O Ortmann

University Hospital Regensburg, Ratisbon, Bavaria, Germany

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Publications (338)617.27 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Susceptibility to ovarian cancer might be affected by genetic variations in genes involved in estrogen biosynthesis, metabolism or signal transduction. In this study we tested the hypothesis that single nucleotide polymorphisms (SNPs) in the promoter of human ESR2 gene, coding for estrogen receptor β, may be associated with increased risk for ovarian cancer. Three SNPs in the promoter region of human ESR2 gene were genotyped by means of allele-specific tetra-primer PCR. A total of 184 ovarian cancer cases and the same numbers of controls were included in the study. With regard to homozygous analysis, the AA genotype of SNP rs3020449 was found to be significantly more frequent in ovarian cancer cases staged as FIGO III+IV than in cases staged as I+II (OR 2.717, p=0.027). With regard to allele frequency, the G allele of this SNP was less frequent in FIGO I+II cases than in cases with higher FIGO stages (OR 1.739, p=0.018). With regard to genotype frequency, allele frequency, allele positivity or haplotype frequency of SNPs rs2987983, rs3020449 and rs3020450 we did not observe a significant difference between the cancer and the control group. Our data suggest that SNPs in the promoter region of ESR2 gene do not affect susceptibility to ovarian cancer, but SNP rs3020449 might affect progression of this disease.
    Gene 05/2014; · 2.20 Impact Factor
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    ABSTRACT: Humanized tumor mice (HTM) were generated by the co-transplantation of human hematopoietic stem cells and human breast cancer cells overexpressing HER2 into neonatal NOD-scid IL2Rγ(null) (NSG) mice. These mice are characterized by the development of a human immune system in combination with human breast cancer growth. Due to concurrent transplantation into newborn mice, transfer of MHC-mismatched tumor cells resulted in solid coexistence and immune cell activation (CD4(+) T cells, natural killer cells, and myeloid cells), but without evidence for rejection. Histological staining of the spleen of HTM revealed co-localization of human antigen-presenting cells together with human T and B cells allowing MHC-dependent interaction, and thereby the generation of T cell-dependent antibody production. Here, we investigated the capability of these mice to generate human tumor-specific antibodies and correlated immunoglobulin titers with tumor outgrowth. We found detectable IgM and also IgG amounts in the serum of HTM, which apparently controlled tumor development when IgG serum concentrations were above 10 µg/ml. Western blot analyses revealed that the tumor-specific antibodies generated in HTM did not recognize HER2/neu antigens, but different, possibly relevant antigens for breast cancer therapy. In conclusion, HTM offer a novel approach to generate complete human monoclonal antibodies that do not require further genetic manipulation (e. g., humanization) for a potential application in humans. In addition, efficacy and safety of the generated antibodies can be tested in the same mouse model under human-like conditions. This might be of particular interest for cancer subtypes with no currently available antibody therapy.
    mAbs 05/2014; 6(4). · 5.28 Impact Factor
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    ABSTRACT: Phase I pharmacokinetic (PK) study assessed circulating estrogens in breast cancer (BC) patients on a non-steroidal aromatase inhibitor (NSAI) with vaginal atrophy using vaginal ultra-low-dose 0.03 mg estriol (E3) and Lactobacillus combination vaginal tablets (Gynoflor(®)). 16 women on NSAI with severe vaginal atrophy applied a daily vaginal tablet of Gynoflor(®) for 28 days followed by a maintenance therapy of 3 tablets weekly for 8 weeks. Primary outcomes were serum concentrations and PK of E3, estradiol (E2), and estrone (E1) using highly sensitive gas chromatography-mass spectrometry. Secondary outcomes were clinical measures for efficacy and side effects; microscopic changes in vaginal epithelium and microflora; and changes in serum FSH, LH, and sex hormone-binding globulin. Compared with baseline, serum E1 and E2 did not increase in any of the women at any time following vaginal application. Serum E3 transiently increased after the first application in 15 of 16 women, with a maximum of 168 pg/ml 2-3 h post-insertion. After 4 weeks, serum E3 was slightly increased in 8 women with a maximum of 44 pg/ml. The vaginal atrophy resolved or improved in all women. The product was well tolerated, and discontinuation of therapy was not observed. The low-dose 0.03 mg E3 and Lactobacillus acidophilus vaginal tablets application in postmenopausal BC patients during AI treatment suffering from vaginal atrophy lead to small and transient increases in serum E3, but not E1 or E2, and therefore can be considered as safe and efficacious for treatment of atrophic vaginitis in BC patients taking NSAIs.
