Pregnancy outcomes following routine early provision of intrauterine device after first-trimester induced abortion-A secondary analysis of a randomized controlled trial with a 5-year follow up.

INTRODUCTION: Women undergoing an induced abortion are highly fertile and at risk of subsequent unplanned pregnancy. We recently completed a randomized clinical trial showing that routine provision of intrauterine device (IUD) at the time of abortion significantly reduced the risk of subsequent abortion during a 5-year follow up. As the use of highly effective contraception may affect all subsequent pregnancies, we analyzed the rate and distribution of all subsequent pregnancies (deliveries, miscarriages, and abortions), and the risk factors for these various pregnancy outcomes in the above-mentioned randomized clinical trial. MATERIAL AND METHODS: We enrolled adult women requesting first-trimester induced abortion and candidates for IUD for post-abortion contraception. Women (n = 751) were randomized to receive an IUD (either levonorgestrel-releasing IUD or copper IUD) by the clinic responsible for abortion care vs. routine care of IUD provision in primary health care with oral contraceptives for interval contraception. In the present secondary analysis, we identified all deliveries, miscarriages, and abortions in the intervention (n = 375) and control (n = 373) cohorts during the 5-year follow up using the Finnish national registries. The trial is registered at Clinical Trials (NTC01223521). RESULTS: The overall delivery, miscarriage, and abortion rates were 42.0, 12.0 and 32.1/1000 years of follow up (yFU). Any new pregnancy occurred in 98 women in the intervention and in 129 women in the control cohort (hazard ratio 0.73, 95% confidence interval 0.56-0.95, p = 0.023). The effect of routine IUD provision in reducing pregnancies was limited to the first 2 yFU. The number of subsequent induced abortions and of women undergoing it were significantly reduced, and time to abortion was prolonged by the intervention. However, the overall number, the number of women with subsequent delivery or miscarriage, and the times to these events were not significantly affected. History of previous pregnancy (delivery or abortion) and smoking were risk factors for subsequent induced abortion, but not for delivery or miscarriage. CONCLUSIONS: Routine provision of IUD as part of abortion care did not reduce the rates of delivery or miscarriage during the 5-year follow up. The rates of all pregnancies and the need of subsequent induced abortion were reduced by IUD provision during the first 2 yFU.

Effect of Surface Modification on the Pulmonary and Systemic Toxicity of Cellulose Nanofibrils.

Cellulose nanofibrils (CNFs) have emerged as sustainable options for a wide range of applications. However, the high aspect ratio and biopersistence of CNFs raise concerns about potential health effects. Here, we evaluated the in vivo pulmonary and systemic toxicity of unmodified (U-CNF), carboxymethylated (C-CNF), and TEMPO (2,2,6,6-tetramethyl-piperidin-1-oxyl)-oxidized (T-CNF) CNFs, fibrillated in the same way and administered to mice by repeated (3×) pharyngeal aspiration (14, 28, and 56 µg/mouse/aspiration). Toxic effects were assessed up to 90 days after the last administration. Some mice were treated with T-CNF samples spiked with lipopolysaccharide (LPS; 0.02-50 ng/mouse/aspiration) to assess the role of endotoxin contamination. The CNFs induced an acute inflammatory reaction that subsided within 90 days, except for T-CNF. At 90 days post-administration, an increased DNA damage was observed in bronchoalveolar lavage and hepatic cells after exposure to T-CNF and C-CNF, respectively. Besides, LPS contamination dose-dependently increased the hepatic genotoxic effects of T-CNF.

Surface functionalization and size modulate the formation of reactive oxygen species and genotoxic effects of cellulose nanofibrils.

BACKGROUND: Cellulose nanofibrils (CNFs) have emerged as a sustainable and environmentally friendly option for a broad range of applications. The fibrous nature and high biopersistence of CNFs call for a thorough toxicity assessment, but it is presently unclear which physico-chemical properties could play a role in determining the potential toxic response to CNF. Here, we assessed whether surface composition and size could modulate the genotoxicity of CNFs in human bronchial epithelial BEAS-2B cells. We examined three size fractions (fine, medium and coarse) of four CNFs with different surface chemistry: unmodified (U-CNF) and functionalized with 2,2,6,6-tetramethyl-piperidin-1-oxyl (TEMPO) (T-CNF), carboxymethyl (C-CNF) and epoxypropyltrimethylammonium chloride (EPTMAC) (E-CNF). In addition, the source fibre was also evaluated as a non-nanosized material. RESULTS: The presence of the surface charged groups in the functionalized CNF samples resulted in higher amounts of individual nanofibrils and less aggregation compared with the U-CNF. T-CNF was the most homogenous, in agreement with its high surface group density. However, the colloidal stability of all the CNF samples dropped when dispersed in cell culture medium, especially in the case of T-CNF. CNF was internalized by a minority of BEAS-2B cells. No remarkable cytotoxic effects were induced by any of the cellulosic materials. All cellulosic materials, except the medium fraction of U-CNF, induced a dose-dependent intracellular formation of reactive oxygen species (ROS). The fine fraction of E-CNF, which induced DNA damage (measured by the comet assay) and chromosome damage (measured by the micronucleus assay), and the coarse fraction of C-CNF, which produced chromosome damage, also showed the most effective induction of ROS in their respective size fractions. CONCLUSIONS: Surface chemistry and size modulate the in vitro intracellular ROS formation and the induction of genotoxic effects by fibrillated celluloses. One cationic (fine E-CNF) and one anionic (coarse C-CNF) CNF showed primary genotoxic effects, possibly partly through ROS generation. However, the conclusions cannot be generalized to all types of CNFs, as the synthesis process and the dispersion method used for testing affect their physico-chemical properties and, hence, their toxic effects.

