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1.
  • Aghajanova, Lusine, et al. (författare)
  • Receptors for thyroid-stimulating hormone and thyroid hormones in human ovarian tissue
  • 2009
  • Ingår i: Reproductive BioMedicine Online. - : Elsevier BV. - 1472-6483 .- 1472-6491. ; 18:3, s. 337-347
  • Tidskriftsartikel (refereegranskat)abstract
    • Dysfunction in thyroid regulation can cause menstrual and ovulatory disturbances, the mechanism of which is not clear. The distribution and activity of the thyroid-stimulating hormone (TSHR), and the thyroid hormone receptors (TR) alpha1, alpha2 and beta1 in human ovarian tissue and in granulosa cells was studied using immunohistochemistry, reverse-transcriptase polymerase chain reaction (RT-PCR), quantitative PCR and immunoassays. Strong immunostaining of TSHR, TRalpha1 and TRbeta1 was observed in ovarian surface epithelium and in oocytes of primordial, primary and secondary follicles, with minimal staining in granulosa cells of secondary follicles. Granulosa cells of antral follicles expressed TSHR, TRalpha1 and TRbeta1 proteins. Messenger RNA for all receptors was present in ovarian tissue. Mature human granulosa cells expressed transcripts for 5' deiodinases types 2 and 3, but not type 1, indicating the possibility of conversion of peripheral thyroid hormone thyroxin (T(4)). Granulosa cells stimulated with TSH showed a significant increase in cAMP concentrations after 2 h of culture (P = 0.047), indicating activation through TSHR. Stimulation with T(4) resulted in increased extracellular signal-regulated kinase 1 and 2 activation after 10, 30, 60 min and 24 h. These data demonstrate that TSH and thyroid hormone receptors may participate in the regulation of ovarian function.
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2.
  • Altmäe, Signe, et al. (författare)
  • Aromatase gene (CYP19A1) variants, female infertility and ovarian stimulation outcome : a preliminary report
  • 2009
  • Ingår i: Reproductive BioMedicine Online. - 1472-6483 .- 1472-6491. ; 18:5, s. 651-657
  • Tidskriftsartikel (refereegranskat)abstract
    • Progress has been made towards ascertaining the genetic predictors of ovarian stimulation in IVF. Aromatase cytochrome P450, encoded by the CYP19A1 gene, catalyses a key step in ovarian oestrogen biosynthesis. Hence, the aromatase gene is an attractive candidate for genetic studies. This study aimed to examine the genetic influences of CYP19A1 TCT trinucleotide insertion/deletion (Ins/Del) and (TTTA)(n) microsatellite intronic polymorphisms on ovarian stimulation outcome and aetiology of female infertility. IVF patients (n = 152) underwent ovarian stimulation according to recombinant FSH and gonadotrophin releasing hormone antagonist protocol. Del/Del homozygous patients with shorter TTTA repeats exhibited decreased ovarian FSH sensitivity in ovarian stimulation, which may reflect variations in aromatase gene expression during early antral follicle development. Accordingly, this study demonstrates correlations between Del allele and shorter (TTTA)(n) repeat sizes with smaller ovaries (r = -0.70, P = 0.047) and fewer antral follicles (r = 0.21, P = 0.018) on days 3-5 of spontaneous menstrual cycle, respectively. Furthermore, Del variation linked with low-repeat-number (TTTA)(n) alleles are involved in enhanced genetic susceptibility to unexplained infertility (adjusted OR = 4.33, P = 0.039) and endometriosis (r = -0.88, P = 0.026), which corroborates evidence on the overlapping patient profiles of ovarian dysfunction in both types of female infertility.
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3.
  • Bortolotti, Lisa, et al. (författare)
  • Reproductive and parental autonomy: an argument for compulsory parental education
  • 2009
  • Ingår i: Reproductive Biomedicine Online. - : Elsevier. - 1472-6491 .- 1472-6483. ; 19:1, s. 5-14
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper we argue that comprehensive and systematic parental education has the potential to equip young adults with the necessary information for the responsible exercise of their autonomy in choices about reproduction and parenting. Education can allow young adults to acquire largely accurate beliefs about reproduction and parenting and the implications of their reproductive and parental choices. Far from being a limitation of individual freedom, the acquisition of relevant information about reproduction and parenting and the acquisition of self-knowledge with respect to reproductive and parenting choices can help give shape to individual life plans. We make a case for compulsory parental education on the basis of the need to respect and enhance individual reproductive and parental autonomy within a culture that presents contradictory attitudes towards reproduction and where decisions about whether to become a parent are subject to significant pressure and scrutiny.
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4.
  • Kartberg, A-J, et al. (författare)
  • Vitrification with DMSO protects embryo membrane integrity better than solutions without DMSO
  • 2008
  • Ingår i: Reproductive BioMedicine Online. - 1472-6483 .- 1472-6491. ; 17:3, s. 378-384
  • Tidskriftsartikel (refereegranskat)abstract
    • Vitrification has become common for cryopreservation of embryos. However, the most Optimal protocol for Vitrification is still to be found. Two vitrification protocols with similar osmolarities were compared: Protocol A. containing dimethyl sulphoxide (DMSO), propane-2-diol, and ethylene glycol. and Protocol B. containing propane-2-diol and ethylene glycol. Viability and the importance of specific incubation times for early embryo recovery. survival. and cleavage were studied. For assessment of cryodamage, embryos were labelled with Alexa Fluor 488-conjugated annexin V and propidium iodide. Vitrification Studies Oil early mouse embryos were followed Up with studies oil human embryos,. The two vitrification protocols did not differ ill embryo survival rates and were equally efficient ill both mouse and human embryo models. Morphological assessment of embryos directly after vitrification was not a useful tool for assessing survival in this study. Extended exposure of embryos with both vitrification protocols showed that the DMSO-containing vitrification solutions did not lead to cell membrane damage and death as quickly as the DMSO-free vitrification solutions. To assess embryo viability, the authors recommend that vitrification of early embryos should be combined with extended culture and assessment of normal blastocyst development before transferring to patients.
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5.
  • Ahlström, Aisling, 1976, et al. (författare)
  • Cross-validation and predictive value of near-infrared spectroscopy algorithms for day-5 blastocyst transfer.