    Breast Cancer Research and Treatment 04/2014; · 4.47 Impact Factor
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    ABSTRACT: Objective Local application of estradiol (E2) to treat vulvovaginal atrophy in postmenopausal breast cancer patients receiving aromatase inhibitors is known to elevate serum estradiol levels and thereby might counteract breast cancer therapy. Thus, vaginal application of estriol (E3) has been recommended for these patients. However, it is unclear to what extent E3 stimulates breast cancer cell growth. In this study, we examined the effect of E3 on growth and gene expression of two human breast cancer cell lines. Methods We used an established in vitro cell culture assay and compared the effect of E2 and E3 on growth of the estrogen receptor alpha-positive breast cancer cell lines MCF-7 and T-47D testing a wide range of hormone concentrations of 10−12 to 10−7 M. E3 effects on gene expression were examined by means of reporter gene assays, RT-qPCR and Western blot analysis. Results E3 acted as a potent estrogen and exerted a mitogenic effect on T-47D and MCF-7 cells at concentrations of 10−9 M (288 pg/ml) and higher. With regard to activation of an estrogen response element (ERE) in breast cancer cells, effects of E3 were visible at 10−10 M. The same concentrations of E3 activated expression of the estrogen-responsive gene PR and of the proliferation genes cyclin A2, cyclin B1, Ki-67, c-myc and b-myb, providing molecular mechanisms underlying the observed growth increase. Conclusions Like E2, low levels of E3 were able to trigger a robust estrogenic response in breast cancer cells. Thus, our data suggest caution regarding use of E3 by breast cancer survivors.
    Maturitas 01/2014; · 2.84 Impact Factor
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    ABSTRACT: Even though randomized controlled clinical trials demonstrated improved survival by adjuvant trastuzumab treatment of HER2-positive breast cancer patients, data on its effect in clinical routine are scarce. This study evaluated the use and efficacy of trastuzumab in routine treatment of HER2-positive breast cancer patients. Data from the clinical cancer registry Regensburg (Germany) were analyzed. The present study investigated 6,991 female patients with primary invasive breast cancer. In premenopausal HER2-positive patients a considerable increase of trastuzumab therapy was observed from 58.1% in 2006 to 90.9% in 2011, whereas in postmenopausal patients trastuzumab was rather used on a constant rate of 49.1%. Best overall survival (OS) was found in HER2/steroid hormone receptor-positive patients receiving guideline concordant treatment with trastuzumab plus chemotherapy (CHT) plus antihormone therapy (AHT) with a 7-year OS rate of 96% compared to the non-trastuzumab group with a 7-year OS rate of 92%. In multivariable analysis, HER2-positive patients treated with CHT or AHT who did not get trastuzumab, had a worse 7-year OS (65%, P = 0.006 versus 79%, P = 0.017) than the control groups. This population-based study demonstrated that guideline concordant use of adjuvant trastuzumab improves OS for HER2-positive breast cancer patients treated in routine clinical care.
    BioMed research international. 01/2014; 2014:137304.
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    ABSTRACT: In this study, we tested the hypothesis that single nucleotide polymorphisms (SNPs) of differentiation-associated human gene icb-1 (C1orf38) may be associated with ovarian cancer susceptibility. For this purpose, we compared the genotype and allele frequencies of the SNPs rs1467465 and rs12048235 in a group of 184 ovarian cancer patients with a control group of 184 age- and gender-matched women without any malignancy. Genotype-phenotype association revealed that A allele of SNP rs1467465 was more frequent in ovarian cancer patients than in the control group (0.40 vs. 0.33, OR 1.37, 95% CI 1.013-1.853, p = 0.04). After analysis of allele positivity we observed that A-positive genotypes were more frequent in the ovarian cancer group (0.65 vs. 0.53, OR 1.63, 95% CI 1.072-2.483, p = 0.02). Furthermore, the heterozygous genotype of rs1467465 was found to be more frequent in the patients group (0.50 vs. 0.41, OR 1.63, 95% CI 1.045-2.045, p = 0.03). No significant results were obtained with regard to SNP rs1204823. Our data suggest, that SNP rs1467465 of human gene icb-1 might affect susceptibility to ovarian cancer.
