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Article ; Online: Co-cultivation of human granulosa cells with ovarian cancer cells leads to a significant increase in progesterone production.

Pietrowski, Detlef / Grgic, Martina / Haslinger, Isabella / Marschalek, Julian / Schneeberger, Christian

2023 Volume 307, Issue 5, Page(s) 1593–1597

Abstract: Purpose: In humans, granulosa cells (GCs) are part of the follicle and nourish the growing oocyte. GCs produce estrogen and, after ovulation, progesterone. They are embedded in a multicellular tissue structure of the ovary, which consists of a variety ... ...

Abstract	Purpose: In humans, granulosa cells (GCs) are part of the follicle and nourish the growing oocyte. GCs produce estrogen and, after ovulation, progesterone. They are embedded in a multicellular tissue structure of the ovary, which consists of a variety of different cell types that are essential for the physiological function of the ovary. However, the extent to which individual ovarian cell types contribute to overall functionality has not yet been fully elucidated. In this study, we aim to investigate the effects of co-culturing human granulosa cells with ovarian cancer cells on their progesterone and estrogen production in an in vitro model. Methods: After seeding, the cells were stimulated with 200 µM forskolin in DMEM for 72 h and the medium of the different cell culture experiments was collected. Subsequently, progesterone and oestradiol concentrations were determined using an Elisa assay. Results: Morphologically, it was striking that the cells self-organize and form spatially separated areas. Compared to culturing granulosa cells alone, co-culturing human granulosa cells together with the ovarian cancer cell line OvCar-3 resulted in a significant increase in progesterone production (20.3 ng/ml versus 50.2 ng/ml; p < 0.01). Conclusions: Using a simple in vitro model, we highlight the importance of cellular crosstalk between different ovarian cells in a complex cellular network and that it strongly influences granulosa cell hormone production. This could have potential implications for the procedure of transplanting endocrine tissues after cryopreservation, as it highlights the importance of survival of all cells for the functionality of the transplanted tissue.
MeSH term(s)	Humans ; Female ; Progesterone/pharmacology ; Apoptosis ; Ovarian Neoplasms/metabolism ; Follicle Stimulating Hormone/pharmacology ; Cells, Cultured ; Cell Line, Tumor ; Granulosa Cells/metabolism ; Estradiol/pharmacology ; Estrogens/metabolism
Chemical Substances	Progesterone (4G7DS2Q64Y) ; Follicle Stimulating Hormone (9002-68-0) ; Estradiol (4TI98Z838E) ; Estrogens
Language	English
Publishing date	2023-01-18
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	896455-5
ISSN	1432-0711 ; 0932-0067
ISSN (online)	1432-0711
ISSN	0932-0067
DOI	10.1007/s00404-023-06914-z
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Article: A case-control study about markers of stress in normal-/overweight women with polycystic ovary syndrome and in controls.

Marschalek, Marie-Louise / Marculescu, Rodrig / Schneeberger, Christian / Marschalek, Julian / Dewailly, Didier / Ott, Johannes

Frontiers in endocrinology

2023 Volume 14, Page(s) 1173422

Abstract: Background: Polycystic ovary syndrome (PCOS) is linked to an elevated risk of psychological disorders, decreased quality of life and emotional distress. Serum cortisol as a potential stress marker has been found to be increased in women with PCOS. The ... ...

