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Zollner U.,Universitats Frauenklinik Wurzburg | Bischofs S.,Evangelisches Krankenhaus Hamm | Lalic I.,Sapient In Vitro Pty Ltd. | Zollner K.-P.,Kinderwunschzentrum Amberg
Asian Pacific Journal of Reproduction | Year: 2012

Objective: There is strong evidence that the cytokines leucemia inhibitory factor (LIF) and tumor necrosis factor (TNF) alpha are related to embryo development and implantation. The aim of this study was to determine the levels of LIF and TNF alpha in embryo culture media and to assess its relationship to the outcome of in-vitro fertilization and embryo transfer. Methods: A total of 99 patients were included in this prospective trial and underwent either IVF or ICSI procedure. A total of 865 oocytes were collected. Embryos were cultured in sequential media until day 5. A standardized morphology evaluation of all embryos, including a detailed pronuclear scoring, was performed daily during this period followed by the replacement of one or two selected embryos. Collected embryo culture fluids of days 3 and 5 were analysed for LIF and TNF alpha on days 3 and 5. Results: Mean TNF alpha concentration in culture media on day 3 was 0.54 and 0.37 pg/mL on day 5 and was significantly lower in women conceiving than in not conceiving (0.43 pg/mL versus 0.59 pg/mL on day 3). Mean LIF concentration on day 3 was 31.5 pg/mL and 35.5 pg/mL on day 5 and was significantly higher in women conceiving (56.2 pg/mL versus 22.2 pg/mL on day 3). Conclusions: The results indicate that LIF could have a function in early embryogenesis and as a factor required for embryo implantation. High TNF alpha concentrations seem to be predictive of implantation failure. © 2012 Hainan Medical College.


Zollner U.,Universitats Frauenklinik Wurzburg | Rehn M.,Universitats Frauenklinik Wurzburg | Girschick G.,Praxis fur Pranatalmedizin | Dietl J.,Universitats Frauenklinik Wurzburg
Zeitschrift fur Geburtshilfe und Neonatologie | Year: 2012

Malformations of the central nervous system are among the most frequent congenital anomalies. At best, a qualified and standardised screening of the foetal brain is possible between the 18th and the 22nd week. The newly decided modification of the maternity directives envisages an extended screening upon request. This extended screening refers to the central nervous system and the representation of the ventricles, the evaluation of the head shape and the cerebellum and the back. The examination of the foetal brain should be carried out in a structured way. Three axial planes, the transventricular, the transthalamic and the transcerebellar planes, suffice to represent and measure all structures which are of importance for the screening. In case of ventricular anomalies, anomalies of the head shape, anomalies of the cerebellum and irregularities of the dorsal skin outlined in the second screening a further diagnostic procedure should be initiated. This diagnostic work-up should include a detailed neurosonography, a diagnostic evaluation of the organs and eventually further examination in the form of a caryotyping, determination of the infectology or a foetal MRI. The present article offers an overview of possible CNS abnormalities which could be recognised during the second screening according to the extended maternity directives and describes which differential diagnostics should be considered. In detail, anomalies of the head size (microcephaly, macrocephaly), of the head size (brachycephaly, dolichocephaly, cavities of the cranium, banana sign, etc.,), ventricular abnormalities, anomalies of the cerebellum (cerebellum hypoplasia, abnormal cerebellum shape) and abnormalities of the intermediate line and the intracerebral space requirements are discussed. © Georg Thieme Verlag KG Stuttgart · New York.


Zollner U.,Universitats Frauenklinik Wurzburg | Schwarz T.F.,Zentrallabor und Impfzentrum
Deutsche Medizinische Wochenschrift | Year: 2011

Human papilloma viruses are responsible for a large number of benign and malignant lesions of the skin. HPV 6 and 11 cause up to 90% of condylomata. Almost each cervical cancer is associated with HPV. HPV 16 und 18 induce up to 70% of cervical neoplasias. The vaccination against HPV is internationally implemented and should be applied to young girls aged 12 to 17 according to STIKO criteria. The vaccination may reduce the rate of cervical cancer by 70% and the rate of cervical intraepithelial neoplasia by 50%. Many studies demonstrated the efficacy and safetyness of both vaccines. Gardasil® offers protection against HPV 6, 11, 16 and 18, Cervarix® against HPV 16 and 18. Protection against condylomata is offered by the quadrivalent vaccine in 90%. The bivalent vaccine has demonstrated type-specific protection against the five most frequent cancer inducing types (16, 18, 31, 33, 45). The production of VLPs is an innovative technology. A comparison of both vaccines, Cervarix® and Gardasil®, showed a higher immunogenicity for Cervarix®. In Germany the immunization rates are still low comparing to other countries. As a method for secondary prevention of cervical cancer the PAP smear is still an effective method. © 2011 Georg Thieme Verlag KG Stuttgart · New York.


