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Early to Middle Miocene sea-level oscillations of approximately 40-60 m estimated from far-field records.sup.1-3 are interpreted to reflect the loss of virtually all East Antarctic ice during peak warmth.sup.2. This contrasts with ice-sheet model experiments suggesting most terrestrial ice in East Antarctica was retained even during the warmest intervals of the Middle Miocene.sup.4,5. Data and model outputs can be reconciled if a large West Antarctic Ice Sheet (WAIS) existed and expanded across most of the outer continental shelf during the Early Miocene, accounting for maximum ice-sheet volumes. Here we provide the earliest geological evidence proving large WAIS expansions occurred during the Early Miocene (~17.72-17.40 Ma). Geochemical and petrographic data show glacimarine sediments recovered at International Ocean Discovery Program (IODP) Site U1521 in the central Ross Sea derive from West Antarctica, requiring the presence of a WAIS covering most of the Ross Sea continental shelf. Seismic, lithological and palynological data reveal the intermittent proximity of grounded ice to Site U1521. The erosion rate calculated from this sediment package greatly exceeds the long-term mean, implying rapid erosion of West Antarctica. This interval therefore captures a key step in the genesis of a marine-based WAIS and a tipping point in Antarctic ice-sheet evolution. Variations in Miocene sea level can be explained by a large marine-based West Antarctic Ice Sheet., Author(s): J. W. Marschalek [sup.1] , L. Zurli [sup.2] , F. Talarico [sup.2] , T. van de Flierdt [sup.1] , P. Vermeesch [sup.3] , A. Carter [sup.4] , F. Beny [...]

Objective: To investigate whether fetal lung signals and fetal lung signal progression over gestation observed on magnetic resonance imaging are different in mothers who reported smoking during pregnancy compared with nonsmoking controls. Method: Cross-sectional retrospective study of 100 consecutive singleton pregnancies that underwent magnetic resonance imaging. Fetal lung-liver signal intensity ratios of 18 fetuses of mothers who reported smoking during pregnancy were compared with 82 fetuses of nonsmoking controls. Results: Average gestational age at magnetic resonance imaging was 26.4 ± 5.2 weeks (Range 18.4-38.2 weeks). Cases reported smoking between 2 and 15 cigarettes per day. The mean number of cigarettes per day for cases was 9.2 ± 3.4. Mean fetal lung-liver signal intensity ratios did not differ significantly between the two groups (p = 0.8). They showed a linear increase with gestational age (r(2) = 0.3). Multiple regression analysis of lung-liver signal intensity ratios using gestational age and smoking status as predictors revealed a significant influence of gestational age (p < 0.0001) but not maternal smoking status (p = 0.8) on fetal lung-liver signal intensity ratios. Conclusions: Fetuses of mothers who reported smoking during pregnancy show similar lung signals and lung signal progression over gestation on magnetic resonance imaging as nonsmoking controls. [ABSTRACT FROM AUTHOR]

Background: In light of the opioid epidemic, opioid-prescribing modalities for postoperative pain management have been discussed controversially and show a wide variation across geographic regions. The aim of this study was to compare postoperative pain treatment regimes. Methods: We performed a matched cohort study of women undergoing hysterectomy in Austria ( n = 200) and Canada ( n = 200). We aimed to compare perioperative opioid medications, converted to morphine equivalent dose (MED) and doses of non-opioid analgesic (NOA) within the first 24 h after hysterectomy, and opioid prescriptions at discharge between the two cohorts. Results: The total MED received intraoperatively, in the post-anaesthesia care unit (PACU) and during the first 24 h after surgery, was similar in both cohorts (145.59 vs. 137.87; p = 0.17). Women in the Austrian cohort received a higher MED intraoperatively compared to the Canadian cohort (117.24 vs. 79.62; p < 0.001) but a lower MED in the PACU (25.96 vs. 30.42; p = 0.04). The primary outcome, MED within 24 h in the postoperative ward, was markedly lower in the Austrian compared to the Canadian cohort (2.36 vs. 27.98; p < 0.001). In a regression analysis, only the variables "Country" and "mode of hysterectomy" affected this outcome. A total of 98.5% in the Canadian cohort were given an opioid prescription at discharge vs. 0% in the Austrian cohort. Conclusions: Our analysis reveals marked differences between Austria and Canada regarding pain management practices following elective hysterectomy; the significantly higher intraoperative and significantly lower postoperative MED administration in the Austrian cohort compared to the Canadian cohort seems to be significantly affected by each country's cultural attitudes towards pain management; this may have significant public health consequences and warrants further research.

