Different Impacts of Cryopreservation in Endothelial and Epithelial Ovarian Cells.

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.

A case-control study about markers of stress in normal-/overweight women with polycystic ovary syndrome and in controls.

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.

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

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.

Basal and dynamic relationships between serum anti-Müllerian hormone and gonadotropins in patients with functional hypothalamic amenorrhea, with or without polycystic ovarian morphology.

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.

Analyses of human granulosa cell vitality by fluorescence activated cell sorting after rapid cooling.

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.

Clinical risk factors for recurrence of pelvic organ prolapse after primary native tissue prolapse repair.

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 POP­Q 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.

Comparison of a practice-based versus theory-based training program for conducting vacuum-assisted deliveries: a randomized-controlled trial.

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 (pall < 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.

Markers of vitality in ovaries of transmen after long-term androgen treatment: a prospective cohort study.

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).

Pregnancy rates after slow-release insemination (SRI) and standard bolus intrauterine insemination (IUI) - A multicentre randomised, controlled trial.

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.

Assessment of Tubal Patency: A Prospective Comparison of Diagnostic Hysteroscopy and Laparoscopic Chromopertubation.

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.

The Prevalence of Incidental Endometriosis in Women Undergoing Laparoscopic Ovarian Drilling for Clomiphene-Resistant Polycystic Ovary Syndrome: A Retrospective Cohort Study and Meta-Analysis.

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.

The impact of repetitive oocyte retrieval on the ovarian reserve: a retrospective cohort study.

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.

Maternal serum mitochondrial DNA (mtDNA) levels are elevated in preeclampsia - A matched case-control study.

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.

Impact of vitrification on granulosa cell survival and gene expression.

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.

Risk and protective factors for obstetric anal sphincter injuries: A retrospective nationwide study.

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.

Dynamics of serum C-type natriuretic peptide as predictor for preeclampsia.

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_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_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.

Influence of Orally Administered Probiotic Lactobacillus Strains on Vaginal Microbiota in Women with Breast Cancer during Chemotherapy: A Randomized Placebo-Controlled Double-Blinded Pilot Study.

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.

The effect of slow release insemination on pregnancy rates: report of two randomized controlled pilot studies and meta-analysis.

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.

The usefulness of CYFRA 21-1 to diagnose and predict preeclampsia: a nested case-control study.

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_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_state group). RESULTS: The CYFRA 21-1 levels were significantly higher in the PE_state group compared to the control group (p < 0.001). In the PE_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.

Risk of Vaginal Infections at Early Gestation in Patients with Diabetic Conditions during Pregnancy: A Retrospective Cohort Study.

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.