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Publisher: Oxford University Press   (Total: 369 journals)

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Showing 1 - 200 of 369 Journals sorted alphabetically
Acta Biochimica et Biophysica Sinica     Hybrid Journal   (Followers: 6, SJR: 0.881, h-index: 38)
Adaptation     Hybrid Journal   (Followers: 8, SJR: 0.111, h-index: 4)
Aesthetic Surgery J.     Hybrid Journal   (Followers: 6, SJR: 1.538, h-index: 35)
African Affairs     Hybrid Journal   (Followers: 57, SJR: 1.512, h-index: 46)
Age and Ageing     Hybrid Journal   (Followers: 79, SJR: 1.611, h-index: 107)
Alcohol and Alcoholism     Hybrid Journal   (Followers: 14, SJR: 0.935, h-index: 80)
American Entomologist     Full-text available via subscription   (Followers: 5)
American Historical Review     Hybrid Journal   (Followers: 120, SJR: 0.652, h-index: 43)
American J. of Agricultural Economics     Hybrid Journal   (Followers: 41, SJR: 1.441, h-index: 77)
American J. of Epidemiology     Hybrid Journal   (Followers: 146, SJR: 3.047, h-index: 201)
American J. of Hypertension     Hybrid Journal   (Followers: 19, SJR: 1.397, h-index: 111)
American J. of Jurisprudence     Hybrid Journal   (Followers: 15)
American journal of legal history     Full-text available via subscription   (Followers: 4, SJR: 0.151, h-index: 7)
American Law and Economics Review     Hybrid Journal   (Followers: 26, SJR: 0.824, h-index: 23)
American Literary History     Hybrid Journal   (Followers: 12, SJR: 0.185, h-index: 22)
Analysis     Hybrid Journal   (Followers: 23)
Annals of Botany     Hybrid Journal   (Followers: 33, SJR: 1.912, h-index: 124)
Annals of Occupational Hygiene     Hybrid Journal   (Followers: 24, SJR: 0.837, h-index: 57)
Annals of Oncology     Hybrid Journal   (Followers: 48, SJR: 4.362, h-index: 173)
Annals of the Entomological Society of America     Full-text available via subscription   (Followers: 9, SJR: 0.642, h-index: 53)
Annals of Work Exposures and Health     Hybrid Journal  
AoB Plants     Open Access   (Followers: 4, SJR: 0.78, h-index: 10)
Applied Economic Perspectives and Policy     Hybrid Journal   (Followers: 18, SJR: 0.884, h-index: 31)
Applied Linguistics     Hybrid Journal   (Followers: 51, SJR: 1.749, h-index: 63)
Applied Mathematics Research eXpress     Hybrid Journal   (Followers: 1, SJR: 0.779, h-index: 11)
Arbitration Intl.     Full-text available via subscription   (Followers: 19)
Arbitration Law Reports and Review     Hybrid Journal   (Followers: 12)
Archives of Clinical Neuropsychology     Hybrid Journal   (Followers: 25, SJR: 0.96, h-index: 71)
Aristotelian Society Supplementary Volume     Hybrid Journal   (Followers: 2, SJR: 0.102, h-index: 20)
Arthropod Management Tests     Hybrid Journal   (Followers: 2)
Astronomy & Geophysics     Hybrid Journal   (Followers: 46, SJR: 0.144, h-index: 15)
Behavioral Ecology     Hybrid Journal   (Followers: 47, SJR: 1.698, h-index: 92)
Bioinformatics     Hybrid Journal   (Followers: 222, SJR: 4.643, h-index: 271)
Biology Methods and Protocols     Hybrid Journal  
Biology of Reproduction     Full-text available via subscription   (Followers: 10, SJR: 1.646, h-index: 149)
Biometrika     Hybrid Journal   (Followers: 18, SJR: 2.801, h-index: 90)
BioScience     Hybrid Journal   (Followers: 28, SJR: 2.374, h-index: 154)
Bioscience Horizons : The National Undergraduate Research J.     Open Access   (Followers: 1, SJR: 0.213, h-index: 9)
Biostatistics     Hybrid Journal   (Followers: 15, SJR: 1.955, h-index: 55)
BJA : British J. of Anaesthesia     Hybrid Journal   (Followers: 132, SJR: 2.314, h-index: 133)
BJA Education     Hybrid Journal   (Followers: 65, SJR: 0.272, h-index: 20)
Brain     Hybrid Journal   (Followers: 61, SJR: 6.097, h-index: 264)
Briefings in Bioinformatics     Hybrid Journal   (Followers: 43, SJR: 4.086, h-index: 73)
Briefings in Functional Genomics     Hybrid Journal   (Followers: 4, SJR: 1.771, h-index: 50)
British J. for the Philosophy of Science     Hybrid Journal   (Followers: 32, SJR: 1.267, h-index: 38)
British J. of Aesthetics     Hybrid Journal   (Followers: 24, SJR: 0.217, h-index: 18)
British J. of Criminology     Hybrid Journal   (Followers: 489, SJR: 1.373, h-index: 62)
British J. of Social Work     Hybrid Journal   (Followers: 77, SJR: 0.771, h-index: 53)
British Medical Bulletin     Hybrid Journal   (Followers: 7, SJR: 1.391, h-index: 84)
British Yearbook of Intl. Law     Hybrid Journal   (Followers: 26)
Bulletin of the London Mathematical Society     Hybrid Journal   (Followers: 3, SJR: 1.474, h-index: 31)
Cambridge J. of Economics     Hybrid Journal   (Followers: 55, SJR: 0.957, h-index: 59)
Cambridge J. of Regions, Economy and Society     Hybrid Journal   (Followers: 9, SJR: 1.067, h-index: 22)
Cambridge Quarterly     Hybrid Journal   (Followers: 10, SJR: 0.1, h-index: 7)
Capital Markets Law J.     Hybrid Journal  
Carcinogenesis     Hybrid Journal   (Followers: 2, SJR: 2.439, h-index: 167)
Cardiovascular Research     Hybrid Journal   (Followers: 11, SJR: 2.897, h-index: 175)
Cerebral Cortex     Hybrid Journal   (Followers: 37, SJR: 4.827, h-index: 192)
CESifo Economic Studies     Hybrid Journal   (Followers: 15, SJR: 0.501, h-index: 19)
Chemical Senses     Hybrid Journal   (Followers: 1, SJR: 1.436, h-index: 76)
Children and Schools     Hybrid Journal   (Followers: 5, SJR: 0.211, h-index: 18)
Chinese J. of Comparative Law     Hybrid Journal   (Followers: 3)
Chinese J. of Intl. Law     Hybrid Journal   (Followers: 19, SJR: 0.737, h-index: 11)
Chinese J. of Intl. Politics     Hybrid Journal   (Followers: 8, SJR: 1.238, h-index: 15)
Christian Bioethics: Non-Ecumenical Studies in Medical Morality     Hybrid Journal   (Followers: 11, SJR: 0.191, h-index: 8)
Classical Receptions J.     Hybrid Journal   (Followers: 17, SJR: 0.1, h-index: 3)
Clinical Infectious Diseases     Hybrid Journal   (Followers: 58, SJR: 4.742, h-index: 261)
Clinical Kidney J.     Open Access   (Followers: 4, SJR: 0.338, h-index: 19)
Community Development J.     Hybrid Journal   (Followers: 23, SJR: 0.47, h-index: 28)
Computer J.     Hybrid Journal   (Followers: 8, SJR: 0.371, h-index: 47)
Conservation Physiology     Open Access   (Followers: 1)
Contemporary Women's Writing     Hybrid Journal   (Followers: 11, SJR: 0.111, h-index: 3)
Contributions to Political Economy     Hybrid Journal   (Followers: 6, SJR: 0.313, h-index: 10)
Critical Values     Full-text available via subscription  
Current Legal Problems     Hybrid Journal   (Followers: 25)
Current Zoology     Full-text available via subscription   (SJR: 0.999, h-index: 20)
Database : The J. of Biological Databases and Curation     Open Access   (Followers: 11, SJR: 1.068, h-index: 24)
Digital Scholarship in the Humanities     Hybrid Journal   (Followers: 12)
Diplomatic History     Hybrid Journal   (Followers: 18, SJR: 0.296, h-index: 22)
DNA Research     Open Access   (Followers: 4, SJR: 2.42, h-index: 77)
Dynamics and Statistics of the Climate System     Open Access   (Followers: 2)
Early Music     Hybrid Journal   (Followers: 13, SJR: 0.124, h-index: 11)
Economic Policy     Hybrid Journal   (Followers: 47, SJR: 2.052, h-index: 52)
ELT J.     Hybrid Journal   (Followers: 25, SJR: 1.26, h-index: 23)
English Historical Review     Hybrid Journal   (Followers: 45, SJR: 0.311, h-index: 10)
English: J. of the English Association     Hybrid Journal   (Followers: 12, SJR: 0.144, h-index: 3)
Environmental Entomology     Full-text available via subscription   (Followers: 11, SJR: 0.791, h-index: 66)
Environmental Epigenetics     Open Access   (Followers: 1)
Environmental History     Hybrid Journal   (Followers: 25, SJR: 0.197, h-index: 25)
EP-Europace     Hybrid Journal   (Followers: 1, SJR: 2.201, h-index: 71)
Epidemiologic Reviews     Hybrid Journal   (Followers: 9, SJR: 3.917, h-index: 81)
ESHRE Monographs     Hybrid Journal  
Essays in Criticism     Hybrid Journal   (Followers: 15, SJR: 0.1, h-index: 6)
European Heart J.     Hybrid Journal   (Followers: 46, SJR: 6.997, h-index: 227)
European Heart J. - Cardiovascular Imaging     Hybrid Journal   (Followers: 9, SJR: 2.044, h-index: 58)
European Heart J. - Cardiovascular Pharmacotherapy     Full-text available via subscription   (Followers: 1)
European Heart J. - Quality of Care and Clinical Outcomes     Hybrid Journal  
European Heart J. Supplements     Hybrid Journal   (Followers: 8, SJR: 0.152, h-index: 31)
European J. of Cardio-Thoracic Surgery     Hybrid Journal   (Followers: 7, SJR: 1.568, h-index: 104)
European J. of Intl. Law     Hybrid Journal   (Followers: 141, SJR: 0.722, h-index: 38)
European J. of Orthodontics     Hybrid Journal   (Followers: 4, SJR: 1.09, h-index: 60)
European J. of Public Health     Hybrid Journal   (Followers: 22, SJR: 1.284, h-index: 64)
European Review of Agricultural Economics     Hybrid Journal   (Followers: 12, SJR: 1.549, h-index: 42)
European Review of Economic History     Hybrid Journal   (Followers: 25, SJR: 0.628, h-index: 24)
European Sociological Review     Hybrid Journal   (Followers: 37, SJR: 2.061, h-index: 53)
Evolution, Medicine, and Public Health     Open Access   (Followers: 11)
Family Practice     Hybrid Journal   (Followers: 13, SJR: 1.048, h-index: 77)
Fems Microbiology Ecology     Hybrid Journal   (Followers: 8, SJR: 1.687, h-index: 115)
Fems Microbiology Letters     Hybrid Journal   (Followers: 19, SJR: 1.126, h-index: 118)
Fems Microbiology Reviews     Hybrid Journal   (Followers: 24, SJR: 7.587, h-index: 150)
Fems Yeast Research     Hybrid Journal   (Followers: 13, SJR: 1.213, h-index: 66)
Foreign Policy Analysis     Hybrid Journal   (Followers: 21, SJR: 0.859, h-index: 10)
Forestry: An Intl. J. of Forest Research     Hybrid Journal   (Followers: 17, SJR: 0.903, h-index: 44)
Forum for Modern Language Studies     Hybrid Journal   (Followers: 6, SJR: 0.108, h-index: 6)
French History     Hybrid Journal   (Followers: 29, SJR: 0.123, h-index: 10)
French Studies     Hybrid Journal   (Followers: 19, SJR: 0.119, h-index: 7)
French Studies Bulletin     Hybrid Journal   (Followers: 10, SJR: 0.102, h-index: 3)
Gastroenterology Report     Open Access   (Followers: 2)