Early provision of intrauterine contraception as part of abortion care-5-year results of a randomised controlled trial.

STUDY QUESTION: Can the incidence of subsequent termination of pregnancy (TOP) be reduced by providing intrauterine contraception as part of the abortion service? SUMMARY ANSWER: Provision of an intrauterine device (IUD) as part of TOP services reduced the need for subsequent TOP but the effect was limited to the first 3 years of the 5-year follow-up. WHAT IS KNOWN ALREADY: An IUD is highly effective in preventing subsequent TOP. Prompt initiation of IUD use leads to a higher usage rate during follow-up, as compliance with post-TOP IUD insertion visits is low. STUDY DESIGN, SIZE, DURATION: The objective of this randomised controlled trial was to assess the effect of early comprehensive provision of intrauterine contraception after TOP, with primary outcome being the incidence of subsequent TOP during the 5 years of follow-up after the index abortion. This study was conducted at a tertiary care centre between 18 October 2010 and 21 January 2013. Altogether, 748 women undergoing a first trimester TOP were recruited and randomised into two groups. The intervention group (n = 375) was provided with an IUD during surgical TOP or 1-4 weeks following medical TOP at the hospital providing the abortion care. Women in the control group (n = 373) were advised to contact primary health care for follow-up and IUD insertion. Subsequent TOPs during the 5-year follow-up were identified from the Finnish Register on induced abortions. PARTICIPANTS/MATERIALS, SETTING, METHODS: The inclusion criteria were age ≥18 years, duration of gestation ≤12 weeks, residence in Helsinki and accepting intrauterine contraception. Women with contraindications to IUD were excluded. MAIN RESULTS AND THE ROLE OF CHANCE: The overall numbers of subsequent TOPs were 50 in the intervention and 72 in the control group (26.7 versus 38.6/1000 years of follow-up, P = 0.027), and those of requested TOPs, including TOPs and early pregnancy failures, were 58 and 76, respectively (30.9 versus 40.8/1000, P = 0.080). Altogether 40 (10.7%) women in the intervention and 63 (16.9%) in the control group underwent one or several subsequent TOPs (hazard ratio 1.67 [95% CI 1.13 to 2.49], P = 0.011). The number of TOPs was reduced by the intervention during years 0-3 (22.2 versus 46.5/1000, P = 0.035), but not during years 4-5 (33.3 versus 26.8/1000, P = 0.631). LIMITATIONS, REASONS FOR CAUTION: Both medical and surgical TOP were used. This may be seen as a limitation, but it also reflects the contemporary practice of abortion care. The immediate post-TOP care was provided by two different organizations, allowing us to compare two different ways of contraceptive service provision following TOP. WIDER IMPLICATIONS OF THE FINDINGS: Providing TOP and IUD insertion comprehensively in the same heath care unit leads to significantly higher rates of attendance, IUD use and a significantly lower risk of subsequent TOP. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by Helsinki University Central Hospital Research funds and by research grants provided by the Jenny and Antti Wihuri Foundation, the Yrjö Jahnsson Foundation and Finska Läkaresällskapet. E.P. has received a personal research grant from the Finnish Medical Society. The City of Helsinki supported the study by providing the IUDs. The funding organisations had no role in planning or execution of the study, or in analysing the study results. TRIAL REGISTRATION NUMBER: The trial was registered at clinicaltrials.gov (NCT01223521). TRIAL REGISTRATION DATE: 18 October 2010. DATE OF FIRST PATIENT'S ENROLMENT: 18 October 2010.

Sexual well-being after first trimester termination of pregnancy: Secondary analysis of a randomized contraceptive trial.

