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1.
Hum Reprod ; 34(11): 2290-2296, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31600391

RESUMO

STUDY QUESTION: Does hormone stimulation during assisted reproductive technology (ART) treatment increase the risk of ovarian cancer? SUMMARY ANSWER: No increased risk of ovarian cancer was found among ART-treated women, with the exception of ART-treated women with endometriosis. WHAT IS KNOWN ALREADY: Previous studies on the association between ovarian stimulation during ART and ovarian cancer have shown conflicting results. The risk of ovarian cancer varies according to the cause of infertility, and only a few studies on ART treatment and risk of ovarian cancer have had sufficient data to address this issue. Endometriosis has been linked to an increased risk of ovarian cancer. STUDY DESIGN, SIZE, DURATION: Women undergoing ART treatment during 1994-2015 were registered in the Danish IVF register. Data were linked with data from the Danish Cancer Register and socio-demographic population registers using an individual person identification number assigned to people residing in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women undergoing ART treatment were age-matched with a random sample of the female background population and followed for up to 22 years. After relevant exclusions, the population consisted of 58 472 ART-treated women and 625 330 untreated women, all with no previous malignancies. Ovarian cancer risk was assessed using multivariable cox regression analyses with adjustment for educational level, marital status, parity and treatment year. Results are shown as hazard ratios (HRs) with corresponding CIs. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 393 (0.06%) women were diagnosed with ovarian cancer during follow-up (mean 9.7 years). Women treated with ART had an increased risk of ovarian cancer (HR 1.20, 95% CI 1.10-1.31), which diminished over time. The increased risk was apparent among women with female factor infertility (HR 1.36, 95% CI 1.25-1.48), whereas no female factor infertility was associated with a lower risk (HR 0.87, 95% CI 0.76-1.00). The risk was increased among women with endometriosis (HR 3.78, 95% CI 2.45-5.84), whereas no increased risk was found among ART-treated women with polycystic ovary syndrome, other female causes of infertility and unexplained infertility. LIMITATIONS, REASONS FOR CAUTION: The association between ART treatment and ovarian cancer is likely influenced by increased detection due to multiple ultrasound scans during ART treatment. WIDER IMPLICATIONS OF THE FINDINGS: Undergoing ART treatment without the presence of endometriosis was not associated with an increased risk of ovarian cancer, which is reassuring. Whether ART treatment increases the risk of ovarian cancer among women with endometriosis needs further investigation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a PhD grant to D.V. from the Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Funding for establishing the Danish National ART-couple II cohort was achieved from Ebba Rosa Hansen Foundation. The funders had no influence on data collection, analyses or results presented. The authors have no conflicts of interest to declare.

2.
Eur Radiol ; 29(1): 287-298, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29948079

RESUMO

OBJECTIVES: Prostate artery embolisation (PAE) is a new minimally invasive treatment for lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). The purpose of this study was to review the efficacy and safety of PAE in the treatment of BPH with LUTS. METHODS: A systematic review performed according to the PRISMA guidelines with a pre-specified search strategy for PubMed, Web of Science, Cochrane Library and Embase databases protocol (PROSPERO ID: CRD42017059196). Trials studying the efficacy of prostate artery embolisation to treat LUTS with more than ten participants and follow-up longer than 6 months were included by two independent authors. Outcomes investigated were International Prostate Symptom Score (IPSS), quality of life (QoL), International Index of Erectile Function (IIEF-5), prostate volume (PV), prostate-specific antigen (PSA), peak void flow (Qmax), post-void residual (PVR) and complications. To summarise mean change from baseline, a meta-analysis was done using the random-effects model. RESULTS: The search returned 210 references, of which 13 studies met the inclusion criteria, representing 1,254 patients. Patients in the included studies with data available for meta-analysis had moderate to severe LUTS and a mean IPSS of 23.5. Statistically significant (p value < 0.05) improvements of all investigated outcomes were seen at 12-month follow-up. Major complications were reported in 0.3% of the cases. CONCLUSIONS: Our findings suggest that PAE can reduce moderate to severe LUTS in men with BPH with a low risk of complications. KEY POINTS: • Prostate artery embolisation (PAE) improved International Prostate Symptom Score (IPSS) by 67%. • Major complications after PAE are very rare. • Use of cone-beam CT may reduce risk of non-target embolisation.


Assuntos
Embolização Terapêutica/métodos , Próstata/irrigação sanguínea , Hiperplasia Prostática/terapia , Artérias , Tomografia Computadorizada de Feixe Cônico , Humanos , Masculino , Próstata/diagnóstico por imagem , Hiperplasia Prostática/diagnóstico , Resultado do Tratamento
3.
BJOG ; 126(2): 261-269, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30276983

RESUMO

OBJECTIVE: To assess academic performance in singletons aged 15-16 years conceived after frozen embryo transfer (FET) compared with singletons born after fresh embryo transfer (ET) in Danish cohorts born from 1995 to 2001. DESIGN: Danish national registry-based cohort study. SETTING: Danish national registries. POPULATION: All 6495 singletons conceived after assisted reproductive technology (ART) treatment in Denmark from 1995 to 2001 [FET (n) = 423; fresh ET (n) = 6072]. METHODS: Mean test scores on a national standardised and international comparable grading-scale. Comparisons of test score were first made in univariate analysis (Model 1) and secondly in a multivariate linear model (Model 2) adjusting for relevant reproductive and socio-demographic covariates such as the occupational and educational level of the parents. Sensitivity analyses on FET-IVF (in vitro fertilisation) versus fresh ET-IVF and FET-ICSI (intracytoplasmic sperm injection) versus fresh ET-ICSI were made. Linear mixed models were used to account for the correlation in test scores of siblings for continuous outcome. MAIN OUTCOME MEASURES: Mean overall test score and test score in Danish, mathematics, English, and physics/chemistry. RESULTS: Crude and adjusted mean test scores were similar for adolescents conceived after FET compared with fresh ET. The crude mean difference was +0.11 (95% CI -0.11; 0.34), and the adjusted mean difference was +0.12 (95% CI -0.09; 0.34). CONCLUSIONS: Adolescents conceived after FET had similar academic performance at 15-16 of years of age compared with children conceived after fresh ET. TWEETABLE ABSTRACT: Using frozen embryos in fertility treatment does not affect school performance in Danish adolescents aged 15-16 years.