Abstract	Background: Polycystic ovary syndrome (PCOS) is linked to an elevated risk of psychological disorders, decreased quality of life and emotional distress. Serum cortisol as a potential stress marker has been found to be increased in women with PCOS. The aim of this study was to evaluate both saliva stress markers and subjective psychological distress in women with PCOS. Methods: In a prospective case-control study, 31 PCOS women and 31 healthy controls were included. Salivary cortisol, and metanephrines were collected in the morning and in the evening. Emotional distress and quality of life were assessed by means of the Perceived Stress Scale (PSS-10) and the Short Form-36 (SF-36). Multivariable generalized linear models were applied to test the influence of various parameters on numerical outcome parameters. Results: After correction for age and body mass index (BMI), there were no statistically significant differences of salivary biomarkers between PCOS women and healthy controls (p>0.05). PCOS patients revealed significantly higher increased PSS total scores and lower quality of life in all SF-36 modules apart from pain (p< 0.05). The PSS total score was positively correlated to prolactin in PCOS women (r= 0.450; p= 0.011). In overweight/obese PCOS patients, a higher BMI, a higher Ferriman Gallwey score and higher age significantly predicted the PSS total score (p< 0.05). Conclusion: Stress measured by salivary biomarkers did not differ between PCOS women and healthy controls, whereas stress scores evaluated by questionnaires were significantly greater in women with PCOS. A higher BMI, hirsutism and a higher age seem to be the main modulators of subjective stress in PCOS. Prolactin might serve as a biomarker for chronic stress in PCOS women.
MeSH term(s)	Female ; Humans ; Male ; Polycystic Ovary Syndrome/complications ; Overweight/complications ; Case-Control Studies ; Hydrocortisone ; Quality of Life ; Prolactin ; Biomarkers
Chemical Substances	Hydrocortisone (WI4X0X7BPJ) ; Prolactin (9002-62-4) ; Biomarkers
Language	English
Publishing date	2023-05-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2023.1173422
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Article ; Online: Different Impacts of Cryopreservation in Endothelial and Epithelial Ovarian Cells.

Marschalek, Julian / Hager, Marlene / Wanderer, Sophie / Ott, Johannes / Frank, Maria / Schneeberger, Christian / Pietrowski, Detlef

International journal of molecular sciences

2023 Volume 24, Issue 15

Abstract: The aim of our laboratory-based study was to investigate the extent of delayed-onset cell death after cryopreservation in endothelial and epithelial cell lines of ovarian origin. We found differences in percentages of vital cells directly after warming ... ...

Abstract	The aim of our laboratory-based study was to investigate the extent of delayed-onset cell death after cryopreservation in endothelial and epithelial cell lines of ovarian origin. We found differences in percentages of vital cells directly after warming and after cultivation for 48 to 72 h. A granulosa cell line of endothelial origin (KGN) and an epithelial cell line (OvCar-3) were used. In both DMSO-containing and DMSO-free protocols, significant differences in vitality rates between the different cell lines when using open and closed vitrification could be shown (DMSO-containing: KGN open vs. OvCar open,
MeSH term(s)	Female ; Humans ; Apoptosis ; Cell Line, Tumor ; Ovarian Neoplasms ; Cryopreservation/methods ; Cryoprotective Agents/pharmacology ; Granulosa Cells ; Dimethyl Sulfoxide/pharmacology
Chemical Substances	Cryoprotective Agents ; Dimethyl Sulfoxide (YOW8V9698H)
Language	English
Publishing date	2023-07-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241512225
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Article ; Online: Comparison of a practice-based versus theory-based training program for conducting vacuum-assisted deliveries: a randomized-controlled trial.

Marschalek, Julian / Kuessel, Lorenz / Stammler-Safar, Maria / Kiss, Herbert / Ott, Johannes / Husslein, Heinrich

Archives of gynecology and obstetrics

2021 Volume 305, Issue 2, Page(s) 365–372

Abstract: Purpose: Vacuum-assisted deliveries (VAD) are complex procedures that require training and experience to be performed proficiently. We aimed to evaluate if a more resource intensive practice-based training program for conducting VAD is more efficient ... ...