INTRODUCTION: Although termination of pregnancy is one of the most common procedures conducted worldwide, little is known about sexual well-being after termination of pregnancy. The objective of this study was to assess sexual well-being after termination of pregnancy, and factors affecting it during a 1-year follow up. MATERIAL AND METHODS: In total, 748 women requesting first trimester termination of pregnancy and participating in a randomized controlled trial on early provision of intrauterine contraception were provided with questionnaires regarding their sexual life, anxiety, quality of life and contraceptive method used at the time of termination of pregnancy, 3 and 12 months after termination of pregnancy. Sexual well-being was measured by the 9-item McCoy Female Sexuality Questionnaire. Anxiety and quality of life were assessed by the State-Trait Anxiety Inventory (STAI) Scale and EuroQoL questionnaire (EQoL). RESULTS: The McCoy index remained unchanged during the follow up. At all three time-points measured, higher (ie, better) McCoy scores were associated with a lower STAI index (mean difference -2.26 [95% CI -3.23 to -1.29], P < 0.001; -3.76 [95% CI -4.79 to -2.74], P < 0.001; -4.50 [95% CI -5.88 to -3.12], P < 0.001) and being in a relationship (1.16 [95% CI 0.08-2.25], P = 0.023; 1.67 [95% CI 0.43-2.89], P < 0.001; 2.81 [95% CI 1.28-4.34], P < 0.001), and correlated positively with a higher EQoL index (r = 0.20, r = 0.20, r = .27, P < 0.001) and higher frequency of intercourse (r = 0.50, r = 0.46, r = 0.42, P < 0.001). Women using intrauterine contraception had higher McCoy index measurements at 3 months compared with others. There were no significant differences between users of hormonal vs non-hormonal contraceptive methods. CONCLUSIONS: Sexual well-being does not change significantly after termination of pregnancy. Instead, it is strongly and positively associated with quality of life, relationship status and frequency of intercourse. Anxiety is negatively associated with sexual well-being.

Genotoxic and inflammatory effects of nanofibrillated cellulose in murine lungs.

Nanofibrillated cellulose (NFC) is a sustainable and renewable nanomaterial, with diverse potential applications in the paper and medical industries. As NFC consists of long fibres of high aspect ratio, we examined here whether TEMPO-(2,2,6,6-tetramethyl-piperidin-1-oxyl) oxidised NFC (length 300-1000nm, thickness 10-25nm), administrated by a single pharyngeal aspiration, could be genotoxic to mice, locally in the lungs or systemically in the bone marrow. Female C57Bl/6 mice were treated with four different doses of NFC (10, 40, 80 and 200 µg/mouse), and samples were collected 24h later. DNA damage was assessed by the comet assay in bronchoalveolar lavage (BAL) and lung cells, and chromosome damage by the bone marrow erythrocyte micronucleus assay. Inflammation was evaluated by BAL cell counts and analysis of cytokines and histopathological alterations in the lungs. A significant induction of DNA damage was observed at the two lower doses of NFC in lung cells, whereas no increase was seen in BAL cells. No effect was detected in the bone marrow micronucleus assay, either. NFC increased the recruitment of inflammatory cells to the lungs, together with a dose-dependent increase in mRNA expression of tumour necrosis factor α, interleukins 1ß and 6, and chemokine (C-X-C motif) ligand 5, although there was no effect on the levels of the respective proteins. The histological analysis showed a dose-related accumulation of NFC in the bronchi, the alveoli and some in the cytoplasm of macrophages. In addition, neutrophilic accumulation in the alveolar lung space was observed with increasing dose. Our findings showed that NFC administered by pharyngeal aspiration caused an acute inflammatory response and DNA damage in the lungs, but no systemic genotoxic effect in the bone marrow. The present experimental design did not, however, allow us to determine whether the responses were transient or could persist for a longer time.

Anxiety and quality of life after first-trimester termination of pregnancy: a prospective study.

INTRODUCTION: Possible effects of termination of pregnancy (TOP) on mental health are a matter of debate. MATERIAL AND METHODS: We assessed anxiety and quality of life during a one-year follow up after first-trimester TOP using the State-Trait Anxiety Inventory (STAI) Scale and EuroQoL Quality of Life Questionnaire (EQ-5D, EQ-VAS) in 742 women participating in a randomized controlled trial on early provision of intrauterine contraception. The measurements were performed before TOP, at 3 months and 1 year after TOP. Inclusion criteria were age ≥18 years, residence in Helsinki, duration of gestation <12 weeks, non-medical indication for TOP, and approval of intrauterine contraception. The trial was registered with Clinical Trials [NCT01223521]. RESULTS: When compared with baseline, the overall anxiety level was significantly lower and quality of life higher at 3 months and at 1 year. Reduction of anxiety and improvement of quality of life was especially evident (p < 0.001) in the 58% of women reporting clinically relevant anxiety at baseline. High levels of anxiety at baseline, history of psychiatric morbidity and smoking predicted significantly greater risk of poorer quality of life and elevated level of anxiety during the follow up. CONCLUSIONS: TOP is associated with a significant overall reduction of anxiety and an improvement of quality of life among women undergoing it for non-medical indications. High baseline anxiety, history of psychiatric morbidity and smoking are risk factors of persistently high levels of anxiety and poor quality of life after an induced abortion. These data are important when designing and providing post-abortion care.

