Fertility Options: IVF Overview

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Mark Perloe, MD Atlanta, 404-843-2229 Learn about the factors that can adversely affect fertility and the tests that can help pinpoint problems. Fertility treatment options including IVF and other high tech options are presented.


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Fertility Options: IVF Overview

  1. 1. Fertility Options Mark Perloe, M.D. Georgia Reproductive Specialists www.ivf.com
  2. 2. Objectives <ul><li>Discuss general fertility factors </li></ul><ul><li>Describe basic evaluation and treatment </li></ul><ul><li>Describe A ssisted R eproductive T echnology (ART) at GRS </li></ul><ul><li>Understand fertility preservation options </li></ul>
  3. 3. Fertility Preservation <ul><li>Indications </li></ul><ul><ul><li>Chemotherapy, radiation therapy, surgery </li></ul></ul><ul><ul><li>On-hold for career </li></ul></ul><ul><ul><li>Haven’t found partner </li></ul></ul><ul><li>Criteria: Age, Antral follicle count, AMH </li></ul><ul><li>Success: 2-5% chance for each stored oocyte </li></ul><ul><li>Cost: </li></ul><ul><ul><li>Cryopreservation cycles: ~$9-$21,000 (1-3x) </li></ul></ul><ul><ul><li>Thaw, culture & transfer: $5,000 </li></ul></ul>
  4. 4. Infertility…. <ul><li>Inability to conceive after an interval of unprotected intercourse </li></ul><ul><ul><ul><li>One year for women under 35 </li></ul></ul></ul><ul><ul><ul><li>Six months for women over 35 </li></ul></ul></ul><ul><li>Medical history and physical findings may dictate earlier evaluation and treatment </li></ul>
  5. 5. Scope <ul><li>At any given time, 10% of reproductive age couples seeking conception are unable to do so </li></ul><ul><ul><li>6.1 million women and their partners </li></ul></ul><ul><li>15% of all reproductive age women have an infertility-related office visit each year </li></ul><ul><li>Half of couples experiencing fertility problems never seek treatment </li></ul>
  6. 6. Fertility Factors <ul><li>Ovulation factors 25% </li></ul><ul><li>Male factor 40% </li></ul><ul><li>Tubal/anatomic factors 35% </li></ul><ul><li>Endometriosis 35% or more </li></ul><ul><li>Multiple factors 25% </li></ul><ul><li>Unexplained 30% </li></ul>
  7. 7. Months % women pregnant Cumulative frequency of pregnancy in couples trying to conceive Let’s look first at how easy, or difficult, it is to get pregnant… Fecundity
  8. 8. Graafian follicle Oocyte Membrana granulosa Theca interna Basement membrane Antrum
  9. 9. -50 -4 +10 -9 +1 -180 Time (days) 0 Very little atresia Ovulation Corpus luteum Large antral Recruited Growing 50 - 80% atresia Primordial Small Antral Pre-ovulatory Possible time of action of nutrition on folliculogenesis Selected
  10. 11. Blastomeres undergo compaction and form morula. Gap junctions and tight junctions will form placenta. The cells gain distinct polarity (i.e. have inside and outside faces) and flatten against each other. Embryo growth
  11. 12. Embryo Cleavage The cleavage divisions produce cells called blastomeres.
  12. 13. Fertilization occurs in the ampulla of the oviduct, implantation in the uterus. Motile systems are important: cilia and smooth muscle. The Fallopian tube produces secretions which control and provide a vehicle for transport. Control over embryo transport may also operate at the ampullary isthmic junction and at the utero-tubal junction. Embryo transport
  13. 14. Hatching from zona The zona pellucida must be lost before the embryo can contact the uterine epithelium. Observations in vitro suggests that the blastocyst squeezes out of fractures in the zona (“hatches”). Identical twins may be produced if the embryo breaks into two during this process. Empty zona Zona free blastocysts
  14. 15. Apposition Attachment Invasion Uterine responses In humans, the maternal epithelium and stroma in invaded by the embryo…
  15. 16. The syncytiotrophoblast proliferates and invades the extracellular matrix of the stroma. Cytotrophoblast cells migrate between the syncytia, followed by fetal stroma - leading to placental villi. Implantation
  16. 17. Ovulation Factors <ul><li>Insulin resistance </li></ul><ul><ul><li>PCOS, hyperandrogenism </li></ul></ul><ul><li>Hypothalamic dysfunction </li></ul><ul><ul><li>Exercise induced, eating disorders, stress </li></ul></ul><ul><li>Pituitary disorders </li></ul><ul><ul><li>hyperprolactinemia </li></ul></ul><ul><li>Ovarian Failure </li></ul><ul><ul><li>Chemotherapy, Age, Surgery </li></ul></ul>
  17. 18. Polycystic Ovary Syndrome <ul><li>Low glycemic diet </li></ul><ul><li>Metformin, TZD, GLP-1 </li></ul><ul><li>Exercise </li></ul><ul><li>Ovarian drilling </li></ul><ul><li>Clomiphene/letrozole </li></ul><ul><li>Injectable gonadotropins </li></ul><ul><ul><li>OHSS risk </li></ul></ul><ul><ul><li>High multiple birth rate </li></ul></ul><ul><li>IVF or IVM </li></ul>
  18. 19. PCOS Ovarian Drilling 65-85% success not effective in smokers 1/3 require ovulation meds requires surgery adhesion formation
  19. 20. Endometriosis <ul><li>Presence of uterine lining in locations outside the uterus </li></ul><ul><li>35-55% of infertile women demonstrate endometriosis at laparoscopy </li></ul><ul><li>Not all women with endometriosis have infertility </li></ul><ul><li>Surgical treatment and Lupron do not enhance success rates </li></ul>
  20. 21. Age related infertility Reduced pregnancy rates Increased miscarriage rates Increased risk fetal anomalies
  21. 22. Pregnancy, Live Birth, and Singleton Live Birth by Age,* 2001 *For consistency, all rates are based on cycles started.