Griesinger G.,University of Lübeck | Schultz L.,University of Lübeck | Bauer T.,IVF Zentrum Augsburg | Broessner A.,Universitatsklinikum Magdeburg | And 2 more authors.
Fertility and Sterility | Year: 2011

Objective: To prospectively study ovarian hyperstimulation syndrome (OHSS) incidence and cumulative live birth rate in a cohort of patients at risk of OHSS undergoing ovarian stimulation in a GnRH antagonist protocol and receiving a GnRH agonist triggering followed by cryopreservation of all two pronuclei (2PN)-stage zygotes by two methods, vitrification or slow-cooling, for later ET. Design: Prospective, clinical cohort study. Setting: Five IVF centers in Germany; time frame: June 2008 to June 2010. Patient(s): Fifty-one female patients undergoing IVF considered at risk of developing severe OHSS (≥20 follicles ≥11 mm and/or E2 level ≥4,000 pg/mL) after ovarian stimulation in a GnRH antagonist protocol. Intervention(s): Triptorelin (0.2 mg SC) for triggering final oocyte maturation. All 2PN-stage zygotes were cryopreserved by vitrification or slow-cooling for later repetitive frozen-thawed ET. Main Outcome Measure(s): Severe OHSS incidence and cumulative live birth rate per patient. Result(s): Of 51 patients, 1 patient (2%, 95% confidence [CI] 0.3%-10.3%) had zero oocyte retrieved, 1 patient did not undergo frozen-thawed ET, and 1 patient had no surviving oocyte after thawing. Thus, 48 patients underwent at least one frozen-thawed ET. The cumulative live birth rate was 37.3% (19/51, 95% CI 25.3%-51.0%). The live birth rate per first frozen-thawed ET was 5.9% (1/17, 95% CI 10.0%-27.0%) and 19.4% (6/31, 95% CI 9.2%-36.3%) in the slow-cooling and vitrification group, respectively (difference: 13.5%, 95% CI of the difference: -9.9%-31.1%). Three cases of OHSS II (3/51, 5.9%, 95% CI 2.0%-15.9%) and one early-onset case of OHSS III (1/51, 2%, 95% CI 0.3%-10.3%) occurred. Conclusion(s): Agonist triggering with cryopreservation is efficacious and safe, although a single case of a severe early-onset OHSS occurred. © 2011 by American Society for Reproductive Medicine.


Zollner U.,Universitats Frauenklinik Wurzburg | Zollner U.,University of Würzburg | Specketer M.-T.,Frauenklinik der Krankenhaus Nordwest GmbH | Dietl J.,Universitats Frauenklinik Wurzburg | Zollner K.-P.,Kinderwunschzentrum Amberg
Archives of Gynecology and Obstetrics | Year: 2012

Purpose: The success of artificial reproductive techniques not only depends on the quality of oocytes and spermatozoa but also on the receptivity of the endometrium. The aim of this study was to assess the value of measurement of endometrial volume by three-dimensional (3D) in comparison to 2D-ultrasound in the prediction of implantation in women having transfer of cryopreserved embryos. Methods: One hundred and eight couples were included in this prospective study. All patients underwent the IVF or ICSI program and had transfer of cryopreserved embryos. Sixty-eight transfers were done in a spontaneous cycle and 40 in an artificial cycle. Endometrial thickness, pattern and three-dimensional volume were measured immediately before embryo transfer. Results: Twenty clinical pregnancies were achieved (PR 18.5 % per transfer), the PR being similar in spontaneous (22.1 %) and artificial (12.5 %, ns) cycles. Three to five days after ovulation (spontaneous cycles) or after the endometrium reached a thickness of at least 8 mm (artificial cycles), a median of three embryos were replaced. In spontaneous cycles, there were no significant differences in endometrial thickness or volume between pregnant (11.9 mm, 2.9 ml) and non-pregnant women (10.7 mm, 3.4 ml). In artificial cycles, the endometrial volume (3.9 vs. 2.5 ml, p<0.05), but not endometrial thickness (10.7 vs. 10.2 mm, ns) was significantly higher in pregnant than in non-pregnant women. Conclusions: In artificial cycles, a low endometrial volume is associated with a poor likelihood of implantation. Endometrial volume measured by 3D-ultrasound is an objective parameter to predict endometrial receptivity. © Springer-Verlag 2012.


