תוצאת חיפוש

גדליה פז, רוני גמזו, חיים יעבץ

המכון לחקר הפוריות, בית חולים ליולדות ליס, המרכז הרפואי סוראסקי ת"א, הפקולטה לרפואה סאקלר, אוניברסיטת ת"א

הגדרות מצבי הפוריות השונים של הגבר בזוג בלתי פורה השתנו בשנים האחרונות. העובדה שניתן להשיג הפריה על-ידי זרעון (חי) יחיד המוזרק לביצית (Intracytoplasmic sperm injection - ICSI), עם סיכוי של כ-40% לקליטת ההריון לאחר החזרת העובר לרחם האישה, הביאה למהפכה בתחום רפואת הפוריות.

ניתן להגדיר את עקרות הגבר כמצב שבו אין מוצאים זרעון חי אחד בביופסיות של אשכים לאחר מספר ניסיונות, או כשבבדיקות גנטיות מעמיקות, כולל הסתייעות בביולוגיה מולקולתית, מזהים חסרים בכרומוזום Y, הגורמים לתיסמונתSCO  (Sertoli Cell Only Syndrome). לפיכך, כל ניסיון מוצלח לבדד זרעונים (אפילו ספורים) מאשך של גבר מוכיח כי הוא בעל פוטנציאל להפרות ביציות בשיטת ה-ICSI, ולזוג המטופל יש סיכוי להרות בדומה לכל זוג המגיע לטיפולי הפריה חוץ-גופית (IVF–In Vitro Fertilization ) – כל זאת כמובן מתוך הנחה שהאישה פורייה על-פי כל קנה-מידה מקובל. שינוי זה בהגדרת העקרות משנה גם את ההגדרות הנהוגות כיום למצבי תת-פוריות (sub-fertility) או חוסר פוריות ללא סיבה ידועה (unexplained infertility).

במאמר להלן נסקר המידע הקיים כיום בשיטות האיבחון השונות של בירור פוריות הגבר, תוך שימת דגש על הנעשה במכון לחקר הפוריות והכלים העומדים לרשותנו לבירור מצב פוריות הגבר הפונה לעזרת צוות המכון.

סנדרה קליימן, לאה יוגב, גדליה פז וחיים יעבץ

כרומוסום Y מכיל גנים המקודדים לחלבונים רבים הממלאים תפקיד בייצור זרעונים באשך. עובדה זו נחשפה כאשר התגלה שבחלק מהגברים הלוקים באי-פוריות (15%-7%) מאובחנים חסרים זעירים בזרוע הארוכה של הכרומוסום. החסרים התגלו בשלושה אזורים, המכונים AZFa, AZFb, ו-AZFc. איבחון מחודש ומעמיק של תבניות היסטולוגיות שניצפו באשכים של גברים שלגביהם הוגדר אורך החסר, סייעה להבנת משמעותם של חסרים אלה. זיהוי חסר זעיר הכולל את אזור AZFa או AZFb בשלמותו, או שני אזורי AZF בשלמותם, מרמז על סיכוי קלוש למצוא תאי זרע בריקמת האשך. כמו כן, חסרים הכוללים את קצה כרומוסום Y גורמים לאי יציבות כרומוסומית ונוטים ליצור תאים עם קריוטיפ 45X0. יתר-על-כן, מימצאים חדשים מרמזים על החמרה הדרגתית ביצירת הזרעונים בגברים עם חסרים ב-AZFc, ולפיכך מומלץ לשקול הקפאת תאי זרע לגברים עם יצירה פחותה של זרעונים בזירמה בעקבות חסר ב-AZFc, על-מנת לחסוך מהם בעתיד ניתוח לאיתור זרעונים באשך. בדיקת חסרים זעירים בכרומוסום Y נחשבת כיום לבדיקה בסיסית, החשובה לבירור האטיולוגיה של ליקוי בפוריות. נוסף על כך, היא מספקת מידע המסייע בבחירת ההוריה הטיפולית.

