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  • 1
    In: Bijdragen, Informa UK Limited, Vol. 33, No. 1 ( 1972-01), p. 89-114
    Type of Medium: Online Resource
    ISSN: 0006-2278 , 1783-1377
    Language: Dutch
    Publisher: Informa UK Limited
    Publication Date: 1972
    detail.hit.zdb_id: 2692945-4
    SSG: 1
    SSG: 5,1
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  • 2
    In: Bijdragen, Informa UK Limited, Vol. 33, No. 4 ( 1972-01), p. 453-464
    Type of Medium: Online Resource
    ISSN: 0006-2278 , 1783-1377
    Language: Dutch
    Publisher: Informa UK Limited
    Publication Date: 1972
    detail.hit.zdb_id: 2692945-4
    SSG: 1
    SSG: 5,1
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  • 3
    In: Journal of Hepatology, Elsevier BV, Vol. 11 ( 1990), p. S29-
    Type of Medium: Online Resource
    ISSN: 0168-8278
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1990
    detail.hit.zdb_id: 2027112-8
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  • 4
    In: Journal of Biochemical Toxicology, Wiley, Vol. 6, No. 2 ( 1991-22), p. 155-159
    Type of Medium: Online Resource
    ISSN: 0887-2082 , 1522-7146
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 1991
    detail.hit.zdb_id: 2001600-1
    detail.hit.zdb_id: 1481995-8
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  • 5
    In: Human Reproduction, Oxford University Press (OUP), Vol. 29, No. 10 ( 2014-10-10), p. 2099-2113
    Type of Medium: Online Resource
    ISSN: 0268-1161 , 1460-2350
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2014
    detail.hit.zdb_id: 1484864-8
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  • 6
    In: Human Reproduction Open, Oxford University Press (OUP), Vol. 2022, No. 3 ( 2022-05-19)
    Abstract: What are the data and trends on ART and IUI cycle numbers and their outcomes, and on fertility preservation (FP) interventions, reported in 2018 as compared to previous years? SUMMARY ANSWER The 22nd ESHRE report shows a continued increase in reported numbers of ART treatment cycles and children born in Europe, a decrease in transfers with more than one embryo with a further reduction of twin delivery rates (DRs) as compared to 2017, higher DRs per transfer after fresh IVF or ICSI cycles (without considering freeze-all cycles) than after frozen embryo transfer (FET) with higher pregnancy rates (PRs) after FET and the number of reported IUI cycles decreased while their PR and DR remained stable. WHAT IS KNOWN ALREADY ART aggregated data generated by national registries, clinics or professional societies have been gathered and analysed by the European IVF-monitoring Consortium (EIM) since 1997 and reported in 21 manuscripts published in Human Reproduction and Human Reproduction Open. STUDY DESIGN, SIZE, DURATION Data on medically assisted reproduction (MAR) from European countries are collected by EIM for ESHRE on a yearly basis. The data on treatment cycles performed between 1 January and 31 December 2018 were provided by either national registries or registries based on initiatives of medical associations and scientific organizations or committed persons of 39 countries. PARTICIPANTS/MATERIALS, SETTING, METHODS Overall, 1422 clinics offering ART services in 39 countries reported a total of more than 1 million (1 007 598) treatment cycles for the first time, including 162 837 with IVF, 400 375 with ICSI, 309 475 with FET, 48 294 with preimplantation