Genome Biology and Evolution     Open Access   (Followers: 10, SJR: 3.22, h-index: 39)
Geophysical J. Intl.     Hybrid Journal   (Followers: 31, SJR: 1.839, h-index: 119)
German History     Hybrid Journal   (Followers: 24, SJR: 0.437, h-index: 13)
GigaScience     Open Access   (Followers: 3)
Global Summitry     Hybrid Journal  
Glycobiology     Hybrid Journal   (Followers: 14, SJR: 1.692, h-index: 101)
Health and Social Work     Hybrid Journal   (Followers: 46, SJR: 0.505, h-index: 40)
Health Education Research     Hybrid Journal   (Followers: 12, SJR: 0.814, h-index: 80)
Health Policy and Planning     Hybrid Journal   (Followers: 21, SJR: 1.628, h-index: 66)
Health Promotion Intl.     Hybrid Journal   (Followers: 19, SJR: 0.664, h-index: 60)
History Workshop J.     Hybrid Journal   (Followers: 25, SJR: 0.313, h-index: 20)
Holocaust and Genocide Studies     Hybrid Journal   (Followers: 22, SJR: 0.115, h-index: 13)
Human Molecular Genetics     Hybrid Journal   (Followers: 10, SJR: 4.288, h-index: 233)
Human Reproduction     Hybrid Journal   (Followers: 74, SJR: 2.271, h-index: 179)
Human Reproduction Update     Hybrid Journal   (Followers: 15, SJR: 4.678, h-index: 128)
Human Rights Law Review     Hybrid Journal   (Followers: 60, SJR: 0.7, h-index: 21)
ICES J. of Marine Science: J. du Conseil     Hybrid Journal   (Followers: 53, SJR: 1.233, h-index: 88)
ICSID Review     Hybrid Journal   (Followers: 8)
ILAR J.     Hybrid Journal   (Followers: 1, SJR: 1.099, h-index: 51)
IMA J. of Applied Mathematics     Hybrid Journal   (SJR: 0.329, h-index: 26)
IMA J. of Management Mathematics     Hybrid Journal   (Followers: 2, SJR: 0.351, h-index: 20)
IMA J. of Mathematical Control and Information     Hybrid Journal   (Followers: 2, SJR: 0.661, h-index: 28)
IMA J. of Numerical Analysis - advance access     Hybrid Journal   (SJR: 2.032, h-index: 44)
Industrial and Corporate Change     Hybrid Journal   (Followers: 8, SJR: 1.37, h-index: 81)
Industrial Law J.     Hybrid Journal   (Followers: 29, SJR: 0.184, h-index: 15)
Information and Inference     Free  
Integrative and Comparative Biology     Hybrid Journal   (Followers: 7, SJR: 1.911, h-index: 90)
Interacting with Computers     Hybrid Journal   (Followers: 10, SJR: 0.529, h-index: 59)
Interactive CardioVascular and Thoracic Surgery     Hybrid Journal   (Followers: 4, SJR: 0.743, h-index: 35)
Intl. Data Privacy Law     Hybrid Journal   (Followers: 27)
Intl. Health     Hybrid Journal   (Followers: 4, SJR: 0.835, h-index: 15)
Intl. Immunology     Hybrid Journal   (Followers: 4, SJR: 1.613, h-index: 111)
Intl. J. for Quality in Health Care     Hybrid Journal   (Followers: 32, SJR: 1.593, h-index: 69)
Intl. J. of Constitutional Law     Hybrid Journal   (Followers: 50, SJR: 0.613, h-index: 19)
Intl. J. of Epidemiology     Hybrid Journal   (Followers: 115, SJR: 4.381, h-index: 145)
Intl. J. of Law and Information Technology     Hybrid Journal   (Followers: 3, SJR: 0.247, h-index: 8)
Intl. J. of Law, Policy and the Family     Hybrid Journal   (Followers: 18, SJR: 0.307, h-index: 15)
Intl. J. of Lexicography     Hybrid Journal   (Followers: 8, SJR: 0.404, h-index: 18)
Intl. J. of Low-Carbon Technologies     Open Access   (Followers: 1, SJR: 0.457, h-index: 12)
Intl. J. of Neuropsychopharmacology     Open Access   (Followers: 4, SJR: 1.69, h-index: 79)
Intl. J. of Public Opinion Research     Hybrid Journal   (Followers: 8, SJR: 0.906, h-index: 33)
Intl. J. of Refugee Law     Hybrid Journal   (Followers: 34, SJR: 0.231, h-index: 21)
Intl. J. of Transitional Justice     Hybrid Journal   (Followers: 13, SJR: 0.833, h-index: 12)
Intl. Mathematics Research Notices     Hybrid Journal   (Followers: 1, SJR: 2.052, h-index: 42)
Intl. Mathematics Research Surveys - advance access     Hybrid Journal  
Intl. Political Sociology     Hybrid Journal   (Followers: 24, SJR: 1.339, h-index: 19)
Intl. Relations of the Asia-Pacific     Hybrid Journal   (Followers: 17, SJR: 0.539, h-index: 17)
Intl. Studies Perspectives     Hybrid Journal   (Followers: 7, SJR: 0.998, h-index: 28)
Intl. Studies Quarterly     Hybrid Journal   (Followers: 33, SJR: 2.184, h-index: 68)
Intl. Studies Review     Hybrid Journal   (Followers: 17, SJR: 0.783, h-index: 38)
ISLE: Interdisciplinary Studies in Literature and Environment     Hybrid Journal   (Followers: 1, SJR: 0.155, h-index: 4)
ITNOW     Hybrid Journal   (Followers: 2, SJR: 0.102, h-index: 4)
J. of African Economies     Hybrid Journal   (Followers: 15, SJR: 0.647, h-index: 30)
J. of American History     Hybrid Journal   (Followers: 38, SJR: 0.286, h-index: 34)
J. of Analytical Toxicology     Hybrid Journal   (Followers: 13, SJR: 1.038, h-index: 60)
J. of Antimicrobial Chemotherapy     Hybrid Journal   (Followers: 20, SJR: 2.157, h-index: 149)
J. of Antitrust Enforcement     Hybrid Journal   (Followers: 1)
J. of Applied Poultry Research     Hybrid Journal   (Followers: 3, SJR: 0.563, h-index: 43)
J. of Biochemistry     Hybrid Journal   (Followers: 43, SJR: 1.341, h-index: 96)
J. of Chromatographic Science     Hybrid Journal   (Followers: 18, SJR: 0.448, h-index: 42)
J. of Church and State     Hybrid Journal   (Followers: 11, SJR: 0.167, h-index: 11)
J. of Competition Law and Economics     Hybrid Journal   (Followers: 34, SJR: 0.442, h-index: 16)
J. of Complex Networks     Hybrid Journal   (Followers: 1, SJR: 1.165, h-index: 5)
J. of Conflict and Security Law     Hybrid Journal   (Followers: 11, SJR: 0.196, h-index: 15)
J. of Consumer Research     Full-text available via subscription   (Followers: 38, SJR: 4.896, h-index: 121)
J. of Crohn's and Colitis     Hybrid Journal   (Followers: 9, SJR: 1.543, h-index: 37)
J. of Cybersecurity     Hybrid Journal   (Followers: 2)
J. of Deaf Studies and Deaf Education     Hybrid Journal   (Followers: 8, SJR: 0.69, h-index: 36)
J. of Design History     Hybrid Journal   (Followers: 15, SJR: 0.166, h-index: 14)
J. of Economic Entomology     Full-text available via subscription   (Followers: 6, SJR: 0.894, h-index: 76)
J. of Economic Geography     Hybrid Journal   (Followers: 32, SJR: 2.909, h-index: 69)
J. of Environmental Law     Hybrid Journal   (Followers: 25, SJR: 0.457, h-index: 20)
J. of European Competition Law & Practice     Hybrid Journal   (Followers: 19)
J. of Experimental Botany     Hybrid Journal   (Followers: 13, SJR: 2.798, h-index: 163)
J. of Financial Econometrics     Hybrid Journal   (Followers: 21, SJR: 1.314, h-index: 27)
J. of Global Security Studies     Hybrid Journal   (Followers: 2)
J. of Heredity     Hybrid Journal   (Followers: 3, SJR: 1.024, h-index: 76)
J. of Hindu Studies     Hybrid Journal   (Followers: 7, SJR: 0.186, h-index: 3)
J. of Hip Preservation Surgery     Open Access  
J. of Human Rights Practice     Hybrid Journal   (Followers: 21, SJR: 0.399, h-index: 10)
J. of Infectious Diseases     Hybrid Journal   (Followers: 39, SJR: 4, h-index: 209)
J. of Insect Science     Open Access   (Followers: 9, SJR: 0.388, h-index: 31)

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Journal Cover Human Reproduction
  [SJR: 2.271]   [H-I: 179]   [74 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0268-1161 - ISSN (Online) 1460-2350
   Published by Oxford University Press Homepage  [369 journals]
  • Euploidy rates in donor egg cycles significantly differ between fertility
    • Authors: Munné SS; Alikani MM, Ribustello LL, et al.
      Abstract: AbstractSTUDY QUESTIONDo external factors affect euploidy in egg donor cycles'SUMMARY ANSWERThe study demonstrates that during human assisted reproduction, embryonic chromosome abnormalities may be partly iatrogenic.WHAT IS KNOWN ALREADYChromosome abnormalities have been linked in the past to culture conditions such as temperature and Ph variations, as well as hormonal stimulation. Those reports were performed with older screening techniques (FISH), or ART methods no longer in use, and the subjects studied were not a homogeneous group.STUDY DESIGN, SIZE, DURATIONA total of 1645 donor oocyte cycles and 13 282 blastocyst biopsies from 42 fertility clinics were included in this retrospective cohort study. Samples from donor cycles with PGS attempted between September 2011 and July 2015 were included.PARTICIPANTS/MATERIALS, SETTING, METHODSPGS cycles from multiple fertility clinics referred to Reprogenetics (Livingston, NJ) that involved only oocyte donation were included in this study. Testing was performed by array comparative genomic hybridization (aCGH). Ploidy data were analyzed using Generalized Linear Mixed Models with logistic regression using a logit link function considering a number of variables that represent fixed and random effects.MAIN RESULTS AND THE ROLE OF CHANCEEuploidy rate was associated with the referring center and independent of almost all the parameters examined except donor age and testing technology. Average euploidy rate per center ranged from 39.5 to 82.5%. The mean expected rate of euploidy was 68.4%, but there are variations in this rate associated with the center effect.LIMITATIONS, REASONS FOR CAUTIONData set does not include details of the donor selection process, donor race or ethnic origin, ovarian reserve or ovarian responsiveness. Due to the retrospective nature of the study, associations are apparent, however, causality cannot be established. Discrepancies in regard to completeness and homogeneity of data exist due to data collection from over 40 different clinics.WIDER IMPLICATIONS OF THE FINDINGSThis is the first study to show a strong association between center-specific ART treatment practices and the incidence of chromosome abnormality in human embryos, although the meiotic or mitotic origin of these abnormalities could not be determined using these technologies. Given the widespread applications of ART in both subfertile and fertile populations, our findings should be of interest to the medical community in general as well as the ART community in particular.STUDY FUNDING/COMPETING INTEREST(S)No external funds were used for this study. S. Munne is a founding principle of Reprogenetics/current employee of Cooper Genomics. M Alikani's spouse is a founding principle of Reprogenetics/current consultant for Cooper Genomics. The remaining authors have no conflicts to declare.