Assuntos
Desempenho Acadêmico/estatística & dados numéricos , Criopreservação/estatística & dados numéricos , Transferência Embrionária/estatística & dados numéricos , Adolescente , Estudos de Coortes , Dinamarca , Transferência Embrionária/efeitos adversos , Transferência Embrionária/métodos , Feminino , Humanos , Modelos Lineares , Masculino , Gravidez , Sistema de Registros
4.
Hum Reprod ; 34(1): 171-180, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30541039

RESUMO

STUDY QUESTION: Is the number of aspirated oocytes in the first ART cycle associated with the cumulative live birthrates (CLBR) in subsequent cycles? SUMMARY ANSWER: The number of aspirated oocytes in the first cycle was associated with CLBR in subsequent cycles. Previous treatment response predicts outcome in future cycles. WHAT IS KNOWN ALREADY: Previous reports have shown a positive association between the number of retrieved oocytes and live birthrate per fresh treatment cycle. This has also been shown for the CLBR in one complete ART-cycle, including possible subsequent frozen-thawed transfers (FER). It has been shown that women with less than five oocytes in the first cycle have poorer outcome within six complete cycles than women with more than 12 oocytes, suggesting that the number of aspirated oocytes in the first cycle may be reproduced in later cycles. However, other studies have shown that an initial low treatment response may be improved with increased gonadotrophin start-dose. STUDY DESIGN, SIZE, DURATION: The Danish National IVF-registry includes all ART treatments in public and private clinics since 1994. Treatment-cycles were cross-linked with the Medical Birth Registry, identifying treatment-related births and natural conception births. This national cohort study includes all women starting ART treatments with homologous eggs between 2002 and 2011, N = 30 486. Subjects were followed for up to four fresh ART-cycles including subsequent FER-cycles (=four complete cycles), until the first livebirth, or until December 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: The CLBR within 1-4 complete ART-cycles were calculated as the proportion of women with a livebirth, out of all women initiating ART-treatment, including drop-outs (no livebirth or no continued treatment within follow-up). In women with one year follow-up from last treatment, multivariate logistic regression analysis assessed impact of retrieved oocytes on CLBR, adjusting results for female age and cause of infertility. Hospital admission due to ovarian hyperstimulation syndrome (OHSS) was reported. MAIN RESULTS AND THE ROLE OF CHANCE: After one, two and three complete ART-cycles, the CLBRs attributable to ART treatment were 26.4% [95%CI 25.9-26.9], 42.6% [42.0-43.1] and 51.3% [50.7-51.9], respectively. The CLBR attributable to non-ART related conception (natural conception or intrauterine insemination) were 5.3% [5.0-5.6], 8.3% [8.0-8.7] and 10.6% [10.3-11.0], after one, two and three complete cycles. In women without a live birth in the first complete cycle, the number of aspirated oocytes predicted the outcome in the second and third cycle: When compared to women with 0-3 aspirated oocytes in the first cycle, the odds for live birth in the second and third cycle was 1.18 [1.07-1.30] for women with 4-9 aspirated oocytes in the first cycle, 1.41 [1.27-1.57] for women with 10-15 aspirated oocytes and 1.63 [1.42-1.88] for women with more than 15 aspirated oocytes. For women without a livebirth in the first and second cycle, the sum of aspirated oocytes predicted outcome in the third complete cycle. Women with a sum larger than six aspirated oocytes, had marked increased odds ratios for livebirth in the third complete cycle, compared to women with a sum of 0-6 oocytes in the first and second fresh cycle. Incidence of hospital-admission due to OHSS was 1.7% in the first cycle, decreasing to 1.3% and 1.0% in the second and third cycles. LIMITATIONS, REASONS FOR CAUTION: Although mandatory, there may be treatment-cycles not registered in the IVF-registry. Missing information in number of aspirated oocytes are most likely random losses of information. There were few observations in women with more than 15 aspirated oocytes and these birthrates should be interpreted cautiously. Information on gonadotrophin dose used for stimulation was not available, nor was information on dose adjustments in subsequent cycles. WIDER IMPLICATIONS OF THE FINDINGS: With these results we can counsel couples returning for fertility treatments, providing an age-stratified revised prognosis for chances of live birth and risk of OHSS, reflecting prior failed attempts and previous ovarian response. STUDY FUNDING/COMPETING INTEREST(S): This study was unconditionally funded by Ferring Pharmaceuticals and ReproUnion. The funders had no role in the study design, data collection and interpretation, or decision to submit the work for publication. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: The study was approved by the Danish Data Protection Agency (J.nr. 2012-41-1330).


Assuntos
Coeficiente de Natalidade , Fertilização In Vitro/métodos , Infertilidade/terapia , Nascimento Vivo , Recuperação de Oócitos/métodos , Adulto , Estudos de Coortes , Dinamarca , Feminino , Fertilização In Vitro/estatística & dados numéricos , Humanos , Masculino , Recuperação de Oócitos/estatística & dados numéricos , Oócitos , Indução da Ovulação , Gravidez , Taxa de Gravidez , Prognóstico , Sistema de Registros/estatística & dados numéricos , Resultado do Tratamento
5.
Artigo em Inglês | MEDLINE | ID: mdl-26955051

RESUMO

Phylogenetic tree reconciliation is an important technique for reconstructing the evolutionary histories of species and genes and other dependent entities. Reconciliation is typically performed in a maximum parsimony framework and the number of optimal reconciliations can grow exponentially with the size of the trees, making it difficult to understand the solution space. This paper demonstrates how a small number of reconciliations can be found that collectively contain the most highly supported events in the solution space. While we show that the formal problem is NP-complete, we give a approximation algorithm, experimental results that indicate its effectiveness, and the new DTL-RnB software tool that uses our algorithms to summarize the space of optimal reconciliations (www.cs.hmc.edu/dtlrnb).


Assuntos
Algoritmos , Biologia Computacional/métodos , Modelos Genéticos , Filogenia , Software
6.
Skin Res Technol ; 24(1): 65-72, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28685861

RESUMO

BACKGROUND/PURPOSE: Our objective was to assess epithelialization of suction blister lesions by optical coherence tomography (OCT) and benchmark it to histology using epidermal thickness (ET) as the primary outcome. METHODS: Thirty-two healthy volunteers were recruited to Study 1 and 2. One 10-mm suction blister was raised on each buttock, and the blister roof was excised. Lesions were covered with moisture-retaining dressing. In Study 1, the lesions were OCT-scanned on day 0 (D0), D2 and D4 and excised for histological examination. In Study 2, the progress of epithelialization and skin barrier function were monitored to D14. RESULTS: ET increased from D0 to D2 by 46 µm (P<.001) and from D2 to D4 by 19 µm (P=.004). Compared with histology, OCT overestimated the presence of the epithelium (P<.0001) and ET on D4. Reliable measurements were obtained when the ET of the lesions reached the ET of the normal epidermis from D5-D7 and onwards. The ET development was reflected in decreased transepidermal water loss. CONCLUSION: We found that the OCT technique was poorly discriminative with respect to the neoepithelium and the moist lesion surface material in the early postinjury period. In the later stages, OCT seemed valuable for estimating the advancement of epithelialization.