  • 2011
  • Ingår i: Reproductive biomedicine online. - : Elsevier BV. - 1472-6491 .- 1472-6483.
  • Tidskriftsartikel (refereegranskat)abstract
    • Near-infrared (NIR) spectroscopic metabolomic profiling of spent embryo-culture media has been used to calculate a viability score for individual embryos. These scores have been found to correlate to the reproductive potential of cleavage-stage embryos. In this study, 137 spent blastocyst media samples were collected after single-embryo transfer and analysed by NIR spectroscopy to generate an algorithm and calculate viability scores. To blindly validate the algorithm development process, another algorithm was trained on 47 preselected samples from clinic 1 and then used to predict the outcome of 42 samples from clinic 2. The overall pregnancy rate from the two clinical sites was 50.4%. A positive correlation (R(2)=0.82, P=0.03) was observed with the increasing viability score quintiles and their associated implantation rates. Cross-validation of an algorithm generated from NIR analysis of media samples at one clinical setting blindly was shown to predict implantation potential of blastocysts cultured at another clinic in a different culture media and culture volume. This study demonstrates that metabolomic profiling by NIR spectroscopic analysis of day-5 spent embryo-culture media can predict the implantation potential of blastocysts. Furthermore, this method may not be restricted to a specific set of culturing conditions. The successes of IVF treatment cycles are in part limited by the ability to select the best single embryo from a cohort of patient embryos for transfer back to the woman. Routine procedures of embryo selection are based on morphology, including cell number and size, and the timing of cell division. These methods are favoured because they are quick and easy to assess. Human embryos are grown in culture solutions, which are specific for their stage of development. Recent studies analysing the culture solution in which the embryo are grown, by near infrared (NIR) spectroscopic analysis, have been able to predict if an embryo will implant or not. As culture conditions often vary between IVF laboratories the questions remained if the NIR technique could be used to independently predict the implantation potential of an embryo cultured at one laboratory using an algorithm trained on embryos at a second clinic, a so-called cross-validation. The results of this study show that NIR spectroscopy can predict the ability of embryos to implant even when grown in different IVF laboratories and in two different culture solutions. This information supports the idea that NIR spectroscopy can be used globally not relying on specific culture conditions or media.
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7.
  • Altmae, Signe, et al. (författare)
  • Endometrial transcriptome analysis indicates superiority of natural over artificial cycles in recurrent implantation failure patients undergoing frozen embryo transfer
  • 2016
  • Ingår i: Reproductive BioMedicine Online. - : Elsevier BV. - 1472-6483 .- 1472-6491. ; 32:6, s. 597-613
  • Tidskriftsartikel (refereegranskat)abstract
    • Little consensus has been reached on the best protocol for endometrial preparation for frozen embryo transfer (FET). It is not known how, and to what extent, hormone supplementation in artificial cycles influences endometrial preparation for embryo implantation at a molecular level, especially in patients who have experienced recurrent implantation failure. Transcriptome analysis of 15 endometrial biopsy samples at the time of embryo implantation was used to compare two different endometrial preparation protocols, natural versus artificial cycles, for FET in women who have experienced recurrent implantation failure compared with fertile women. IPA and DAVID were used for functional analyses of differentially expressed genes. The TRANSFAC database was used to identify oestrogen and progesterone response elements upstream of differentially expressed genes. Cluster analysis demonstrated that natural cycles are associated with a better endometrial receptivity transcriptome than artificial cycles. Artificial cycles seemed to have a stronger negative effect on expression of genes and pathways crucial for endometrial receptivity, including ESR2, FSHR, LEP, and several interleukins and matrix metalloproteinases. Significant overrepresentation of oestrogen response elements among the genes with deteriorated expression in artificial cycles (P < 0.001) was found; progesterone response elements predominated in genes with amended expression with artificial cycles (P = 0.0052).
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8.
  • Andersen, Claus Yding, et al. (författare)
  • Preovulatory progesterone concentration associates significantly to follicle number and LH concentration but not to pregnancy rate
  • 2011
  • Ingår i: Reproductive BioMedicine Online. - : Elsevier BV. - 1472-6491 .- 1472-6483. ; 23:2, s. 187-195
  • Tidskriftsartikel (refereegranskat)abstract
    • Using data from a large prospective randomized controlled trial that evaluated the effect of recombinant LH (rLH) co-administration for ovarian stimulation, the present study assessed whether progesterone concentration on the day of human chorionic gonadotrophin (HCG) administration was associated with pregnancy outcome. Progesterone concentration was measured on stimulation day 1 and on the day of HCG administration in 475 patients who underwent IVF/intracytoplasmic sperm injection treatment following ovarian stimulation with gonadotrophin-releasing hormone (GnRH) agonist and recombinant FSH with or without rLH administration from day 6 of stimulation. There was no significant association between the late-follicular-phase progesterone concentration and the clinical pregnancy rate. However, progesterone concentration was strongly associated with the number of follicles and retrieved oocytes. Late-follicular-phase LH concentration also showed a significant positive association with progesterone concentration (P = 0.018). Administration of rLH during ovarian stimulation did not affect progesterone concentration. The present study does not support an association between progesterone concentration on the day of HCG administration and the probability of clinical pregnancy in women undergoing ovarian stimulation with GnRH agonists and gonadotrophins for assisted reproduction treatment. Instead, late-follicular-phase progesterone concentration appears to be governed by the number of preovulatory follicles and LH concentration. (C) 2011, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
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9.
  • Bergh, Christina, 1953, et al. (författare)
  • Corifollitropin alfa for ovarian stimulation in IVF: a randomized trial in lower-body-weight women.
