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Infertility seminar


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Infertility seminar

  2. 2. Grading of evidence  (A) Systematic review and meta-analysis of randomised controlled trials or at least one randomised controlled trial  (B) At least one well-designed controlled study without randomisation or at least one other type of well-designed quasi- experimental study.  (C) Well-designed non-experimental descriptive studies, such as comparative studies, correlation studies or case studies or extrapolated recommendation from either A or B  (D)Expert committee reports or opinions and/or clinical experience of respected authorities or extrapolated recommendation from either grade A,BorC.  Good practice point (GPP) :- The view of the guide line development group
  3. 3. Subfertility Inability to conceive after one year of regular unprotected intercourse in the absence of known reproductive pathology. Peak monthly pregnancy rate ~ 30%  cumulative rate in 1 year ~ 85%  cumulative rate in 2 years ~ 95%
  4. 4. After 2 years of unexplained infertility, the pregnancy rate is 1.1% per month Crosignani 1991 (18026 patient-cycles)
  5. 5. Incidence 10 – 15% of couples affected
  6. 6. Causes of subfertility Multiple factors are common Female factors (2/3) ovulatory tubal endometriosis others
  7. 7. Causes of subfertility Male factors (1/3)  Subnormal semen due to production defects e.g. idiopathic, endocrine, trauma, genetic  No sperm due to obstructive defects e.g. absent vas, vasectomy  Coital Unexplained  Ovulation, patent tubes and normal semen
  8. 8. The causes of infertility among Malaysian couples, based on the study done in HUSM, include:  ovulatory dysfunction (46%)  unexplained infertility (22%)  mixed factors (13%)  male infertility (6%)  tubal factor (5%)  cervical factor (3%)  others (5%)
  9. 9. Five important causes 1. Ovulatory dysfunction 2. Tubal problems 3. Endometriosis 4. Male factors 5. Unexplained
  10. 10. History Age Menstrual cycle  regularity History of PID or pelvic surgery Previous investigations and treatment Age / occupation Past health Coital history Smoking/alcoholic
  11. 11. People who are concerned about their fertility should be informed that female fertility declines with age, but that the effect of age on male fertility is less clear. (C)
  12. 12. In women both active and passive smoking will affect fertility. (B) In men smoking reduced semen quality but the impact of this on male infertility is uncertain (GPP) SMOKING
  13. 13. History of present complaint Type of infertility Duration of infertility • Sexual history  Libdo, Impotance Frequency of intercourse • Medical History Recent febrile illness  Mumps Orchitis Venereal disease Renal failure Secondary Infertility is not congenital Reflects testosterone level Depresses spermatogenesis Testicular damage Obstruction Testicular failure History Items Relevance in Oligo/Azoospermia
  14. 14. History Items Relevance Oligo/Azoospermia Medical History Liver failure Chemotherapy/radiotherapy Multiple Sclerosis Diebetes Mellitus Spinal Cord injury Surgical History Orchidopexy Vasectomy Inguinal Hernia Repair Pelvic/Scrotal Injury/ Urethral Surgery Prostatectomy Hormonal abnormality Testicular damage Ejaculatory dysfunction Ejaculatory dysfunction Ejaculatory dysfunction Indicative of previous maldecent/torsion Obstruction Obstruction Ejaculatory dysfunction/obstruction Ejaculatory dysfunction
  15. 15. History Items Relevance in Oligo/Azoospermia Testicular History Maldecent, Torsion, trauma Drug History Cimetidine, Spironolactone Anabolic steroids, GnrH agonist Chemotherapy Occupational & recreational exposure Pesticides,herbicides, X- Ray Excess heat Radiation Alcohol/ drug abuse Systems review Headache/ visual disturbance Anosmia Galactorrhoea Testicular Damage Anti-androgen Inhibit pituitary gonadotrophin secretion Testicular damage Testicular damage Testicular damage Testicular damage Testicular damage Pituitary tumours Kallmans,s syndrome Hyperprolactinaemia