Abstract	Purpose: Vacuum-assisted deliveries (VAD) are complex procedures that require training and experience to be performed proficiently. We aimed to evaluate if a more resource intensive practice-based training program for conducting VAD is more efficient compared to a purely theory-based training program, with respect to immediate training effects and persistence of skills 4-8 weeks after the initial training. Methods: In this randomized-controlled study conducted in maternity staff, participants performed a simulated low-cavity non-rotational vacuum delivery before (baseline test) and immediately after the training (first post-training test) as well as 4-8 weeks thereafter (second post-training test). The study's primary endpoint was to compare training effectiveness between the two study groups using a validated objective structured assessment of technical skills (OSATS) rating scale. Results: Sixty-two participants were randomized to either the theory-based group (n = 31) or the practice-based group (n = 31). Total global and specific OSATS scores, as well as distance of cup application to the flexion point improved significantly from baseline test to the first post-training test in both groups (p Conclusion: A practice-based training program for conducting VAD results in comparable immediate improvement of skills compared to a theory-based training program, but the retention of skills 4-8 weeks after training is superior in a practice-based program. Future studies need to evaluate, whether VAD simulation training improves maternal and neonatal outcome after VAD.
MeSH term(s)	Clinical Competence ; Educational Measurement ; Female ; Humans ; Infant, Newborn ; Internship and Residency ; Pregnancy ; Simulation Training/methods ; Vacuum Extraction, Obstetrical
Language	English
Publishing date	2021-08-07
Publishing country	Germany
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	896455-5
ISSN	1432-0711 ; 0932-0067
ISSN (online)	1432-0711
ISSN	0932-0067
DOI	10.1007/s00404-021-06159-8
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Article ; Online: Basal and dynamic relationships between serum anti-Müllerian hormone and gonadotropins in patients with functional hypothalamic amenorrhea, with or without polycystic ovarian morphology.

Hager, Marlene / Ott, Johannes / Marschalek, Julian / Marschalek, Marie-Louise / Kinsky, Clemens / Marculescu, Rodrig / Dewailly, Didier

Reproductive biology and endocrinology : RB&E

2022 Volume 20, Issue 1, Page(s) 98

Abstract: Background: To evaluate in women with functional hypothalamic amenorrhea (FHA), whether there is a difference between patients with and without polycystic ovarian morphology (PCOM) concerning the response to a gonadotropin releasing hormone (GnRH) ... ...

Abstract	Background: To evaluate in women with functional hypothalamic amenorrhea (FHA), whether there is a difference between patients with and without polycystic ovarian morphology (PCOM) concerning the response to a gonadotropin releasing hormone (GnRH) stimulation test and to pulsatile GnRH treatment. Methods: In a retrospective observational study, 64 women with FHA who underwent a GnRH stimulation test and 32 age-matched controls without PCOM were included. Pulsatile GnRH treatment was provided to 31 FHA patients and three-month follow-up data were available for 19 of these. Results: Serum levels of gonadotropins and estradiol were lower in FHA women than in controls (p < 0.05). FHA patients revealed PCOM in 27/64 cases (42.2%). FHA patients without PCOM revealed lower anti-Müllerian hormone (AMH) levels than controls (median 2.03 ng/mL, IQR 1.40-2.50, versus 3.08 ng/mL, IQR 2.24-4.10, respectively, p < 0.001). Comparing FHA patients with and without PCOM, the latter revealed lower AMH levels, a lower median LH increase after the GnRH stimulation test (240.0%, IQR 186.4-370.0, versus 604.9%, IQR 360.0-1122.0; p < 0.001) as well as, contrary to patients with PCOM, a significant increase in AMH after three months of successful pulsatile GnRH treatment (median 1.69 ng/mL at baseline versus 2.02 ng/mL after three months of treatment; p = 0.002). Conclusions: In women with FHA without PCOM, the phenomenon of low AMH levels seems to be based on relative gonadotropin deficiency rather than diminished ovarian reserve. AMH tended to rise after three months of pulsatile GnRH treatment. The differences found between patients with and without PCOM suggest the former the existence of some PCOS-specific systemic and/or intra-ovarian abnormalities.
MeSH term(s)	Amenorrhea/drug therapy ; Anti-Mullerian Hormone ; Female ; Gonadotropin-Releasing Hormone ; Gonadotropins ; Humans ; Polycystic Ovary Syndrome/complications ; Polycystic Ovary Syndrome/drug therapy
Chemical Substances	Gonadotropins ; Gonadotropin-Releasing Hormone (33515-09-2) ; Anti-Mullerian Hormone (80497-65-0)
Language	English
Publishing date	2022-07-04
Publishing country	England
Document type	Journal Article ; Observational Study
ZDB-ID	2119215-7
ISSN	1477-7827 ; 1477-7827
ISSN (online)	1477-7827
ISSN	1477-7827
DOI	10.1186/s12958-022-00961-y
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Article ; Online: Assessment of Tubal Patency: A Prospective Comparison of Diagnostic Hysteroscopy and Laparoscopic Chromopertubation.

