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| 2. |
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| 3. |
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| 4. |
- Aghajanova, Lusine, et al.
(författare)
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No evidence for mutations in NLRP7, NLRP2 or KHDC3L in women with unexplained recurrent pregnancy loss or infertility
- 2015
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 30:1, s. 232-238
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Are mutations in NLRP2/7 (NACHT, LRR and PYD domains-containing protein 2/7) or KHDC3L (KH Domain Containing 3 Like) associated with recurrent pregnancy loss (RPL) or infertility?SUMMARY ANSWER: We found no evidence for mutations in NLRP2/7 or KHDC3L in unexplained RPL or infertility.WHAT IS KNOWN ALREADY: Mutations in NLRP7 and KHDC3L are known to cause biparental hydatidiform moles (BiHMs), a rare form of pregnancy loss. NLRP2, while not associated with the BiHM pathology, is known to cause recurrent Beckwith Weidemann Syndrome (BWS).STUDY DESIGN, SIZE, AND DURATION: Ninety-four patients with well characterized, unexplained infertility were recruited over a 9-year period from three IVF clinics in Sweden. Blood samples from 24 patients with 3 or more consecutive miscarriages of unknown etiology were provided by the Recurrent Miscarriage Clinic at St Mary's Hospital, London, UK.PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were recruited into both cohorts following extensive clinical studies. Genomic DNA was isolated from peripheral blood and subject to Sanger sequencing of NLRP2, NLRP7 and KHDC3L. Sequence electropherograms were analyzed by Sequencher v5.0 software and variants compared with those observed in the 1000 Genomes, single nucleotide polymorphism database (dbSNP) and HapMap databases. Functional effects of non-synonymous variants were predicted using Polyphen-2 and sorting intolerant from tolerant (SIFT).MAIN RESULTS AND THE ROLE OF CHANCE: No disease-causing mutations were identified in NLRP2, NLRP7 and KHDC3L in our cohorts of unexplained infertility and RPL.LIMITATIONS, REASONS FOR CAUTION: Due to the limited patient size, it is difficult to conclude if the low frequency single nucleotide polymorphisms observed in the present study are causative of the phenotype. The design of the present study therefore is only capable of detecting highly penetrant mutations.WIDER IMPLICATIONS OF THE FINDINGS: The present study supports the hypothesis that mutations in NLRP7 and KHDC3L are specific for the BiHM phenotype and do not play a role in other adverse reproductive outcomes. Furthermore, to date, mutations in NLRP2 have only been associated with the imprinting disorder BWS in offspring and there is no evidence for a role in molar pregnancies, RPL or unexplained infertility.STUDY FUNDING/COMPETING INTERESTS: This study was funded by the following sources: Estonian Ministry of Education and Research (Grant SF0180044s09), Enterprise Estonia (Grant EU30020); Mentored Resident research project (Department of Obstetrics and Gynecology, Baylor College of Medicine); Imperial NIHR Biomedical Research Centre; Grant Number C06RR029965 from the National Center for Research Resources (NCCR; NIH). No competing interests declared.
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| 5. |
- Ahlström, Aisling, 1976, et al.
(författare)
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A double-blind randomized controlled trial investigating a time-lapse algorithm for selecting Day 5 blastocysts for transfer
- 2022
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 37:4, s. 708-717
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION Can use of a commercially available time-lapse algorithm for Day 5 blastocyst selection improve pregnancy rates compared with morphology alone? SUMMARY ANSWER The use of a time-lapse selection model to choose blastocysts for fresh single embryo transfer on Day 5 did not improve ongoing pregnancy rate compared to morphology alone. WHAT IS KNOWN ALREADY Evidence from time-lapse monitoring suggests correlations between timing of key developmental events and embryo viability. No good quality evidence exists to support improved pregnancy rates following time-lapse selection. STUDY DESIGN, SIZE, DURATION A prospective multicenter randomized controlled trial including 776 randomized patients was performed between 2018 and 2021. Patients with at least two good quality blastocysts on Day 5 were allocated by a computer randomization program in a proportion of 1:1 into either the control group, whereby single blastocysts were selected for transfer by morphology alone, or the intervention group whereby final selection was decided by a commercially available time-lapse model. The embryologists at the time of blastocyst morphological scoring were blinded to which study group the patients would be randomized, and the physician and patients were blind to which group they were allocated until after the primary outcome was known. The primary outcome was number of ongoing pregnancies in the two groups. PARTICIPANTS/MATERIALS, SETTING, METHODS From 10 Nordic IVF clinics, 776 patients with a minimum of two good quality blastocysts on Day 5 (D5) were randomized into one of the two