genetic testing, 80 641 with egg donation (ED), 532 with IVM of oocytes and 5444 cycles with frozen oocyte replacement (FOR). A total of 1271 institutions reported data on IUI cycles using either husband/partner’s semen (IUI-H; n = 148 143) or donor semen (IUI-D; n = 50 609) in 31 countries and 25 countries, respectively. Sixteen countries reported 20 994 interventions in pre- and post-pubertal patients for FP including oocyte, ovarian tissue, semen and testicular tissue banking. MAIN RESULTS AND THE ROLE OF CHANCE In 21 countries (21 in 2017) in which all ART clinics reported to the registry, 410 190 treatment cycles were registered for a total population of ∼ 300 million inhabitants, allowing a best estimate of a mean of 1433 cycles performed per million inhabitants (range: 641–3549). Among the 39 reporting countries, for IVF, the clinical PR per aspiration slightly decreased while the PR per transfer remained similar compared to 2017 (25.5% and 34.1% in 2018 versus 26.8% and 34.3% in 2017). In ICSI, the corresponding rates showed similar evolutions in 2018 compared to 2017 (22.5% and 32.1% in 2018 versus 24.0% and 33.5% in 2017). When freeze-all cycles were not considered for the calculations, the clinical PRs per aspiration were 28.8% (29.4% in 2017) and 27.3% (27.3% in 2017) for IVF and ICSI, respectively. After FET with embryos originating from own eggs, the PR per thawing was 33.4% (versus 30.2% in 2017), and with embryos originating from donated eggs 41.8% (41.1% in 2017). After ED, the PR per fresh embryo transfer was 49.6% (49.2% in 2017) and per FOR 44.9% (43.3% in 2017). In IVF and ICSI together, the trend towards the transfer of fewer embryos continues with the transfer of 1, 2, 3 and ≥4 embryos in 50.7%, 45.1%, 3.9% and 0.3% of all treatments, respectively (corresponding to 46.0%, 49.2%. 4.5% and 0.3% in 2017). This resulted in a reduced proportion of twin DRs of 12.4% (14.2% in 2017) and similar triplet DR of 0.2%. Treatments with FET in 2018 resulted in twin and triplet DRs of 9.4% and 0.1%, respectively (versus 11.2% and 0.2%, respectively in 2017). After IUI, the DRs remained similar at 8.8% after IUI-H (8.7% in 2017) and at 12.6% after IUI-D (12.4% in 2017). Twin and triplet DRs after IUI-H were 8.4% and 0.3%, respectively (in 2017: 8.1% and 0.3%), and 6.4% and 0.2% after IUI-D (in 2017: 6.9% and 0.2%). Among 20 994 FP interventions in 16 countries (18 888 in 13 countries in 2017), cryopreservation of ejaculated sperm (n = 10 503, versus 11 112 in 2017) and of oocytes (n = 9123 versus 6588 in 2017) were the most frequently reported. LIMITATIONS, REASONS FOR CAUTION The results should be interpreted with caution as data collection systems and completeness of reporting vary among European countries. Some countries were unable to deliver data about the number of initiated cycles and/or deliveries. WIDER IMPLICATIONS OF THE FINDINGS The 22nd ESHRE data collection on ART, IUI and FP interventions shows a continuous increase of reported treatment numbers and MAR-derived livebirths in Europe. Although it is the largest data collection on MAR in Europe, further efforts towards optimization of both the collection and reporting, with the aim of improving surveillance and vigilance in the field of reproductive medicine, are awaited. STUDY FUNDING/COMPETING INTEREST(S) The study has received no external funding and all costs are covered by ESHRE. There are no competing interests.
