Serum erythropoietin level is increased during stimulation for IVF but not in OHSS.

BACKGROUND: Erythropoietin (Epo) is a potent vascular growth factor that induces angiogenesis and antiapoptotic signalling. We investigated whether the development of numerous follicles and corpora lutea during in vitro fertilization (IVF) cycle affects circulating Epo levels and further, if Epo could be used as a novel marker for ovarian hyperstimulation syndrome (OHSS). METHODS: 24 women were included in the uncomplicated IVF group and 35 women in the OHSS group. Repeated blood samples from both groups were analysed for Epo, progesterone, blood haemoglobin, and creatinine. Follicular fluid from the IVF group was analysed for Epo and progesterone. Repeated measure analysis was performed for the variables and circulating Epo levels were compared between the IVF group and early OHSS. Furthermore, related growth factors, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 (HIF-1) were analysed from subgroup of women to test for correlation with Epo. RESULTS: During IVF, circulating Epo increased from natural mid-luteal phase to stimulated mid-luteal phase (median 9.5; 95% CI 7.2-13.4 IU/L and 12.5; 10.3-13.4 IU/L; p = 0.003). In cycles resulting in pregnancy, Epo level decreased 14 days after oocyte pick-up (OPU) and remained low thereafter. In cycles not resulting in pregnancy, Epo level increased again 35 days after OPU. Follicle fluid Epo concentration was 1.5 times higher than the serum concentration (median 15.4; 95% CI 10.4-19.2 IU/L vs. 10.2; 8.8-12.7; p = 0.006). There was no difference in circulating Epo concentration between early OHSS and uncomplicated IVF. Circulating Epo did not correlate with VEGF or HIF-1. CONCLUSIONS: Circulating Epo levels fluctuate during IVF cycle. We hypothesise this may suggest Epo's involvement in ovarian physiology and angiogenesis. However, Epo was not a clinical marker for OHSS.

Quality of life and sexual function after tension-free vaginal tape and polyacrylamide hydrogel injection for primary stress urinary incontinence: 3-year follow-up from a randomized clinical trial.

INTRODUCTION AND HYPOTHESIS: To assess quality of life (QoL) and sexual function outcomes at 3 years after tension-free vaginal tape (TVT) and polyacrylamide hydrogel injection (PAHG) for stress urinary incontinence (SUI). METHODS: In this randomized trial comparing TVT (n = 104) and PAHG (n = 108), we assessed changes in QoL and sexuality using the Urogenital Distress Inventory (UDI-6), Incontinence Impact Questionnaire, Short Form (IIQ-7), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) and RAND-36 Item Health Survey (RAND-36) at baseline and at 3 years. This is a secondary analysis of a randomized, noninferiority trial comparing patient satisfaction after TVT and PAHG. RESULTS: In both groups, incontinence-related QoL improved from the baseline (p < 0.00), except for difficulty emptying the bladder and pain/discomfort. Total scores of UDI-6 and IIIQ-7 were lower for TVT compared to PAHG (p < 0.00) indicating better QoL at 3 years. Urinary incontinence with sexual activity or fear of incontinence restricting sexual activity improved in both groups (p < 0.00), with higher scores for physical section subscale in PISQ-12 (p = 0.02) for TVT. Physical and social functioning (RAND-36) improved from the baseline in both groups (p < 0.01) with a better outcome in the TVT group for physical functioning (p = 0.00). CONCLUSIONS: Both TVT and PAHG improve QoL and sexual function in primary SUI with better incontinence and health-related QoL scores in the TVT group compared to the PAHG group at 3 years.

Association of serum cortisol and cortisone levels and risk of recurrence after endocrine treatment in breast cancer.

