205 results on '"Michael J. Tucker"'
Search Results
2. Discovery of a Potent and Orally Bioavailable Zwitterionic Series of Selective Estrogen Receptor Degrader-Antagonists
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James S. Scott, Darren Stead, Bernard Barlaam, Jason Breed, Rodrigo J. Carbajo, Elisabetta Chiarparin, Natalie Cureton, Paul R. J. Davey, David I. Fisher, Eric T. Gangl, Tyler Grebe, Ryan D. Greenwood, Sudhir Hande, Holia Hatoum-Mokdad, Samantha J. Hughes, Thomas A. Hunt, Tony Johnson, Stefan L. Kavanagh, Teresa C. M. Klinowska, Carrie J. B. Larner, Mandy Lawson, Andrew S. Lister, David Longmire, Stacey Marden, Thomas M. McGuire, Caroline McMillan, Lindsay McMurray, Christopher J. Morrow, J. Willem M. Nissink, Thomas A. Moss, Daniel H. O’Donovan, Radoslaw Polanski, Stephen Stokes, Kumar Thakur, Dawn Trueman, Caroline Truman, Michael J. Tucker, Haixia Wang, Nicky Whalley, Dedong Wu, Ye Wu, Bin Yang, and Wenzhan Yang
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Drug Discovery ,Molecular Medicine - Published
- 2023
3. Building a Reliable Mutable File System on Peer-to-Peer Storage.
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Christopher A. Stein, Michael J. Tucker, and Margo I. Seltzer
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- 2002
- Full Text
- View/download PDF
4. Addition of Fluorine and a Late-Stage Functionalization (LSF) of the Oral SERD AZD9833
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Michael J. Tucker, Thomas A. Moss, James S. Scott, Barlaam Bernard Christophe, Paul R. J. Davey, Ryan Greenwood, Stephen Stokes, Gary Fairley, Radoslaw Polanski, Holia Hatoum-Mokdad, David Longmire, Eric Gangl, Bin Yang, Andrew Lister, and Jeffrey G. Varnes
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Chemistry ,Organic Chemistry ,Drug Discovery ,Advanced stage ,Lipophilicity ,Late stage ,Fluorine ,Surface modification ,chemistry.chemical_element ,Biochemistry ,Combinatorial chemistry - Abstract
[Image: see text] Herein we describe our efforts using a late stage functionalization together with more traditional synthetic approaches to generate fluorinated analogues of the clinical candidate AZD9833. The effects of the addition of fluorine on the lipophilicity, permeability, and metabolism are discussed. Many of these changes were tolerated in terms of pharmacology and resulted in high quality molecules which reached advanced stages of profiling in the testing cascade.
- Published
- 2020
5. IMPACT OF CHRONIC PROGESTERONE ELEVATION (PRE-TRIGGER) ON FROZEN EMBRYO TRANSFER OUTCOMES
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Ali Borazjani, Samad Jahandideh, Shan Dawood, Kathleen Devine, and Michael J. Tucker
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Reproductive Medicine ,Obstetrics and Gynecology - Published
- 2022
6. In vitro fertilization and andrology laboratory in 2030: expert visions
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Kathleen A. Miller, Markus Montag, Denny Sakkas, Filippo Maria Ubaldi, Marcos Meseguer, Philip Xie, Stephanie Cheung, Liesl Nel-Themaat, Laura Rienzi, Zev Rosenwaks, David K. Gardner, Gianpiero D. Palermo, Derek Keating, Alison Campbell, Federica Innocenti, Danilo Cimadomo, Carlos Simón, and Michael J. Tucker
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Automation, Laboratory ,Male ,Engineering ,Vision ,business.industry ,Obstetrics and Gynecology ,Fertilization in Vitro ,Clinical Laboratory Services ,History, 21st Century ,Andrology ,Reproductive Medicine ,Pregnancy ,Infertility ,Humans ,Female ,Diffusion of Innovation ,business ,Policy Making ,Forecasting - Abstract
The aim of this article is to gather 9 thought leaders and their team members to present their ideas about the future of in vitro fertilization and the andrology laboratory. Although we have seen much progress and innovation in the laboratory over the years, there is still much to come, and this article looks at what these leaders think will be important in the future development of technology and processes in the laboratory.
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- 2021
7. In vitro fertilization and andrology laboratories in 2030
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Marcos Meseguer, Laura Rienzi, Liesl Nel-Themaat, David K. Gardner, Derek Keating, Gianpiero D. Palermo, Zev Rosenwaks, Federica Innocenti, Denny Sakkas, Philip Xie, Stephanie Cheung, Michael J. Tucker, Markus Montag, Kathleen A. Miller, Danilo Cimadomo, Carlos Simón, Alison Campbell, and Filippo Maria Ubaldi
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Andrology ,Engineering ,medicine.medical_specialty ,In vitro fertilisation ,Reproductive Medicine ,business.industry ,medicine.medical_treatment ,medicine ,Reproductive medicine ,Obstetrics and Gynecology ,Reproductive technology ,business - Abstract
The in vitro fertilization and andrology laboratories are at the center of assisted reproductive technologies and the place where technicians and embryologists manipulate gametes and preimplantation-stage embryos with the goal of achieving the best embryo for transfer. Through the years, these laboratories have seen developments in technique, technology, and testing. The goal of this Views and Interviews series is to bring together the thought leaders in the field and envision what the laboratories will look like in the next 10 years.
- Published
- 2021
8. Discovery of AZD9833, a Potent and Orally Bioavailable Selective Estrogen Receptor Degrader and Antagonist
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Haixia Wang, Stefan Kavanagh, Radoslaw Polanski, Eric Gangl, Michael J. Tucker, Jason Breed, Thomas Anthony Hunt, Paul R. J. Davey, Mandy Lawson, Darren Stead, Oona Delpuech, Ye Wu, J. Willem M. Nissink, Barlaam Bernard Christophe, Dedong Wu, Sudhir M. Hande, Amber Balazs, Dermot F. McGinnity, Wenzhan Yang, Thomas A. Moss, Bin Yang, Sladjana Gagrica, Kumar Thakur, Stacey Marden, Tyler Grebe, Daniel Hillebrand O'donovan, Teresa Klinowska, Samantha Jayne Hughes, Kara Herlihy, David I Fisher, Stephen Stokes, Holia Hatoum-Mokdad, Tony Johnson, James S. Scott, Elisabetta Chiarparin, Bo Peng, Sophie L. M. Janbon, Scott Throner, Ryan Greenwood, David Matthew Wilson, Andrew Lister, Stephen Fawell, Hoan Huynh, Jeffrey G. Varnes, Christopher J. Morrow, and Rodrigo J. Carbajo
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Selective Estrogen Receptor Modulators ,Estrogen receptor ,Administration, Oral ,Biological Availability ,Antineoplastic Agents ,Breast Neoplasms ,Pharmacology ,Crystallography, X-Ray ,01 natural sciences ,03 medical and health sciences ,Structure-Activity Relationship ,In vivo ,Oral administration ,Cell Line, Tumor ,Drug Discovery ,medicine ,Structure–activity relationship ,Humans ,030304 developmental biology ,Cell Proliferation ,0303 health sciences ,Fulvestrant ,Molecular Structure ,Chemistry ,Drug discovery ,Antagonist ,Lipids ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Cyclization ,Lipophilicity ,Molecular Medicine ,Female ,medicine.drug - Abstract
Herein we report the optimization of a series of tricyclic indazoles as selective estrogen receptor degraders (SERD) and antagonists for the treatment of ER+ breast cancer. Structure based design together with systematic investigation of each region of the molecular architecture led to the identification of N-[1-(3-fluoropropyl)azetidin-3-yl]-6-[(6S,8R)-8-methyl-7-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-3H-pyrazolo[4,3-f]isoquinolin-6-yl]pyridin-3-amine (28). This compound was demonstrated to be a highly potent SERD that showed a pharmacological profile comparable to fulvestrant in its ability to degrade ERα in both MCF-7 and CAMA-1 cell lines. A stringent control of lipophilicity ensured that 28 had favorable physicochemical and preclinical pharmacokinetic properties for oral administration. This, combined with demonstration of potent in vivo activity in mouse xenograft models, resulted in progression of this compound, also known as AZD9833, into clinical trials.
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- 2020
9. Improving metabolic stability and removing aldehyde oxidase liability in a 5-azaquinazoline series of IRAK4 inhibitors
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James M. Smith, Rana Anjum, Sébastien L. Degorce, Ina Terstiege, Turner Paul, Stuart E. Pearson, Michael J. Tucker, Alexandra L. Orton, Charlene Fallan, Graeme Scarfe, Anna Aagaard, James S. Scott, Oliver R. Steward, Yafeng Xue, Iain A. Cumming, Tony Johnson, Gail L. Wrigley, Karl-Johan Leuchowius, Stephen D. Wilkinson, Graeme R. Robb, Coura R. Diène, and Alan Rosen
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Cell Survival ,Clinical Biochemistry ,Pharmaceutical Science ,Molecular Dynamics Simulation ,Crystallography, X-Ray ,Biochemistry ,Mice ,Structure-Activity Relationship ,Dogs ,Drug Stability ,Cell Line, Tumor ,Drug Discovery ,Bruton's tyrosine kinase ,Animals ,Humans ,Molecular Biology ,Aldehyde oxidase ,Protein Kinase Inhibitors ,Binding Sites ,biology ,Chemistry ,Organic Chemistry ,Metabolism ,IRAK4 ,In vitro ,Rats ,Aldehyde Oxidase ,Interleukin-1 Receptor-Associated Kinases ,Covalent bond ,biology.protein ,Microsome ,Hepatocytes ,Microsomes, Liver ,Quinazolines ,Molecular Medicine ,Acalabrutinib ,Half-Life - Abstract
In this article, we report our efforts towards improving in vitro human clearance in a series of 5-azaquinazolines through a series of C4 truncations and C2 expansions. Extensive DMPK studies enabled us to tackle high Aldehyde Oxidase (AO) metabolism and unexpected discrepancies in human hepatocyte and liver microsomal intrinsic clearance. Our efforts culminated with the discovery of 5-azaquinazoline 35, which also displayed exquisite selectivity for IRAK4, and showed synergistic in vitro activity against MyD88/CD79 double mutant ABC-DLBCL in combination with the covalent BTK inhibitor acalabrutinib.