Menstrual characteristics and ultrasonographic uterine cavity measurements predict bleeding and pain in nulligravid women using intrauterine contraception.

STUDY QUESTION: Is small uterine cavity size as assessed by ultrasonography associated with bleeding problems or pain in nulligravid women using intrauterine contraception, or do other factors affect these parameters? SUMMARY ANSWER: Among levonorgestrel intrauterine system (LNG-IUS) users, small uterine cavity size is not associated with worsened clinical outcome, but is beneficial as women with the smallest cavity measurements were frequently amenorrhoeic and painless at the end of the first year but among copper intrauterine device (IUD) users, no associations between uterine cavity dimensions and clinical outcome were found. WHAT IS KNOWN ALREADY: Nulligravid and nulliparous women have smaller uterine dimensions than parous women. Previously, many studies have revealed increased discontinuation rates of IUD use as a result of bleeding, pain or expulsion in these women, while recent studies with current models of IUS/IUDs indicate similar continuation and satisfaction rates irrespective of parity. STUDY DESIGN, SIZE, DURATION: In a pilot study, 165 adult nulligravid women requesting their first IUD between 1 January 2011 and 31 July 2012 were given a free choice between two IUDs with equal frames measuring 32 × 32 mm-the LNG-IUS 52 mg or a copper-releasing IUD. The women were followed for 1 year. PARTICIPANTS/MATERIAL, SETTING, METHODS: The LNG-IUS was chosen by 113 women (68.5%) and the copper IUD by 52 (31.5%). Prior to insertion the women were interviewed concerning their menstrual characteristics and uterine cavity size was measured by 2-D ultrasonography. After insertion the women kept daily records of bleeding and pain for two reference periods of 90 days during the first year (Months 1-3 and 10-12). The correlation between uterine cavity measurements and numbers of days of bleeding/spotting and pain during the reference periods was analysed. Continuation rates were assessed and reasons for discontinuation as well as the effects of baseline participant characteristics on outcomes were analysed in regression models. MAIN RESULTS AND THE ROLE OF CHANCE: Both uterine cavity size and baseline menstrual characteristics prior to IUD insertion predicted the numbers of days of bleeding/spotting and pain in LNG-IUS users. Women with small uterine cavity dimensions reported less bleeding/spotting in both reference periods and less pain in the second reference period compared with women with larger dimensions. Baseline scanty spontaneous menstrual bleeding prior to LNG-IUS use (OR 9.4, 95% CI 1.7-51.8, P = 0.01) and smoking (OR 7.8, 95% CI 1.8-33.8, P = 0.006) predicted amenorrhoea in the second reference period. Women with baseline dysmenorrhoea reported more pain with both IUDs. Continuation rates and reasons for discontinuation were similar with both IUDs. LIMITATIONS, REASONS FOR CAUTION: No sample size could be calculated to estimate the power as this was a pilot study. As the majority of women chose the LNG-IUS we did not achieve our initial aim of equally sized IUD groups and thus the size of the copper IUD group may have been insufficient to detect differences. WIDER IMPLICATIONS OF THE FINDINGS: These data further encourage promotion of intrauterine contraception among nulligravid women. Routine use of ultrasonography to assess uterine cavity dimensions prior to IUD insertion is not indicated. STUDY FUNDING/COMPETING INTERESTS: Supported by Helsinki University Central Hospital research funds, the Swedish Cultural Foundation in Finland and Finska Läkaresällskapet, who provided funds for J.K. O.H. serves on advisory boards for Bayer Healthcare, Gedeon Richter and MSD Finland (part of Merck & Co. Inc.) and has designed educational events with these companies. S.S. has lectured in educational events at Bayer and MSD Finland (part of Merck & Co. Inc.) and is a member of the Advisory Board for Contraception at MSD Finland. The other authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: www.clinicaltrials.gov, NCT01685164.

Provision of intrauterine contraception in association with first trimester induced abortion reduces the need of repeat abortion: first-year results of a randomized controlled trial.

