| 1. |
- Zhou, K., et al.
(författare)
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An overlooked subset of Cx3cr1(wt/wt) microglia in the Cx3cr1(CreER-Eyfp/wt) mouse has a repopulation advantage over Cx3cr1(CreER-Eyfp/wt) microglia following microglial depletion
- 2022
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Fluorescent reporter labeling and promoter-driven Cre-recombinant technologies have facilitated cellular investigations of physiological and pathological processes, including the widespread use of the Cx3cr1(CreER-Eyfp/wt) mouse strain for studies of microglia. Methods Immunohistochemistry, Flow Cytometry, RNA sequencing and whole-genome sequencing were used to identify the subpopulation of microglia in Cx3cr1(CreER-Eyfp/wt) mouse brains. Genetically mediated microglia depletion using Cx3cr1(CreER-Eyfp/wt)Rosa26(DTA/wt) mice and CSF1 receptor inhibitor PLX3397 were used to deplete microglia. Primary microglia proliferation and migration assay were used for in vitro studies. Results We unexpectedly identified a subpopulation of microglia devoid of genetic modification, exhibiting higher Cx3cr1 and CX3CR1 expression than Cx3cr1(CreER-Eyfp/wt)Cre(+)Eyfp(+) microglia in Cx3cr1(CreER-Eyfp/wt) mouse brains, thus termed Cx3cr1(high)Cre(-)Eyfp(-) microglia. This subpopulation constituted less than 1% of all microglia under homeostatic conditions, but after Cre-driven DTA-mediated microglial depletion, Cx3cr1(high)Cre(-)Eyfp(-) microglia escaped depletion and proliferated extensively, eventually occupying one-third of the total microglial pool. We further demonstrated that the Cx3cr1(high)Cre(-)Eyfp(-) microglia had lost their genetic heterozygosity and become homozygous for wild-type Cx3cr1. Therefore, Cx3cr1(high)Cre(-)Eyfp(-) microglia are Cx3cr1(wt/wt)Cre(-)Eyfp(-). Finally, we demonstrated that CX3CL1-CX3CR1 signaling regulates microglial repopulation both in vivo and in vitro. Conclusions Our results raise a cautionary note regarding the use of Cx3cr1(CreER-Eyfp/wt) mouse strains, particularly when interpreting the results of fate mapping, and microglial depletion and repopulation studies.
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| 2. |
- Shao, Linus Ruijin, 1964, et al.
(författare)
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Down-Regulation of Cilia-Localized IL-6R{alpha} by 17{beta}-Estradiol in Mouse and Human Fallopian Tubes.
- 2009
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Ingår i: American journal of physiology. Cell physiology. - : American Physiological Society. - 0363-6143 .- 1522-1563. ; 297:1, s. C140-51
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Tidskriftsartikel (refereegranskat)abstract
- The action of Interleukin-6 (IL-6) impacts female reproduction. Although IL-6 was recently shown to inhibit cilia activity in human fallopian tubes in vitro, the molecular mechanisms underlying IL-6 signaling to tubal function remain elusive. Here, we investigate the cellular localization, regulation, and possible function of two IL-6 receptors (IL-6Ralpha and gp130) in mouse and human fallopian tubes in vivo. We show that IL-6Ralpha is restricted to the cilia of epithelial cells in both mouse and human fallopian tubes. Exogenous 17beta-estradiol (E2), but not progesterone (P4), causes a time-dependent decrease in IL-6Ralpha expression which is blocked by the estrogen receptor (ER) antagonist ICI 182,780. Exposure of different ER-selective agonists, PTT or DPN, demonstrated an ER subtype-specific regulation of IL-6Ralphaalpha in mouse fallopian tubes. In contrast to IL-6Ralpha, gp130 was detected in tubal epithelial cells in mice but not in humans. In humans, gp130 was found in the muscle cells and was decreased in the periovulatory and luteal phases during the reproductive cycles, indicating a species-specific expression and regulation of gp130 in the fallopian tube. Expression of tubal IL-6Ralpha and gp130 in IL-6 knockout mice was found to be normal; however, E2 treatment increased IL-6Ralpha, but not gp130, in IL-6 knockout mice compared to wild-type mice. Furthermore, expression levels of IL-6Ralpha, but not gp130, decreased in parallel with estrogenic accelerated oocyte-cumulus complex (OCC) transport in mouse fallopian tubes. Our findings unveil a potential role for cilia-specific IL-6Ralpha in the regulation of OCC transport and suggest an estrogen-regulatory pathway of IL-6Ralpha in the fallopian tube. Key words: estrogen, IL-6R, cilia, fallopian tube.
