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ABSTRACT: For most azoospermic men testicular sperm extraction (TESE) is the only treatment, however it presents challenges for the ART laboratory, as the retrieval of motile spermatozoa is difficult. In the absence of sperm movement no unequivocal distinction can be made between either dead or immotile, but vital spermatozoa. However, a single laser shot directed to the tip of the tail allows recognition of viability because the flagellum coils at the area of impact. To rank the quality and the maturity of oocytes, polarization microscopy can be used. The zona score and the visualization of the meiotic spindle correlate with implantation and pregnancy rates. We compared 65 TESE-ICSI cycles of the years 2007 and 2008 (Group 1, G1) with 58 TESE-ICSI cycles of the years 2009 and 2010 (Group 2, G2). Testicular spermatozoa were injected according to motility and morphology into selected oocytes. In G1 both, oocyte and spermatozoa were rated using light microscopy only, whereas in G2 the laser was used for sperm selection and the oocytes were rated by light and polarization microscopy. In G2 we enhanced our fertilization rate (FR) significantly in comparison to G1 (G1 42.1% vs. G2 52.7%, p < 0.001). The fertilization rate with immotile, but vital spermatozoa improved significantly when applying laser-based selection (p = 0.006). The laser selection of immotile spermatozoa and the use of polarization microscopy can enhance the FR of TESE-ICSI. No negative effect of the laser was seen on birth rates. The FR with immotile, but vital spermatozoa clearly benefits from laser selection and is a non-hazardous and safe method for the selection of viable but immotile sperm. To our knowledge this is the first report using new technology creating novel endpoints for the analysis of spermatozoa and oocytes in TESE-ICSI.
Andrology. 01/2013; 1(1):67-74.
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ABSTRACT: Die Hormonersatztherapie in der Menopause ist eine der meist rezeptierten medikamentösen Behandlungen der Frau. Die Therapie
führt in den meisten Fällen zu einer deutlichen Linderung der klimakterischen Beschwerden und somit zu einer Steigerung der
Lebensqualität. Die Indikation zur Therapie sollte jedoch nur streng im Sinne der Leitlinienempfehlungen gestellt werden.
Die Entstehung der 3häufigsten gynäkologischen Tumorerkrankungen wird durch eine Hormonersatztherapie in Abhängigkeit von
Präparat, Applikationsart und Dauer in unterschiedlicher Weise beeinflusst. Vor Beginn der Hormontherapie sollte daher eine
differenzierte Aufklärung der Patientin unter Abwägung des individuellen Risikos erfolgen, sodass die mündige Patientin in
die Therapieentscheidung miteinbezogen werden kann.
Hormone replacement therapy is one of the most regularly prescribed medications among menopausal women. Estrogen or combined
estrogen-gestagen therapy leads to a significant reduction of climacteric symptoms and therefore improves the quality of life.
There are clear guidelines concerning indications for hormone substitution which have to be followed. The three most common
gynecological cancer types are influenced (according to specific substance, type of application and durance of intake) in
different ways. Before starting hormone therapy, the medical specialist is beholden to precisely inform the patient about
individual risk factors and expected benefits so that the patient can make an objective decision.
SchlüsselwörterHormonersatztherapie–Leitlinien–Mammakarzinom–Ovarialkarzinom–Endometriumkarzinom
KeywordsHormone replacement therapy–Guidelines–Breast cancer–Ovarian cancer–Endometrial cancer
Gynäkologische Endokrinologie 05/2012; 9(3):161-164.