    Journal of Ovarian Research 01/2014; 7:42. · 2.43 Impact Factor
  • A. Ignatov, C. Lattrich, O. Ortmann
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    ABSTRACT: Uterusmyome sind gutartige, hormonsensitive Tumoren. Sie sind die häufigsten pelvinen Tumoren der Frau und in der Regel asymptomatisch. Die wichtigsten Symptome bei einem Uterus myomatosus sind Blutungsstörungen, Drucksymptomatik und reproduktive Dysfunktion. Sie treten meist bei prämenopausalen Frauen auf. Nach der Menopause beobachtet man bei den meisten Frauen eine Schrumpfung der Myome. Nur Frauen mit symptomatischen Myomen sollten behandelt werden. Interventionen sollten in Abhängigkeit des Patientinnenalters, des Kinderwunsches, Lage bzw. Größe der Myome und symptomorientiert durchgeführt werden. Am häufigsten eingesetzt werden orale Kontrazeptiva, Levonorgestrel-haltige intrauterine Spiralen, Gonadotropin-releasing-Hormon-Agonisten und Progesteronrezeptormodulatoren. Es ist zu beachten, dass zwei Drittel aller konservativ Behandelten innerhalb von 2 Jahren operiert werden.
    Der Gynäkologe 01/2014; 47(1).
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    W Janni, O. Ortmann
    Der Gynäkologe 01/2014;
  • J.B. Engel, O. Ortmann
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    ABSTRACT: Uterusmyome können ein Konzeptionshindernis darstellen und auch in einer bestehenden Schwangerschaft zu Komplikationen führen. Die Arbeit gibt eine Übersicht des aktuellen Kenntnisstandes zu Ätiologie und Therapiemöglichkeiten. Das Evidenzniveau, auf dessen Basis Therapieempfehlungen gegeben werden können, ist aufgrund der unzureichenden Datenlage niedrig. Patientinnen mit unerfülltem Kinderwunsch und submukösen oder intramural/submukösen Myomen scheinen von einer Myomenukleation hinsichtlich der Schwangerschaftsrate zu profitieren. Allerdings sollte diese erst nach Durchführung einer generellen Sterilitätsdiagnostik des Paares erfolgen. Offene und laparoskopische Myomenukleationen scheinen hinsichtlich der Schwangerschaftsrate gleichwertige Verfahren darzustellen. Ein laparoskopisches Vorgehen ist mit weniger perioperativem Blutverlust und Schmerzen sowie schnellerer Rekonvaleszenz assoziiert. Ob sich eine Patientin mit Kinderwunsch, jedoch ohne Sterilitätsanamnese und bekanntem Uterusmyom vor Anstreben der Schwangerschaft einer operativen Therapie unterziehen sollte oder nicht ist unklar. Aufgrund der insgesamt unzureichenden Datenlage scheint sowohl nach hysteroskopischer Myomenukleation als auch nach offener oder laparoskopischer Myomentfernung unter entsprechender Überwachung ein vaginaler Entbindungsversuch möglich.
    Der Gynäkologe 01/2014; 47(1).
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    O Ortmann
    Archives of Gynecology 11/2013; · 0.91 Impact Factor
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    ABSTRACT: On account of the good prognosis for patients with breast cancer, improving or maintaining the quality of life in the aftercare period is becoming more and more important. In particular, the increasing usage of aromatase inhibitors in the past few years has led to an increased incidence of vaginal atrophy with symptoms such as vaginal dryness, petechial bleeding, dyspareunia and recurrent cystitis. And just these symptoms have a detrimental impact on the quality of life of breast cancer patients. Application of a topical estrogen therapy represents the most effective means to treat vaginal atrophy. The use of a systemic or, respectively, topical hormone therapy is, however, contraindicated for breast cancer patients. Further clinical trials are needed in order to assess the safety of vaginal estrogen therapy.