Assuntos
Vesícula/diagnóstico por imagem , Epiderme/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Cicatrização/fisiologia , Adulto , Bandagens , Biópsia , Vesícula/patologia , Vesícula/fisiopatologia , Vasos Sanguíneos/patologia , Método Duplo-Cego , Epiderme/patologia , Epiderme/fisiologia , Feminino , Humanos , Estudos Longitudinais , Vasos Linfáticos/patologia , Masculino , Pessoa de Meia-Idade , Pele/irrigação sanguínea , Sucção , Perda Insensível de Água/fisiologia , Adulto Jovem
7.
Radiother Oncol ; 123(3): 466-471, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28460825

RESUMO

BACKGROUND AND PURPOSE: For the first time, delivered dose to the rectum has been calculated and accumulated throughout the course of prostate radiotherapy using megavoltage computed tomography (MVCT) image guidance scans. Dosimetric parameters were linked with toxicity to test the hypothesis that delivered dose is a stronger predictor of toxicity than planned dose. MATERIAL AND METHODS: Dose-surface maps (DSMs) of the rectal wall were automatically generated from daily MVCT scans for 109 patients within the VoxTox research programme. Accumulated-DSMs, representing total delivered dose, and planned-DSMs, from planning CT data, were parametrised using Equivalent Uniform Dose (EUD) and 'DSM dose-width', the lateral dimension of an ellipse fitted to a discrete isodose cluster. Associations with 6 toxicity endpoints were assessed using receiver operator characteristic curve analysis. RESULTS: For rectal bleeding, the area under the curve (AUC) was greater for accumulated dose than planned dose for DSM dose-widths up to 70Gy. Accumulated 65Gy DSM dose-width produced the strongest spatial correlation (AUC 0.664), while accumulated EUD generated the largest AUC overall (0.682). For proctitis, accumulated EUD was the only reportable predictor (AUC 0.673). Accumulated EUD was systematically lower than planned EUD. CONCLUSIONS: Dosimetric parameters extracted from accumulated DSMs have demonstrated stronger correlations with rectal bleeding and proctitis, than planned DSMs.


Assuntos
Neoplasias da Próstata/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Reto/efeitos da radiação , Idoso , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica
8.
Hum Reprod ; 32(7): 1439-1449, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28472455

RESUMO

STUDY QUESTION: What are the long-term chances of having a child for couples starting fertility treatments and how many conceive with ART, IUI and without treatment? SUMMARY ANSWER: Total 5-year live birthrates were strongly influenced by female age and ranged from 80% in women under 35-26% in women ≥40 years, overall, 14% of couples conceived naturally and one-third of couples starting treatments with intrauterine insemination delivered from that treatment. WHAT IS KNOWN ALREADY: Few studies report success rates in fertility treatments across a couple's complete fertility treatment history, across clinics, evaluating live births after insemination, ART and natural conceptions. STUDY DESIGN, SIZE, DURATION: This register-based national cohort study from Denmark includes all women initiating fertility treatments in public and private clinics with homologous gametes in 2007-2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women were identified in the Danish ART Registry and were cross-linked with the Medical Birth Registry to identify live births. Subfertile couples were followed 2 years (N = 19 884), 3 years (N = 14 445) and 5 years (N = 5165), or until their first live birth. Cumulative live birthrates were estimated 2, 3 and 5 years from the first treatment cycle, in all women, including drop-outs. Birthrates were stratified by type of first treatment (ART/IUI), mode of conception (ART/IUI/natural conception) and female age. MAIN RESULTS AND THE ROLE OF CHANCE: Within 5 years, in women aged <35 years (N = 3553), 35-39 years (N = 1156) and ≥40 years (N = 451), a total of 64%, 49% and 16% had a live birth due to treatment, respectively. Additionally, in women aged < 35 years, 35-39 years and ≥40 years, 16%, 11% and 10% delivered after natural conception, yielding total 5-year birthrates of 80%, 60% and 26%. In women starting treatments with IUI (N = 3028), 35% delivered after IUI within 5 years, 24% delivered after shift to ART treatments and 17% delivered after natural conception. Within 5 years from starting treatments with ART (N = 2137), 53% delivered after ART, 11% delivered after natural conception and 0.6% delivered after IUI. LIMITATIONS, REASONS FOR CAUTION: Birthrates are most likely higher compared to countries without national coverage of treatments and results are influenced by laws and regulations. Information on duration of infertility prior to treatment was not available. Future prospective intervention studies should focus on the role of expectant management. WIDER IMPLICATIONS OF THE FINDINGS: Our results can provide couples with a comprehensible age-stratified prognosis at start of treatment. STUDY FUNDING/COMPETING INTEREST(S): This study was unconditionally funded by Ferring Pharmaceuticals and the Augustinus foundation. All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: S.S.M. received an unconditional grant from Ferring Pharmaceuticals; A.A.H. has received personal fees from Ferring Pharmaceuticals not related to this work; A.N.A. reports grants and personal fees from Ferring Pharmaceuticals, personal fees from Merck Serono, grants and personal fees from MSD, outside the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work. TRIAL REGISTRATION NUMBER: The study was approved by the Danish Data Protection Agency (J.nr. 2012-41-1330).