Metabolic reprogramming in breast cancer involves changes in steroid hormone synthesis and metabolism. Alterations in estrogen levels in both breast tissue and blood may influence carcinogenesis, breast cancer growth, and response to therapy. Our aim was to examine whether serum steroid hormone concentrations could predict the risk of recurrence and treatment-related fatigue in patients with breast cancer. This study included 66 postmenopausal patients with estrogen receptor-positive breast cancer who underwent surgery, radiotherapy, and adjuvant endocrine treatment. Serum samples were collected at six different time points [before the start of radiotherapy (as baseline), immediately after radiotherapy, and then 3, 6, 12 months, and 7-12 years after radiotherapy]. Serum concentrations of eight steroid hormones (cortisol, cortisone, 17α-hydroxyprogesterone, 17ß-estradiol, estrone, androstenedione, testosterone, and progesterone) were measured using a liquid chromatography-tandem mass spectrometry-based method. Breast cancer recurrence was defined as clinically proven relapse/metastatic breast cancer or breast cancer-related death. Fatigue was assessed with the QLQ-C30 questionnaire. Serum steroid hormone concentrations measured before and immediately after radiotherapy differed between relapse and relapse-free patients [(accuracy 68.1%, p = 0.02, and 63.2%, p = 0.03, respectively, partial least squares discriminant analysis (PLS-DA)]. Baseline cortisol levels were lower in patients who relapsed than in those who did not (p < 0.05). The Kaplan-Meier analysis showed that patients with high baseline concentrations of cortisol (≥ median) had a significantly lower risk of breast cancer recurrence than patients with low cortisol levels (

Effect of the maternal childbirth experience on a subsequent birth: a retrospective 7-year cohort study of primiparas in Finland.

OBJECTIVE: To study the effect of the childbirth experience on the likelihood and interval to a subsequent live birth. DESIGN: Retrospective analysis of a 7-year cohort. SETTING: Childbirths in Helsinki University Hospital delivery units. PARTICIPANTS: All parturients giving birth to a term and living baby from a single pregnancy in Helsinki University Hospital delivery units from January 2012 to December 2018 (n=120 437). Parturients delivering their first child (n=45 947) were followed until the birth of a subsequent child or the end of 2018. MAIN OUTCOME MEASURE: The interval to a subsequent childbirth connected to the experience of the first childbirth was the primary outcome of the study. RESULTS: A negative first childbirth experience decreases the likelihood of delivering a subsequent child during the follow-up (adjusted HR=0.81, 95% CI 0.76 to 0.86) compared with those experiencing the first childbirth as positive. For parturients with a positive childbirth experience, the median interval to a subsequent delivery was 3.90 years (3.84-3.97) compared with 5.29 years (4.86-5.97) after a negative childbirth experience. CONCLUSION: The negative childbirth experience influences reproductive decisions. Consequently, more focus should be placed on understanding and managing the antecedents of positive/negative childbirth experiences.

Sex Steroid Hormone Analysis in Human Tear Fluid Using a Liquid Chromatography-Mass Spectrometry Method.

The marked sexual dimorphism prevalent in inflammatory/autoimmune diseases is mostly due to sex hormone actions. One common eye disease that disproportionately affects women is dry eye. Thus, our aim was to optimise our highly sensitive liquid chromatography-tandem mass spectrometry method for steroid hormone quantification in tear fluid (TF). We used tears and matched serum samples from 10 heathy individuals. Estrone, estradiol testosterone, progesterone, androstenedione, and dehydroepiandrosterone, were quantified with an HPLC coupled with a Triple Quad 5500 MS. Estrone was measured in 80% of female and 20% of male TF samples (mean ± SD, 68.9 ± 62.2 pmol/L), whereas estradiol was undetectable in tears. Progesterone was identified in half of the female tear samples (2.91 ± 3.47 nmol/L) but in none of the male samples, whereas testosterone was quantifiable only in male tears (0.24 ± 0.1 nmol/L). TF hormone levels were, on average, from 1.4% to 55% of systemic values. Estrone, progesterone, and testosterone levels in tears correlated with the matching serum samples (r = 0.82, 0.79, and 0.85, respectively), but androstenedione and dehydroepiandrosterone showed no correlations. Our LC-MS/MS method could detect five out of the six steroid hormones studied in individual human TF samples and could therefore be used to analyse the role of sex steroids in eye diseases.

Pre-eclampsia and cardiovascular risk: a long-term nationwide cohort study on over 120 000 Finnish women.