STUDY QUESTION: Can the need of subsequent abortion be reduced by providing intrauterine contraception as a part of the abortion service? SUMMARY ANSWER: Provision of intrauterine devices (IUDs) in association with first trimester abortion more than halved the incidence of repeat abortion during the first year of follow-up. WHAT IS KNOWN ALREADY: Following abortion, the incidence of subsequent abortion is high, up to 30-40%. In cohort studies, intrauterine contraception has reduced the need of repeat abortion by 60-70%. STUDY DESIGN, SIZE, DURATION: A randomized controlled trial. The main outcome measure was the incidence of subsequent induced abortions during the follow-up. Altogether 751 women seeking first trimester induced abortion were recruited and randomized into two groups. Randomization was accomplished by computer-assisted permuted-block randomization with random block sizes of four to six. The investigators did not participate in randomization, which was done before commencing the study. The participants were recruited between 18 October 2010 and 21 January 2013. PARTICIPANTS, SETTINGS, METHODS: The inclusion criteria were age ≥18 years, duration of pregnancy ≤12 weeks, accepting intrauterine contraception, residence in Helsinki and signing the informed consent form. Women with contraindications to intrauterine contraception, such as uterine anomaly, acute genital infection or pap-smear change requiring surgical treatment were ineligible to participate.This study was conducted in collaboration between the Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, and Centralized family planning of the City of Helsinki.The intervention group (n = 375) was provided with intrauterine contraception (either the levonorgestrel-releasing intrauterine system or copper-releasing intrauterine device) immediately following surgical abortion (18.1%) or at a follow-up 2-4 weeks after medical abortion (81.9%). Women in the control group were prescribed oral contraceptives and advised to contact their primary healthcare unit for a follow-up visit and further contraceptive services according to national guidelines. The women were followed-up to 28 February 2014 by using the Finnish National Abortion Registry, Helsinki University Hospital electronic database and clinical follow-up visit at 1 year. MAIN RESULTS AND THE ROLE OF CHANCE: The median age of the whole study group was 27 years and 44% had a history of induced abortion(s). During the follow-up year the number of women requesting subsequent abortion was significantly lower in the intervention than in the control group (9/375 [2.4%] versus 20/373 [5.4%], difference -3.0 [95% CI -6.0 to -0.2] percentage points, P = 0.038, according to intention-to-treat analysis and 5/346 [1.4%] versus 20/357 [5.6%], difference -4.2(-7.2 to -1.4) percentage points, P = 0.003, according to per-protocol analysis, respectively). Provision of intrauterine contraception was safe with rate of infection and expulsion similar to those reported previously. LIMITATIONS, REASONS FOR CAUTION: The power calculation was calculated for a 5-year follow-up. However, significant differences between the two groups were already seen after 1 year. The present study was performed in a single clinic, where, ∼15% of all abortions in Finland are performed. WIDER IMPLICATIONS OF THE FINDINGS: In order to decrease the need of subsequent abortions, IUDs should be provided at the time of abortion. TRIAL REGISTRATION: The study was registered at www.clinicaltrials.gov (NCT01223521). TRIAL REGISTRATION DATE: 18 October 2010. DATE OF FIRST PATIENT'S ENROLMENT: 18 October 2010.

Free radical scavenging and formation by multi-walled carbon nanotubes in cell free conditions and in human bronchial epithelial cells.

BACKGROUND: Certain multi-walled carbon nanotubes (MWCNTs) have been shown to elicit asbestos-like toxicological effects. To reduce needs for risk assessment it has been suggested that the physicochemical characteristics or reactivity of nanomaterials could be used to predict their hazard. Fibre-shape and ability to generate reactive oxygen species (ROS) are important indicators of high hazard materials. Asbestos is a known ROS generator, while MWCNTs may either produce or scavenge ROS. However, certain biomolecules, such as albumin - used as dispersants in nanomaterial preparation for toxicological testing in vivo and in vitro - may reduce the surface reactivity of nanomaterials. METHODS: Here, we investigated the effect of bovine serum albumin (BSA) and cell culture medium with and without BEAS 2B cells on radical formation/scavenging by five MWCNTs, Printex 90 carbon black, crocidolite asbestos, and glass wool, using electron spin resonance (ESR) spectroscopy and linked this to cytotoxic effects measured by trypan blue exclusion assay. In addition, the materials were characterized in the exposure medium (e.g. for hydrodynamic size-distribution and sedimentation rate). RESULTS: The test materials induced highly variable cytotoxic effects which could generally be related to the abundance and characteristics of agglomerates/aggregates and to the rate of sedimentation. All carbon nanomaterials were found to scavenge hydroxyl radicals (•OH) in at least one of the solutions tested. The effect of BSA was different among the materials. Two types of long, needle-like MWCNTs (average diameter >74 and 64.2 nm, average length 5.7 and 4.0 µm, respectively) induced, in addition to a scavenging effect, a dose-dependent formation of a unique, yet unidentified radical in both absence and presence of cells, which also coincided with cytotoxicity. CONCLUSIONS: Culture medium and BSA affects scavenging/production of •OH by MWCNTs, Printex 90 carbon black, asbestos and glass-wool. An unidentified radical is generated by two long, needle-like MWCNTs and these two CNTs were more cytotoxic than the other CNTs tested, suggesting that this radical could be related to the adverse effects of MWCNTs.

Factors affecting female sexual well-being: a 5-year follow-up of a randomised clinical trial on post-abortion contraception.