    Geburtshilfe und Frauenheilkunde 10/2013; 73(10):1017-1022. · 0.85 Impact Factor
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    ABSTRACT: Purpose: The aim of this study was to investigate the value of intraoperative ultrasound in breast-conserving operations and to compare it with standard procedures. Methods: For this purpose 307 women with palpable breast cancers and 116 patients with non-palpable breast cancers were compared retrospectively. In the group with palpable breast cancers 177 patients were treated by US-guided operations and 130 patients underwent palpation-guided breast-conserving operations. As primary outcomes, the resection margins and the rate of re-operations were evaluated. Results: With regard to disease-free resection margins, intraoperative ultrasound was significantly superior to palpation alone. In the group of patients in whom the tumours were extirpated with the help of palpation, R1 resections were observed almost twice as often (16.9 %) as in the US-guided group (8.5 %). In the group with non-palpable breast cancers, intraoperative ultrasound was employed in 61 patients. As a control, 43 cases were evaluated in whom the breast-conserving operation was performed after wire marking. In this group US-guided tumour removal proved to be superior to that after wire marking for tumours that did not exhibit any intraductal components. Otherwise the redo resection rate was reduced by use of ultrasound. Furthermore, the surgeon was able by means of intraoperative ultrasound to identify "problematic" margins and to excise them in the same sitting. Conclusions: The US-guided, breast-conserving operations led to a lower rate of R1 resections and redo operations in comparison to operations with palpation alone or those after wire marking.
    Geburtshilfe und Frauenheilkunde 10/2013; 73(10):1028-1034. · 0.85 Impact Factor
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    ABSTRACT: Not only four but rather seven different human epidermal growth factor receptor related (Her) receptor tyrosine kinases (RTKs) have been described to be expressed in a variety of normal and neoplastic tissues: Her1, Her2, Her3, and additionally four Her4 isoforms have been identified. A differential expression of Her4 isoforms does not, however, play any role in either the molecular diagnostics or treatment decision for breast cancer patients. The prognostic and predictive impact of Her4 expression in breast cancer is basically unclear. We quantified the Her4 variants JM-a/CYT1, JM-a/CYT2, JM-b/CYT1, and JM-b/CYT2 by isoform-specific polymerase chain reaction (qPCR) in (i) triple-negative, (ii) Her2 positive breast cancer tissues and (iii) in benign breast tissues. In all three tissue collectives we never found the JM-b/CYT1 or the JM-b/CYT2 isoform expressed. In contrast, the two JM-a/CYT1 and JM-a/CYT2 isoforms were always simultaneously expressed but at different ratios. We identified a positive prognostic impact on overall survival (OS) in triple-negative and event-free survival (EFS) in Her2 positive patients. This finding is independent of the absolute JM-a/CYT1 to JM-a/CYT2 expression ratio. In Her2 positive patients, Her4 expression only has a favorable effect in estrogen-receptor (ER)-positive but not in ER-negative individuals. In summary, JM-a/CYT1 and JM-a/CYT2 but not JM-b isoforms of the Her4 receptor are simultaneously expressed in both triple-negative and Her2 positive breast cancer tissues. Although different expression ratios of the two JM-a isoforms did not reveal any additional information, Her4 expression basically indicates a prolonged EFS and OFS. An extended expression analysis that takes all Her receptor homologs, including the Her4 isoforms, into account might render more precisely the molecular diagnostics required for the development of optimized targeted therapies.
