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Infertility.(By Craig)

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Infertility.(By Craig)

  1. 1. INFERTILITY: Update on Evaluation & Treatment LaTasha B. Craig, M.D. Assistant Professor Division of Reproductive Endocrinology University of Oklahoma Health Sciences Center
  2. 2. With Kind Regards  I have reproduced this topic as such in origion for the benefit of students only.  I express my sincere thanks and kind regards to the author from deepest core of my heart. Prof, M.C.Bansal
  3. 3. Objectives  Understand the different causes of infertility and the specific evaluations to diagnose each cause.  Comprehend the available infertility treatment options including their chance of pregnancy, complications and chance of multiple gestations.  Have an understanding of the process and success of in vitro fertilization (IVF) & the concerns for long term outcomes of children born from IVF.
  4. 4. Speaker Disclosure  I have no financial relationships or affiliations to disclose.  Many of the medications used in in vitro fertilization are not FDA approved for this indication.
  5. 5. Considerations Pre-Pregnancy  Nutritional issues  Medical conditions  Medications  Immunization history  Family history and genetic risk  Tobacco, alcohol, caffeine & substance use  Occupational & environmental exposures
  6. 6. How to time conception  Cycle Day (CD) 1 is the first day of full- flow bleeding  Have intercourse every 2 -3 days (especially between CD 10-20)  Avoid most over-the- counter lubricants  Things to consider:  Ovulation Predictor Kits  Basal Body Temperature Charting  Things to avoid:  Over the counter fertility tests  Salivary hormone tests  Hormonal supplements
  7. 7. Basal Body Temperature Monitoring Newill RG, Katz M. The basal body temperature chart in artificial insemination by donor pregnancy cycles. Fertil Steril 1982 Oct;38(4):431-8
  8. 8. Ovulation Predictor Kits:
  9. 9. What to Expect--Fecundability: Cumulative pregnancy rate 0 10 20 30 40 50 60 70 80 90 100 % Pregnant 3 mos 6 mos 1 year 2 years Duration of exposure Guttmacher, 1956
  10. 10. Definition of Infertility Failure to conceive after 1 year of unprotected intercourse The exception: For women ≥ 35 years old, 6 months unprotected intercourse without conception
  11. 11. Infertility  Incidence  Diagnostic evaluation  Treatment options
  12. 12. Historical perspective on fertility  In 1790 U.S. census, birth rate was 55 per 1000 population with avg. of 8 births per woman  1995 National Survey of Family Growth (NSGF), birth rate of 15.5 per 1000, with avg. births of 1.2 per woman Popular explanations for declining U.S. fertility  Changing roles & aspirations for women  Postponement of marriage  Delayed age of childbearing  Increasing use of contraception  Liberalized abortion Speroff. Clinical Gynecologic Endocrinology & Infertility. Sixth edition.
  13. 13. Components of Normal Fertility
  14. 14. Etiologies by percent in couples presenting for infertility
  15. 15. Male Infertility Evaluation: Semen Analysis Volume 2.0 - 5.0 mL pH >7.2 Concentration >20 million / mL Total sperm number >40 million / ejaculate Motility >50% Forward progression >2 (scale 0-4) Sperm morphology >30% normal (WHO 1992) >14% normal (WHO 1999)
  16. 16. Female Infertility Evaluation: Tubal/Pelvic Factor
  17. 17. Hysterosalpingogram (HSG) Normal Bilateral Blocked Tubes
  18. 18. Female Infertility Evaluation: Confirm ovulation by  History of regular cycles  Symptoms of ovulation  Ovulation predictor kits  Basal body temperature  Progesterone level around CD 21  Ultrasound monitoring Ovulation Dysfunction
  19. 19. Ovarian Aging: Depletion of primordial follicles Picture from: http://embryology.med.unsw.edu.au/Notes/im ages/week1/ovary/oocytenumber.jpg
  20. 20. Ten various populations ranging from 17th to mid- 20th century. Marital fertility rates by 5-year age groups Menken J, Trussel J, Larsen U. Age and infertility. Science 1986;23:1389-1394.