Pliocene global temperatures periodically exceeded modern levels, offering insights into ice sheet sensitivity to warm climates. Ice-proximal geologic records from this period provide crucial but limited glimpses of Antarctic Ice Sheet behavior. We use an ice sheet model driven by climate model snapshots to simulate transient glacial cyclicity from 4.5 to 2.6 Ma, providing spatial and temporal context for geologic records. By evaluating model simulations against a comprehensive synthesis of geologic data, we translate the intermittent geologic record into a continuous reconstruction of Antarctic sea level contributions, revealing a dynamic ice sheet that contributed up to 25 m of glacial-interglacial sea level change. Model grounding line behavior across all major Antarctic catchments exhibits an extended period of receded ice during the mid-Pliocene, coincident with proximal geologic data around Antarctica but earlier than peak warmth in the Northern Hemisphere. Marine ice sheet collapse is triggered with 1.5 °C model subsurface ocean warming., (© 2024. The Author(s).)

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, p = 0.001; KGN closed vs. OvCar closed, p = 0.001; DMSO-free: KGN open vs. OvCar open, p = 0.001; KGN closed vs. OvCar closed, p = 0.031). Furthermore, there was a marked difference in the percentage of vital cells immediately after warming and after cultivation for 48 to 72 h; whereas the KGN cell line showed a loss of cell viability of 41% using a DMSO-containing protocol, the OvCar-3 cell loss was only 11% after cultivation. Using a DMSO-free protocol, the percentages of late-onset cell death were 77% and 48% for KGN and OvCar-3 cells, respectively. Our data support the hypothesis that cryopreservation-induced damage is cell type and cryoprotective agent dependent.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Marschalek, Marculescu, Schneeberger, Marschalek, Dewailly and Ott.)

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., (© 2023. The Author(s).)

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., (© 2022. The Author(s).)

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.

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 all  < 0.007). Skill deterioration after 4-8 weeks was only found in the theory-based group, whereas skills remained stable in the practice-based group., 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., (© 2021. The Author(s).)

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., (© 2021. The Author(s).)

Prosthetic services and resources globally are insufficient to meet the needs of individuals with lower limb loss worldwide, particularly in low resource countries. The lack of trained prosthetists, high cost, and inaccessibility of prosthetic services leave many patients in these countries without a prosthesis. To address this problem, an immediate fit, adjustable, modular, prosthetic system was developed. Six individuals in Jamaica with transtibial lower limb loss who were in need of a prosthesis visited a local therapy clinic. They were fit with the prosthetic system by a physical therapist certified and trained in the proper fitting of these devices. All patients were fit on the first visit and walked out with a comfortable prosthesis after some rehabilitation gait training. Five of the patients returned for follow-up and reported that they continued to use these devices for daily wear. No adverse events or socket component failures were reported despite rigorous daily use in a rugged environment. This new prosthetic care delivery model-a modular system distributed to patient locations and fit by trained allied rehabilitation professionals-holds potential for meeting the large demand for lower limb prosthetics in developing countries., (© 2021 The Authors.)

Objective: The purpose of this investigation was to assess participants' self-reported satisfaction with an adjustable, immediate fit transtibial prosthetic system as compared to their conventionally fabricated prosthetic device., Design: A prospective study involving a two-week single-group pre-post intervention design., Setting: Physical medicine and rehabilitation clinic of a university hospital., Participants: Adults (N=27) with transtibial limb loss., Intervention: Participants were fit with the iFIT prosthetic system and instructed to wear it for a two-week evaluation period., Main Outcome Measure: A modified PEQ scale was completed on the participant's conventional prosthetic during the initial visit and the iFIT system after the two weeks., Results: Twenty-seven persons with lower limb loss were enrolled. Three were lost to follow up leaving twenty-four subjects with completed data. Three subjects had recent amputations with no conventional device for comparison. The Modified PEQ scores were significantly higher for the iFIT prosthetic in comparison to their conventional device (29.18 [SD= 4.63] vs 23.82 [SD=6.38], p <0.01 ). Subjects were also found to perceive significantly better temperature control with the iFIT prosthetic system (4.19 [SD= 0.68] vs 2.97 [SD=1.02], p <0.001 ). Subjects did not report any skin breakdown, prosthetic issues, or falls., Conclusion: This immediate fit, adjustable transtibial prosthesis demonstrated significantly better patient satisfaction and temperature perception compared to conventional devices. These results are consistent with previous findings and further support the efficacy of an immediate fit adjustable transtibial prosthetic system. Longer term studies in the United States and internationally are underway to assess the durability and efficacy of this new prosthesis in different populations and settings.