  16. 16. Physical examination Body weight Vaginal examination  uterine size  mobility  adnexal mass ? Necessary Testicular size Vas and epididymis Varicocele
  17. 17. Body weight •Women with BMI>29 are likely to take longer to conceive and losing weight is likely to increase their chance of conception (B). •Participating in a group program involving exercise and dietary advice leads to more pregnancies than weight loss advice alone. (A) •Men who have a body mass index of more than 29 should be informed that they are likely to have reduced fertility. (B)
  18. 18. Women who have a body mass index of more than 29 and who are not ovulating should be informed that losing weight is likely to increase their chance of conception. (B) Women who have a body mass index of less than 19 and who have irregular menstruation or are not menstruating should be advised that increasing body weight is likely to improve their chance of conception. (B)
  19. 19. TESTICULAR PROBLEM High testesVaricocoele Inguinal hernia Testicular injury
  21. 21. Basic Investigations
  22. 22. Semen analysis
  23. 23. Semen analysis Produced by masturbation after 2-7 days of sexual abstinence Do not use lubrication 2 to 3 samples required; additional if abnormal Protect against extreme temperatures (<20 C / >40 C) Analysis within one hour of collection (WHO Manual)
  24. 24. Semen Analysis Semen Analysis (WHO 2000) - Volume – 2 ml or more - Liquifaction time - within 60 min - pH - 7.2 or more - Concentration/ml – 20 mil/ml or more - Motility – 50% grade a and b - Total count – 40 mil per ejaculate or more - Morphology – 15% - WBC/Pus cells - < 1 mil/ml - Vitality – 75% or more
  25. 25. Semen analysis WHO criteria (2010):  volume: >=1.5 ml  concentration: >=15 million / ml  motility: >=32% progressive motility  normal forms: >=4% (strict criteria) Low predictive values
  26. 26. Semen analysis If the result of the first semen analysis is abnormal, a repeat confirmatory test should be offered. (B) Repeat confirmatory tests should ideally be undertaken 3 months after the initial analysis to allow time for the cycle of spermatozoa formation to be completed. However, if a gross spermatozoa deficiency (azoospermia or severe oligozoospermia) has been detected the repeat test should be undertaken as soon as possible. (GPP)
  27. 27. Investigations-- a. Ovulation  Mid-luteal progesterone (eg D21- 28 day Cyc.)  Irregular cycles FSH & LH (D2),prolactin, thyroxine, Ultrasound--ovarian morphology (PCO)  Regular cycles prolactin or thyroxine not indicated
  28. 28. Assessment of Ovulation Women with fertility problems should be asked about the frequency and regularity of menstrual cycles. Women with regular monthly menstrual cycles are likely to be ovulating. (Grade B) The use of basal body temperature charts to confirm ovulation does not reliably predict ovulation and is not recommended. (Grade B)
  29. 29. - λ Measure 7 days before expected period λ Interpret after next LMP known <16 nmol/L -ovulation induction >16 but <30 nmol/L -repeated >30 nmol/L -ovulation If corrected timed, interpret as below Serum progesterone
  30. 30. Pelvic ultrasound
  31. 31. Transvaginal scanning
  32. 32. Ultrasound assessment: international consensus definitions 1. ≥12 follicles of 2-9 mm in diameter in at least one ovary or 2. Increased ovarian volume (>10 cm3 ) (Balen et al., 2003)
  33. 33. Revised PCOS diagnostic criteria Two out of three: 1. Oligo- and/or anovulation 2. Clinical and/or biochemical signs of hyperandrogenism and exclusion of other aetiologies (congenital adrenal hyperplasias, androgen-secreting tumours, Cushing’s syndrome) 3. Polycystic ovaries on scanning (PCOS consensus workshop group, Rotterdam, May 2003)
