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  • 1
    In: Journal of Assisted Reproduction and Genetics, Springer Science and Business Media LLC, Vol. 38, No. 6 ( 2021-06), p. 1293-1302
    Type of Medium: Online Resource
    ISSN: 1058-0468 , 1573-7330
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2016722-2
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  • 2
    In: Human Reproduction, Oxford University Press (OUP), Vol. 36, No. 7 ( 2021-06-18), p. 1821-1831
    Abstract: Does the addition of oral dydrogesterone to vaginal progesterone as luteal phase support improve pregnancy outcomes during frozen embryo transfer (FET) cycles compared with vaginal progesterone alone? SUMMARY ANSWER Luteal phase support with oral dydrogesterone added to vaginal progesterone had a higher live birth rate and lower miscarriage rate compared with vaginal progesterone alone. WHAT IS KNOWN ALREADY Progesterone is an important hormone that triggers secretory transformation of the endometrium to allow implantation of the embryo. During IVF, exogenous progesterone is administered for luteal phase support. However, there is wide inter-individual variation in absorption of progesterone via the vaginal wall. Oral dydrogesterone is effective and well tolerated when used to provide luteal phase support after fresh embryo transfer. However, there are currently no data on the effectiveness of luteal phase support with the combination of dydrogesterone with vaginal micronized progesterone compared with vaginal micronized progesterone after FET. STUDY DESIGN, SIZE, DURATION Prospective cohort study conducted at an academic infertility center in Vietnam from 26 June 2019 to 30 March 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS We studied 1364 women undergoing IVF with FET. Luteal support was started when endometrial thickness reached ≥8 mm. The luteal support regimen was either vaginal micronized progesterone 400 mg twice daily plus oral dydrogesterone 10 mg twice daily (second part of the study) or vaginal micronized progesterone 400 mg twice daily (first 4 months of the study). In women with a positive pregnancy test, the appropriate luteal phase support regimen was continued until 7 weeks’ gestation. The primary endpoint was live birth after the first FET of the started cycle, with miscarriage & lt;12 weeks as one of the secondary endpoints. MAIN RESULTS AND THE ROLE OF CHANCE The vaginal progesterone + dydrogesterone group and vaginal progesterone groups included 732 and 632 participants, respectively. Live birth rates were 46.3% versus 41.3%, respectively (rate ratio [RR] 1.12, 95% CI 0.99–1.27, P = 0.06; multivariate analysis RR 1.30 (95% CI 1.01–1.68), P = 0.042), with a statistically significant lower rate of miscarriage at & lt;12 weeks in the progesterone + dydrogesterone versus progesterone group (3.4% versus 6.6%; RR 0.51, 95% CI 0.32–0.83; P = 0.009). Birth weight of both singletons (2971.0 ± 628.4 versus 3118.8 ± 559.2 g; P = 0.004) and twins (2175.5 ± 494.8 versus 2494.2 ± 584.7; P = 0.002) was significantly lower in the progesterone plus dydrogesterone versus progesterone group. LIMITATIONS, REASONS FOR CAUTION The main limitations of the study were the open-label design and the non-randomized nature of the sequential administration of study treatments. However, our systematic comparison of the two strategies was able to be performed much more rapidly than a conventional randomized controlled trial. In addition, the single ethnicity population limits external generalizability. WIDER IMPLICATIONS OF THE FINDINGS Our findings study suggest a role for oral dydrogesterone in addition to vaginal progesterone as luteal phase support in FET cycles to reduce the miscarriage rate and improve the live birth rate. Carefully planned prospective cohort studies with limited bias could be used as an alternative to randomized controlled clinical trials to inform clinical practice. STUDY FUNDING/COMPETING INTERESTS This study received no external funding. LNV has received speaker and conference fees from Merck, grant, speaker and conference fees from Merck Sharpe and Dohme, and speaker, conference and scientific board fees from Ferring; TMH has received speaker fees from Merck, Merck Sharp and Dohme, and Ferring; R.J.N. has received scientific board fees from Ferring and receives grant funding from the National Health and Medical Research Council (NHMRC) of Australia; BWM has acted as a paid consultant to Merck, ObsEva and Guerbet, and is the recipient of grant money from an NHMRC Investigator Grant. TRIAL REGISTRATION NUMBER NCT0399876.