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).

This multicentre, randomised, controlled cross-over trial was designed to investigate the effect of intra-uterine slow-release insemination (SRI) on pregnancy rates in women with confirmed infertility or the need for semen donation who were eligible for standard bolus intra-uterine insemination (IUI). Data for a total of 182 women were analysed after randomisation to receive IUI (n = 96) or SRI (n = 86) first. The primary outcome was serological pregnancy defined by a positive beta human chorionic gonadotropin test, two weeks after insemination. Patients who did not conceive after the first cycle switched to the alternative technique for the second cycle: 44 women switched to IUI and 58 switched to SRI. In total, there were 284 treatment cycles (IUI: n = 140; SRI: n = 144). Pregnancy rates following SRI and IUI were 13.2% and 10.0%, respectively, which was not statistically significant (p = 0.202). A statistically significant difference in pregnancy rates for SRI versus IUI was detected in women aged under 35 years. In this subgroup, the pregnancy rate with SRI was 17% compared to 7% with IUI (relative risk 2.33; p = 0.032) across both cycles. These results support the hypothesis that the pregnancy rate might be improved with SRI compared to standard bolus IUI, especially in women aged under 35 years.

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., (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Background: There exists a need for an adjustable socket to accommodate residual limb volume and shape changes. Further, limb loss rates globally are rising and there is a large unmet need for affordable and accessible prosthetic systems., Objective: To assess the utility of an immediate fit modular prosthetic system (iFIT Prosthetics, LLC)., Design: Prospective feasibility study involving a 2-week single-group pre-post intervention study., Setting: Physical Medicine and Rehabilitation gait laboratory., Participants: Participants were at least 6 months post amputation and walking with a conventional prosthesis. They were free of skin wounds, other neurological disorders, and severe pain conditions., Methods: Participants were fit with an immediate fit prosthesis and instructed to wear it for a 2-week evaluation period. They were given a progressive wearing schedule and they completed outcome measurements at the 2-week follow-up., Main Outcome Measurements: Self-reported satisfaction, gait biomechanics, and intrasocket peak pressures., Results: Twenty-six participants entered the study, with 22 completing the single group pre-post study. They averaged 50 years (SD ±10.2) of age; four were female. Sixteen were dysvascular and 10 were traumatic in etiology. Significant differences (P = .03) in self-reported satisfaction were found in favor of the iFIT device 29.33 (SD ± 4.51) versus the conventional device 25.52 (SD ± 6.8). No falls or limb ischemia were reported. Gait biomechanics revealed no differences across any temporal characteristics. Intrasocket peak pressures were significantly lower for the iFIT prostheses overall (P = .0014), at the anterior tibia (P = .0002), and the lateral side of the residual limb (P = .013)., Conclusions: The iFIT transtibial prosthetic system appears to be safe in this short-term single-group pre-post study. This study provided preliminary evidence to support the feasibility of the iFIT system. It compared favorably to participants' conventional prostheses across all outcome measures. With its cost, adjustability, and accessibility advantages, this device may prove useful for persons with transtibial amputations. A larger multicenter study is needed to confirm these results., Level of Evidence: III., (© 2019 American Academy of Physical Medicine and Rehabilitation.)

To evaluate the incidence of endometriosis in polycystic ovary syndrome (PCOS) patients who did not present with any endometriosis symptoms and underwent laparoscopic ovarian drilling (LOD) for clomiphene citrate (CC) resistance, 225 and 630 women with CC-resistant PCOS without classic endometriosis symptoms were included in a retrospective study and a meta-analysis, respectively. All women underwent LOD. The main outcome parameter was the prevalence of incidental endometriosis. Laparoscopy revealed endometriosis in 38/225 (16.9%) women (revised American Fertility Society (rAFS) stage I: 33/38, 86.8%; rAFS stage II: 5/38, 13.2%). When women with CC-resistant PCOS without endometriosis were compared, lower body mass index (BMI) and lower 25-hydroxy-vitamin D levels were associated with the presence of endometriosis at laparoscopy (odds ratios (OR): 0.872, 95% confidence intervals (95%CI): 0.792-0.960; p = 0.005 and OR: 0.980, 95%CI: 0.962-0.999; p = 0.036; respectively). The inclusion criteria for the meta-analysis were fulfilled by 4/230 reports about LOD. After correction for study heterogeneity, the pooled prevalence of incidental endometriosis was 7.7% in women with CC-resistant PCOS. In conclusion, the rate of incidental endometriosis in women with CC-resistant PCOS might reflect the prevalence of asymptomatic endometriosis. All cases were affected by minimal or mild disease. Since the literature lacks reports on associated clinical outcomes, the relevance of this entity in such patients should be the subject of further studies.