- Published
- 2020
10. Donor oocyte recipients do not benefit from preimplantation genetic testing for aneuploidy to improve pregnancy outcomes
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Kate Devine, Michael J. Levy, Heidi Hayes, Micah J. Hill, Allison A. Eubanks, Michelle Gainty, N. Doyle, Alan H. DeCherney, Joe Doyle, Samad Jahandideh, and Michael J. Tucker
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Infertility ,Aneuploidy ,Miscarriage ,Andrology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,medicine ,Humans ,Genetic Testing ,030304 developmental biology ,Retrospective Studies ,0303 health sciences ,030219 obstetrics & reproductive medicine ,business.industry ,Meiosis II ,Rehabilitation ,Pregnancy Outcome ,Obstetrics and Gynecology ,Oocyte cryopreservation ,Original Articles ,medicine.disease ,Oocyte ,Embryo transfer ,medicine.anatomical_structure ,Reproductive Medicine ,Oocytes ,Female ,business ,Live birth - Abstract
STUDY QUESTION Do donor oocyte recipients benefit from preimplantation genetic testing for aneuploidy (PGT-A)? SUMMARY ANSWER PGT-A did not improve the likelihood of live birth for recipients of vitrified donor oocytes, but it did avoid embryo transfer in cycles with no euploid embryos. WHAT IS KNOWN ALREADY Relative to slow freeze, oocyte vitrification has led to increased live birth from cryopreserved oocytes and has led to widespread use of this technology in donor egg IVF programs. However, oocyte cryopreservation has the potential to disrupt the meiotic spindle leading to abnormal segregation of chromosome during meiosis II and ultimately increased aneuploidy in resultant embryos. Therefore, PGT-A might have benefits in vitrified donor egg cycles. In contrast, embryos derived from young donor oocytes are expected to be predominantly euploid, and trophectoderm biopsy may have a negative effect relative to transfer without biopsy. STUDY DESIGN, SIZE, DURATION This is a paired cohort study analyzing donor oocyte-recipient cycles with or without PGT-A performed from 2012 to 2018 at 47 US IVF centers. PARTICIPANTS/MATERIALS, SETTING, METHODS Vitrified donor oocyte cycles were analyzed for live birth as the main outcome measure. Outcomes from donors whose oocytes were used by at least two separate recipient couples, one couple using PGT-A (study group) and one using embryos without PGT-A (control group), were compared. Generalized estimating equation models controlled for confounders and nested for individual donors contributing to both PGT-A and non-PGT-A cohorts, enabling a single donor to serve as her own control. MAIN RESULTS AND THE ROLE OF CHANCE In total, 1291 initiated recipient cycles from 223 donors were analyzed, including 262 cycles with and 1029 without PGT-A. The median aneuploidy rate per recipient was 25%. Forty-three percent of PGT-A cycles had only euploid embryos, whereas only 12.7% of cycles had no euploid embryos. On average 1.09 embryos were transferred in the PGT-A group compared to 1.38 in the group without PGT-A (P LIMITATIONS, REASONS FOR CAUTION Pooled clinical data from 47 IVF clinics introduced PGT-A heterogeneity as genetic testing were performed using different embryology laboratories, PGT-A companies and testing platforms. WIDER IMPLICATIONS OF THE FINDINGS PGT-A testing in donor oocyte-recipient cycles does not improve the chance for live birth nor decrease the risk for miscarriage in the first transfer cycle but does increase cost and time for the patient. Further studies are required to test if our findings can be applied to the young infertility patient population using autologous oocytes. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used for this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.
- Published
- 2020
11. Discovery of N-(4-{[5-Fluoro-7-(2-methoxyethoxy)quinazolin-4-yl]amino}phenyl)-2-[4-(propan-2-yl)-1H-1,2,3-triazol-1-yl]acetamide (AZD3229), a Potent Pan-KIT Mutant Inhibitor for the Treatment of Gastrointestinal Stromal Tumors
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Darren Stead, Michael J. Tucker, Steve Stokes, Martin J. Packer, Christopher Hardy, Ross Overman, Scott Boyd, Stuart E. Pearson, Deepa Bhavsar, Andrew D. Campbell, Derek Ogg, Michael Grondine, Sylvie Guichard, Evan Barry, Marianne Schimpl, James M. Smith, Yang Ye, Kristin Goldberg, Thomas Anthony Hunt, Aaron Smith, Crystal Brown, Jason Grant Kettle, Wenlin Shao, Olga Moleva, Rana Anjum, Xiuwei Li, and Rhys D.O. Jones
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Models, Molecular ,0301 basic medicine ,Stromal cell ,Gastrointestinal Stromal Tumors ,Protein Conformation ,Mutant ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Drug Discovery ,Tumor Cells, Cultured ,Humans ,Potency ,Tissue Distribution ,Protein Kinase Inhibitors ,Gastrointestinal Neoplasms ,Kinase ,Quinoline ,Triazoles ,Proto-Oncogene Proteins c-kit ,030104 developmental biology ,chemistry ,Cell culture ,030220 oncology & carcinogenesis ,Mutation ,Quinazolines ,Cancer research ,Molecular Medicine ,Mutant Proteins ,Tyrosine kinase ,Acetamide - Abstract
While the treatment of gastrointestinal stromal tumors (GISTs) has been revolutionized by the application of targeted tyrosine kinase inhibitors capable of inhibiting KIT-driven proliferation, diverse mutations to this kinase drive resistance to established therapies. Here we describe the identification of potent pan-KIT mutant kinase inhibitors that can be dosed without being limited by the tolerability issues seen with multitargeted agents. This effort focused on identification and optimization of an existing kinase scaffold through the use of structure-based design. Starting from a series of previously reported phenoxyquinazoline and quinoline based inhibitors of the tyrosine kinase PDGFRα, potency against a diverse panel of mutant KIT driven Ba/F3 cell lines was optimized, with a particular focus on reducing activity against a KDR driven cell model in order to limit the potential for hypertension commonly seen in second and third line GIST therapies. AZD3229 demonstrates potent single digit nM growth inhibition across a broad cell panel, with good margin to KDR-driven effects. Selectivity over KDR can be rationalized predominantly by the interaction of water molecules with the protein and ligand in the active site, and its kinome selectivity is similar to the best of the approved GIST agents. This compound demonstrates excellent cross-species pharmacokinetics, shows strong pharmacodynamic inhibition of target, and is active in several in vivo models of GIST.
- Published
- 2018
12. COMPARISON OF FOUR NATIONAL REPRODUCTIVE GENETICS LAB PGT-A Results FROM VITRIFIED DONOR EGGS
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Michael J. Tucker, Jonah D. Bardos, Jeanne O'Brien, Alan H. DeCherney, W. Caswell, Samad Jahandideh, Micah J. Hill, and Melissa O. Stratton
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Reproductive Medicine ,Obstetrics and Gynecology ,Zoology ,Biology ,Reproductive genetics - Published
- 2021
13. Cobalt versus Osmium: Control of Both trans and cis Selectivity in Construction of the EFG Rings of Pectenotoxin 4
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Michael J. Tucker, Timothy J. Donohoe, Ahria Esphandiar Roushanbakhti, Wasim M. Akhtar, Yifan Liu, Daryl S. Walter, Gail L. Wrigley, and Paul C. M. Winship
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inorganic chemicals ,Natural product ,010405 organic chemistry ,Stereochemistry ,chemistry.chemical_element ,General Medicine ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Osmium ,Stereoselectivity ,Metal catalyst ,Selectivity ,Cobalt - Abstract
Catalytic oxidative cyclisation reactions have been employed for the synthesis of the E and F rings of the complex natural product target pectenotoxin 4. The choice of metal catalyst (cobalt- or osmium-based) allowed for the formation of THF rings with either trans or cis stereoselectivity. Fragment union using a modified Julia reaction then enabled the synthesis of an advanced synthetic intermediate containing the EF and G rings of the target.
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- 2017
14. Assisted Hatching of Human Embryos for Successful Implantation
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Kristine A. Milne, Matteo A. Avella, Michael J. Tucker, Shagufta Dawood, and Adam Dawood
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Infertility ,animal structures ,urogenital system ,Hatching ,Preimplantation Embryos ,Embryo ,Biology ,medicine.disease ,Uterine walls ,Andrology ,Assisted hatching ,medicine.anatomical_structure ,embryonic structures ,medicine ,Blastocyst ,Zona pellucida ,reproductive and urinary physiology - Abstract
For successful implantation, the human embryo must breach the zona pellucida, an extracellular glycoproteic matrix surrounding ovulated eggs and preimplantation embryos. This process, defined as “hatching,” is a necessary step in reproduction and occurs when the embryo reaches the blastocyst stage. Due to the blastocyst’s expansions and contractions and still undefined molecular mechanisms, the zona matrix becomes thinner, which helps the embryo to escape and eventually implant in the uterine walls. Indeed, any obstacle impairing blastocyst hatching might result in failure of implantation and consequently, infertility.
