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Infertility management 2019

ABOUBAKR ELNASHAR

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Infertility management 2019

  1. 1. MANAGEMENT OF INFERTILITY Prof. Aboubakr Elnashar Benha university Hospital, Egypt ABOUBAKR ELNASHAR
  2. 2. CONTENTS  INTRODUCTION 1. MALE FACTOR 2. ENDOMETRIOSIS ASSOCIATED INFERTILITY 3. OVARIAN FACTOR 4. TUBAL FACTOR 5. UTERINE FACTOR 6. UNEXPLAINED INFERTILITY ABOUBAKR ELNASHAR
  3. 3. INTRODUCTION When to refer a couple for investigations? After 40 y Immediate evaluation in women. 35-40 Y After 6 months of unprotected intercourse without conception <35 y After one year ABOUBAKR ELNASHAR
  4. 4. European Society of Human Reproduction & Embryology (ESHRE) (2000) Infertility testing should be classified into 3 groups depending on correlation with pregnancy rates I. Tests that have an established association with pregnancy: 1. Conventional semen analysis 2. Tubal patency tests, 3. Tests of ovulation ABOUBAKR ELNASHAR
  5. 5. II. Tests that are not consistently associated with pregnancy: Post-coital test, Antisperm antibody tests Zona-free hamster egg penetration test III. Tests that have no association with pregnancy: Endometrial biopsy Premenstrual endometrial biopsy Varicocele assessment Chlamydia testing ABOUBAKR ELNASHAR
  6. 6. 1. MALE INFERTILITY Prof. Aboubakr Elnashar Benha University, Egypt elnashar53@hotmail.com ABOUBAKR ELNASHAR
  7. 7. I. STANDARD SEMEN ANALYSIS IV. GENETIC TESTS 1. Karyotyping 2. Y chromosome microdeletions 3. Cystic fibrosis conductance regulator (CFTR) gene mutation II. SPECIALIZED SEMEN ANALYSIS 1. Sperm autoantibodies 2. Semen Fructose 3. Semen culture 4. Sperm function tests CASA S DF S ROS III. ENDOCRINE TESTS 1. T 2. LH and FSH 3. Prolactin INVESTIGATIONS ABOUBAKR ELNASHAR
  8. 8. I. STANDARD SEMEN ANALYSIS A. Macroscopic 1. Delayed liquefaction 2. Increased viscosity 3. Semen volume 4. pH B. Microscopy 1. Agglutination 2. Concentration 3. Motility 4. Morphology 5. Round cells 6. Leukocytes ABOUBAKR ELNASHAR
  9. 9. Semen analysis: WHO, 2010 : : Lower reference limitParameter 1.5 mlVolume 7.2pH 15 million/mlConcentration 39 million/ejaculateTotal sperm number 40% or PR: 32% Total motility: (PR+NP) 58% live spermatozoaVitality 4% (strict criteria).Normal forms Motility: progressive: rapid (a)+ slow (b) A and b Not used in WHO 2010 Non progressive (c) ABOUBAKR ELNASHAR
  10. 10. Prediction of fertility The likelihood of infertility increased with decreases in any of the 3 parameters: M NM C Normal morphology had the greatest discriminatory power. ABOUBAKR ELNASHAR
  11. 11. II. SPECIALIZED SEMEN ANALYSIS Not routinely performed used to determine the cause of male infertility 1. Sperm autoantibodies 2. Semen biochemistry (semen fructose) 3. Semen culture 4. Sperm cervical mucus interaction tests 5. Sperm function tests Computer aided sperm analysis (CASA) Sperm chromatin/DNA assays Sperm reactive oxygen species generation ABOUBAKR ELNASHAR
  12. 12. 1. Sperm autoantibodies 4 to 8%of subfertile men. Agglutination: Stick of motile spermatozoa to each other. ≥10%: suggestive but not conclusive of immunological infertility. should be confirmed by Mixed antiglobulin reaction (MAR) Immunobead test both of which detect sperm surface antibodies. ABOUBAKR ELNASHAR
  13. 13. 2. Semen biochemistry Rarely useful in clinical practice. Fructose marker of seminal vesicle function. Low or non-detectable: congenital absence of the vas deferens and seminal vesicles or ejaculatory duct obstruction ABOUBAKR ELNASHAR