OBJECTIVES: To investigate the impact of pre-eclampsia on the future cardiovascular risk in Finnish women DESIGN: A registry-based nationwide controlled cohort study. SETTING: Women hospitalised for pre-eclampsia in 1969-1993 and control women with a history of normotensive pregnancies followed from the pre-eclampsia diagnosis until 2019 for cardiovascular outcomes. PARTICIPANTS: 31 688 women with and 91 726 control women without a history of pre-eclampsia. PRIMARY OUTCOME MEASURES: Incidences of and deaths from ischaemic heart disease (IHD), myocardial infarction (MI) and stroke. RESULTS: In total, 25 813 (81.5%) women had pre-eclampsia without severe features, 4867 (15.4%) had pre-eclampsia with severe features and 1006 (3.2%) women developed eclampsia. Women with a history of pre-eclampsia showed elevated risks for IHD (HR 1.52, 95% CI 1.44 to 1.59), MI (HR 1.66, 95% CI 1.52 to 1.81) and stroke (HR 1.40, 95% CI 1.32 to 1.48). The risks for death from IHD (HR 1.50, 95% CI 1.28 to 1.75), MI (1.63, 95% CI 1.30 to 2.05) and stroke (1.44, 95% CI 1.03 to 2.01) were also elevated. Pre-eclampsia with severe features or eclampsia was accompanied with 15% higher IHD risk, 19% higher MI risk and 26% higher stroke risk than pre-eclampsia without severe features. The highest risk elevations of 30% for IHD, 32% for MI and 30% for stroke were observed in women with recurrent pre-eclampsia (n=4180). CONCLUSION: Pre-eclampsia-related significant elevations in CVD risks of Finnish women with inherently high risk for these diseases were of the same magnitude as reported previously from other countries. Thus, women with a history of pre-eclampsia should be screened and treated early for modifiable cardiovascular risk factors.

Effect of hysterectomy on re-operation for stress urinary incontinence: 10 year follow-up.

PURPOSE: Hysterectomy and mid-urethral sling (MUS) are common operations, but little is known about how hysterectomy after MUS affects the risk for stress urinary incontinence (SUI) relapse. METHODS: We included 49 women with a MUS before hysterectomy and 41 women with a MUS concomitant with hysterectomy. The controls, matched by age (± 2 years), MUS type (retropubic vs transobturator) and operation year (± 2 years), included 201 women who underwent the MUS operation without a subsequent hysterectomy. We used health care registers for follow-up of 12.4 years in median (IQR 10.9-14.7) after the MUS operation to compare the number of SUI re-operations and hospital re-visits for urinary incontinence. RESULTS: The re-operation rates for SUI did not differ between the women with MUS before hysterectomy (n = 2, 4.1%), women with MUS concomitant with hysterectomy (n = 2, 4.9%) and their controls (n = 4, 4.9%, p = 0.8 and n = 6, 5.0%, p = 1.0, respectively). There were significantly fewer urinary incontinence re-visits among women who had a MUS concomitant with the hysterectomy compared to their matched controls (n = 2 and 31, 5 and 31%, p < 0.01) and to the women with a MUS prior to hysterectomy (n = 2 and 10, 5 and 20%, respectively, p = 0.03). CONCLUSION: Hysterectomy after or concomitant with MUS does not seem to increase the risk for SUI re-operation or hospital re-visits for urinary incontinence. These results can be used to counsel women considering hysterectomy after MUS operation or concomitant with MUS operation.

Tension-Free Vaginal Tape and Polyacrylamide Hydrogel Injection for Primary Stress Urinary Incontinence: 3-Year Followup from a Randomized Clinical Trial.