INTRODUCTION: Sexual well-being is associated with general well-being. Several factors, such as overweight, infertility, anxiety and sex hormones, also play a role, but the effects of hormonal contraception remain a point of debate. We characterised the factors associated with sexual well-being in fertile-aged women following induced abortion. METHODS: A 5-year follow-up of a nested, longitudinal, cohort study examining the effects of routine provision of intrauterine contraception as part of abortion care. Sexual well-being, anxiety and quality of life were assessed annually using validated questionnaires (McCoy Female Sexuality Questionnaire, State-Trait Anxiety Inventory and EuroQoL), along with data on general and reproductive health, and relationship status. Of the 742 women participating in the trial, 290 (39%) provided sufficient follow-up data and were included in this study. RESULTS: Based on trajectories of McCoy scores across the 5-year follow-up, two groups were identified: those with stable and higher (n=223, 76.9%) and those with declining sexual well-being (n=67, 23.1%). Women in the group of declining sexual well-being had significantly higher levels of anxiety and lower quality of life at all time points. They also had chronic diseases more often and were less happy in their relationships. No differences were found in method of contraception when classified as hormonal versus non-hormonal, or long-acting versus short-acting reversible contraception. CONCLUSIONS: Lower anxiety and higher quality of life are associated with stable and higher sexual well-being. Method of contraception or relationship status are not associated with sexual well-being during long-term follow-up in fertile-aged women.

Uterine perforation caused by intrauterine devices: clinical course and treatment.

STUDY QUESTIONS: What are the symptoms of uterine perforation caused by modern copper intrauterine devices (Cu-IUDs) and the levonorgestrel-releasing intrauterine system (LNG-IUS); how is perforation detected and what are the findings in abdominal surgery? SUMMARY ANSWER: Symptoms are mostly mild and ∼30% of women are asymptomatic. Surgical findings are mainly minimal; no visceral complications were found in this study. However, adhesions as well as pregnancies seem to be more common among women using Cu-IUDs. WHAT IS KNOWN ALREADY: Prior studies and case reports have suggested that uterine perforation by modern IUDs/IUSs is rarely serious. STUDY DESIGN, SIZE, DURATION: A retrospective study of 75 patients (54 LNG-IUS and 21 Cu-IUD) treated surgically for uterine perforation between 1996 and 2009. PARTICIPANTS/MATERIALS, SETTING, METHODS: The patients treated for uterine perforation by an IUD/IUS at clinics of the Helsinki and Uusimaa Hospital District were identified using the National Care Register for Health Institutions in Finland. The clinical data were collected from individual patient records. MAIN RESULTS AND THE ROLE OF CHANCE: The majority of patients (n = 53; 71%) had mild symptoms of abnormal bleeding or abdominal pain or both, in combination with missing IUD/IUS threads. Asymptomatic patients (n = 22; 29%) were examined because of missing threads or pregnancy. Failure to remove the IUD/IUS by pulling visible threads was the reason for referral in seven women (9%) requesting removal of the device. Eleven women (15%) were pregnant. Misplaced IUDs/IUSs were localized by a combination of vaginal ultrasonography (US) and X-ray, hysteroscopy or curettage. Only after this were patients treated by means of laparoscopy. The majority (n = 44; 65%) of the 68 intra-abdominal devices were located in the omentum, the remaining 24 (35%) around the uterus. Partial perforation or myometrial embedding was diagnosed in all seven cases (9%) with visible threads, but unsuccessful removal by pulling. During laparoscopy, filmy adhesions were found in 21 patients (30%). Pregnancy (33 versus 7%, P = 0.009) and intra-abdominal adhesions (58 versus 20%, P = 0.002) were significantly more common in the Cu-IUD group. Infections were rare; one non-specific acute abdominal infection, later found to be unrelated to the IUD, led to laparoscopy and in four cases the IUD was surrounded by pus, but there were no symptoms of infection. LIMITATIONS, REASONS FOR CAUTION: The study setting revealed only surgically treated symptomatic patients and asymptomatic women attending regular follow-up. Women not treated, but only followed or not attending follow-up, were not identified, excluding the possibility to analyse missed undiagnosed perforations, or conservative follow-up as a treatment option. WIDER IMPLICATIONS OF THE FINDINGS: As surgical findings are minimal, asymptomatic women may need no treatment at all. An alternative form of contraception is, however, important as pregnancies do occur. If a woman plans a pregnancy, a misplaced LNG-IUS should be removed, as it may act as a contraceptive.

Impact of physico-chemical properties on the toxicological potential of reduced graphene oxide in human bronchial epithelial cells.