    Type of Medium: Online Resource
    ISSN: 2399-3529
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2899901-0
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  • 7
    In: Human Reproduction Open, Oxford University Press (OUP), Vol. 2021, No. 3 ( 2021-06-29)
    Abstract: What are the data on ART and IUI cycles, and fertility preservation (FP) interventions reported in 2017 as compared to previous years, as well as the main trends over the years? SUMMARY ANSWER The 21st ESHRE report on ART and IUI shows the continual increase in reported treatment cycle numbers in Europe, with a decrease in the proportion of transfers with more than one embryo causing an additional slight reduction of multiple delivery rates (DR) as well as higher pregnancy rates (PR) and DR after frozen embryo replacement (FER) compared to fresh IVF and ICSI cycles, while the number of IUI cycles increased and their outcomes remained stable. WHAT IS KNOWN ALREADY Since 1997, ART aggregated data generated by national registries, clinics or professional societies have been gathered and analyzed by the European IVF-monitoring Consortium (EIM) and communicated in a total of 20 manuscripts published in Human Reproduction and Human Reproduction Open. STUDY DESIGN, SIZE, DURATION Data on European medically assisted reproduction (MAR) are collected by EIM for ESHRE on a yearly basis. The data on treatments performed between 1 January and 31 December 2017 in 39 European countries were provided by either National Registries or registries based on personal initiatives of medical associations and scientific organizations. PARTICIPANTS/MATERIALS, SETTING, METHODS Overall, 1382 clinics offering ART services in 39 countries reported a total of 940 503 treatment cycles, including 165 379 with IVF, 391 379 with ICSI, 271 476 with FER, 37 303 with preimplantation genetic testing (PGT), 69 378 with egg donation (ED), 378 with IVM of oocytes, and 5210 cycles with frozen oocyte replacement (FOR). A total of 1273 institutions reported data on 207 196 IUI cycles using either husband/partner’s semen (IUI-H; n = 155 794) or donor semen (IUI-D; n = 51 402) in 30 countries and 25 countries, respectively. Thirteen countries reported 18 888 interventions for FP, including oocyte, ovarian tissue, semen and testicular tissue banking in pre- and postpubertal patients. MAIN RESULTS AND THE ROLE OF CHANCE In 21 countries (20 in 2016) in which all ART clinics reported to the registry, 473 733 treatment cycles were registered for a total population of approximately 330 million inhabitants, allowing a best-estimate of a mean of 1435 cycles performed per million inhabitants (range: 723–3286). Amongst the 39 reporting countries, the clinical PR per aspiration and per transfer in 2017 were similar to those observed in 2016 (26.8% and 34.6% vs 28.0% and 34.8%, respectively). After ICSI the corresponding rates were also similar to those achieved in 2016 (24% and 33.5% vs 25% and 33.2% in 2016). When freeze all cycles were removed, the clinical PRs per aspiration were 30.8% and 27.5% for IVF and ICSI, respectively. After FER with embryos originating from own eggs the PR per thawing was 30.2%, which is comparable to 30.9% in 2016, and with embryos originating from donated eggs it was 41.1% (41% in 2016). After ED the PR per fresh embryo transfer was 49.2% (49.4% in 2016) and per FOR 43.3% (43.6% in 2016). In IVF and ICSI together, the trend towards the transfer of fewer embryos continues with the transfer of 1, 2, 3 and ≥4 embryos in 46.0%, 49.2%, 4.5% and in 0.3% of all treatments, respectively (corresponding to 41.5%, 51.9%. 6.2% and 0.4% in 2016). This resulted in a reduced proportion of twin DRs of 14.2% (14.9% in 2016) and stable triplet DR of 0.3%. Treatments with FER in 2017 resulted in a twin and triplet DR of 11.2% and 0.2%, respectively (vs 11.9% and 0.2% in 2016). After IUI, the DRs remained similar at 8.7% after IUI-H (8.9% in 2016) and at 12.4% after IUI-D (12.4.0% in 2016). Twin and triplet DRs after IUI-H were 8.1% and 0.3%, respectively (in 2016: 8.8% and 0.3%) and 6.9% and 0.2% after IUI-D (in 2016: 7.7% and 0.4%). Amongst 18 888 FP interventions in 13 countries, cryopreservation of ejaculated sperm (n = 11 112 vs 7877 from 11 countries in 2016) and of oocytes (n = 6588 vs 4907 from eight countries in 2016) were the most frequently reported. LIMITATIONS, REASONS FOR CAUTION As the methods of data collection and levels of reporting vary amongst European countries, interpretation of results should remain cautious. Some countries were unable to deliver data about the number of initiated cycles and deliveries. WIDER IMPLICATIONS OF THE FINDINGS The 21st ESHRE report on ART, IUI and FP interventions shows a continuous increase of reported treatment numbers and MAR-derived livebirths in Europe. Being already the largest data collection on MAR in Europe, efforts should continue to optimize data collection and reporting with the perspective of improved quality control, transparency and vigilance in the field of reproductive medicine. STUDY FUNDING/COMPETING INTEREST(S) The study has received no external funding and all costs are covered by ESHRE. There are no competing interests.