- Published
- 2019
15. An efficient and flexible route to novel triazolopiperazine scaffolds
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Michael J. Tucker, Olivier Lorthioir, Ryan Greenwood, and Andrew Lister
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chemistry.chemical_classification ,chemistry ,010405 organic chemistry ,Drug discovery ,Organic Chemistry ,Drug Discovery ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Combinatorial chemistry ,0104 chemical sciences ,Amino acid - Abstract
In this work we describe the preparation of novel fused, spirocyclic and chiral triazolopiperazines. We have developed a practical, rapid and robust synthetic route to these scaffolds that allows control of regio- and stereochemistry. This method utilises mild conditions and uses widely available and diverse amino acids and amidines as starting materials. These complex unprecedented 5,6,7,8-tetrahydro-[1–2,4]triazolo[1,5-a]pyrazines represent attractive building blocks for drug discovery.
- Published
- 2020
16. Overview of Carlin-Type Prospects of the Nadaleen Trend: A Yukon Analogue to Carlin-Type Gold Mineralization of the Great Basin
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Michael J. Tucker, Craig J.R. Hart, and Julia C. Lane
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Geochemistry ,Gold mineralization ,Structural basin ,Geology - Published
- 2018
17. Human Oocyte and Embryo Cryopreservation
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Matthew VerMilyea, Joshua Lim, and Michael J. Tucker
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Andrology ,medicine.anatomical_structure ,Embryo cryopreservation ,medicine ,Biology ,Oocyte - Published
- 2018
18. Larger oocyte cohorts maximize fresh IVF cycle birth rates and availability of surplus high-quality blastocysts for cryopreservation
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Kevin S. Richter, Alan H. DeCherney, Kate Devine, Matthew T. Connell, Michael J. Tucker, Michael J. Levy, J. Doyle, and Micah J. Hill
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0301 basic medicine ,Adult ,Pregnancy Rate ,Ovarian hyperstimulation syndrome ,Oocyte Retrieval ,Fertilization in Vitro ,Biology ,Cryopreservation ,Birth rate ,Andrology ,03 medical and health sciences ,Ovarian Hyperstimulation Syndrome ,0302 clinical medicine ,Embryo cryopreservation ,Ovulation Induction ,Pregnancy ,medicine ,Humans ,Retrospective Studies ,030219 obstetrics & reproductive medicine ,Obstetrics and Gynecology ,Retrospective cohort study ,medicine.disease ,Oocyte ,030104 developmental biology ,medicine.anatomical_structure ,Blastocyst ,Reproductive Medicine ,Cohort ,Female ,Live birth ,Developmental Biology - Abstract
How does oocyte cohort size affect IVF treatment outcomes?Retrospective cohort analysis of 10,193 fresh autologous oocyte retrievals among good-prognosis patients35 years from 2009 to 2015. The primary outcome was live birth from a fresh transfer; secondary outcomes included cumulative live birth potential from the retrieved cohort and frequency of severe ovarian hyperstimulation syndrome (OHSS).Live birth per fresh transfer increased as the oocyte cohort increased up to 11-15 oocytes, then plateaued. Beyond 15 oocytes, live birth rates from fresh transfer did not decrease, even at the highest oocyte yields. When accounting for the availability of cryopreserved high-quality supernumerary blastocysts, the cumulative number of potential live births per retrieval continued to increase as oocyte yield increased. Rates of severe OHSS increased rapidly with increasing cohort size above 7-10 oocytes when final oocyte maturation was triggered with human chorionic gonadotrophin (HCG), up to nearly 7% of HCG-triggered retrievals of25 oocytes, but when triggered with gonadotrophin-releasing hormone (GnRH) agonist the severe OHSS rate remained relatively low and stable at approximately 1% even among retrievals of the largest oocyte cohorts.Live birth rates per fresh embryo transfer are highest among cycles with retrieval of 11 or more oocytes. Larger cohorts are not associated with any decline in fresh transfer birth rates. Total potential births per retrieval continue to increase as the number of retrieved oocytes increases. Rates of OHSS remain relatively low after retrieval of large oocyte cohorts if final maturation is triggered with GnRH agonist rather than HCG.
- Published
- 2017
19. Chapter 14 Establishing an Oocyte Cryobank Network
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James K. Graham, J. Lim, and Michael J. Tucker
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0301 basic medicine ,030219 obstetrics & reproductive medicine ,Donor egg ,Donor oocyte ,Oocyte cryopreservation ,Oocyte ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Quality management system ,Risk analysis (engineering) ,Oocyte donation ,medicine ,Business ,Fertility preservation ,Donor sperm - Abstract
Improvements in oocyte cryopreservation has prompted wider acceptance of this technology leading to its use for several reasons. Notably, in addition to elective and medically driven reasons for oocyte cryostorage for fertility preservation, donor oocyte cryobanking is beginning to gain traction, potentially replacing fresh oocyte donation in assisted reproduction. Donor "egg banking," while not totally analogous to donor sperm banking, does provide strong benefits in terms of scheduling flexibility and improved clinical efficiencies, while providing a wider immediate inventory choice. The development of a successful cryobank "network" and subsequent growth into a full-access donor egg bank are only possible through adoption of a series of key steps involving establishment of a repeatable vitrification protocol with a strong clinical record, incorporation of a comprehensive database and quality management system, and strict control over the logistics of inventory and shipping and receiving, to establish a flawless chain from donor to recipient. Confidence will grow in this potentially difficult process over time.
- Published
- 2017
20. Do donor oocyte recipients benefit from preimplantation genetic testing for aneuploidy(PGT-A) to improve pregnancy outcomes?
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J.R. Graham, Michael J. Tucker, Alan H. DeCherney, J. Lim, W. Caswell, M. Gainty, J. Doyle, N. Doyle, H. Hayes, Micah J. Hill, and Michael J. Levy
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Reproductive Medicine ,medicine.diagnostic_test ,business.industry ,medicine ,Obstetrics and Gynecology ,Aneuploidy ,Donor oocyte ,medicine.disease ,Bioinformatics ,Pregnancy outcomes ,business ,Genetic testing - Published
- 2018
21. Birth rates following euploid blastocyst transfer declines rapidly with previous unsuccessful transfers of euploid blastocysts
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Kevin S. Richter, Caleb B. Kallen, Kate Devine, I. Sasson, Michael J. Tucker, Micah J. Hill, Jessica R. Zolton, J.R. Graham, E.A. Widra, and Alan H. DeCherney
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Andrology ,Reproductive Medicine ,Blastocyst Transfer ,Obstetrics and Gynecology ,Biology ,Birth rate - Published
- 2018
22. Near futility of rescue intracytoplasmic sperm injection (ICSI) and the advantage of vitrification over fresh transfer
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E.A. Widra, J.R. Graham, B. Slocum, Michael J. Tucker, and Kevin S. Richter
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Andrology ,Reproductive Medicine ,Chemistry ,medicine.medical_treatment ,medicine ,Obstetrics and Gynecology ,Vitrification ,Intracytoplasmic sperm injection - Published
- 2018
23. Cryo tank quality control: how to detect a tank that is ‘failing’
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Cristina L. Applegate, Michael J. Tucker, Seamus R. Graham, and J.R. Graham
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Reproductive Medicine ,media_common.quotation_subject ,Control (management) ,Obstetrics and Gynecology ,Environmental science ,Quality (business) ,Automotive engineering ,media_common - Published
- 2019
24. Factors associated with birth outcomes from cryopreserved blastocysts: experience from 4,597 autologous transfers of 7,597 cryopreserved blastocysts
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S.K. Shipley, Kevin S. Richter, Michael J. Tucker, J. Lim, J.R. Graham, Daniella K. Ginsburg, and Michael J. Levy
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0301 basic medicine ,medicine.medical_specialty ,Blastomeres ,Time Factors ,Pregnancy Rate ,Fertilization in Vitro ,Cryopreservation ,Birth rate ,Andrology ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Risk Factors ,medicine ,Single Embryo Transfer ,Humans ,Blastocyst ,Embryo Implantation ,Retrospective Studies ,030219 obstetrics & reproductive medicine ,Obstetrics ,business.industry ,Blastocyst Transfer ,Obstetrics and Gynecology ,medicine.disease ,Embryo Transfer ,Pregnancy, Triplet ,Embryo transfer ,Pregnancy rate ,030104 developmental biology ,medicine.anatomical_structure ,Fertility ,Treatment Outcome ,Reproductive Medicine ,Infertility ,Pregnancy, Twin ,Female ,Live birth ,business - Abstract
To evaluate factors associated with cryopreserved blastocyst transfer birth outcomes, including age, expansion time, cryopreservation protocol, cryodamage, and number of embryos transferred.Retrospective cohort study.Private infertility practice.Cryopreserved blastocyst transfer patients from January 2003 to April 2012.None.Birth per transfer and children per embryo.Overall live birth per transfer was 32%, with 17% twin births and 0.3% triplets. Live birth per transfer was significantly higher for vitrification compared with slow-freeze (day 5 cryopreservation: 47% vs. 35%; day 6 cryopreservation: 46% vs. 24%), as was live born children per transferred embryo (39% vs. 29% for day 5; 36% vs. 18% for day 6). Birth rates declined only slightly with increasing age at cryopreservation through 37 years, followed by an increasingly rapid decline in success with increasing age thereafter. Live birth rates declined rapidly (49%-18% for vitrification and 37%-10% for slow-freeze) as the percentage of intact cells after cryopreservation decreased from 95%-100% to 70%-79%, with almost no births when the percentage of intact cells was70%. Increasing numbers of embryos per transfer were associated with significant increase in live birth per transfer but significant decrease in children per transferred embryo. Birth rates were much lower for blastocysts with delayed expansion on day 7 (10% per transfer).Birth outcomes from cryopreserved blastocyst transfer are influenced by age, timing of expansion, cryopreservation protocol, visible cryodamage, and the number of embryos transferred. Vitrification substantially improves outcomes versus slow freezing.