study groups. A commercial time-lapse model decided the final selection of blastocysts for 387 patients in the intervention (time-lapse) group, and blastocysts with the highest morphological score were transferred for 389 patients in the control group. Only single embryo transfers in fresh cycles were performed. MAIN RESULTS AND THE ROLE OF CHANCE In the full analysis set, the ongoing pregnancy rate for the time-lapse group was 47.4% (175/369) and 48.1% (181/376) in the control group. No statistically significant difference was found between the two groups: mean difference -0.7% (95% CI -8.2, 6.7, P = 0.90). Pregnancy rate (60.2% versus 59.0%, mean difference 1.1%, 95% CI -6.2, 8.4, P = 0.81) and early pregnancy loss (21.2% versus 18.5%, mean difference 2.7%, 95% CI -5.2, 10.6, P = 0.55) were the same for the time-lapse and the control group. Subgroup analyses showed that patient and treatment characteristics did not significantly affect the commercial time-lapse model D5 performance. In the time-lapse group, the choice of best blastocyst changed on 42% of occasions (154/369, 95% CI 36.9, 47.2) after the algorithm was applied, and this rate was similar for most treatment clinics. LIMITATIONS, REASONS FOR CAUTION During 2020, the patient recruitment rate slowed down at participating clinics owing to coronavirus disease-19 restrictions, so the target sample size was not achieved as planned and it was decided to stop the trial prematurely. The study only investigated embryo selection at the blastocyst stage on D5 in fresh IVF transfer cycles. In addition, only blastocysts of good morphological quality were considered for transfer, limiting the number of embryos for selection in both groups: also, it could be argued that this manual preselection of blastocysts limits the theoretical selection power of time-lapse, as well as restricting the results mainly to a good prognosis patient group. Most patients were aimed for blastocyst stage transfer when a minimum of five zygotes were available for extended culture. Finally, the primary clinical outcome evaluated was pregnancy to only 6-8 weeks. WIDER IMPLICATIONS OF THE FINDINGS The study suggests that time-lapse selection with a commercially available time-lapse model does not increase chance of ongoing pregnancy after single blastocyst transfer on Day 5 compared to morphology alone. STUDY FUNDING/COMPETING INTEREST(S) The study was financed by a grant from the Swedish state under the ALF-agreement between the Swedish government and the county councils (ALFGBG-723141). Vitrolife supported the study with embryo culture dishes and culture media. During the study period, T.H. changed his employment from Livio AB to Vitrolife AB. All other authors have no conflicts of interests to disclose. DATE OF FIRST PATIENT'S ENROLMENT 11 June 2018.
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| 6. |
- Ahlström, A., et al.
(författare)
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No major differences in perinatal and maternal outcomes between uninterrupted embryo culture in time-lapse system and conventional embryo culture
- 2023
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Ingår i: Human Reproduction. - : Oxford University Press. - 0268-1161 .- 1460-2350. ; 38:12, s. 2400-2411
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Is embryo culture in a closed time-lapse system associated with any differences in perinatal and maternal outcomes in comparison to conventional culture and spontaneous conception?SUMMARY ANSWER: There were no significant differences between time-lapse and conventional embryo culture in preterm birth (PTB, <37 weeks), low birth weight (LBW, >2500 g) and hypertensive disorders of pregnancy for singleton deliveries, the primary outcomes of this study.WHAT IS KNOWN ALREADY: Evidence from prospective trials evaluating the safety of time-lapse incubation for clinical use show similar embryo development rates, implantation rates, and ongoing pregnancy and live birth rates when compared to conventional incubation. Few studies have investigated if uninterrupted culture can alter risks of adverse perinatal outcomes presently associated with IVF when compared to conventional culture and spontaneous conceptions.STUDY DESIGN, SIZE, DURATION: This study is a Swedish population-based retrospective registry study, including 7379 singleton deliveries after fresh embryo transfer between 2013 and 2018 from selected IVF clinics. Perinatal outcomes of singletons born from time-lapse-cultured embryos were compared to singletons from embryos cultured in conventional incubators and 71 300 singletons from spontaneous conceptions. Main perinatal outcomes included PTB and LBW. Main maternal outcomes included hypertensive disorders of pregnancy (pregnancy hypertension and preeclampsia).PARTICIPANTS/MATERIALS, SETTING, METHODS: From nine IVF clinics, 2683 singletons born after fresh embryo transfer in a time-lapse system were compared to 4696 singletons born after culture in a conventional incubator and 71 300 singletons born after spontaneous conception matched for year of birth, parity, and maternal age. Patient and treatment characteristics from IVF deliveries were cross-linked with the Swedish Medical Birth Register, Register of Birth Defects, National Patient Register