| 1. |
- Cesta, Carolyn E., et al.
(författare)
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A prospective investigation of perceived stress, infertility-related stress, and cortisol levels in women undergoing in vitro fertilization : influence on embryo quality and clinical pregnancy rate
- 2018
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : WILEY. - 0001-6349 .- 1600-0412. ; 97:3, s. 258-268
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionWomen undergoing fertility treatment experience high levels of stress. However, it remains uncertain if and how stress influences in vitro fertilization (IVF) cycle outcome. This study aimed to investigate whether self-reported perceived and infertility-related stress and cortisol levels were associated with IVF cycle outcomes.Material and methodsA prospective cohort of 485 women receiving fertility treatment was recruited from September 2011 to December 2013 and followed until December 2014. Data were collected by online questionnaire prior to IVF start and from clinical charts. Salivary cortisol levels were measured. Associations between stress and cycle outcomes (clinical pregnancy and indicators of oocyte and embryo quality) were measured by logistic or linear regression, adjusted for age, body mass index, education, smoking, alcohol and caffeine consumption, shiftwork and night work. ResultsUltrasound verified pregnancy rate was 26.6% overall per cycle started and 32.9% per embryo transfer. Stress measures were not associated with clinical pregnancy: when compared with the lowest categories, the adjusted odds ratio (OR) and 95% confidence interval (CI) for the highest categories of the perceived stress score was 1.04 (95% CI 0.58-1.87), infertility-related stress score was OR = 1.18 (95% CI 0.56-2.47), morning and evening cortisol was OR = 1.18 (95% CI 0.60-2.29) and OR = 0.66 (95% CI 0.34-1.30), respectively.ConclusionsPerceived stress, infertility-related stress, and cortisol levels were not associated with IVF cycle outcomes. These findings are potentially reassuring to women undergoing fertility treatment with concerns about the influence of stress on their treatment outcome.
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| 2. |
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| 4. |
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| 5. |
- Iliadou, Anastasia N., et al.
(författare)
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The Uppsala-Stockholm Assisted Reproductive Techniques (UppStART) study
- 2019
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Ingår i: BMJ Open. - : BMJ PUBLISHING GROUP. - 2044-6055. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The Uppsala-Stockholm Assisted Reproductive Techniques (UppStART) study is a prospectively recruited sample of couples undergoing assisted reproduction in Stockholm and Uppsala county in Sweden. The study was initiated to (1) investigate possible changes in the epigenetic profile of infants inferred through the ART procedures and their consequence and (2) to assess the impact of lifestyle and health exposures on treatment outcome.Participants: Recruitment took place between September 2011 and December 2013, and in vitro fertilisation (IVF) cycles initiated and pregnancies conceived during this time were followed until December 2014. The cohort includes 971 participants (n= 514 women; n= 457 men), and 129 pregnancies were achieved from the first IVF cycle included in the study.Findings to date: Self-reported demographic, health and lifestyle data were collected from a baseline questionnaire, and to assess changes to lifestyle, a follow-up questionnaire was issued at the time of oocyte retrieval, and at subsequent IVF cycles. Questionnaire data were linked to data extracted from medical records. Biological samples were collected at baseline: blood for extraction of serum, plasma and DNA, morning and evening saliva samples for cortisol measurement and at delivery including samples of maternal blood, placenta and amniotic fluid, and cord blood for epigenetic analysis.Future plans: Through the unique identification number assigned to each Swedish citizen at birth or immigration, UppStART study participants will be linked to the Swedish population-based national and quality registers to provide data from prenatal, obstetrical, neonatal and infant care, and subsequent updates will provide data on childhood health and educational outcomes. Collaboration and use of UppStART data is encouraged, and more information about access can be found at www.ki.se/meb/uppstart
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| 6. |
- Karlström, Per-Olof, et al.
(författare)
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Does ovarian stimulation regimen affect IVF outcome? : a two-centre, real-world retrospective study using predominantly cleavage-stage, single embryo transfer
- 2018
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Ingår i: Reproductive BioMedicine Online. - : ELSEVIER SCI LTD. - 1472-6483 .- 1472-6491. ; 36:1, s. 59-66
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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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| 7. |
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| 8. |
- Lind, Tekla, et al.