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ABSTRACT: Die Endometriose ist eine häufige, klinisch relevante Erkrankung, die Lebensqualität und Leistungsfähigkeit einschränkt. Die
Symptomatik ist uncharakteristisch, die Differenzialdiagnose schwierig und die Behandlungsoptionen – gleich ob operativ oder
medikamentös – sind letztlich symptomatisch. Neben notwendiger Forschung, um die Erkrankung zu verstehen, soll die Situation
für die Patientin dadurch verbessert werden, dass durch interdisziplinäre Zusammenarbeit sowohl die Diagnoseschritte optimiert
und die Zeit bis zu Diagnose verkürzt als auch die Behandlungsmöglichkeiten individuell und besser einsetzt werden. Die strukturellen
Voraussetzungen dafür werden in Endometriosezentren verwirklicht, die in Deutschland seit 2006 durch externes Audit von der
Stiftung Endometriose-Forschung zusammen mit der Endometriose-Vereinigung e.V. und der Europäischen Endometriose-Liga zertifiziert
werden. Neben der multimodalen Behandlung müssen die Zentren eine suffiziente Ausbildung des medizinischen Personals leisten
und durch Information der Bevölkerung und Unterstützung der Selbsthilfegruppen das Verständnis für die Erkrankung verbessern.
Während Struktur- und Prozessqualität gut überprüfbar sind, fehlt bisher in Deutschland die Möglichkeit, die Ergebnisqualität
zu vergleichen. Ähnliches gilt für andere europäische Länder.
Endometriosis is a frequent and clinically relevant disease. It affects the quality of life and reduces the ability of work.
Patient complaints are uncharacteristic, differential diagnosis is difficult and the therapeutic options are symptomatic—this
is true for surgical procedures and medication as well. Quality improvement in the management of endometriosis should be achieved
through basic research and better interdisciplinary cooperation in the wide area of diagnostic and therapeutic procedures.
Centres specialised in treating endometriosis can be certified by external audit in Germany since 2006. Criteria for the structure
of such centres, for cooperation and for clinical pathways have been defined by the Stiftung Endometriose-Forschung together with the Endometriose-Vereinigung Deutschland e.V. and Europäische Endometriose-Liga. In addition to the multidisciplinary treatment of the patients, the centres must teach and qualify both physicians and other
medical staff as well as inform the patients and the public to improve awareness of this disease. Up to now methods are missing
in Germany to compare the results of treatments by benchmarking for example. A similar situation can be observed in other
European countries.
SchlüsselwörterForschungsqualität-Strukturqualität-Ergebnisqualität-Zertifizierung-Rezertifizierung-Weiterbildungskompetenz
KeywordsResearch quality-Structure quality-Quality of results-Certification-Recertification-Continuing education competency
Der Gynäkologe 04/2012; 43(3):233-240.
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ABSTRACT: Die Ovarien besitzen sowohl eine exokrine als auch eine endokrine Funktion: Neben dem zyklischen Heranreifen von Oozyten sind
sie auch für die Produktion und Freisetzung von Hormonen, insbesondere Östrogen und Progesteron, zuständig. Dabei unterliegen
sie der hormonellen Regulation durch das hypothalamische-hypophysäre System. Eine entscheidende Rolle spielt insbesondere
das follikelstimulierende Hormon (FSH), aber auch das luteiniserende Hormon (LH), die Östrogene, Inhibine, Activin, Follistatin
und verschiedene Wachstumsfaktoren sind in ihrer Bedeutung im Rahmen der Follikelreifung nicht zu vernachlässigen. Die Follikulogenese
stellt einen bedeutenden Mechanismus im Leben einer jeden geschlechtsreifen Frau dar. In diesem Beitrag werden die Abläufe
der Follikelreifung vom Primordialfollikel bis hin zum reifen Graaf-Follikel und der anschließenden Ovulation bzw. Gelbkörperbildung
sowie deren hormonelle und funktionelle Regulationsmechanismen genauer erläutert. Ferner soll ein Ausblick geschaffen werden,
warum ein verbessertes Wissen um die Follikelreifung unbedingt notwendig sein wird.
The ovaries’ task in the hormonal cycle can be divided into an exocrine and endocrine function: Besides stimulating the maturation
of oocytes, the ovaries control synthesis and excretion of hormones (predominantly estrogen and progesterone) while being
subject to regulation by the hypothalamus and pituitary gland. Regarding the maturation process one of the most influential
hormones is the follicle-stimulating hormone (FSH). Estrogens (e.g., inhibins, activins, and follistatin), the luteinizing
hormone (LH), and several growth factors also affect this process. Follicle maturation is considered to be a decisive mechanism
in the life of pubescent women. This article deals with the course of follicle genesis, the consequent ovulation such as the
synthesis of the yellow body and explains their function in the hormonal cycle. The information given will clarify the importance
and need for further research on this topic.