and Statistics Sweden. Children born after sperm and oocyte donation cycles and after Preimplantation Genetic testing cycles were excluded. Odds ratio (OR) and adjusted OR were calculated, adjusting for relevant confounders.MAIN RESULTS AND THE ROLE OF CHANCE: In the adjusted analyses, no significant differences were found for risk of PTB (adjusted OR 1.11, 95% CI 0.87-1.41) and LBW (adjusted OR 0.86, 95% CI 0.66-1.14) or hypertensive disorders of pregnancy; preeclampsia and hypertension (adjusted OR 0.99, 95% CI 0.67-1.45 and adjusted OR 0.98, 95% CI 0.62-1.53, respectively) between time-lapse and conventional incubation systems. A significantly increased risk of PTB (adjusted OR 1.31, 95% CI 1.08-1.60) and LBW (adjusted OR 1.36, 95% CI 1.08-1.72) was found for singletons born after time-lapse incubation compared to singletons born after spontaneous conceptions. In addition, a lower risk for pregnancy hypertension (adjusted OR 0.72 95% CI 0.53-0.99) but no significant difference for preeclampsia (adjusted OR 0.87, 95% CI 0.68-1.12) was found compared to spontaneous conceptions. Subgroup analyses showed that some risks were related to the day of embryo transfer, with more adverse outcomes after blastocyst transfer in comparison to cleavage stage transfer.LIMITATIONS, REASONS FOR CAUTION: This study is retrospective in design and different clinical strategies may have been used to select specific patient groups for time-lapse versus conventional incubation. The number of patients is limited and larger datasets are required to obtain more precise estimates and adjust for possible effect of additional embryo culture variables.WIDER IMPLICATIONS OF THE FINDINGS: Embryo culture in time-lapse systems is not associated with major differences in perinatal and maternal outcomes, compared to conventional embryo culture, suggesting that this technology is an acceptable alternative for embryo incubation.
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| 7. |
- Ahlström, Aisling, 1976, et al.
(författare)
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Prediction of live birth in frozen-thawed single blastocyst transfer cycles by pre-freeze and post-thaw morphology.
- 2013
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Ingår i: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 28:5, s. 1199-209
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Tidskriftsartikel (refereegranskat)abstract
- What pre-freeze and post-thaw morphological parameters can be used to predict live birth outcomes after frozen-thawed blastocyst transfer cycles? SUMMARY ANSWER: Pre-freeze blastocoele expansion and trophectoderm (TE) grade and post-thaw degree of re-expansion are the most significant predictors of live birth in frozen-thawed blastocyst transfer cycles. WHAT IS KNOWN ALREADY: Currently, blastocoele re-expansion after thawing is used to indicate blastocyst cryosurvival and reproductive potential. The predictive roles of other pre-freeze and post-thaw morphological parameters are neglected. STUDY DESIGN, SIZE, DURATION: This was a retrospective study of all the patients who received a frozen-thawed single blastocyst transfer (n = 1089) at our clinic between March 2008 and October 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: Pre-freeze morphological parameters analyzed for all blastocysts included grade of blastocoele expansion, inner cell mass and TE. A group of blastocysts (n = 243) were also graded for post-thaw parameters: degree of blastocoele re-expansion, viability and cell contour. Univariate and multivariate generalized estimating equations (GEEs) models were used to identify the confounders that statistically significantly affected live birth outcomes and to investigate the independent effect of significant pre-freeze and post-thaw morphological parameters. Stepwise logistic regression analysis was used to select the best independent morphological predictors of live birth. Pearson correlations and linear regression analyses were performed to determine the relationship between morphological parameters and possible covariates. MAIN RESULTS AND THE ROLE OF CHANCE: Multivariate GEE models estimated that the odds of live birth increased by ∼36% for each grade of expansion (P = 0.0061) and decreased by 29% for blastocysts with grade B TE compared with grade A TE (P = 0.0099). Furthermore, the odds of live birth increased by ∼39% (P = 0.0042) for each 10% increase in degree of re-expansion. Blastocoele expansion and TE grade were selected as the most significant pre-freeze morphological predictors of live birth and degree of re-expansion was selected as the best post-thaw parameter for prediction of live birth. LIMITATIONS, REASONS FOR CAUTION: Blastocysts with poorer grades of morphology were not cryopreserved or transferred, limiting the ability to generalize our findings for grades of morphology not included in this study. WIDER IMPLICATIONS OF THE FINDINGS: Blastocysts with higher pre-freeze grades of expansion and TE, irrespective of day of cryopreservation, should be given priority when thawing. Subsequently, re-expanding blastocysts, assessed within 2-4 h, with >60% viability should be transferred. STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for this study. There was no competing interest.