  • 2010
  • Ingår i: Reproductive biomedicine online. - : Elsevier BV. - 1472-6491 .- 1472-6483. ; 21:1, s. 66-76
  • Tidskriftsartikel (refereegranskat)abstract
    • In this double-blind, double-dummy, randomized, equivalence trial (Ensure), 396 women weighing 60kg or less who underwent controlled ovarian stimulation prior to IVF or intracytoplasmic sperm injection were randomized in a 2:1 ratio to a single dose of 100mug corifollitropin alfa or daily 150IU recombinant FSH (rFSH) for the first 7days of stimulation in a gonadotrophin-releasing hormone antagonist protocol. The mean +/- SD number of oocytes retrieved per started cycle was 13.3 +/- 7.3 for corifollitropin alfa versus 10.6 +/- 5.9 for rFSH. The estimated treatment difference of +2.5 oocytes (95% CI 1.2-3.9) in favour of corifollitropin alfa (P<0.001) was well within the predefined equivalence margin. The median (range) duration of stimulation was 9 (6-15) days in both groups. In 32.8% of the patients, one injection of corifollitropin alfa was sufficient to reach the human chorionic gonadotrophin criterion. The incidence of moderate and severe ovarian hyperstimulation syndrome was 3.4% for corifollitropin alfa and 1.6% for rFSH. A dose of 100mug corifollitropin alfa offers a simplified treatment option for potential normal responder patients with a lower body weight.
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15.
  • Gunnarsson Payne, Jenny, 1976- (författare)
  • Autonomy in altruistic surrogacy, conflicting kinship grammars and intentional multilineal kinship
  • 2018
  • Ingår i: Reproductive BioMedicine Online. - : Elsevier. - 1472-6483 .- 1472-6491 .- 2405-6618. ; 7, s. 66-75
  • Tidskriftsartikel (refereegranskat)abstract
    • Since 1982, when the first baby conceived by in-vitro fertilization (IVF) in Sweden was born, Swedish legislation on assisted reproduction has gradually become more liberal and inclusive. Today, gamete donation and IVF are permitted not only for heterosexual couples, but also for lesbian couples and single women, and embryo donation is expected to become legalized shortly which will further increase the chances for involuntarily childless people to become parents. In recent years, the possibility of allowing surrogacy has been debated increasingly, with strongly polarized arguments both for and against it. Recent reports by the Swedish National Council of Medical Ethics and a governmental investigation agreed that the possibilities for involuntarily childless people should be increased in several ways, but reached opposing conclusions concerning surrogacy. While the former argued in favour of it (in certain circumstances), the latter argued against it (in all circumstances). One difference in their argumentation centred around the issue of bodily autonomy and self-determination in surrogacy. These two opposing conclusions raise crucial questions about what the principle of reproductive intent implies for questions concerning reproductive autonomy in surrogacy. Does it matter when in the reproductive process the declaration of intent is made, and what happens if we consider the possibility of changing intentions in relation to autonomy and self-determination in surrogacy? Is the mater est rule compatible with an intersectional, queer and non-discriminatory approach to reproductive justice, and if so, under what circumstances? Are there any possibilities of thinking beyond the ‘either/or’ between these two principles?
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16.
  • Haroun, Sally, et al. (författare)
  • Association between trefoil factor 3 gene variants and idiopathic recurrent spontaneous abortion
  • 2014
  • Ingår i: Reproductive BioMedicine Online. - : Elsevier BV. - 1472-6483 .- 1472-6491. ; 29:6, s. 737-44
  • Tidskriftsartikel (refereegranskat)abstract
    • Trefoil factor 3 (TFF3) gene is an inflammatory mediator expressed in human endometrium during the window of implantation. The aim of this study was to evaluate the possible genetic association of TFF3 variants in recurrent spontaneous abortion. Women with a history of recurrent spontaneous abortion (n = 164) and healthy pregnant women (n = 143) were genotyped for five TFF3 polymorphisms (rs225439 G/A, rs533093 C/T, rs225361 A/G, rs11701143 T/C and rs77436142 G/C). In addition, haplotypes formed within the gene were analysed. Within the recurrent spontaneous abortion group, women who at some point had given birth and childless women had 4.19 ± 1.75 and 5.34 ± 3.42 consecutive spontaneous abortions, respectively. Women who had experience recurrent spontaneous abortions had a lower allele frequency of the rs11701143 promoter region minor C allele compared with fertile women (0.02 versus 0.05, P = 0.015). Patients with rs225361 AG genotype had significantly more successful pregnancies before spontaneous abortion than those with homozygous AA and GG genotypes (P = 0.014). No significant differences in haplotype frequencies between patients and controls were detected. Possible genetic risk factors identified that might contribute to the pathogenesis of idiopathic recurrent spontaneous abortion were TFF3 gene variants.
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17.
  • Hassan, Jasmin, et al. (författare)
  • Reference standards for follicular density in ovarian cortex from birth to sexual maturity
  • 2023
  • Ingår i: Reproductive BioMedicine Online. - : Elsevier. - 1472-6483 .- 1472-6491. ; 47:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Research question: Are age-normalized reference values for human ovarian cortical follicular density adequate for tissue quality control in fertility preservation?Design: Published quantitative data on the number of follicles in samples without known ovarian pathology were converted into cortical densities to create reference values. Next, a sample cohort of 126 girls (age 1-24 years, mean +/- SD 11 +/- 6) with cancer, severe haematological disease or Turner syndrome were used to calculate Z-scores for cortical follicular density based on the reference values.Results: No difference was observed between Z-scores in samples from untreated patients (0.3 +/- 3.5, n = 30) and patients treated with (0.5 +/- 2.9, n = 48) and without (0.1 +/- 1.3, n = 6) alkylating chemotherapy. Z-scores were not correlated with increasing cumulative exposure to cytostatics. Nevertheless, Z-scores in young treated patients (0-2 years -2.1 +/- 3.1, n = 10, P = 0.04) were significantly lower than Z-scores in older treated patients (11-19 years, 2 +/- 1.9, n = 15). Samples from patients with Turner syndrome differed significantly from samples from untreated patients (-5.2 +/- 5.1, n = 24, P = 0.003), and a Z-score of -1.7 was identified as a cut-off showing good diagnostic value for identification of patients with Turner syndrome with reduced ovarian reserve. When this cut-off was applied to other patients, analysis showed that those with indications for reduced ovarian reserve (n = 15) were significantly younger (5.9 +/- 4.2 versus 10.7 +/- 5.9 years, P = 0.004) and, when untreated, more often had non-malignant haematologic diseases compared with those with normal ovarian reserve (n = 24, 100% versus 19%, P = 0.009).Conclusion: Z-scores allow the estimation of genetic- and treatment-related effects on follicular density in cortical tissue from young patients stored for fertility preservation. Understanding the quality of cryopreserved tissue facilitates its use during patient counselling. More research is needed regarding the cytostatic effects found in this study.