Purpose: To investigate a possible influence of repetitive micro-traumata on the ovaries in the course of oocyte retrieval during IVF/ICSI treatment on serum anti-Müllerian hormone (AMH) levels., Methods: The study included retrospectively collected data from women who underwent three or more consecutive IVF/ICSI treatments between 2007 and 2017. The primary endpoint of the study was to evaluate changes in serum AMH levels on cycle days 1-3 during the course of repetitive IVF/ICSI treatments., Results: A total of 125 patients were included in this study. Median AMH levels before the first, second and third IVF/ICSI cycles were 3.8 ng/mL (IQR 1.8-7.1), 3.3 ng/mL (IQR 1.8-6.1) and 3.0 ng/mL (IQR 1.6-5.3), respectively (p = n.s.). In patients who underwent IVF/ICSI due to polycystic ovary syndrome (PCOS), we found a significant decrease in AMH serum levels between the first [AMH 9.7 ng/mL (IQR 7.4-14.4)] and the third [AMH 5.3 ng/mL (IQR 3.3-10.4)] IVF/ICSI cycles (p = 0.026). When performing a generalized linear model, we found PCOS to be an independent predictor for serum AMH decrease during the course of three oocyte retrievals (p < 0.001)., Conclusions: When comparing the indications for IVF/ICSI, we observed a significant decrease in AMH serum levels after repetitive oocyte retrievals only in women with PCOS, while the decrease in AMH was not significant in patients with tubal factor, endometriosis, male factor and unexplained infertility. This finding leads us to hypothesize that repetitive micro-traumata on the ovarian cortex might diminish/normalize functional ovarian reserve in women with PCOS. Further prospective studies are highly warranted to allow firm conclusions.