- Published
- 2016
25. PGS does not improve pregnancy outcomes in IVF cycles using vitrified donor oocytes
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Kate Devine, N. Doyle, J. Graham, J. Lim, Melissa O. Stratton, W. Caswell, M.J. Hill, Michael J. Tucker, H. Hayes, J. Doyle, Michael J. Levy, and Alan H. DeCherney
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medicine.medical_specialty ,Reproductive Medicine ,Obstetrics ,business.industry ,medicine ,Obstetrics and Gynecology ,Pregnancy outcomes ,business - Published
- 2017
26. Association between the number of retrieved mature donor oocytes and live birth in IVF donor recipient cycles using frozen donor eggs
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J. Lim, H. Hayes, J. Graham, J. Doyle, Michael J. Levy, Alan H. DeCherney, N. Doyle, Michael J. Tucker, Kate Devine, W. Caswell, Melissa O. Stratton, and M.J. Hill
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Andrology ,03 medical and health sciences ,030219 obstetrics & reproductive medicine ,0302 clinical medicine ,Reproductive Medicine ,Obstetrics and Gynecology ,030209 endocrinology & metabolism ,Biology ,Live birth - Published
- 2017
27. Routine Gamete Intrafallopian Transfer (GIFT): A Highly Successful Option for Treatment of Non-Tubal Infertility
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Milton Leong, Michael J. Tucker, Helen H. Y. Chan, Colleen J. Y. Wong, Vicky M. Marriott, Yuen Mun Chan, and Clement K. M. Leung
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Gynecology ,Infertility ,medicine.medical_specialty ,Pregnancy ,In vitro fertilisation ,Intrauterine insemination ,Obstetrics ,business.industry ,medicine.medical_treatment ,education ,Idiopathic infertility ,Endometriosis ,Obstetrics and Gynecology ,medicine.disease ,Gamete Intrafallopian Transfer ,humanities ,Pregnancy rate ,medicine ,Humans ,Female ,Gamete intrafallopian transfer ,business ,health care economics and organizations - Abstract
Gamete intrafallopian transfer (GIFT) is increasingly accepted as a realistic alternative to in vitro fertilization (IVF), or intrauterine insemination (IUI) for treatment of non-tubal infertility. The lack of information on fertilization capacity of the gametes, the greater cost relative to IUI, and the partly unsubstantiated claims of higher success rates, caused us some concern with the readiness with which GIFT had been accepted as a standard infertility treatment. So we undertook a provisional GIFT programme with these considerations in mind, and we report on the first 91 GIFT cycles performed in our clinic. Sixty of the patients (62 cycles) treated suffered from idiopathic infertility, 12 from minimal endometriosis, 9 from male factor infertility, and 8 from ovulatory dysfunction. An initial clinical pregnancy rate of 41% (38/91) was achieved; pregnancy loss was 23% (9/38), giving a continuing pregnancy rate of 32% (29/91). Given this undeniably encouraging result, and the potential for diagnostic IVF, embryo freezing, and ovum donation with surplus oocytes collected from this GIFT programme, we now have adopted GIFT permanently as a treatment to complement our IVF and IUI programmes.
- Published
- 2010
28. Association between Human in vitro Fertilization Rate and Pregnancy Outcome: A Possible Involvement of Spermatozoal Quality in Subsequent Embryonic Viability
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Milton Leong, Steven Y.W. Chan, Michael J. Tucker, and Clement K. M. Leung
- Subjects
Male ,In vitro fertilisation ,Spermatozoon ,Cell Survival ,medicine.medical_treatment ,Obstetrics and Gynecology ,Embryo ,Fertilization in Vitro ,Reproductive technology ,Biology ,Oocyte ,Spermatozoa ,Embryo transfer ,Andrology ,Treatment Outcome ,Human fertilization ,medicine.anatomical_structure ,Pregnancy ,medicine ,Humans ,Gamete ,Female - Abstract
A conventional view of mammalian fertilization is that the active component of the process: the spermatozoon, by virtue of its progressive motility and acrosomal enzymes, penetrates an otherwise passive oocyte. This concept has placed bias on spermatozoal normality as largely determining the outcome of fertilization; once this has been achieved then the contribution of the spermatozoon is often forgotten, and attention switches to the maternally derived "blue-print" for early embryonic development. Paternal genomic contribution is known to start at the eight-cell stage in the human, but this is usually after the time when early cleavage stage (2 to 8-cell stage) embryos are replaced in human assisted reproductive technologies (ART) procedures such as in vitro fertilization and embryo transfer (IVF-ET). Hence, fundamental abnormal contributions to embryogenesis derived from the fertilizing spermatozoon have often been ignored. Human IVF-ET has permitted far greater powers of analysis of the fertilization event, and fertilization success appears to be determined in such a system by three main factors: spermatozoal quality, oocyte quality, and quality of in vitro culture conditions (the gamete environment). If the second two factors are more carefully controlled than the first, as is the usual emphasis in routine human IVF practice, then any large variation in fertilization rates that are also significantly related to embryonic viability and ultimately pregnancy outcome, may be thought to be more directly associated with original quality of the fertilizing spermatozoon. An analysis of results of 758 IVF cases provides preliminary evidence to show that there is a close association between human in vitro fertilization rate and subsequent embryo viability following replacement. In accepting this hypothesis as a possibility, we should drastically change our attitude from one of the spermatozoon as a robust, simple initiator of embryonic development, and embrace the idea of the vulnerability of such germ cells both during and after their production, and how detrimental influences on this might profoundly affect embryogenesis after successful fertilization.
- Published
- 2010
29. Intrauterine Insemination as Frontline Treatment for Non-Tubal Infertility
- Author
-
Yuen-Mun Chan, Colleen J. Y. Wong, Michael J. Tucker, Clement K. M. Leung, and Milton Leong
- Subjects
Adult ,Male ,Infertility ,medicine.medical_specialty ,medicine.drug_class ,Natural cycle ,media_common.quotation_subject ,medicine.medical_treatment ,Human chorionic gonadotropin ,Pregnancy ,Patient age ,medicine ,Humans ,Ovulation ,Insemination, Artificial ,Insemination, Artificial, Homologous ,media_common ,Gynecology ,Intrauterine insemination ,business.industry ,Obstetrics ,Artificial insemination ,Uterus ,Infant, Newborn ,Obstetrics and Gynecology ,medicine.disease ,Female ,Pregnancy, Multiple ,Gonadotropin ,business ,Infertility, Female - Abstract
Eighty-one clinical pregnancies occurred from 508 cycles of intrauterine insemination (IUI) in 242 patients. Following 20 miscarriages 30 pregnancies have been delivered, and 31 remain ongoing at 16 weeks and beyond. This represents a 12% delivered/ongoing pregnancy outcome per cycle of IUI, in women of average age 30.9 years who with their partners had suffered on average 3.65 years of infertility. All forms of non-tubal infertility were treated with pregnancies occurring in all primary categories. No pregnancies occurred in 5 women who underwent IUI in 18 natural cycles. All pregnancies arose in the 237 women who received clomiphene citrate, human menopausal gonadotropin, or a combination of both with ovulation triggered by human chorionic gonadotropin. Dependent upon patient age and duration of infertility, we implement IUI as a frontline treatment for all cases of non-tubal infertility prior to subjecting patients to the more costly and invasive tubal transfer techniques.
- Published
- 2010
30. Blastocyst freeze-all strategy versus fresh transfer in anonymous oocyte donation cycles
- Author
-
N. Doyle, J. Graham, Alan H. DeCherney, R.J. Stillman, Kevin S. Richter, J. Doyle, Michael J. Tucker, and Michael J. Levy
- Subjects
Andrology ,Freeze all ,medicine.anatomical_structure ,Reproductive Medicine ,Chemistry ,Oocyte donation ,medicine ,Obstetrics and Gynecology ,Blastocyst - Published
- 2018
31. The diagnostic value of seminal adenosine triphosphate (ATP) in an in vitro fertilization (IVF) program: Der diagnostische Wert von ATP in einem IVF-Programm
- Author
-
Michael J. Tucker, S. Y. W. Chan, Y. M. Chan, C. K. M. Leung, and M. K. H. Leong
- Subjects
endocrine system ,medicine.medical_specialty ,In vitro fertilisation ,urogenital system ,Urology ,medicine.medical_treatment ,Artificial insemination ,Stepwise discriminant analysis ,Motility ,Semen ,General Medicine ,Biology ,Oocyte ,Andrology ,chemistry.chemical_compound ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Internal medicine ,medicine ,Adenosine triphosphate ,Sperm motility - Abstract
The level of adenosine triphosphate (ATP) was quantitated in semen samples used for in vitro fertilization of human oocytes. Seminal ATP level correlated with the concentration and percentage motility of spermatozoa but not with the in vitro fertilization rate of human oocytes. Seminal ATP measurement appears to have little diagnostic value in predicting the fertilizing capacity of spermatozoa as evaluated by the multivariate stepwise discriminant analysis.
