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Isachenko V.,Universitatsfrauenklinik Cologne | Isachenko E.,Universitatsfrauenklinik Cologne | Keck G.,Universitatsfrauenklinik Dresden | Dittrich R.,Friedrich - Alexander - University, Erlangen - Nuremberg | And 7 more authors.
Clinical Laboratory | Year: 2012

Background: The problem of post-cancer infertility is of significant concern. The cryopreservation of ovarian tissue before cancer therapy with retransplantation after convalescence is the key to solving this problem. Methods: Cryopreservation of ovarian tissue was performed in 2005 after surgical operation, post-operative low-temperature 22 hour transportation, and freezing using a special, original design block constructed for the initiation of ice formation (ice-seeding). We present the construction and function of this block. Results: In 2011, it was noted that a baby was born after thawing and re-transplantation of ovarian tissue. The technical and biological aspects of initiated crystals formation in the process of cryopreservation are emphasised and discussed. Conclusions: The first live birth in Germany after re-transplantation of cryopreserved ovarian tissue was noted. This cryopreservation was performed using the protocol described here. Block for auto-seeding of principally new construction recommended.


Isachenko V.,Universitatsfrauenklinik Cologne | Dittrich R.,Frauenklinik des Universitatsklinikums Erlangen | Keck G.,Universitatsfrauenklinik Dresden | Isachenko E.,Universitatsfrauenklinik Cologne | And 8 more authors.
Geburtshilfe und Frauenheilkunde | Year: 2012

Purpose: In many cases cancer therapy leads to an irreversible reduction or even loss of ovarian reserve. Cryopreservation of ovarian tissue with subsequent thawing and re-transplantation of tissue after the cancer is in remission constitutes a promising method to preserve fertility in women. To date, more than 25 cases of live births after re-transplantation of cryopreserved ovarian tissue have been published worldwide. In Germany the first live birth after re-transplantation of cryopreserved tissue was in 2011. Material and Methods: After surgical removal of ovarian tissue in the Gynaecological Clinic of Dresden University, the tissue was sent to the Gynaecological Clinic of Bonn University in a special transport container at 5°C and was frozen the next day using 1.5M dimethyl sulfoxide cryosolution. In 2010 this ovarian tissue was thawed using a sucrose solution in the Gynaecological Clinic of Erlangen University Clinical Centre and was laparoscopically re-transplanted into the patient. Results: The patient became pregnant, the pregnancy was uneventful, and she gave birth to a healthy boy. Conclusion: Freezing of ovarian tissue with subsequent re-transplantation as described here is a viable method to preserve fertility in cancer patients. © Georg Thieme Verlag KG Stuttgart · New York.


Breidenbach M.,Universitatsfrauenklinik Aachen | Schmidt T.,Universitatsfrauenklinik Cologne | Volkmer A.,Universitatsfrauenklinik Dusseldorf | Rath W.,Universitatsfrauenklinik Aachen | And 6 more authors.
Geburtshilfe und Frauenheilkunde | Year: 2011

Purpose: Endometriosis is a common gynecological disease associated with pain and infertility. Endoscopic surgery with removal of endometriotic lesions is regarded as the best therapeutic option. However, in patients with deep infiltrating endometriosis and/or recurrent disease, effective non-operative treatment alternatives are lacking. Thus, a specific targeted therapy would be a useful approach for a systemic therapy of endometriosis. This study aimed to evaluate potential molecular targets for a targeted therapy of endometriosis. Material and Methods: Immunostaining and gene expression analysis was performed to evaluate the expression of VEGF, Midkine, angiopoietin- 2 and heparanase in eutopic endometrium, endometriotic lesions and normal peritoneum. The expression levels of VEGF and heparanase were evaluated in superficial endometriotic lesions and deep infiltrating endometriosis. A VEGF-targeted recombinant adenovirus (Ad5VEGFE1) was evaluated with regard to viral replication in endometriosis cells and induction of apoptosis. The biodistribution of the VEGF-targeted conditionally replicative adenovirus (CRAd) was examined in a mouse model. Results: VEGF and heparanase show specific expression in ectopic endometrium compared to eutopic endometrium and normal peritoneum. In addition, the corresponding promoters of both genes are active in endometriotic cells. A correlation between the promoter activity and the clinical stage of disease could only be demonstrated for the VEGF promoter. The recombinant conditionally replicative adenovirus Ad5VEGFE1 showed efficient induction of apoptosis in purified primary endometriotic cells in vitro and demonstrated comparable lower targeting to the liver and uterus in a mouse model. Conclusions: Ad5VEGFE1 is a promising candidate to treat endometriosis and exhibits potential for clinical testing. © Georg Thieme Verlag KG.


