עקרות ע קב חסר זרע פרופסור אייבי לוין וה אשה מחלקת נשים ו יו לדות פוריות הגבר והאוניב רסיטה העברית ירושל ים

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1 עקרות ע קב חסר זרע אייבי לוין פרופסור פוריות הגבר וה אשה מחלקת נשים ו יו לדות ביי"ח הד סה עין-כרם והאוניב רסיטה העברית ירושל ים

2 הגדרה: חסר זר עונים בז ירמה Azoospermia = azoos (lifeless) + sperma (seed)

3 בקרה הורמונלית על ייצור הזרע

4 תהליך ייצור Spermatogenesis הזרעונים בתאי האשך:

5 שני סוגים של חסר זרע בזירמה: חסימתי ולא-חסימתי

6 סיבות לחסר זרע חסימתי Congenital Agenesis of Vas Deference (Cystic Fibrosis) Infections Surgery Sterilization

7 הט יפ ו ל: ש א יבת זרע מ י ותרת הא שך Success rate: 90%-100%

8 חסר ז רע לא חסימתי Non-Obstructive Azoospermia משני לחסר הורמונלי Secondary Hypogonadotropic Hypogonadism Primary Testicular failure ראשוני עקב כשל האשך

9 Hypogonadotropic Hypogonadism

10 Non-Obstructive Azoospermia סיבות לכשל ראשוני של האשך Idiopathic Maturation arrest Idiopathic Sertoli cells only Cryptorchidism Klinefelter`s Syndrome (Tubular Hyalinization) Infection (Mumps, Tuberculosis, Syphilis) Chromosome Y deletions Chemotherapy and Irradiation

11 עצירת ההבשלה

12 תאי סר טולי בלבד

13 תסמונת קליי נפלטר שכיחות 1:500 בילודים פנוטיפים זכרים נגרם X ע י עודף כרומוזום XXY, XXXY, XXXXY כמעט תמיד יגרום לעקרות עקב ניוון האבוביות באשכים וחוסר יכו לת לייצר זרע

14 חסרים בכרומוזום Y AZFa, AZFb, AZFc deletions

15 אשך טמיר Atrophy

16 דלקות (Mumps, Tuberculosis, Syphilis) Mumps Orchitis

17 כימותרפיה והקרנות Diffuse atrophy

18 Treatment of Non-Obstructive Azoospermia No corrective approach available - except for Hypogonadotropic- Hypogonadism Is there any chance for sperm recovery?

19 First successful attempts to retrieve testicular spermatozoa in nonobstructive azoospermia TESE (Testicular Sperm Extraction) Devroey et al. Hum Reprod 1995 TEFNA (Testicular and Epididymal fine needle aspiration) Lewin et al. Hum Reprod 1996 Focal spermatogenesis

20 Are there criteria for surgical sperm recovery? Pre-treatment evaluation Ejaculate high velocity centrifugation Serum FSH, T Doppler-US and Testicular size Karyotype (XXY) Y-deletions (AZF-a, AZF-b, AZF-c) Serum Inhibin B Diagnostic Biopsy/FNA

21 No selective criteria for surgical sperm search Surgical methods: Testicular biopsy (TESE) Testicular aspiration (TEFNA)

22 TESE open multiple biopsies

23 Microsurgical TESE

24 ? Diffuse distribution of spermatogenesis in non-obstructive azoospermia Silber, Hum Reprod 15:2278, 2000

25

26

27 TEFNA Testicular Fluid Testis

28 Culture Medium

29

30

31

32 Results of TESE procedures

33 TESE sperm recovery rates Amer et al. Human Reproduction 1999;14(12): Hypospermatogenesis Early spermatid arrest Mixed pathology Primary spermatocyte arrest Sertoli cell-only syndrome Tubular hyalinization Klinefelter's syndrome (47,XXY) 6/7 (85.7) 8/10 (80.0) 22/30 (73.3) 2/6 (33.3) 9/27 (33.3) 1/8 (12.5) 0/4 (0) 48/92 (52.2) Total

34 Microsurgical TESE Reprod 15:2278, 2000 Sperm recovery: Silber, Hum Sertoli cells only 57% Maturation arrest 54%

35 Cochrane reviews Comparative study of Conventional TESE vs Microsurgical TESE Study Intervention n Sperm retrieved Amer 2000 Patients as their own control Convention al TESE Microsurgic al TESE 100 Each prcedure on one side Conventional 30% Microsurgery 47%.

36 TEFNA Results Mature testicular spermatozoa could be recovered in 127/236 (53.8%) cycles Lewin et al. ASRM annual meeting, San-Diego, Oct. 2000

37 Embryo Transfer Results Clinical pregnancy rate of fresh cycles - 31% 6 additional pregnancies using frozen sperm from TEFNA A cumulative pregnancy rate of 38.1%

38 Complications associated with surgical sperm retrieval Immediate Hematoma Fibrosis Long-term Devascularization Testicular atrophy Amer et al. Hum Reprod Mar;15(3): Schlegel and Su, Human Reproduction 1997;12(8):

39 Superiority of the Microsurgical approach in terms of Complications of TESE and Microsurgery (US findings) Hematoma Micro-TESE TESE P 1 9 (15.0) 35 (58.3) < (6.7) 31 (51.7) < (10.0)... Focal echogenic lesion (fibrosis) (3.3) (3.3) 18 (30.0) < 0.05 Segmental Devascularization 1 2 (3.3) 7 (11.7) NS 3 2 (3.3) 3 (5.0) NS Amer et al. Hum Reprod (3):

40 Complications of TEFNA Usually only Mild postoperative pain Not infections 2 patients - self-resolving hematoma Complication rate 2/236 = <1%

41 השפעות לטווח הארוך? 30 מטופלים נבדקו באולטרסאונד\דופלר לא נצפו שינויים במראה האשכים באולטרסאונד ובזרימת הדם באשכים.

42 מה הסיכוי למצוא זרע בדיקור 70% successful 2nd TEFNA 11% after failed TEFNA החוזר? Hum Reprod 2002 Jan;17(1): Fasouliotis SJ, Safran A, Porat A, Simon A, Laufer N, Lewin A.

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