Zollner U.,Universitats Frauenklinik Wurzburg | Zollner U.,Nightingale | Neumann C.,Universitats Frauenklinik Wurzburg | Neumann C.,Nightingale | And 2 more authors.
Journal of Reproductive Medicine | Year: 2013

OBJECTIVE: To find out which forms of conservative infertility therapy led to the highest pregnancy rate and which factors influence the occurrence of a pregnancy. STUDY DESIGN: A total of 433 conservative treatment cycles were retrospectively evaluated. Ovarian stimulation was performed with clomiphene citrate (CC) or gonadotropins (follicle stimulating hormone [FSH] or human menopausal gonadotropin) with ovulation induction and luteal phase support in some cases. Patients then received intrauterine insemination (IUI) or had timed intercourse (TI). RESULTS: The pregnancy rates were 2.7% in CC/TI cycles, 8.2% in FSH/TI cycles, 10.3% in CC/IUI cycles, and 15.5% in FSH/IUI cycles. A cycle regulation by means of an ovulation induction and a luteal phase-supporting medication resulted in significantly higher pregnancy rates. When the TI and/or the IUI were carried out postovulatorily and in the case of already beginning endogenous ovulation (increase of the luteinizing hormone value shown in the last control), the success rate was significantly lower. CONCLUSION: Not only the choice of the optimal form of treatment but also a sufficient supportive medication in terms of an ovulation induction and a luteal phase support as well as exact timing are vital for the treatment success in conservative infertility treatment. © Journal of Reproductive Medicine®, Inc.


Zollner U.,Universitats Frauenklinik Wurzburg | Rehn M.,Universitats Frauenklinik Wurzburg | Girschick G.,Universitats Frauenklinik Wurzburg | Dietl J.,Universitats Frauenklinik Wurzburg
Zeitschrift fur Geburtshilfe und Neonatologie | Year: 2011

Intrauterine growth restriction (IGUR) can have different etiologies, but placental insufficiency is the clinically most relevant. Fetuses with IUGR have a significantly higher morbidity and mortality than normally grown fetuses of the same gestational age. It is important to distinguish a growth restricted fetus from a normal, small fetus and from a fetus being small because of a disease, e.g., an aneuploidy. This differentiation requires the knowledge of the gestational age and the use of multiple imaging modalities. Serial assessments of fetal growth by ultrasound are necessary to recognize declining growth. Doppler sonography can detect changes in the uteroplacentar and the fetal perfusion. Blood vessels of clinical relevance are the uterine arteries, the umbilical artery, the middle cerebral artery and the ductus venosus. When no fetal anomalies can be detected, fetal growth is parallel to the percentiles and Doppler sonography measurements are normal, IUGR is unlikely. In most IUGR fetuses, a typical sequence of circulatory changes and ultrasound findings can be observed. As there is no evidence-based treatment option for IUGR until now, obstetric management consists in defining the optimal time of delivery. This means weighing the risks of prematurity against the risks of a potentially hostile intrauterine environment. © Georg Thieme Verlag KG Stuttgart · New York.