Background: In view of the reported increase in obstetric anal sphincter injuries, the objective of this study was to evaluate the incidence of such injuries over time and the associated risk and protective factors., Methods: This was a retrospective cohort study from a national database of 168 137 primiparous women with term, singleton, cephalic, vaginal delivery between 2008 and 2014. The main outcome measure was obstetric anal sphincter injury. A multivariate regression model was used to identify risk and protective factors., Results: Age >19 years, birthweight >4000 g, and operative vaginal delivery were independent risk factors for obstetric anal sphincter injuries. Mediolateral episiotomy increased the risk for obstetric anal sphincter injuries in spontaneous vaginal birth (number needed to harm 333), whereas it was protective in vacuum delivery (number needed to treat 50). From 2008 to 2014, there was an increase in the rate of obstetric anal sphincter injuries (2.1% vs 3.1%, P < .01), vacuum deliveries (12.1% vs 12.8%, P < .01), and cesarean delivery after labor (17.1% vs 19.4%, P < .01), while forceps deliveries (0.4% vs 0.1%, P < .01) and episiotomy rate decreased (35.9% vs 26.4%, P < .01)., Conclusions: Episiotomy may be a risk or protective factor depending on the type of episiotomy and the clinical setting in which it is used. Our study supports a restrictive use of mediolateral episiotomy in spontaneous vaginal deliveries. In vacuum deliveries mediolateral episiotomy may help prevent obstetric anal sphincter injuries., (© 2018 the Authors. Birth published by Wiley Periodicals, Inc.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To evaluate serum levels of the amino-terminal propeptide of C-type natriuretic peptide (NTproCNP) in uneventful pregnancies and pregnancies complicated by preeclampsia (PE) and NTproCNP's accuracy for prediction of PE., Study Design: Nested case control pilot study including women with uneventful pregnancy (Control, n = 100) and asymptomatic women who later developed PE (PE&#95;long, n = 12). NTproCNP levels were measured in a maximum of ten sequential blood samples per patient (seven visits during pregnancy, three afterwards), which had been collected prospectively., Results: In controls, NTproCNP decreased from weeks 11-13 on, reaching a nadir at the end of the second trimester (weeks 23-27), and subsequently reached the highest levels at the end of pregnancy. In comparison, the PE&#95;long group showed a significantly different NTproCNP course (p = .042), including significantly elevated levels in weeks 18-22 (p = .034) and 23-27 (p = .016). Significant predictive power of single time point measurements of NTproCNP for predicting short-term occurrence of preeclampsia in asymptomatic women was found in weeks 28-32 (p = .023) and 33-36 (p = .014). Furthermore, an increase > -0.038 pmol/l per week between weeks 11-13 and 14-17 was also predictive for PE (area under the curve, AUC: 0.75; p < .001; sensitivity: 90%; specificity: 60%), as was an increase of > 0.084 pmol/l per week between weeks 11-13 and 18-22 (AUC: 0.69, p = .048; sensitivity: 55%; specificity: 88%)., Conclusions: Measurement of NTproCNP in pregnancy might be useful to increase diagnostic awareness in women who will develop PE., (Copyright © 2018 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objective: Oxidative stress and mitochondrial dysfunction may play a crucial role in preeclampsia (PE). The aim of this study was to investigate differences in maternal levels of serum-mitochondrial (mt) DNA, a proposed biomarker for mitochondrial dysfunction, in women with PE compared to healthy pregnant women., Study Design: Using samples obtained from the prospective Biobank study, we measured serum-mtDNA levels in pregnant women diagnosed with PE and in women with uneventful pregnancies, matched for gestational and maternal age, BMI, and smoking status. In a second step, we performed a generalized linear model to detect associations between mtDNA-serum-levels and certain conditions during pregnancy., Results: Mean mtDNA levels were significantly higher in PE (n = 20) than in matched controls (n = 20) and were 0.00767 (SD 0.00255) U/L and 0.00513 (SD 0.00458) U/L, respectively (p = 0.038). We did not find a significant correlation between higher mtDNA levels and early onset PE, IUGR, maternal age, or maternal BMI. Interestingly, increased mtDNA levels were significantly associated with female fetal sex (p = 0.003)., Conclusion: Our findings strengthen the hypothesis postulating that oxidative stress and mitochondrial dysfunction are key factors in the pathophysiology of PE. More prospective studies are highly warranted to further investigate the role of mtDNA in PE and assess the usefulness as a possible biomarker for PE., (Copyright © 2018 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Background: Due to chemotherapy and estrogen deprivation therapy, genitourinary syndrome of menopause is a common condition in breast cancer patients. We aimed to determine the effect of an orally administered Lactobacillus preparation on the vaginal microbiota in breast cancer patients., Methods: Postmenopausal breast cancer patients receiving chemotherapy, with vaginal atrophy and an intermediate vaginal microbiota (Nugent score 4-6), were either randomized to the intervention group receiving probiotic capsules of 4 Lactobacillus species or to the control group receiving placebo twice daily for 2 weeks. Consecutive vaginal swabs were taken at baseline, 1 day after administration of the last capsule (follow-up 1), and after 1 week (follow-up 2) in 22 patients (11 vs. 11)., Results: We observed a positive influence on the vaginal microbiota in 7/11 (63%) women in the intervention group, and 4/11 (36%) women in the control group. There was a shift in Nugent score towards normal microbiota levels in the intervention group (-1.3 at follow-up 1, -0.45 at follow-up 2) and a significant deterioration of the Nugent score in the control group (+0.4 at follow-up 1, +2.5 at follow-up 2)., Conclusion: The orally administered Lactobacillus preparation has the potential to improve the vaginal microbiota in women undergoing chemotherapy for breast cancer.