SchlüsselwörterFollikulogenese-Gonadotropine-Ovulation-Ovarieller Zyklus-Atresie
KeywordsFolliculogenesis-Gonadotropins-Ovulation-Ovarian cycle-Atresia
Gynäkologische Endokrinologie 04/2012; 8(3):175-179.
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ABSTRACT: Das Konzept, dass endometriale Stammzellen für die zyklische Regeneration des Endometriums verantwortlich sind, stößt auf
zunehmende Akzeptanz. Die Expression von Stammzellmarkern wie Oct-4, Telomerase und Musashi-1 im Endometrium und der Nachweis
multipotenter Differenzierungseigenschaften klonaler endometrialer Zellen unterstützt diese These. Adulte endometriale Stammzellen
repräsentieren nur einen geringen Prozentsatz aller Stroma- und Drüsenzellen, sodass die Identifizierung spezifischer Marker
zur weiteren Differenzierung dieser Zellen von großer Bedeutung ist. Eine Dysregulation der Stammzellfunktion wird mit der
Pathogenese proliferativer Endometriumerkrankungen wie der Endometriose, der ektopen Manifestation von Endometrium außerhalb
des Uterus, in Verbindung gebracht. Eine induzierte Differenzierung dieser Stammzellen könnte ein zukünftiges neues Therapiekonzept
darstellen. Neben der Existenz gewebsständiger Stammzellen gibt es Hinweise auf einen Ursprung endometrialer Stammzellen im
Knochenmark, und auf das Vorkommen von Stammzellen im Menstruationsblut. Letztere könnten regenerative Therapieoptionen z.B.
für Patienten mit einem Myokardinfarkt entscheidend erweitern.
In recent years the concept of adult stem cells mediating cyclic endometrial regeneration has become increasingly accepted.
This hypothesis is supported by the identification of endometrial expression of stem cell markers such as Oct-4, Musashi-1
and telomerase, and by demonstration of the multi-lineage differentiation potential of clonal endometrial cells. Adult stem
cells only represent a small percentage of all stromal and glandular cells of the endometrium; therefore, identification of
additional specific markers to further characterize these cells is needed. A dysregulation of stem cell function is implicated
in the pathogenesis of proliferative diseases of the endometrium, including endometriosis, the growth of ectopic endometrial
tissue outside the uterine cavity. An induced differentiation of these cells may prove to be a fruitful therapeutic concept
in the near future. Apart from endometrial tissue stem cells, bone marrow-derived stem cells have been identified in the endometrium,
in addition to menstrual blood-derived stem cells. The latter may expand therapeutic options in regenerative medicine, e.g.
for patients suffering from myocardial infarction.
Gynäkologische Endokrinologie 04/2012; 7(3):185-189.
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ABSTRACT: Polycystic ovary syndrome (PCOS) is a frequent heterogenic disorder with a familial background. Androgenic effects, determining the clinical features of the syndrome, are mediated by the androgen receptor (AR), whose activity is modulated by a genetic polymorphism. We investigated the role of the CAG repeat polymorphism of the androgen receptor in PCOS.
In the infertility unit of a university clinic, 72 PCOS patients were compared with 179 ovulatory controls undergoing a standardized diagnostic work-up. The number of CAG repeats was determined by PCR, labelling with IR-800 and PAGE. X-chromosome inactivation was assessed by a methylation-sensitive assay.
Compared to controls, PCOS patients displayed a shorter mean CAG repeat length, encoding for higher AR activity (P=0.001). CAG repeat length correlated inversely with oligomenorrhea, a central androgen dependent feature of the syndrome (P=0.005). In a binomial regression analysis including BMI, LH and free testosterone, CAG repeat length was identified as an independent risk factor for PCOS (P=0.002).
The CAG repeat polymorphism could constitute one of the genetic factors modulating the syndrome's phenotype, contributing to its clinical heterogeneity and associated metabolic consequences.