    Type of Medium: Online Resource
    ISSN: 0268-1161 , 1460-2350
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1484864-8
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  • 3
    In: Fertility and Sterility, Elsevier BV, ( 2024-9)
    Type of Medium: Online Resource
    ISSN: 0015-0282
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2024
    detail.hit.zdb_id: 1500469-7
    SSG: 12
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  • 4
    In: Journal of Assisted Reproduction and Genetics, Springer Science and Business Media LLC, Vol. 40, No. 4 ( 2023-04), p. 827-835
    Type of Medium: Online Resource
    ISSN: 1058-0468 , 1573-7330
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2016722-2
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  • 5
    In: Fertility and Sterility, Elsevier BV, Vol. 112, No. 3 ( 2019-09), p. e435-e436
    Type of Medium: Online Resource
    ISSN: 0015-0282
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
    detail.hit.zdb_id: 1500469-7
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Endocrinology Vol. 12 ( 2021-3-12)
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 12 ( 2021-3-12)
    Abstract: To estimate the prevalence of low-prognosis patients according to the POSEIDON criteria using real-world data. Design Multicenter population-based cohort study. Settings Fertility clinics in Brazil, Turkey, and Vietnam. Patients Infertile women undergoing assisted reproductive technology using standard ovarian stimulation with exogenous gonadotropins. Interventions None. Main outcome measures Per-period prevalence rates of POSEIDON patients (overall, stratified by POSEIDON groups and by study center) and the effect of covariates on the probability that a patient be classified as “POSEIDON”. Results A total of 13,146 patients were included. POSEIDON patients represented 43.0% (95% confidence interval [CI] 42.0–43.7) of the studied population, and the prevalence rates varied across study centers (range: 38.6–55.7%). The overall prevalence rates by POSEIDON groups were 44.2% (group 1; 95% CI 42.6–45.9), 36.1% (group 2; 95% CI 34.6–37.7), 5.2% (group 3; 95% CI 4.5–6.0), and 14.4% (group 4; 95% CI: 13.3–15.6). In general, POSEIDON patients were older, had a higher body mass index (BMI), lower ovarian reserve markers, and a higher frequency of female factor as the primary treatment indication than non-POSEIDON patients. The former required larger doses of gonadotropin for ovarian stimulation, despite achieving a 2.5 times lower number of retrieved oocytes than non-POSEIDON patients. Logistic regression analyses revealed that female age, BMI, ovarian reserve, and a female infertility factor were relevant predictors of the POSEIDON condition. Conclusions The estimated prevalence of POSEIDON patients in the general population undergoing ART is significant. These patients differ in clinical characteristics compared with non-POSEIDON patients. The POSEIDON condition is associated with female age, ovarian reserve, BMI, and female infertility. Efforts in terms of diagnosis, counseling, and treatment are needed to reduce the prevalence of low-prognosis patients.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2592084-4
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  • 7
    In: BMJ Open, BMJ, Vol. 8, No. 12 ( 2018-12), p. e023413-
    Abstract: In vitro maturation (IVM) is a potential alternative to conventional in vitro fertilisation (IVF) to avoid ovarian hyperstimulation syndrome (OHSS). This is particularly relevant in women with a high antral follicle count (AFC) and/or polycystic ovary syndrome (PCOS), who are at increased risk for OHSS. However, no randomised controlled trials of IVM versus IVF in women with high AFC have reported both pregnancy and OHSS rates. The aim of this study is to compare the effectiveness and safety of one IVM cycle and one IVF with segmentation cycle within women with PCOS or high AFC-related subfertility. Methods and analysis This randomised controlled trial will be conducted at a specialist IVF centre in Vietnam. Eligible subfertile women with PCOS and/or high AFC will be randomised to undergo either IVM or IVF. The primary outcome is live birth after the first embryo transfer of the started treatment cycle. Cycles in which no embryo is available for transfer will be considered as failures. The study has a non-inferiority design, with a maximal acceptable between-group difference of 5%. Rates of OHSS will also be reported. Ethics and dissemination Ethical approval was obtained from the participating centre, and informed patient consent was obtained before study enrolment. Results of the study will be submitted for publication in a peer-reviewed journal. Trial registration number NCT03405701 ; Pre-results.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    Language: English