  14. 14. 3. Semen culture Indicated: semen samples contain inflammatory cells Precautions during sample collection to prevent skin contamination. Results: usually not diagnostic. The yield of semen culture may be improved by performing a prostatic massage before sample collection. ABOUBAKR ELNASHAR
  15. 15. 5. Sperm function tests Routine: Impractical and costly Selective when the standard semen analysis is normal or near normal ABOUBAKR ELNASHAR
  16. 16. Computer-aided sperm analysis: CASA Assess: 1. Concentration 2. Morphology. 3. Motility: Quantitative measurement (curvilinear, straight line, average path) Amplitude of lateral displacement other derived functions. ABOUBAKR ELNASHAR
  17. 17. Useful in: Male unexplained infertility predicting in vivo and in vitro fertilizing capacity, toxicology studies. Accuracy depend upon: technology analytic conditions technical training of the operators. ABOUBAKR ELNASHAR
  18. 18. ABOUBAKR ELNASHAR
  19. 19. Normal= 10 Fragmented= 4 DFI= 4X100/10+4 =28.5% normal normal normal normal normal normal normal normal normal fragmented fragmented fragmented fragmented normal ≥30: male infertility 15-30: RM. ≤15: Excellent to Good fertility potential ABOUBAKR ELNASHAR
  20. 20. There is insufficient evidence to recommend the routine use of SDF testing in evaluation and treatment of infertile couple {level C} ????????? For diagnostic test 1. Results must be reproducible 2. Applicable to a given patient 3. Change management of patient ABOUBAKR ELNASHAR
  21. 21. III. ENDOCRINE TESTS 1. Serum testosterone (T) 2. Serum LH and FSH 3. Prolactin ABOUBAKR ELNASHAR
  22. 22. 1. Serum testosterone (T) Morning T In men with borderline values: Repeat FT ABOUBAKR ELNASHAR
  23. 23. 2. Serum LH and FSH Indication: T is low Interpretation: high FSH and LH: primary hypogonadism low or normal: secondary hypogonadism. low LH + low sperm counts +well-androgenized: exogenous anabolic or androgenic steroid abuse. ABOUBAKR ELNASHAR
  24. 24. 3. Prolactin Indication:  low T normal to low LH 4. Inhibin low serum inhibin concentrations may be an even more sensitive test of primary testicular dysfunction than high serum FSH concentrations, provided the assay is specific for inhibin B ABOUBAKR ELNASHAR
  25. 25. IV. GENETIC TESTS 1. Karyotyping 2. Y chromosome microdeletions 3. Cystic fibrosis conductance regulator (CFTR) gene mutation ABOUBAKR ELNASHAR
  26. 26. ABOUBAKR ELNASHAR
  27. 27. Abnormal semen ICSI TT of varicocele if palpable Hormonal tt if low FSH &Testost. Treatment of infection ? Mild:≥2 NM, ≥5M, ≥10%TM Severe or Azoospermia 3 trial IUI ABOUBAKR ELNASHAR TREATMENT
  28. 28. Varicocele: (AUA&ASRM, 2004 & AFU, 2006) Imaging examinations: not indicated to characterize the varicocele. TT when all of the following conditions are present: 1. Varicocele: Palpable 2. Semen: Abnormal (at least one abnormality) 3. Couple's infertility: Documented 4. Female infertility problem: Curable ABOUBAKR ELNASHAR
  29. 29. 2. ENDOMETRIOSIS ASSOCIATED INFERTILITY Prof. ABOUBAKR ELNASHAR Benha university, Egypt ABOUBAKR ELNASHAR
  30. 30. INVESTIGATIONS 1. Laparoscopy with biopsy and histology: gold standard for diagnosis Negative diagnostic laparoscopy: highly accurate for excluding endometriosis Positive laparoscopy without taking biopsies less informative of limited value (Wykes et al., 2004). To obtain tissue for histology in women undergoing surgery for endometrioma and/or deep infiltrating disease {exclude rare instances of malignancy} {GPP} ABOUBAKR ELNASHAR
  31. 31. Histopathologic confirmation necessary for the diagnosis of endometriosis ectopic endometrial stroma and glands (Berker, Seval, 2015) ABOUBAKR ELNASHAR