Experimental and Clinical Endocrinology & Diabetes 11/2011; 120(2):73-9. · 1.69 Impact Factor
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ABSTRACT: Background. Proliferation and differentiation of the endometrium are regulated by estrogen and progesterone. The enormous regenerative capacity of the endometrium is thought to be based on the activity of adult stem cells. However, information on endocrine regulatory mechanisms in human endometrial stem cells is scarce. In the present study, we investigated the expression of ERα, ERβ, and PR in clonal cultures of human endometrial stem cells derived from transcervical biopsies. Methods. Endometrial tissue of 11 patients was obtained by transcervical biopsy. Stromal cell suspensions were plated at clonal density and incubated for 15 days. Expression of ERα, ERβ and PR was determined by qPCR prior to and after one cloning round, and normalized to 18 S rRNA expression. Results. Expression of ERα and ERβ was downregulated by 64% and 89%, respectively (P = 0.002 and P < 0.001). In contrast, PR was not significantly downregulated, due to a more heterogenous expression pattern. Conclusions. Culture of human endometrial stroma cells results in a downregulation of ERα and ERβ, while expression of PR remained unchanged in our patient collective. These results support the hypothesis that stem cells may not be subject to direct stimulation by sex steroids, but rather by paracrine mechanisms within the stem cell niche.
TheScientificWorldJOURNAL 01/2011; 11:1762-9. · 1.66 Impact Factor
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M Götte,
C Mohr,
C-Y Koo,
C Stock,
A-K Vaske,
M Viola,
S A Ibrahim,
S Peddibhotla,
Y H-F Teng,
J-Y Low,
K Ebnet, L Kiesel,
G W Yip
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ABSTRACT: Micro RNAs are small non-coding RNAs, which regulate fundamental cellular and developmental processes at the transcriptional and translational level. In breast cancer, miR-145 expression is downregulated compared with healthy control tissue. As several predicted targets of miR-145 potentially regulate cell motility, we aimed at investigating a potential role for miR-145 in breast cancer cell motility and invasiveness. Assisted by Affymetrix array technology, we demonstrate that overexpression of miR-145 in MDA-MB-231, MCF-7, MDA-MB-468 and SK-BR-3 breast cancer cells and in Ishikawa endometrial carcinoma cells leads to a downregulation of the cell-cell adhesion protein JAM-A and of the actin bundling protein fascin. Moreover, podocalyxin and Serpin E1 mRNA levels were downregulated, and gamma-actin, transgelin and MYL9 were upregulated upon miR-145 overexpression. These miR-145-dependent expression changes drastically decreased cancer cell motility, as revealed by time-lapse video microscopy, scratch wound closure assays and matrigel invasion assays. Immunofluorescence microscopy demonstrated restructuring of the actin cytoskeleton and a change in cell morphology by miR-145 overexpression, resulting in a more cortical actin distribution, and reduced actin stress fiber and filopodia formation. Nuclear rotation was observed in 10% of the pre-miR-145 transfected MDA-MB-231 cells, accompanied by a reduction of perinuclear actin. Luciferase activation assays confirmed direct miR-145-dependent regulation of the 3'UTR of JAM-A, whereas siRNA-mediated knockdown of JAM-A expression resulted in decreased motility and invasiveness of MDA-MB-231 and MCF-7 breast cancer cells. Our data identify JAM-A and fascin as novel targets of miR-145, firmly establishing a role for miR-145 in modulating breast cancer cell motility. Our data provide a rationale for future miR-145-targeted approaches of antimetastatic cancer therapy.