    BMC Cancer 09/2013; 13(1):437. · 3.33 Impact Factor
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    ABSTRACT: Abstract SCUBE2 (Signal peptide-CUB-epidermal growth factor-like domain-containing 2) gene codes for a cell-surface glycoprotein. In breast cancer, SCUBE2 transcript levels are part of important prognostic and predictive gene signatures and are linked to expression of estrogen receptor α (ERα). To elucidate the role of this gene in endometrial cancer, we compared SCUBE2 expression in malignant and normal endometrial tissue specimens. We then examined its correlation with steroid hormone receptors and PTEN and compared it to SCUBE2 expression in breast cancer samples. Expression of SCUBE2 was found to be decreased in G3 endometrial cancer when compared to postmenopausal endometrium or to G1 tumors (p < 0.05). In postmenopausal endometrium, SCUBE2 transcript levels were more than twice as high as in premenopausal women. In breast cancer, SCUBE2 expression was found to be notably reduced particularly in ERα-negative G3 tumors. Both in endometrial and breast cancer we observed a significant positive correlation of SCUBE2 transcript levels with expression of ERα, PR and PTEN. Our data suggest that SCUBE2, like in breast cancer, associates with ERα and might have a potential as prognostic or predictive marker in endometrial cancer.
    Gynecological Endocrinology 09/2013; · 1.30 Impact Factor
  • Geburtshilfe und Frauenheilkunde 09/2013; 73(9):874-889. · 0.85 Impact Factor
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    ABSTRACT: The development of endometrial cancer is known to be affected by estrogens. Thus, genetic variations like single nucleotide polymorphisms (SNPs) in genes involved in estrogen biosynthesis, metabolism, and signal transduction might affect risk for endometrial cancer. In this study, we tested the hypothesis that polymorphisms in the promoter of ESR2 gene may be associated with susceptibility to this disease. We compared the frequency of three SNPs in the promoter region of ESR2 gene (rs2987983, rs3020450, and rs3020449) in 135 women with endometrial cancer and 135 healthy women serving as controls by means of allele-specific tetra-primer PCR. Regarding allele frequency, allele positivity or genotype frequencies of these SNPs we did not observe any significant difference between healthy women and women with endometrial cancer. Our data clearly suggest that the tested SNPs in the promotor region of human ESR2 gene are not associated with the development of endometrial cancer.
    Archives of Gynecology 08/2013; · 0.91 Impact Factor
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    ABSTRACT: The G protein-coupled estrogen receptor (GPER, GPR30) is suggested to be involved in non-nuclear estrogen signaling and is expressed in a variety of hormone dependent cancer entities. This study was performed to further elucidate the role of this receptor in endometrial adenocarcinoma. We first analyzed GPER expression at the mRNA level in 88 endometrial cancer or normal endometrial tissue samples and compared it to those of nuclear steroid hormone receptors. GPER transcript levels were found to be about 6-fold reduced, but still present in endometrial cancer. Expression of this receptor was decreased in all grading subgroups when compared to pre- or postmenopausal endometrium. GPER mRNA expression was associated with PR mRNA levels (Spearmańs rho 0.4610, p<0.001). We then tested the effect of the GPER ligand G-1 on growth of three endometrial cancer cell lines with different GPER expression. GPER protein levels were highest in RL95-2 cells, moderate in HEC-1A cells and not detectable in HEC-1B cells. The moderate expression level in HEC-1A cells was similar to average tumor tissue expression. Treatment with G-1 significantly inhibited growth of the GPER-positive cell lines RL95-2 and HEC-1A in a dose-dependent manner, whereas the GPER-negative line HEC-1B was not affected. Though GPER transcript levels were found to be reduced in endometrial cancer, our in vitro data suggest that moderate GPER expression might be sufficient to mediate growth-inhibitory effects triggered by its agonist G-1.
    Steroids 08/2013; · 2.80 Impact Factor
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    ABSTRACT: Coexpression of estrogen receptors (ER) α and β is present in about half of all breast cancer cases. Whereas ERα is a well-established target for endocrine therapy with the selective estrogen receptor modulator tamoxifen, the applicability of ERβ as target in breast cancer therapy is unclear. In this study, we examined the effects of two synthetic ERβ agonists alone and in combination with tamoxifen on ERα/β-positive breast cancer cells. We treated MCF-7 and T-47D breast cancer cells with the ERβ agonists ERB-041 and WAY-200070 and measured the effects on cell growth. In addition, transcriptome analyses were performed by means of Affymetrix GeneChip arrays. When given alone, ERβ agonists ERB-041 and WAY-200070 did not affect the growth of MCF-7 or T-47D cells. In contrast, addition of these drugs to tamoxifen increased its growth-inhibitory effect on both cell lines. This effect was more pronounced under serum-free conditions, but was also observed in the presence of serum in T-47D cells. Transcriptome analyses revealed a set of genes regulated after addition of ERβ agonists including S100A8 and CD177. The observed enhanced growth-inhibitory effects of a combination of tamoxifen and ERβ agonists in vitro encourage further studies to test its possible use in the clinical setting.