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| 8. |
- Aittomaki, K, et al.
(författare)
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Safety issues in assisted reproduction technology: should ICSI patients have genetic testing before treatment? A practical proposition to help patient information
- 2004
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Ingår i: Hum Reprod. - : Oxford University Press (OUP). ; 19:3, s. 472-476
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Tidskriftsartikel (refereegranskat)abstract
- ICSI is a highly efficient treatment of male factor infertility and therefore increasingly used to treat infertile men successfully. However, when used to treat patients with a genetic cause for their infertility, there may be an increased risk for the offspring. Chromosome aberrations, Y chromosome microdeletions and CFTR (cystic fibrosis transmembrane conductance regulator) mutations alone may explain up to 25% of azoospermia and severe oligozoospermia. These genetic defects could be identified before treatment, in which case informed decisions could be made by the couple to be treated concerning the treatment, prenatal testing or preimplantation genetic diagnosis. Therefore, we propose that men with very low sperm counts (<5 x 10(6)/ml) considering ICSI should always be informed of the possibility of genetic testing. The information should include a precise statement of the implications of the results for the patient, his family and his offspring, and reassurance that a decision to test or not to test, or the subsequent test results will not be used as a reason for withholding treatment. Testing should always remain voluntary, and the couples themselves should decide whether or not they choose to be tested. If an abnormality is identified, patients should be referred to specialist genetic counselling.
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| 9. |
- Akre, O, et al.
(författare)
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Does a testicular dysgenesis syndrome exist?
- 2009
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Ingår i: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 24:9, s. 2053-2060
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Tidskriftsartikel (refereegranskat)
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| 10. |
- Algovik, M, et al.
(författare)
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No mutations found in candidate genes for dystocia
- 1999
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Ingår i: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 14:10, s. 2451-2454
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Tidskriftsartikel (refereegranskat)
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| 11. |
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| 12. |
- Ancel, P-A., et al.
(författare)
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History of induced abortion as a risk factor for preterm birth in European countries:results of the EUROPOP suvery
- 2004
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 19:3, s. 734-740
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The objective of this study was to investigate the relationship between history of induced abortion and preterm delivery in various parts of Europe, and according to the main cause of preterm birth. METHODS: We used data from a case–control survey, the EUROPOP study; 2938 preterm births and 4781 controls at term from ten European countries were included. Based on national statistics, we distinguished three groups of countries with high, intermediate and low rates of induced abortion. RESULTS: Previous induced abortions were significantly associated with preterm delivery and the risk of preterm birth increased with the number of abortions. Odds ratios did not differ significantly between the three groups of countries. The extent of association with previous induced abortion varied according to the cause of preterm delivery. Previous induced abortions significantly increased the risk of preterm delivery after idiopathic preterm labour, preterm premature rupture of membranes and ante-partum haemorrhage, but not preterm delivery after maternal hypertension. The strength of the association increased with decreasing gestational age at birth. CONCLUSIONS: Identifying subgroups of preterm births on the basis of the complications involved in delivery increases our understanding of the mechanisms by which previous induced abortion affects subsequent pregnancy outcomes.
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| 13. |
- Anderheim-Söderqvist, Lisbeth, 1952, et al.
(författare)
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Does psychological stress affect the outcome of in vitro fertilization?
- 2005
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 20:10, s. 2969-75
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of the study was to investigate the effect of psychological stress before and during IVF treatment on the outcome of IVF, controlling for known physiological predictors METHODS: This is a prospective, longitudinal study A total of 166 women were studied during their first IVF treatment They answered questionnaires concerning psychological and social factors on two occasions Psychological well-being was measured by the Psychological General Well-Being (PGWB) index and psychological effects of infertility were assessed by 14 items RESULTS: In the analysis of the psychological variables, no differences were found between pregnant and non-pregnant women The total number of good quality embryos, the number of good quality embryos transferred, and the number of embryos transferred were significantly higher in the pregnant than in the non-pregnant group In a multivariate analysis, the number of good quality embryos transferred was the only variable that was independently associated with pregnancy CONCLUSIONS: We found no evidence that psychological stress had any influence on the outcome of IVF treatment When counselling infertile couples, it might be possible to reduce the stress they experience during the treatment procedure by informing them of these findings
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| 14. |
- Andersson, E., et al.