      PubDate: 2017-03-02
  • Improving oocyte quality by transfer of autologous mitochondria from fully
           grown oocytes
    • Authors: Kristensen S; Pors S, Andersen C.
      Abstract: AbstractOlder women are often the most challenging group of patients in fertility clinics due to a decline in both number and overall quality of oocytes. The quality of oocytes has been linked to mitochondrial dysfunction. In this mini-review, we discuss this hypothesis and suggest alternative treatment options using autologous mitochondria to potentially augment pregnancy potential in ART. Autologous transfer of mitochondria from the patient's own germline cells has attracted much attention as a possible new treatment to revitalize deficient oocytes. IVF births have been reported after transfer of oogonial precursor cell-derived mitochondria; however, the source and quality of the mitochondria are still unclear. In contrast, fully grown oocytes are loaded with mitochondria which have passed the genetic bottleneck and are likely to be of high quality. An increased supply of such oocytes could potentially be obtained by in vitro follicle activation of ovarian cortical biopsies or from surplus immature oocytes collected from women undergoing ART or fertility preservation of ovarian tissue. Taken together, autologous oocytes are not necessarily a limiting resource in ART as fully grown oocytes with high quality mitochondria can be obtained from natural or stimulated ovaries and potentially be used to improve both quality and quantity of oocytes available for fertility treatment.
      PubDate: 2017-03-02
  • Dysmorphic patterns are associated with cytoskeletal alterations in human
    • Authors: Dal Canto M; Guglielmo M, Mignini Renzini M, et al.
      Abstract: AbstractSTUDY QUESTIONAre specific morphological anomalies in human mature oocytes, as revealed by transmitted light microscopy, associated with intrinsic damage to the meiotic spindle and actin cytoskeleton'SUMMARY ANSWERAggregates of smooth endoplasmic reticulum (SER) and domains of centrally localized granular cytoplasm (GC) reflect intrinsic damage to the oocyte cytoskeleton, namely alterations in spindle size, chromosome misalignment and cortical actin disorganization.WHAT IS KNOWN ALREADYIn preparation for ICSI, oocytes are often selected for use in treatment by morphological criteria, but the rationale and implications of this practice are controversial. Very little information is available on the relationship between oocyte morphology and intrinsic cellular characteristics, such as the actin cytoskeleton, meiotic spindle and chromosome alignment.STUDY DESIGN, SIZE, DURATIONA total of 170 metaphase II (MII) oocytes were donated by consenting IVF patients and analysed; 62 were classified as morphologically normal (control), 54 had SER clusters and 54 had centrally localized GC.PARTICIPANTS/MATERIALS, SETTING, METHODSSupernumerary oocytes were fixed within 3 h from recovery and stained for tubulin, chromatin and actin. Spindles were analysed for 1D and 2D characteristics by high-performance confocal microscopy. Chromosomes were classified as scattered or aligned and the conformation and intensity of cortical actin was evaluated.MAIN RESULTS AND THE ROLE OF CHANCEIn comparison with control oocytes, both SER and GC oocytes showed greater spindle length (P = 0.033 and 0.003, respectively) and GC oocytes also showed greater spindle width (P= 0.049) and area (P= 0.036). Control and SER oocytes had statistically comparable rates of chromosome displacement from the metaphase plate, unlike GC oocytes where chromosome displacement occurred at higher rate (P = 0.013). In situations where a complete Z-stack was reconstructed from a polar angle, chromosome disposition was classified as being normal when two sets of concentric arrays were visible. Based on these parameters, the proportions of oocytes with normal chromosomal arrangement or partial/total disarrangement was not statistically different between control and SER oocytes. Conversely, in GC oocytes, chromosome disarrangement was higher (P = 0.002). All control oocytes displayed a continuous meshwork of suboolemmal actin, which appeared as an uninterrupted ring in thin optical sections. In contrast, in SER and  GC groups, integrity of suboolemmal actin was observed in only 66.7 and 42.9% of oocytes, respectively (P = 0.0001).LARGE SCALE DATAN/A.LIMITATIONS REASON FOR CAUTIONOnly two of several known oocyte dysmorphisms were investigated, while oocyte quality was assessed only by cytoskeletal criteria.WIDER IMPLICATIONS OF THE FINDINGSThis study represents a significant step toward a more objective assessment of oocyte morphology, offering information that can assist embryologists to make a more aware and rationally founded decision on whether, and with what possible implications, oocytes with certain dysmorphic characters should be used for treatment or discarded. More generally, it also demonstrates that morphometric parameters of the cytoskeleton and chromosome organization can be used as biomarkers of oocyte quality.STUDY FUNDING AND COMPETING INTEREST(S)This study was funded by Biogenesi Reproductive Medicine Centre (Monza, Italy). All authors declare no conflict of interests.
      PubDate: 2017-03-01
  • Clustering of PCOS-like traits in naturally hyperandrogenic female rhesus
    • Authors: Abbott DH; Rayome BH, Dumesic DA, et al.
      Abstract: AbstractSTUDY QUESTIONDo naturally occurring, hyperandrogenic (≥1 SD of population mean testosterone, T) female rhesus monkeys exhibit traits typical of women with polycystic ovary syndrome (PCOS)'SUMMARY ANSWERHyperandrogenic female monkeys exhibited significantly increased serum levels of androstenedione (A4), 17-hydroxyprogesterone (17-OHP), estradiol (E2), LH, antimullerian hormone (AMH), cortisol, 11-deoxycortisol and corticosterone, as well as increased uterine endometrial thickness and evidence of reduced fertility, all traits associated with PCOS.WHAT IS KNOWN ALREADYProgress in treating women with PCOS is limited by incomplete knowledge of its pathogenesis and the absence of naturally occurring PCOS in animal models. A female macaque monkey, however, with naturally occurring hyperandrogenism, anovulation and polyfollicular ovaries, accompanied by insulin resistance, increased adiposity and endometrial hyperplasia, suggests naturally occurring origins for PCOS in nonhuman primates.STUDY DESIGN, SIZE, DURATIONAs part of a larger study, circulating serum concentrations of selected pituitary, ovarian and adrenal hormones, together with fasted insulin and glucose levels, were determined in a single, morning blood sample obtained from 120 apparently healthy, ovary-intact, adult female rhesus monkeys (Macaca mulatta) while not pregnant or nursing. The monkeys were then sedated for somatometric and ultrasonographic measurements.PARTICIPANTS/MATERIALS, SETTING, METHODSFemale monkeys were of prime reproductive age (7.2 ± 0.1 years, mean ± SEM) and represented a typical spectrum of adult body weight (7.4 ± 0.2 kg; maximum 12.5, minimum 4.6 kg). Females were defined as having normal (n = 99) or high T levels (n = 21; ≥1 SD above the overall mean, 0.31 ng/ml). Electronic health records provided menstrual and fecundity histories. Steroid hormones were determined by tandem LC–MS-MS; AMH was measured by enzymeimmunoassay; LH, FSH and insulin were determined by radioimmunoassay; and glucose was read by glucose meter. Most analyses were limited to 80 females (60 normal T, 20 high T) in the follicular phase of a menstrual cycle or anovulatory period (serum progesterone
      PubDate: 2017-03-01
  • Polycystic ovary syndrome is associated with anogenital distance, a marker
           of prenatal androgen exposure
    • Authors: Wu Y; Zhong G, Chen S, et al.
      Abstract: AbstractSTUDY QUESTIONIs the presence of polycystic ovary syndrome (PCOS) associated with anogenital distance (AGD), a biomarker for the prenatal hormonal environment'SUMMARY ANSWERThe presence of PCOS is associated with longer AGD.WHAT IS KNOWN ALREADYAlthough the aetiology of PCOS is unclear, emerging data suggest that the natural history of PCOS may originate from intrauterine life. Prenatal exposure to androgen hormones is considered an important factor of PCOS. AGD is the distance measured from the anus to the genital tubercle and there is considerable evidence in humans and animals to support AGD as a sensitive biomarker of prenatal androgen activity.STUDY DESIGN, SIZE, DURATIONThis case–control study of 156 PCOS patients and 180 reproductively healthy women (control subjects) was performed from October 2015 to July 2016.PARTICIPANTS/MATERIALS, SETTING, METHODSThe patients and controls were recruited from the out-patient Department of Gynecology of Sun Yat-sen Memorial Hospital. Participants completed health questionnaires and provided a blood sample for evaluation of serum reproductive hormone profiles. Anthropometric indices of AGDAF (anus-fourchette) and AGDAC (anus-clitoris) were measured in all subjects. We used logistic regression to estimate the association between the presence of PCOS and AGD measurements while accounting for important confounders, including age and BMI. Multiple linear regression was used to analyse the relationships between PCOS characteristics (e.g. polycystic ovaries and total testosterone (T)) and two measurements of AGD in the PCOS group and controls.MAIN RESULTS AND THE ROLE OF CHANCEOverall, logistic regression showed that women with AGDAF in the highest tertile were 18.8 times (95% CI 9.6–36.6; P < 0.001) more likely to have PCOS compared with those in the lowest tertile. Women with AGDAC in the highest tertile were 6.7 times (95% CI 3.7–12.1; P < 0.001) more likely to have PCOS than those in the lowest tertile. In the PCOS group, multiple linear regression analyses revealed that both AGD measurements were positively associated with T levels (β = 0.246 for AGDAC, β = 0.368 for AGDAF; P = 0.003 and P < 0.001, respectively), and AGDAF was positively associated with the presence of polycystic ovaries (β = 0.279; P < 0.001). In the controls, a positive association was found only between T levels with AGDAF (β = 0.177, P = 0.020), whereas no associations were found between the remaining covariates and AGD measurements.LIMITATIONS, REASONS FOR CAUTIONAs this was an observational study, causal inference cannot be obtained.WIDER IMPLICATIONS OF THE FINDINGSThis study suggests that PCOS may originate in intrauterine life, and be affected by prenatal exposure to androgens.STUDY FUNDING/COMPETING INTEREST(S)This study was supported by funds obtained from the Science Technology Research Project of Guangdong Province (2010B031600058 and 2015A030310083) and the Major Science Technology Research Project of Guangdong Province (ZKM05602S). The authors have no competing interests to declare.TRIAL REGISTRATION NUMBERNot applicable.