Purpose: A modified application technique of intrauterine insemination (IUI) is slow release insemination (SRI), first described by Muharib et al. (Hum Reprod 7(2):227-229, 1992), who postulated higher pregnancy rates with a slow release of spermatozoa for 3 h., Methods: To investigate this approach, two randomized controlled, cross-over pilot studies were performed from 2004 to 2006 in Israel and Germany to compare SRI with the standard bolus IUI. We aimed to present the results and perform a meta-analysis on available data for SRI. Univariate comparisons of pregnancy rates were performed using one-tailed z tests for method superiority. For meta-analysis, a fixed-effect Mantel-Haentzel weighted average of relative risk was performed., Results: Fifty treatment cycles (IUI: n = 25, SRI: n = 25) were performed in Germany, achieving four pregnancies (IUI: 4%, SRI: 12%, p > 0.05). Thirty-nine treatment cycles (IUI: n = 19, SRI: n = 20) were performed in Israel achieving six pregnancies (IUI: 10.5%, SRI: 20%; p > 0.05). Meta-analysis of all eligible studies for SRI (n = 3) revealed a combined relative risk for pregnancy after SRI of 2.64 (95% CI 1.04-6.74), p = 0.02)., Conclusions: In conclusion, these results lend support to the hypothesis that the pregnancy rate might be improved by SRI compared to the standard bolus technique.

Background: The ability to identify patients at risk for developing preeclampsia is important for preventing morbidity and mortality in both the mother and child. Although CYFRA 21-1 (a fragment of Cytokeratin 19) is considered a promising biomarker for diagnosing preeclampsia, little is known regarding the levels of CYFRA 21-1 during pregnancy. Here, we measured serum CYFRA 21-1 levels in women with an uneventful pregnancy and in women whose pregnancy was complicated by preeclampsia. Furthermore we evaluated whether maternal CYFRA 21-1 levels can be used to predict and/or diagnose preeclampsia., Methods: Longitudinal, sequential blood samples were collected prospectively at seven predetermined visits during pregnancy. Maternal CYFRA 21-1 levels were measured in 50 women with an uneventful pregnancy (control group) and in 10 asymptomatic women whose pregnancy was later complicated by preeclampsia (PE&#95;long group). In addition, CYFRA 21-1 levels were measured from a single sample collected from a separate group of 50 pregnant women with symptomatic preeclampsia (PE&#95;state group)., Results: The CYFRA 21-1 levels were significantly higher in the PE&#95;state group compared to the control group (p < 0.001). In the PE&#95;long group, CYFRA 21-1 levels were lower from gestational week 11 through 17, but were higher than the control group from gestational weeks 18 through 36. Out of the ROC curves that were calculated to investigate the predictive and diagnostic properties of CYFRA 21-1 levels for preeclampsia, the ROC curve for diagnosing preeclampsia in gestational week 28-32 showed the largest AUC of 0.92, at a cut-off point of 3.1 ng/ml, leading to sensitivity of 92 % and specificity of 80 %., Conclusions: The elevated serum levels of CYFRA 21-1 observed in both groups of women with preeclampsia may reflect endothelial damage and/or dysfunction. Our results suggest that maternal serum CYFRA 21-1 is a promising biomarker for diagnosing preeclampsia. Although its value for predicting the long-term occurrence of subsequent preeclampsia may be limited, our findings indicate a trend towards elevated maternal CYFRA 21-1 levels preceding the short-term occurrence of preeclampsia in asymptomatic women. Additional prospective longitudinal studies are needed in order to determine the value of measuring maternal serum CYFRA 21-1 in predicting preeclampsia.

Objective: Transplantation results in a 5-time elevated risk for a variety of malignancies (Kaposi sarcoma, skin, liver, lung, gastrointestinal cancer). A patient's risk for malignancies could be of particular interest for the follow-up programs of patients and risk adaption after kidney transplantation. The aim of this study was to identify independent risk factors for de novo malignancies in women after renal transplantation., Methods and Materials: This is a multicenter transversal study, conducted at the Medical University of Vienna and Hospital Rudolfstiftung, Vienna, Austria. We included female kidney graft recipients who were transplanted between 1980 and 2012 and followed-up at our institutions (N = 280). Clinical data of patients were extracted from hospital charts and electronic patient files. Patients were interviewed using a standardized questionnaire regarding their medical history, history of transplantation, and malignant diseases. Detailed information about present and past immunosuppressive regimens, rejection episodes and therapies, renal graft function, and information about primary disease was obtained. Diagnostic work-up and/or surgical exploration was performed if any presence of malignancy was suspected during routine follow-up. Histological specimens were obtained from all patients., Main Outcome Measures: the presence of de novo malignancy after kidney transplantation., Results: Two hundred sixty-two women were included for statistical analysis. Median (interquartile range) follow-up period after transplantation was 101.1 (27.3-190.7) months. Thirty-two patients (12.2%) developed a malignancy: dermatologic malignancies (5.7%), breast cancer (3.4%), cervical cancer (0.8%), lung cancer (0.4%), gastrointestinal malignancies (1.5%), vulvar cancer (0.4%), and unclassified malignancies (1.9%). Median (interquartile range) time to malignancy after transplantation was 185.9 (92.0-257.6) months. Cumulative cancer rates were 4.9% (1 year), 14.4% (3 years), 16.4% (5 years), and 21.8% (10 years). Second transplantations were identified as independent risk factor for development of malignancy after transplantation., Conclusions: Long-term risk of developing a malignancy after kidney transplantation is high, which might justify a follow-up of more than 10 years.