(författare)
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Reduced live-birth rates after IVF/ICSI in women with previous unilateral oophorectomy : results of a multicentre cohort study
- 2018
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Ingår i: Human Reproduction. - : Oxford University Press. - 0268-1161 .- 1460-2350. ; 33:2, s. 238-247
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Tidskriftsartikel (refereegranskat)abstract
- Is there a reduced live-birth rate (LBR) after IVF/ICSI treatment in women with a previous unilateral oophorectomy (UO)? A significantly reduced LBR after IVF/ICSI was found in women with previous UO when compared with women with intact ovaries in this large multicentre cohort, both crudely and after adjustment for age, BMI, fertility centre and calendar period and regardless of whether the analysis was based on transfer of embryos in the fresh cycle only or on cumulative results including transfers using frozen-thawed embryos. Similar pregnancy rates after IVF/ICSI have been previously reported in case-control studies and small cohort studies of women with previous UO versus women without ovarian surgery. In all previous studies multiple embryos were transferred. No study has previously evaluated LBR in a large cohort of women with a history of UO. This research was a multicentre cohort study, including five reproductive medicine centres in Sweden: Carl von Linn, Clinic (A), Karolinska University Hospital (B), Uppsala University Hospital (C), Linkoping University Hospital (D) and A-rebro University Hospital (E). The women underwent IVF/ICSI between January 1999 and November 2015. Single embryo transfer (SET) was performed in approximately 70% of all treatments, without any significant difference between UO exposed women versus controls (68% versus 71%), respectively (P = 0.32), and a maximum of two embryos were transferred in the remaining cases. The dataset included all consecutive treatments and fresh and frozen-thawed cycles. The exposed cohort included 154 women with UO who underwent 301 IVF/ICSI cycles and the unexposed control cohort consisted of 22 693 women who underwent 41 545 IVF/ICSI cycles. Overall, at the five centres (A-E), the exposed cohort underwent 151, 34, 35, 41 and 40 treatments, respectively, and they were compared with controls of the same centre (18 484, 8371, 5575, 4670 and 4445, respectively). The primary outcome was LBR, which was analysed per started cycle, per ovum pick-up (OPU) and per embryo transfer (ET). Secondary outcomes included the numbers of oocytes retrieved and supernumerary embryos obtained, the Ovarian Sensitivity Index (OSI), embryo quality scores and cumulative pregnancy rates. We used a Generalized Estimating Equation (GEE) model for statistical analysis in order to account for repeated treatments. MAIN RESULTS AND THE ROLE OF CHANCE: The exposed (UO) and control women's groups were comparable with regard to age and performance of IVF or ICSI. Significant differences in LBR, both crude and age-adjusted, were observed between the UO and control groups: LBR per started cycle (18.6% versus 25.4%, P = 0.007 and P = 0.014, respectively), LBR/OPU (20.3% versus 27.1%, P = 0.012 and P = 0.015, respectively) and LBR/ET (23.0% versus 29.7%, P = 0.022 and P = 0.025, respectively). The differences in LBR remained significant after inclusion of both fresh and frozen-thawed transfers (both crude and age-adjusted data): LBR/OPU (26.1% versus 34.4%, P = 0.005 and P = 0.006, respectively) and LBR/ET (28.3% versus 37.1%, P = 0.006 and P = 0.006, respectively). The crude cancellation rate was significantly higher among women with a history of UO than in controls (18.9% versus 14.5%, P = 0.034 and age-adjusted, P = 0.178). In a multivariate GEE model, the cumulative odds ratios for LBR (fresh and frozen-thawed)/OPU (OR 0.70, 95% CI 0.52-0.94, P = 0.016) and LBR (fresh and frozen-thawed)/ET (OR 0.68, 95% CI 0.51-0.92, P = 0.012) were approximately 30% lower in the group of women with UO when adjusted for age, BMI, reproductive centre, calendar period and number of embryos transferred when appropriate. The OSI was significantly lower in women with a history of UO than in controls (3.6 versus 6.0) and the difference was significant for both crude and age-adjusted data (P =< 0.001 for both). Significantly fewer oocytes were retrieved in treatments of women with UO than in controls (7.2 versus 9.9, P = < 0.001, respectively). LIMITATIONS, REASONS FOR CAUTION: Due to the nature of the topic, this is a retrospective analysis, with all its inherent limitations. Furthermore, the cause for UO was not possible to obtain in all cases. A diagnosis of endometriosis was also more common in the UO group, i. e. a selection bias in terms of poorer patient characteristics in the UO group cannot be completely ruled out. However, adjustment for all known confounders did not affect the general results. WIDER IMPLICATIONS OF THE FINDINGS: To date, this is the largest cohort investigated and the first study indicating an association of achieving reduced live birth after IVF/ICSI in women with previous UO. These findings are novel and contradict the earlier notion that IVF/ICSI treatment is not affected, or is only marginally affected by previous UO.