- Published
- 2009
32. Laser assisted hatching in good prognosis patients undergoing in vitro fertilization-embryo transfer: a randomized controlled trial
- Author
-
Kevin S. Richter, E.A. Widra, Arthur W. Sagoskin, Michael J. Tucker, and Michael J. Levy
- Subjects
Adult ,Infertility ,medicine.medical_specialty ,animal structures ,medicine.medical_treatment ,Fertilization in Vitro ,Micromanipulation ,Pregnancy ,Outcome Assessment, Health Care ,Humans ,Medicine ,Gynecology ,Assisted reproductive technology ,In vitro fertilisation ,Maryland ,business.industry ,Obstetrics ,Pregnancy Outcome ,Obstetrics and Gynecology ,Embryo Transfer ,Prognosis ,medicine.disease ,Embryo transfer ,Treatment Outcome ,Reproductive Medicine ,embryonic structures ,Gestation ,Female ,Laser Therapy ,business ,Live birth ,Infertility, Female ,Microdissection ,Embryo quality - Abstract
Objective To evaluate whether assisted hatching improves clinical outcomes of embryo transfers to good prognosis patients, defined as patients ≤39 years with normal follicle-stimulating hormone (FSH) and E 2 levels, no more than one previous unsuccessful cycle of in vitro fertilization (IVF)–embryo transfer, and good embryo quality. Design Prospective randomized controlled trial. Setting Private assisted reproductive technology (ART) center. Patient(s) One hundred ninety-nine good prognosis patients undergoing IVF–embryo transfer. Intervention(s) In vitro fertilization followed by embryo transfer on day 3 after oocyte retrieval with or without assisted hatching using a 1,480-nm wavelength infrared laser. Main Outcome Measure(s) Clinical intrauterine pregnancy, spontaneous pregnancy loss, and live birth. Result(s) Rates of clinical intrauterine pregnancy with fetal cardiac activity (53% vs. 54% per cycle), spontaneous pregnancy loss (13% vs. 16% per pregnancy), and live birth (47% vs. 46% per cycle) were very similar between treatment cycles with laser-assisted hatching and control cycles in which embryos were transferred without assisted hatching. There were no significant differences between treatment and control groups in any measured clinical outcome parameters. Conclusion(s) Assisted hatching does not improve clinical outcomes among good prognosis patients.
- Published
- 2007
33. Scrying the future: The ongoing transformation of reproductive medicine through vitrification
- Author
-
Kevin S. Richter, Michael J. Tucker, and J.R. Graham
- Subjects
medicine.medical_specialty ,Oocyte donation ,Political science ,Reproductive medicine ,medicine ,Engineering ethics ,Fertility preservation ,Embryo transfer - Abstract
Reproductive medicine is in the midst of an exhilarating revolution. Few innovations have had as transformative an impact on the eld of assisted reproduction as vitri- cation. is impact will only increase as development and renement of vitrication technology and methodology continues. e benets associated with vitrication of cells and tissues have profound consequences for nearly every aspect of assisted reproductive practices. Damagefree storage of gametes and embryos, made possible for the rst time through vitrication, dramatically improves the ecacy and practicality of a variety of current procedures and unlocks an entirely new realm of possibilities for fertilization and embryo transfer strategies, oocyte donation, and elective fertility preservation.
- Published
- 2015
34. Successful elective and medically indicated oocyte vitrification and warming for autologous in vitro fertilization, with predicted birth probabilities for fertility preservation according to number of cryopreserved oocytes and age at retrieval
- Author
-
J.R. Graham, J. Doyle, Robert J. Stillman, Michael J. Tucker, Joshua Lim, and Kevin S. Richter
- Subjects
0301 basic medicine ,Adult ,medicine.medical_specialty ,Pregnancy Rate ,medicine.medical_treatment ,Oocyte Retrieval ,Fertilization in Vitro ,Intracytoplasmic sperm injection ,Andrology ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Risk Factors ,medicine ,Humans ,Fertility preservation ,Retrospective Studies ,Gynecology ,Cryopreservation ,030219 obstetrics & reproductive medicine ,In vitro fertilisation ,business.industry ,Age Factors ,Obstetrics and Gynecology ,Fertility Preservation ,Oocyte cryopreservation ,Oocyte ,Embryo Transfer ,Vitrification ,Embryo transfer ,Pregnancy rate ,030104 developmental biology ,medicine.anatomical_structure ,Treatment Outcome ,Reproductive Medicine ,Oocytes ,Female ,Live birth ,business ,Live Birth - Abstract
Objective To evaluate a single treatment center's experience with autologous IVF using vitrified and warmed oocytes, including fertilization, embryonic development, pregnancy, and birth outcomes, and to estimate the likelihood of live birth of at least one, two, or three children according to the number of mature oocytes cryopreserved by elective fertility preservation patients. Design Retrospective cohort study. Setting Private practice clinic. Patient(s) Women undergoing autologous IVF treatment using vitrified and warmed oocytes. Indications for oocyte vitrification included elective fertility preservation, desire to limit the number of oocytes inseminated and embryos created, and lack of available sperm on the day of oocyte retrieval. Intervention(s) Oocyte vitrification, warming, and subsequent IVF treatment. Main Outcome Measure(s) Post-warming survival, fertilization, implantation, clinical pregnancy, and live birth rates. Result(s) A total of 1,283 vitrified oocytes were warmed for 128 autologous IVF treatment cycles. Postthaw survival, fertilization, implantation, and birth rates were all comparable for the different oocyte cryopreservation indications; fertilization rates were also comparable to fresh autologous intracytoplasmic sperm injection cycles (70% vs. 72%). Implantation rates per embryo transferred (43% vs. 35%) and clinical pregnancy rates per transfer (57% vs. 44%) were significantly higher with vitrified–warmed compared with fresh oocytes. However, there was no statistically significant difference in live birth/ongoing pregnancy (39% vs. 35%). The overall vitrified–warmed oocyte to live born child efficiency was 6.4%. Conclusion(s) Treatment outcomes using autologous oocyte vitrification and warming are as good as cycles using fresh oocytes. These results are especially reassuring for infertile patients who must cryopreserve oocytes owing to unavailability of sperm or who wish to limit the number of oocytes inseminated. Age-associated estimates of oocyte to live-born child efficiencies are particularly useful in providing more explicit expectations regarding potential births for elective oocyte cryopreservation.
- Published
- 2015
35. Recent Advances in Cancer Therapeutics
- Author
-
A. Elisa Pasqua, Nicola E. A. Chessum, Michael J. Tucker, and Keith Jones
- Subjects
Clinical trial ,Low toxicity ,Kinase ,medicine ,Oncology drug ,Imatinib ,Histone deacetylase ,Epigenetics ,Pharmacology ,Biology ,Chronic myeloid leukaemia ,Bioinformatics ,medicine.drug - Abstract
In the past 20 years, cancer therapeutics has undergone a paradigm shift away from the traditional cytotoxic drugs towards the targeting of proteins intimately involved in driving the cancer phenotype. The poster child for this alternative approach to the treatment of cancer is imatinib, a small-molecule kinase inhibitor designed to target chronic myeloid leukaemia driven by the BCR-ABL translocation in a defined patient population. The improvement in survival achieved by treatment of this patient cohort with imatinib is impressive. Thus, the aim is to provide efficacy but with low toxicity. The role of the medicinal chemist in oncology drug discovery is now closely aligned with the role in most other therapeutic areas with high-throughput and/or fragment-based screening, structure-based design, selectivity, pharmacokinetic optimisation and pharmacodynamic biomarker modulation, all playing a familiar part in the process. In this chapter, we selected four areas in which compounds are either approved drugs or in clinical trials. These are chaperone inhibitors, kinase inhibitors, histone deacetylase inhibitors and inhibitors of protein-protein interactions. Even within these areas, we have been selective, particularly for kinase inhibitors, and our aim has been to exemplify newer approaches and novel aspects of medicinal chemistry.
- Published
- 2015
36. Comparison of vitrification and conventional cryopreservation of day 5 and day 6 blastocysts during clinical application
- Author
-
Juergen Liebermann and Michael J. Tucker
- Subjects
Adult ,medicine.medical_specialty ,Pregnancy Rate ,Cell Survival ,Biology ,Cryopreservation ,Andrology ,Pregnancy ,medicine ,Humans ,Vitrification ,Blastocyst ,Survival rate ,reproductive and urinary physiology ,Gynecology ,Obstetrics and Gynecology ,Embryo ,Embryo Transfer ,medicine.disease ,United States ,Embryo transfer ,Pregnancy rate ,Treatment Outcome ,medicine.anatomical_structure ,Reproductive Medicine ,embryonic structures ,Female ,Infertility, Female - Abstract
Objective To evaluate implantation of day 5 and day 6 vitrified and slow-frozen blastocysts. Design Retrospective analysis comparing two cryopreservation techniques. Setting Private IVF clinic. Patient(s) Five hundred eight cryopreserved embryo transfer candidates. Intervention(s) Supernumerary day 5 and day 6 blastocysts were vitrified or slow-frozen and transfered after warming or thawing. Main Outcome Measure(s) Comparison of two cryopreservation techniques with respect to survival rate, implantation, and pregnancy rates of day 5 and day 6 blastocysts. Result(s) In 254 vitrified transfer cycles, survival, embryonic implantation, and clinical pregnancy rates for day 5 blastocysts were 95.9%, 33.4%, 48.7%, respectively, and for day 6 blastocysts 97.5%, 25.9%, 42.8%. In 254 slow-frozen transfer cycles, survival, embryonic implantation, and clinical pregnancy rates for day 5 blastocysts were 91.4%, 29.6%, 42.8%, respectively, and for day 6 blastocysts 94.8%, 28.2%, 43.1%. Overall there was a slightly, but not significantly, higher outcome regarding implantation and clinical pregnancy with the use of day 5 blastocysts (31.3% and 45.4%, respectively) versus day 6 blastocysts (26.7, and 42.9%, respectively). Conclusion(s) Vitrification technique yields the same implantation and pregnancy rate as slow-frozen blastocyst transfers. Slow growing embryos can be cryopreserved on day 6, because they yield a satisfactory survival, implantation, and pregnancy rate.