  34. 34. Investigations-- b. Tubal patency
  35. 35. Tubal patency tests 1. HSG 2. Laparoscopy and dye 3. Hysterosalpingo-contrast-sonography (HyCoSy)- USS, no radiation 4. Salpingoscopy or falloposcopy
  36. 36. Hydrosalpinx
  37. 37. Hysterosalpingogram False positive because of spasm in proximal ends Peritubal adhesion not detected 4-5% pelvic inflammatory disease after hysterosalpingogram
  38. 38. Assessment of tubal factor The results of semen analysis and assessment of ovulation should be known before a test for tubal patency is performed. Women who are not known to have co-morbidities (such as pelvic inflammatory disease, previous ectopic pregnancy or endometriosis) should be offered HSG to screen for tubal occlusion because this is a reliable test for ruling out tubal occlusion, and it is less invasive and makes more efficient use of resources than laparoscopy. (Grade B)
  39. 39. Laparoscopy- diagnostic / therapeutic
  40. 40. Tubal pathology detected at laparoscopy has a stronger effect on future fertility than that detected at HSG. (B) Women who are thought to have comorbidities should be offered laparoscopy and dye so that tubal and other pelvic pathology can be assessed at the same time. (B)
  41. 41. Investigations NOT indicated in clinical practice Serum antisperm antibody Postcoital test Sperm function test Endometrial biopsy Hysteroscopy Ultrasound of endometrium
  42. 42. Endometrial biopsy
  43. 43. Hysteroscopy
  44. 44. Ultrasound of endometrium
  45. 45. Treatment
  46. 46. General advice (Female) folic acid whilst trying to conceive and during the first 12 wks of pregnancy to prevent neural tube defects Reduce body weight in obese women Stop smoking Avoid excessive alcohol
  47. 47. Good health Free from illness eg thyroid, blood pressure, diabetes Avoid food fads Balanced diet Folic Acid Supplements
  48. 48. General advice (Male) Stop smoking Avoid excessive alcohol Men with poor quality sperm advised to  wear loose fitting underwear and trousers and  avoid occupational or social situations that might cause testicular hyperthermia
  49. 49. Causes of subfertility Ovulatory Tubal factors Male factors Unexplained/min. endometriosis
  50. 50. Ovulation induction Development of a single follicle
  51. 51. Ovulation Induction FSH & Prolactin Prolactin Normal FSH FSH Hyperprolactinaemia -Bromocriptine -Cabergoline PCOS/Hypothalamic -Optimize weight -Drugs -Surgery Ovarian failure -Donor eggs USS
  52. 52. Ovulation induction Weight reduction Drugs  Clomiphene citrate  Gonadotrophin releasing hormone  Gonadotrophin  Others: insulin sensitising agents (metformin),  letrozole Surgery  ovarian drilling
  53. 53. Mx 1) Starting dose is 50 mg daily for 5 days, can be started b/t day 2- 6 of menses, 2) Check for ovulation 3) If there is ovulation, continue the same dose for 3-6 cycles, either with timed coitus or with IUI. 4) No response, increase dose by 5o mg in each cycle, until a maximum of 150mg per day. 5) If no response to the maximum dose, further increase is not effective and therefore not advisable.
  54. 54. Mx Gonadotrophin therapy In women with PCOD Aim:  Ripen follicles with repeated doses of FSH  Stimulate ovulation with injection of LH or hCG Drugs in use:  HMG– 75 iu FSH, 25-75 iu LH  Urofollitrophin—75 iu FSH n almost no LH  Recombinant FSH—75 iu FSH  hCG—1000-5000 iu hCG
  55. 55. Anovulatory women with polycystic ovary syndrome who have not responded to clomifene citrate and who have a body mass index of >25 should be offered metformin combined with clomifene citrate because this increases ovulation and pregnancy rates. (A) Metformin
  56. 56. Women with polycystic ovary syndrome who have not responded to clomifene citrate should be offered laparoscopic ovarian drilling because it is as effective as gonadotrophin treatment and is not associated with an increased risk of multiple pregnancy. Ovarian Drilling