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| 9. |
- Tobi, Elmar W., et al.
(författare)
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DNA methylation differences at birth after conception through ART
- 2021
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Ingår i: Human Reproduction. - : Oxford University Press. - 0268-1161 .- 1460-2350. ; 36:1, s. 248-259
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Is there a relation between ART and DNA methylation (DNAm) patterns in cord blood, including any differences between IVF and ICSI?SUMMARY ANSWER: DNAm at 19 CpGs was associated with conception via ART, with no difference found between IVF and ICSI.WHAT IS KNOWN ALREADY: Prior studies on either IVF or ICSI show conflicting outcomes, as both widespread effects on DNAm and highly localized associations have been reported. No study on both IVF and ICSI and genome-wide neonatal DNAm has been performed.STUDY DESIGN, SIZE, DURATION: This was a cross-sectional study comprising 87 infants conceived with IVF or ICSI and 70 conceived following medically unassisted conception. The requirement for inclusion in the study was an understanding of the Swedish language and exclusion was the use of donor gametes.PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were from the UppstART study, which was recruited from fertility and reproductive health clinics, and the Born into Life cohort, which is recruited from the larger LifeGene study. We measured DNAm from DNA extracted from cord blood collected at birth using a micro-array (450k array). Group differences in DNAm at individual CpG dinucleotides (CpGs) were determined using robust linear models and post-hoc Tukey's tests.MAIN RESULTS AND THE ROLE OF CHANCE: We found no association of ART conception with global methylation levels, imprinted loci and meta-stable epialleles. In contrast, we identify 19 CpGs at which DNAm was associated with being conceived via ART (effect estimates: 0.5-4.9%, P-FDR < 0.05), but no difference was found between IVF and ICSI. The associated CpGs map to genes related to brain function/development or genes connected to the plethora of conditions linked to subfertility, but functional annotation did not point to any likely functional consequences.LIMITATIONS, REASONS FOR CAUTION: We measured DNAm in cord blood and not at later ages or in other tissues. Given the number of tests performed, our study power is limited and the findings need to be replicated in an independent study.WIDER IMPLICATIONS OF THE FINDINGS: We find that ART is associated with DNAm differences in cord blood when compared to non-ART samples, but these differences are limited in number and effect size and have unknown functional consequences in adult blood. We did not find indications of differences between IVF and ICSI.
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| 10. |
- Anders, Larsson, et al.