    Publisher: BMJ
    Publication Date: 2018
    detail.hit.zdb_id: 2599832-8
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  • 8
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2020
    In:  Journal of Assisted Reproduction and Genetics Vol. 37, No. 2 ( 2020-02), p. 347-357
    In: Journal of Assisted Reproduction and Genetics, Springer Science and Business Media LLC, Vol. 37, No. 2 ( 2020-02), p. 347-357
    Abstract: Standard oocyte in vitro maturation (IVM) usually results in lower pregnancy rates than in vitro fertilization (IVF). IVM preceded by a prematuration step improves the acquisition of oocyte developmental competence and can enhance embryo quality (EQ). This study evaluated the effectiveness of a biphasic culture system incorporating prematuration and IVM steps (CAPA-IVM) versus standard IVM in women with polycystic ovarian morphology (PCOM). Methods Eighty women (age 〈  38 years, ≥ 25 follicles of 2–9 mm in both ovaries, no major uterine abnormalities) were randomized to undergo CAPA-IVM ( n  = 40) or standard IVM ( n  = 40). CAPA-IVM uses two steps: a 24-h prematuration step with C-type natriuretic peptide-supplemented medium, then 30 h of culture in IVM media supplemented with follicle-stimulating hormone and amphiregulin. Standard IVM was performed using routine protocols. Results A significantly higher proportion of oocytes reached metaphase II at 30 h after CAPA-IVM versus standard IVM (63.6 vs 49.0; p   〈  0.001) and the number of good quality embryos per cumulus-oocyte complex tended to be higher (18.9 vs 12.7; p  = 0.11). Clinical pregnancy rate per embryo transfer was 63.2% in the CAPA-IVM versus 38.5% in the standard IVM group ( p  = 0.04). Live birth rate per embryo transfer was not statistically different between the CAPA-IVM and standard IVM groups (50.0 vs 33.3% [ p  = 0.17]). No malformations were reported and birth weight was similar in the two treatment groups. Conclusions Use of the CAPA-IVM system significantly improved maturation and clinical pregnancy rates versus standard IVM in patients with PCOM. Furthermore, live births after CAPA-IVM are reported for the first time.
    Type of Medium: Online Resource
    ISSN: 1058-0468 , 1573-7330
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2016722-2
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  • 9
    In: Human Reproduction, Oxford University Press (OUP), Vol. 36, No. 8 ( 2021-07-19), p. 2157-2169
    Abstract: What is the cumulative delivery rate (CDR) per aspiration IVF/ICSI cycle in low-prognosis patients as defined by the Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria? SUMMARY ANSWER The CDR of POSEIDON patients was on average ∼50% lower than in normal responders and varied across POSEIDON groups; differences were primarily determined by female age, number of embryos obtained, number of embryo transfer (ET) cycles per patient, number of oocytes retrieved, duration of infertility, and BMI. WHAT IS KNOWN ALREADY The POSEIDON criteria aim to underline differences related to a poor or suboptimal treatment outcome in terms of oocyte quality and quantity among patients undergoing IVF/ICSI, and thus, create more homogenous groups for the clinical management of infertility and research. POSEIDON patients are presumed to be at a higher risk of failing to achieve a live birth after IVF/ICSI treatment than normal responders with an adequate ovarian reserve. The CDR per initiated/aspiration cycle after the transfer of all fresh and frozen–thawed/warmed embryos has been suggested to be the critical endpoint that sets these groups apart. However, no multicenter study has yet substantiated the validity of the POSEIDON