  57. 57. Causes of subfertility Ovulatory Tubal factors Male factors Unexplained/min. endometriosis
  58. 58. Tubal factors Tubal surgery  microsurgical technique  laparotomy or laparoscopy  adhesiolysis, re-anastomosis, salpingostomy  results In vitro fertilization and embryo transfer (IVF-ET)
  59. 59. Mx Tubal surgery
  60. 60. Male Factor
  61. 61. Treatment 1-Medical -Empirical - unexplained male subfertility Treatment Concensus Studies with pregnancy as an outcome HMG/FSH Androgens Anti-estrogens Dopamine agonists Glucocorticoids Kalikrein Aromatase inhibitors Antioxidants Mast cell blocker (Tranilast) Studies with sperm parameters GnRH Growth Hormone Tribestan (herbal) No benefit No benefit No benefit No benefit No benefit No benefit No benefit. (only one RCT) Potential benefit, but needs further evaluation as an outcome No benefit No benefit
  62. 62. Antibiotics In the absence of any clinical symptoms, the role antibiotics therapy still uncertain according to prospective studies and small RCT. 2- Surgery Obstructive Azoospermia
  63. 63. 2- Surgery Obstructive Azoospermia - appropriate expertise is available, should offered surgical correction of epididymal blockage to improve fertility, - surgical correction should be considered as an alternative to surgical sperm recovery and in vitro fertilization Varicoceles - varicocele correction does not improve pregnancy rates
  64. 64. 3-Reproductive Technique (ART) I- Intrauterine Insemination (IUI)  IUI is not beneficial unless a total motile sperm count above 10 mil.  at least three and a maximum of six IUI cycles can be proposed depending on the women’s age II- IVF/ICSI  if no pregnancy after IUI  Total sperm count< 10 mil  + TESA/PESA – if Azoospermia
  66. 66. ♦Ejaculatory failure - Hypospadius- Vaginismus- Impotence- retrograde ej. ♦Cervical factor - mucus hostility-poor mucus ♦Male subfertility - Mild, moderate ♦Immunological - Male sperm female antisperm a.b ♦Unexplained Infertility INDICATIONS FOR IUI
  67. 67. ♦Endometriosis (mild). ♦Ovulatory. INDICATIONS FOR IUI
  68. 68. For IUI, sperm are first washed and placed into a sterile medium. The sperm are then concentrated in a small volume of medium and are injected directly into the uterus.
  69. 69. Outcomes of Treatment Unexplained Infertility 0 10 20 30 40 50 60 70 80 90 0 1 2 3 4 5 6 months/treatment cycles %pregnant IUI HMG HMG+IUI IVF
  70. 70. Success Rate of IUI ♦ Published Rates: Low as 5% to as high as 70% ♦ Usual acceptable clinical pregnancy rate for all aetiologies is 10-20% ♦ When combined with COH in unexplained infertility , cumulative pregnancy rates may approach those of IVF.
  72. 72. (A) INVITRO FERTILIZATION (IVF) Indication:Indication: - Severe tubal damage/ blockage. - Bilateral salpingectomy. - Endometriosis. - Mild male infertility. - Unexplained infertility. - Immunologic infertility.. Successful rate:Successful rate: About 20-30%%. Cost per attempt:Cost per attempt: RM 3,000-4,000 (HSNZ) ASSISTED REPRODUCTIVE TECHNIQUE (ART)
  73. 73. (B) Intracytoplasmic Sperm Injection (ICSI) Indication : (Male factors)Indication : (Male factors) - Oligozoospermia. - Asthenospermia. - Teratozoospermia. - Antisperm Ab. - Fertilization failure after conventional IVF. - Ejaculatory disorder.
  74. 74. (C) Intracytoplasmic Sperm Injection (ICSI)
  75. 75. World HSNZ 1st Test Tube Baby 1978-UK 31 Aug 2010 1st Test Tube Baby Twin 1982-UK 28 Dec 2010 1 st Frozen Embryo Birth 1983-US 8 Feb 2012 1st ICSI Baby Birth 1992-UK 31 Aug 2010 1st TESA/PESA Baby Birth 1993 27 Oct 2012 Fertility Milestone – World Vs HSNZ
  76. 76. World HSNZ 1st Test Tube baby Triplets Birth 17 June 2013 1st TESA/PESA + ICSI twin baby birth 27 Oct 2012 Fertility Milestone – World Vs HSNZ
  77. 77. THANK YOU