      PubDate: 2017-03-01
  • Overweight and obese but not normal weight women with PCOS are at
           increased risk of Type 2 diabetes mellitus—a prospective
           population-based cohort study
    • Authors: Ollila MM; West SS, Keinänen-Kiukaaniemi SS, et al.
      PubDate: 2017-02-25
  • Changes in practice make analysis of historical databases irrelevant for
           comparison between Natural and Stimulated IVF
    • Authors: Nargund G; Campbell S.
      PubDate: 2017-02-25
  • Reply: Rapid changes in practice make analysis of historical databases
           irrelevant for contemporary counselling
    • Authors: Sunkara S; LaMarca A, Polyzos N, et al.
      PubDate: 2017-02-25
  • Soluble VCAM-1/soluble ICAM-1 ratio is a promising biomarker for
           diagnosing endometriosis
    • Authors: Kuessel L; Wenzl R, Proestling K, et al.
      Abstract: AbstractSTUDY QUESTIONDo cell adhesion molecules play a role in endometriosis, and can they be used as a biomarker for diagnosing endometriosis'SUMMARY ANSWERAltered expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in the endometrium and peritoneum may play a key role in endometriosis and the soluble VCAM-1/soluble ICAM-1 ratio is a promising biomarker.WHAT IS KNOWN ALREADYCell adhesion molecules are cell surface proteins that mediate cellular adherence, inflammatory and immune responses, and cancer-related biological processes. Altered expression of VCAM-1 and ICAM-1 in women with endometriosis has been investigated previously; however, gene expression levels in tissues and protein levels in the serum have not been investigated in the same patients.STUDY DESIGN SIZE, DURATIONWe performed a prospective, longitudinal study (the Endometriosis Marker Austria) in patients who underwent a laparoscopy for benign gynecological pathology in a university-based tertiary referral center for endometriosis. From a total of 138 women who were included in the study from July 2013 through September 2014, 97 had not received hormonal treatment for at least 3 months prior to recruitment and were included in the analysis; 49 (50.5%) of these women had endometriosis, and the 48 (49.5%) who did not have endometriosis served as a control group.PARTICIPANTS/MATERIALS SETTING METHODSDuring laparoscopy, tissue samples were obtained from ectopic and eutopic endometrium, and from normal pelvic peritoneum. In addition, serum samples were collected immediately before and 6–10 weeks after surgery. The mRNA levels of VCAM-1, ICAM-1 and epithelial cell adhesion molecule (EpCAM) were measured using quantitative real-time PCR, and serum protein levels of soluble VCAM-1 (sVCAM-1), ICAM-1 (sICAM-1) and EpCAM (sEpCAM) were measured using ELISA and correlated with endometriosis status.MAIN RESULTS AND THE ROLE OF CHANCEThe mRNA levels of both VCAM-1 and ICAM-1 were higher in ectopic endometriotic lesions than in eutopic endometrium (P < 0.001). Moreover, the mRNA levels of both VCAM-1 and ICAM-1 were higher in normal peritoneum samples obtained from women with endometriosis compared to those from controls (P = 0.038 and P = 0.009). The mRNA levels of VCAM-1 were also higher in the eutopic endometrium samples obtained from women with endometriosis compared to controls (P = 0.018). With respect to serum protein levels, compared to controls, the women with endometriosis had lower serum levels of sICAM-1 (P = 0.042) and higher levels of sVCAM-1 (P < 0.001). Our analysis revealed that the serum levels of sVCAM-1 were not affected by lesion entity, menstrual cycle phase or disease severity. An receiver operating characteristics curve, calculated to determine whether preoperative serum sVCAM-1 concentration can be used to predict endometriosis, found an AUC of 0.868 with 80% specificity and 84% sensitivity at a cutoff value of 370 pg/ml. This predictive performance can be further improved by calculation of the sVCAM-1/sICAM-1 ratio, leading to an AUC of 0.929 with 86.7% specificity and 90.3% sensitivity at a cutoff ratio value of 1.55.LARGE SCALE DATANot applicable.LIMITATIONS REASONS FOR CAUTIONThe relatively small sample size in the expression analyses is a possible limitation of this study.WIDER IMPLICATIONS OF THE FINDINGSOur findings could contribute to an improved understanding of the pathogenesis of endometriosis and the role of cell adhesion molecules. In addition, the results may lead to the development of new, non-invasive tools for diagnosing endometriosis. The ability to diagnose patients by measuring serum sVCAM-1 levels or the sVCAM-1/sICAM-1 ratio would have considerable clinical value.STUDY FUNDING/COMPETING INTEREST(S)The Ingrid Flick Foundation (Grant no. FA751C0801), which played no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors declare no competing interests.
      PubDate: 2017-02-23
  • Gay fathers’ motivations for and feelings about surrogacy as a path
           to parenthood
    • Authors: Blake LL; Carone NN, Raffanello EE, et al.
      Abstract: AbstractSTUDY QUESTIONWhy do gay men choose to start their families through surrogacy'SUMMARY ANSWERMost fathers chose surrogacy because they considered adoption to be a less desirable and/or accessible path to parenthood.WHAT IS KNOWN ALREADYLittle is known of gay fathers’ motivations to use surrogacy as a path to parenthood over and above other forms of family building, such as adoption, and no studies have examined fathers’ satisfaction with the surrogacy process.STUDY DESIGN, SIZE, DURATIONThis study used a cross-sectional design as part of a larger investigation of parent–child relationships and child adjustment in 40 gay father surrogacy families. Multiple strategies (e.g. surrogacy agencies, social events and snowballing) were used to recruit as diverse a sample as possible. Data were obtained from 74 fathers (in 6 families only 1 father was available for interview).PARTICIPANTS/MATERIALS, SETTING, METHODSemi-structured interviews, lasting ~1 h, were conducted in the family home (65%) or over Skype (35%) with 74 gay fathers (35 genetic fathers, 32 non-genetic fathers and 7 fathers who did not know or did not disclose who the genetic father was), when the children were 3–9 years old.MAIN RESULTS AND THE ROLE OF CHANCEGenetic and non-genetic fathers were just as likely to want to become parents and had similar motivations for choosing surrogacy as a path to parenthood. Most fathers (N = 55, 74%) were satisfied with surrogacy and were satisfied (N = 31. 42%) or had neutral feelings (N = 21, 28%) about their choice of who would be the genetic father. Most fathers received supportive reactions to their decision to use surrogacy from both families of origin (e.g. parents, siblings) (N = 47, 64%) and from friends (N = 63, 85%).LIMITATIONS, REASONS FOR CAUTIONAlthough diverse recruitment strategies were used, data were obtained from a volunteer sample. Therefore, the possibility that fathers who had a positive surrogacy experience may have been more likely to participate in the study, and therefore introduce bias, cannot be ruled out. Due to the high average annual income of the fathers in the study, findings may not generalize to gay fathers with lower incomes.WIDER IMPLICATIONS OF THE FINDINGSIt is often assumed that parents’ primary motivation for using ART is to have a genetic connection to the child. This study revealed that whilst genetic fatherhood was important for some gay fathers in surrogacy families, it was not important for all. This information will be of use to surrogacy agencies and organizations supporting men who are considering the different routes to parenthood.STUDY FUNDING/COMPETING INTEREST(S)This work was funded by the Wellcome Trust [097857/Z/11/Z] and the Jacob's Foundation. None of the authors has any conflict of interest to declare.TRIAL REGISTRATION NUMBERN/A.
      PubDate: 2017-02-23
  • Impact of thyroid autoimmunity in euthyroid women on live birth rate after
    • Authors: Unuane DD; Velkeniers BB, Bravenboer BB, et al.
      Abstract: AbstractSTUDY QUESTIONDoes thyroid autoimmunity (TAI) predict live birth rate in euthyroid women after one treatment cycle in IUI patients'SUMMARY ANSWERTAI as such does not influence pregnancy outcome after IUI treatment.WHAT IS KNOWN ALREADYThe role of TAI on pregnancy outcome in the case of IVF/ICSI is largely debated in the literature. This is the first study to address this issue in the case of IUI.STUDY DESIGN, SIZE, DURATIONThis was a retrospective cohort study. A two-armed study design was performed: patients anti-thyroid peroxidase (TPO)+ and patients anti-TPO−. All patients who started their first IUI cycle in our fertility center between 1 January 2010 and 31 December 2014 were included. After exclusion of those patients with or being treated for thyroid dysfunction, 3143 patients were finally included in the study.PARTICIPANTS/MATERIALS, SETTING, METHODSAfter approval by the institutional review board we retrospectively included all patients who started their first IUI cycle in our center between 1 January 2010 and 31 December 2014 with follow-up of outcome until 31 December 2015. Patients with clinical thyroid dysfunction were excluded (thyroid-stimulating hormone (TSH) 5 mIU/l) as were patients under treatment with levothyroxine or anti-thyroid drugs. These patients were then divided into two main groups: patients anti-TPO+ and patients anti-TPO− (= control group). Live birth delivery after 25 weeks of gestation was taken as the primary endpoint of our study. As a secondary endpoint, we evaluated differences in live birth delivery after IUI according to different upper limits of preconception TSH thresholds (
      PubDate: 2017-02-23
  • Levels of trophectoderm mitochondrial DNA do not predict the reproductive
           potential of sibling embryos
    • Authors: Treff NR; Zhan Y, Tao X, et al.
      Abstract: AbstractSTUDY QUESTIONWhat is the predictive value of trophectoderm mitochondrial DNA (mtDNA) quantity for blastocyst reproductive potential'SUMMARY ANSWERThis study demonstrates that, within a given cohort, mtDNA quantitation does not distinguish between embryos that implant and embryos that do not implant after double embryo transfer (DET).WHAT IS ALREADY KNOWNAn association between implantation failure and increased quantities of mtDNA has been observed in two studies but not in a third.STUDY DESIGN, SIZE AND DURATIONA total of 187 patients (nine who received donor oocytes) with DET of one male and one female euploid blastocyst were included in this retrospective study, with 69 singleton deliveries providing the primary dataset to evaluate the predictive value of mtDNA for reproductive potential between January 2010 and July 2016.PARTICIPANTS/MATERIALS, SETTING AND METHODMtDNA was quantified in cell lines to validate the quantitative PCR assay on limited quantities of starting material and then applied to 374 blastocyst biopsies. Pregnancies resulting in a singleton outcome were analyzed and newborn gender was utilized as a means to identify the implanted embryo. MtDNA quantity was then compared between implanted and non-implanted embryos in order to define the predictive value of mtDNA content for reproductive potential in this subset of patients.MAIN RESULTS AND THE ROLE OF CHANCEAn initial comparison of mtDNA levels between all successful and unsuccessful embryos revealed no significant differences. In order to control for patient-specific variables, gender was subsequently used to identify the implanted embryo in DETs resulting in a singleton (n = 69). No systematic difference in relative mtDNA quantity was detected between implanted and non-implanted embryos.LIMITATIONS, REASONS FOR CAUTIONThis study was conducted at a single center and did not evaluate the entire cohort of embryos from each patient to evaluate cohort specific variation in mtDNA quantity. Although the largest of its kind so far, the sample size of DETs leading to a singleton was relatively small.WIDER IMPLICATIONS OF THE FINDINGSThese data highlight the importance of control over patient-specific variables when evaluating candidate biomarkers of reproductive potential. All current available data suggest that mtDNA quantification needs further study before its clinical use to augment embryo selection.STUDY FUNDING/COMPETING INTERESTSThe authors have no potential conflict of interest to declare. No external funding was obtained for this study.TRIAL REGISTRATION NUMBERNot applicable.