    Type of Medium: Online Resource
    ISSN: 2399-3529
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2899901-0
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  • 8
    In: Human Reproduction, Oxford University Press (OUP), Vol. 35, No. 12 ( 2020-12-01), p. 2832-2849
    Abstract: How has the performance of the European regional register of the European IVF-monitoring Consortium (EIM)/European Society of Human Reproduction and Embryology (ESHRE) evolved from 1997 to 2016, as compared to the register of the Centres for Disease Control and Prevention (CDC) of the USA and the Australia and New Zealand Assisted Reproduction Database (ANZARD)? SUMMARY ANSWER It was found that coherent and analogous changes are recorded in the three regional registers over time, with a different intensity and pace, that new technologies are taken up with considerable delay and that incidental complications and adverse events are only recorded sporadically. WHAT IS KNOWN ALREADY European data on ART have been collected since 1997 by EIM. Data collection on ART in Europe is particularly difficult due to its fragmented political and legal landscape. In 1997, approximately 78.1% of all known institutions offering ART services in 23 European countries submitted data and in 2016 this number rose to 91.8% in 40 countries. STUDY DESIGN, SIZE, DURATION We compared the changes in European ART data as published in the EIM reports (2001–2020) with those of the USA, as published by CDC, and with those of Australia and New Zealand, as published by ANZARD. PARTICIPANTS/MATERIALS, SETTING, METHODS We performed a retrospective analysis of the published EIM data sets spanning the 20 years observance period from 1997 to 2016, together with the published data sets of the USA as well as of Australia and New Zealand. By comparing the data sets in these three large registers, we analysed differences in the completeness of the recordings together with differences in the time intervals on the occurrence of important trends in each of them. Effects of suspected over- and under-reporting were also compared between the three registers. X2 log-rank analysis was used to assess differences in the data sets. MAIN RESULTS AND THE ROLE OF CHANCE During the period 1997–2016, the numbers of recorded ART treatments increased considerably (5.3-fold in Europe, 4.6-fold in the USA, 3.0-fold in Australia and New Zealand), while the number of registered treatment modalities rose from 3 to 7 in Europe, from 4 to 10 in the USA and from 5 to 8 in Australia and New Zealand, as published by EIM, CDC and ANZARD, respectively. The uptake of new treatment modalities over time has been very different in the three registers. There is a considerable degree of underreporting of the number of initiated treatment cycles in Europe. The relationship between IVF and ICSI and between fresh and thawing cycles evolved similarly in the three geographical areas. The freeze-all strategy is increasingly being adopted by all areas, but in Europe with much delay. Fewer cycles with the transfer of two or more embryos were reported in all three geographical areas. The delivery rate per embryo transfer in thawing cycles bypassed that in fresh cycles in the USA in 2012, in Australia and New Zealand in 2013, but not yet in Europe. As a result of these changing approaches, fewer multiple deliveries have been reported. Since 2012, the most documented adverse event of ART in all three registers has been premature birth ( & lt;37 weeks). Some adverse events, such as maternal death, ovarian hyperstimulation syndrome, haemorrhage and infections, were only recorded by EIM and ANZARD. LIMITATIONS, REASONS FOR CAUTION The methods of data collection and reporting were very different among European countries, but also among the three registers. The better the legal background on ART surveillance, the more complete are the data sets. Until the legal obligation to report is installed in all European countries together with an appropriate quality control of the submitted data the reported numbers and incidences should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS The growing number of reported treatments in ART, the higher variability in treatment modalities and the rising contribution to the birth rates over the last 20 years point towards the increasing impact of ART. High levels of completeness in data reporting have been reached, but inconsistencies and inaccuracies still remain and need to be identified and quantified. The current trend towards a higher diversity in treatment modalities and the rising impact of cryostorage, resulting in improved safety during and after ART treatment, require changes in the organization of surveillance in ART. The present comparison must stimulate all stakeholders in ART to optimize surveillance and data quality assurance in ART. STUDY FUNDING/COMPETING INTEREST(S) This study has no external funding and all costs are covered by ESHRE. There are no competing interests. TRIAL REGISTRATION NUMBER N/A.