Assuntos
Fertilização , Infertilidade Feminina/terapia , Infertilidade Masculina/terapia , Técnicas de Reprodução Assistida , Adulto , Coeficiente de Natalidade , Estudos de Coortes , Dinamarca/epidemiologia , Características da Família , Feminino , Fertilização In Vitro , Humanos , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/fisiopatologia , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/fisiopatologia , Inseminação Artificial , Nascimento Vivo , Masculino , Idade Materna , Gravidez , Prognóstico , Sistema de Registros , Índice de Gravidade de Doença
9.
Clin Radiol ; 72(9): 772-779, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28427743

RESUMO

AIMS: To assess the feasibility of undertaking microbubble-guided vacuum-assisted biopsy (VAB) of the sentinel lymph node (SLN) and determine its sensitivity in detecting metastases. Patient experience and the impact of VAB on subsequent axillary surgery were also evaluated. MATERIALS AND METHODS: Patients with a normal axillary ultrasound or benign core biopsy planned for surgical SLN biopsy were recruited. Part 1 of the study was used to establish the technique of ultrasound microbubble contrast to detect the SLN. In Part 2 microbubble detection of the SLN was followed by 13 G VAB. All patients subsequently had surgical histological correlation. RESULTS: One hundred and thirty-nine patients were recruited: 36 to Part 1 and 103 to Part 2. Of the 100 patients in Part 2 included for analysis, 82 (82%) underwent successful biopsy. Sensitivity for detecting metastases was 58.8% (95% confidence interval: 32.9%, 81.6%). The procedure was generally well tolerated; however, VAB interfered adversely with subsequent surgical SLN biopsy with surgeons reporting moderate or severe interference in 48% of patients and an additional 8.3% with complete failure of SLNB. CONCLUSION: It is possible to perform VAB of microbubble-detected SLNs. Although the sensitivity for detecting metastases was reasonable, the adverse effect on subsequent surgery was significant.


Assuntos
Neoplasias da Mama/patologia , Biópsia Guiada por Imagem/métodos , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Biópsia de Linfonodo Sentinela/métodos , Ultrassonografia Mamária , Adulto , Idoso , Axila , Meios de Contraste , Estudos de Viabilidade , Feminino , Humanos , Microbolhas , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Medição da Dor , Fosfolipídeos , Hexafluoreto de Enxofre , Vácuo
10.
Hum Reprod ; 32(2): 447-456, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28057876

RESUMO

STUDY QUESTION: Is academic performance in adolescents aged 15-16 years and conceived after ART, measured as test scores in ninth grade, comparable to that for spontaneously conceived (SC) adolescents? SUMMARY ANSWER: ART singletons had a significantly lower mean test score in the adjusted analysis when compared with SC singletons, yet the differences were small and probably not of clinical relevance. WHAT IS KNOWN ALREADY: Previous studies have shown similar intelligence quotient (IQ) levels in ART and SC children, but only a few have been on adolescents. Academic performance measured with standardized national tests has not previously been explored in a complete national cohort of adolescents conceived after ART. STUDY DESIGN, SIZE, DURATION: A Danish national registry-based cohort including all 4766 ART adolescents (n = 2836 singletons and n = 1930 twins) born in 1995-1998 were compared with two SC control cohorts: a randomly selected singleton population (n = 5660) and all twins (n = 7064) born from 1995 to 1998 in Denmark. Nine children who died during the follow-up period were excluded from the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Mean test scores on a 7-point-marking scale from -3 to 12 were compared, and adjustments were made for relevant reproductive and socio-demographic covariates including occupational and educational level of the parents. MAIN RESULTS AND THE ROLE OF CHANCE: The crude mean test score was higher in both ART singletons and ART twins compared with SC adolescents. The crude mean differences were +0.41 (95% CI 0.30-0.53) and +0.45 (95% CI 0.28-0.62) between ART and SC singletons and between ART and SC twins, respectively. However, the adjusted mean overall test score was significantly lower for ART singletons compared with SC singletons (adjusted mean difference -0.15 (95% CI -0.29-(-0.02))). For comparison, the adjusted mean difference was +2.05 (95% CI 1.82-2.28) between the highest and the lowest parental educational level, suggesting that the effect of ART is weak compared with the conventional predictors. The adjusted analyses showed significantly lower mean test scores in mathematics and physics/chemistry for ART singletons compared with SC singletons. Comparing ART twins with SC twins yielded no difference in academic performance in the adjusted analyses. Similar crude and adjusted overall mean test scores were found when comparing ART singletons and ART twins. LIMITATIONS, REASONS FOR CAUTION: Missing data on educational test scores occurred in 6.6% of adolescents aged 15-16 years for the birth cohorts 1995-1997, where all of the children according to their age should have passed the ninth grade exam at the time of data retrieval. As sensitivity analyses yielded no significant difference in the adjusted risk of having missing test scores between any of the groups, it is unlikely that this should bias our results. Adjustment for body mass index and smoking during pregnancy was not possible. WIDER IMPLICATIONS OF THE FINDINGS: As our results are based on national data, our findings can be applied to other populations. The findings of this paper suggest that a possible small negative effect of parental subfertility or ART treatment is counterbalanced by the higher educational level in the ART parents. STUDY FUNDING/COMPETING INTERESTS: The Danish Medical Association in Copenhagen (KMS) funded this study with a scholarship grant. None of the authors had any competing interests. TRIAL REGISTRATION NO STATISTICS DENMARK: 704676.


Assuntos
Desempenho Acadêmico , Técnicas de Reprodução Assistida , Adolescente , Estudos de Coortes , Dinamarca , Feminino , Humanos , Masculino , Gravidez , Gravidez de Gêmeos , Sistema de Registros , Instituições Acadêmicas , Gêmeos
11.
BJOG ; 124(4): 561-572, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27592694

RESUMO

BACKGROUND: Approximately 50 000 oocyte donation (OD) treatment cycles are now performed annually in Europe and the US. OBJECTIVES: To ascertain whether the risk of adverse obstetric and perinatal/neonatal outcomes is higher in pregnancies conceived by OD than in pregnancies conceived by conventional in-vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) or spontaneously. SEARCH STRATEGY: A systematic search was performed in the PubMed, Cochrane and Embase databases from 1982-2016. Primary outcomes were hypertensive disorders of pregnancy, pre-eclampsia (PE), gestational diabetes mellitus, postpartum haemorrhage, caesarean section, preterm birth, low birthweight and small for gestational age. SELECTION CRITERIA: Inclusion criteria were original studies including at least five OD pregnancies with a control group of pregnancies conceived by conventional IVF/ICSI or spontaneous conception, and case series with >500 cases reporting one or more of the selected complications. Studies not adjusting for plurality were excluded. DATA COLLECTION AND ANALYSIS: Thirty-five studies met the inclusion criteria. A random-effects model was used for the meta-analyses. MAIN RESULTS: For OD pregnancies versus conventional IVF/ICSI pregnancies the risk of PE was adjusted odds ratio (AOR) 2.11 (95% CI, 1.42-3.15) in singleton and AOR 3.31 (95% CI, 1.61-6.80) in multiple pregnancies. The risks of preterm birth and low birthweight in singletons were AOR 1.75 (95% CI, 1.39-2.20) and 1.53 (95% CI, 1.16-2.01), respectively. CONCLUSIONS: OD conceptions are associated with adverse obstetric and neonatal outcomes. To avoid the additional increase in risk from multiplicity, single-embryo transfer should be the choice of option in OD cycles. TWEETABLE ABSTRACT: Oocyte donation pregnancies have increased risk of a range of obstetric and neonatal complications.