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| 3. |
- Brandell, K., et al.
(författare)
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Medical Abortion before Confirmed Intrauterine Pregnancy: A Systematic Review
- 2022
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Ingår i: Seminars in Reproductive Medicine. - : Georg Thieme Verlag KG. - 1526-8004 .- 1526-4564. ; 40:05/06, s. 258-263
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Tidskriftsartikel (refereegranskat)abstract
- "Very early medical abortion " (VEMA) refers to medical abortion (with mifepristone and misoprostol) before intrauterine pregnancy is visualized on ultrasound. Our aim is to present the current evidence on efficacy, safety (focused on ectopic pregnancies), and how to assess treatment success of VEMA. We conducted a systematic review of studies reporting outcomes of VEMA. The field is small and so our objective was to map all relevant literature, without conducting meta-analysis. We searched PubMed, Medline, and Embase on April 19, 2022. We conducted a narrative synthesis of the evidence. A total of 373 articles were identified. Six articles (representing four observational and one pilot trial) were included in the final review. Across all included studies, treatment efficacy ranged between 91 and 100%. Prevalence of ectopic pregnancy was low and very few cases ( n = 2) of ruptures were reported. Most studies used serial serum human chorionic gonadotrophin (s-hCG) levels to determine success of abortion; one study used low sensitivity urine hCG. From the available evidence, VEMA appears to be efficacious and does not appear to cause harm to ectopic pregnancies. Treatment can be assessed with pre- and postabortion s-hCG. Good quality, randomized controlled trial evidence is needed to best inform practice.
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| 4. |
- Hognert, Helena, 1973, et al.
(författare)
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Immediate versus delayed insertion of an etonogestrel releasing implant at medical abortion-a randomized controlled equivalence trial
- 2016
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 31:11, s. 2484-2490
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Tidskriftsartikel (refereegranskat)abstract
- Does a progestin releasing subdermal contraceptive implant affect the efficacy of medical abortion if inserted at the same visit as the progesterone receptor modulator, mifepristone, at medical abortion? A etonogestrel releasing subdermal implant inserted on the day of mifepristone did not impair the efficacy of the medical abortion compared with routine insertion at 2-4 weeks after the abortion. The etonogestrel releasing subdermal implant is one of the most effective long acting reversible contraceptive methods. The effect of timing of placement on the efficacy of mifepristone and impact on prevention of subsequent unintended pregnancy is not known. This multicentre, randomized controlled, equivalence trial with recruitment between 13 October 2013 and 17 October 2015 included a total of 551 women with pregnancies below 64 days gestation opting for the etonogestrel releasing subdermal implant as postabortion contraception. Women were randomized to either insertion at 1 hour after mifepristone intake (immediate) or at follow-up 2-4 weeks later (delayed insertion). An equivalence design was used due to advantages for women such as fewer visits to the clinic with immediate insertion. The primary outcome was the percentage of women with complete abortion not requiring surgical intervention within 1 month. Secondary outcomes included insertion rates, pregnancy and repeat abortion rates during 6 months follow-up. Analysis was per protocol and by intention to treat. Women aged 18 years and older who had requested medical termination of a pregnancy up to 63 days of gestation and opted for an etonogestrel releasing contraceptive implant were recruited in outpatient family planning clinics in six hospitals in Sweden and Scotland. Efficacy of medical abortion was 259/275 (94.2%) in the immediate insertion group and 239/249 (96%) in the routine insertion group with a risk difference of 1.8% (95% CI -0.4 to 4.1%), which was within the +/- 5% margin of equivalence. The insertion rate was 275/277 (98.9%) in the immediate group compared to 187/261 (71.6%) women in the routine group (P < 0.001). At 6 months