  32. 32. 2. TVS: To diagnose or to exclude ovarian endometrioma (Moore et al., 2002).{A}  rectal endometriosis (Hudelist et al., 2011).{A} ABOUBAKR ELNASHAR
  33. 33. Diagnosis of endometrioma •Ground glass echogenicity •1-4 compartments •No papillary structures •Detectable blood flow (Van Holsbeke et al., 2010).{GPP} ABOUBAKR ELNASHAR
  34. 34. Endometrioma. Sagittal TVS an ovarian mass with multiple fine internal echoes (arrows) and several hyperechoic mural foci (arrowheads). ABOUBAKR ELNASHAR
  35. 35. Ovarian endometrioma (A, B). The structure is hypoechoic and exhibits low amplitude uniformly distributed echotexture in the cavities of the cysts.ABOUBAKR ELNASHAR
  36. 36. 3D ultrasound To diagnose rectovaginal endometriosis is not well established (Pascual et al., 2010).{D} MRI To diagnose peritoneal endometriosis is not well established (Stratton et al., 2003) {D} ABOUBAKR ELNASHAR
  37. 37. ABOUBAKR ELNASHAR TREATMENT
  38. 38. 3. OVARIAN FACTOR INFERTILITY Prof. Aboubakr Elnashar Benha university Hospital, Egypt ABOUBAKR ELNASHAR
  39. 39. INVESTIGATIONS  Routine 1. Ultrasound folliculometry Costly Time consuming To be reserved for induction ovulation or COS (NICE, 2013; Practice Committee of the ASRM, 2015; UpToDat,2016) ABOUBAKR ELNASHAR
  40. 40.  Diagnosis of Spontaneous Ovulation 1. Mature F. (contain mature oocyte) = 17 – 25 mm (Inner dimensions) 2. Reduction in mature follicle size (40%) Or Disappearance (60%) 3. Intra peritoneal fluid -Normal: 1-3 ml -With ovulation: 4- 5 ml 4. CL: 4-8 days after ovulation  Irregular thick wall .  Hypoechoic  May contain internal echos (hge.)  15 mm ABOUBAKR ELNASHAR
  41. 41. 2. Mid luteal serum progesterone in regular and irregular cycles Mid-luteal  7 days before the next expected period day 21 and day 28 in 28-day and 35-day cycles, respectively. In irregular prolonged cycles depending upon the timing of menstrual periods, conducted later in the cycle (for example day 28 of a 35-day cycle) and repeated weekly thereafter until the next menstrual cycle starts Advantages: Reliable Safe Inexpensive ABOUBAKR ELNASHAR
  42. 42. 3. LH surge in urine Commercially available urinary LH detection kits can detect the LH surge and can be used to time intercourse with ovulation induction  Inexpensive,  Pinpoint the day of ovulation  Reduced the uncertainty in interpretation of progesterone levels by better-identifying the time of peak progestrone secretion at which to obtain serum ABOUBAKR ELNASHAR
  43. 43. May be done 1. Basal FSH and LH  Only in irregular prolonged cycles 2. Prolactin Only in ovulatory disorder galactorrhoea or pituitary tumour 3. TSH: only if symptoms of thyroid disease ABOUBAKR ELNASHAR
  44. 44. 4. Ovarian reserve testing  Woman’s age: An initial predictor of overall chance of success through natural conception or with IVF  Predictors of ovarian response to Gnt stimulation High responseLow response 16 or more4 or lessTotal AFC 3.5 or more 25 0.8 or less 5.5 AMH ng/ml pmol/l Conversion ratio:7 4 or less8.9 or moreFSH IU/L ABOUBAKR ELNASHAR
  45. 45.  Do not use ovarian volume ovarian blood flow inhibin B E2 ABOUBAKR ELNASHAR
  46. 46. Not recommended Historically, the effects of progesterone on basal body temperature, endometrial histology or cervical mucus were commonly used. 1. PMEB: histologic dating is not a valid diagnostic method lacks both accuracy and precision To evaluate the luteal phase: No {no evidence that medical tt of luteal phase defect improves pregnancy rates] ABOUBAKR ELNASHAR
  47. 47. 2. BBT  Stressful  Predicted the day of ovulation in10% of cycles  Less accurate for confirming ovulation (Guermandi et al, 2001) ABOUBAKR ELNASHAR