Assuntos
Doação de Oócitos/efeitos adversos , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Cesárea/estatística & dados numéricos , Feminino , Fertilização In Vitro/efeitos adversos , Humanos , Recém-Nascido , Gravidez , Complicações na Gravidez/etiologia
12.
Psychol Med ; 46(15): 3105-3116, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27534802

RESUMO

BACKGROUND: Post-traumatic stress disorder (PTSD) has been linked to hypertension, but most research on PTSD and hypertension is cross-sectional, and potential mediators have not been clearly identified. Moreover, PTSD is twice as common in women as in men, but understanding of the PTSD-hypertension relationship in women is limited. We examined trauma exposure and PTSD symptoms in relation to incident hypertension over 22 years in 47 514 civilian women in the Nurses' Health Study II. METHOD: We used proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for new-onset hypertension (N = 15 837). RESULTS: PTSD symptoms assessed with a screen were modestly associated with incident hypertension in a dose-response fashion after adjusting for potential confounders. Compared to women with no trauma exposure, women with 6-7 PTSD symptoms had the highest risk of developing hypertension (HR 1.20, 95% CI 1.12-1.30), followed by women with 4-5 symptoms (HR 1.17, 95% CI 1.10-1.25), women with 1-3 symptoms (HR 1.12, 95% CI 1.06-1.18), and trauma-exposed women with no symptoms (HR 1.04, 95% CI 1.00-1.09). Findings were maintained, although attenuated, adjusting for hypertension-relevant medications, medical risk factors, and health behaviors. Higher body mass index and antidepressant use accounted for 30% and 21% of the PTSD symptom-hypertension association, respectively. CONCLUSIONS: Screening for hypertension and reducing unhealthy lifestyle factors, particularly obesity, in women with PTSD may hold promise for offsetting cardiovascular risk.


Assuntos
Hipertensão/epidemiologia , Trauma Psicológico/epidemiologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Adulto , Antidepressivos/uso terapêutico , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Incidência , Estudos Longitudinais , Pessoa de Meia-Idade , Obesidade/epidemiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença
13.
J Fish Biol ; 88(6): 2275-302, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27188827

RESUMO

The diets of black oreo Allocyttus niger, smooth oreo Pseudocyttus maculatus, spiky oreo Neocyttus rhomboidalis and orange roughy Hoplostethus atlanticus were determined from examination of contents of 240, 311, 76 and 415 non-empty stomachs, from fishes sampled by bottom trawl on Chatham Rise to the east of South Island, New Zealand. Hoplostethus atlanticus had an opportunistic predatory strategy with a broad diet dominated by prawns and mesopelagic teleosts, but with substantial components of mysids and cephalopods. Pseudocyttus maculatus was strongly specialized on gelatinous zooplankton (jellyfish and salps). Allocyttus niger consumed mainly salps and hyperiid amphipods, and to a lesser extent fishes, prawns, mysids and copepods. Neocyttus rhomboidalis primarily consumed salps, along with mysids, euphausiids and fishes. Only P. maculatus did not exhibit significant ontogenetic variation in diet. The diets were also influenced by year and bottom depth. Differences in the distributions and diets of the four species probably reduce conflicts in resource use.


Assuntos
Dieta , Comportamento Alimentar , Peixes/fisiologia , Comportamento Predatório , Animais , Nova Zelândia
14.
Eur J Neurol ; 23(7): 1158-64, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27061733

RESUMO

BACKGROUND AND PURPOSE: Elevated plasma uric acid has been inconsistently associated with an increased risk of total stroke; however, data are sparse amongst women. The association between plasma uric acid concentrations and ischaemic stroke amongst women was examined and the effect modification by key cardiovascular risk factors was evaluated. METHODS: A nested case-control design with matching by age, race/ethnicity, smoking status, menopausal status, postmenopausal hormone therapy use, date of blood draw and fasting status was utilized amongst female participants of the Nurses' Health Study who provided blood samples between 1989 and 1990. Plasma uric acid was measured on stored blood samples. The National Survey of Stroke criteria were utilized to confirm 460 incident cases of ischaemic stroke by medical records from 1990 to 2006. Multivariable conditional logistic regression models were estimated. RESULTS: In matched analysis, risk of ischaemic stroke increased by 15% for each 1 mg/dl increase in plasma uric acid [95% confidence interval (CI) 3%-28%], but was no longer significant after adjustment for cardiovascular risk factors, particularly history of hypertension. The highest quartile of uric acid was significantly associated with greater risk of ischaemic stroke (relative risk 1.56; 95% CI 1.06-2.29, extreme quartiles) in matched analysis, but estimates were no longer significant after adjustment for cardiovascular risk factors (relative risk 1.43; 95% CI 0.93-2.18). Significant effect modification by key cardiovascular risk factors was not observed. CONCLUSIONS: Plasma uric acid levels were not independently associated with increased risk of ischaemic stroke in this cohort of women. Whilst plasma uric acid was associated with stroke risk factors, it was not independently associated with stroke risk.