Cells-Preliminary Report Immunohistochemical Identification of Testicular Germ

Batia Bar-Shira Maymon, Gedalia Paz, Leah Yogev, Ron Hauser, Letizia Schreiber, Amnon Botchan, Haim Yavetz

Institute for Fertility Study, Lis Maternity Hospital; Pathology Institute, Tel Aviv-Sourasky Medical Center; and Sackler Faculty of Medicine, Tel Aviv University

The use of testicular spermatozoa for intracytoplasmic sperm injection introduced a new treatment modality for management of male infertility.

Since testicular biopsies of non-obstructive azoospermic men are not homogenous in their histological patterns, identification with certainty of focal spermatogenesis might be difficult, particularly in those with small foci of spermatogenesis. We used an immunohistochemical marker of the male germ line, an antibody generated against RBM (RNA-binding-motif), to recognize with high precision the presence of germ cells in the biopsy. Biopsies of 30 men with azoospermia, most with non-obstructive azoospermia and a few with obstruction of the vas deferens, were evaluated.

Immunohistochemical staining for RBM protein contributed to the detection and accuracy of the identification of germ cells. Furthermore, this immunohistochemical technique aided the histopathologist to focus on even small foci of spermatogenesis. Absence of the protein expression confirmed the diagnosis of Sertoli-cell-only syndrome. The results indicate that expression of RBM can be a diagnostic marker for identifying the germ cells of small concentrations of spermatogenesis. This method can enhance the accuracy of histopathological evaluation of testicular biopsies that had formerly relied mainly on hematoxylin-and-eosin staining.

Follicle-Stimulating Hormone in Azoospermia in Prediction of Spermatogenic Patterns

David B. Weiss, Shoshana Gottschalk-Sabag, Zvi Zukerman, Elchanan Bar-On, Zvi Kahana

Kupat Holim Me'uhedet; and Dept. of Pathology and Cytology and Male Infertility Unit, Shaare Zedek Medical Center, Jerusalem; Andrology Unit, Rabin Medical Center (Beilinson Campus), Petah Tikva; and Paper Research Consultant Institute, Jerusalem

Follicle-stimulating hormone (FSH) is considered to be the most important plasma hormone correlated with spermatogenesis. Elevated FSH plasma levels were shown to be associated with complete damage to testicular seminiferous tubule germinal epithelium. Recently, there have been conflicting reports with regard to the value of FSH plasma levels in predicting seminiferous tubule histology in the azoospermic patient and hence, as a guide for therapy in assisted reproduction using testicular sperm retrieval. The aim of this study was to evaluate whether FSH plasma levels can predict spermatogenic pattern in the testes of the azoospermic infertile patient. 69 infertile men with non-obstructive azoospermia and 18 with very severe oligospermia were studied. In all, plasma levels of testosterone, free testosterone, prolactin, luteinizing hormone and follicle-stimulating hormone were measured by enzyme immunoassay. In the azoospermic patients the seminiferous tubule spermatogenic pattern was determined in testicular aspirates obtained by multiple fine needle aspiration and categorized according to the most mature spermatogenic cell type in the aspirates: Sertoli cells only, spermatogenic maturation arrest or full spermatogenesis. There were no significant differences in plasma levels of any hormone measured except in very severely oligospermic and azoospermic patients. Both normal and elevated levels were detected in all, regardless of seminiferous tubule cytological pattern or plasma FSH in azoospermic patients. It is concluded that plasma levels of FSH can not be used as a predictive parameter, neither for the presence of spermatozoa nor for any other seminiferous tubule cytological pattern in azoospermic infertile men. They cannot serve as guides for selection of azoospermic men for trials of testicular sperm retrieval in assisted reproduction.

Does Testicular Volume Reflect Spermatogenic Pattern in Azoospermia?

David B. Weiss, Elchanan Bar-On, Shoshana Gottschalk-Sabag, Zvi Zukerman

Kupat Holim Mehuhedet and Male Infertility and Cytology Units, Shaare Zedek Medical Center, Jerusalem; and Andrology Unit, Rabin Medical Center (Beilinson Campus) Petah Tikva

The aim of this study was to determine whether testicular volume can serve to predict patterns of spermatogenesis in azoospermia. In 27 tests of azoospermic infertile men, cytological specimens from several sites from each testis were obtained by fine needle aspiration. Testes were classified according to the most mature spermatogenic cell type. Classifications were testes with spermatozoa, with arrested spermatogenic development, and with only Sertoli cells. Prior to fine needle aspiration the 3 dimensions of each testis were determined ultrasonically and its volume calculated. Mean testicular volume (±‏SD) was 7.71 (±5.95) ml for testes with spermatozoa and 7.55 (±2.35) and 7.31 (±4.42) ml for testes with spermatogenic maturation arrest and with only Sertoli cells, respectively (differences not significant). It is concluded that testicular volume can not be used as a predictive parameter, neither for the presence of spermatozoa nor for the cytological pattern of the testes of azoospermic infertile men.