    Type of Medium: Online Resource
    ISSN: 0268-1161 , 1460-2350
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1484864-8
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  • 9
    In: Human Reproduction, Oxford University Press (OUP), Vol. 38, No. Supplement_1 ( 2023-06-22)
    Abstract: Does administration of 2 months of transdermal testosterone prior to ovarian stimulation for IVF/ICSI increase clinical pregnancy rates in Bologna criteria poor ovarian responders? Summary answer Pre-treatment with 5.5mg testosterone for 2 months prior to ovarian stimulation for IVF/ICSI does not increase clinical pregnancy rates as compared with placebo. What is known already The role of androgens in the treatment of infertile women has been extensively investigated over the last 20 years. Early animal studies and small human studies supported a potentially beneficial role of androgen pretreatment for the management of poor ovarian responders. Still, available evidence regarding androgen administration remains inconclusive, and clinical guidelines do not support their use in infertile women, mainly due to the lack of robust evidence regarding efficacy, the small sample sizes, the lack of data regarding safety, and the lack of uniform dose and duration of testosterone pretreatment for poor ovarian responders. Study design, size, duration T-TRANSPORT is the first multicenter multinational superiority phase III, double-blind placebo-controlled randomized trial aiming to detect differences in clinical pregnancy rates between testosterone transdermal gel or placebo for the treatment of poor responders. A sample size of 400 women was calculated, with an interim analysis prespecified to be performed after 70% of recruitment, to determine continuation, sample size re-calculation, or early termination for futility, based on the conditional power reached (≥80%, 40-80% and & lt;20%, respectively). Participants/materials, setting, methods T-TRANSPORT included women 18-43 years old from 10 centers and 4 European countries (Spain, Belgium, Denmark and Switzerland) randomized between 2015-2022. Women with poor ovarian response according to the Bologna criteria were randomly assigned 1:1 (stratified by center and age group ( & lt;36, 36-39 and ≥40 years old)) to receive either 5.5mg of transdermal testosterone or placebo for ∼60 days prior to initiation of ovarian stimulation for IVF/ICSI. Main results and the role of chance Overall, 316 poor responders were included and 290 patients were randomized. Based on the prespecified interim analysis, recruitment stopped when 70% of the patients have completed their treatment and blinded data were analyzed. Patients were categorized as group A and Group B until the decision of the DSMB board to break the randomization code is taken. Ovarian stimulation outcomes did not differ between groups, with a (mean ± SD) number of oocytes retrieved 3.42±2.25 vs. 3.69±2.72, number of MII oocytes 2.75±2.06 vs. 2.83±1.91 and number of embryos 1.46±1.22 vs. 1.90±1.92, for the comparison of Group A vs. Group B, respectively. Clinical pregnancy rates were comparable between groups, Group A: 17.42% vs. Group B 16.30%, RR (95%CI):1.07(0.64-1.79). Analysis of the results per-age strata also failed to demonstrate significant differences between groups in women & lt;36 (Group A:24% vs. Group B: 17.9%), 36-39 (A: 21.4% vs. B:20%) and ≥40 years old (A:10% vs. B:12.3%) Finally, no severe adverse events were observed in any of the groups that led to treatment discontinuation. Comparison of androgenic adverse events showed differences for hirsutism A:7.10% vs. B:14.07% and acne A:16.13% vs. B:21.48%, whereas very few cases of alopecia A:1.29% vs. B:2.22% and voice deepening (A:1.29% vs. B:0%) were reported. Limitations, reasons for caution All patients, per protocol, underwent D3 embryo transfer. In addition, the