Assuntos
Isquemia Encefálica/etiologia , Hipertensão/complicações , Acidente Vascular Cerebral/etiologia , Ácido Úrico/sangue , Adulto , Idoso , Isquemia Encefálica/sangue , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Fumar/efeitos adversos , Acidente Vascular Cerebral/sangue
15.
Hum Reprod ; 31(5): 1034-45, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26965431

RESUMO

STUDY QUESTION: Do infertile patients below the age of 40 years have a lower ovarian reserve, estimated by anti-Müllerian hormone (AMH) and total antral follicle count (AFC), than women of the same age with no history of infertility? SUMMARY ANSWER: Serum AMH and AFC were not lower in infertile patients aged 20-39 years compared with a control group of the same age with no history of infertility. WHAT IS KNOWN ALREADY?: The management of patients with a low ovarian reserve and a poor response to controlled ovarian stimulation (COS) remains a challenge in assisted reproductive technologies (ART). Both AMH levels and AFC reflect the ovarian reserve and are valuable predictors of the ovarian response to exogenous gonadotrophins. However, there is a large inter-individual variation in the age-related depletion of the ovarian reserve and a broad variability in the levels of AMH and AFC compatible with conception. Women with an early depletion of the ovarian reserve may experience infertility as a consequence of postponement of childbearing. Thus, low ovarian reserve is considered to be overrepresented among infertile patients. STUDY DESIGN, SIZE, DURATION: A prospective cohort study including 382 women with a male partner referred to fertility treatment at Rigshospitalet, Copenhagen, Denmark during 2011-2013 compared with a control group of 350 non-users of hormonal contraception with no history of infertility recruited during 2008-2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: Included patients and controls were aged 20-39 years. Women with polycystic ovary syndrome were excluded. On Cycle Days 2-5, AFC and ovarian volume were measured by transvaginal sonography, and serum levels of AMH, FSH and LH were assessed. MAIN RESULTS AND THE ROLE OF CHANCE: Infertile patients had similar AMH levels (11%, 95% confidence interval (CI): -1;24%) and AFC (1%, 95% CI: -7;8%) compared with controls with no history of infertility in an age-adjusted linear regression analysis. The prevalence of very low AMH levels (<5 pmol/l) was similar in the two cohorts (age-adjusted odds ratio: 0.9, 95% CI: 0.5;1.7). The findings persisted after adjustment for smoking status, body mass index, gestational age at birth, previous conception and chronic disease in addition to age. LIMITATIONS, REASON FOR CAUTION: The comparison of ovarian reserve parameters in women recruited at different time intervals could be a reason for caution. However, all women were examined at the same centre using the same sonographic algorithm and AMH immunoassay. WIDER IMPLICATIONS OF THE FINDINGS: This study indicates that the frequent observation of patients with a poor response to COS in ART may not be due to an overrepresentation of women with an early depletion of the ovarian reserve but rather a result of the expected age-related decline in fertility. STUDY FUNDING/COMPETING INTERESTS: The study received funding from MSD and the Interregional European Union (EU) projects 'ReproSund' and 'ReproHigh'. The authors have no conflict of interest. TRIAL REGISTRATION NUMBER: Not applicable.


Assuntos
Hormônio Antimülleriano/sangue , Infertilidade Feminina/metabolismo , Reserva Ovariana , Adulto , Fatores Etários , Estudos de Coortes , Intervalos de Confiança , Dinamarca , Feminino , Humanos , Infertilidade Feminina/epidemiologia , Folículo Ovariano/diagnóstico por imagem , Indução da Ovulação
16.
Hum Reprod ; 30(10): 2364-75, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26311148

RESUMO

STUDY QUESTION: To what extent does oral contraception (OC) impair ovarian reserve parameters in women who seek fertility assessment and counselling to get advice on whether their remaining reproductive lifespan is reduced? SUMMARY ANSWER: Ovarian reserve parameters defined by anti-Müllerian hormone (AMH), antral follicle count (AFC) and ovarian volume were found to be significantly decreased by 19% (95% CI 9.1-29.3%), 18% (95% CI 11.2-24.8%) and 50% (95% CI 45.1-53.7%) among OC users compared with non-users. WHAT IS KNOWN ALREADY: AMH and AFC have proved to be reliable predictors of ovarian ageing. In women, AMH declines with age and data suggest a relationship with remaining reproductive lifespan and age at menopause. OC may alter parameters related to ovarian reserve assessment but the extent of the reduction is uncertain. STUDY DESIGN, SIZE, DURATION: A cross-sectional study of 887 women aged 19-46 attending the Fertility Assessment and Counselling Clinic (FACC) from 2011 to 2014 comparing ovarian reserve parameters in OC users with non-OC users. PARTICIPANTS/MATERIALS, SETTING, METHODS: The FAC Clinic was initiated to provide individual fertility assessment and counselling. All women were examined on a random cycle day by a fertility specialist. Consultation included; transvaginal ultrasound (AFC, ovarian volume, pathology), a full reproductive history and AMH measurement. Women were grouped into non-users and users of OC (all combinations of estrogen-progestin products and the contraceptive vaginal ring). Non-users included women with an intrauterine device (IUD) or no hormonal contraception. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 887 women, 244 (27.5%) used OC. In a linear regression analyses adjusted for age, ovarian volume was 50% lower (95% CI 45.1-53.7%), AMH was 19% lower (95% CI 9.1-29.3%), and AFC was 18% lower (95% CI 11.2-24.8%) in OC users compared with non-users. Comparison of AMH at values of <10 pmol/l OC was found to have a significant negative influence on AMH (OR 1.6, 95% CI 1.1; 2.4, P = 0.03). Furthermore, we found a significant decrease in antral follicles sized 5-7 mm (P < 0.001) and antral follicles sized 8-10 mm (P < 0.001) but an increase in antral follicles sized 2-4 mm (P = 0.008) among OC users. The two groups (OC users versus non-users) were comparable regarding age, BMI, smoking and maternal age at menopause. LIMITATIONS, REASON FOR CAUTION: The study population comprised women attending the FAC Clinic. Recruitment was based on self-referral, which could imply a potential selection bias. Ovarian reserve was examined at a random cycle day. However, both AMH and AFC can be assessed independently of the menstrual cycle. The accuracy in predicting residual reproductive lifespan is still needed in both users and non-users of OC. WIDER IMPLICATIONS OF THE FINDINGS: OC has a major impact on the ovarian volume, and a moderate impact on AFC and AMH with a shift towards the smaller sized antral follicle subclasses. The most evident reduction occurs in the antral follicles of 5-7 and 8-10 mm with the highest number of AMH secreting granulosa cells. It is essential to be aware of the impact of OC use on ovarian reserve parameters when guiding OC users on their fertility status and reproductive lifespan. STUDY FUNDING/COMPETING INTERESTS: The FAC Clinic was established in 2011 as part of the ReproHigh collaboration. This study received funding through the Capital Region Research Fund and by EU-regional funding. There are no competing interests. TRIAL REGISTRATION NUMBER: The biobank connected to FAC Clinic is approved by the Scientific Ethical Committee (H-1-2011-081).