(författare)
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Higher levels of Hepatocyte Growth Factor (HGF) in human seminal plasma in comparison with blood plasma and negative association with several motile sperm cells
- 2023
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Ingår i: Global Journal of Fertility and Research. - 2640-7884. ; 8:1, s. 008-013
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Tidskriftsartikel (refereegranskat)abstract
- Context: Semen is a complex fluid with many functions, some of them well-known, others more obscure.Aims: The aim of this study was to investigate the levels of Hepatocyte Growth Factor (HGF) in human seminal plasma in comparison with blood plasma levels.Methods: HGF concentrations were measured in seminal plasma from 40 men utilizing commercial ELISA kits. Blood plasma from 40 healthy blood donors served as a comparison group.Results: Median seminal plasma HGF was approximately five times higher than the levels found in blood plasma (5717.5 pg/mL vs. 1124.6 pg/mL). There was a negative correlation between HGF values in seminal plasma and the number of sperm cells.Conclusion: The study shows that seminal plasma contains high levels of HGF and that HGF binds to prostasomes. Male HGF can thus reach the female reproductive tract during unprotected sexual intercourse. Further studies are warranted to evaluate the effect of this on fertility.
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| 11. |
- Bellavia, Andrea, et al.
(författare)
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Association between chemical mixtures and female fertility in women undergoing assisted reproduction in Sweden and Estonia
- 2023
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 216:Part 1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Women of reproductive age are exposed to ubiquitous chemicals such as phthalates, parabens, and per -and polyfluoroalkyl substances (PFAS), which have potential endocrine disrupting properties and might affect fertility. Our objective was to investigate associations between potential endocrine-disrupting chemicals (EDCs) and female fertility in two cohorts of women attending fertility clinics.Methods: In a total population of 333 women in Sweden and Estonia, we studied the associations between chemicals and female fertility, evaluating ovarian sensitivity index (OSI) as an indicator of ovarian response, as well as clinical pregnancy and live birth from fresh and frozen embryo transfers. We measured 59 chemicals in follicular fluid samples and detected 3 phthalate metabolites, di-2-ethylhexyl phthalate (DEHP) metabolites, 1 paraben, and 6 PFAS in > 90% of the women. Associations were evaluated using multivariable-adjusted linear or logistic regression, categorizing EDCs into quartiles of their distributions, as well as with Bayesian Kernel Ma-chine Regression.Results: We observed statistically significant lower OSI at higher concentrations of the sum of DEHP metabolites in the Swedish cohort (Q4 vs Q1, beta =-0.21, 95% CI:-0.38,-0.05) and methylparaben in the Estonian cohort (Q3 vs Q1, beta =-0.22, 95% CI:-0.44,-0.01). Signals of potential associations were also observed at higher concentrations of PFUnDA in both the combined population (Q2 vs. Q1,beta =-0.16, 95% CI-0.31,-0.02) and the Estonian population (Q2 vs. Q1,beta =-0.27, 95% CI-0.45,-0.08), and for PFOA in the Estonian population (Q4 vs. Q1, beta =-0.31, 95% CI-0.61,-0.01). Associations of chemicals with clinical pregnancy and live birth presented wide confidence intervals.Conclusions: Within a large chemical mixture, we observed significant inverse associations levels of DEHP me-tabolites and methylparaben, and possibly PFUnDA and PFOA, with OSI, suggesting that these chemicals may contribute to altered ovarian function and infertility in women.
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| 12. |
- Bjorvang, Richelle D., et al.
(författare)
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Follicular fluid and blood levels of persistent organic pollutants and reproductive outcomes among women undergoing assisted reproductive technologies
- 2022
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 208
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Tidskriftsartikel (refereegranskat)abstract
- Persistent organic pollutants (POPs) are industrial chemicals resistant to degradation and have been shown to have adverse effects on reproductive health in wildlife and humans. Although regulations have reduced their levels, they are still ubiquitously present and pose a global concern. Here, we studied a cohort of 185 women aged 21-43 years with a median of 2 years of infertility who were seeking assisted reproductive technology (ART) treatment at the Carl von Linne Clinic in Uppsala, Sweden. We analyzed the levels of 9 organochlorine pesticides (OCPs), 10 polychlorinated biphenyls (PCBs), 3 polybrominated diphenyl ethers (PBDEs), and 8 perfluoroalkyl substances (PFASs) in the blood and follicular fluid (FF) samples collected during ovum pick-up. Impact of age on chemical transfer from blood to FF was analyzed. Associations of chemicals, both individually and as a mixture, to 10 ART endpoints were investigated using linear, logistic, and weighted quantile sum regression, adjusted for age, body mass index, parity, fatty fish intake and cause of infertility. Out of the 30 chemicals, 20 were detected in more than half of the blood samples and 15 in FF. Chemical transfer from blood to FF increased with age. Chemical groups in blood crossed the blood-follicle barrier at different rates: OCPs > PCBs > PFASs. Hexachlorobenzene, an OCP, was associated with lower anti-Miillerian hormone, clinical pregnancy, and live birth. PCBs and PFASs were associated with higher antral follicle count and ovarian response as measured by ovarian sensitivity index, but also with lower embryo quality. As a mixture, similar findings were seen for the sum of PCBs and PFASs. Our results suggest that age plays a role in the chemical transfer from blood to FF and that exposure to POPs significantly associates with ART outcomes. We strongly encourage further studies to elucidate the underlying mechanisms of reproductive effects of POPs in humans.