      PubDate: 2017-02-23
  • ‘Forever Young’†—Testosterone replacement therapy: a blockbuster
           drug despite flabby evidence and broken promises
    • Authors: Busnelli A; Somigliana E, Vercellini P.
      Abstract: AbstractIn the last decade, testosterone replacement therapy (TRT) has been increasingly prescribed to treat a controversial condition known as ‘late-onset hypogonadism (LOH)’. This syndrome is diagnosed in men who, for no discernible reason other than older age, obesity or ill health have serum testosterone concentrations below the normal range for healthy young men and report one or more of the following symptoms: muscle weakness or wasting, mood, behaviour and cognition-related symptoms and sexual function or libido impairment. However, recent evidence has demonstrated that testosterone drugs do not substantially ameliorate these symptoms and, more worryingly, that their long-term use may be associated with severe adverse effects (i.e. increased risk of prostate cancer, stroke and myocardial infarction, worsening of benign prostatic hyperplasia symptoms and testicular atrophy). Nonetheless, testosterone drugs have exhibited extraordinary commercial success and their pharmaceutical sales are steadily rising. Behind this apparently unjustifiable trend there are deliberate, well designed direct and indirect pharmaceutical marketing initiatives that exploit the conviction rooted in contemporary society that testosterone can reverse the effects of ageing and ensure social accomplishment. Commercial mechanisms have laid the foundation for disease mongering of LOH and also have resulted a considerable expansion of the indications for treatment. This promotion model deserves particular attention since it is applicable to any drug with a purportedly favourable risk-benefit ratio not supported by evidence.
      PubDate: 2017-02-23
  • Influence of the disease label ‘polycystic ovary syndrome’ on
           intention to have an ultrasound and psychosocial outcomes: a randomised
           online study in young women
    • Authors: Copp T; McCaffery K, Azizi L, et al.
      Abstract: AbstractSTUDY QUESTIONDoes the disease label ‘polycystic ovary syndrome’ (PCOS) have an impact on desire for medical testing and psychosocial outcomes'SUMMARY ANSWERWhen given the disease label PCOS in a hypothetical scenario, participants had higher intention to have an ultrasound, perceived the condition to be more severe and had lower self-esteem than those not given the disease label.WHAT IS KNOWN ALREADYWidening diagnostic criteria and improved imaging sensitivity have increased the number of reproductive-aged women diagnosed with PCOS from 4% to 8% to up to 21%. The uncertain clinical benefit of knowing this diagnosis needs to be weighed against the potential for poor psychological outcomes in women labelled with PCOS.STUDY DESIGN, SIZE, DURATIONThis experimental online study randomised 181 young women to receive one of four hypothetical scenarios of a doctor's visit in a 2 (PCOS disease label versus no disease label) x 2 (information about unreliability of ultrasounds in clarifying diagnosis versus no information) design.PARTICIPANTS/MATERIALS, SETTING, METHODSParticipants were university students (mean age: 19.4). After presenting the scenario, intention to have an ultrasound, negative affect, self-esteem, perceived severity of condition, credibility of the doctor and interest in a second opinion were measured. Participants were then presented with a second scenario, where the possibility of PCOS overdiagnosis was mentioned. Change in intention and perceived severity were then measured.MAIN RESULTS AND THE ROLE OF CHANCEParticipants given the PCOS label had significantly higher intention to have an ultrasound (mean = 6.62 versus mean = 5.76, P = 0.033, 95% CI(difference) = 0.069–1.599), perceived the condition to be more severe (17.17 versus 15.82, P = 0.019, 95% CI(difference) = 0.229–2.479) and had lower self-esteem (25.86 versus 27.56, P = 0.031, 95% CI(difference) = −3.187 to −0.157). After receiving overdiagnosis information, both intention and perceived severity decreased, regardless of condition (both P < 0.001).LIMITATIONS, REASONS FOR CAUTIONThis study used hypothetical scenarios; it is likely that for women facing a real diagnosis of PCOS, outcomes would be more affected than in the current study. The hypothetical design, however, allowed the symptoms and risks of PCOS to be held constant across conditions, the impact on intention and psychosocial outcomes directly attributable to the effect of the disease label.WIDER IMPLICATIONS OF THE FINDINGSThese findings demonstrate the potential negative consequences of PCOS labelling. It is crucial we consider the impact of the label before diagnosing more women with PCOS when clinical benefit of this diagnosis is uncertain.STUDY FUNDING/COMPETING INTEREST(S)This paper was written with support from a NHMRC grant awarded to the Screening and Test Evaluation Program. J.J. is supported by an NHMRC Early Career Fellowship. K.M. is supported by an NHMRC Career Development Fellowship. The authors declare that no competing interests exist.TRIAL REGISTRATION NUMBERACTRN12617000111370TRIAL REGISTRATION DATE20/01/2017DATE OF FIRST PATIENT'S ENROLMENT01/06/2015
      PubDate: 2017-02-18
  • Gonadotrophin stimulation in IVF alters the immune cell profile in
           follicular fluid and the cytokine concentrations in follicular fluid and
    • Authors: Kollmann ZZ; Schneider SS, Fux MM, et al.
      Abstract: AbstractSTUDY QUESTIONAre the immune cell profiles and the cytokine concentrations in follicular fluid (FF) and serum at the preovulatory stage different in conventional exogenous gonadotrophin stimulated IVF (c-IVF) compared with natural cycle IVF (NC-IVF)'SUMMARY ANSWERThe cell counts of CD45+ leucocytes and T cell subpopulations and the cytokine concentrations in FF and serum are different in c-IVF compared to NC-IVF.WHAT IS KNOWN ALREADYFF-derived cells are heterogeneous. Immune cells are involved in intra-ovarian processes and cytokines are required for normal follicular development. Gonadotrophins stimulate the regulatory intrafollicular system and influence the local distribution of immune cells and the intrafollicular release of cytokines. Administration of exogenous gonadotrophins may have a significant effect on this local regulatory system, which then in turn could influence oocyte quality.STUDY DESIGN, SIZE, DURATIONThe study included 105 patients, 69 undergoing c-IVF and 36 undergoing NC-IVF. c-IVF was performed by exogenous ovarian stimulation with hMG and GnRH antagonists.PARTICIPANTS/MATERIALS, SETTING, METHODSFF samples were collected from the first dominant follicle in c-IVF without pooling and from single leading preovulatory follicles in NC-IVF. Three different approaches were used to analyze FF samples: (i) microscopic investigation of CD45+ leucocytes, (ii) fluorescence-activated cell sorting to determine CD19+ B cells and CD3+ T cells including T cell subpopulations (CD4+, CD8+), and (iii) evaluation of tumour necrosis factor-alpha (TNF-α), interferon-gamma (INF-γ), interleukins (IL)−2, −6, −8, −10 and vascular endothelial growth factor (VEGF) levels in matched FF and serum samples using the Bio-Plex® platform.MAIN RESULTS AND THE ROLE OF CHANCEFF obtained from c-IVF contained proportionally more CD45+ leucocytes (P = 0.0384), but fewer CD8+ cytotoxic T cells than FF from NC-IVF. CD3+ T lymphocytes were the most common type of lymphocytes, and the number thereof was comparable in the two study groups. In c-IVF, serum VEGF levels were higher (P = 0.007) than in NC-IVF while FF contained marginally decreased concentrations of IL-8 in c-IVF in comparison to NC-IVF. The cytokine concentration gradient between FF and serum in c-IVF was 10-fold for IL-8 and 8-fold for VEGF and thereby markedly lower than in NC-IVF, where the differences were 32-fold and 30-fold, respectively. Strong positive correlations were determined between FF- IL-10 and FF- VEGF in c-IVF (r = 0.85, P < 0.0001) and in NC-IVF (r = 0.81, P < 0.0001).LARGE SCALE DATAN/A.LIMITATION, REASONS FOR CAUTIONThe ovulation of NC-IVF follicles was induced by the exogenous administration of hCG, which means that the environment did not fully correspond to the physiological situation.WIDER IMPLICATIONS OF THE FINDINGSThe differences in the immune profile and the cytokine concentrations in c-IVF and NC-IVF follicles support the hypothesis that conventional ovarian stimulation affects indirectly and heterogeneously the intrafollicular milieu, and thereby possibly affects the oocyte quality and the IVF outcome. However, further studies are needed to confirm our findings and to refine stimulation protocols in the context of optimizing the intrafollicular environment during oocyte maturation.STUDY FUNDING/COMPETING INTEREST(S)The study was supported by a research grant from IBSA Institut Biochimique SA and MSD Merck Sharp & Dohme GmbH. The authors are clinically involved in low dose mono-follicular stimulation and IVF-therapies, using gonadotrophins from all gonadotrophins distributors on the Swiss market, including Institut Biochimique SA and MSD Merck Sharp & Dohme GmbH.
      PubDate: 2017-02-15
  • Accuracy of hysterosalpingo-foam sonography in comparison to
           hysterosalpingo-contrast sonography with air/saline and to laparoscopy
           with dye
    • Authors: Ludwin II; Ludwin AA, Wiechec MM, et al.