  21. 21. 2009 Assisted Reproductive Technology Success Rates, National Summary and Fertility Clinic Reports (CDC)
  22. 22. 2009 Assisted Reproductive Technology Success Rates, National Summary and Fertility Clinic Reports (CDC)
  23. 23.  Female age  Cycle day 3 FSH & estradiol  AMH level  Vaginal ultrasound for antral follicles Assessment of Ovarian Reserve
  24. 24. Treatment Options  Directly correct a problem if possible (i.e. thyroid tx, Bromocriptine, weight loss, etc)  If unable to correct the underlying problem, then use empiric treatment:  Intrauterine insemination (IUI or AI)  Ovulation Induction  Assisted Reproductive Technology (i.e. in vitro fertilization – IVF)
  25. 25. Treatment Options: Intrauterine Insemination (IUI) Picture from Familydoctor.co.uk
  26. 26. Treatment Options: Ovulation Induction  By mouth: Clomiphene (Clomid) or Letrozole (Femara)  Pregnancy rate is 10% per cycle (higher in PCOS patients).  Risk of twins 8-10% and risk of triplets or more less than 1%  Side Effects: hot flushes, nausea, headaches, mood swings, blurred vision, thin uterine lining, poor cervical mucus.
  27. 27.  Injectable medications: Gonadotropins (FSH, LH)  Pregnancy rate is 10-20% each cycle (controversial)  Risk of twins up to 30% and risk of triplets or more 5-10%  Side effects of medication are minimal because it is a natural hormone. Chance of overstimulation and canceling cycle. Treatment Options: Ovulation Induction
  28. 28. Gonadotropins
  29. 29. Polycystic Ovarian Syndrome (PCOS)
  30. 30. Adjunct to Ovulation Induction in PCOS  1500-2000 mg/ day  May not be covered by insurance in non-diabetics  Re-introduce clomid Metformin Ovarian Drilling  Ovulation rates, 50-80%  Adhesion risk, 10-15%  Longest study, 5 year follow-up1 (206 patients)  70% Pregnancy rate (1/2 treated)  50% Live birth rate 1 Naether OG et al., Human Reprod 9(12):2342-9, 1994
  31. 31. Which of the following do you believe:  All patients with PCOS should be on metformin  All PCOS patients wanting to conceive should be on metformin  Metformin is only indicated if a patient has diabetes or impaired glucose tolerance.
  32. 32. Metformin in PCOS 0 10 20 30 40 50 60 70 80 90 placebo placebo+CC metformin met+CC ovulation Nestler JE, et al. NEJM 338(26):1876-80, 1998
  33. 33. Metformin in PCOS BeforeBefore AfterAfter InsulinInsulin microU/mLmicroU/mL 2626 2222 TestosteroneTestosterone ng/dLng/dL 6161 4747 Glueck CJ, et al. Metabolism Apr;48(4):511-9, 1999
  34. 34. Is metformin more effective than clomid?  Randomized controlled trial of metformin 850 mg bid vs. clomiphene citrate 150 mg qd cycle days 5-9  Cumulative ovulation rate not different (63 vs. 67%)  Pregnancy rate/cycle = 15.1% metformin; 7.2% clomiphene (p = 0.009) Palomba et al. JCEM 90(7): 4068-74, 2005Palomba et al. JCEM 90(7): 4068-74, 2005
  35. 35. Does metformin decrease the spontaneous miscarriage rate in PCOS?  Randomized controlled trial of metformin 850 mg bid vs. clomiphene citrate 150 mg qd cycle days 5-9  Metformin group miscarriage = 3/31 (9.7%)  Clomid group miscarriage = 6/16 (37.5%)  P = 0.045 Palomba et al. JCEM 90(7): 4068-74, 2005Palomba et al. JCEM 90(7): 4068-74, 2005
  36. 36. Is metformin more effective than clomid? Legro et al. NEJM 356,6: 551-66, 2007Legro et al. NEJM 356,6: 551-66, 2007 Metformin +Metformin + placeboplacebo Clomid + placeboClomid + placebo Metformin +Metformin + ClomidClomid nn 208208 209209 209209 % of cycles that% of cycles that were ovulatorywere ovulatory 29%29% 49%49% 60%60% % pregnant/% pregnant/ ovulatory cycleovulatory cycle 8.4%8.4% 13.4%13.4% 13.7%13.7% % live birth% live birth 7.2%7.2% 22.5%22.5% 26.8%26.8%
  37. 37. What if all the tests are normal? Unexplained Infertility ~10% of couples
  38. 38. Guzick et al. Efficacy of treatment for unexplained infertility.Fertil Steril. 1998 Aug;70(2):207-13.) Treatment % preg No treatment 2.6% IUI 3.8% Clomiphene 5.6% Clomiphene+IUI 8.3% Gonadotropins 7.7% Gonadotropins+IUI 17.1% IVFIVF 20.7%20.7% Treatment Options: Unexplained Infertility See next slide
  39. 39. OU Reproductive Medicine IVF Statistics ( (Delivered per embryo transfer in 2010) Age group (years) %PregnantorDelivered * A comparison of clinic success rates may not be meaningful because patient medical characteristics, treatment approaches and entrance criteria for ART may vary from clinic to clinic.