PURPOSE: We sought to determine whether polyacrylamide hydrogel (PAHG) is noninferior to tension-free vaginal tape (TVT) in the treatment of women with primary stress urinary incontinence (SUI). MATERIALS AND METHODS: In this noninferiority trial, 223 women eligible for operative SUI treatment were randomized for TVT (110) or PAHG (113). Primary outcome was patient satisfaction and the noninferiority margin for the difference was 20%. Secondary outcomes were effectiveness and complications. RESULTS: At 3 years, 188 (84.3%) women attended the followup. The satisfaction score (visual analogue scale 0-100) median was 98.5 (IQR 90-100) in the TVT group and 90.0 (IQR 70-100) in the PAHG group, whereas a score ≥80 was reached in 87 (94.6%) and 65 (67.7%), respectively (difference 26.9%, 95% CI 16.7% to 36.8%). Thus, PAHG did not meet the noninferiority criteria set in our study. The cough stress test was negative in 88 (95.7%) of TVT patients vs 75 (78.1%) of PAHG patients (difference 17.5%, 95% CI 8.6% to 26.9%). Any peri- or postoperative complication before crossover between the groups was detected in 40 (43.5%) women in the TVT group and 23 (24.0%) women in the PAHG group (difference 19.5%, 95% CI 6.8% to 31.4%). CONCLUSIONS: In midterm followup, PAHG did not reach in patient satisfaction the noninferiority set in our study. Furthermore, mid urethral TVT slings show better subjective and objective cure rates than PAHG. However, complications were more often associated with TVT. Since the majority of PAHG treated women were also cured or improved, primary SUI women can be offered PAHG as a safe and durable alternative treatment.

Maternal childbirth experience and induction of labour in each mode of delivery: a retrospective seven-year cohort study of 95,051 parturients in Finland.

BACKGROUND: Childbirth experience has been shown to depend on the mode of delivery. However, it is unclear how labour induction influences the childbirth experience in different modes of delivery. Thus, we assessed the childbirth experience among mothers with spontaneous and induced labours. DESIGN: A retrospective cohort study. SETTING: Childbirths in four delivery hospitals in Helsinki and Uusimaa District, Finland, in 2012-2018. SAMPLE: 95051 childbirths excluding elective caesarean sections. METHODS: Obstetric data combined to maternal childbirth experience measured by Visual Analogue Scale (VAS) was analysed with univariate linear modelling and group comparisons. The primiparas and multiparas were analysed separately throughout the study due to the different levels of VAS. MAIN OUTCOME MEASURES: Maternal childbirth experience measured by VAS. RESULTS: The negative effect of labour induction on the childbirth experience was discovered in each mode of delivery. Operative deliveries were perceived more negatively when they were preceded by labour induction. The rate of poor childbirth experience (VAS≤5) was higher for mothers with labour induction (ORs varying from 1.43 to 1.77) except in emergency caesarean sections. The negative effect of labour induction was smaller than the effect of mode of delivery, while successful vaginal delivery with induction (meanPRIMI=8.00 [95% CI 7.96-8.04], meanMULTI=8.50 [8.47-8.53]) was perceived more positive than operational deliveries with spontaneous labour (meansPRIMI≤7.66 [7.61-7.70], meansMULTI≤7.96 [7.89-8.03]). However, labour induction more than doubled the risk of caesarean section for both primiparas and multiparas. CONCLUSIONS: Labour induction generates more negative experiences for both primiparas and multiparas. The negative effect of labour induction is detected for all modes of delivery, being worst among labour induction resulting in operative delivery. The parturients facing cumulative obstetric interventions require special support and counselling during and after delivery.

Maternal childbirth experience and pain relief methods: a retrospective 7-year cohort study of 85 488 parturients in Finland.