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| 13. |
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| 14. |
- Brodin, Thomas, et al.
(författare)
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Antimüllerian hormone levels are strongly associated with live-birth rates after assisted reproduction
- 2013
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 98:3, s. 1107-1114
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Tidskriftsartikel (refereegranskat)abstract
- Context: Previous studies have suggested that antimullerian hormone (AMH) levels are positively associated with in vitro fertilization (IVF) outcome through their relationship with oocyte yield and not by reflecting oocyte or embryo quality. Objective: The aim was to investigate whether AMH levels are associated with pregnancy and live-birth rates and whether the results may also reflect qualitative aspects of oocytes and embryos. Design: The study was a prospective cohort study between April 2008 and June 2011. Setting: The study was done at a university-affiliated private infertility center. Patients: The study cohort consisted of 892 consecutive women undergoing 1230 IVF-intracytoplasmic sperm injection cycles. Intervention(s): AMH levels, analyzed using the DSL ELISA kit, were statistically adjusted for repeated treatments and age and analyzed for associations with treatment outcome. Main Outcome Measures: Pregnancy rates, live-birth rates, and stimulation outcome parameters were measured. Results: AMH was log-normally distributed with a mean (SD) of 2.3 (2.5) ng/mL. Live-birth rates per started cycle (mean [95% confidence interval]) increased log-linearly from 10.7% [7.2-14.1] for AMH < 0.84 ng/mL (25th percentile) to 30.8% [25.7-36.0] for AMH > 2.94 ng/mL (75th percentile), P-trend < .0001, being superior in women with polycystic ovaries. These findings were significant also after adjustments were made for age and oocyte yield. AMH was also associated with ovarian response variables and embryo scores. Conclusions: AMH is strongly associated with live-birth rates after IVF-intracytoplasmic sperm injection. AMH may therefore serve as a prognostic factor for the chance of a pregnancy and live birth. Treatment outcome was superior in patients with polycystic ovaries. The findings also indicate that AMH may partially comprise information about oocyte quality.
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| 15. |
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| 16. |
- Brodin, Thomas, et al.
(författare)
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Comparing four ovarian reserve markers : associations with ovarian response and live births after assisted reproduction
- 2015
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 94:10, s. 1056-1063
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. We compared the ability of four different ovarian reserve tests (ORTs) to predict live births per started in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) cycle, and poor and excessive response to controlled ovarian hyperstimulation. Material and methods. This was a cohort study in a private infertility center in collaboration with Uppsala University, comprising 1230 IVF-ICSI cycles in 892 consecutive women between April 2008 and June 2011. Anti-Mullerian hormone (AMH) levels, antral follicle counts (AFC), combinations of basal levels of follicle-stimulating hormone and luteinizing hormone, and menstrual cycle lengths were analyzed for correlation and treatment outcome prediction in age-adjusted statistical models. Stepwise multivariable generalized estimating equation analyses were carried out in a sub-group with complete data on all four ORTs (620 cycles in 443 women). Odds ratios and c-statistics were calculated in the largest available set of data for each significant variable. Primary outcomes were live birth rate per started cycle and poor and excessive ovarian response to controlled ovarian hyperstimulation (defined by the ovarian sensitivity index). Results. All ORTs correlated significantly with each other, with the strongest correlation between AFC and AMH (r = 0.71, p < 0.0001). Univariately, AMH and age equivalently predicted live birth (c-statistic 0.61), and together they provided a significantly better model (c-statistic 0.64). For prediction of poor and excessive response the best model included AMH, AFC and age (c-statistic 0.89). Conclusions. AMH improves the ability to estimate live birth rates after assisted reproduction compared with female age alone. AMH, AFC and age together constituted the best model for prediction of ovarian response.