Oncogene 12/2010; 29(50):6569-80. · 6.37 Impact Factor
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RöFo - Fortschritte auf dem Gebiet der R 11/2010; 182(11):1016; author reply 1016-7. · 2.76 Impact Factor
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Ultrasound in Obstetrics and Gynecology 10/2010; 36(S1):4-5. · 3.01 Impact Factor
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Ultrasound in Obstetrics and Gynecology 10/2010; 36(S1):5. · 3.01 Impact Factor
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Ultrasound in Obstetrics and Gynecology 10/2010; 36(S1):76. · 3.01 Impact Factor
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Ultrasound in Obstetrics and Gynecology 10/2010; 36(S1):74. · 3.01 Impact Factor
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Ultrasound in Obstetrics and Gynecology 10/2009; 34(S1):190. · 3.01 Impact Factor
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Ultrasound in Obstetrics and Gynecology 10/2009; 34(S1):74. · 3.01 Impact Factor
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Ultrasound in Obstetrics and Gynecology 10/2009; 34(S1):10. · 3.01 Impact Factor
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Ultrasound in Obstetrics and Gynecology 10/2009; 34(S1):192. · 3.01 Impact Factor
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Ultraschall in der Medizin 07/2009; 30(3):223-6. · 2.40 Impact Factor
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ABSTRACT: Adult stem cells are thought to be responsible for the high regenerative capacity of the human endometrium, and have been implicated in the pathology of endometriosis and endometrial carcinoma. The RNA-binding protein Musashi-1 is associated with maintenance and asymmetric cell division of neural and epithelial progenitor cells. We investigated expression and localization of Musashi-1 in endometrial, endometriotic and endometrial carcinoma tissue specimens of 46 patients. qPCR revealed significantly increased Musashi-1 mRNA expression in the endometrium compared to the myometrium. Musashi-1 protein expression presented as nuclear or cytoplasmic immunohistochemical staining of single cells in endometrial glands, and of single cells and cell groups in the endometrial stroma. Immunofluorescence microscopy revealed colocalization of Musashi-1 with its molecular target Notch-1 and telomerase. In proliferative endometrium, the proportion of Musashi-1-positive cells in the basalis layer was significantly increased 1.5-fold in the stroma, and three-fold in endometrial glands compared to the functionalis. The number of Musashi-1 expressing cell groups was significantly increased (four-fold) in proliferative compared to secretory endometrium. Musashi-1 expressing stromal cell and cell group numbers were significantly increased (five-fold) in both endometriotic and endometrial carcinoma tissue compared to secretory endometrium. A weak to moderate, diffuse cytoplasmic glandular staining was observed in 50% of the endometriosis cases and in 75% of the endometrioid carcinomas compared to complete absence in normal endometrial samples. Our results emphasize the role of Musashi-1-expressing endometrial progenitor cells in proliferating endometrium, endometriosis and endometrioid uterine carcinoma, and support the concept of a stem cell origin of endometriosis and endometrial carcinoma.
The Journal of Pathology 08/2008; 215(3):317-29. · 6.32 Impact Factor
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ABSTRACT: To assess the accuracy of categorization of breast ultrasound findings based on scoring for malignancy using the sonographic breast imaging-reporting and data system (BI-RADS).
Breast ultrasound was performed in 2462 patients between 2001 and 2004 at our unit. Sonographic findings were scored using analog criteria as in BI-RADS for breast ultrasound (mass shape, margin, orientation, posterior acoustic features, lesion boundary, echo pattern). Each lesion was described using these features and classified into categories 1 to 5 according to the BI-RADS for breast ultrasound. Categorization and biopsy results were compared.
In twenty-two (0.9%) patients breast ultrasound could not be evaluated because of extreme density of tissue. Normal breast ultrasound belonging to Category 1 was found in 871 (35.4%) patients. Simple cysts classified as Category 2 were observed in 712 (28.9%) women. In 491 (19.9%) patients, apparently benign solid masses (Category 3) were found. Suspicious masses were observed in 225 (9.1%) women and masses highly suggestive of malignancy were found in 141 (5.7%) patients (Categories 4 and 5, respectively). Histological examinations were available from 84 (17.1%) masses that had been classified by BI-RADS as Category 3, in 97 (43.1%) from Category 4 and 106 (75.2%) from Category 5. Accordingly, the rate of malignant findings was 1.2% (n = 1) in Category 3, 17% (n = 16) in Category 4 and 94% (n = 100) in Category 5.
Scoring breast ultrasound findings for malignancy based on criteria used for BI-RADS breast ultrasound has a high accuracy, comparable to that obtained by BI-RADS for mammography.
Ultrasound in Obstetrics and Gynecology 04/2008; 32(4):573-8. · 3.01 Impact Factor
