to the