Ott, Johannes / Hager, Marlene / Nouri, Kazem / Marschalek, Julian / Kurz, Christine

Journal of minimally invasive gynecology

2019 Volume 27, Issue 1, Page(s) 135–140

Abstract: Study objective: To evaluate whether the presence of a visualizable "flow" effect in the fallopian tube ostia in hysteroscopy was predictive of tubal patency.: Design: A prospective cohort study.: Setting: In a prospective study, infertile women ... ...

Abstract	Study objective: To evaluate whether the presence of a visualizable "flow" effect in the fallopian tube ostia in hysteroscopy was predictive of tubal patency. Design: A prospective cohort study. Setting: In a prospective study, infertile women who underwent surgery because of infertility between March and November 2018 were included. The main outcome parameter was fallopian tube patency assessed by laparoscopic chromopertubation. The predictive parameter tested was the presence of hysteroscopic tube flow. Patients: Seventy-two infertile women. Interventions: Combined hysteroscopy and laparoscopy with chromopertubation. Results: One-hundred forty-four fallopian tubes were evaluated, with 88 (61.1%) patent tubes at laparoscopic chromopertubation. A positive hysteroscopic flow effect was recorded for 94 (65.3%) ostia and was accurate in predicting patency (p < .001), with a sensitivity of 85.3% (95% confidence interval [CI], 76.1-91.9) and a specificity of 66.1% (95% CI, 52.2-78.2). A multivariate binary regression model revealed that the presence of a hydrosalpinx (odds ratio = 8.216; 95% CI, 1.062-63.574; p = .044) and peritubal adhesions (odds ratio = 3.439; 95% CI, 1.142-10.353; p = .028) were associated with a false-normal flow result. A hazy hysteroscopic picture was found in 15 of 21 (71.4%) and 5 of 51 (9.8%) cases with and without bilateral tubal occlusion, respectively (p < .001, sensitivity = 71.4% [95% CI, 47.8-88.7], specificity = 90.2% [95% CI, 78.6-96.7]). Conclusions: The presence of hysteroscopic tubal flow was a reliable indicator of tubal patency. A hydrosalpinx or peritubal adhesions increase the risk for a false-normal result. A hazy hysteroscopic picture suggests bilateral tubal occlusion. Using the hysteroscopic flow effect, one can provide additional information for the patient.
MeSH term(s)	Adolescent ; Adult ; Fallopian Tube Diseases/complications ; Fallopian Tube Diseases/diagnosis ; Fallopian Tube Patency Tests/methods ; Fallopian Tube Patency Tests/standards ; Female ; Humans ; Hysteroscopy/adverse effects ; Hysteroscopy/methods ; Indigo Carmine/administration & dosage ; Infertility, Female/diagnosis ; Infertility, Female/etiology ; Laparoscopy/adverse effects ; Laparoscopy/methods ; Middle Aged ; Predictive Value of Tests ; Prospective Studies ; Sensitivity and Specificity ; Staining and Labeling/methods ; Young Adult
Chemical Substances	Indigo Carmine (D3741U8K7L)
Language	English
Publishing date	2019-03-15
Publishing country	United States
Document type	Clinical Trial ; Journal Article
ZDB-ID	2186934-0
ISSN	1553-4669 ; 1553-4650
ISSN (online)	1553-4669
ISSN	1553-4650
DOI	10.1016/j.jmig.2019.03.006
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Article ; Online: Markers of vitality in ovaries of transmen after long-term androgen treatment: a prospective cohort study.

Marschalek, Julian / Pietrowski, Detlef / Dekan, Sabine / Marschalek, Marie-Louise / Brandstetter, Maximilian / Ott, Johannes

Molecular medicine (Cambridge, Mass.)

2020 Volume 26, Issue 1, Page(s) 83

Abstract: Background: Gender-affirming hormone therapy has been hypothesized to reduce the patient's reproductive potential in transmen, although the exact long-term effects on future fertility are unknown.: Methods: In this prospective cohort study we aimed ... ...