  40. 40. Treatment Options: In Vitro Fertilization (IVF) & ART  Blocked tubes  Severe male factor  Unexplained infertility  Endometriosis/peritoneal factor infertility  Failure to conceive with less aggressive treatment  Ovarian failure/↓ ovarian reserve (donor eggs)
  41. 41. MDsMDs LabLab • Embryology• Embryology • Andrology• Andrology • Endocrine• Endocrine NursingNursing StaffStaff Office &Office & ClinicClinic StaffStaff ART Team
  42. 42. Assisted Reproductive Technology—ART  1978/1981 In vitro fertilization—IVF  1984 Donor oocyte (egg) cycle  1985 Cryopreserved Embryo Transfer  1990 Preimplantation Genetic Diagnosis—PGD  1992 Intracytoplasmic Sperm Injection—ICSI As of 2004, more than 1 million children born worldwide as a result of ART
  43. 43. IVF Luteal Leuprolide Protocol OCPs 14-28 days Lupron 24-30 days Gonadotropins 8-12 days hCG Retrieval Transfer 2 days 3-6 days
  44. 44. Monitoring Follicles IVF Ultrasound 
  45. 45. Sonographic Egg Recovery
  46. 46. Sonographic Egg Recovery
  47. 47. Intracytoplasmic sperm injection—ICSI  Discovered “by accident” in 1991 in a Belgian IVF lab  Successfully treats almost all forms of severe male factor infertility
  48. 48. ICSI
  49. 49. Timing of Embryo Transfer Day 3 Embryo Transfer Day 5–6 Embryo Transfer “Blastocyst Transfer” Veeck LL, Zaninovic N. An Atlas of Human Blastocysts. 1st ed. New York: Parthenon Publishing, 2003;118.
  50. 50. Embryo Transfer
  51. 51. • Loading Catheter
  52. 52. Embryo Transfer
  53. 53. Outcomes— Children
  54. 54. Children of ART Possible Risks  Multiple pregnancy  Low birth weight  Congenital anomalies  Transmission of parental genetic abnormalities (e.g., male factor)  Imprinting defects  Developmental abnormalities
  55. 55. OCTOMOM: Nadya Suleman
  56. 56. 2009 Assisted Reproductive Technology Success Rates, National Summary and Fertility Clinic Reports (CDC)
  57. 57. Octomom’s Clinic: West Coast IVF Clinic, Inc. In 2007, 19 patients < 35 years old 2 became pregnant 1 delivered Average # embryos transferred: 4.1
  58. 58. Preimplantation Genetic Testing  Preimplantation Genetic Screening (PGS)  Advanced reproductive age  Recurrent pregnancy loss  Multiple failed IVF cycles  Preimplantation Genetic Diagnosis (PGD)  Sex-linked disorders (FISH or PCR)  Single gene disease  Autosomal recessive (PCR)  Autosomal dominant (PCR)  Translocations (FISH)
  59. 59. A FE C D B An Atlas of Preimplantation Genetic Diagnosis pg 91
  60. 60. The Technology: PGS and Chromosome Translocations Fluorescent In-Situ Hybridization (FISH) Alternatives in the near future: Comparative Genomic Hybridization (CGH) Multiple Displacement Amplification Gene Chips Pyro Sequencing
  61. 61. Trisomy 21 Embryo Chromosome 21 Chromosome 21 Chromosome 21 An Atlas of Preimplantation Genetic Diagnosis pg
  62. 62. When should you refer your patient:  You’ve been trying to conceive for > 1year  You do not have regular periods  You are > 35 years old  You have a history of sexually transmitted diseases (i.e. chlamydia)
  63. 63. Conclusions  Basic Infertility Evaluation  Understand the treatment options  Understand the complications of treatments  We do not know all of the long-term effects of ART because it is still a relatively young field of study.
  64. 64. THANK YOU QUESTIONS? LaTasha B Craig, MD University of Oklahoma Health Sciences Center Section of Reproductive Endocrinology & Infertility Department of Obstetrics & Gynecology www.OUInfertility.com

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