- Published
- 2006
37. Cryopreservation in Assisted Reproductive Technology: New Trends
- Author
-
Gohar Rahimi, Juergen Liebermann, Frank Nawroth, Michael J. Tucker, Maike Liebermann, Vladimir Isachenko, and Eugenia Isachenko
- Subjects
Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Reproductive medicine ,Ovary ,Biology ,Cryopreservation ,Andrology ,Cryoprotective Agents ,Endocrinology ,Pregnancy ,Physiology (medical) ,medicine ,Humans ,Vitrification ,Assisted reproductive technology ,Ovarian tissue ,Obstetrics and Gynecology ,Spermatozoa ,Autotransplantation ,In vitro maturation ,medicine.anatomical_structure ,Reproductive Medicine ,Oocytes ,Female - Abstract
During the last few years, cryopreservation has become a relevant addition to therapeutic concepts in reproductive medicine. New data and publications have made it difficult to maintain an overview of all of the new developments and their results. The focus of interest more recently, especially with the cryopreservation of human oocytes and human ovarian tissue, has been vitrification as an interesting alternative to slow freezing methods. Even though studies investigating the slow freezing of human mature oocytes have resulted in very different survival rates, it could be an option for donor oocyte programs, in the case of threatened ovarian loss or when there is an objection to embryo freezing. An optimal freezing protocol and later use of thawed human ovarian tissue is still a point of discussion. There are encouraging results regarding different kinds of autotransplantation, and recently the first birth after orthotopic autotransplantation of cryopreserved/thawed human ovarian tissue was described in the literature. Independent of any objections to cryopreservation in general, vitrification is a potential and effective alternative to conventional slow cryopreservation, especially for oocytes and embryos. Vitrification might be also be an option for human ovarian tissue; however this is only in its infancy and requires much additional investigation. Our article discusses new trends and results of actual studies regarding these issues.
- Published
- 2005
38. Human oocyte cryopreservation: a valid alternative to embryo cryopreservation?
- Author
-
Paula C. Morton, Michael J. Tucker, and Juergen Liebermann
- Subjects
Cryopreservation ,In vitro fertilisation ,medicine.medical_treatment ,Obstetrics and Gynecology ,Fertilization in Vitro ,Oocyte cryopreservation ,Biology ,Embryo, Mammalian ,Oocyte ,Embryo transfer ,In vitro maturation ,Andrology ,medicine.anatomical_structure ,Reproductive Medicine ,Embryo cryopreservation ,Pregnancy ,embryonic structures ,Oocytes ,medicine ,Humans ,Female ,Ovarian tissue cryopreservation - Abstract
Embryo cryopreservation has become an ethical necessity due to the way human in vitro fertilization (IVF) infertility therapy has developed. Limited embryonic implantation has by necessity driven IVF therapy to adopt ways to maximize the harvest of oocytes following ovarian hyperstimulation with its attendant risks. Collection of more oocytes has allowed more embryos to be generated to compensate for poor embryonic viability, often leading to transfer of multiple embryos to increase per transfer pregnancy rates. In an era of improving embryonic viability and prevailing trend toward single embryo transfers, production of excessive numbers of surplus embryos appears increasingly inappropriate. At which stage embryo cryopreservation can be undertaken most effectively remains controversial. Embryo cryopreservation nevertheless represents the current solution to the problem of excessive embryo production, but inherently raises ethical concerns for certain couples uncomfortable with what they might perceive to be "experimental" cryostorage, who in extreme circumstances may even choose to limit the number of oocytes inseminated to obviate the production of spare embryos. On a more practical level, cryostored embryos are co-owned by two people who may separate, and as such the embryos then face an uncertain fate, commonly decided in courts of law. Oocyte cryopreservation, if consistent and successful, offers a way to avoid the above complications of routine IVF therapy. Oocytes may need to be cryostored in the event of unforeseen non-production of sperm during IVF therapy, allowing a more measured consideration of donor sperm use or other means of sperm retrieval. Beyond IVF for infertility therapy using a couple's own gametes, oocyte cryopreservation provides a wonderful opportunity to optimize donor oocyte cryo-banking, reducing costs and improving convenience. Meanwhile, frozen embryo donation is an approach that many couples are uncomfortable with, and allows only for retrospective donor screening, and less gametic choice. Advances in ovarian tissue cryopreservation will probably provide the best approach for long term storage of female gametes for women wishing to elect to prolong their reproductive potential, or prior to cancer therapy. However, improved consistency with vitrification technology through standardization of protocols and cell-carrying systems is bringing routine single oocyte cryostorage, at all stages of egg maturity, closer to reality. This, coupled with in vitro maturation, will aid development of oocyte collection protocols using minimal amounts of gonadotropins. All of which will help drive IVF programs to consider cryostorage of excess oocytes and not embryos, inseminating post-thaw/warming only a limited number of oocytes at any one time, in anticipation of the need for only one or two embryos at transfer. The question then is how close are we to being able to provide routine clinical application of human oocyte cryostorage, and when will it be appropriate?
- Published
- 2004
39. Genetic and epigenetic modifications associated with human ooplasm donation and mitochondrial heteroplasmy – considerations for interpreting studies of heritability and reproductive outcome
- Author
-
Gianpiero D. Palermo, Michael J. Tucker, E Scott Sills, and Takumi Takeuchi
- Subjects
Cytoplasm ,Mitochondrial DNA ,Mitochondrial translation ,Gene Expression ,Genomics ,Context (language use) ,Fertilization in Vitro ,Biology ,Bioinformatics ,DNA, Mitochondrial ,Human mitochondrial genetics ,Epigenesis, Genetic ,Species Specificity ,Pregnancy ,Animals ,Humans ,Inheritance Patterns ,Epigenesis ,Genetics ,Oocyte Donation ,Pregnancy Outcome ,General Medicine ,Heteroplasmy ,Oocytes ,Female ,Forecasting - Abstract
The mitochondrial heteroplasmy present in offspring from IVF and human ooplasm donation is troublesome and merits further exploration in a debate that is already complex and controversial. Improving the understanding of mitochondrial genomics in this context is important because mitochondriopathies can impact crucial cellular processes in renal, cardiovascular, central nervous, and endocrine systems. Relevant epigenetic consequences of mitochondrial heteroplasmy include associated abnormalities in mitochondrial translation products. Furthermore, as transmission and inheritance patterns of mtDNA are species-specific, it remains to be proven if findings derived from animal studies are applicable to human offspring. As an alternative to gamete research and proteomics based on animal experimentation, continued molecular characterization of the de novo human mitochondriopathies is posed to offer further insights regarding mitochondrial heteroplasmy. In this context, because knowledge of human mitochondrial genetics remains limited and the risks associated with ooplasm donation cannot be quantified, we do not favor its use for our patients at present. However, the small number of infants already conceived from this experimental approach warrant careful longitudinal evaluation. In particular, observational study of the few children born after ooplasm donation could provide opportunities to assess human mtDNA transmission and inheritance. Such findings could help identify features distinguishing natural mtDNA heteroplasmy from heteroplasmy observed after ooplasm donation. Future investigations should also quantify the degree any such heteroplasmy can exist innocuously. Disclosure of mtDNA mutations potentially affecting children conceived from IVF and ooplasm donation must be included during patient education at centers contemplating such treatment.
- Published
- 2004
40. Retrieval of larger oocyte cohorts maximizes in vitro fertilization (IVF) birth rates per cycle
- Author
-
J. Graham, M.J. Hill, M.T. Connell, Michael J. Levy, Alan H. DeCherney, Kevin S. Richter, and Michael J. Tucker
- Subjects
0301 basic medicine ,030219 obstetrics & reproductive medicine ,In vitro fertilisation ,medicine.medical_treatment ,Obstetrics and Gynecology ,Biology ,Oocyte ,Birth rate ,Andrology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Reproductive Medicine ,medicine - Published
- 2016
41. Absence of profound hyperinsulinism in polycystic ovary syndrome is associated with subtle elevations in the plasminogen activator inhibitor system
- Author
-
Gianpiero D. Palermo, Carolyn R Kaplan, Carey Drews, E Scott Sills, Michael J. Tucker, and Mark Perloe
- Subjects
medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Insulin ,medicine.medical_treatment ,Hyperandrogenism ,Obstetrics and Gynecology ,Biology ,medicine.disease ,Polycystic ovary ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Internal medicine ,Plasminogen activator inhibitor-1 ,medicine ,Hyperinsulinemia ,Plasminogen activator ,Body mass index ,Hyperinsulinism - Abstract
In order to describe potential hypofibrinolytic tendencies in young (< 35 years) polycystic ovary syndrome (PCOS) patients, we studied plasminogen activator inhibitor (PAI-1) system components in women without laboratory evidence of hyperinsulinism or hyperandrogenism. The study was a prospective, observational comparison and took place in a major urban infertility referral center. Age, body mass index, ovulatory status, selected androgen levels, fasting insulin and plasma lipids were measured in subjects with PCOS (n = 39) and normal control subjects (n = 20). Women with PCOS had higher mean serum total testosterone and androstenedione levels compared with controls (56.4 versus 40.3 ng/dl, p = 0.03, and 179 versus 133 microg/ml, p = 0.03, respectively). Mean fasting insulin levels were higher among PCOS women (p < 0.01) and were strongly correlated with PAI-1 antigen (Ag) (r = 0.46), PAI-1 activity (r = 0.43), and tissue plasminogen activator (t-PA) (r = 0.5). Correlations were evident in both PCOS and control subjects. Mean PAI-1 Ag, PAI-1 activity, and t-PA levels were significantly elevated (p = 0.003, 0.001, and 0.001, respectively) in PCOS. ANOVA was performed to control for insulin effect; a trend toward elevated PAI-1 in PCOS persisted but was no longer statistically significant (p = 0.24). PAI-1 activity elevation remained in PCOS women with mean fasting insulin levels < 10 mIU/ml (p = 0.02), yet the difference became less significant when insulin was controlled (p = 0.38). Although these data confirm known associations between insulin and PAI-1 derangements, this is the first study to quantify discrete PAI-1 elevations that persist in the setting of PCOS even with normal or low ambient insulin levels. Additional prospective studies are needed to determine whether this altered PAI-1 state is associated with a clinically important hypofibrinolytic condition and subsequent poor reproductive outcome.