(författare)
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Isolation of human cationic antimicrobial protein-18 from seminal plasma and its association with prostasomes.
- 2002
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 17:10, s. 34-2529
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cathelicidins are a group of antibiotic peptides with broad antimicrobial activity. They are considered to be an essential part of the innate immune system. The only known human cathelicidin is the human cationic antimicrobial protein (hCAP-18), from which the antimicrobial peptide LL-37 is released. METHODS AND RESULTS: In the present study, we purified hCAP-18 from seminal plasma and confirmed its identity by N-terminal amino acid sequencing. Gel filtration of seminal plasma showed the presence of hCAP-18 in both a low and a high molecular weight peak. Fractions corresponding to the high molecular form of hCAP-18 also contained dipeptidyl peptidase IV (CD26), a prostasome marker. This finding suggested that hCAP-18 found in fractions corresponding to high molecular weight molecules, is prostasome-associated. Flow cytometry confirmed the association of hCAP-18 with prostasomes and indicated that the molecule is surface bound. Western blot showed the presence of intact hCAP-18 in sperm, prostasomes and ultracentrifuged seminal plasma. CONCLUSIONS: These findings suggest that hCAP-18 may have an important role in antimicrobial defence during human reproduction. The binding of hCAP-18 to prostasomes indicates that protasomes can serve as a reservoir of this precursor of the antibiotic peptide LL-37.
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| 22. |
- Axelsson, Jonatan, et al.
(författare)
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No secular trend over the last decade in sperm counts among Swedish men from the general population.
- 2011
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 26, s. 1012-1016
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION Based on historical data, a decline in sperm counts during the years 1940-1990 has been suggested and aetiologically linked to a concomitant increase in the incidence of testicular cancer. This study, focusing on possible changes in sperm parameters among young Swedish men, during the past 10 years, was specifically designed in order to answer the question of whether there is a continuing decline in sperm counts. METHODS During the period 2008-2010, 295 young (17-20 years; median 18) men born and raised in Sweden were recruited at the age they were supposed to undergo medical examination prior to military service. The participants filled in questionnaires, underwent andrological examination and delivered an ejaculate. Their semen parameters were compared with those of a similar cohort of men (n = 216) recruited in the year 2000-2001. RESULTS No significant changes (means; 2000-2001 versus 2008-2010) in sperm concentration (78 × 10(6)/ml versus 82 × 10(6)/ml; P = 0.54), semen volume (3.1 ml versus 3.0 ml; P = 0.26) or total sperm counts (220 × 10(6) versus 250 × 10(6); P = 0.18) were found. The proportion of progressively motile spermatozoa also remained unchanged. CONCLUSIONS Between the years 2000 and 2010 we found no evidence of time-related deterioration of semen parameters among young Swedish men from the general population. This finding does not exclude that such a decrease may have taken place before year 2000. If the risk of testicular cancer is linked to the sperm counts, the increase in incidence of this malignancy should be levelling off in southern Sweden in the next 10-15 years.
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| 23. |
- Axmon, Anna, et al.
(författare)
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Factors affecting time to pregnancy
- 2006
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 21:5, s. 1279-1284
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Both lifestyle factors and occupational and environmental factors have been suggested to affect the female reproductive system. In the present study, the separate and joint effects of several such factors are investigated. METHODS: Information on time to pregnancy (TTP) was available for 1578 women randomly selected from the general Swedish population. The information was collected retrospectively by using self-administered questionnaires. By means of logistic regression of survival data, fecundability odds ratios were determined for many factors. Multivariate models were used to determine which factors had the most impact on TTP. RESULTS: Several lifestyle factors were found to associate with TTP. However, only use of oral contraceptives prior to attempting to conceive, menstrual cycle length, age at conception and parity remained in the multivariate models. Together, these factors explained 14% of the variance in TTP. Excluding first and second month conceptions, only age at conception and menstrual cycle length remained in the multivariate models, together explaining only 8% of the variance in TTP. CONCLUSIONS: Although information on several factors was available, the multivariate model explained only a small fraction of the variation in the observed time to pregnancies. Furthermore, female biological factors seemed more important predictors of TTP than lifestyle factors.