Abstract	Background: Gender-affirming hormone therapy has been hypothesized to reduce the patient's reproductive potential in transmen, although the exact long-term effects on future fertility are unknown. Methods: In this prospective cohort study we aimed to evaluate ovaries of 20 transmen by using hormone serum levels, histomorphological analysis and fluorescence activated cells sorting (FACS) analysis - in order to assess the amount of vital cells. Results: The median total number of follicles per field of view was 39 (IQR 12-122). Of all follicles (n = 1661), the vast majority was primordial (n = 1505, 90.6%), followed by primary (n = 76, 4.6%), abnormal (n = 63, 3.8%) and secondary follicles (n = 17, 1.0%). FACS analysis was available for 13 samples (65.0%) and the median frequency of vital cells was 87.5% (IQR, 77.7-95.4%). Both a higher age (p = 0.032) and a lower BMI (p = 0.003) were significantly associated with a higher frequency of vital cells. Conclusion: The majority of ovarian cells after long-term androgen treatment were vital in FACS analysis and histomorphological evaluation revealed a normal cortical follicle distribution. These results are currently exploratory, but might be promising for issues on fertility preservation. Trial registration: The study was approved by the ethics committee of the Medical University of Vienna (EK 2240/2016) and was retrospectively registered in the Current Controlled Trials Register (registration number NCT03649087 , date of registration: 28.08.2018).
MeSH term(s)	Adolescent ; Adult ; Androgens/administration & dosage ; Biomarkers ; Female ; Flow Cytometry ; Humans ; Immunohistochemistry ; Immunophenotyping ; Ovary/drug effects ; Ovary/metabolism ; Reproduction ; Transgender Persons ; Young Adult
Chemical Substances	Androgens ; Biomarkers
Language	English
Publishing date	2020-09-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1283676-x
ISSN	1528-3658 ; 1076-1551
ISSN (online)	1528-3658
ISSN	1076-1551
DOI	10.1186/s10020-020-00214-x
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Article ; Online: Analyses of human granulosa cell vitality by fluorescence activated cell sorting after rapid cooling.

Pietrowski, Detlef / Mladek, Raphaela / Frank, Maria / Erber, Julia / Marschalek, Julian / Schneeberger, Christian

Human fertility (Cambridge, England)

2020 Volume 25, Issue 3, Page(s) 478–486

Abstract: In reproductive medicine, the technique of rapid cooling becomes increasingly important for the preservation of tissue and cells. In order to protect the cells, incubation in different cryopreservation solutions is essential. The speed of the cooling ... ...

Abstract	In reproductive medicine, the technique of rapid cooling becomes increasingly important for the preservation of tissue and cells. In order to protect the cells, incubation in different cryopreservation solutions is essential. The speed of the cooling process also makes a pivotal contribution to the success of this method. Using Flourescence Activated Cell Sorting (FACS), we investigated the impact of an open rapid and a closed rapid cooling technique on the vitality of human granulosa cells. Furthermore, we examined effects of the different solutions used for rapid cooling and warming before and after rapid cooling. We found a significant lower proportion of vital cells after rapid cooling compared to untreated controls independently of the technique and the tube size. However, we did not find any significant differences between open and closed rapid cooling. In both, a lower proportion of vital granulosa cells were found after incubation in rapid cooling solution only compared to warming solution only. Our results lend support to the conclusion that the difference of cooling-speed between open and closed rapid cooling is, in our settings, not crucial for the success of the procedure and that cryoprotective agents in the rapid cooling solutions have a higher potential to cause severe cell damage than agents used for warming.
MeSH term(s)	Cell Survival ; Cryopreservation/methods ; Cryoprotective Agents/pharmacology ; Female ; Flow Cytometry ; Granulosa Cells ; Humans
Chemical Substances	Cryoprotective Agents
Language	English
Publishing date	2020-09-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2086960-5
ISSN	1742-8149 ; 1464-7273
ISSN (online)	1742-8149
ISSN	1464-7273
DOI	10.1080/14647273.2020.1817578
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Article ; Online: Impact of vitrification on granulosa cell survival and gene expression.

Kokotsaki, Maria / Mairhofer, Mario / Schneeberger, Christian / Marschalek, Julian / Pietrowski, Detlef

Cryobiology

2018 Volume 85, Page(s) 73–78

Abstract: Introduction: Cryopreservation of ovarian tissue is an essential step in Ovarian Tissue Banking. In order to prevent the formation of ice crystals, typically the tissue is slowly frozen using a cryoprotectant. As an alternative the method of ultra-fast ... ...