      Abstract: AbstractSTUDY QUESTIONWhat is the diagnostic accuracy of 2D/3D hysterosalpingo-foam sonography (HyFoSy) and 2D/3D-high-definition flow Doppler (HDF)-HyFoSy in comparison to laparoscopy with dye chromotubation (as the reference method) and 2D air/saline-enhanced hysterosalpingo-contrast sonography (HyCoSy) (as the initial index test)'SUMMARY ANSWER2D/3D-HDF-HyFoSy had the best diagnostic accuracy and was the only method that did not significantly differ from the reference method, while both 2D/3D-HyFoSy and 2D/3D-HDF-HyFoSy had significantly higher accuracy than 2D-air/saline-HyCoSy.WHAT IS KNOWN ALREADYPrevious studies on X-ray hysterosalpingography and laparoscopy and dye as the reference standard have undermined the impact of older commercial contrast agents on the accuracy of ultrasound tubal patency tests. Recently, HyFoSy was reported to have very high accuracy in a small pilot study in comparison to laparoscopy and dye, and had a very high positive predictive value (PPV) for medical tubal occlusion. A new Doppler sonographic technique, known as HDF imaging with better axial resolution, fewer blooming artifacts and higher sensitivity than color and power Doppler imaging, has been introduced.STUDY DESIGN, SIZE, DURATIONA prospective observational study was performed on 132 women (259 Fallopian tubes) consecutively enrolled between 2013 and 2015.PARTICIPANTS/MATERIALS, SETTING, METHODSThis study included infertile women of reproductive age who previously had not been examined for tubal patency and who presented for the evaluation to the university hospital, private hospital and clinic at which this study was conducted. 2D-Air/saline-HyCoSy, 2D/3D-HyFoSy and 2D/3D-HDF-HyFoSy and laparoscopy were performed independently by experienced readers. During HyFoSy, the 3D mode was used for standardization of pelvic scanning and observations of contrast flow without diagnosis after volume acquisition. Sensitivity, specificity, negative and positive predictive value (NPV and PPV), negative and positive-likelihood ratio (LR− and LR+) and 95% CI were calculated. McNemar's test and relative predictive values (a comparison of NPV and PPV) were used to compare all the index tests.MAIN RESULTS AND THE ROLE OF CHANCE2D-Air/saline-HyCoSy, 2D/3D-HyFoSy and 2D/3D-HDF-HyFoSy indicated that 46 (17.8%), 27 (10.4%) and 24 (9.2%) of the 259 tubes were occluded, respectively; additionally, inconclusive results were obtained for 8 (3%), 5 (1.9%) and 3 (1.2%) tubes, respectively. The reference method revealed 18 (6.9%) occluded Fallopian tubes. 2D-Air/saline-HyCoSy had a high NPV (99.5%) that was similar to that of 2D/3D-HyFoSy (99%) and 2D/3D-HDF-HyFoSy (99.6%) (P > 0.05), but had a very low PPV (30.4%). The use of 2D/3D-HyFoSy, especially 2D/3D-HDF-HyFoSy, which had a significantly higher PPV (48% and 71%, P < 0.05 and P < 0.01; respectively), resulted in fewer false positive and inconclusive findings than the use of 2D-air/saline-HyCoSy. The LR− and LR+ was 0.14 and 14.8, respectively, for 2D/3D-HyFoSy, 0.06 and 32.1, respectively, for 2D/3D-HDF-HyFoSy, and 0.08 and 6.9, respectively, for 2D-air/saline-HyCoSy. The number of inconclusive or positive results per patient was significantly fewer with 2D/3D-HyFoSy (odds ratio, OR = 0.5, CI = 0.3–0.95, P < 0.05) and 2D/3D-HDF-HyFoSy (OR = 0.4, 95% CI = 0.2–0.8, P < 0.01) than with 2D-air/saline-HyCoSy.LIMITATIONS, REASONS FOR CAUTIONAn unselected infertile population with a low prevalence of tubal occlusion is suitable for estimating the diagnostic accuracy of imaging tests only as a screening tool.WIDER IMPLICATIONS OF THE FINDINGSThese findings can be used to establish a diagnostic strategy with high accuracy but minimum invasiveness and limited use of contrast agents and sophisticated technology. 2D-Air/saline-HyCoSy, which has a high NPV, is suitable as an initial test and basic screening method, but 2D/3D-HDF-HyFoSy, which has a significantly higher PPV, can be used as a standard to verify any questionable or positive results obtained with 2D HyCoSy. This strategy may signficantly reduce the need for laparoscopy as a reference standard.STUDY FUNDING/COMPETING INTEREST(S)There was no external funding for this study, and the authors have no conflicts of interest to declare.TRIAL REGISTRATION NUMBERN/A.
      PubDate: 2017-02-10
  • Fallopian tube catheterization in the treatment of proximal tubal
           obstruction: a systematic review and meta-analysis
    • Authors: De Silva PM; Chu J, Gallos ID, et al.
      Abstract: STUDY QUESTIONWhat is the chance of clinical pregnancy when fallopian tube catheterization is used for proximal tubal obstruction'SUMMARY ANSWERThe pooled clinical pregnancy rate of tubal catheterization after proximal tubal obstruction is 27% (95% CI 25–30%).WHAT IS KNOWN ALREADYRestoring fallopian tube patency by performing tubal catheterization has fallen out of favour since the increased availability of IVF. Our study is the first systematic review and meta-analysis to investigate reproductive outcomes following tubal catheterization for proximal tubal obstruction.STUDY DESIGN, SIZE, DURATIONWe undertook a systematic review and meta-analysis of 27 observational studies consisting of 1720 patients undergoing tubal catheterization for proximal tubal obstruction, who attempted to conceive naturally after the procedure.PARTICIPANTS/MATERIALS, SETTING, METHODSSystematic literature searches were performed in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. A total of 2195 titles and abstracts were reviewed. Only studies that reported outcomes when tubal catheterization was performed with no other tubal surgery were included. Twenty-seven cohort studies matched the inclusion criteria for the meta-analysis.MAIN RESULTS AND THE ROLE OF CHANCEThe meta-analysis showed a pooled clinical pregnancy rate of 27% (95% CI 25–30%) after the use of tubal catheterization for unilateral or bilateral proximal tubal obstruction (27 studies, 1556 patients). In women with bilateral obstruction (14 studies, 617 patients), the clinical pregnancy rate was 27% (95% CI 23–32%). Our meta-analysis demonstrated that the pooled cumulative clinical pregnancy rates were 22.3% (95% CI 17.8–27.8%) at 6 months, 25.8% (95% CI 21.1–31.5%) at 9 months, 26.4% (95% CI 23.0–30.2%) at 12 months, 26.0% (95% CI 22.8–29.7%) at 18 months, 27.0% (95% CI 24.0–30.5%) at 24 months, 27.9% (95% CI 24.9–31.3%) at 36 months and 28.5% (95% CI 25.5–31.8%) at 48 months. The pooled live birth rate (14 studies, 551 patients) was 22% (95% CI 18–26%). The pooled ectopic pregnancy rate (27 studies, 1556 patients) was 4% (95% CI 3–5%). The included studies scored satisfactorily on the Newcastle-Ottawa quality assessment scale.LIMITATIONS, REASONS FOR CAUTIONThe pooled clinical pregnancy rate after tubal catheterization was found to be almost comparable to that after IVF. However, included studies were small, non-comparative series with significant clinical heterogeneity in population characteristics, follow-up and surgical equipment, technique and experience.WIDER IMPLICATIONS OF THE FINDINGSThese findings suggest fallopian tube catheterization as an alternative strategy to IVF in patients presenting with proximal tubal obstruction. Further research should focus on comparing different surgical techniques of fallopian tube catheterization with IVF and provide cumulative reproductive outcomes over long-term follow-up.STUDY FUNDING/COMPETING INTEREST(S)No funding was required and the authors have no competing interests to declare.REGISTRATION NUMBERN/A
      PubDate: 2017-02-10
  • Children's thoughts and feelings about their donor and security of
           attachment to their solo mothers in middle childhood
    • Authors: Zadeh SS; Jones CM, Basi TT, et al.
      Abstract: AbstractSTUDY QUESTIONWhat is the relationship between children's thoughts and feelings about their donor and their security of attachment to their solo mothers in middle childhood'SUMMARY ANSWERChildren with higher levels of secure–autonomous attachment to their mothers were more likely to have positive perceptions of the donor, and those with higher levels of insecure–disorganized attachment to their mothers were more likely to perceive him negatively.WHAT IS KNOWN ALREADYThere is limited understanding of the factors that contribute to children's thoughts and feelings about their donor in solo mother families. In adolescence, an association was found between adolescents’ curiosity about donor conception and their security of attachment to their mothers.STUDY DESIGN, SIZE, DURATION19 children were administered the Friends and Family Interview and Donor Conception Interview between December 2015 and March 2016 as part of the second phase of a longitudinal, multi-method, multi-informant study of solo mother families.PARTICIPANTS/MATERIALS, SETTING, METHODSAll children were aged between 7 and 13 years and had been conceived by donor insemination to solo mothers. Interviews were conducted in participants’ homes. The Friends and Family Interview was rated according to a standardized coding scheme designed to measure security of attachment in terms of secure–autonomous, insecure–dismissing, insecure–preoccupied and insecure–disorganized attachment patterns. Quantitative analyses of the Donor Conception Interview yielded two factors: interest in the donor and perceptions of the donor. Qualitative analyses of the Donor Conception Interview were conducted using qualitative content analysis and thematic analysis.MAIN RESULTS AND THE ROLE OF CHANCEStatistically significant associations were found between the perception of the donor scale and the secure–autonomous and insecure–disorganized attachment ratings. Children with higher levels of secure–autonomous attachment to their mothers were more likely to have positive perceptions of the donor (r = 0.549, P = 0.015), and those with higher levels of insecure–disorganized attachment to their mothers were more likely to perceive him negatively (r = −0.632, P = 0.004). Children's narratives about the donor depicted him as a stranger (n = 8), a biological father (n = 4), a social parent (n = 3), or in ambivalent terms (n = 4).LIMITATIONS, REASONS FOR CAUTIONFindings are limited by the wide age range of children within a small overall sample size. Participants were those willing and able to take part in research on donor conception families. The statistical significance of correlation coefficients was not corrected for multiple comparisons.WIDER IMPLICATIONS OF THE FINDINGSFindings highlight the importance of situating children's ideas about the donor within family contexts. It is recommended that those working with donor conception families consider this when advising parents about whether, what and how to tell children about donor conception.STUDY FUNDING/COMPETING INTEREST(S)This study was funded by the Wellcome Trust [097857/Z/11/Z]. The authors have no conflicts of interest to declare.
      PubDate: 2017-02-10
  • Genome-wide genetic analyses highlight mitogen-activated protein kinase
           (MAPK) signaling in the pathogenesis of endometriosis
    • Authors: Uimari O; Rahmioglu N, Nyholt DR, et al.
      Abstract: AbstractSTUDY QUESTIONDo genome-wide association study (GWAS) data for endometriosis provide insight into novel biological pathways associated with its pathogenesis'SUMMARY ANSWERGWAS analysis uncovered multiple pathways that are statistically enriched for genetic association signals, analysis of Stage A disease highlighted a novel variant in MAP3K4, while top pathways significantly associated with all endometriosis and Stage A disease included several mitogen-activated protein kinase (MAPK)-related pathways.WHAT IS KNOWN ALREADYEndometriosis is a complex disease with an estimated heritability of 50%. To date, GWAS revealed 10 genomic regions associated with endometriosis, explaining
      PubDate: 2017-02-09
  • Platelets impair natural killer cell reactivity and function in
           endometriosis through multiple mechanisms
    • Authors: Du Y; Liu X, Guo S.