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20.
  • Karlström, Per-Olof, et al. (författare)
  • Does ovarian stimulation regimen affect IVF outcome? : a two-centre, real-world retrospective study using predominantly cleavage-stage, single embryo transfer
  • 2018
  • Ingår i: Reproductive BioMedicine Online. - : ELSEVIER SCI LTD. - 1472-6483 .- 1472-6491. ; 36:1, s. 59-66
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study, ovarian stimulation using highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) for IVF were compared in two large assisted reproduction technique centres in Sweden. A total of 5902 women underwent 9631 oocyte retrievals leading to 8818 embryo transfers (7720 on day 2): single embryo transfers (74.2%); birth rate per embryo transfer (27.7%); multiple birth rate (5.0%); incidence of severe ovarian hyperstimulation syndrome (0.71%). Compared with ovarian stimulation with rFSH, women who received HP-HMG were older, had higher dosages of gonadotrophins administered, fewer oocytes retrieved and more embryos transferred. After multivariate analysis controlling for age and generalized estimating equation model, no differences were found in delivery outcomes per embryo transfers between HP-HMG and rFSH, independent of gonadotrophin releasing hormone analogue (GnRH) used. Logit curves for live birth rate suggested differences for various subgroups, most prominently for women with high oocyte yield or when high total doses were used. Differences were not significant, perhaps owing to skewed distributions of the FSH compounds versus age and other covariates. These 'real-life patients' had no differences in live birth rate between HP-HMG and rFSH overall or in subgroups of age, embryo score, ovarian sensitivity or use of GnRH analogue regimen.
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23.
  • Laanpere, M, et al. (författare)
  • Folate-metabolizing gene variants and pregnancy outcome of IVF
  • 2011
  • Ingår i: Reproductive BioMedicine Online. - : Elsevier BV. - 1472-6483 .- 1472-6491. ; 22:6, s. 603-614
  • Tidskriftsartikel (refereegranskat)abstract
    • There is growing evidence that folate status and variation in folate-metabolizing genes are involved in female reproductive functions. This study evaluated the influence of maternal blood folate, vitamin B(12), homocysteine and 10 folate pathway gene variants on IVF outcome. Also, the prevalence of these polymorphisms was compared in 439 female IVF patients and 225 fertile controls. MTHFR 677 CT heterozygotes had a higher proportion of good-quality embryos and an increased chance of pregnancy. MTHFR 1793 GA heterozygosity was associated with a lower percentage of previously failed IVF treatments. Heterozygosity for FOLR1 1816 C/delC and 1841 G/A was associated with a raised risk of pregnancy loss. The CTH 1208 GT genotype was associated with an increased chance of pregnancy and a smaller number of previously failed IVF cycles and the genotype frequency was lower in IVF patients with three or more previously failed IVF treatments compared with fertile controls. SLC19A1 80 GA heterozygotes had a decreased number of previously failed IVF treatments and were more prevalent among fertile controls. In conclusion, polymorphisms in folate-metabolizing genes may affect ovarian stimulation and pregnancy outcome of IVF, and heterozygous individuals, rather than the wild-type homozygotes, appeared to have more favourable outcomes.
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24.
  • Lewis, Sheena E. M., et al. (författare)
  • The impact of sperm DNA damage in assisted conception and beyond: recent advances in diagnosis and treatment
  • 2013
  • Ingår i: Reproductive BioMedicine Online. - : Elsevier BV. - 1472-6491 .- 1472-6483. ; 27:4, s. 325-337
  • Forskningsöversikt (refereegranskat)abstract
    • Sperm DNA damage is a useful biomarker for male infertility diagnosis and prediction of assisted reproduction outcomes. It is associated with reduced fertilization rates, embryo quality and pregnancy rates, and higher rates of spontaneous miscarriage and childhood diseases. This review provides a synopsis of the most recent studies from each of the authors, all of whom have major track records in the field of sperm DNA damage in the clinical setting. It explores current laboratory tests and the accumulating body of knowledge concerning the relationship between sperm DNA damage and clinical outcomes. The paper proceeds to discuss the strengths, weaknesses and clinical applicability of current sperm DNA tests. Next, the biological significance of DNA damage in the male germ line is considered. Finally, as sperm DNA damage is often the result of oxidative stress in the male reproductive tract, the potential contribution of antioxidant therapy in the clinical management of this condition is discussed. DNA damage in human spermatozoa is an important attribute of semen quality. It should be part of the clinical work up and properly controlled trials addressing the effectiveness of antioxidant therapy should be undertaken as a matter of urgency. (c) 2013, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
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26.
  • Liffner, Susanne, et al. (författare)
  • Birth characteristics in men with infertility
  • 2020
  • Ingår i: Reproductive BioMedicine Online. - : ELSEVIER SCI LTD. - 1472-6483 .- 1472-6491. ; 41:3, s. 455-463
  • Tidskriftsartikel (refereegranskat)abstract
    • Research question: Are low birth weight, prematurity, being born small for gestational age, or both, associated with a higher risk of male factor infertility in adulthood? Design: Retrospective study of a clinical sample of 892 men, diagnosed with an infertility factor (male, female, combined or unexplained) together with their female partner at a University Hospital clinic in Sweden between 2005 and 2010. Data on birth weight and gestational age at birth were retrieved from the Swedish Medical Birth Register. The distribution of non-optimal birth characteristics in relation to infertility factor was described. A control group was created consisting of two men for each index man, born in Sweden in the same year as each index men, as well as a reference group consisting of all men born in Sweden the same years. Results: The likelihood of having been born small for gestational age was almost fivefold higher in men with male factor infertility than in men with unexplained infertility (OR 4.84, 95% CI 1.32 to 1780). Men with male factor infertility were more often born with non-optimal birth characteristics than the control group (14.8% versus 8.5%; P = 0.010) and the reference group (14.8% versus 11.4%; P < 0.001). Men with azoospermia were more often born with non-optimal birth characteristics, compared with men without azoospermia (21.3% versus 12.1%; P = 0.038). Conclusions: The results suggest an association between intrauterine growth restriction and male factor infertility in adulthood.