OBJECTIVES: The aim of this study was to analyse the relation between the used labour pain relief and childbirth experience measured by Visual Analogue Scale (VAS). DESIGN: A retrospective cohort study. SETTING: Childbirth in five Helsinki University Hospital delivery units from 2012 to 2018. PRIMARY OUTCOME MEASURE: Childbirth experience measured by VAS and classified in three groups (negative VAS=1-5, positive VAS=6-8 and highly positive=9-10). RESULTS: The use of epidural or non-epidural compared with non-medical pain relief methods decreased the likelihood to experience highly positive childbirth for primiparous (adjusted OR (aOR)EPIDURAL=0.64, 95% CI 0.57 to 0.73; and aORNON-EPIDURAL=0.76, 95% CI 0.66 to 0.87) and multiparous (aOREPIDURAL=0.90, 95% CI 0.84 to 0.97 and aORNON-EPIDURAL=0.80, 95% CI 0.74 to 0.86) parturients. The effects of epidural differed between primiparas and multiparas. In multiparas epidural was associated with decreased odds for experiencing negative childbirth compared with the non-medical group (aOR=0.70, 95% CI 0.57 to 0.87), while the effect of epidural was considered insignificant in primiparas (aOR=1.28, 95% CI 0.93 to 1.77). CONCLUSION: While the use of medical-epidural and non-epidural-pain relief methods were not associated with odds for experiencing negative childbirth in primiparas, using epidural helps to avoid negative experience in multiparas. However, the odds for experiencing highly positive childbirth were decreased if the parturients used any medical pain relief for both primiparas and multiparas. Consequently, the effect of pain relief on the childbirth experience is strongly confounded by indication. Thus, the use of pain relief per se plays a limited role in the complex formation of the overall childbirth experience.

Direct Ink Writing of Biocompatible Nanocellulose and Chitosan Hydrogels for Implant Mesh Matrices.

Direct ink writing via single or multihead extrusion is used to synthesize layer-by-layer (LbL) meshes comprising renewable polysaccharides. The best mechanical performance (683 ± 63 MPa modulus and 2.5 ± 0.4 MPa tensile strength) is observed for 3D printed structures with full infill density, given the role of electrostatic complexation between the oppositely charged components (chitosan and cellulose nanofibrils). The LbL structures develop an unexpectedly high wet stability that undergoes gradual weight loss at neutral and slightly acidic pH. The excellent biocompatibility and noncytotoxicity toward human monocyte/macrophages and controllable shrinkage upon solvent exchange make the cellular meshes appropriate for use as biomedical implants.

Maternal childbirth experience and time of delivery: a retrospective 7-year cohort study of 105 847 parturients in Finland.

OBJECTIVES: To explore how the time of delivery influences childbirth experience. DESIGN: A retrospective cohort study. SETTING: Childbirth in the four Helsinki and Uusimaa Hospital District hospitals, Finland, from 2012 to 2018. PARTICIPANTS: 105 847 childbirths with a singleton live fetus. MAIN OUTCOME MEASURES: Childbirth experience measured by Visual Analogue Scale (VAS). RESULTS: The major difference in average childbirth experience measured by VAS was between primiparas (8.03; 95% CI 8.01 to 8.04) and multiparas (8.47; 95% CI 8.45 to 8.48). Risk ratio (RR) of the low VAS (≤5) was 2.3 when primiparas were compared with multiparas. Differences in VAS between distinct periods were found in two stages: annual and time of day. The decrease in VAS from 2012-2016 to 2017-2018 in primiparas was from 7.97 (95% CI 7.95 to 7.99) to 7.80 (95% CI 7.77 to 7.83) and from 2014-2016 to 2017-2018 in multiparas from 8.60 (95% CI 8.58 to 8.61) to 8.49 (95% CI 8.47 to 8.52). Corresponding RRs of low VAS were 1.3 for primiparas and 1.2 for multiparas. Hourly differences in VAS were detected in primiparas between office hours 08:00-15:59 (7.97; 95% CI 7.94 to 7.99) and other times (night 00:00-07:59; 7.91; 95% CI 7.88 to 7.94; and evening 16:00-23:59; 7.90; 95% CI 7.87 to 7.92). In multiparas differences in VAS were detected between evening (8.52; 95% CI 8.50 to 8.54) and other periods (night; 8.56; 95% CI 8.54 to 9.58; and office hours; 8.57; 95% CI 8.55 to 8.59). CONCLUSION: The maternal childbirth experience depended on the time of delivery. Giving birth during the evening led to impaired childbirth experience in both primiparas and multiparas, compared with delivery at other times. The impact of labour induction on childbirth experience should be further examined. The reorganisation of delivery services and the reduction of birth preparations might affect annual VAS. VAS is a simple method of measuring the complex entity of childbirth experience, and our results indicate its ability to capture temporal variation.

Adipose tissue estrogen production and metabolism in premenopausal women.