  48. 48. TREATMENT  Types of anovulation WHO
  49. 49. Types of ovarian stimulation Controlled ovarian stimulation Super ovulation Induction of ovulation Anovulatory or ovulatoryAnovulatoryPatient Multiple> oneOne mature follicle Objective IVFIUI Unexp infert AnovulatoryExample Down regulation Stimulation Prevent premature LH surge StimulationStimulationMethod ABOUBAKR ELNASHAR
  50. 50. Amenorrhea or severe oligomenorrhea FSH & LH: low Prolactin: normal I. Hypogonadotrophic hypoestrogenic Type I ABOUBAKR ELNASHAR
  51. 51. 1. Reverse the life style factors: Increase wt if BMI <19 When the metabolic state is normalized reflected by a normal BMI (>20 kg/m2), a regular menstrual cycle will be restored in the majority of patients. (Stafford, 2005) Moderating exercise if high levels of exercise. Treat stress CC: not effective ABOUBAKR ELNASHAR
  52. 52. 2. Gonadotrphins with LH activity or Pulsatile GnRH (pump) 3. luteal support hCG or progesterone from time of ovulation induction until sufficient hCG production by trophoblast cells is necessary. (Beckers et al., 2006) ABOUBAKR ELNASHAR
  53. 53. II. Normogonadotrophic Normoestrogenic Type II PCOS 2 of 3 (Roterdam definition,2003): •U/S PCO •Hyperandrogenism (Clinical or Laboratory) •Irregular or absent ovulation ABOUBAKR ELNASHAR
  54. 54. Weight reduction letrozole or CC Obese &overweight Normal weight &No weight loss & No ovulation LODGnT No ovulation after 3 cycles. No pregnancy after 6 cycles. No pregnancy after 6 cycles. No pregnancy after spontaneous, CC, FSH ovulation IVF Other surgical indication Difficult follow up Less aggressive No desire for surgery Add metformin IGT &IR ABOUBAKR ELNASHAR
  55. 55. III. Hypergonadotrophic hypoestrogenic < 40 yr, 2ndry amenorrhea Repeated FSH > 20 IU/L Causes 1. Idiopathic. 2. Genetic. 3. Autoimmune 3. Viral/bacterial infection 4. Pelvic surgery, chemotherapy 5. Galactosemia ABOUBAKR ELNASHAR
  56. 56. 1. Oral contraceptive suppression of gonadotrpins followed by discontinuation to allow a rebound in gonadotropins & ovarian function. 2. GnRHa suppression of gonadotropins secretion followed by high dose gonadotropin injection 3. Glucocorticoids suppression of immune system. Non of these tts has demonstrated efficacy in RCT ABOUBAKR ELNASHAR
  57. 57. IV. Hyperprolactinaemia I. Idiopathic Dopamine agonist (anxiety, pregnancy). Stop during pregnancy II. Microadenoma Dopamine agonist (anxiety, pregnancy). Stop after 2-3 yr. Surgery (rapid growth). III. Macroadenoma Dopamine agonist: long term Surgery (No response, suprasellar extension, pregnancy). ABOUBAKR ELNASHAR
  58. 58. 4. TUBAL FACTOR INFERTILITY Prof. Aboubakr Elnashar Benha university Hospital, Egypt ABOUBAKR ELNASHAR
  59. 59. INVESTIGATIONS 1. Hysterosalpingography The most commonly performed screening test for tubal patency. Advantages: 1.Position of tubal occlusion 2. Unilateral patency can be dd from bilateral patency. 3. Degree of damage to tubal endothelium 4. Peritubal adhesion. 5. Uterine cavity ABOUBAKR ELNASHAR
  60. 60. 6. Relatively cheap & simple. 7. HSG is in agreement with the laparoscopic findings approximately two thirds of the time. Sensitivity: 73 Specificity: 83% High specificity makes it useful in ruling in tubal obstruction ABOUBAKR ELNASHAR
  61. 61. Disadvantages 1. The pelvis including the ovaries is exposed to radiation: significant problem if the patient had an early pregnancy. 2. Abdominal pain which peaks 5 min after starting usually settles within 30 min. ABOUBAKR ELNASHAR
  62. 62. 3. Intravasation Network of streaklike opacities adjacent to the uterine cavity extend toward the pelvic side walls and subsequently migrate in a cephalad direction. Early detection: minimizes complications injection should be discontinued immediately, regardless of the contrast medium used. ABOUBAKR ELNASHAR