      Abstract: AbstractSTUDY QUESTIONDo platelets have any role in the reduced cytotoxicity of natural killer (NK) cells in endometriosis'SUMMARY ANSWERPlatelets impair NK cell reactivity and function in endometriosis through multiple mechanisms.WHAT IS KNOWN ALREADYPlatelets play an important role in the development of endometriosis, and platelet-derived transforming growth factor-β1 (TGF-β1) suppresses the expression of NK Group 2, Member D (NKG2D) on NK cells, resulting in reduced cytotoxicity in women with endometriosis.STUDY DESIGN SIZE, DURATIONExperiments on mice with induced endometriosis in which either platelets, NK cells or both were depleted and controls (none depleted). In vitro experiments with NK cells, platelets and, as target cells, endometriotic epithelial cell and endometrial stromal cell lines.PARTICIPANTS/MATERIALS SETTING METHODSImmunohistochemistry analysis of ectopic endometrial tissues from mice with induced endometriosis receiving either platelet depletion (PD), NK cell depletion, or both or none. Immunofluorescence, flow cytometry and gene expression analysis for major histocompatibility complex class I (MHC-I) expression in target cells. Cytotoxicity and degranulation assays and the measurement of interferon (IFN)-γ secretion for the evaluation of NK cytotoxicity. Flow cytometry and gene expression for the expression of NK cell receptors.MAIN RESULTS AND THE ROLE OF CHANCEPD resulted in significantly reduced lesion weight in mice with induced endometriosis, but NK cell depletion as well as concomitant platelet and NK cell depletion increased the weight, suggesting that the anti-endometriosis effect of PD is mediated, at least in part, by increased NK cell cytotoxicity against endometriotic cells. Co-incubation of target cells with platelets resulted in rapid platelet coating as well as increased MHC-I expression in these cells, effectively providing a cloak of ‘pseudo-self’ to these cells to shield against NK cell lysis. It also reduced the expression of NKG2D ligands MICA and MICB and reduced the NK cell cytotoxicity. In addition, co-incubation of NK cells with platelets impaired the NK cell cytotoxicity as well. This impaired NK cell cytotoxicity was not due to the increased NK cell apoptosis, but, rather, through reduced NK cell degranulation and IFN-γ production, and reduced expression of activating receptors NKG2D and NKp46 and increased expression of inhibitory receptor KIR2DL1 in NK cells. Inhibition of TGF-β1 signaling partially restored the aberrant expression of NKG2D, NKp46 and KIR2DL1, and partially restored the impaired NK cell cytotoxicity induced by activated platelets and their releasate.LARGE SCALE DATANot applicable.LIMITATIONS REASONS FOR CAUTIONThis study is confined by the limitation of animal and in vitro experimentation and the lack of direct human data.WIDER IMPLICATIONS OF THE FINDINGSAnti-platelet treatment holds promise in treating endometriosis.STUDY FUNDING/COMPETING INTERESTSThe National Natural Science Foundation of China (81471434 to S.W.G., 81270676 to S.W.G., 81370695 to X.S.L. and 81671436 to X.S.L). None of the authors has anything to disclose.
      PubDate: 2017-02-09
  • Randomized, open trial comparing a modified double-lumen needle follicular
           flushing system with a single-lumen aspiration needle in IVF patients with
           poor ovarian response
    • Authors: von Horn K; Depenbusch M, Schultze-Mosgau A, et al.
      Abstract: AbstractSTUDY QUESTIONIs a modified double-lumen aspiration needle system with follicular flushing able to increase the mean oocyte yield by at least one in poor response IVF patients as compared to single-lumen needle aspiration without flushing'SUMMARY ANSWERFollicular flushing with the modified flushing system did not increase the number of oocytes, but increased the procedure duration.WHAT IS KNOWN ALREADYMost studies on follicular flushing were performed with conventional double-lumen needles in patients who were normal responders. Overall, these studies indicated no benefit of follicular flushing.STUDY DESIGN SIZE, DURATIONProspective, single-centre, randomized, controlled, open, superiority trial comparing the 17 G Steiner-Tan Needle® flushing system with a standard 17 G single-lumen aspiration needle (Gynetics®); time frame February 2015–March 2016.PARTICIPANTS/MATERIALS SETTING METHODSEighty IVF patients, 18–45 years, BMI >18 kg/m2 to 10 mm in both ovaries at the end of the follicular phase were randomized to either aspirating and flushing each follicle 3× with the Steiner-Tan-Needle® automated flushing system (n = 40) or a conventional single-lumen needle aspiration (n = 40). Primary outcome was the number of cumulus-oocyte-complexes (COCs). Procedure duration, burden (Depression Anxiety and Stress Scale; DASS-21) and post-procedure pain were also assessed.MAIN RESULTS AND THE ROLE OF CHANCEFlushing was not superior with a mean (SD) number of COCs of 2.4 (2.0) and 3.1 (2.3) in the Steiner-Tan Needle® and in the Gynectics® group, respectively (mean difference −0.7, 95% CI: 0.3 to −1.6; P = 0.27). Likewise no differences were observed in metaphase II  oocytes, two pronuclear oocytes, number of patients having an embryo transfer and DASS 21 scores. The procedure duration was significantly 2-fold increased.LIMITATIONS REASONS FOR CAUTIONTesting for differences in the number of patients achieving an embryo transfer or differences in pregnancy rate would require a much larger sample size.WIDER IMPLICATIONS OF THE FINDINGSThe use of follicular flushing is unlikely to benefit the prognosis of patients with poor ovarian response.STUDY FUNDING/COMPETING INTEREST(S)The Steiner-Tan Needles® and the flushing system were provided for free by the manufacturer. K.v.H. has received personal fees from Finox and non-financial support from Merck-Serono; M.D. has received personal fees from Finox and non-financial support from Merck-Serono. A.S.-M. has received personal fees and non-financial support from M.D., Ferring, Merck-Serono, Finox, TEVA. G.G. has received personal fees and non-financial support from M.D., Ferring, Merck-Serono, Finox, TEVA, IBSA, Glycotope, as well as personal fees from VitroLife, NMC Healthcare LLC, ReprodWissen LLC and ZIVA LLC.TRIAL REGISTRATION NUMBERNCT 02365350 ( REGISTRATION DATESixth of February 2015.DATE OF FIRST PATIENT'S ENROLMENTNinth of February 2015.
      PubDate: 2017-02-09
  • Protective effect of hormone therapy among women with
    • Authors: Chen LL; Mishra GD, Dobson AJ, et al.
      Abstract: AbstractSTUDY QUESTIONDoes exposure to menopausal hormone therapy (MHT) in mid-aged women alter their risk of cardiovascular disease (CVD) mortality and all-cause mortality'SUMMARY ANSWERMHT soon after menopause is unlikely to increase the risk of CVD mortality or all-cause mortality and may have a protective effect for women with hysterectomy/oophorectomy.WHAT IS KNOWN ALREADYThe balance of benefits and risks of MHT are currently unclear and may differ according to when treatment starts and whether women have an intact uterus.STUDY DESIGN, SIZE, DURATIONA total of 13 715 participants from the mid-aged population-based cohort (born 1946–1951) of the Australian Longitudinal Study on Women's Health (ALSWH) were followed from 1998 to 2013.PARTICIPANTS/MATERIALS, SETTING, METHODSThe measures included cardiovascular and all-cause mortality, exposure to MHT and menopausal status (based on 3-yearly self-reports). Electronic prescriptions data on MHT were also available from mid-2002 onwards. At each follow-up survey wave, participants were classified as: an existing user of MHT, an initiator of MHT or a non-initiator of MHT.MAIN RESULTS AND THE ROLE OF CHANCEAfter adjusting for confounding variables, existing users of MHT had a reduced risk (hazard ratio 0.63; 95% CI, 0.43–0.92) of CVD mortality compared with non-initiators. Insufficient evidence of an association was identified for initiators of MHT (0.66; 0.35–1.24). For all-cause mortality, risks were reduced for both initiators (0.69; 0.55–0.87) and existing users (0.80; 0.70–0.91). In a subgroup analysis, women with hysterectomy/oophorectomy had lower risks of CVD mortality for both initiators (0.14; 0.02–0.98) and existing users (0.55; 0.34–0.90), but no evidence of an association was found for women whose MHT commenced during or after menopause. Similarly for all-cause mortality, only the women with hysterectomy/oophorectomy had lower risks for both initiators (0.47; 0.31–0.70) and existing users (0.69; 0.58–0.82).LIMITATIONS, REASONS FOR CAUTIONLimitations include the observational nature of the study, the small number of deaths, MHT use being self-reported and the classification of menopausal status also being based on self-reported information.WIDER IMPLICATIONS OF THE FINDINGSWomen considering MHT soon after menopause can be reassured that the treatment is unlikely to increase their risk of CVD mortality or all-cause mortality.STUDY FUNDING/COMPETING INTEREST(S)The Australian Longitudinal Study on Women's Health is funded by the Australian Department of Health. G.D.M. is funded by the Australian Research Council Future Fellowship. L.C. was funded by a China scholarship council (CSC) graduate scholarship. All authors report no conflict of interest.TRIAL REGISTRATION NUMBERN/A
      PubDate: 2017-02-09
  • Genetic evidence of ‘genuine’ empty follicle syndrome: a novel
           effective mutation in the LHCGR gene and review of the literature
    • Authors: Yuan P; He Z, Zheng L, et al.
      Abstract: AbstractEmpty follicle syndrome (EFS) is a reproductive disorder in which no oocytes are retrieved during IVF. The existence of genuine EFS (GEFS) is still controversial, and to date, only one missense mutation of Luteinizing Hormone/Choriogonadotropin Receptor (LHCGR) has been reported to be associated with this disease. Here, we describe a GEFS patient in a non-consanguineous family from China. A 27-year-old woman presented with a 5-year history of primary infertility and LH resistance-like ovaries of unequal sizes, but with normal levels of circulating LH. In spite of a satisfactory ovarian reserve and response, no oocytes were retrieved after two cycles of IVF. Her condition did not appear to be failure of the hCG injection. It is more likely to be a genetic cause. A novel homozygous mutation in LHCGR gene, c.1345G>A (p.Ala449Thr), was detected in this patient. Each of her parents is heterozygous for this change, and the change was absent from 407 control subjects. Alanine at this amino acid position was highly conserved and replacement of threonine was predicted to disrupt the third transmembrane helix of the rhodopsin-like G protein-coupled receptor domain. Protein localization studies revealed that a portion of the mutant LHCGR protein molecules was retained intracellularly. Signalling studies demonstrated that this mutation had differing effects on the response of LHCGR to hCG or LH at different concentrations. Specifically, at a concentration 1 IU/ml), the mutant was activated by both hCG and LH. These data suggest that screening for mutations in the LHCGR gene may assist in the diagnosis of patients with GEFS. The literature describing the relationship between phenotype and genotypes in females is reviewed, and possible aetiologies and treatment options for this disease are proposed based on our and other studies.
      PubDate: 2017-02-08
  • Should we individualize lipid profiling in women with polycystic ovary
    • Authors: Poromaa I; Mellembakken J, Morin-Papunen L, et al.
      PubDate: 2017-02-08
  • Assessment of ‘one-step’ versus ‘sequential’ embryo culture
           conditions through embryonic genome methylation and hydroxymethylation
    • Authors: Salvaing JJ; Peynot NN, Bedhane MN, et al.
      PubDate: 2017-02-08
  • The roles of protein disulphide isomerase family A, member 3 (ERp57) and
           surface thiol/disulphide exchange in human spermatozoa–zona pellucida
    • Authors: Wong C; Lam KW, Lee C, et al.