Assuntos
Anticoncepcionais Orais/uso terapêutico , Fertilidade/efeitos dos fármacos , Folículo Ovariano/patologia , Reserva Ovariana/efeitos dos fármacos , Ovário/efeitos dos fármacos , Adulto , Envelhecimento , Hormônio Antimülleriano/metabolismo , Anticoncepção , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Pessoa de Meia-Idade , Ovário/fisiologia , Estudos Prospectivos , Reprodução , Inquéritos e Questionários , Adulto Jovem
17.
Hum Reprod ; 30(3): 710-6, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25605701

RESUMO

STUDY QUESTIONS: Has the perinatal outcome of children conceived after assisted reproductive technology (ART) improved over time? SUMMARY ANSWER: The perinatal outcomes in children born after ART have improved over the last 20 years, mainly due to the reduction of multiple births. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: A Swedish study has shown a reduction in unwanted outcomes over time in children conceived after ART. Our analyses based on data from more than 92 000 ART children born in four Nordic countries confirm these findings. STUDY DESIGN: Nordic population-based matched cohort study with ART outcome and health data from Denmark, Finland, Norway and Sweden. PARTICIPANTS, SETTING AND METHODS: We analysed the perinatal outcome of 62 379 ART singletons and 29 758 ART twins, born from 1988 to 2007 in four Nordic countries. The ART singletons were compared with a control group of 362 215 spontaneously conceived singletons. Twins conceived after ART were compared with all spontaneously conceived twins (n = 122 763) born in the Nordic countries during the study period. The rates of several adverse perinatal outcomes were stratified into the time periods: 1988-1992; 1993-1997; 1998-2002 and 2003-2007 and presented according to multiplicity. MAIN RESULTS AND ROLE OF CHANCE: For singletons conceived after ART, a remarkable decline in the risk of being born preterm and very preterm was observed. The proportion of ART singletons born with a low and very low birthweight also decreased. Finally, the stillbirth and infant death rates have declined among both ART singletons and twins. Throughout the 20 year period, fewer ART twins were stillborn or died during the first year of life compared with spontaneously conceived twins, presumably due to the lower proportion of monozygotic twins among the ART twins. LIMITATIONS, REASONS FOR CAUTION: We were not able to adjust for some potential confounders such as BMI, smoking, length or cause of infertility. The Nordic ART populations have changed over time, and in recent years, both less as well as severely reproductive ill couples are being treated. This may have affected the observed trends. WIDER IMPLICATIONS OF THE FINDINGS: It is assuring that data from four countries confirm an overall improvement over time in the perinatal outcomes of children conceived after ART. Furthermore, data show the beneficial effect of single embryo transfer, not only in regard to lowering the rate of multiples but also concerning the health of singletons. STUDY FUNDING/COMPETING INTERESTS: The European Society for Human Reproduction and Embryology (ESHRE), the University of Copenhagen and the Danish Agency for Science, Technology and Innovation has supported the project. The CoNARTaS group has received travel and meeting funding from the Nordic Federation of Obstetrics and Gynecology (NFOG). None of the authors has any competing interests to declare.


Assuntos
Técnicas de Reprodução Assistida/estatística & dados numéricos , Estudos de Coortes , Feminino , Humanos , Gravidez , Resultado da Gravidez , Gravidez de Gêmeos/estatística & dados numéricos , Países Escandinavos e Nórdicos
18.
Eye (Lond) ; 28(6): 662-71, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24603425

RESUMO

AIMS: Vascular perfusion may be impaired in primary open-angle glaucoma (POAG); thus, we evaluated a panel of markers in vascular tone-regulating genes in relation to POAG. METHODS: We used Illumina 660W-Quad array genotype data and pooled P-values from 3108 POAG cases and 3430 controls from the combined National Eye Institute Glaucoma Human Genetics Collaboration consortium and Glaucoma Genes and Environment studies. Using information from previous literature and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we compiled single-nucleotide polymorphisms (SNPs) in 186 vascular tone-regulating genes. We used the 'Pathway Analysis by Randomization Incorporating Structure' analysis software, which performed 1000 permutations to compare the overall pathway and selected genes with comparable randomly generated pathways and genes in their association with POAG. RESULTS: The vascular tone pathway was not associated with POAG overall or POAG subtypes, defined by the type of visual field loss (early paracentral loss (n=224 cases) or only peripheral loss (n=993 cases)) (permuted P≥0.20). In gene-based analyses, eight were associated with POAG overall at permuted P<0.001: PRKAA1, CAV1, ITPR3, EDNRB, GNB2, DNM2, HFE, and MYL9. Notably, six of these eight (the first six listed) code for factors involved in the endothelial nitric oxide synthase activity, and three of these six (CAV1, ITPR3, and EDNRB) were also associated with early paracentral loss at P<0.001, whereas none of the six genes reached P<0.001 for peripheral loss only. DISCUSSION: Although the assembled vascular tone SNP set was not associated with POAG, genes that code for local factors involved in setting vascular tone were associated with POAG.


Assuntos
Endotélio Vascular/metabolismo , Predisposição Genética para Doença , Glaucoma de Ângulo Aberto/genética , Músculo Liso Vascular/fisiologia , Polimorfismo de Nucleotídeo Único , Transdução de Sinais/genética , Proteínas Quinases Ativadas por AMP/genética , Idoso , Estudos de Casos e Controles , Caveolina 1/genética , Dinaminas/genética , Feminino , Proteínas de Ligação ao GTP/genética , Genótipo , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Receptores de Inositol 1,4,5-Trifosfato/genética , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo III/genética , Receptor de Endotelina B , Receptores de Endotelina/genética
19.
Hum Reprod ; 29(5): 1090-6, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24578477