- Published
- 2003
42. Recent developments in human oocyte, embryo and blastocyst vitrification: where are we now?
- Author
-
Michael J. Tucker, Juergen Liebermann, Johannes Dietl, and Pierre Vanderzwalmen
- Subjects
Cryopreservation ,Cryobiology ,Cryoprotectant ,Cell Survival ,Obstetrics and Gynecology ,Embryo ,Fertilization in Vitro ,Biology ,Embryo Transfer ,Oocyte ,Cell biology ,Blastocyst ,medicine.anatomical_structure ,Reproductive Medicine ,Embryo cryopreservation ,Botany ,Oocytes ,medicine ,Humans ,Female ,Vitrification ,Developmental Biology - Abstract
The target of any cryopreservation procedure should be to ensure high survival rates of living cells after thawing. Two important parameters determine the success of any cryopreservation protocol: the manner in which cells regain equilibrium in response to cooling, and the speed of freezing (cooling rate). Slow-rate freezing protocols result in the formation of ice crystals during cooling and warming. Vitrification, in which high cooling rates in combination with a high concentration of cryoprotectant are used, does not produce any ice crystals during cooling and warming. However, there is a practical limit to the attainable cooling speed, and also a biological limit to the concentration of cryoprotectant tolerated by the cells during vitrification. Although post-warming survival depends on the species, the developmental stage and the quality of the embryos being vitrified, it seems clear that vitrification methods are increasingly successful and might be a better method than slow cooling procedures in the field of cryobiology. Many of the potential problems and benefits underlying vitrification as a method of choice for embryo cryopreservation in clinical embryology will be discussed in this review.
- Published
- 2003
43. Uncomplicated pregnancy and normal singleton delivery after surgical excision of heterotopic (cornual) pregnancy following in vitro fertilization/embryo transfer
- Author
-
Eric Scott Sills, P. C. Morton, Mark Perloe, Carolyn R Kaplan, C. L. Sweitzer, and Michael J. Tucker
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Cornual Pregnancy ,Context (language use) ,Fertilization in Vitro ,Controlled ovarian hyperstimulation ,Ultrasonography, Prenatal ,Pregnancy ,Risk Factors ,Salpingectomy ,Humans ,Medicine ,Progesterone ,Gynecology ,Heterotopic pregnancy ,In vitro fertilisation ,Cesarean Section ,business.industry ,Obstetrics ,Incidence ,Infant, Newborn ,Pregnancy Outcome ,Obstetrics and Gynecology ,General Medicine ,Embryo Transfer ,medicine.disease ,Embryo transfer ,Pregnancy, Ectopic ,Treatment Outcome ,Gestation ,Female ,business - Abstract
A 39 year-old woman with previous salpingectomy developed a symptomatic heterotopic right cornual pregnancy identified by transvaginal ultrasonography at six weeks' gestation. The patient had previously undergone an ipsilateral partial salpingectomy, and the conception was established four months later after one cycle of controlled ovarian hyperstimulation, in vitro fertilization (IVF) and embryo transfer. We performed immediate surgical excision of the ectopic implantation with conservation of the intrauterine pregnancy. Progesterone was administered as 200 mg/d lozenge (troche) plus 200 mg/d rectal suppository, maintained from day of embryo transfer through the perioperative period and until 11th gestational week. Following an uneventful obstetrical course, a healthy male infant was delivered by cesarean at term. In this report, we review the incidence and significance of heterotopic gestation in the context of IVF/embryo transfer. Risk factors for complex intra- and extra-uterine pregnancies are also outlined. Additionally, the clinical management of heterotopic pregnancy, including a novel approach to progesterone supplementation, is discussed.
- Published
- 2002
44. Advanced embryo development during extendedin vitroculture: Observations of formation and hatching patterns in non-transferred human blastocysts
- Author
-
Richard N. Porter, J. Graham, Michael J. Tucker, and E Scott Sills
- Subjects
Adult ,Male ,Time Factors ,animal structures ,Population ,Fertilization in Vitro ,Biology ,Cryopreservation ,Andrology ,Embryonic and Fetal Development ,Human fertilization ,Culture Techniques ,medicine ,Humans ,Sperm Injections, Intracytoplasmic ,Blastocyst ,education ,reproductive and urinary physiology ,Genetics ,education.field_of_study ,Hatching ,Embryogenesis ,Obstetrics and Gynecology ,Embryo ,General Medicine ,In vitro ,medicine.anatomical_structure ,Reproductive Medicine ,embryonic structures ,Female ,Follicle Stimulating Hormone ,Maternal Age - Abstract
Human embryos not chosen for fresh transfer or cryopreservation were maintained in extended in vitro culture for up to 9 days after fertilization to observe blastocyst formation and hatching features. These non-transferred embryos were derived from 64 consecutive IVF cycles, and were not cryopreserved either because of compromised morphology or because the patients did not consent to cryopreservation for personal reasons. Embryos were cultured individually to monitor daily growth until developmental arrest, and differential blastocyst formation and hatching were analysed among groups of patients and embryos. In the population studied, hatching occurred most commonly on day 7 after fertilization (range 5-9 days). A total of 301 blastocysts was observed, of which 116 (38.5%) eventually hatched in vitro irrespective of day of formation. A trend towards earlier blastocyst formation and a greater likelihood of hatching was noted in this population. Both blastocyst formation and hatching appeared negatively correlated with increasing maternal age and higher basal serum FSH concentrations on day 3 of development, although these trends did not reach statistical significance. Comparison of intracytoplasmic sperm injection (ICSI) (n = 25) and conventional insemination (n = 39) cycles showed a similar rate of blastocyst formation in both groups (54 and 52%, respectively; P0.05), but hatching patterns varied significantly between these groups (4.1 versus 61.6%, respectively; P0.0001). The discovery of marked impairment of hatching among non-transferred ICSI embryos supports the case for reconsideration of the appropriateness of assisted blastocyst hatching in selected cases.
- Published
- 2002
45. COMPARISON OF CENTRIFUGATION- AND NONCENTRIFUGATION-BASED TECHNIQUES FOR RECOVERY OF MOTILE HUMAN SPERM IN ASSISTED REPRODUCTION
- Author
-
Carolyn R Kaplan, Eric Scott Sills, Gianpiero D. Palermo, Michael J. Tucker, Mark Perloe, and K. M. Wittkowski
- Subjects
Adult ,Male ,Reproductive Techniques, Assisted ,Density gradient ,Cell number ,medicine.medical_treatment ,media_common.quotation_subject ,Semen analysis ,Biology ,Andrology ,Endocrinology ,Centrifugation, Density Gradient ,medicine ,Humans ,Centrifugation ,media_common ,In vitro fertilisation ,medicine.diagnostic_test ,urogenital system ,Povidone ,Motile sperm ,Silicon Dioxide ,Spermatozoa ,Sperm ,Sperm Motility ,Reproduction - Abstract
To compare standard density gradient centrifugation sperm preparation with a novel non-centrifugation-based dual-chamber capillary dish in efficiency for motile human sperm separation, approximately 3 mL fresh ejaculate specimens was obtained from 21 men (median age = 32 years. range 26-42 years) undergoing infertility evaluation. For each specimen, half of the sample was processed with a standard 45%/90% density gradient preparation (PureSperm. Nidacon International, Gothenburg, Sweden) followed by semen analysis. The other half was incubated in the Zech glass capillary dish (Astromedtec, Salzburg, Austria) consisting of 2 concentric wells overlaid by a U-ring and coverglass. After approximately 3 h, a 1-mL sample was taken from the central chamber and analyzed. Percentage motile sperm recovery, absolute (motile) cell number, and path velocities were compared for spermatozoa obtained from both methods. Both techniques reduced overall sperm concentration while enriching specimens with more motile spermatozoa. A trend towards higher % recovery of motile spermatozoa (p = .264) was observed with the Zech device, but at a cost of fewer absolute numbers of higher velocity cells (p = .004). The Zech device, therefore, localized a very small population of motile sperm without exposure to centrifugation stress, which has been considered potentially harmful to spermatozoa. This technique could theoretically improve efficiency by reducing time required to identify motile cells in in vitro fertilization where intracytoplasmic sperm injection is planned. However, refinements in incubation interval and suspension volumes are needed before this technique can be considered comparable to the density gradient method in recovering sperm for use in intrauterine insemination.