Pregnant women with gestational diabetes mellitus (GDM) are reported to be at increased risk for infections of the genital tract. This study aimed to compare the prevalence of asymptomatic bacterial vaginosis (BV) and Candida colonization at early gestation between pregnant women with and without diabetic conditions during pregnancy. We included data from 8, 486 singleton pregnancies that underwent an antenatal infection screen-and-treat programme at our department. All women with GDM or pre-existing diabetes were retrospectively assigned to the diabetic group (DIAB), whereas non-diabetic women served as controls (CON). Prevalence for BV and Candida colonization was 9% and 14% in the DIAB group, and 9% and 13% in the CON group, respectively (n.s.). No significant difference regarding stillbirth and preterm delivery (PTD), defined as a delivery earlier than 37 + 0 (37 weeks plus 0 days) weeks of gestation was found. We could not find an increased risk of colonization with vaginal pathogens at early gestation in pregnant women with diabetes, compared to non-diabetic women. Large prospective studies are needed to evaluate the long-term risk of colonization with vaginal pathogens during the course of pregnancy in these women.

Introduction and Hypothesis: Cycling has become a popular athletic activity worldwide and can lead to genital and pelvic floor dysfunction. This review summarizes the current body of evidence about the epidemiology of genital and pelvic floor symptoms in female cyclists, the therapy, and preventive interventions., Methods: Two electronic meta-databases, OvidSP™ and Deutsches Institut für Medizinische Dokumentation und Information (DIMDI), comprising 40 individual databases, were searched for studies that described genital and pelvic floor symptoms in association with cycling and studies that tested possible therapies and prophylactic measures. For the literature search we explored the search terms "female", "bicycling", "pelvic floor", "lower urinary tract symptoms", and "vulvar diseases"., Results: The search retrieved 1,219 articles, leaving 763 articles after removal of duplicates, and finally 12 articles eligible for review. We assessed 10 observational and 2 experimental studies. Genital and pelvic floor symptoms related to bicycling were pain, tenderness, neuropathy, urological dysfunction and skin lesions. Broader and conventionally shaped saddles were associated with fewer symptoms compared with cut-out saddle designs., Conclusion: The quality of existing studies is generally low, but there is evidence that female cyclists suffer from similar problems to male cyclists, ranging from minor skin lesions to severe sequelae such as pain and neurological deficiencies.

Background: Cytomegalovirus (CMV) is the most prevalent congenital viral infection and thus places an enormous disease burden on newborn infants. Seroprevalence of maternal antibodies to CMV due to CMV exposure prior to pregnancy is currently the most important protective factor against congenital CMV disease. The aim of this study was to identify potential predictors, and to develop and evaluate a risk-predicting model for the maternal CMV serostatus in early pregnancy., Methods: Maternal and paternal background information, as well as maternal CMV serostatus in early pregnancy from 882 pregnant women were analyzed. Women were divided into two groups based on their CMV serostatus, and were compared using univariate analysis. To predict serostatus based on epidemiological baseline characteristics, a multiple logistic regression model was calculated using stepwise model selection. Sensitivity and specificity were analyzed using ROC curves. A nomogram based on the model was developed., Results: 646 women were CMV seropositive (73.2%), and 236 were seronegative (26.8%). The groups differed significantly with respect to maternal age (p = 0.006), gravidity (p<0.001), parity (p<0.001), use of assisted reproduction techniques (p = 0.018), maternal and paternal migration background (p<0.001), and maternal and paternal education level (p<0.001). ROC evaluation of the selected prediction model revealed an area under the curve of 0.83 (95%CI: 0.8-0.86), yielding sensitivity and specificity values of 0.69 and 0.86, respectively., Conclusion: We identified predictors of maternal CMV serostatus in early pregnancy and developed a risk-predicting model based on baseline epidemiological characteristics. Our findings provide easy accessible information that can influence the counseling of pregnant woman in terms of their CMV-associated risk.