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27.
  • Lind, Judith, 1971- (författare)
  • Child welfare assessments and the regulation of access to publicly funded fertility treatment
  • 2020
  • Ingår i: Reproductive BioMedicine Online. - : Elsevier. - 1472-6483 .- 1472-6491 .- 2405-6618. ; 10, s. 19-27
  • Tidskriftsartikel (refereegranskat)abstract
    • Assessment of the psychological and social circumstances of candidates for assisted reproduction is commonly justified with references to the welfare of the intended child. In nine focus group discussions with 64 clinic staff at four public fertility clinics in Sweden, the responsible use of public resources constituted another important justification for such assessments. Theoretically, this study draws on Julia Black’s (2002) identification of the role of regulatory conversations in decision makers’ policy interpretations. Focus groups defined the desired outcome of assisted reproductive technology (ART) treatment as a well - functioning family , and represented the aim of ART treatment as solving problems without creating new problems for the candidates, the intended child or society. In the discourse of solving and preventing problems, the welfare of the child argument, the responsible use of resources argument and the discourse of personal responsibility merge. Lack of consideration for the circumstances in which the child will grow up was not considered a responsible use of resources because ART treatment would then risk creating more problems than it solved. The results of this study suggest that while publicly funded subsidization of fertility treatment has increased accessibility to ART treatment for candidates who lack the financial means to pay, clinic staff justified restricting access to ART treatment with concern for how public resources are spent.
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28.
  • Lindgren, Karin E, 1984-, et al. (författare)
  • The effect of a specific histidine-rich glycoprotein polymorphism on male infertility and semen parameters.
  • 2016
  • Ingår i: Reproductive BioMedicine Online. - : Elsevier BV. - 1472-6483 .- 1472-6491. ; 33:2, s. 180-188
  • Tidskriftsartikel (refereegranskat)abstract
    • In women, there is evidence that a single nucleotide polymorphism (SNP) in the histidine-rich glycoprotein (HRG) named HRG C633T is relevant for a number of fertility outcomes including recurrent miscarriage, ovarian response and pregnancy outcome after IVF. This case-control study was designed to investigate whether the HRG C633T SNP is important for male infertility and pregnancy rate following IVF. Cases were 139 infertile couples and controls were 196 pregnant couples. The 335 couples all contributed with one blood sample per partner. Genomic DNA was extracted and genotyping was performed using a TaqMan® SNP Genotyping Assay. Information on pregnancy rate and semen parameters was derived from medical records. Infertile couples in which the male partner was a homozygous carrier of the HRG C633T SNP had significantly lower (P < 0.01) pregnancy rate following IVF in comparison with couples where the male partner was a heterozygous HRG C633T SNP carrier. Male homozygous HRG 633T SNP carriers had overall lower total sperm count, sperm concentration, motility score and yield after preparation. In conclusion, once infertility is established the HRG C633T SNP seems to be important for male infertility and pregnancy rate following IVF.
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29.
  • Morrell, Jane, et al. (författare)
  • Single layer centrifugation of stallion spermatozoa improves sperm quality compared with sperm washing
  • 2010
  • Ingår i: Reproductive BioMedicine Online. - : Elsevier. - 1472-6483 .- 1472-6491. ; 21:3, s. 429-436
  • Tidskriftsartikel (refereegranskat)abstract
    • This study compared the effect on semen quality of different handling methods used in the preparation of stallion semen doses for artificial insemination. The three methods were (i) extending the ejaculate to 30-50 x 10(6)/ml, (ii) single layer centrifugation (SLC) and (iii) sperm washing (centrifugation without a colloid). An additional treatment was to add seminal plasma (SP) in various proportions to some SLC preparations. The resulting samples were evaluated for sperm motility by computer assisted sperm analysis, membrane integrity using the Nucleocounter SP-100 and chromatin integrity by the sperm chromatin structure assay. SLC samples consistently had better sperm quality than the extended samples. Sperm washing did not confer any beneficial effect compared with the extended samples and these samples had significantly worse sperm quality than the SLC samples (motility, P less than 0.01; viability, P less than 0.001). There was no evidence to suggest that adding SP to the SLC samples could enhance sperm motility for more than a few hours. Longer term cold storage of spermatozoa in the presence of small concentrations of SP resulted in a reduction in total motility and progressive motility compared with SLC alone. High concentrations of SP were detrimental to sperm survival. (C) 2010, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
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30.
  • Murto, Tiina, et al. (författare)
  • Folic acid supplementation and IVF pregnancy outcome in women with unexplained infertility
  • 2014
  • Ingår i: Reproductive BioMedicine Online. - : Elsevier. - 1472-6483 .- 1472-6491. ; 28:6, s. 766-772
  • Tidskriftsartikel (refereegranskat)abstract
    • Folic acid supplements are commonly used by infertile women and lead to a positive folate status. However, the effect of folic acid supplements on pregnancy outcome in women with unexplained infertility has not been well investigated. This study evaluated folic acid supplement use and folate status in women with unexplained infertility in relation to pregnancy outcome. In addition, use of folic acid supplements and folate status were compared between women with unexplained infertility and fertile, nonpregnant control women. Women with unexplained infertility used significantly more folic acid supplements and had higher median total folic acid intake from supplements compared with fertile control women (both P < 0.001). Women with unexplained infertility also had significantly higher median plasma folate and lower median plasma homocysteine concentrations than fertile women (both P < 0.001), but folic acid supplementation or folate status were not related to pregnancy outcome in women with unexplained infertility. In conclusion, folic acid supplementation or good folate status did not have a positive effect on pregnancy outcome following infertility treatment in women with unexplained infertility.
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31.