      Abstract: AbstractSTUDY QUESTIONAre multimeric sperm plasma membrane protein complexes, ERp57 and sperm surface thiol content involved in human spermatozoa–zona pellucida (ZP) interaction'SUMMARY ANSWERERp57 is a component of a multimeric spermatozoa–ZP receptor complex involved in regulation of human spermatozoa–ZP binding via up-regulation of sperm surface thiol content.WHAT IS KNOWN ALREADYA spermatozoon acquires its fertilization capacity within the female reproductive tract by capacitation. Spermatozoa–ZP receptor is suggested to be a composite structure that is assembled into a functional complex during capacitation. Sperm surface thiol content is elevated during capacitation. ERp57 is a protein disulphide isomerase that modulates the thiol-disulphide status of proteins.STUDY DESIGN, SIZE, DURATIONThe binding ability and components of protein complexes in extracted membrane protein fractions of spermatozoa were studied. The roles of capacitation, thiol-disulphide reagent treatments and ERp57 on sperm functions and sperm surface thiol content were assessed.PARTICIPANTS/MATERIALS, SETTING, METHODSSpermatozoa were obtained from semen samples from normozoospermic men. Human oocytes were obtained from an assisted reproduction programme. Blue native polyacrylamide gel electrophoresis, western ligand blotting and mass spectrometry were used to identify the components of solubilized ZP/ZP3-binding complexes. The localization and expression of sperm surface thiol and ERp57 were studied by immunostaining and sperm surface protein biotinylation followed by western blotting. Sperm functions were assessed by standard assays.MAIN RESULTS AND THE ROLE OF CHANCESeveral ZP-binding complexes were isolated from the cell membrane of capacitated spermatozoa. ERp57 was a component of one of these complexes. Capacitation significantly increased the sperm surface thiol content, acrosomal thiol distribution and ERp57 expression on sperm surface. Sperm surface thiol and ERp57 immunoreactivity were localized to the acrosomal region of spermatozoa, a region responsible for ZP-binding. Up-regulation of the surface thiol content or ERp57 surface expression in vitro stimulated ZP-binding capacity of human spermatozoa. Blocking of ERp57 function by specific antibody or inhibitors against ERp57 reduced the surface thiol content and ZP-binding capacity of human spermatozoa.LARGE SCALE DATAN/ALIMITATIONS, REASONS FOR CAUTIONThe mechanisms by which up-regulation of surface thiol content stimulates spermatozoa–ZP binding have not been depicted.WIDER IMPLICATIONS OF THE FINDINGSThiol-disulphide exchange is a crucial event in capacitation. ERp57 modulates the event and the subsequent fertilization process. Modulation of the surface thiol content of the spermatozoa of subfertile men may help to increase fertilization rate in assisted reproduction.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by The Hong Kong Research Grant Council Grant HKU764611 and HKU764512M to P.C.N.C. The authors have no competing interests.
      PubDate: 2017-02-08
  • The addition of anti-Müllerian hormone in an algorithm for individualized
           hormone dosage did not improve the prediction of ovarian response—a
           randomized, controlled trial
    • Authors: Magnusson ÅÅ; Nilsson LL, Oleröd GG, et al.
      Abstract: AbstractSTUDY QUESTIONDoes the addition of anti-Müllerian hormone (AMH) to a conventional dosage regimen, including age, antral follicle count (AFC) and BMI, improve the rate of targeted ovarian response, defined as 5–12 oocytes after IVF'SUMMARY ANSWERThe addition of AMH did not alter the rate of targeted ovarian response, 5–12 oocytes, or decreased the rate of ovarian hyperstimulation syndrome (OHSS) or cancelled cycles due to poor ovarian response.WHAT IS KNOWN ALREADYControlled ovarian hyperstimulation (COH) in connection with IVF is sometimes associated with poor ovarian response resulting in low pregnancy and live birth rates or leading to cycle cancellations, but also associated with excessive ovarian response, causing an increased risk of OHSS. Even though it is well-established that both AMH and AFC are strong predictors of ovarian response in IVF, few randomized trials have investigated their impact on achieving an optimal number of oocytes.STUDY DESIGN, SIZE AND DURATIONBetween January 2013 and May 2016, 308 patients starting their first IVF treatment were randomly assigned, using a computerized randomization program with concealed allocation of patients and in the proportions of 1:1, to one of two dosage algorithms for decisions on hormone starting dose, an algorithm, including AMH, AFC, age and BMI (intervention group), or an algorithm, including only AFC, age and BMI (control group). The study was blinded to patients and treating physicians.PARTICIPANTS/MATERIALS, SETTING, METHODSWomen aged >18 and
      PubDate: 2017-02-08
  • The genetic regulation of transcription in human endometrial tissue
    • Authors: Fung JN; Girling JE, Lukowski SW, et al.
      Abstract: AbstractSTUDY QUESTIONDo genetic effects regulate gene expression in human endometrium'SUMMARY ANSWERThis study demonstrated strong genetic effects on endometrial gene expression and some evidence for genetic regulation of gene expression in a menstrual cycle stage-specific manner.WHAT IS KNOWN ALREADYGenetic effects on expression levels for many genes are tissue specific. Endometrial gene expression varies across menstrual cycle stages and between individuals, but there are limited data on genetic control of expression in endometrium.STUDY DESIGN, SIZE, DURATIONWe analysed genome-wide genotype and gene expression data to map cis expression quantitative trait loci (eQTL) in endometrium.PARTICIPANTS/MATERIALS, SETTING, METHODSWe recruited 123 women of European ancestry. DNA samples from blood were genotyped on Illumina HumanCoreExome chips. Total RNA was extracted from endometrial tissues. Whole-transcriptome profiles were characterized using Illumina Human HT-12 v4.0 Expression Beadchips. We performed eQTL mapping with ~8 000 000 genotyped and imputed single nucleotide polymorphisms (SNPs) and 12 329 genes.MAIN RESULTS AND THE ROLE OF CHANCEWe identified a total of 18 595 cis SNP-probe associations at a study-wide level of significance (P < 1 × 10−7), which correspond to independent eQTLs for 198 unique genes. The eQTLs with the largest effect in endometrial tissue were rs4902335 for CHURC1 (P = 1.05 × 10−32) and rs147253019 for ZP3 (P = 8.22 × 10−30). We further performed a context-specific eQTL analysis to investigate if genetic effects on gene expression regulation act in a menstrual cycle-specific manner. Interestingly, five cis-eQTLs were identified with a significant stage-by-genotype interaction. The strongest stage interaction was the eQTL for C10ORF33 (PYROXD2) with SNP rs2296438 (P = 2.0 × 10−4), where we observe a 2-fold difference in the average expression levels of heterozygous samples depending on the stage of the menstrual cycle.LARGE SCALE DATAThe summary eQTL results are publicly available to browse or download.LIMITATIONS, REASONS FOR CAUTIONA limitation of the present study was the relatively modest sample size. It was not powered to identify trans-eQTLs and larger sample sizes will also be needed to provide better power to detect cis-eQTLs and cycle stage-specific effects, given the substantial changes in expression across the menstrual cycle for many genes.WIDER IMPLICATIONS OF THE FINDINGSIdentification of endometrial eQTLs provides a platform for better understanding genetic effects on endometriosis risk and other endometrial-related pathologies.STUDY FUNDING/COMPETING INTEREST(S)Funding for this work was provided by NHMRC Project Grants GNT1026033, GNT1049472, GNT1046880, GNT1050208, GNT1105321 and APP1083405. There are no competing interests.
      PubDate: 2017-02-08
  • Predicting the likelihood of live birth for elective oocyte
           cryopreservation: a counseling tool for physicians and patients
    • Authors: Goldman RH; Racowsky CC, Farland LV, et al.
      Abstract: AbstractSTUDY QUESTIONCan a counseling tool be developed for women desiring elective oocyte cryopreservation to predict the likelihood of live birth based on age and number of oocytes frozen'SUMMARY ANSWERUsing data from ICSI cycles of a population of women with uncompromised ovarian reserve, an evidence-based counseling tool was created to guide women and their physicians regarding the number of oocytes needed to freeze for future family-building goals.WHAT IS KNOWN ALREADYElective oocyte cryopreservation is increasing in popularity as more women delay family building. By undertaking elective oocyte freezing at a younger age, women hope to optimize their likelihood of successful live birth(s) using their thawed oocytes at a future date. Questions often arise in clinical practice regarding the number of cryopreserved oocytes sufficient to achieve live birth(s) and whether or not additional stimulation cycles are likely to result in a meaningful increase in the likelihood of live birth. As relatively few women who have electively cryopreserved oocytes have returned to use them, available data for counseling patients wishing to undergo fertility preservation are limited.STUDY DESIGN, SIZE, DURATIONA model was developed to determine the proportion of mature oocytes that fertilize and then form blastocysts as a function of age, using women with presumably normal ovarian reserve based on standard testing who underwent ICSI cycles in our program from January, 2011 through March, 2015 (n = 520). These included couples diagnosed exclusively with male-factor and/or tubal-factor infertility, as well as cycles utilizing egg donation. Age-specific probabilities of euploidy were estimated from 14 500 PGS embryo results from an external testing laboratory. Assuming survival of thawed oocytes at 95% for women
      PubDate: 2017-02-06
  • Genome-wide interactions between FSH and insulin-like growth factors in
           the regulation of human granulosa cell differentiation
    • Authors: Stocco C; Baumgarten SC, Armouti M, et al.
      Abstract: AbstractSTUDY QUESTIONIs the genome-wide response of human cumulus cells to FSH and insulin-like growth factors (IGFs) comparable to the response observed in undifferentiated granulosa cells (GCs)'SUMMARY ANSWERFSH actions in human cumulus cells mimic those observed in preantral undifferentiated GCs from laboratory animals, and approximately half of the regulated genes are dependent on the simultaneous activation of the IGF1 receptor (IGF1R).WHAT IS KNOWN ALREADYAnimal studies have shown that FSH and the IGFs system are required for follicle growth and maturation. In humans, IGF levels in the follicular fluid correlate with patients’ responses to IVF protocols. The main targets of FSH and IGFs in the ovary are the GCs; however, the genomic mechanisms involved in the response of GCs to these hormones are unknown.STUDY DESIGN, SIZE, DURATIONHuman cumulus cells isolated from IVF patients were cultured for 48 h in serum-free media in the presence of vehicle, FSH, IGF1R inhibitor or their combination.PARTICIPANTS/MATERIALS, SETTING, METHODSDiscarded cumulus cells were donated to research by reproductive-aged women undergoing IVF due to non-ovarian etiologies of infertility at a university-affiliated clinic. The effect of FSH and/or IGF1R inhibition on cumulus cell function was evaluated using Affymetrix microarrays, quantitative PCR, western blot, promoter assays and hormone level measurements.MAIN RESULTS AND THE ROLE OF CHANCEThe findings demonstrate that human cumulus cells from IVF patients respond to FSH with the expression of genes known to be markers of the preantral to preovulatory differentiation of GCs. These results also demonstrate that ~50% of FSH-regulated genes require IGF1R activity and suggest that several aspects of follicle growth are coordinately regulated by FSH and IGFs in humans. This novel approach will allow for future mechanistic and molecular studies on the regulation of human follicle maturation.LARGE SCALE DATAData set can be accessed at Gene Expression Omnibus number GSE86427.LIMITATIONS, REASONS FOR CAUTIONExperiments were performed using primary human cumulus cells. This may not represent the response of intact follicles.WIDER IMPLICATIONS OF THE FINDINGSUnderstanding the mechanisms involved in the regulation of GC differentiation by FSH and IGF in humans will contribute to improving treatments for infertility.STUDY FUNDING/COMPETING INTEREST(S)The project was financed by the National Instituted of Health grant number R56HD086054 and R01HD057110 (C.S.). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We have no competing interests to declare.
      PubDate: 2017-01-31
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Heriot-Watt University
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