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| 28. |
- Barbuscia, Anna, et al.
(författare)
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Maternal age and risk of low birth weight and premature birth in children conceived through medically assisted reproduction. Evidence from Finnish population registers
- 2020
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 35:1, s. 212-220
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Does the risk of low birth weight and premature birth increase with age among mothers who conceive through medically assisted reproduction (MAR)?SUMMARY ANSWER: Among MAR mothers, the risk of poorer birth outcomes does not increase with maternal age at birth except at very advanced maternal ages (40+).WHAT IS KNOWN ALREADY: The use of MAR treatments has been increasing over the last few decades and is especially diffused among women who conceive at older ages. Although advanced maternal age is a well-known risk factor for adverse birth outcomes in natural pregnancies, only a few studies have directly analysed the maternal age gradient in birth outcomes for MAR mothers.STUDY DESIGN, SIZE, DURATION: The base dataset was a 20% random sample of households with at least one child aged 0-14 at the end of 2000, drawn from the Finnish population register and other administrative registers. This study included children who were born in 1995-2000, because the information on whether a child was conceived through MAR or naturally was available only from 1995 onwards.PARTICIPANTS/MATERIALS, SETTING, METHODS: The outcome measures were whether the child had low birth weight (LBW, <2500 g at birth) and whether the child was delivered preterm (<37 weeks of gestation). Conceptions through MAR were identified by examining data on purchases of prescription medication from the National Prescription Register. Linear probability models were used to analyse and compare the maternal age gradients in birth outcomes of mothers who conceived through MAR or naturally before and after adjustment for maternal characteristics (i.e. whether the mother suffered from acute/chronic conditions before the pregnancy, household income and whether the mother smoked during pregnancy).MAIN RESULTS AND THE ROLE OF CHANCE: A total of 56026 children, 2624 of whom were conceived through MAR treatments, were included in the study. Among the mothers who used MAR to conceive, maternal age was not associated with an increased risk of LBW (the overall prevalence was 12.6%) at ages 25-39. For example, compared to the risk of LBW at ages 30-34, the risk was 0.22 percentage points lower (95% CI: -3.2, 2.8) at ages 25-29 and was 1.34 percentage points lower (95% CI: -4.5, 1.0) at ages 35-39. The risk of LBW was increased only at maternal ages >= 40 (six percentage points, 95% CI: 0.2, 12). Adjustment for maternal characteristics only marginally attenuated these associations. In contrast, among the mothers who conceived naturally, the results showed a clear age gradient. For example, compared to the risk of LBW (the overall prevalence was 3.3%) at maternal ages 30-34, the risk was 1.1 percentage points higher (95% CI: 0.6, 1.6) at ages 35-39 and was 1.5 percentage points higher (95% CI: 0.5, 2.6) at ages >= 40. The results were similar for preterm births.LIMITATIONS, REASON FOR CAUTION: A limited number of confounders were included in the study because of the administrative nature of the data used. Our ability to reliably distinguish mothers based on MAR treatment type was also limited. WIDERIMPLICATIONS OF THE FINDINGS: This is the first study to analyse the maternal age gradient in the risk of adverse birth outcomes among children conceived through MAR using data from a nationally representative sample and controlling for important maternal health and socio-economic characteristics. This topic is of considerable importance in light of the widespread and increasing use of MAR treatments.
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| 35. |
- Bergh, Christina, 1953, et al.
(författare)
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A prospective randomized multicentre study comparing vaginal progesterone gel and vaginal micronized progesterone tablets for luteal support after in vitro fertilization/intracytoplasmic sperm injection.