  • Nordgren, Anders, 1953- (författare)
  • Analysis of an epigenetic argument against human reproductive cloning
  • 2006
  • Ingår i: Reproductive BioMedicine Online. - 1472-6483 .- 1472-6491. ; 13:2, s. 278-283
  • Tidskriftsartikel (refereegranskat)abstract
    • Human reproductive cloning is a much disputed ethical issue. This technology is often condemned as being contrary to human dignity. However, there are also risk arguments. An ethical argument that is often put forward by scientists but seldom developed in more detail focuses on health risks in animal cloning. There is a high risk that animal clones exhibit abnormalities and these are increasingly believed to be due to errors in epigenetic reprogramming. The argument is that human reproductive cloning should not be carried out because human clones are also likely to exhibit abnormalities due to inappropriate epigenetic reprogramming. Different versions of this epigenetic argument are analysed, a categorical version and a non-categorical. The non-categorical version is suggested to be more well-considered. With regard to policy making on human reproductive cloning, the categorical version can be used to prescribe a permanent ban, while the non-categorical version can be used to prescribe a temporary ban. The implications of the precautionary principle - as interpreted in the European Union - are investigated. The conclusion is that it seems possible to support a temporary ban by reference to this principle.
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32.
  • Nordqvist, Sarah, 1962-, et al. (författare)
  • Histidine-Rich Glycoprotein Polymorphism and Pregnancy Outcome : a pilot study
  • 2011
  • Ingår i: Reproductive BioMedicine Online. - : Elsevier BV. - 1472-6483 .- 1472-6491. ; 23:2, s. 213-219
  • Tidskriftsartikel (refereegranskat)abstract
    • Histidine-rich glycoprotein (HRG) is involved in fibrinolysis and coagulation, the immune system and angiogenesis. These processes are all crucial in establishing and maintaining pregnancy. The primary aim of this pilot study was to determine if HRG affects pregnancy outcome. The secondary aim was to investigate if a specific genetic polymorphism (rs9898 C/T) in the HRG gene is associated with pregnancy results. The polymorphism leads to expression of either a serine or proline residue at position 186 in the protein sequence. In this study, women undergoing IVF were included. The genetic polymorphism in the HRG gene was analysed by Western blot and single nucleotide polymorphism analysis. None of the women homozygous for the serine at residue 186 became pregnant whereas the women homozygous for proline at residue 186 had higher than expected pregnancy rates. As far as is known,this is the first study to show that a specific genetic polymorphism in the HRG gene of a woman affects her chances of becoming pregnant after IVF. The results may be essential in improving advice and IVF treatment for couples with unexplained infertility.We have found a new test which might potentially improve advice and treatment for infertile couples considering IVF treatment. Histidine-rich glycoprotein (HRG) is involved in the system preventing blood clots or excess bleeding, the immune system and the system regulating blood vessel formation. Tight regulation of these processes is necessary for a pregnancy to be successful. This study examines how a specific genetic variant of HRG can affect pregnancy rates after IVF. The genetic polymorphism leads to expression of two different protein variations. One variation has a serine amino acid attached at position 186 and the other variation has a proline amino acid attached at the same position. Which variation a women produces is inherited co-dominantly. In this study, women undergoing IVF were included. To determine which variation each woman had, two different methods were used: Western blot and single nucleotide polymorphism analysis. The experimental results were then related to the woman’s medical records. None of the women who only produced the variation of HRG with a serine attached became pregnant, whereas the women who produced only the proline variation had higher than expected pregnancy rates. We show for the first time that the genetic background of a woman may affect her chances of becoming pregnant after IVF. The results might be essential in improving advice and IVF treatment for infertile couples.
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33.
  • Nordqvist, Sarah, 1962-, et al. (författare)
  • Ovarian Response is Affected by a Specific Histidine-Rich Glycoprotein Polymorphism : a preliminary study
  • 2015
  • Ingår i: Reproductive BioMedicine Online. - : Elsevier BV. - 1472-6483 .- 1472-6491. ; 30:1, s. 74-81
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic polymorphisms involved in angiogenesis, apoptosis and chemokine signalling are associated with varying ovarian response and oocyte quality. The protein, histidine-rich glycoprotein (HRG), is involved in these processes, but its effect on ovarian response in IVF has not been previously studied. A single nucleotide polymorphism (SNP) in the HRG gene (C633T) seems to affect pregnancy results in IVF. Women with the C/C genotype had higher pregnancy rates, C/T had moderate rates and none of those in the T/T group conceived. The aim of this study was to investigate if the HRG C633T SNP affects ovarian response. The HRG C633T SNP genotype of 67 women with unexplained infertility undergoing IVF was analysed and related to medical data. The T/T genotype obtained fewer oocytes, including mature oocytes, despite higher dosages of FSH administered. Additionally, the highest proportion of women who had exclusively poor-quality embryos was in the T/T group. No differences in demographic factors known to affect these parameters were found. The results suggest that the HRG C633T SNP influences ovarian response. Further studies of this SNP may increase knowledge about the biological processes involved in oocyte development and, furthermore, improve predicted ovarian response and fertilization.
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34.
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35.
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36.
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37.
  • Parn, Triin, et al. (författare)
  • Physical activity, fatness, educational level and snuff consumption as determinants of semen quality : findings of the ActiART study
  • 2015
  • Ingår i: Reproductive BioMedicine Online. - : Elsevier BV. - 1472-6483 .- 1472-6491. ; 31:1, s. 108-119
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study, the association between physical activity and other potential determinants, objectively measured by accelerometry, was examined. Sixty-two men attending an infertility clinic participated in the study. Obese men (body mass index >= 30) and those with a waist circumference 102 cm or more had lower semen volume than the other men (P < 0.05). Higher values in sperm parameters were observed in participants who completed university studies and those who did not consume snuff, compared with the other participants (P < 0.05). Finally, men who spent an average number of 10 min-bouts of moderate-to-vigorous physical activity had significantly better semen quality than those who engaged in low or high numbers of bouts of activity (P < 0.05). No associations were found for sedentary or moderate-to-vigorous physical activity time when it was not sustained over 10 min, i.e. not in bouts. Men who have average levels of physical activity over sustained periods of 10 min are likely to have better semen quality than men who engage in low or high levels of such activity. Similarly, high levels of total and central adiposity, low educational level and snuff consumption are negatively related to semen quality.
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38.
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39.
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40.
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41.