OBJECTIVE: Although the ovaries produce the majority of estrogens in women before menopause, estrogen is also synthesized in peripheral tissues such as adipose tissue (AT). The typical female AT distribution, concentrated in subcutaneous and femoro-gluteal regions, is estrogen-mediated, but the significance of estrogen synthesis in AT of premenopausal women is poorly understood. DESIGN AND METHODS: Serum and subcutaneous and visceral AT homogenates from 28 premenopausal women undergoing non-malignant surgery were analyzed for estrone, estradiol, and serum estrone sulfate (E1S) concentrations with liquid chromatography-tandem mass spectrometry. Isotopic precursors were used to measure enzyme activities of estrone-producing steroid sulfatase and estradiol-producing 17ß-hydroxysteroid dehydrogenases (17ß-HSD). Messenger RNA (mRNA) expression levels of genes for estrogen-metabolizing enzymes were analyzed using real-time reverse transcription quantitative polymerase chain reaction. RESULTS: While estradiol was the predominant circulating active estrogen, estrone dominated in AT, with a higher concentration in visceral than subcutaneous AT (median, 2657 vs 1459 pmol/kg; P = 0.002). Both AT depots converted circulating E1S to estrone, and estrone to estradiol. Median levels of estrone were five to ten times higher in subcutaneous and visceral AT than in serum (P < 0.001) and the estradiol level in visceral AT was 1.3 times higher than in serum (P < 0.005). The local estrone concentration in visceral AT correlated positively with mRNA expression of estrone-producing enzyme aromatase (r = 0.65, P = 0.003). Waist circumference correlated positively with increased estradiol production in subcutaneous AT (r = 0.60, P = 0.039). CONCLUSIONS: Premenopausal AT demonstrated high estrogenic enzyme activity and considerable local estrogen concentrations. This may be a factor promoting female-typical AT distribution in premenopausal women.

Long-term outcomes of pelvic organ prolapse repair using a mesh-capturing device when comparing single- versus multicenter use.

PURPOSE: The aim of this study was to compare long-term effects of high-volume surgery at a single-center to multicenter use when using a mesh-capturing device for pelvic organ prolapse (POP) repair. METHODS: Five years after surgery 101 (88%) at the single center were compared with 164 (81.2%) in the multicenter trial. Outcome measurements included clinical examination, prolapse-specific symptom questionnaires [Pelvic Floor Distress Inventory 20 (PFDI-20), Pelvic Floor Impact Questionnaire-short form (PFIQ-7), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12)] and pain estimation by VAS (0-10). RESULTS: Optimal apical segment outcome was 95% in the single- compared to 83.3% in the multicenter study (p < 0.001). POP recurrence in the anterior and posterior walls (POP-Q, Ba and Bp ≥ 0) was more common at the multicenter as compared to the single center [(19.8% vs 5.4%) and (26% vs 2.7%), (p < 0.001)]. Reoperations for POP and mesh-related complications were more frequent in the multicenter study [31/202 (15.3%) vs 7/116 (6.1%), p < 0.001]. Total PFDI-20, PFIQ-7 and PISQ-12 scores were comparable between the cohorts. There were no significant differences in overall pain scores in-between the cohorts during follow-up. At the single center, 1/81 patients (1.2%) had VAS 7/10, i.e. severe pain, as compared to 3/131 (2.3%) in the multicenter study (p = 0.277). CONCLUSIONS: Despite the high objective and subjective long-term effectiveness of the procedure in both regular use, and at a high-volume center, centralizing the use of a standardized capturing-device guided transvaginal mesh for POP repair reduced secondary interventions by more than half.

Pregnancy and delivery after mid-urethral sling operation.

