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Recent Trends In Art Presentation Transcript

  • 1. RECENT ADVANCES IN ART Dr. Kamini A. Rao DGO, DCh, MCh, FRCOG, FICOG,PGDMLE,FNAMS Medical Director BANGALORE ASSISTED CONCEPTION CENTRE
  • 2. History
    • Walter Heap – late 19 th century credited with first successful transfer of embryos flushed from oviducts of one species of rabbit to another.
    • 1959 - Chang successfully carried out IVF with rabbit oocytes and sperm.
  • 3. Bars to successful IVF in humans
    • Development of suitable media for culture .
    • Obtain suitable sperm which was acrosome reacted.
    • Obtain oocytes ripe enough but before ovulation.
  • 4. FEW MILESTONES
    • Patrick Steptoe – pioneer of laparoscopy in UK
    • 1960 s – superovulation with HMG
    • 1960 - Steptoe and Edwards achieved human pregnancy ,unfortunately turned out to be ectopic.
    • 1978 – birth of LOUISE BROWN
    • unstimulated natural cycle IVF
  • 5. Miracle baby-Louise Brown
  • 6. FIRST IVF BABY
    • Since the birth of the first IVF baby, Louise Brown, at 11.47pm on July 25, 1978, in Oldham, there have been well over a million "test tube babies" born worldwide
  • 7.
    • “ We are at the end of the beginning – not the beginning of the end.”
    • - Patrick Steptoe 1978 .
  • 8. WHAT ARE WE LOOKING AT ???
    • Evidence based medicine
    • Quality control in the labs
    • Simplifying diagnosis & treatment
    • Better pregnancy rates
  • 9. What has the last decade given us ??!!
    • Endoscopy
    • Sperm Preparation methods
    • Micromanipulation techniques -ICSI, SUZI
    • Embryo and sperm preservation
    • Prenatal diagnosis & treatment
  • 10. ESTABLISHED TECHNIQUES
    • ICSI
    • Polar body biopsy
    • Assisted hatching
    • Fragment removal
    • Blastomere biopsy
    • Trophectoderm biopsy
  • 11. Alternative assisted conception techniques
    • Direct intraperitoneal insemination- first described by Manhes and Hermabessiere.
    • Fallopian tube sperm perfusion or intrafallopian insemination.
    • Peritoneal oocyte sperm transfer (POST).
    • ZIFT
    • PROST
  • 12. Alternative assisted conception techniques
    • TET (tubal embryo transfer)
    • Surgical embryo transfer or transmyometrial embryo transfer.
    • GIFT
    • MESA / PESA
    • TESA
  • 13.
    • The first step towards solving
    • a problem
    • is to
    • begin
  • 14. COH
    • COH was first acheived with clomiphene citrate but this was later superceded with the use of HMGs and urinary FSH preparations.
    • Introduction of GnRH agonists permitted the down regulation of pituitary gland in order to eliminate any premature LH surge and various protocols were suggested and used successfully.
    • GnRH antagonists.
  • 15. Odds ratio for clinical pregnancy rates with various stimulation protocols 1.21 Recombinant vs urinary FSH 0.79 GnRH antagonists vs agonist 1.8 GnRH a vs HMG 1.47 Long vs ultrashort 1.27 Long vs short protocol 1.32 Long vs short and ultrashort 1.70 Urinary FSH vs HMG ODDS RATIO STIMULATION PROTOCOL
  • 16. Urinary to recombinant Gn
    • Bye-bye urinary gonadotrophins?
    • Recombinant FSH: A real progress in ovulation induction and IVF?*
    • ?COST
  • 17. Recombinant gonadotrophins
    • pure ( recombinant) product in principle preferable to an impure ( urinary) product
    • - human ( urinary) products carried a risk of infection by slow-viruses, raising concerns
    • - human products, since impure, carried a risk of immunogenicity
    • - human products had repeatedly been demonstrated to be uneven in biological potency.
  • 18. LABORATORY ISSUES
    • CO -CULTURE systems
    • V ero cell line, granulosa cells as well as autologous cryopreserved endometrial cells
    • Improvement in cleavage rate, embryo morphology and blastocyst formation rate reported.
    • RCTs have failed to confirm an increase in pregnancy rates.
    • Veiga et al ,Human Rep ,14
  • 19. LABORATORY ISSUES
    • DAY 3 TRANSFER AND BLASTOCYST CULTURE
    • Prolonged culture of embryos are suggested to select the embryos with best potential for survival.
    • RCTs did not find significant changes in pregnancy or implantation rates when embryos were replaced on day 2 or 3 after oocyte retreival.
  • 20. Assisted hatching Laser Zona Drilling
  • 21. Assisted hatching
    • Advanced maternal age
    • Repeated IVF failures
    • Elevated basal FSH
    • Thick ZP
    • frozen thawed embryo
    • Excessive fragmentation >20 %
  • 22. LABORATORY ISSUES
    • RCTs have not so far shown any clinical advantage in using co-culture systems, group culture ,in vitro maturation or assisted hatching.
    • Embryo selection methods and blastocyst culture do not improve pregnancy rates but diminish the incidence of multiple pregnancies.
    • Hassan Salam ,Recent advances in Obs and Gyn,22
  • 23. IN VITRO MATURATION
    • IVM of human oocytes was suggested in order to achieve fertilization of immature oocytes retreived
    • - during stimulated cycles
    • - oocytes from PCOS patients to avoid OHSS
    • -after freezing -thawing of immature oocytes.