The increasing use of graphene-based materials (GBM) requires their safety evaluation, especially in occupational settings. The same physico-chemical (PC) properties that confer GBM extraordinary functionalities may affect the potential toxic response. Most toxicity assessments mainly focus on graphene oxide and rarely investigate GBMs varying only by one property. As a novelty, the present study assessed the in vitro cytotoxicity and genotoxicity of six reduced graphene oxides (rGOs) with different PC properties in the human bronchial epithelial 16HBE14o - cell line. Of the six materials, rGO1-rGO4 only differed in the carbon-to-oxygen (C/O) content, whereas rGO5 and rGO6 were characterized by different lateral size and number of layers, respectively, but similar C/O content compared with rGO1. The materials were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, laser diffraction and dynamic light scattering, and Brunauer-Emmett-Teller analysis. Cytotoxicity (Luminescent Cell Viability and WST-8 assays), the induction of reactive oxygen species (ROS; 2',7'-dichlorofluorescin diacetate-based assay), the production of cytokines (enzyme-linked immunosorbent assays) and genotoxicity (comet and micronucleus assays) were evaluated. Furthermore, the internalization of the materials in the cells was confirmed by laser confocal microscopy. No relationships were found between the C/O ratio or the lateral size and any of the rGO-induced biological effects. However, rGO of higher oxygen content showed higher cytotoxic and early ROS-inducing potential, whereas genotoxic effects were observed with the rGO of the lowest density of oxygen groups. On the other hand, a higher number of layers seems to be associated with a decreased potential for inducing cytotoxicity and ROS production.

Role of Chemical Reduction and Formulation of Graphene Oxide on Its Cytotoxicity towards Human Epithelial Bronchial Cells.

Graphene-based materials may pose a potential risk for human health due to occupational exposure, mainly by inhalation. This study was carried out on bronchial epithelial 16HBE14o- cells to evaluate the role of chemical reduction and formulation of graphene oxide (GO) on its cytotoxic potential. To this end, the effects of GO were compared to its chemically reduced form (rGO) and its stable water dispersion (wdGO), by means of cell viability reduction, reactive oxygen species (ROS) generation, pro-inflammatory mediators release and genotoxicity. These materials induced a concentration-dependent cell viability reduction with the following potency rank: rGO > GO >> wdGO. After 24 h exposure, rGO reduced cell viability with an EC50 of 4.8 µg/mL (eight-fold lower than that of GO) and was the most potent material in inducing ROS generation, in contrast to wdGO. Cytokines release and genotoxicity (DNA damage and micronucleus induction) appeared low for all the materials, with wdGO showing the lowest effect, especially for the former. These results suggest a key role for GO reduction in increasing GO cytotoxic potential, probably due to material structure alterations resulting from the reduction process. In contrast, GO formulated in a stable dispersion seems to be the lowest cytotoxic material, presumably due to its lower cellular internalization and damaging capacity.

Intrauterine contraception: incidence and factors associated with uterine perforation--a population-based study.

STUDY QUESTION: What are the incidence and factors associated with uterine perforation by modern copper intrauterine device (Cu-IUD) and the levonorgestrel-releasing intrauterine system (LNG-IUS)? SUMMARY ANSWER: Perforation incidence was similar to that reported in prior studies and did not vary between Cu-IUD and LNG-IUS groups. Lactation, amenorrhoea and a post-partum period of <6 months were common. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: The study supports findings in prior studies. The incidence rate was low and factors associated with uterine perforation were similar to those in earlier reports. DESIGN AND DATA COLLECTION METHOD: This retrospective population-based registry study included 68 patients surgically treated for uterine perforation by an intrauterine device (IUD)/intrauterine system (IUS) at clinics in the Helsinki and Uusimaa hospital district. PARTICIPANTS AND SETTING: Records of 108 patients with probable uterine perforation by an IUD/IUS were analysed, leaving 68 patients treated for uterine perforation. RECRUITMENT/SAMPLING STRATEGY: Patients with diagnostic and surgical treatment codes indicating uterine perforation by an IUD/IUS between 1996 and 2009 were retrospectively selected from the Finnish National Hospital Register. DATA ANALYSIS METHOD: Patients with Cu-IUDs (n = 17) and the LNG-IUS (n = 51) were analysed as one group and also compared using Mann-Whitney and chi-square tests. IUD/IUS sales numbers were used to calculate incidences. MAIN FINDINGS: The overall incidence of perforation was 0.4/1000 sold devices, varying annually from 0 to 1.2/1000. The proportion of both sold and perforating LNG-IUSs increased during the study period, but perforation incidence was not affected. Demographic characteristics in the Cu-IUD and LNG-IUS groups were similar. More than half of the devices (55%) were inserted at <6 months post-partum. Breastfeeding at the time of insertion was common, comprising 32% of all patients. Moreover, of the breastfeeding women, 90% had delivered within 6 month prior to insertion. IMPLICATIONS: The population-based study setting represents a good overview of patients experiencing uterine perforation with an IUD/IUS. As previously reported, the post-partum period, lactation and amenorrhoea may increase the risk of perforation. BIAS, LIMITATIONS AND GENERALIZABILITY: As the study setting revealed only symptomatic patients or those attending regular follow-up, the true incidence might be somewhat higher. As there is no specific diagnostic code for uterine perforation or treatment, it is unlikely that all cases of uterine perforation can be identified in a retrospective study.

Genotoxicity of inhaled nanosized TiO(2) in mice.