Zollner U.,Universitats Frauenklinik Wurzburg | Ahmadi M.,Universitats Frauenklinik Wurzburg | Dietl J.,Universitats Frauenklinik Wurzburg
Zeitschrift fur Geburtshilfe und Neonatologie | Year: 2011

Background: Gestational diabetes mellitus (GDM) occurs in 3-5% of all pregnant women. As there is no general screening in Germany, many cases remain undetected. Maternal as well as foetal morbidity are increased in GDM. The aim of this study was to investigate whether amniotic fluid insulin or C-peptide levels, collected by genetic amniocentesis in early pregnancy, are predictive for gestational diabetes. Patients at risk for developing GDM might be identified and treated very early. Patients and Methods: 260 patients having a genetic amniocentesis were included in this prospective trial. Insulin and C-peptide levels were identified in frozen amniotic fluid samples. All patients should undergo an oral glucose tolerance (oGTT) test at 2428 weeks of gestation. Only cases with normal genetic screening, normal foetal sonomorphology and birth at term were included in this trial. 90 of 260 patients having an amniocentesis underwent the oGTT and fulfilled all inclusion criteria. Results: GDM was diagnosed in 8 patients, in another 6 patients only one glucose level was out of the normal range. Neither amniotic fluid insulin nor C-peptide levels showed significant differences between normal and GDM pregnancies. The insulin and C-peptide levels did not correlate with blood glucose levels or with foetal weight. Conclusions: >In contrast to literature reports, according to these data no relationship between amniotic fluid insulin or C-peptide levels and gestational diabetes can be assumed. Amniotic fluid insulin or C-peptide levels are not predictive for GDM. © Georg Thieme Verlag KG, Stuttgart · New York.


PubMed | Universitats Frauenklinik Wurzburg and Kinderwunschzentrum Amberg
Type: Journal Article | Journal: The Journal of reproductive medicine | Year: 2014

To determine the levels of interleukin-1 beta (IL-1beta) in follicular fluid and embryo culture fluid after controlled ovarian hyperstimulation and to assess the association of this cytokine with the outcome of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment and embryo transfer.A total of 256 couples undergoing the IVF/ICSI program were included in this prospective study. Zygote quality, embryo and blastocyst morphology were evaluated, and embryo transfer was performed 5 days after oocyte recovery. IL-1beta concentrations were measured in follicular fluid and embryo culture fluid of the third and fifth culture days.Embryo replacement was performed with a median of 2 embryos per cycle. In all, 44 clinical pregnancies were achieved in 256 assisted reproductive technology (ART) cycles (pregnancy rate: 19.8% per transfer). Follicular fluid concentrations of IL-1P were not significantly different in pregnant (2.1 pg/mL) and nonpregnant women (2.7 pg/mL). Follicular fluid of lVF, but not ICSI, patients with good fertilization rates (> 90%) contained significantly higher levels of IL-1beta (3.3 pg/ mL) than did follicular fluid of women with fertilization rates < or = 90% (2.0 pg/mL, p < 0.05). No correlation was found between intrafollicular IL-1beta and zygote morphology, day 3 and day 5 embryo morphology. There was no relationship between IL-1beta in culture fluid supernatants and embryonic development.In IVF patients high levels of intrafollicular IL-1beta were associated with good fertilization rates. There seems to be no correlation between IL-1beta concentrations in follicular fluid or embryo culture fluid and embryo morphology or pregnancy outcome of ART cycles.


PubMed | Universitats Frauenklinik Wurzburg
Type: Journal Article | Journal: The Journal of reproductive medicine | Year: 2013

To find out which forms of conservative infertility therapy led to the highest pregnancy rate and which factors influence the occurrence of a pregnancy.A total of 433 conservative treatment cycles were retrospectively evaluated. Ovarian stimulation was performed with clomiphene citrate (CC) or gonadotropins (follicle stimulating hormone [FSH] or human menopausal gonadotropin) with ovulation induction and luteal phase support in some cases. Patients then received intrauterine insemination (IUI) or had timed intercourse (TI).The pregnancy rates were 2.7% in CC/TI cycles, 8.2% in FSH/TI cycles, 10.3% in CC/IUI cycles, and 15.5% in FSH/IUI cycles. A cycle regulation by means of an ovulation induction and a luteal phase-supporting medication resulted in significantly higher pregnancy rates. When the TI and/or the IUI were carried out postovulatorily and in the case of already beginning endogenous ovulation (increase of the luteinizing hormone value shown in the last control), the success rate was significantly lower.Not only the choice of the optimal form of treatment but also a sufficient supportive medication in terms of an ovulation induction and a luteal phase support as well as exact timing are vital for the treatment success in conservative infertility treatment.

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