  63. 63. 2. Sono hystero salpingography An US contrast dye or saline (10-40 ml) is injected into the uterus through the cervix by a Foley catheter the passage of the dye is followed by TVS. 76% concordance rate with laparoscopy dye The addition of pulsed wave or color Doppler imaging may improve the predictive value of TV sonosalpingography Experience effective alternative to HSG (NICE, 2013) The ideal test is HyCoSy which combines cavity check with tubal assessment. ABOUBAKR ELNASHAR
  64. 64. 3. Laparoscopy Indication 1. Abnormal HSG or US 2.History or symptoms suggestive of pelvic disease. Normal HSG or no history suggestive of tubal disease: probability of clinically relevant tubal disease or endometriosis is very low: laparoscopy is not justified or cost effective (Fatum et al, 2002). ABOUBAKR ELNASHAR
  65. 65. Hysteroscopy Not an initial investigation unless clinically indicated {effectiveness of surgical treatment of uterine abnormalities on improving pregnancy rates has not been established}. (NICE, 2013) ABOUBAKR ELNASHAR
  66. 66. 4. Transvaginal hydrolaparoscopy (THL) ±Method of choice for the clarification of mechanical infertility factors in symptom free patients with no suspicion of pelvic pathologies (Nawroth et al,2001). THL in association with minihysteroscopy: more information better tolerated than HSG in outpatient infertility investigation ABOUBAKR ELNASHAR
  67. 67. 5. Chlamydia antibody testing (CAT) HSG is more accurate than CAT in predicting tubal disease (Elnashar et al,2000). If both tests were negative the tubal disease was identified on laparoscopy in only 4 % of case. ABOUBAKR ELNASHAR
  68. 68. TREATMENT IVF Main player for tt of tubal factor. Indication 1. Moderate to severe tubal disease A. Distal tubal occlusion with hydrosalpiges >1.5 cm in diameter. B. Distortion of the intraluminal architecture or endotubal adhesions detected by HSG, salpingoscopy or falloscopy 2. Other factors A. Sperm dysfunction B. Age >36 yr ABOUBAKR ELNASHAR
  69. 69. 1. Laparoscopic Surgery: Fimbrioplasty Lysis of fimbrial adhesions or the dilation of fimbrial strictures. Neosalpingostomy Creation of a new opening in a fallopian tube with a distal occlusion. Adhesiolysis more likely to work in the presence of patent tubes & filmy adhesions ABOUBAKR ELNASHAR
  70. 70. 2. Transcervical cannulation of the proximal fallopian tube Methods hysteroscopy fluoroscopy, or sonography Results successful catheterization 80% to 90% cumulative pregnancy 23% and 39% within the first 6 to 12 months. Ectopic pregnancy 5% to 13% ABOUBAKR ELNASHAR
  71. 71. Selective salpingography plus tubal catheterisation, or hysteroscopic tubal cannulation Proximal tubal disease If pregnancy has not occurred within 12 mo of surgery: IVF ABOUBAKR ELNASHAR
  72. 72. 3. Microsurgical reanastomosis of the fallopian tubes:  for tubal ligation reversal. performed by Laparotomy Laparoscopy comparable rates of success ABOUBAKR ELNASHAR
  73. 73. IVF or ICSI: IVF should be the initial treatment of choice (Aboulghar et al,1996; Bukulmez et al,2000). {No significant difference in PR. or take-home baby}. ABOUBAKR ELNASHAR
  74. 74. Hydrosalpinges salpingectomy, or tubal disconnection preferably by laparoscopy, before IVF treatment {improves the chance of a live birth}. ABOUBAKR ELNASHAR
  75. 75. 5. UTERINE FACTOR INFERTILITY Prof. Aboubakr Elnashar Benha university Hospital, Egypt ABOUBAKR ELNASHAR
  76. 76. INVESTIGATION 1. HSG 2. TVS 3. SIS 1. 3DUS 2. MRI 3. Hysteroscopy. ABOUBAKR ELNASHAR