classification in identifying relevant subpopulations of patients with low-prognosis in IVF/ICSI treatment using real-world data. STUDY DESIGN, SIZE, DURATION Multicenter population-based retrospective cohort study involving 9073 patients treated in three fertility clinics in Brazil, Turkey and Vietnam between 2015 and 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants were women with infertility between 22 and 42 years old in their first IVF/ICSI cycle of standard ovarian stimulation whose fresh and/or frozen embryos were transferred until delivery of a live born or until all embryos were used. Patients were retrospectively classified according to the POSEIDON criteria into four groups based on female age, antral follicle count (AFC), and the number of oocytes retrieved or into a control group of normal responders (non-POSEIDON). POSEIDON patients encompassed younger ( & lt;35 years) and older (35 years or above) women with an AFC ≥5 and an unexpected poor ( & lt;4 retrieved oocytes) or suboptimal (4–9 retrieved oocytes) response to stimulation, and respective younger and older counterparts with an impaired ovarian reserve (i.e. expected poor responders; AFC  & lt;5). Non-POSEIDON patients were those with AFC ≥5 and & gt;9 oocytes retrieved. CDR was computed per one aspirated cycle. Logistic regression analysis was carried out to examine the association between patient classification and CDR. MAIN RESULTS AND ROLE OF CHANCE The CDR was lower in the POSEIDON patients than in the non-POSEIDON patients (33.7% vs 50.6%; P  & lt; 0.001) and differed across POSEIDON groups (younger unexpected poor responder [Group 1a; n = 212]: 27.8%, younger unexpected suboptimal responder [Group 1b; n = 1785] : 47.8%, older unexpected poor responder [Group 2a; n = 293] : 14.0%, older unexpected suboptimal responder [Group 2b; n = 1275]: 30.5%, younger expected poor responder [Group 3; n = 245] : 29.4%, and older expected poor responder [Group 4; n = 623]: 12.5%. Among unexpected suboptimal/poor responders (POSEIDON Groups 1 and 2), the CDR was twice as high in suboptimal responders (4–9 oocytes retrieved) as in poor responders ( & lt;4 oocytes) (P = 0.0004). Logistic regression analysis revealed that the POSEIDON grouping, number of embryos obtained, number of ET cycles per patient, number of oocytes collected, female age, duration of infertility and BMI were relevant predictors for CDR (P  & lt; 0.001). LIMITATIONS, REASONS FOR CAUTION Our study relied on the antral follicle count as the biomarker used for patient classification. Ovarian stimulation protocols varied across study centers, potentially affecting patient classification. WIDER IMPLICATIONS OF THE FINDINGS POSEIDON patients exhibit lower CDR per aspirated IVF/ICSI cycle than normal responders; the differences are mainly determined by female age and number of oocytes retrieved, thereby reflecting the importance of oocyte quality and quantity. Our data substantiate the validity of the POSEIDON criteria in identifying relevant subpopulations of patients with low-prognosis in IVF/ICSI treatment. Efforts in terms of early diagnosis, prevention, and identification of specific interventions that might benefit POSEIDON patients are warranted. STUDY FUNDING/COMPETING INTEREST(S) Unrestricted investigator-sponsored study grant (MS200059_0013) from Merck KGaA, Darmstadt, Germany. The funder had no role in study design, data collection, analysis, decision to publish or manuscript preparation. S.C.E. declares receipt of unrestricted research grants from Merck and lecture fees from Merck and Med.E.A. H.Y. declares receipt of payment for lectures from Merck and Ferring. L.N.V. receives speaker fees and conferences from Merck, Merck Sharp and Dohme (MSD) and Ferring and research grants from MSD and Ferring. J.F.C. declares receipt of statistical services fees from ANDROFERT Clinic. T.M.H. received speaker fees and conferences from Merck, MSD and Ferring. P.H. declares receipt of unrestricted research grants from Merck, Ferring, Gedeon Richter and IBSA and lecture fees from Merck, Gedeon Richter and Med.E.A. C.A. declares receipt of unrestricted research grants from Merck and lecture fees from Merck. The remaining authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER N/A.