  22. 23. Miscarriage Rates by Age, 2001
  23. 24. Male Factor Infertility <ul><li>Causes </li></ul><ul><ul><li>varicocele </li></ul></ul><ul><ul><li>infection </li></ul></ul><ul><ul><li>smoking </li></ul></ul><ul><ul><li>genetic </li></ul></ul><ul><ul><li>cancer, radiation, chemorx </li></ul></ul><ul><ul><li>hot tub </li></ul></ul><ul><ul><li>bicycle riding </li></ul></ul><ul><ul><li>medications </li></ul></ul><ul><li>Testing </li></ul><ul><ul><li>Semen analysis </li></ul></ul><ul><ul><li>SCSA/SDFA: DNA fragmentation </li></ul></ul>
  24. 25. Sperm Chromatin Structure Assay SCSA®/SDFA test is a good predictor, relative to other sperm measures, for the clinical diagnosis of male infertility
  25. 26. DNA Fragmentation Study Results <ul><li>998 cycles from 637 patients </li></ul><ul><li>Unexplained infertility, with sufficient sperm count did IUI </li></ul><ul><li>Female factor infertility did IVF </li></ul><ul><li><500,000 sperm after gradient did ICSI </li></ul>Bungum, Human Reprod , 2007
  26. 27. P34H Testing
  27. 28. P34H Testing Sullivan, Fertil & Steril, 2006
  28. 29. SDD <ul><li>Study A </li></ul><ul><ul><li>Retrospective study of 58 patients receiving IUI or IVF (w/o ICSI) </li></ul></ul><ul><ul><ul><li>None with abnormal SDD had live birth </li></ul></ul></ul><ul><ul><ul><li>Those with normal SDD had a 28% success rate </li></ul></ul></ul><ul><li>Study B </li></ul><ul><ul><li>Prospective ICSI only study..50 patients </li></ul></ul><ul><ul><ul><li>20 with abnormal SDD </li></ul></ul></ul><ul><ul><ul><li>30 with normal SDD </li></ul></ul></ul><ul><ul><li>ICSI success rates were not statistically different </li></ul></ul>
  29. 30. Advanced Sperm Testing Panel
  30. 31. Uterine Evaluation
  31. 32. Uterine Fibroids
  32. 33. 5. Analyze Results <ul><li>Real-time continuous monitoring with 3D dose accumulation and thermometry determines whether treatment can proceed as planned or has to be changed. </li></ul><ul><li>This interactive process continues until the entire region of treatment has been ablated. </li></ul>
  33. 34. Congenital Uterine Anomalies Bicornuate Vs Septate Uterus
  34. 35. Hydrosalpinx
  35. 36. Abnormal Hysterosalpingogram
  36. 37. Pelvic Adhesions
  37. 38. Hydrosalpinx
  38. 39. What do we know about pregnancy losses?? 6 20 40 Weeks gestation 100 50 % Pregnancies can easily be recognized clinically by 6 wks. Ovulation rates are high! So probably are fertilization rates! Early human embryos may show a high incidence of developmental abnormalities. 10-15% of of all clinically recognised pregnancies are lost in the 1st trimester; 2-3% are lost later. 50% of these losses have cytogenetic abnormalities. 1/3 of all pregnancies are lost soon after implantation - before they are clinically recognised.