In vitro studies have suggested that nanosized titanium dioxide (TiO(2)) is genotoxic. The significance of these findings with respect to in vivo effects is unclear, as few in vivo studies on TiO(2) genotoxicity exist. Recently, nanosized TiO(2) administered in drinking water was reported to increase, e.g., micronuclei (MN) in peripheral blood polychromatic erythrocytes (PCEs) and DNA damage in leukocytes. Induction of micronuclei in mouse PCEs was earlier also described for pigment-grade TiO(2) administered intraperitoneally. The apparent systemic genotoxic effects have been suggested to reflect secondary genotoxicity of TiO(2) due to inflammation. However, a recent study suggested that induction of DNA damage in mouse bronchoalveolar lavage (BAL) cells after intratracheal instillation of nanosized or fine TiO(2) is independent of inflammation. We examined here, if inhalation of freshly generated nanosized TiO(2) (74% anatase, 26% brookite; 5 days, 4 h/day) at 0.8, 7.2, and (the highest concentration allowing stable aerosol production) 28.5 mg/m(3) could induce genotoxic effects in C57BL/6J mice locally in the lungs or systematically in peripheral PCEs. DNA damage was assessed by the comet assay in lung epithelial alveolar type II and Clara cells sampled immediately following the exposure. MN were analyzed by acridine orange staining in blood PCEs collected 48 h after the last exposure. A dose-dependent deposition of Ti in lung tissue was seen. Although the highest exposure level produced a clear increase in neutrophils in BAL fluid, indicating an inflammatory effect, no significant effect on the level of DNA damage in lung epithelial cells or micronuclei in PCEs was observed, suggesting no genotoxic effects by the 5-day inhalation exposure to nanosized TiO(2) anatase. Our inhalation exposure resulted in much lower systemic TiO(2) doses than the previous oral and intraperitoneal treatments, and lung epithelial cells probably received considerably less TiO(2) than BAL cells in the earlier intratracheal study.

One- and two-day dosing intervals between mifepristone and misoprostol in second trimester medical termination of pregnancy--a randomized trial.

BACKGROUND: The recommended time interval between mifepristone and misoprostol in medical second trimester termination of pregnancy (TOP) has been 36-48 h. However, a more flexible interval would be of value. The aim of this investigation was to compare one- and two-day intervals in second trimester medical TOP. The main outcome measures were induction-to-abortion time and the rate of surgical evacuation. METHODS: This open randomized trial included 227 women undergoing TOP between gestational weeks 13-24. Mifepristone (200 mg) was followed by misoprostol (400 mcg) after one (17-28 h) or two (41- 45 h) days. RESULTS: In intention-to-treat analysis, the median induction-to-abortion interval was 1h longer in the one-day group (8.5 versus 7.2 h, P = 0.038), but in per-protocol analysis, the rate of surgical evacuation was higher in the 2-day group [30/115 (25%) versus 40/112 (37%); 95% confidence interval 0.3-24.1, P = 0.044]. A subgroup analysis showed that the median induction-to-abortion interval was 3h longer in the one-day group, amongst women without previous vaginal deliveries (10.1 versus 7.6, P = 0.013) and when gestation exceeded 16 weeks (10.8 versus 7.2, P = 0.024). CONCLUSIONS: Both one- and two-day dosing intervals seem to be suitable for second trimester medical TOP, but women with no previous deliveries and those whose gestation exceeds 16 weeks may benefit from the longer interval. However, evaluated on the basis of surgical evacuation, the one-day interval could be supported as an option for second trimester medical TOP. Effective use of both one- and two-day dosing intervals is important when optimizing clinical service. TRIAL REGISTRATION: ISRCTN09944151.

Immediate adverse events after second trimester medical termination of pregnancy: results of a nationwide registry study.

BACKGROUND Increasing gestational age is associated with an increased risk of complications in studies assessing surgical termination of pregnancy (TOP). Medical TOP is widely used during the second trimester and little is known about the frequency of complications. This epidemiological study was undertaken to assess the frequency of adverse events following the second trimester medical TOP and to compare it with that after first trimester medical TOP. METHODS This register-based cohort study covered 18 248 women who underwent medical TOP in Finland between 1 January 2003 and 31 December 2006. The women were identified from the Abortion Registry. Adverse events related to medical TOP within 6 weeks were obtained from the Hospital Discharge Registry. RESULTS When compared with first trimester medical TOP, second trimester medical TOP increased the risk of surgical evacuation [Adj. odds ratio (OR) 7.8; 95% confidence interval (CI) 6.8-8.9], especially immediately after fetal expulsion (Adj. OR 15.2; 95% CI 12.8-18.0). The risk of infection was also elevated (Adj. OR 2.1; 95% CI 1.5-2.9). Within the second trimester, increased length of gestation did not influence the risk of surgical evacuation or infection after medical TOP. CONCLUSIONS Medical TOP during the second trimester is generally safe. Surgical evacuation of the uterus is avoided in about two-thirds of cases, though it is much more common than after first trimester medical TOP. The risks of surgical evacuation and infection do not increase with gestational weeks in the second trimester TOP.