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| 17. |
- Brodin, Thomas, et al.
(författare)
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High basal LH levels in combination with low basal FSH levels are associated with high success rates at assisted reproduction
- 2009
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 24:11, s. 2755-2759
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The objective of this study was to evaluate the associations of basal gonadotrophins with pregnancy and delivery rates at IVF/ICSI. METHODS A prospective observational study was conducted at a university-affiliated private infertility centre. Patients were 745 women, who underwent 1328 IVF/ICSI treatment cycles. Basal FSH, basal LH and combinations of FSH and LH versus treatment data and pregnancy and delivery rates were measured. RESULTS Combinations of FSH and LH gave significantly better information than the LH:FSH ratio, or each gonadotrophin alone: highest mean pregnancy rate (39%) was achieved in women with low FSH (<6.7 U/l) and with high LH levels (>4.9 U/l), whereas pregnancy rate was lowest (22%) in women with high FSH and low LH levels. Pregnancy rates were intermediate (27-28%) if FSH and LH were either both low or both high (P for trend = 0.0004). Associations to delivery rates and measures of ovarian response and embryo quality followed the same pattern. CONCLUSIONS Basal LH modifies and improves the information given by basal FSH alone. Low FSH level combined with high LH probably reflects a well-preserved ovarian reserve and is associated with the highest success rates at IVF/ICSI.
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| 18. |
- Brodin, Thomas, et al.
(författare)
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Menstrual cycle length is an age-independent marker of female fertility : results from 6271 treatment cycles of in vitro fertilization
- 2008
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 90:5, s. 1656-1661
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate whether menstrual cycle length correlates with success rates at IVF/intracytoplasmic sperm injection (ICSI) and could be used as a marker of ovarian reserve. DESIGN: Prospective observational study. SETTING: Private infertility centre. PATIENT(S): A total of 6271 IVF/ICSI treatment cycles. INTERVENTION(S): Self-reported mean number of menstrual days during the last year was recorded before initiation of IVF/ICSI treatment. MAIN OUTCOME MEASURE(S): Relations between menstrual cycle length and pregnancy and delivery rates. RESULT(S): Increasing age was associated with a subtle shortening of mean menstrual cycle length. Menstrual cycle length correlated linearly with pregnancy and delivery rates, even after age adjustment. The chance of delivery after IVF/ICSI was almost doubled for women with a menstrual cycle length >34 days compared with women with a menstrual cycle length <26 days. Menstrual cycle length was also significantly associated with ovarian response to FSH/hMG stimulation and embryo quality. CONCLUSION(S): Mean menstrual cycle length is highly related to success rates in assisted reproduction, independently of age. A precise menstrual cycle history could be used as a simple marker of ovarian reserve.