RESUMO

STUDY QUESTION: Is the risk of stillbirth and perinatal deaths increased after assisted reproductive technology (ART) compared with pregnancies established by spontaneous conception (SC)? SUMMARY ANSWER: A significantly increased risk of stillbirth in ART singletons was only observed before 28 + 0 gestational weeks. WHAT IS KNOWN ALREADY: The current literature indicates that children born after ART have an increased risk of perinatal death. The knowledge on stillbirth in ART pregnancies is limited. STUDY DESIGN, SIZE, DURATION: A population based case-control study. PARTICIPANTS/MATERIALS, SETTING AND METHODS: A total of 62 485 singletons and 29 793 twins born after ART in Denmark, Finland, Norway and Sweden, from 1982 to 2007, were compared with 362 798 spontaneously conceived (SC) singletons and 132 181 twins. MAIN RESULTS AND THE ROLE OF CHANCE: The adjusted rate ratio for stillbirth at gestational weeks 22 + 0 to 27 + 6 was 2.08 [95% confidence interval (CI) 1.55-2.78] for ART versus SC singletons. After 28 + 0 gestational weeks there was no significant difference in the risk of stillbirth between ART and SC singletons. ART twins had a lower risk of stillbirth compared with SC twins, but when restricting the analysis to opposite-sex twins and excluding all monozygotic twins, there was no significant difference between the groups. Singletons conceived by ART had an overall increased risk of early neonatal death (adjusted odds ratio 1.54, 95% CI 1.28-1.85) and death within the first year after birth (1.45, 1.26-1.68). No difference regarding these two parameters was found when further adjusting for the gestational age [(0.97, 0.80-1.18) and (0.99, 0.85-1.16), respectively]. ART twins had a lower risk of early neonatal and infant deaths than SC twins, but no difference was found when restricting the analyses to opposite-sex twins. LIMITATIONS, REASON FOR CAUTION: We were not able to adjust for potential confounders, such as a prior history of stillbirth, induction of labour, body mass index or smoking. WIDER IMPLICATIONS OF THE FINDINGS: The risk of stillbirth in ART versus SC singletons was only increased for very early gestational ages (before 28 weeks). This might indicate that the current clinical management of ART pregnancies is sufficient regarding prevention of stillbirth during the third trimester. STUDY FUNDING/COMPETING INTEREST(S): No conflict of interest was reported. The European Society for Human Reproduction and Embryology (ESHRE), the University of Copenhagen, Denmark, the Danish Agency for Science, Technology and Innovation and Sahlgrenska University Hospital, Gothenburg, Sweden supported the project. The CoNARTaS group has received travel and meeting funding from the Nordic Society of Obstetrics and Gynecology (NFOG).


Assuntos
Peso ao Nascer/fisiologia , Morte do Lactente/etiologia , Técnicas de Reprodução Assistida/efeitos adversos , Natimorto/epidemiologia , Adulto , Estudos de Casos e Controles , Dinamarca/epidemiologia , Feminino , Finlândia/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Noruega/epidemiologia , Gravidez , Técnicas de Reprodução Assistida/estatística & dados numéricos , Risco , Suécia/epidemiologia
20.
Hum Reprod ; 29(4): 791-801, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24435776

RESUMO

STUDY QUESTION: What is the prevalence in a normal population of polycystic ovary syndrome (PCOS) according to the Rotterdam criteria versus revised criteria including anti-Müllerian hormone (AMH)? SUMMARY ANSWER: The prevalence of PCOS was 16.6% according to the Rotterdam criteria. When replacing the criterion for polycystic ovaries by antral follicle count (AFC) > 19 or AMH > 35 pmol/l, the prevalence of PCOS was 6.3 and 8.5%, respectively. WHAT IS KNOWN ALREADY?: The Rotterdam criteria state that two out of the following three criteria should be present in the diagnosis of PCOS: oligo-anovulation, clinical and/or biochemical hyperandrogenism and polycystic ovaries (AFC ≥ 12 and/or ovarian volume >10 ml). However, with the advances in sonography, the relevance of the AFC threshold in the definition of polycystic ovaries has been challenged, and AMH has been proposed as a marker of polycystic ovaries in PCOS. STUDY DESIGN, SIZE, DURATION: From 2008 to 2010, a prospective, cross-sectional study was performed including 863 women aged 20-40 years and employed at Copenhagen University Hospital, Rigshospitalet, Denmark. PARTICIPANTS/MATERIAL, SETTING, METHODS: We studied a subgroup of 447 women with a mean (±SD) age of 33.5 (±4.0) years who were all non-users of hormonal contraception. Data on menstrual cycle disorder and the presence of hirsutism were obtained. On cycle Days 2-5, or on a random day in the case of oligo- or amenorrhoea, sonographic and endocrine parameters were measured. MAIN RESULTS AND THE ROLE OF CHANCE: The prevalence of PCOS was 16.6% according to the Rotterdam criteria. PCOS prevalence significantly decreased with age from 33.3% in women < 30 years to 14.7% in women aged 30-34 years, and 10.2% in women ≥ 35 years (P < 0.001). In total, 53.5% fulfilled the criterion for polycystic ovaries with a significant age-related decrease from 69.0% in women < 30 years to 55.8% in women aged 30-34 years, and 42.8% in women ≥ 35 years (P < 0.001). AMH or age-adjusted AMH Z-score was found to be a reliable marker of polycystic ovaries in women with PCOS according to the Rotterdam criteria [area under the curve (AUC) 0.994; 95% confidence interval (CI): 0.990-0.999] and AUC 0.992 (95% CI: 0.987-0.998), respectively], and an AMH cut-off value of 18 pmol/l and AMH Z-score of -0.2 showed the best compromise between sensitivity (91.8 and 90.4%, respectively) and specificity (98.1 and 97.9%, respectively). In total, AFC > 19 or AMH > 35 occurred in 17.7 and 23.0%, respectively. The occurrence of AFC > 19 or AMH > 35 in the age groups < 30, 30-34 and ≥ 35 years was 31.0 and 35.7%, 18.8 and 21.3%, and 9.6 and 18.7%, respectively. When replacing the Rotterdam criterion for polycystic ovaries by AFC > 19 or AMH > 35 pmol/l, the prevalence of PCOS was 6.3 or 8.5%, respectively, and in the age groups < 30, 30-34 and ≥ 35 years, the prevalences were 17.9 and 22.6%, 3.6 and 5.6%, and 3.6 and 4.8%, respectively. LIMITATIONS, REASON FOR CAUTION: The participants of the study were all health-care workers, which may be a source of selection bias. Furthermore, the exclusion of hormonal contraceptive users from the study population may have biased the results, potentially excluding women with symptoms of PCOS. WIDER IMPLICATIONS OF THE FINDINGS: AMH may be used as a marker of polycystic ovaries in PCOS. However, future studies are needed to validate AMH threshold levels, and AMH Z-score may be appropriate to adjust for the age-related decline in the AFC. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: Not applicable.


Assuntos
Hormônio Antimülleriano/sangue , Síndrome do Ovário Policístico/epidemiologia , Adulto , Fatores Etários , Área Sob a Curva , Estudos Transversais , Dinamarca , Feminino , Humanos , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/diagnóstico por imagem , Prevalência , Estudos Prospectivos , Curva ROC , Ultrassonografia
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