of follow-up significantly fewer women in the immediate group had become pregnant again (2/277, 0.8%) compared to the routine group (10/261, 3.8%) P = 0.018. For the main outcome loss to follow-up data was minimized through access to patient records. Efforts were made to reduce loss to follow-up also for secondary outcomes. The results of the sensitivity analysis did not differ from the intention to treat or per protocol analysis. Guidelines on postabortion contraception should be amended to include insertion of the etonogestrel releasing implant at the time of mifepristone intake for medical abortion up to and including a gestation of 63 days. This study was funded by the Swedish Research Council (2012-2844), Stockholm City County and Karolinska Institutet (ALF). The contraceptive implants were provided by Merck and supplied by MSD Sweden. HKK and KGD have received honorariums for giving lectures for MSD/Merck and have participated in the national (HKK and KGD) and international (KGD) medical advisory boards for MSD/Merck. The other authors have nothing to declare.
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| 5. |
- Lundberg, F. E., et al.
(författare)
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Ovarian stimulation and risk of breast cancer in Swedish women
- 2017
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 108:1, s. 137-144
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate whether ovarian stimulation for treating infertility is associated with the risk of breast cancer. Patient(s): In a cohort of 1,340,211 women who gave birth 1982-2012, we investigated the relationship between assisted reproductive technology (ART) and incidence of breast cancer. Associations between any ovarian stimulation since 2005 and breast cancer incidence were studied in a separate cohort of 1,877,140 women born 1960-92. Both cohorts were followed through 2012. Main Outcome Measure(s): Hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer. Result(s): There was no increased risk of breast cancer in women who gave birth after ART compared with women who gave birth after spontaneous conception (adjusted HR, 0.84; 95% CI, 0.74-0.95). The incidence of breast cancer was not increased among women who received controlled ovarian stimulation or among women who received other hormonal fertility treatments since 2005, regardless of live birth (adjusted HR, 0.86; 95% CI, 0.69-1.07; and adjusted HR, 0.79; 95% CI, 0.60-1.05, respectively). Conclusion(s): No increased incidence of breast cancer was found among women who had gone through ovarian stimulations, including ART. These results are consistent with other studies and reassuring given the widespread and increasing use of ART. (C) 2017 The Authors. Published by Elsevier Inc. on behalf of the American Society for Reproductive Medicine.
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| 6. |
- Ahrendt, Hans-Joachim, et al.
(författare)
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Efficacy, acceptability and tolerability of the combined contraceptive ring, NuvaRing, compared with an oral contraceptive containing 30 mug of ethinyl estradiol and 3 mg of drospirenone
- 2006
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Ingår i: Contraception. - : Elsevier BV. - 0010-7824. ; 74:6, s. 451-457
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: This randomized multicenter, open-label, trial compared efficacy, acceptability, tolerability and compliance of NuvaRing with a combined oral contraceptive (COC), containing 30 mug of ethinyl estradiol (EE) and 3 mg of drospirenone. METHOD: In this 13-cycle study, 983 women were randomized and treated (intent-to-treat population) with NuvaRing or COC. RESULTS: One in-treatment pregnancy occurred with NuvaRing (Pearl Index=0.25) (95% confidence interval [CI]: 0.006, 1.363) and four with the COC (Pearl Index=0.99) (95% CI: 0.269, 2.530). For both groups, compliance (89.2% NuvaRing, 85.5% COC) and satisfaction (84% NuvaRing; 87% COC) were high; the vast majority of women found NuvaRing easy to insert (96%) and remove (97%). Tolerability was similar; the most frequent adverse events with NuvaRing were related to ring use, whereas estrogen-related events were more common with the COC. CONCLUSION: NuvaRing has comparable efficacy and tolerability to a COC containing 30 mug of EE and 3 mg drospirenone. User acceptability of both methods was high.