Are Testes in Oligo/Azoospermia Homogenous or Heterogenous?

David B. Weiss, Shoshana Gottschalk-Sabag, Elchanan Bar-On, Zvi Zukerman

Kupat Cholim Meuhedet, Jerusalem; Male Infertility and Cytology Units, Shaare Zedek Medical Center, Jerusalem; and Andrology Unit, Rabin (Beilinson) Medical Center, Petah Tikva

We determined whether a single testicular specimen is sufficient to represent qualitatively the spermatogenic process within the testes of azoospermic or severely oligospermic infertile men. In 191 testes of azoospermic patients and in 26 of those with severe oligospermia, fine needle aspirations at 3 different sites of each testis were performed. Aspirated material from each puncture was stained and in each smear all spermatogenic cells, as well as Sertoli cells, were identified. Testes were classified according to the most mature spermatogenic cell type present, or the presence of only Sertoli cells. The homogeneity of the testicular spermatogenic process was then evaluated. There was an overall intratesticular difference between aspirates in 14.1% of azoospermic testes and in 26.9% of severely oligospermic testes with regard to the most mature spermatogenic cell type. When spermatozoa were the most mature cell type, they were detected in all of the 3 aspirates in 71.4% of the testes. In 18.4% or 10.2% of this group of testes they were retrieved in only 1 or 2 of the aspirates, respectively. In testes in which spermatids or spermatocytes were the most mature spermatogenic stage, these cell types were detected in all 3 aspirates in only 36.4% and 68.0%, respectively. In azoospermic patients with full testicular spermatogenesis, the likelihood of retrieving spermatozoa from the testes was 84.3%, 92.7% and 100% in 1, 2 and 3 specimens, respectively. The following conclusions were drawn: There is a wide range of testicular heterogeneity in azoospermia or very severe oligospermia for diagnosing the testicular spermatogenic pattern. In azoospermia, specimens from several testicular sites are required. It is strongly recommended that no assisted fertilization be offered to azoospermic patients unless prior evaluation of the spermatogenic pattern in the seminiferous tubules is determined.

Seminiferous Tubule Cytological Pattern in Infertile, Azoospermic Men in Diagnosis and Therapy

David B. Weiss, Shoshana Gottschalk-Sabag, Elchanan Bar-On, Zvi Zukerman, Yigal Gat, Benjamin Bartoov

Male Infertility and Cytology Units, Shaare Zedek Medical Center, Jerusalem; Andrology Unit, Rabin Medical Center (Beilinson Campus), Petah Tikva and Male Infertility Laboratory, Dept. of Life Sciences, Bar-Illan University, Ramat Gan

We determined spermatogenic patterns of seminiferous tubules in azoospermic infertile men and evaluated the prevalence of bilateral testicular homogeneity. 185 azoospermic men underwent bilateral testicular fine-needle aspiration (TFNA) in which each testis was punctured at 3 different positions. Aspirated material was stained and classified according to the most mature spermatogenic cell type present or whether only Sertoli cells were present. 35.7% had spermatozoa in their testes, 36.2% had spermatogenic maturation arrest, and 28.1% had only Sertoli cells in their seminiferous tubules. In 15.6% of all patients, the diagnosis in 1 testis differed from that in the other. In only 73.2% of those with testicular spermatozoa was it bilateral. In the remaining 26.9%, only Sertoli cells, spermatocytes or spermatids were found as the most mature cell type in the other testis. The study definitely indicates that fertilization with retrieved testicular spermatozoa should not be offered to azoospermic patients without prior evaluation of the seminiferous tubue spermatogenic pattern in both testes.