  77. 77. Tubal patency Ut cavity Developmental defects Endometriosis or PAD Ovaries HSG + + - +/- - TVS - +/- +/- - + 3-D TVS - + + - + SIS - + +/- - + MR Imaging - + + - + Hysteroscopy - + + (with laparoscopy) - - Laparoscopy + - + (with hysteroscopy) + + (Hoffman et al., 2012). PAD=Pelvic adhesive disease ABOUBAKR ELNASHAR
  78. 78. 1. HSG Assess patency of the fallopian tubes contour of the endometrial cavity presence of any complex communications in the setting of a müllerian anomaly. Disadvantages: 1. Sensitivity to detect intrauterine abnormalities can be as low as 50% 2. lack of information about the external uterine contour: limits its utility for evaluating a uterine anomaly. use of TVS or HSG to evaluate the uterine cavity in women with suspected abnormalities may lead to suboptimal assessment of the uterus. ABOUBAKR ELNASHAR
  79. 79. 2. TVS Routine diagnostic tool for assessment of the pelvis, including the uterus and adnexa. Timing: Secretory phase of the menstrual cycle: better visualization of the endometrium, and contour of the uterine cavity. Advantages: Specificity and sensitivity for detecting uterine abnormalities: high Accuracy: excluding endometrial hyperplasia: high Disadvantages: dd SM fibroids & polyps: low (A). ABOUBAKR ELNASHAR
  80. 80. Information Uterus Assessment: Dimension, Endometrial: thickness, appearance Abnormalities: Anomalies, Tumors Ovaries Assessment: Position, Mobility, Volume, AFC Abnormalities: PCOS, Cysts, Tumors Tube Hydrosalpinx, Patency Pelvis Free fluid, Mass Basal Vaginal U/S The Pivotal US (performed D8-12) ± Saline infusion sonography (SIS) ABOUBAKR ELNASHAR
  81. 81. 3. SIS: experience effective alternative to HSG (NICE, 2013) Effectively delineate intracavitary space internal and external uterine contours. Most accurate for evaluating the size, location, and intracavitary component of the myoma. SIS Vs office hysteroscopy: •Comparable •easier •less uncomfortable •less expensive ABOUBAKR ELNASHAR
  82. 82. 4. 3 DUS highly accurate imaging of pelvic anatomy including detailed assessment of the uterus. ABOUBAKR ELNASHAR
  83. 83. 5. MRI Excellent delineation of internal and external uterine contours gold standard ” for the diagnosis of müllerian anomalies can identify rudimentary uterine structures and the presence of unctional endometrium. can differentiate  leiomyomas, adenomyosis and adenomyomas. ABOUBAKR ELNASHAR
  84. 84. Hysteroscopy As a routine procedure in the infertility work-up: still under debate no consensus on its efficacy and effectiveness in improving the prognosis of infertile couples (Sardo et al., 2016). Not an initial investigation unless clinically indicated (NICE, 2013) {its effectiveness on improving reproductive outcome has not been established } ABOUBAKR ELNASHAR
  85. 85. Endometrial biopsy: 1. Irregular or intermenstrual bleeding. 2. Abnormal endometrial thickening on TVS ABOUBAKR ELNASHAR
  86. 86. TREATMENT 1. CONGENITAL (MULLERIAN) ANOMALIES Prevalence Fertile and infertile women 3 – 4% Normal reproductive outcomes 3.2% 1st T RM: 5%-10% 2nd T RM: 25% (Khati, et al., 2012; Grimbizis et al., 2016). ABOUBAKR ELNASHAR
  87. 87. I- Uterine septum for primary infertility: (NICE 2015)  Current evidence on efficacy is inadequate: should only be done:  Multidisciplinary team  specialists in reproductive medicine  uterine imaging  hysteroscopic surgery.  Clear written consent:  uncertain efficacy  risks  audit or research  special arrangements for clinical governance ABOUBAKR ELNASHAR