  • Sjögren, Anita, 0, et al. (författare)
  • Human blastocysts for the development of embryonic stem cells
  • 2004
  • Ingår i: Reproductive BioMedicine Online. - 1472-6483 .- 1472-6491. ; 9:3, s. 326-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Establishment of human embryonic stem cells (hES) from surplus human IVF embryos has been successful when both fresh and frozen-thawed cleavage stage embryos have been cultured to the blastocyst stage. This study reports the characteristics of the starting material, the blastocysts, for hES cell lines that were first derived at the University of Gothenburg, Sahlgrenska University Hospital in 1999. Twenty-two hES cell lines were derived by Cellartis AB from 114 blastocysts, giving an overall success rate of 19.3%. The blastocysts from which the hES cell lines were established were of varying morphological quality, both fresh and frozen-thawed. Two techniques of hES establishment were applied, i.e. direct application of the blastocysts on feeder cells or the standard immunosurgery method. It was further found that the efficiency by which frozen-thawed embryos gave rise to new hES cell lines was 3.7 times better than with fresh surplus embryos. These findings suggest that frozen-thawed embryos are superior to fresh surplus human embryos in hES cell establishment, which also avoids specific ethical problems associated with embryo donation in a fresh IVF cycle.
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42.
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43.
  • Sydsjö, Gunilla, et al. (författare)
  • Long-term follow-up of mental health and satisfaction in a Swedish sample of sperm and egg donors after open-identity donation
  • 2023
  • Ingår i: Reproductive BioMedicine Online. - : Elsevier. - 1472-6483 .- 1472-6491. ; 47:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Research question: How is the mental health of open-identity gamete donors and their satisfaction with their contributions 14–17 years after acceptance as a donor?Design: The Swedish Study on Gamete Donation is a longitudinal study comprising women and men who were accepted as donors at seven Swedish university clinics between 2005 and 2008. The latest (fifth) follow-up included 215 open-identity donors (response rate 87%): 123 oocyte donors and 92 sperm donors. The donors answered a questionnaire regarding their perceptions, experiences and expectations after gamete donation 14–17 years previously.Results: The donors were satisfied with the experience of donating, and no differences were detected between sperm and oocyte donors. Oocyte donors were more than twice as likely to feel that family and friends were proud of their donation compared with sperm donors (51% versus 23%, P < 0.001). In total, six donors regretted their donation: four oocyte donors and two sperm donors. Sperm donors were more frequently satisfied with the financial compensation compared with oocyte donors (P = 0.005). No difference in the development of symptoms of anxiety or depression was detected 14–17 years post-donation.Conclusion: Long-term follow-up studies on donors are important for recruiting donors, and for recipients and the children who will be conceived with donated gametes. The results from the current study indicate that donors, generally, have good mental health and do not regret their decision to donate gametes. These findings are reassuring for all parties involved.
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44.
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45.
  • Vaegter, Katarina Kebbon, et al. (författare)
  • Construction and validation of a prediction model to minimize twin rates at preserved high live birth rates after IVF
  • 2019
  • Ingår i: Reproductive BioMedicine Online. - : Elsevier. - 1472-6483 .- 1472-6491. ; 38:1, s. 22-29
  • Tidskriftsartikel (refereegranskat)abstract
    • Research question: Elective single-embryo transfer (eSET) at blastocyst stage is widely used to reduce the frequency of multiple pregnancies after IVF. There are, however, concerns about increased risks for the offspring with prolonged embryo culture. Is it possible to select embryos for transfer at the early cleavage stage and still achieve low twin rates at preserved high live birth rates? Design: A prediction model (PM) was developed to optimize eSET based on variables known 2 days after oocyte retrieval (fresh day 2 embryo transfers; double-embryo transfers 1999-2002 (n=2846) and SET 1999-2003 (n=945); n total=3791). Seventy-five variables were analysed for association with pregnancy chance and twin risk and combined for PM construction. This PM was validated in 2004-2016 including frozen-thawed transfers (FET), to compare cumulative live birth rate (CLBR) and twin rate before (1999-2002 fresh embryo transfers plus FET from the same oocyte retrievals until the end of 2007, n=3495) and after (2004-2011 fresh embryo transfers plus FET from the same oocyte retrievals until the end of 2016, n=11195) implementing the model. Results: The PM was constructed from four independent variables: female age, embryo score, ovarian sensitivity and treatment history. The calibration, i.e. the fit of observed versus predicted results, was excellent both at construction and at validation. Without compromising CLBR, twin rate was reduced from 25.2% to 3.8%, accompanied by profound improvements in perinatal outcome. Conclusion: The results provide the first successful construction, validation and impact analysis of a day 2 transfer PM to reduce multiple pregnancies.
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46.
  • Valdimarsdottir, Ragnheidur, et al. (författare)
  • Pregnancy and neonatal complications in women with polycystic ovary syndrome in relation to second-trimester anti-Müllerian hormone levels
  • 2019
  • Ingår i: Reproductive BioMedicine Online. - : Elsevier. - 1472-6483 .- 1472-6491. ; 39:1, s. 141-148
  • Tidskriftsartikel (refereegranskat)abstract
    • Research Question: An association has been found between high anti-Müllerian hormone (AMH) levels during pregnancy and the development of polycystic ovary syndrome (PCOS)-like phenotypic traits in mouse offspring. The aim of this study was to determine whether AMH levels are associated with maternal testosterone levels, and whether high AMH concentration influences the risk of developing PCOS-related adverse pregnancy outcomes.Design: Maternal serum AMH, testosterone and sex hormone binding globulin levels were measured in blood samples taken in early second-trimester pregnancies from women with PCOS (n = 159) and healthy controls matched for body mass index (n = 320). Possible associations with preeclampsia, gestational hypertension, gestational diabetes, preterm birth and birthweight was explored by logistic and linear regression models.Results: Women with PCOS had higher AMH, higher total testosterone levels and higher free androgen index than controls (P < 0.001 for all three parameters). Among women with PCOS, high testosterone levels (B = 2.7; β = 0.26; P = 0.001) and low first trimester body mass index (B = -0.5; β = -0.17; P = 0.043) remained independently associated with AMH. High AMH levels were associated with decreased risk of gestational hypertension (adjusted OR 0.55; 95% CI 0.34 to 0.87), but no association was found with other adverse pregnancy outcomes or birthweight.Conclusions: Women with PCOS had higher AMH levels during pregnancy compared with controls, but high AMH was not associated with increased risk of adverse pregnancy outcomes or birthweight.