  39. 40. Unexplained Infertility Letrozole or Clomid/IUI Letrozole/HMG/IUI IVF
  40. 41. Injectable Gonadotropins
  41. 42. Assisted Reproductive Technology (ART) <ul><li>In vivo = inside the body </li></ul><ul><li>In vitro = in glass = outside the body </li></ul><ul><li>IVF = in vitro fertilization </li></ul><ul><li>ART involves both the sperm and the egg in the laboratory </li></ul><ul><li>Fertilization and early embryo development usually achieved in vivo accomplished in vitro </li></ul>
  42. 43. In vitro fertilization Screening Optimize reproductive health Psychological counseling Financial counseling Nursing education Ovarian hyperstimulation Egg retrieval Embryo culture Embryo transfer Cryopreservation The wait!
  43. 44. Lifestyle <ul><li>Smoking </li></ul><ul><ul><li>Up to 13% of infertility problems may be attributable to smoking </li></ul></ul><ul><ul><li>Conception delay </li></ul></ul><ul><ul><li>Egg depletion and diminished quality </li></ul></ul><ul><ul><li>Higher miscarriage rates, ectopic pregnancies </li></ul></ul><ul><ul><li>Passive smoking equivalent to active smoking </li></ul></ul><ul><ul><li>Possibly lower IVF delivery rates </li></ul></ul><ul><ul><li>Male smoking may pose greater risk </li></ul></ul>
  44. 45. Emotional Support <ul><li>Psychological counseling requirement prior to cycle initiation; continued referral as necessary </li></ul><ul><li>Patient support groups, AFA, INCIID, RESOLVE </li></ul><ul><li>“Mind, Body…Baby” Program </li></ul><ul><ul><li>Acupuncture </li></ul></ul><ul><ul><li>Massage </li></ul></ul><ul><ul><li>Exercise </li></ul></ul><ul><ul><li>Support </li></ul></ul>
  45. 46. Financial Support <ul><li>Assisted Reproductive Technology Financial Options </li></ul><ul><ul><li>“ Making IVF Affordable Plan” </li></ul></ul><ul><ul><ul><li>Includes all Frozen Embryo Transfers </li></ul></ul></ul><ul><ul><ul><li>No “Hidden Fees” for extra visits or ICSI </li></ul></ul></ul><ul><ul><ul><li>FREE second IVF treatment cycle </li></ul></ul></ul><ul><ul><li>Shared Risk Program Refund IVF </li></ul></ul><ul><ul><li>Global Fee IVF </li></ul></ul><ul><ul><li>Global Frozen Embryo Transfer </li></ul></ul><ul><ul><li>IVF PLUS </li></ul></ul><ul><ul><li>Advanced Reproductive Care (ARC) financing </li></ul></ul><ul><li>60% of patients have some degree of insurance coverage </li></ul>
  46. 47. IVF Overview <ul><li>Stimulation phase ~ 8-12 days </li></ul><ul><ul><li>Over-ride usual ovulation status </li></ul></ul><ul><ul><li>Intentionally hyperstimulate ovaries with injectable hormones </li></ul></ul><ul><ul><li>Monitor closely with vaginal ultrasound and blood hormone levels </li></ul></ul><ul><ul><li>Anticipate 4-6 clinic visits </li></ul></ul>
  47. 48. IVF Overview <ul><li>Retrieval ~ 20 minutes </li></ul><ul><ul><li>Outpatient minor surgery under IV sedation </li></ul></ul><ul><ul><li>Vaginal ultrasound guided oocyte retrieval </li></ul></ul><ul><ul><li>All visible follicles entered and aspirated </li></ul></ul><ul><ul><li>Recovery ~ 1 hour in clinic, remainder of day at home </li></ul></ul><ul><ul><li>Goal: multiple eggs to work with in the laboratory </li></ul></ul>
  48. 49. IVF Overview <ul><li>Laboratory ~ 3-5 days </li></ul><ul><ul><li>Provide semen specimen </li></ul></ul><ul><ul><li>Combine sperm and eggs at appropriate intervals </li></ul></ul><ul><ul><li>Inject sperm into eggs as required </li></ul></ul><ul><ul><li>Incubate and allow to grow for 3-5 days </li></ul></ul><ul><ul><li>Embryologists update patients regarding progress </li></ul></ul>
  49. 50. IVF Overview <ul><li>Transfer </li></ul><ul><ul><li>Plan transfer for Day 3 or 5 after retrieval </li></ul></ul><ul><ul><li>Abdominal ultrasound visualization requires a FULL bladder; Valium available </li></ul></ul><ul><ul><li>Transfer catheter containing embryos threaded though cervix </li></ul></ul><ul><ul><li>Embryos gently injected into uterus </li></ul></ul><ul><ul><li>Normal activity after transfer </li></ul></ul>