  88. 88. II. Unicornuate uterus (with obstructed uterine horn) {at higher risk for infertility, endometriosis, premature labor, and breech presentations}. Excision of the obstructed rudimentary blind horn prevent endometriosis by eliminating reflux development of a pregnancy (and pregnancy complications) in the obstructed uterine horn (Khati, et al., 2012) . ABOUBAKR ELNASHAR
  89. 89. III. The Mayer-Rokitansky-Küster-Hauser syndrome =congenital absence of the vagina with variable uterine development {müllerian agenesis}. (Iverson et al ., 2016) 2014: First live birth following uterus transplantation uterine factor infertility, even when considered absolute, is now treatable (Brannstrom et al. 2015). 3 more births proving the outcome of uterus transplantation in this early stage of clinical implementation to be astonishing (Brannstrom 2015) ABOUBAKR ELNASHAR
  90. 90. 2. FIBROID Prevalence Women of reproductive age 20- 40% Associated with infertility: 5- 10%. Only cause of infertility: 2- 3% ABOUBAKR ELNASHAR
  91. 91.  Indications of Myomectomy: 1. Distorting the cavity Submucous: (Gambadauro,2012). Intramural: 2. Not distorting 1. >5 cm 2. Multiple >3 (3 cm) (Bajekal & Li, 2000) 3. only cause of infertility Myomectomy of IM fibroid not distorting cavity: no study has yet confirmed improvement of outcome (Paulson, 2016; Khalaf ,2016) ABOUBAKR ELNASHAR
  92. 92. 3. ADENOMYOSIS  Diagnosis: 1. TVS: 3 or more of the followings: 1. Globular uterus: 95% of cases. 2. Asymmetrical thickening: Anterior or posterior myometrial wall appearing thicker than its counterpart 3. Mottled heterogeneous myometrial texture: All cases. 4. Small myometrial hypoechoic cysts, which are cystic glands within ectopic endometrial foci: 82%. 5. “Shaggy” indistinct endometrial strips: 82%. 6. Striated projections extending from the endometrium into the myometrium ABOUBAKR ELNASHAR
  93. 93. Adenomyosis. Sagittal TVS Globular uterine enlargement Asymmetric thickening Heterogeneity of the myometrium (arrows) Poor definition of the endomyometrial junction (arrowheads). E = endometrium. ABOUBAKR ELNASHAR
  94. 94. Interrogation Sign
  95. 95. 2. Color or power Doppler Adenomyosis: diffuse vascularity Fibroid: peripheral vascularity ABOUBAKR ELNASHAR
  96. 96. Color Doppler imaging showing radial arteries running straight rather than the typical circular vascularization of fibroids
  97. 97. 3. MRI Indication: diagnosis is inconclusive  when further delineation would affect patient management when coexisting uterine myomas distort anatomy (ACOG, 2014). ABOUBAKR ELNASHAR
  98. 98. ABOUBAKR ELNASHAR
  99. 99. Treatment: (Tsui et al, 2015). 1. Routine infertility investigation plus ORT Normal: long agonist protocol and natural conception Abnormal: IVF 2. Failed natural conception or IVF: repeat IVF 3. Failed IVF: conservative surgery IVF after 3 m (Tsui et al, 2015). ABOUBAKR ELNASHAR
  100. 100. 4. ENDOMETRIAL POLYPS Define: hyperplastic overgrowths of endometrial glands and stroma that forms a projection from the surface of the endometrium (Stewart 2016). ABOUBAKR ELNASHAR
  101. 101. Treatment ABOUBAKR ELNASHAR
  102. 102. 5. INTRAUTERINE ADHESIONS Prevalence HSG: 1.5 % History of postpartum uterine curettage 21.5 % (hysteroscopy) (Deans, 2010). ABOUBAKR ELNASHAR
  103. 103. Treatment Hysteroscopic adhesolysis. The goal is to restore the size and shape of the uterine cavity, as well as endometrial function and fertility (Yu et al., 2008). An experienced hysteroscopic surgeon. Guidance with US: help define the cervical canal and the junction between the cervical internal os and the intrauterine cavity guide dissection. A small (5 mm) rigid hysteroscope can be used to pass through the cervical canal and into the uterine cavity under direct visualization to decrease the creation of a false passage (Cedars and Yanett, 2016). ABOUBAKR ELNASHAR