    Type of Medium: Online Resource
    ISSN: 0268-1161 , 1460-2350
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1484864-8
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  • 10
    In: Human Reproduction, Oxford University Press (OUP), Vol. 36, No. 6 ( 2021-05-17), p. 1530-1541
    Abstract: What is the agreement between antral follicle count (AFC) and anti-Müllerian hormone (AMH) levels when used to patient classification according to the Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria? SUMMARY ANSWER Our study indicates a strong agreement between the AFC and the AMH levels in classifying POSEIDON patients; thus, either can be used for this purpose, although one in four women will have discordant values when both biomarkers are used WHAT IS KNOWN ALREADY According to the POSEIDON criteria, both AFC and AMH may be used to classify low-prognosis patients. Proposed AFC and AMH thresholds of 5 and 1.2 ng/ml, respectively, have their basis in published literature; however, no study has yet determined the reproducibility of patient classification in comparing one biomarker with the other, nor have their thresholds ever been validated within this patient population. STUDY DESIGN, SIZE, DURATION A population-based cohort study involving 9484 consecutive patients treated in three fertility clinics in Brazil, Turkey and Vietnam between 2015 and 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants were infertile women between 22 and 46 years old in their first in vitro fertilization/intracytoplasmic sperm injection cycle of standard ovarian stimulation with exogenous gonadotropins whose baseline ovarian reserves had been assessed by both AFC and AMH. Details of pre- and post-treatment findings were input into a coded research file. Two indicators of interest were created to classify patients according to the POSEIDON criteria based upon AFC and AMH values. Patients who did not fit any of the four POSEIDON groups were classified as non-POSEIDON. AFC was determined in the early follicular phase using two-dimensional (2D) transvaginal ultrasonography, whereas AMH values were based on the modified Beckman Coulter generation II enzyme-linked immunosorbent assay. Agreement rates were computed between AFC and AMH to classify patients using Cohen’s kappa statistics. Logistic regression analyzes were carried out to examine the association between ovarian markers and low ( & lt;4) and suboptimal (4–9) oocyte yield. MAIN RESULTS AND THE ROLE OF CHANCE The degree of agreement in classifying patients according to POSEIDON groups was strong overall (kappa = 0.802; 95% CI: 0.792–0.811). A total of 73.8% of individuals were classified under the same group using both biomarkers. The disagreement rates were ∼26% and did not diverge when AFC or AMH was used as the primary biomarker criterion. Significant regression equations were found between ovarian markers and oocyte yield (P  & lt; 0.0001). For low oocyte yield, the optimal AFC and AMH cutoff values were 5 and 1.27 ng/ml with sensitivities of 0.61 and 0.66, specificities of 0.81 and 0.72, and AUC receiver operating characteristics of 0.791 and 0.751, respectively. For suboptimal oocyte yield respective AFC and AMH cutoffs were 12 and 2.97 ng/ml with sensitivities of 0.74 and 0.69, specificities of 0.76 and 0.66 and AUCs of 0.81 and 0.80. LIMITATIONS, REASONS FOR CAUTION Our study relied on 2D transvaginal sonography to quantify the AFC and manual Gen II assay for AMH determination and classification of patients. AMH data must be interpreted in an assay-specific manner. Treatment protocols varied across centers potentially affecting patient classification. WIDER IMPLICATIONS OF THE FINDINGS Three of four patients will be classified the same using either AFC or AMH values. Both biomarkers provide acceptable and equivalent accuracy in predicting oocyte yield further supporting their use and proposed thresholds in daily clinical practice for patient classification according to the POSEIDON criteria. However, the sensitivity of POSEIDON thresholds in predicting low oocyte yield is low. Clinicians should adopt the biomarker that may best reflect their clinical setting. STUDY FUNDING/COMPETING INTEREST(S) Unrestricted investigator-sponsored study grant (MS200059_0013) from Merck KGaA, Darmstadt, Germany. The funder had no role in study design, data collection, analysis, decision to publish or manuscript preparation. S.C.E. declares receipt of unrestricted research grants from Merck and lecture fees from Merck and Med.E.A. H.Y. declares receipt of payment for lectures from Merck and Ferring. L.N.V. receives speaker fees and conferences from Merck, Merck Sharp and Dohme (MSD) and Ferring and research grants from MSD and Ferring. T.M.H. received speaker fees and conferences from Merck, MSD and Ferring. The remaining authors have nothing to disclose. TRIAL REGISTRATION NUMBER not applicable.
    Type of Medium: Online Resource
    ISSN: 0268-1161 , 1460-2350
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1484864-8
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