- 2012
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Ingår i: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 27:12, s. 3467-73
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Tidskriftsartikel (refereegranskat)abstract
- SUMMARY QUESTION: Is vaginal progesterone gel equivalent to vaginal micronized progesterone tablets concerning ongoing pregnancy rate and superior concerning patient convenience when used for luteal support after IVF/ICSI? SUMMARY ANSWER: Equivalence of treatments in terms of ongoing live intrauterine pregnancy rate has not been demonstrated; the 95% confidence interval (CI) for the difference in ongoing pregnancy rate (-8.2 to 0.1%) did not lie entirely within the pre-specified equivalence interval -7 to 7%. WHAT IS KNOWN ALREADY: No significant differences in clinical pregnancy rates have been observed between vaginal progesterone gel and other vaginal progesterone products in earlier studies. However, all previous studies included a limited number of patients. STUDY DESIGN, SIZE AND DURATION: This was a randomized, multicentre, controlled, assessor-blinded equivalence trial in 18 fertility centres in Denmark and Sweden between March 2006 and January 2010. A web-based randomization program was used with concealed allocation of patients. Patients were randomized to one of two groups: vaginal progesterone gel or vaginal micronized progesterone tablets. There was no blinding of patients. PARTICIPANTS AND SETTING: A total of 2057 women ≤ 40 years of age were included and down-regulated, using the long agonist protocol and rFSH for stimulation. Luteal support was given for 19 days after embryo transfer or until a negative pregnancy test Day 14 after embryo transfer. Patient convenience was assessed using questionnaires to be filled in 14 days after embryo transfer, before pregnancy test. MAIN RESULTS AND THE ROLE OF CHANCE: Ongoing intrauterine pregnancy rates were 299/991 (30.2%) (95% CI 27.3-33.0%) in the progesterone gel group and 324/992 (32.7%) (29.7-35.6%) in the micronized progesterone tablet group. The difference in ongoing pregnancy rates between the groups was -4.1% (-8.2 to 0.1%) and the difference in live birth rates was -3.4% (-7.4 to 0.7%), both calculated after correction for significant confounders. Patient convenience and ease of use (1 = very convenient, 10 = very inconvenient) was in favour of progesterone gel, as the overall score was 2.9 (2.7-3.0) for progesterone gel and 4.8 (4.7-5.0; P < 0.0001) for micronized progesterone tablets. This large equivalence trial shows that, even though equality could not be demonstrated, there is no substantial difference in ongoing pregnancy rate between vaginal progesterone gel and vaginal micronized progesterone tablets. It also shows that progesterone gel is considered more convenient by the patients. BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: Blinding of patients was not possible in this study, but since the outcome (pregnancy) is robust, blinding would have been unlikely to affect the results. Unfortunately, owing to an error in the randomization, the intended age distribution allocated older women to the micronized progesterone tablet group. In the analysis of results, adjustments were made for age and number of embryos transferred. GENERALIZABILITY TO OTHER POPULATIONS: The results can be generalized to other women ≥ 18 and ≤ 40 years of age undergoing IVF/ICSI who have regular menstrual cycles (25-35 days), both ovaries present and no more than two previous failed IVF attempts. STUDY FUNDING/COMPETING INTEREST: Merck Serono supported the study but had no influence on the design of the study and was not involved in the analysis of the results or preparation of the manuscript. TRIAL REGISTRATION NUMBER: The trial was issued with the EudraCT number 2005-001248-22 with the Protocol code number 95576471.
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- Bergqvist, A, et al.
(författare)
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Uterus and endometrium: Flow cytometric DNA analysis in endometriotic tissue compared to normal uterine endometrium
- 1996
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 11:8, s. 1731-1735
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Tidskriftsartikel (refereegranskat)abstract
- Endometriotic tissue sometimes shows an invasive pattern. but the growth regulation of the tissue is insufficiently characterized. In a research programme on factors regulating endometriotic growth, the DNA ploidy status and S-phase fraction (SPF) were studied. Fresh-frozen endometriotic tissue from 14 women and endometrium from 11 of them were studied using flow cytometry. A clear diploid pattern was seen in most cases of endometriotic (8/14) and endometrial (8/11) samples. In the remaining cases the G0/G1 peak was broad and skewed, which might indicate a near-diploid cell population. To clarify this, a second group was studied, consisting of 29 formalin-fixed endometriotic samples from 22 women and endometrium from five of them. All these samples were diploid, with one having a broad G0/G1 peak. No convincing difference in SPF between endometrium and endometriotic tissue was found, as the calculations had to be handled with caution because of debris in many samples. Although the study of fresh-frozen samples gave some indications of differences in DNA ploidy status, flow of cytometric DNA analysis of formalin fixed samples of endometriosis showed a diploid DNA pattern in all samples. In conclusion, DNA flow cytometry did not show a convincing aneuploid DNA pattern in endometriotic tissue.
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- Bjelland, E. K., et al.