    Archives of Gynecology 08/2013; · 0.91 Impact Factor
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    ABSTRACT: It is known that the new membrane-bound estrogen receptor GPER-1 acts suppressive in breast cancer cells and its expression decreases during disease progression. This study was conducted to evaluate the GPER-1 expression in ovarian cancer and its correlation with progression. Its function was tested in vitro in ovarian cancer cells.Patients and methods: GPER-1 expression was analyzed by immunohistochemistry in 35 benign ovarian tumors, 35 tumors of low-malignant potential and in 124 ovarian cancers. GPER-1 expression was correlated to the prospectively evaluated disease-free survival of ovarian cancer patients. We also tested GPER-1 expression in ovarian cancer cells and the effect of GPER-1 stimulation on cell growth. GPER-1 expression was significantly lower in ovarian cancer tissue than in benign and low-malignant ovarian tumors. GPER-1 expression was observed in 83.1% of malignant tumors and was higher in early stage cancers and tumors with high histological differentiation. GPER-1 expression was associated with favourable clinical outcome. The difference in 2-year disease-free survival by GPER-1 expression was significant, 28.6% for GPER-1 negative and 59.2% for GPER-1 positive cases (p = 0.002). GPER-1 expression was observed in SKOV-3 and OVCAR-3 ovarian cancer cell lines. G-1, a selective GPER-1 agonist, suppressed proliferation of the two cell types via inhibition of cell cycle progression in G2/M phase and stimulation of caspase-dependent apoptosis. The blockade in G2/M phase was associated with increased expression of cyclin B1 and Cdc2 and phosphorylation of histone 3. GPER-1 emerges as a new tumor suppressor with unsuspected therapeutic potential for ovarian cancer.
    Journal of Ovarian Research 07/2013; 6(1):51. · 2.43 Impact Factor
  • The Lancet 06/2013; 381(9883):2078. · 39.06 Impact Factor

Publication Stats

3k Citations
617.27 Total Impact Points

Institutions

  • 2009–2014
    • University Hospital Regensburg
      Ratisbon, Bavaria, Germany
    • South Florida Veterans Affairs Foundation for Research and Education
      Miami, Florida, United States
  • 2005–2014
    • Caritas-Krankenhaus St. Josef
      Ratisbon, Bavaria, Germany
    • Sichuan University
      • Department of Obstetrics and Gynecology
      Chengdu, Sichuan Sheng, China
  • 2003–2014
    • Universität Regensburg
      • Department of Gynecology and Obstetrics
      Ratisbon, Bavaria, Germany
    • Universitätsklinikum Schleswig - Holstein
      • Klinik für Gynäkologie und Geburtshilfe (Kiel)
      Kiel, Schleswig-Holstein, Germany
  • 2013
    • Medical University of Lublin
      • Department of Gynecology
      Lyublin, Lublin Voivodeship, Poland
    • St. Joseph Krankenhaus
      Berlín, Berlin, Germany
  • 1985–2009
    • Universität zu Lübeck
      • • Department of Obstetrics and Gynecology
      • • Klinik für Frauenheilkunde und Geburtshilfe
      Lübeck, Schleswig-Holstein, Germany
  • 2004
    • University Medical Center Schleswig-Holstein
      • Department of Pediatrics
      Kiel, Schleswig-Holstein, Germany
  • 2000
    • Universitätsmedizin Göttingen
      • Department of Gynecology and Obstetrics
      Göttingen, Lower Saxony, Germany
    • Ankara University
      • Department of Obstetrics and Gynecology
      Ankara, Ankara, Turkey
  • 1991–1998
    • Philipps University of Marburg
      Marburg, Hesse, Germany
  • 1990
    • West Georgia Obstetrics and Gynecology
      Georgetown, Georgia, United States
  • 1988–1989
    • National Institute of Child Health and Human Development
      Maryland, United States