    • ?No advantage in terms of clinical pregnancy and implantation rates.
  • 24. Towards single embryo transfer
    • Multiple gestations is the most common side effect of an ART programme.
    • Increasing inclination towards minimum to single embryo transfer.
    • Daunting challenge encountered –identifying best embryo without compromising the pregnancy rate.
  • 25. Embryo selection
    • ?Best approach
    • Blastocyst culture.
    • Embryo selection based on morphology.
    • Oocyte morphology as a predictor of embryo morphology.
    • Polar body morphology as an indicator of embryo quality.
    • Pronuclear stage scoring.
    • PGD.
  • 26. Pre implantation genetic diagnosis
    • Useful in recurrent spontaneous abortions and repeated IVF failures
    • PGD involves embryo biopsy and genetic analysis which can be performed on
    • - oocyte /zygote – polar body biopsy
    • - blastomere from cleavage stage embryo
    • - trophectoderm biopsy from blastocysts.
  • 27. PGD
    • PGD can be applied for monogenic disorders or chromosomal abnormalities using diagnostic techniques like
    • PCR
    • FISH
    • CGH – comparative genomic hybridization is a molecular cytogenetic technique tried for PGD which gives an overview of the whole genome.
  • 28. EMBRYO TRANSFER
    • Various techniques have been suggested in order to optimize this apparently simple step.
    • The value of using soft catheters vigorous flushing of the cervical canal and the routine use of antibiotics has not been established.
  • 29. EMBRYO TRANSFER
    • RCTs have shown that ultrasound guided embryo transfer ,a trial transfer prior to the actual procedure and depositing the embryos 2 cm below the uterine fundus are associated with higher pregnancy rates.
    • Bed rest and sexual intercourse do not affect the results.
    • Human Rep ,17,2002.
  • 30. MALE INFERTILITY
    • Introduction of ICSI in 1991 by Palermo revolutionised male factor infertility.
    • Arthur Kostler said “ the more original a discovery ,the more obvious it seems afterwards” ,the technique of ICSI today appears so obvious that it is hard to believe it took decades to master it.
  • 31. When ICSI?
    • Poor sperm motility
    • Low sperm count
    • Abnormally high amount of morphologically atypical sperms
    • Experienced fertilization failure in a previous IVF cycle due to unknown reason
    • Retrograde ejaculation
    • Immunological factors
    • Obstructive azoospermia.
  • 32. ICSI
  • 33. NEW TRENDS
    • Cryopreservation
    • Cytoplasmic transfer
    • Egg freezing
    • Somatic cell nuclear transfer
  • 34. Cryopreservation
    • Cryopreservation serves as potential
    • “ reproductive insurance ”
    • for couples.
  • 35. Cryopreservation
    • Discovery of cryo protectants in a London laboratory.
    • 1940 s- Audrey Smith successfully stored spermatazoa at - 80 degree using glycerol as cryo protectant.
    • New generation cryo protectants - dimethylsulfoxide ethylene glycol and propylene glycol.
  • 36. Cryopreservation
    • Aggressive chemotherapy and radiotherapy, as well as bone marrow transplantation, results in >90% cure in many cancers of children and young women
    • Ovarian tissue cryopreservation and transplantation has emerged against this background
  • 37. Case report
    • Belgian day-old baby Tamara Bouanati nestles in the arms of her mother Ouarda Touirat, 32. Touirat beat cancer and gave birth after an ovarian tissue transplant
  • 38. Ovarian tissue banking
    • Orthotopic transplant –resumption of cyclicity – conception.
    • Hetrotopic transplant –autograft
    • -xenograft
  • 39. Storage of eggs and embryos
    • Plausible explanations for difficulty of storing human oocytes -
    • Zona pellucida hardens during the process
    • Premature cortical granule exocytosis.
    • Spindle is a dyanamic structure – depolymerization of the spindle apparatus.
  • 40. CYTOPLASMIC TRANSFER
    • STILL EXPERIMENTAL !
    • Only in limited number of cases.
    • Transfer of mtDNA - inheritance ?
    • Recipient offsprings receive - nDNA + mtDNA
    • Potential interaction between nuclear and mitochondrial
    • Genome needs to be understood
  • 41.
    • STEM CELL THERAPY
  • 42.
    • Make the decisions now
    • even if action is future
  • 43. SOURCES OF STEM CELLS
    • Embryonic Stem Cells
    • Embryonic Germ Cells
    • Adult Stem Cells
  • 44. STEM CELL THERAPY
    • THE ANSWER TO DONOR ORGAN
    • TRANSPLANTATION !!
  • 45. Novel therapeutics
    • Though stem cell science is still in infancy yet it promises clinical application in various debilitating and disabling disorders -- diabetes ,neurodegenerative diseases etc.
    • Most fascinating area of biology today.
  • 46. Stem cell based transplantation
    • Unlimited supply of pleuripotent stem cells
    • Possibility of “universal donor cells”.
    • Stem cells may serve as vehicles for gene therapy.
  • 47. Cloning
    • Somatic cell nuclear transfer into enucleated oocytes followed by creation of an embryo.
    • Reproductive cloning
    • Therapeutic cloning.
    • Will the cloning doctors go from villains to heroes?
  • 48.
    • A thorough introduction of genetic services into the infertility management program is the need of the future
  • 49.
    • Problems are a sign of life –
    • the only people who have no problems are in cemeteries.
  • 50.
    • Thank you ..