Isachenko V.,Universitatsfrauenklinik Ulm | Isachenko V.,Universitatsfrauenklinik Cologne | Nawroth F.,Zentrum fur Endokrinologie | Rahimi G.,Universitatsfrauenklinik Cologne | And 9 more authors.
Geburtshilfe und Frauenheilkunde | Year: 2011

Purpose: Previously there were only two effective ways to determine the quality of cryopreservation procedures for ovarian tissue after thawing: xenotransplantation and in vitro culture in a big volume of medium with permanent mechanical agitation. The Belgian group of J. Donnez has shown that the chorioallantoic membrane (CAM) culture system offers a new approach to study human ovarian tissue transplantation in its first ischemic stages, yielding information on the timing of tissue changes before neovascularization is established. The aim of this study was to compare the effectiveness after thawing of human ovarian tissue cultured in vitro in a big volume of medium with agitation with a CAM culture system. Material and Methods: Ovarian tissue fragments from 5 patients were transported within 20min at 3234°C to the laboratory. The fragments were divided into smaller pieces (12×0.71mm), frozen, thawed and randomly divided into the following two groups: Group 1: tissue cultured in vitro for 7 days in a big volume of medium with mechanical agitation; Group 2: tissue cultured in a CAM system for 5 days. The viability of the tissue from the respective method of cultivation was evaluated by immunohistochemistry (cytokeratin and Ki-67) and assessed according to the development of follicles and follicular cell proliferation. Results: 85 and 87% of the follicles were morphologically normal in group 1 and group 2, respectively. Immunohistochemical analysis showed that the proliferative characteristics of follicular cells after culture in the CAM system were significantly increased. Conclusion: Both the CAM system and in vitro culturing in a big volume of medium with permanent mechanical agitation are suitable for culturing human ovarian tissue. However, the CAM system provides more information. © Georg Thieme Verlag KG Stuttgart - New York.


Gottschalk I.,Universitatsfrauenklinik Cologne | Berg C.,Universitatsfrauenklinik Cologne | Berg C.,Universitatsklinikum Bonn | Geipel A.,Universitatsklinikum Bonn | Strizek B.,Universitatsklinikum Bonn
Gynakologe | Year: 2016

This article presents the spectrum of congenital intrathoracic and intra-abdominal malformations. In addition to a summary of epidemiological associations, prenatal observations of sonographic morphological and echocardiographic characteristics, pathogenetic hypotheses and consideration of possible associated syndromes or anomalies and comorbidities, prenatal and postnatal therapy options are also discussed. © 2016, Springer-Verlag Berlin Heidelberg.


Gnoth C.,Kinderwunschzentrum Grevenbroich Green ivf | Gnoth C.,Universitatsfrauenklinik Cologne
Gynakologische Endokrinologie | Year: 2011

Anti-Mullerian hormone (AMH) is a sensitive marker for assessing the ovarian reserve and an important factor for estimating the individual reproductive potential. By comparing individual AMH levels with values in percentile normograms information about the biological clock can be obtained which might have been put back or forward. By this means AMH measurements can be used to support clinical decisions regarding the wish to have children especially in women over 30 years old and especially in women over 35 years. © 2011 Springer-Verlag.


Isachenko V.,Universitatsfrauenklinik Ulm | Isachenko V.,Universitatsfrauenklinik Cologne | Isachenko E.,Universitatsfrauenklinik Cologne | Rahimi G.,Universitatsfrauenklinik Cologne | And 5 more authors.
Gynakologische Endokrinologie | Year: 2012

Until recently there were only two possibilities with which to assess the effectiveness of cryopreservation protocols for ovarian tissue after thawing: xenotransplantation and in vitro culture in a large volume of medium under permanent mechanical mixing. The chorioallantoic membrane (CAM) culture system, which was investigated by a Belgian research group of J. Donnez, is suitable for culturing ovarian tissue in the first phase prior to neovascularisation. Therefore, it can be assumed that this method is an effective procedure for cultivation of cryopreserved human ovarian tissue (CAM system). The aim of this study was to assess the effectiveness of the procedure. © 2012 Springer-Verlag.


Gnoth C.,Green ivf | Gnoth C.,Universitatsfrauenklinik Cologne
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz | Year: 2013

Background: In the last 40 years, fertility rates in Western societies have been declining as a result of lifestyle and generative behavior. Aim: This review summarizes current evidence-based knowledge on natural infertility and epidemiological aspects of subfertility. Methods: A literature search on natural infertility and epidemiological aspects of subfertility was performed and the available data were structured and put in context. Results: After six unsuccessful cycles, slight or potentially severe subfertility should be assumed. Female age, number of unsuccessful cycles, ovarian reserve, and the results of sperm analysis determine the reproductive potential of a subfertile couple. An early measurement of anti-müllerian hormone levels and a sperm analysis are recommended. Conclusions: Fertility awareness has gained increasing importance, not only in contraceptive use but also in optimizing individual fertility. © 2013 Springer-Verlag Berlin Heidelberg.

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