  104. 104. 6. REFRACTORY ENDOMETRIUM Prevalence Low: 2.4% (Kasius et al., 2014), Causes I. Surgical: dilation and curettage partial ablation aggressive myomectomy II. Radiotherapy III. Infections IV. Congenital Müllerian anomalies V. Idiopathic ABOUBAKR ELNASHAR
  105. 105. According to the most recent evidence: EnT≤7 mm would define a refractory endometrium with compromised success rates (Dix and Check, 2010; Kasius et al., 2014). ABOUBAKR ELNASHAR
  106. 106.  Treatment I. Hysteroscopic adhesiolysis II. Hormonal manipulation Estrogen:High dose 6−8 mg from cycle day 1 High doses for long periods, up to 9 ws vaginal HCG injection in the proliferative phase:1500 iu SC, daily starting from day 8 of the cycle For 7 days or until EnT 7mm Midluteal GnRHa: Single dose: Triptorelin: 0.1 SC 6 days after ICSI. Multiple doses: Triptorelin: daily 0.1 mg SC until day of beta-HCG or 14 days after OR ABOUBAKR ELNASHAR
  107. 107. III. Improving endometrial perfusion LDA Pentoxifylline and vitamin E. Pentoxifylline: 800 mg vit E: 1000 IU daily for 6-9 months Sildenafil: 25 mg/6 h in vaginal supp in the proliferative phase, stopped prior to HCG administration or ET. L-arginin: 6 g/day Nitroglycerin IV. New modalities Granulocyte colony-stimulating factor Autologous platelet-rich plasma Endometrial stem cells from bone marrow ABOUBAKR ELNASHAR
  108. 108. 6. UNEXPLAINED INFERTILITY Prof. Aboubakr Elnashar Benha university Hospital, Egypt ABOUBAKR ELNASHAR
  109. 109. DEFINITION Inability to conceive (before 35 y) after one year with routine (standard, basic) investigations of infertility showing no abnormality. (RCOG guidelines,1998; Randolph,2000) ABOUBAKR ELNASHAR
  110. 110. INVESTIGATIONS  Tests that have an established association with pregnancy: 1. Conventional semen analysis 2. Tubal patency tests, 3. Tests of ovulation  35-40 After 6 months After 40 y Immediate evaluation in women. ABOUBAKR ELNASHAR
  111. 111. Laparoscopy should be omitted in couples with unexplained infertility 1.Laparoscopy may reveal minimal or mild endometriosis or peritubal adhesions: Surgery or medical tt has not been proven to improve fecundity. 2. In women with unexplained infertility laparoscopy did not increase the PR (Badawy et al, 2010) ABOUBAKR ELNASHAR
  112. 112. Hysteroscopy Not routine in investigation of infertility except when an intrauterine lesion is suspected. Not an initial investigation unless clinically indicated {effectiveness of surgical treatment of uterine abnormalities on improving pregnancy rates has not been established}. (NICE, 2013) ABOUBAKR ELNASHAR
  113. 113. TREATMENT  By definition: Empiric  {does not address a specific defect or functional impairment} (Soules,2000 , Balen,2003; ASRM, 2006)  Dependent on:  Resources  Patients’ age  Duration of infertility.  The standard protocol is to:  Progress from simple to complex  Balance the effectiveness against the cost and side effects. (Ray et al,2012) ABOUBAKR ELNASHAR
  114. 114.  Lines of treatment I. Expectant management (EM) II. Ovulation-inducing agents 1. CC: 2. Aromatase inhibitors (AI) 3. Gonadotropins III. IUI IV. ICSI Tubal flushing or perturbation Fallopian tube sperm perfusion ABOUBAKR ELNASHAR
  115. 115.  Protocol for Management (Ray et al, 2012) 6 4 2 ABOUBAKR ELNASHAR
  116. 116. ABOUBAKR ELNASHAR You can get this lecture from: 1.My scientific page on Face book: Aboubakr Elnashar Lectures. https://www.facebook.com/groups/2277 44884091351/ 2.Slide share web site 3.elnashar53@hotmail.com
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