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| 7. |
- Bizjak, I., et al.
(författare)
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Efficacy and safety of very early medical termination of pregnancy: a cohort study
- 2017
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Ingår i: BJOG: An International Journal of Obstetrics and Gynaecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 124:13, s. 1993-1999
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 Royal College of Obstetricians and Gynaecologists Objective: To assess the efficacy and safety of medical termination of pregnancy (MTOP) when no intrauterine pregnancy (IUP) is confirmed on ultrasound. Design: Retrospective case-note review. Setting: Two gynaecological clinics in Vienna, Austria, and Gothenburg, Sweden. Population: All women with gestations of ≤49 days undergoing an MTOP during 2004–14 (Vienna) and 2012–15 (Gothenburg). Methods: Two study cohorts were created: women with and women without a confirmed IUP. An IUP was defined as the intrauterine location of a yolk sac or fetal structure visible by ultrasound. Women with an IUP were selected randomly and included in the IUP cohort. Main outcome measures: Efficacy of MTOP, defined as no continuing pregnancy and with no need of surgery for incomplete TOP. Results: After excluding 11 women diagnosed with an extra-uterine or molar pregnancy, 2643 cases were included in the final analysis; 1120 (98.2%) had a successful TOP in the no-IUP group, compared with 1458 (97.1%) in the IUP group, with a risk difference of 1.09% (95% confidence interval, 95% CI, −0.14, 2.32%; P = 0.077). Significantly more women with confirmed IUP were diagnosed with incomplete TOP, and were treated with either surgery or additional medical treatment of misoprostol [64 (4.3%) versus 21 (1.8%); risk difference −2.42%; 95% CI −3.9, −1.1%; P < 0.001]. Conclusions: There was no difference between the groups in efficacy of MTOP, whereas early treatment resulted in significantly fewer interventions for incomplete TOP. The risk of ectopic pregnancy needs to be considered if treatment is initiated before an IUP is confirmed, but with structured clinical protocols the possibility of the early detection of an ectopic pregnancy in an asymptomatic phase may increase. Tweetable abstract: MTOP before confirmed intrauterine pregnancy is as effective as at later gestation with less incomplete TOP.
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| 8. |
- Hognert, Helena, 1973, et al.
(författare)
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Ecological study on the use of hormonal contraception, abortions and births among teenagers in the Nordic countries
- 2018
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 8:10
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Tidskriftsartikel (refereegranskat)abstract
- RESULTS: Both annual birth rates and abortion rates fell in all the Nordic countries during the study period. The highest user rate of hormonal contraceptives among 15-19-year-olds was observed in Denmark (from 51% to 47%) followed by Sweden (from 39% to 42%) and Norway (from 37% to 41%). Combined oral contraceptives were the most commonly used methods in all countries. The use of long-acting reversible contraceptives (LARC), implants and the levonorgestrel-releasing intrauterine systems, were increasing, especially in Sweden and Norway. In the subgroup of 18-19-year-old teenagers, the user rates of hormonal contraceptives varied between 63% and 61% in Denmark, 56% and 61% in Norway and 54% and 56% in Sweden. In the same subgroup, the steepest increase of LARC was seen, from 2% to 6% in Denmark, 2% to 9% in Norway and 7% to 17% in Sweden. CONCLUSIONS: Birth and abortion rates continuously declined in the Nordic countries among teenagers. There was a high user rate of hormonal contraceptives, with an increase in the use of LARC especially among the oldest teenagers. OBJECTIVES: Compare hormonal contraceptive use, birth and abortion rates among teenagers in the Nordic countries. A secondary aim was to explore plausible explanations for possible differences between countries. DESIGN: Ecological study using national registry data concerning births and abortions among all women aged 15-19 years residing in Denmark, Finland, Iceland, Norway and Sweden 2008-2015. Age-specific data on prescriptions for hormonal contraceptives for the period 2008-2015 were obtained from national databases in Denmark, Norway and Sweden. SETTING: Denmark, Finland, Iceland, Norway and Sweden. PARTICIPANTS: Women 15-19 years old in all Nordic countries (749 709) and 13-19 years old in Denmark, Norway and Sweden (815 044). © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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| 9. |
- Jar-Allah, Tagrid, et al.
