Recent Trends In Art (1)

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Recent Trends In Art (1)

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

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