study duration exceeded 7 years, owing to a temporary halt during the COVID-19 pandemic. Finally, the results presented here are blinded data which will be unblinded by the time of presentation based on the interim analysis performed. Wider implications of the findings Testosterone pre-treatment prior to IVF/ICSI does not increase clinical pregnancy rates in poor ovarian responders. Planned posthoc analyses within the T-TRANSPORT trial aim to investigate whether testosterone may affect ovarian reserve markers, follicular fluid biomarkers, cumulus cells gene expression, and libido in women with poor ovarian response. Study funding Yes. Funding source Funding by commercial/corporate company(ies). The study received Unrestricted grants by Ferring Pharmaceuticals, BESINS international and Roche Diagnostics. Testosterone and placebo gel were provided by BESINS INTERNATIONAL. Trial registration number NCT02418572
    Type of Medium: Online Resource
    ISSN: 0268-1161 , 1460-2350
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1484864-8
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  • 10
    In: Molecular Oncology, Wiley, Vol. 5, No. 6 ( 2011-12), p. 504-516
    Abstract: Risk assessment of future breast cancer risk through exposure to sex steroids currently relies on clinical scorings such as mammographic density. Knowledge about the gene expression patterns in existing breast cancer tumors may be used to identify risk factors in the breast tissue of women still free of cancer. The differential effects of estradiol, estradiol together with gestagens, or tibolone on breast cancer‐related gene expression in normal breast tissue samples taken from postmenopausal women may be used to identify gene expression profiles associated with a higher breast cancer risk. Breast tissue samples were taken from 33 healthy postmenopausal women both before and after a six month treatment with either 2mg micronized estradiol [E2], 2mg micronized estradiol and 1mg norethisterone acetate [E2+NETA] , 2.5mg tibolone [T] or [no HRT] . Except for [E2], which was only given to women after hysterectomy, the allocation to each of the three groups was randomized. The expression of 102 mRNAs and 46 microRNAs putatively involved in breast cancer was prospectively determined in the biopsies of 6 women receiving [no HRT] , 5 women receiving [E2], 5 women receiving [E2+NETA] , and 6 receiving [T]. Using epithelial and endothelial markers genes, non‐representative biopsies from 11 women were eliminated. Treatment of postmenopausal women with [E2+NETA] resulted in the highest number of differentially (p 〈 0.05) regulated genes (16.2%) compared to baseline, followed by [E2] (10.1%) and [T] (4.7%). Among genes that were significantly down‐regulated by [E2+NETA] ranked estrogen‐receptor‐1 (ESR1, p=0.019) and androgen receptor (AR, p=0.019), whereas CYP1B1, a gene encoding an estrogen‐metabolizing enzyme, was significantly up‐regulated (p=0.016). Mammary cells triggered by [E2+NETA] and [E2] adjust for steroidogenic up‐regulation through down‐regulation of the estrogen‐receptor pathway. In this prospective study, prolonged administration of [E2+NETA] and to a lesser extent of [E2] but not [T] were associated in otherwise healthy breast tissue with a change in the expression of genes putatively involved in breast cancer. Our data suggest that normal mammary cells triggered by [E2+NETA] adjust for steroidogenic up‐regulation through down‐regulation of the estrogen‐receptor pathway. This feasibility study provides the basis for whole genome analyses to identify novel markers involved in increased breast cancer risk.
    Type of Medium: Online Resource
    ISSN: 1574-7891 , 1878-0261
    Language: English
    Publisher: Wiley
    Publication Date: 2011
    detail.hit.zdb_id: 2322586-5
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