Abstract	Introduction: Cryopreservation of ovarian tissue is an essential step in Ovarian Tissue Banking. In order to prevent the formation of ice crystals, typically the tissue is slowly frozen using a cryoprotectant. As an alternative the method of ultra-fast freezing by vitrification becomes more attention for freezing ovarian tissue because it has successfully been used for oocytes, embryos and sperm. However the impact of vitrification on granulosa cells, which are an essential part of ovarian tissue is uncertain. Aim: In this study, we have therefore analysed the influence of vitrification on the survival rates of granulosa cells, the impact of DMSO or ethylenglycol containing vitrification protocols and investigated to what extent the gene expression of apoptosis- and temperature-sensitive genes changes. Material and methods: We used the human granulosa cell line KGN as a model for human granulosa cells and determined the survival rate and cell cycle stages by FACS analyses. The change in gene expression was determined by quantitative PCR analyses. Results: Our results show that vitrification is possible in granulosa cells but it reduces cell viability and leads to fluctuations in the cell cycle. The DMSO containing protocol results in a lower amount of dead cells than the ethylenglycol containing protocol. Gene expression analysis reveals that TNF-alpha expression is strongly increased after vitrification, while other apoptosis or temperature-related genes seem to stay unaffected. Conclusion: We conclude that vitrification influences the viability of human granulosa cells. Furthermore, our results suggest that this could be mediated by a change in TNF-alpha gene expression.
MeSH term(s)	Cell Line ; Cell Survival/drug effects ; Cryopreservation/methods ; Cryoprotective Agents/pharmacology ; Female ; Fertility Preservation/methods ; Freezing ; Gene Expression/drug effects ; Granulosa Cells/cytology ; Granulosa Cells/drug effects ; Granulosa Cells/physiology ; Humans ; Vitrification/drug effects
Chemical Substances	Cryoprotective Agents
Language	English
Publishing date	2018-09-25
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80098-3
ISSN	1090-2392 ; 0011-2240
ISSN (online)	1090-2392
ISSN	0011-2240
DOI	10.1016/j.cryobiol.2018.09.006
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Article ; Online: Clinical risk factors for recurrence of pelvic organ prolapse after primary native tissue prolapse repair.

Bodner-Adler, Barbara / Bodner, Klaus / Carlin, Greta / Kimberger, Oliver / Marschalek, Julian / Koelbl, Heinz / Umek, Wolfgang

Wiener klinische Wochenschrift

2021 Volume 134, Issue 1-2, Page(s) 73–75

Abstract: Objective: To define potential risk factors for recurrence of prolapse.: Methods: This short report included all women who presented with recurrence of prolapse as well as without any recurrence signs after a vaginal approach of native tissue ... ...

Abstract	Objective: To define potential risk factors for recurrence of prolapse. Methods: This short report included all women who presented with recurrence of prolapse as well as without any recurrence signs after a vaginal approach of native tissue prolapse repair at an urogynecological center in Austria. Results: A total of 124 recurrence cases and 64 women with no signs of recurrence after their index prolapse surgery were included. Multivariate analysis identified advanced preoperative POP‑Q stage (pelvic organ prolapse-quantification) as an independent risk factor for postoperative recurrence of prolapse (p = 0.045). Conclusion: Initial proper preoperative counseling is of particular importance to modulate patients' expectations after prolapse surgery.
MeSH term(s)	Austria ; Female ; Humans ; Pelvic Organ Prolapse/epidemiology ; Pelvic Organ Prolapse/surgery ; Postoperative Period ; Recurrence ; Risk Factors ; Surgical Mesh ; Treatment Outcome
Language	English
Publishing date	2021-04-30
Publishing country	Austria
Document type	Journal Article
ZDB-ID	200462-8
ISSN	1613-7671 ; 0043-5325 ; 0300-5178
ISSN (online)	1613-7671
ISSN	0043-5325 ; 0300-5178
DOI	10.1007/s00508-021-01861-8
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