- Published
- 2002
46. Donor egg banking & egg efficiency: what is an optimum number per egg lot?
- Author
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Melissa O. Stratton, H. Hayes, J. Lim, Alan H. DeCherney, W. Caswell, Michael J. Levy, N. Doyle, J. Graham, Michael J. Tucker, and J. Doyle
- Subjects
Animal science ,Reproductive Medicine ,Donor egg ,Obstetrics and Gynecology ,Biology - Published
- 2017
47. Abstract LB-304: Discovery of chemical probe CCT251236: An orally bioavailable efficacious pirin ligand from an HSF1 phenotypic screen
- Author
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Keith Jones, Nicola E. A. Chessum, Elisa A. Pasqua, Matthew D. Cheeseman, Susan Lepri, Lisa O’Fee, Lindsay E. Evans, Emmanuel de Billy, Birgit Wilding, Robert te Poele, Carl S. Rye, Asadh Miah, Paul Workman, Alan T. Henley, Rosemary Burke, Michael J. Tucker, Loredana Pellegrino, Salyha Ali, Martin G. Rowlands, Suzanne A. Eccles, Meirion Richards, Swee Y. Sharp, Rob L. M. van Montfort, Florence I. Raynaud, Angela Hayes, and Marissa V. Powers
- Subjects
Cancer Research ,Chemistry ,Drug discovery ,Phenotypic screening ,medicine.disease_cause ,Hsp90 inhibitor ,chemistry.chemical_compound ,Oncology ,medicine ,Cancer research ,Growth inhibition ,Heat shock ,Carcinogenesis ,HSF1 ,Transcription factor - Abstract
Heat shock factor 1 (HSF1) was originally identified as a master regulator of the classical ‘cytoprotective’ heat shock response. However, a large body of evidence has now verified the importance of HSF1 to tumorigenesis and cancer progression. HSF1 is activated by various elements of the cancer state, reprogramming the transcriptome in a way that is overlapping with, but distinct from, the canonical heat-shock response. Also, there is a strong correlation between the expression of activated HSF1 in tumors and adverse clinical outcomes. This evidence indicates that the inhibition of HSF1-mediated transcription could be a viable strategy in cancer treatment. Inhibiting the HSF1 stress pathway represents an attempt at targeting non-oncogene addiction and proteotoxic stress, which has been proposed to be advantageous. However, HSF1 is a ligandless transcription factor and is unlikely to be amenable to standard drug discovery strategies and direct inhibition with small molecules. Therefore, we proposed that inhibitors of HSF1-mediated transcription, which antagonize the HSF1 pathway but without necessarily binding directly to HSF1, could be discovered and developed via a cell-based phenotypic screen. We carried out a high throughput Arrayscan assay of 200,000 compounds to measure the inhibition of HSF1-mediated HSP72 expression stimulated by pre-treatment with an HSP90 inhibitor. We identified a singleton hit with a bisamide core, CCT245232. This compound showed potent growth inhibition in a range of human cancer cell lines but had poor physicochemical properties leading to an unacceptable pharmacokinetic profile. Improvement of the physicochemical properties of CCT245232 whilst maintaining potency versus our cell-based assays led to the orally bioavailable tool compound CCT251236. This compound shows potent growth inhibition (GI50 values in low nanomolar range) of human ovarian cancer cell lines in vitro and good efficacy against human ovarian cancer xenografts in nude mice in vivo. We applied chemo-proteomic strategies to identify the molecular target using a probe based on CCT251236 and discovered pirin as a high affinity molecular target. Binding of CCT251236 to recombinant pirin was confirmed in biophysical assays. CCT251236 recapitulates the reported anti-migratory phenotype for a pirin ligand although binding to pirin alone does not explain the cellular phenotype observed with our chemical tool. We are currently using CCT251236 as a chemical probe while further optimizing its properties to identify a clinical candidate. Citation Format: Matthew D. Cheeseman, Nicola E. Chessum, Carl S. Rye, Elisa A. Pasqua, Michael J. Tucker, Birgit Wilding, Lindsay E. Evans, Susan Lepri, Meirion Richards, Swee Y. Sharp, Salyha Ali, Martin Rowlands, Lisa O'Fee, Asadh Miah, Angela Hayes, Alan T. Henley, Marissa Powers, Robert te Poele, Emmanuel De Billy, Loredana Pellegrino, Florence Raynaud, Rosemary Burke, Robert L. van Montfort, Suzanne A. Eccles, Keith Jones, Paul Workman. Discovery of chemical probe CCT251236: An orally bioavailable efficacious pirin ligand from an HSF1 phenotypic screen [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-304. doi:10.1158/1538-7445.AM2017-LB-304
- Published
- 2017
48. Plasma Homocysteine, Fasting Insulin, and Androgen Patterns among Women with Polycystic Ovaries and Infertility
- Author
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Mark Perloe, J. Alexander Bralley, Michael J. Tucker, Glenn L. Schattman, E Scott Sills, and Marc G. Genton
- Subjects
Adult ,Blood Glucose ,Infertility ,medicine.medical_specialty ,Homocysteine ,medicine.drug_class ,medicine.medical_treatment ,Population ,Body Mass Index ,chemistry.chemical_compound ,Internal medicine ,Humans ,Insulin ,Medicine ,Testosterone ,education ,Methylenetetrahydrofolate Reductase (NADPH2) ,Ultrasonography ,Oxidoreductases Acting on CH-NH Group Donors ,education.field_of_study ,biology ,Dehydroepiandrosterone Sulfate ,business.industry ,Ovary ,Hyperandrogenism ,Androstenedione ,Obstetrics and Gynecology ,Fasting ,medicine.disease ,Androgen ,Polycystic ovary ,Endocrinology ,chemistry ,Methylenetetrahydrofolate reductase ,Mutation ,Androgens ,biology.protein ,Female ,business ,Infertility, Female ,Polycystic Ovary Syndrome - Abstract
Objective: To measure plasma homocysteine, androgen, and insulin concentrations in women with normal and polycystic-appearing ovaries in an infertility setting. Methods: Among women referred for infertility evaluation (n = 54), homocysteine, androstenedione, DHEAS, total testosterone, fasting insulin/glucose and methyltetrahydrofolate reductase (MTHFR) polymorphism status (C677T mutation) were studied. Ovaries were examined via transvaginal sonogram by one observer and scored as either normal (n = 18) or polycystic (n = 36). Results: When polycystic ovaries were identified, mean total testosterone was significantly higher than when non-polycystic ovaries were present (p = 0.01), although no measured androgen was outside the normal reference range in either group. Average BMI was higher in the polycystic group, but the difference was not significant (p = 0.10). We observed a trend toward higher mean fasting insulin levels in women with polycystic ovaries, but this increase did not reach statistical significance (p = 0.07). Median plasma homocysteine was identical (7.0 mmol/l) in both populations, and no study subject exceeded the current recommended maximum reference value. Conclusions: In this population, the presence of polycystic ovaries was associated with higher serum androgens (especially total testosterone) although none of the measured androgens were above the normal range. While fasting insulin levels were also higher in this group, median plasma homocysteine levels were similar irrespective of ovarian morphology. Concomitant plasma homocysteine derangements in this population of young, lean patients with polycystic-appearing ovaries seem unlikely. Further studies are needed to clarify the role(s) of homocysteine in human reproductive physiology.
- Published
- 2001
49. Positive outcome after preimplantation diagnosis of aneuploidy in human embryos *
- Author
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Jacques Cohen, Cristina Magli, Michael J. Tucker, David B. Sable, Sasha Sadowy, Luca Gianaroli, Carmen Márquez, Joe B. Massey, Anna Pia Ferraretti, P.C. Morton, Richard T. Scott, and Santiago Munné
- Subjects
medicine.medical_specialty ,Embryonic Development ,Aneuploidy ,Fertilization in Vitro ,Biology ,Miscarriage ,Andrology ,Pregnancy ,Prenatal Diagnosis ,medicine ,Humans ,Embryo Implantation ,Gynecology ,Estradiol ,Rehabilitation ,Pregnancy Outcome ,Obstetrics and Gynecology ,Embryo ,Heart Rate, Fetal ,Embryo Transfer ,medicine.disease ,Embryo transfer ,Reproductive Medicine ,embryonic structures ,Chromosome abnormality ,Gestation ,Female ,Trisomy ,Maternal Age - Abstract
usromosomal abnormalities are responsible for a great deal of embryo wastage, which is reflected, at least partially, in decreased implantation and increased miscarriage in older women. To address this problem the transfer of only chromosomally normal embryos previously selected by preimplantation genetic diagnosis (PGD) has been proposed. We designed a multi-centre in-vitro fertilization (IVF) study to compare controls and a test group that underwent embryo biopsy and PGD for aneuploidy. Patients were matched retrospectively, but blindly, for average maternal age, number of previous IVF cycles, duration of stimulation, oestradiol concentrations on day +1, and average mature follicles. All these parameters were similar in test and control groups. Only embryos classified as normal for those chromosomes were transferred after PGD. The results showed that the rates of fetal heart beat (FHB)/embryo transferred between the control and test groups were similar. However, spontaneous abortions, measured as FHB aborted/FHB detected, decreased after PGD (P0.05), and ongoing pregnancies and delivered babies increased (P0.05) in the PGD group of patients. Two conclusions were obtained: (i) PGD of aneuploidy reduced embryo loss after implantation; (ii) implantation rates were not significantly improved, but the proportion of ongoing and delivered babies was increased.
- Published
- 1999
50. The application of co-culture in assisted reproduction: 10 years of experience with human embryos
- Author
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Klaus Wiemer, Michael J. Tucker, Robert A. Godke, and Jacques Cohen
- Subjects
Cryopreservation ,Fetus ,medicine.medical_specialty ,Rehabilitation ,Embryogenesis ,Uterus ,Obstetrics and Gynecology ,Embryo ,Blastomere ,Biology ,Embryo, Mammalian ,Coculture Techniques ,Andrology ,Embryonic and Fetal Development ,Follicle-stimulating hormone ,Reproductive Techniques ,medicine.anatomical_structure ,Endocrinology ,Reproductive Medicine ,Internal medicine ,medicine ,Humans ,Blastocyst - Abstract
Co-culture techniques using fetal bovine uterine fibroblasts or bovine oviductal epithelial cells have improved embryonic development prior to replacement in humans. In initial co-culture trials, embryo development and implantation rates increased after just 1 day in culture. The most overt characteristics noted following co-culture were improved blastomere development and characteristics, reduced fragmentation, and the appearance of swollen blastomeres. In addition, an increase in the incidence of zona thickness variation was detected. Improved development of polyspermic and supernumerary embryos to the blastocyst stage was noted in initial trials. Retrospective analysis indicated that certain patient subgroups benefit the most from co-culture. As a result, co-culture is now applied routinely to patients that have previously failed attempts at in-vitro fertilization (IVF) and/or have endocrine imbalances such as polycystic ovarian syndrome and elevated day 3 concentrations of follicle stimulating hormone (FSH). The use of co-culture prior to or following cryopreservation has also proven to be beneficial to human embryos. The proposed beneficial mechanisms thought to improve embryonic development include a secretory and/or a scavenging role. Evidence describing the postulated benefits is discussed.
- Published
- 1998
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