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47.
  • Valdimarsdottir, Ragnheidur, et al. (författare)
  • Pregnancy outcome in women with polycystic ovary syndrome in relation to second-trimester testosterone levels
  • 2021
  • Ingår i: Reproductive BioMedicine Online. - : Elsevier BV. - 1472-6483 .- 1472-6491. ; 42:1, s. 217-225
  • Tidskriftsartikel (refereegranskat)abstract
    • RESEARCH QUESTION: Do women with polycystic ovary syndrome (PCOS) have higher testosterone levels during pregnancy and what role does high testosterone play in the development of obstetric complications?DESIGN: Retrospective cohort study from Uppsala University Hospital, Sweden. The study population consisted of women with PCOS (n = 159) and a comparison group of women without PCOS matched for body mass index (n = 320). Plasma testosterone levels were measured in the early second trimester by liquid chromatography with tandem mass spectrometry, and women with PCOS were grouped into tertiles according to their testosterone levels. Possible associations with obstetric complications, maternal metabolic factors and offspring birth weight were explored by multivariable logistic and linear regression models.RESULTS: Compared with women who do not have PCOS, women with PCOS had higher total testosterone (median 1.94, interquartile range [IQR] 1.21-2.64 versus 1.41, IQR 0.89-1.97; P < 0.001), and free androgen index (median 0.25, IQR 0.15-0.36 versus 0.18, IQR 0.11-0.28; P < 0.001). Women with PCOS who had the highest levels of testosterone had increased risk for preeclampsia, even when adjusted for age, parity, country of birth and smoking (adjusted OR 6.16, 95% CI 1.82 to 20.91). No association was found between high testosterone in women with PCOS and other obstetric complications.CONCLUSIONS: Women with PCOS have higher levels of total testosterone and free androgen index during pregnancy than women without PCOS matched for body mass index. Preliminary evidence shows that women with PCOS and the highest maternal testosterone levels in early second trimester had the highest risk of developing preeclampsia. This finding, however, is driven by a limited number of cases and should be interpreted with caution.
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48.
  • Vanni, Valeria Stella, et al. (författare)
  • Anti-Müllerian hormone concentration as an indicator of female general health status : a cross-sectional study
  • 2022
  • Ingår i: Reproductive BioMedicine Online. - : Elsevier. - 1472-6483 .- 1472-6491. ; 44:1, s. 119-126
  • Tidskriftsartikel (refereegranskat)abstract
    • Research question: To evaluate the correlation between clinical and hormonal parameters and comorbidity burden in Caucasian women presenting for fertility treatment.Design: Monocentric cross-sectional study including a cohort of 3163 Caucasian women seeking medical care for fertility treatment. All patients underwent centralized laboratory testing for hormonal assessment. Complete clinical and laboratory data from the entire cohort were retrospectively analysed. Comorbidity burden score was assessed by the Charlson Comorbidity Index (CCI; categorized as 0 versus 1 versus >= 2).Results: Descriptive statistics and regression models tested the associations between clinical and laboratory parameters and CCI. Among the entire cohort of patients, a CCI = 0 was found in 2977 women (94.1%), and CCI = 1 and CCI >= 2 were found in 113 (3.6%) and 73 (2.3%) patients, respectively. Age (P = 0.009), gravidity (P = 0.001), anti-Mullerian hormone (AMH, P < 0.001) and TSH (P = 0.003) values were significantly different among CCI groups. In regression models, age at presentation and AMH emerged as independent indicators of CCI >= 1. Age at presentation <36 years (odds ratio [OR] 1.742, 95% confidence interval [CI] 1.284-2.364) and an AMH concentration <= 2.3 ng/ml (OR 1.864, 95% CI 1.29-2.69) were the most informative cut-off values for CCI >= 1 in the study population.Conclusions: A younger age at presentation and lower AMH concentrations are significant independent indicators of decreased general health in women requiring clinical evaluation for fertility treatment. As observed for sperm parameters in men, AMH might serve as a proxy of women's general health status.
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49.
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50.
  • Vexö, LE, et al. (författare)
  • Low-grade inflammation is negatively associated with live birth in women undergoing IVF
  • 2023
  • Ingår i: Reproductive Biomedicine Online. - : Elsevier BV. - 1472-6483 .- 1472-6491. ; 46:2, s. 302-311
  • Tidskriftsartikel (refereegranskat)abstract
    • Research question: Is low-grade inflammation, detected by C-reactive protein (CRP), a marker of IVF outcome addressing both blastocyst quality and pregnancy outcome? Design: This sub-study of a multicentre randomized controlled trial included 440 women undergoing IVF treatment with a gonadotrophin-releasing hormone (GnRH) antagonist protocol. Serum CRP was measured on cycle day 2-3 (baseline) and on the day of ovulation triggering. The association between CRP concentrations and reproductive outcomes (number of retrieved oocytes, number of good-quality blastocysts, pregnancy, pregnancy loss and live birth), were analysed, adjusting for relevant confounders. Results: A negative association was found between higher baseline CRP concentrations and live birth rate (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.62-0.96, P = 0.02) and higher CRP concentrations at baseline were associated with pregnancy loss among women who conceived (OR 1.37, 95% CI 1.07-1.76, P = 0.01). When testing for a specific cut-off, CRP concentrations above 2.34 (the highest quartile) were more likely to be associated with pregnancy loss (P = 0.02) and a lower chance of live birth (P = 0.04) compared with the lowest quartile. No associations were found between CRP concentrations and pregnancy outcomes on the day of ovulation triggering, and there were no associations between CRP concentrations and the number of good-quality blastocysts. Conclusions: Higher CRP concentrations at cycle day 2-3, before starting ovarian stimulation, are negatively associated with chance of live birth, possibly because of an increased risk of pregnancy loss. No association was found between the number of good-quality blastocysts and CRP concentration. More studies are needed to investigate the impact of low-grade inflammation.
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