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| 19. |
- Brodin, Thomas, 1963-
(författare)
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Ovarian Reserve and Assisted Reproduction
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Treatment success in IVF-ICSI is mainly limited by female age, but differences in ovarian reserve (OR; the remaining pool of oocytes and their quality) between individuals modify treatment prerequisites among women of similar age. OR may be assessed by OR tests (ORTs). The main aims of this work were to study menstrual cycle length (MCL), basal levels of circulating gonadotrophins, antral follicle count (AFC) and serum Anti-Müllerian hormone (AMH) levels and their associations with and prognostic capacities regarding IVF-ICSI outcome in large cohorts of unselected women.Age-adjusted MCL was positively and linearly associated with pregnancy rates (PRs), live-birth rates (LBRs) and ovarian response to controlled ovarian hyperstimulation. An MCL of >34 days almost doubled the LBR compared with an MCL of <26 days.The grouped variable ‘combined FSH and LH levels’ was superior to both individual gonadotrophin levels and the LH:FSH ratio. The highest mean PR was seen in connection with a combination of FSH <6.7 U/l with LH >4.9 U/l; PRs were lowest when FSH-LH levels were opposite to this (high-low) and intermediate when FSH-LH levels were low-low or high-high. Associations with LBR and ovarian response were similar as those for PR.AFCs and serum AMH levels were positively and log-linearly associated with PR, LBR and ovarian response. Success rates levelled out above AFC 30 or AMH 5 ng/ml. Treatment outcome was superior among women with polycystic ovaries.Among the studied ORTs, logAFC and logAMH concentration correlated most strongly. After multivariate testing, entering all studied ORTs, AMH and female age remained independently associated with LBR. AMH + AFC + age predicted both poor and excessive ovarian responses with high accuracy.Adjusting for age and oocyte yield, all ORTs remained significant for LBR, implying that ORTs also capture information on oocyte quality.In conclusion, measures of OR are strongly associated with PR, LBR and ovarian response in a log-linear fashion, and partly reflect oocyte quality. The OR spectrum is continuous, from small ‘oligofollicular’ ovaries (the low extreme) to polycystic ovaries (the high extreme). Among the studied ORTs, AMH together with age provide the most powerful basal estimate for IVF/ICSI outcome.
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| 20. |
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| 21. |
- d'Amore, Francesco, et al.
(författare)
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Up-Front Autologous Stem-Cell Transplantation in Peripheral T-Cell Lymphoma : NLG-T-01
- 2012
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 30:25, s. 3093-3099
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Systemic peripheral T-cell lymphomas (PTCLs) respond poorly to conventional therapy. To evaluate the efficacy of a dose-dense approach consolidated by up-front high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) in PTCL, the Nordic Lymphoma Group (NLG) conducted a large prospective phase II study in untreated systemic PTCL. This is the final report, with a 5-year median follow-up, of the NLG-T-01 study. Patients and Methods Treatment-naive patients with PTCL age 18 to 67 years (median, 57 years) were included. Anaplastic lymphoma kinase (ALK) -positive anaplastic large-cell lymphoma (ALCL) was excluded. An induction regimen of six cycles of biweekly CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone) was administered (in patients age > 60 years, etoposide was omitted). If in complete or partial remission, patients proceeded to consolidation with HDT/ASCT. Results Of 166 enrolled patients, 160 had histopathologically confirmed PTCL. The majority presented with advanced-stage disease, B symptoms, and elevated serum lactate dehydrogenase. A total of 115 underwent HDT/ASCT, with 90 in complete remission at 3 months post-transplantation. Early failures occurred in 26%. Treatment-related mortality was 4%. At 60.5 months of median follow-up, 83 patients were alive. Consolidated 5-year overall and progression-free survival (PFS) were 51% (95% CI, 43% to 59%) and 44% (95% CI, 36% to 52%), respectively. Best results were obtained in ALK-negative ALCL. Conclusion Dose-dense induction followed by HDT/ASCT was well tolerated and led to long-term PFS in 44% of treatment-naive patients with PTCL. This represents an encouraging outcome, particularly considering the high median age and adverse risk profile of the study population. Therefore, dose-dense induction and HDT/ASCT are a rational up-front strategy in transplantation-eligible patients with PTCL. J Clin Oncol 30: 3093-3099. (C) 2012 by American Society of Clinical Oncology
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| 22. |
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| 23. |
- Eriksson, Olle, 1954-, et al.