  50. 51. IVF Overview <ul><li>Number of embryos transferred based on patient age and embryo quality </li></ul><ul><ul><li>General for Day 3: </li></ul></ul><ul><ul><ul><li>< 35 years: 2-3 embryos </li></ul></ul></ul><ul><ul><ul><li>35-37: 3 embryos </li></ul></ul></ul><ul><ul><ul><li>38-40: 3-4 embryos </li></ul></ul></ul><ul><ul><ul><li>>40: 4-5 embryos </li></ul></ul></ul><ul><ul><li>Blastocysts (Day 5): 2 embryos up to age 40 </li></ul></ul>
  51. 52. Embryos <ul><li>Day 3 </li></ul><ul><li>Day 5 </li></ul>
  52. 53. IVF Overview <ul><li>14 days after retrieval… </li></ul><ul><ul><li>Check pregnancy test </li></ul></ul><ul><li>Progesterone supplementation from just after retrieval until outcome known </li></ul><ul><ul><li>Intramuscular progesterone </li></ul></ul><ul><ul><li>Continues through the 10 th week of pregnancy </li></ul></ul>
  53. 54. Special Issues <ul><li>Intracytoplasmic sperm injection (ICSI) </li></ul><ul><ul><li>Individual sperm can be injected into each egg </li></ul></ul><ul><ul><li>Important for profound male factor </li></ul></ul><ul><li>Pre-implantation genetic diagnosis (PGD) </li></ul><ul><ul><li>Prevention of genetic disease </li></ul></ul><ul><ul><li>Recurrent pregnancy loss </li></ul></ul><ul><li>Egg donation </li></ul><ul><ul><li>anonymous vs. known donor </li></ul></ul><ul><li>Fertility preservation </li></ul>
  54. 55. Special Issues <ul><li>ICSI </li></ul><ul><li>PGD </li></ul>
  55. 56. Success Rates (2001 SART Data) Age Clinical Pregnancy Live Birth < 35 47.1% 36.5% 35-37 28.6% 23.8% 38-40 21.4% 14.3% 41-42 3/5 2/5
  56. 57. 2007 GRS IVF Statistics Age <35 35-37 38-40 >40 Donor # cycles 105 63 39 12 28 birth/cycle 33.3% 27.0% 28.2% 2/12 60.7% Avg # ET %Twins %FET del 2.3 29.2 30.8 2.4 29.2 33.2 2.9 7.6 42.8 3.3 - - 2.0 - 36.8
  57. 58. Success Rates: What do they mean? Pregnancies per cycle Live births per retrieval Live births per cycle Live births per transfer Singleton live births per transfer Singleton live births per cycle
  58. 59. Live Birth Rates by Diagnosis, 2001
  59. 60. Live Birth Rates by Woman’s Age and Previous Live Births, 2001
  60. 61. Live Birth Rates by Age and History of Miscarriage, with No Prior Births,* 2001 *Women reporting only previous ectopic pregnancies or pregnancies that ended in induced abortion were not included in the above statistics.
  61. 62. Live Birth Rates by Woman’s Age and History of Previous ART Cycles, 2001
  62. 63. Live Births per Transfer and % Multiple Births in Women <35 by Number of Embryos Transferred, 2001 (100.0)* (59.3)* (39.6)* (53.4)* (38.8)* (7.8)* (49.1)* (41.3)* (9.6)* (43.3)* (46.8)* (9.9)* *Percentages of live births that were singletons, twins, and triplets or more are in parentheses. Note: In rare cases a single embryo may divide and thus produce twins. For this reason a small percentage of triplets resulted when two embryos were transferred. 30.0 51.7 46.9 42.9 43.1 (1.2)*
  63. 64. Frozen Embryos vs. Fresh Embryos, 2001 Frozen embryos Fresh embryos
  64. 65. Live Births per Transfer Using Fresh Embryos From Own and Donor Eggs, by ART Patient’s Age, 2001
  65. 66. Success Rates vs. Multiple Births Type of ART
  66. 67. Embryo Evaluation “omics” <ul><li>GENomics </li></ul><ul><ul><li>FISH </li></ul></ul><ul><ul><li>CGH </li></ul></ul><ul><ul><li>SNPs </li></ul></ul><ul><li>TRANSCIPTomics </li></ul><ul><ul><li>Gene transcription </li></ul></ul><ul><li>PROTEomics </li></ul><ul><ul><li>Proteins </li></ul></ul><ul><ul><li>Secretomics </li></ul></ul><ul><li>METABOLomics </li></ul><ul><ul><li>Metabolites </li></ul></ul><ul><ul><li>Amino Acids </li></ul></ul>
  67. 68. Multiple Births rates are NOT 1996, 2000 and 2001
  68. 76. GRS <ul><li>Meridian Mark </li></ul><ul><ul><li>Drs. Perloe, Kaplan and Singleton </li></ul></ul><ul><li>Alpharetta </li></ul><ul><ul><li>Dr. Conway </li></ul></ul><ul><li>DeKalb Medical Center </li></ul><ul><ul><li>Dr. Kaplan </li></ul></ul>Please join us for a complimentary 20 minute visit…. Please join us for a complimentary 20 minute visit….

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