Objective: Gonadotropin releasing hormone agonists (GnRHa) decrease the expression of growth factors involved in the development of human endometriotic tissue. As endometriosis has been found to be associated with a mild increase in prolactin (PRL) serum levels, we aimed to evaluate changes in PRL serum levels as well as other hormones relevant to endometriosis and infertility during long-term administration of GnRHas in women with endometriosis., Study Design: In this prospective pilot study we obtained blood samples on the first day of leuporeline administration and then subsequently after 4, 8 and 12 weeks in 22 patients., Results: Median PRL levels were unchanged after 4 weeks, but significantly decreased 8 and 12 weeks after the first leuporeline administration (p1=0.085, p2=0.020, p3=0.001). There was no significant decrease in serum anti-Mullerian hormone (AMH) levels over the whole period of down regulation with leuporeline (p1-3>0.05)., Conclusion: Our data support the hypothesis that the decrease of PRL levels might contribute to the known effect of GnRH treatment in patients with endometriosis via suppression of VEGF expression in endometriotic lesions. Moreover this study lends support to the thesis that AMH remains stable under GnRHa therapy and therefore can be also used as a marker of ovarian function prior to IVF-stimulation during down regulation., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: Renal transplant patients are at increased risk for human papillomavirus-related malignancies of the lower genital tract. Our aim was to describe the incidence of genital dysplasia, assess the most common cervical cancer screening intervals and identify independent risk factors for the development of genital dysplasia in renal transplant patients., Design: Retrospective, non-interventional study from two centers., Setting: Post-transplant nephrologic follow-up visit at the Medical University of Vienna and a Viennese teaching hospital., Population: 262 consecutive female renal transplant patients with renal transplant performed between 1980 and 2012 at the Medical University of Vienna., Methods: Sociodemographic patient characteristics, frequency of gynecological examinations, histo- and cytopathological test results were collected., Main Outcome Measures: Dysplasia rates in renal transplant patients., Results: 16 patients (6.2%) with genital dysplasia after renal transplant were observed. The 1-year, 3-year and 10-year proportional incidence rates for genital dysplasia in general and cervical dysplasia in particular were 1.3 and 1.3%, 3.3 and 2.7%, and 13.6 and 12.0%, respectively. Patients attended cervical cancer screening on a regular basis once a year in 82.7% of cases. In multivariate analysis re-transplantation [odds ratio 12.1 (1.5-96.3)], and renal transplant at a young age [odds ratio 0.6 (0.4-0.9)] were identified as independent risk factors for the development of female genital dysplasia., Conclusions: Female renal transplant patients have an increased risk for the development of genital dysplasia in general and of cervical dysplasia in particular. Within this cohort, women at a young age at the time of transplantation and after re-transplantation are at highest risk for the development of genital dysplasia., (© 2015 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: Vaginal infection in early pregnancy is associated with preterm birth. This study evaluates long-term results after integrating an antenatal screen-and-treat program for asymptomatic vaginal infections into routine pregnancy care., Methods: We retrospectively analyzed data of all women with singleton high-risk pregnancies delivering at our tertiary referral center between 2005 and 2014. The intervention group included women who presented for a prenatal visit for a planned birth between 10 + 0 and 16 + 0 gestational weeks. Women were routinely screened for asymptomatic infections using Gram stain. In cases of bacterial vaginosis, candidiasis or trichomoniasis, women were treated according to our clinical protocol. The control group included women who did not undergo the program. Prenatal care was equal in both groups. Preterm birth served as the primary outcome variable., Results: Of the 20,052 women with singleton pregnancies, 8,490 (42.3%) participated in the antenatal prevention program. The mean gestational age at birth was 38.8 ± 2.6 weeks and 37.5 ± 4.3 weeks in the intervention and control groups, respectively (p < 0.001). The incidence of preterm birth was significantly lower in the intervention group than in the control group (9.7% vs 22.3%; p < 0.001). Low-birthweight neonates, stillbirths, and late miscarriages were less frequent in the intervention group (p < 0.001)., Conclusions: Long-term results support the use of an antenatal infection screen-and-treat program to prevent preterm birth. If integrated into routine pregnancy care at a high-risk obstetrical setting, this simple public health intervention could lead to a significant reduction in preterm birth, low infant birthweight, and adverse pregnancy outcomes., (© 2015 Wiley Periodicals, Inc.)