(författare)
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Detection of ectopic pregnancy and serum beta hCG levels in women undergoing very early medical abortion: a retrospective cohort study : Detection of ectopic pregnancy and serum beta hCG levels in women undergoing very early medical abortion: a retrospective cohort stud
- 2022
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Ingår i: European Journal of Contraception and Reproductive Health Care. - : Informa UK Limited. - 1362-5187 .- 1473-0782. ; 27:3, s. 240-246
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate the outcome of the very early medical abortion (VEMA) protocol and whether it could increase early diagnosis and treatment of an asymptomatic ectopic pregnancy (EP). To investigate serum beta-hCG levels correlated to ultrasound findings, and decline in beta-hCG after successful VEMA. Study design A retrospective case-note review. The population consisted of all women undergoing a VEMA during 2004-14 in Austria and 2012-13 in Sweden. Two cohorts identified based on sonography findings; 106 women with an empty uterine cavity were classified as a pregnancy of unknown location (PUL) and 576 women with an intrauterine sac-like structure without a yolk sac or foetal structure were classified as probable intrauterine pregnancy (probable IUP). Results Overall, 660 women (97.6%) had a successful VEMA, 94/101 women (93.1%) in the PUL group and 566/575 women (98.4%) in the probable IUP group (p < 0.001). We identified six asymptomatic EP (0.88%). A gestational sac (< 10 mm) was detected at a median/range beta-hCG level 2728 (1600-4497) IU/l. The mean decline in beta-hCG was 93%, (95% CI 91.7-94.2) 5-10 days after successful abortion. Conclusions VEMA may be of particular clinical benefit for women. Apart from offering a possibility to start an abortion without delay as soon as the woman has sought abortion care, it may also offer an opportunity to detect and treat EP at an early gestational age. However, the rate of EP was very low.
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| 10. |
- Lindh, Ingela, 1954, et al.
(författare)
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Reproductive changes among women in their 40s: A cross-sectional study
- 2022
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Ingår i: Acta Obstetricia Et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 101:42, s. 248-255
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The aim was to describe and compare changes in the reproductive pattern of women in their 40s observed over a decade in Scandinavia. Material and Methods: Cross-sectional study using the total population of women aged 40-49 years between 2008-2018 in Denmark, Norway and Sweden (on average n = 1.5 million). Aggregated data concerning birth and induced abortion rate were collected and analyzed from national health registers. National data on redeemed prescriptions of hormonal contraceptives in the three countries were collected from prescription registers. Births after spontaneous and assisted conceptions were identified by using cross-linked data on deliveries from the Medical Birth Registers and National Registers of Assisted Reproduction in the three countries. Results: Use of hormonal contraception increased among women aged 40-44 years in Denmark from 24% to 31%, in Sweden from 27% to 30%, and in Norway from 22% to 24%. The levonorgestrel-releasing intrauterine device was the most frequently used method in all countries. Birth rates among women 40-44 years increased continuously from 9.5 to 12/1000 women in Denmark and from 11.7 to 14.3/1000 in Sweden, but remained stable in Norway at similar to 11/1000 women. There was a doubling of assisted conceptions in Denmark from 0.71 to 1.71/1000 women, Sweden from 0.43 to 0.81/1000 and Norway from 0.25 to 0.53/1000 women 40-49 years of age. Sweden had the highest induced abortion rate (7.7 to 8.1/1000 women) in women aged 40-49 years during the study period. Conclusions: From 2008 to 2018, birth rates continuously increased among women aged 40-49 years in Denmark and Sweden and births resulting from assisted reproductive technology doubled in all three countries.
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