INTRODUCTION AND HYPOTHESES: There is no consensus regarding pregnancy after mid-urethral sling (MUS) operation, and some clinicians recommend postponing the MUS operation if a woman considers further pregnancies or routinely suggest cesarean section as the delivery method after MUS operations. Our primary aim was to assess the risk for stress urinary incontinence (SUI) re-procedure after delivery in women with a MUS operation prior to pregnancy. We also analyzed SUI re-visits and MUS-related complications during pregnancy and postpartum. METHODS: We conducted a register-based case-control study of women with a MUS operation in Finland during 1996-2016. We identified 94 cases with a subsequent pregnancy and 330 controls without subsequent pregnancies matched by age, operation type and year. RESULTS: The median follow-up time was 10.7 years (IQR 7.1-13.7). The number of SUI re-procedures did not differ between the cases (n = 3, 3.2%) and controls (n = 17, 5.2%; OR 0.6, 95% CI 0.2-2.1). There was no significant difference in re-visits for stress or mixed urinary incontinence between the cases (n = 23, 24.5%) and controls (n = 86, 26.1%; OR 0.9, 95% CI 0.5-1.6), but 35% of the re-visits in the case group occurred already before the delivery after MUS. The rate of vaginal delivery was lower after MUS operation (57%) than in deliveries before MUS (91%, P < 0.001). CONCLUSIONS: Pregnancy after MUS did not increase the odds for SUI re-procedure or re-visit. Considering on our results, future pregnancy does not need to be viewed as an absolute contraindication for MUS operation.

Quality of life and sexual function after TVT surgery versus Bulkamid injection for primary stress urinary incontinence: 1 year results from a randomized clinical trial.

INTRODUCTION AND HYPOTHESIS: To assess changes in quality of life (QoL) and sexual function outcomes at 1 year after tension-free vaginal tape (TVT) versus polyacrylamide hydrogel injection (PAHG). METHODS: In a randomized trial comparing TVT (n = 111) and PAHG (n = 113) treatments of stress urinary incontinence (SUI), we compared urinary incontinence and health-related QoL using the Urogenital Distress Inventory (UDI-6), Incontinence Impact Questionnaire, Short Form (IIQ-7), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) and RAND-36 Item Health Survey (RAND-36) at baseline and 1 year. RESULTS: UDI-6 and IIQ-7 showed improved incontinence-related QoL (p = 0.001) from baseline in both groups except for difficulty emptying the bladder and pain/discomfort. At 1 year, TVT patients experienced less urinary symptom-related distress compared to PAHG (p < 0.001). Sexual function improved in both groups (p < 0.001 for TVT and p = 0.01 for PAHG) with higher scores for the physical section subscale (p < 0.001) for TVT. Health-related QoL (RAND-36) improved from baseline in both groups in physical and social functioning (p < 0.001) with better outcome in the TVT group for physical functioning (p < 0.001). Increase in pain from baseline (p = 0.02) was detected for TVT, but not for PAHG. However, there was no difference between the groups (p = 0.78). CONCLUSIONS: In primary SUI, TVT and PAHG treatments both improved QoL and sexual function at 1 year. However, incontinence and health-related QoL scores were better in the TVT group. More pain compared to the baseline was reported after TVT, although there was no difference between groups. Clinical significance needs to be evaluated in long-term follow-up.

Human adipocyte differentiation and composition of disease-relevant lipids are regulated by miR-221-3p.

MicroRNA-221-3p (miR-221-3p) is associated with both metabolic diseases and cancers. However, its role in terminal adipocyte differentiation and lipid metabolism are uncharacterized. miR-221-3p or its inhibitor was transfected into differentiating or mature human adipocytes. Triglyceride (TG) content and adipogenic gene expression were monitored, global lipidome analysis was carried out, and mechanisms underlying the effects of miR-221-3p were investigated. Finally, cross-talk between miR-221-3p expressing adipocytes and MCF-7 breast carcinoma (BC) cells was studied, and miR-221-3p expression in tumor-proximal adipose biopsies from BC patients analyzed. miR-221-3p overexpression inhibited terminal differentiation of adipocytes, as judged from reduced TG storage and gene expression of the adipogenic markers SCD1, GLUT4, FAS, DGAT1/2, AP2, ATGL and AdipoQ, whereas the miR-221-3p inhibitor increased TG storage. Knockdown of the predicted miR-221-3p target, 14-3-3γ, had similar antiadipogenic effects as miR-221-3p overexpression, indicating it as a potential mediator of mir-221-3p function. Importantly, miR-221-3p overexpression inhibited de novo lipogenesis but increased the concentrations of ceramides and sphingomyelins, while reducing diacylglycerols, concomitant with suppression of sphingomyelin phosphodiesterase, ATP citrate lyase, and acid ceramidase. miR-221-3p expression was elevated in tumor proximal adipose tissue from patients with invasive BC. Conditioned medium of miR-221-3p overexpressing adipocytes stimulated the invasion and proliferation of BC cells, while medium of the BC cells enhanced miR-221-3p expression in adipocytes. Elevated miR-221-3p impairs adipocyte lipid storage and differentiation, and modifies their ceramide, sphingomyelin, and diacylglycerol content. These alterations are relevant for metabolic diseases but may also affect cancer progression.