(författare)
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Ovarian morphology in premenstrual dysphoria
- 2012
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 37:6, s. 742-751
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian cyclicity is a prerequisite for premenstrual dysphoria (PMD), as illustrated by the fact that this condition is effectively eliminated by ovariectomy or by treatment with a GnRH agonist. Despite the possibility of differences in ovarian function between women with and without PMD, no study comparing ovarian morphology in these two groups has ever been published. Fifty-two women were recruited for this study; 26 had premenstrual dysphoria, fulfilling criteria slightly modified from those of the premenstrual dysphoric disorder, and 26 were asymptomatic age-matched controls. Ovarian morphology was assessed using transvaginal 7MHz ultrasonography on day 5 after the start of menses, and venous blood was sampled for hormone analysis on days 3 and 8, the expected day of ovulation, and day -4 of the menstrual cycle. There were no significant differences between the groups with respect to the prevalence of polycystic ovaries (PCO), the total number of follicles, the total ovarian volume or serum levels of androgen hormones. In addition, serum free testosterone levels in late premenstrual phase showed an inverse association to premenstrual symptoms of irritability and a similar inverse association trend to symptoms of depressed mood. Unexpectedly, the prevalence of ovaries with fewer than five antral or growing follicles was significantly higher in women with PMD than in controls (p=0.016). While the results do not support a role for PCO or androgen hormones in eliciting late luteal phase irritability, the possible relationship between oligofollicular ovaries and PMD deserves further study.
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- Hallberg, Ida, et al.
(författare)
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Associations between lifestyle factors and levels of per- and polyfluoroalkyl substances (PFASs), phthalates and parabens in follicular fluid in women undergoing fertility treatment
- 2023
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Ingår i: Journal of Exposure Science and Environmental Epidemiology. - : Springer Nature. - 1559-0631 .- 1559-064X. ; 33, s. 699-709
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Tidskriftsartikel (refereegranskat)abstract
- Background: Concerns have been raised whether exposure to endocrine-disrupting chemicals (EDCs) can alter reproductive functions and play a role in the aetiology of infertility in women. With increasing evidence of adverse effects, information on factors associated with exposure is necessary to form firm recommendations aiming at reducing exposure.Objective: Our aim was to identify associations between lifestyle factors including the home environment, use of personal care products (PCP), and dietary habits and concentrations of EDCs in ovarian follicular fluid.Methods: April-June 2016, 185 women undergoing ovum pick-up for in vitro fertilisation in Sweden were recruited. Correlation analyses were performed between self-reported lifestyle factors and concentration of EDCs analysed in follicular fluid. Habits related to cleaning, PCPs, and diet were assessed together with concentration of six per- and polyfluoroalkyl substances (PFASs) [PFHxS, PFOA, PFOS, PFNA, PFDA and PFUnDA], methyl paraben and eight phthalate metabolites [MECPP, MEHPP, MEOHP, MEHP, cxMinCH, cxMiNP, ohMiNP, MEP, MOHiBP]. Spearman's partial correlations were adjusted for age, parity and BMI.Results: Significant associations were discovered between multiple lifestyle factors and concentrations of EDCs in ovarian follicular fluid. After correcting p values for multiple testing, frequent use of perfume was associated with MEP (correlation rho = 0.41 (confidence interval 0.21-0.47), p < 0.001); hens' egg consumption was positively associated with PFOS (rho = 0.30 (0.15-0.43), p = 0.007) and PFUnDA (rho = 0.27 (0.12-0.40), p = 0.036). White fish consumption was positively associated with PFUnDA (rho = 0.34 (0.20-0.47), p < 0.001) and PFDA (rho = 0.27 (0.13-0.41), p = 0.028). More correlations were discovered when considering the raw uncorrected p values. Altogether, our results suggest that multiple lifestyle variables affect chemical contamination of follicular fluid.Impact statement: This study shows how lifestyle factors correlate with the level of contamination in the ovary by both persistent and semi-persistent chemicals in women of reproductive age. Subsequently, these data can be used to form recommendations regarding lifestyle to mitigate possible negative health outcomes and fertility problems associated with chemical exposure, and to inform chemical policy decision making. Our study can also help form the basis for the design of larger observational and intervention studies to examine possible effects of lifestyle changes on exposure levels, and to unravel the complex interactions between biological factors, lifestyle and chemical exposures in more detail.
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