(författare)
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Hormonal contraception and pelvic girdle pain during pregnancy : a population study of 91 721 pregnancies in the Norwegian Mother and Child Cohort
- 2013
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 28:11, s. 3134-3140
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Tidskriftsartikel (refereegranskat)abstract
- Is pre-pregnancy hormonal contraception use associated with the development of pelvic girdle pain during pregnancy? In contrast to combined oral contraceptive pills, long lifetime exposure to progestin-only contraceptive pills or the use of a progestin intrauterine device during the final year before pregnancy were associated with pelvic girdle pain. Pelvic girdle pain severely affects many women during pregnancy. Smaller studies have suggested that hormonal contraceptive use is involved in the underlying mechanisms, but evidence is inconclusive. A population study during the years 19992008. A total of 91 721 pregnancies included in the Norwegian Mother and Child Cohort Study. Data were obtained by two self-administered questionnaires during pregnancy weeks 17 and 30. Pelvic girdle pain was present in 12.9 of women who had used combined oral contraceptive pills during the last pre-pregnancy year, 16.4 of women who had used progestin-only contraceptive pills, 16.7 of women who had progestin injections and 20.7 of women who had used progestin intrauterine devices, compared with 15.3 of women who did not report use of hormonal contraceptives. After adjustment for other study factors, the use of a progestin intrauterine device was the only factor based on the preceding year associated with pelvic girdle pain [adjusted odds ratios (OR) 1.20; 95 confidence interval (CI): 1.111.31]. Long lifetime exposure to progestin-only contraceptive pills was also associated with pelvic girdle pain (adjusted OR 1.49; 95 CI: 1.012.20). The participation rate was 38.5. However, a recent study on the potential biases of skewed selection in the Norwegian Mother and Child Cohort Study found the prevalence estimates but not the exposure-outcome associations to be influenced by the selection. The results suggest that combined oral contraceptives can be used without fear of developing pelvic girdle pain during pregnancy. However, the influence of progestin intrauterine devices and long-term exposure to progestin-only contraceptive pills requires further study. The present study was supported by the Norwegian Research Council. None of the authors has a conflict of interest.
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- Bjelland, Elisabeth Krefting, et al.
(författare)
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The relation of age at menarche with age at natural menopause : a population study of 336 788 women in Norway
- 2018
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Ingår i: Human Reproduction. - : Oxford University Press. - 0268-1161 .- 1460-2350. ; 33:6, s. 1149-1157
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Is age at menarche associated with age at menopause or with duration of the reproductive period (interval between menarche and menopause)? SUMMARY ANSWER: The association of age at menarche with age at menopause was weak and non-linear, and the duration of the reproductive period decreased by increasing age at menarche. WHAT IS KNOWN ALREADY: It remains uncertain whether age at menarche is associated with age at menopause. Some studies report that women with early menarche also have early menopause. Other studies report that women with early menarche have late menopause, or they report no association. The duration of the reproductive period may be an indicator of the cumulative endogenous exposure to estrogens and progestogens during life course and is associated with risk of breast cancer and endometrial cancer. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study of 336 788 women, aged 48-71 years, in the BreastScreen Norway during the years 2006-2014 was performed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Information about age at menarche and menopausal status was obtained by self-administered questionnaires. We used time to event approaches to estimate the associations. MAIN RESULTS AND THE ROLE OF CHANCE: Median age at menopause was 51 years in most menarche groups. Women with menarche at age 16 years or age >= 17 years had menopause 1 year later [median: 52 years, interquartile range (IQR): 49-54 years] than women with menarche at age 13 years (median: 51 years, IQR: 49-54 years, reference) (crude hazard ratio (HR) = 0.95; 95% CI: 0.93-0.97 and 0.95; 95% CI: 0.92-0.99, Pnon-linearity < 0.001). The reproductive period decreased with increasing age at menarche (Pnon-linearity < 0.001), and women with menarche at age <= 9 years had 9 years longer median reproductive period than women with menarche at age >= 17 years (median: 43 versus 34 years). Adjustment for year of birth did not change the HR estimates notably. LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: Information about age at menarche and age at menopause was based on self-reports. Particularly for age at menarche, the long time interval between the event and data collection may have caused imprecise reporting. WIDER IMPLICATIONS OF THE FINDINGS: Our study suggests that age at menarche is a strong indicator for the duration of women's reproductive period. Our findings should encourage studies of the independent role of duration of the reproductive period on the risk of breast cancer and endometrial cancer, since these cancers have been associated with exposure to estrogens and progestogens. STUDY FUNDING/COMPETING INTEREST(S): The present study was funded by the Norwegian Cancer Society [Grant number 6863294-2015]. The authors declare no conflicts of interest.
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- Bjorndahl, L, et al.
(författare)
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Development of a novel home sperm test
- 2006
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Ingår i: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 21:1, s. 145-149
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Tidskriftsartikel (refereegranskat)
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