Plasma pentraxin 3 is higher in early ovarian hyperstimulation syndrome than in uncomplicated in vitro fertilization cycle of high-risk women.

PURPOSE: Pentraxin 3 (PTX3) is a locally secreted, quicker responsive pro-inflammatory protein than C-reactive protein (CRP). We evaluated the value of PTX3 in the prediction of ovarian hyperstimulation syndrome (OHSS), a severe complication of in vitro fertilization (IVF). METHODS: This two-year prospective follow-up study included 27 women with uncomplicated IVF-cycles (IVF group) and 31 patients diagnosed with moderate or severe early OHSS (OHSS group). PTX3 was analysed from follicular fluid (FF) and serial blood samples with enzyme-linked immunoassay and CRP with particle-enhanced immunoturbidimetric assay. The value of PTX3 and CRP in detecting OHSS was examined with receiver operating characteristic (ROC) curve analysis and expressed as the area under the curve (AUC). RESULTS: The circulating PTX3 level peaked at two days after oocyte pick-up (OPU2), and in the OHSS group the level was 1.9 times higher (P = 0.006) than in the IVF group. However, in ROC curve analysis PTX3 (AUC 0.79, best cut off 1.1 µg/L) was not superior to CRP (AUC 0.87; best cut off 9.5 mg/L) in predicting early OHSS. In the IVF group, the FF-PTX3 concentration was 15-20 times higher than in the plasma. PTX3 level at OPU2 correlated with the number of punctured follicles (r = 0.56, n = 22, P = 0.006). Triggering with human chorionic gonadotrophin or early pregnancy had no effect on PTX3 level. CONCLUSION: The elevated PTX3 concentration in OHSS at OPU2, when freeze-all embryos strategy is still possible to consider, indicates that PTX3 level could provide additional benefit in the risk assessment for early OHSS.

Long-term re-procedure rate after mid-urethral slings for stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: Long-term safety concerns have risen over the mid-urethral sling operation (MUS) for stress urinary incontinence (SUI), which in some countries has led to litigations and even suspending MUS insertions. We examined the long-term re-procedure rate after MUS operations. The main outcome was re-procedures for SUI. The secondary outcome was surgical interventions due to complications. METHODS: We analysed a retrospective population cohort of 3531 women with MUS operations in 2000-2006 and followed them up until 31 December 2016. Data were collected from a national hospital register and from hospital patient records. RESULTS: The median follow-up time was 13 years (IQR 11.6-14.8) for the 3280 women with a retropubic MUS (RP-MUS) and 11 years (IQR 10.3-11.9) for the 245 women with a transobturator MUS (TO-MUS). The cumulative number of re-procedures for SUI was 16 (0.5%) at 1 year, 66 (1.9%) at 5 years, 97 (2.8%) at 10 years and 112 (3.2%) at 17 years. This risk was higher after TO-MUS than after RP-MUS operations (OR 3.6, 95% CI 2.5-5.2, p < 0.001). The cumulative number of any long-term re-procedure was 43 (1.2%) at year 1, 105 (3.0%) at year 5, 144 (4.1%) at year 10 and 163 (4.6%) at year 17. CONCLUSIONS: Re-procedures occur up to 17 years after primary MUS insertion, but their incidence is low after the first few postoperative years. Re-procedures for recurrent SUI are more common after TO-MUS than RP-MUS.