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Publisher: Oxford University Press   (Total: 370 journals)

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Showing 1 - 200 of 370 Journals sorted alphabetically
Acta Biochimica et Biophysica Sinica     Hybrid Journal   (Followers: 6, SJR: 0.881, h-index: 38)
Adaptation     Hybrid Journal   (Followers: 9, SJR: 0.111, h-index: 4)
Aesthetic Surgery J.     Hybrid Journal   (Followers: 6, SJR: 1.538, h-index: 35)
African Affairs     Hybrid Journal   (Followers: 60, SJR: 1.512, h-index: 46)
Age and Ageing     Hybrid Journal   (Followers: 86, SJR: 1.611, h-index: 107)
Alcohol and Alcoholism     Hybrid Journal   (Followers: 18, SJR: 0.935, h-index: 80)
American Entomologist     Full-text available via subscription   (Followers: 6)
American Historical Review     Hybrid Journal   (Followers: 152, SJR: 0.652, h-index: 43)
American J. of Agricultural Economics     Hybrid Journal   (Followers: 38, SJR: 1.441, h-index: 77)
American J. of Epidemiology     Hybrid Journal   (Followers: 175, SJR: 3.047, h-index: 201)
American J. of Hypertension     Hybrid Journal   (Followers: 25, SJR: 1.397, h-index: 111)
American J. of Jurisprudence     Hybrid Journal   (Followers: 20)
American J. of Legal History     Full-text available via subscription   (Followers: 9, SJR: 0.151, h-index: 7)
American Law and Economics Review     Hybrid Journal   (Followers: 28, SJR: 0.824, h-index: 23)
American Literary History     Hybrid Journal   (Followers: 13, SJR: 0.185, h-index: 22)
Analysis     Hybrid Journal   (Followers: 23)
Annals of Botany     Hybrid Journal   (Followers: 35, SJR: 1.912, h-index: 124)
Annals of Occupational Hygiene     Hybrid Journal   (Followers: 28, SJR: 0.837, h-index: 57)
Annals of Oncology     Hybrid Journal   (Followers: 47, SJR: 4.362, h-index: 173)
Annals of the Entomological Society of America     Full-text available via subscription   (Followers: 8, 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: 53, 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: 21)
Arbitration Law Reports and Review     Hybrid Journal   (Followers: 14)
Archives of Clinical Neuropsychology     Hybrid Journal   (Followers: 31, 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: 51, SJR: 1.698, h-index: 92)
Bioinformatics     Hybrid Journal   (Followers: 285, SJR: 4.643, h-index: 271)
Biology Methods and Protocols     Hybrid Journal  
Biology of Reproduction     Full-text available via subscription   (Followers: 9, SJR: 1.646, h-index: 149)
Biometrika     Hybrid Journal   (Followers: 20, SJR: 2.801, h-index: 90)
BioScience     Hybrid Journal   (Followers: 30, 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: 16, SJR: 1.955, h-index: 55)
BJA : British J. of Anaesthesia     Hybrid Journal   (Followers: 165, SJR: 2.314, h-index: 133)
BJA Education     Hybrid Journal   (Followers: 65, SJR: 0.272, h-index: 20)
Brain     Hybrid Journal   (Followers: 66, SJR: 6.097, h-index: 264)
Briefings in Bioinformatics     Hybrid Journal   (Followers: 47, 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: 35, SJR: 1.267, h-index: 38)
British J. of Aesthetics     Hybrid Journal   (Followers: 27, SJR: 0.217, h-index: 18)
British J. of Criminology     Hybrid Journal   (Followers: 577, SJR: 1.373, h-index: 62)
British J. of Social Work     Hybrid Journal   (Followers: 87, 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: 30)
Bulletin of the London Mathematical Society     Hybrid Journal   (Followers: 4, SJR: 1.474, h-index: 31)
Cambridge J. of Economics     Hybrid Journal   (Followers: 59, SJR: 0.957, h-index: 59)
Cambridge J. of Regions, Economy and Society     Hybrid Journal   (Followers: 10, SJR: 1.067, h-index: 22)
Cambridge Quarterly     Hybrid Journal   (Followers: 11, SJR: 0.1, h-index: 7)
Capital Markets Law J.     Hybrid Journal   (Followers: 2)
Carcinogenesis     Hybrid Journal   (Followers: 2, SJR: 2.439, h-index: 167)
Cardiovascular Research     Hybrid Journal   (Followers: 12, SJR: 2.897, h-index: 175)
Cerebral Cortex     Hybrid Journal   (Followers: 45, SJR: 4.827, h-index: 192)
CESifo Economic Studies     Hybrid Journal   (Followers: 17, SJR: 0.501, h-index: 19)
Chemical Senses     Hybrid Journal   (Followers: 1, SJR: 1.436, h-index: 76)
Children and Schools     Hybrid Journal   (Followers: 6, SJR: 0.211, h-index: 18)
Chinese J. of Comparative Law     Hybrid Journal   (Followers: 4)
Chinese J. of Intl. Law     Hybrid Journal   (Followers: 22, SJR: 0.737, h-index: 11)
Chinese J. of Intl. Politics     Hybrid Journal   (Followers: 9, 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: 24, SJR: 0.1, h-index: 3)
Clinical Infectious Diseases     Hybrid Journal   (Followers: 62, SJR: 4.742, h-index: 261)
Clinical Kidney J.     Open Access   (Followers: 3, SJR: 0.338, h-index: 19)
Community Development J.     Hybrid Journal   (Followers: 25, SJR: 0.47, h-index: 28)
Computer J.     Hybrid Journal   (Followers: 9, SJR: 0.371, h-index: 47)
Conservation Physiology     Open Access   (Followers: 2)
Contemporary Women's Writing     Hybrid Journal   (Followers: 11, SJR: 0.111, h-index: 3)
Contributions to Political Economy     Hybrid Journal   (Followers: 5, SJR: 0.313, h-index: 10)
Critical Values     Full-text available via subscription  
Current Legal Problems     Hybrid Journal   (Followers: 27)
Current Zoology     Full-text available via subscription   (Followers: 1, SJR: 0.999, h-index: 20)
Database : The J. of Biological Databases and Curation     Open Access   (Followers: 10, SJR: 1.068, h-index: 24)
Digital Scholarship in the Humanities     Hybrid Journal   (Followers: 13)
Diplomatic History     Hybrid Journal   (Followers: 19, SJR: 0.296, h-index: 22)
DNA Research     Open Access   (Followers: 5, SJR: 2.42, h-index: 77)
Dynamics and Statistics of the Climate System     Open Access   (Followers: 3)
Early Music     Hybrid Journal   (Followers: 15, SJR: 0.124, h-index: 11)
Economic Policy     Hybrid Journal   (Followers: 38, SJR: 2.052, h-index: 52)
ELT J.     Hybrid Journal   (Followers: 25, SJR: 1.26, h-index: 23)
English Historical Review     Hybrid Journal   (Followers: 55, SJR: 0.311, h-index: 10)
English: J. of the English Association     Hybrid Journal   (Followers: 14, 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: 3)
Environmental History     Hybrid Journal   (Followers: 28, SJR: 0.197, h-index: 25)
EP-Europace     Hybrid Journal   (Followers: 2, 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: 16, SJR: 0.1, h-index: 6)
European Heart J.     Hybrid Journal   (Followers: 52, SJR: 6.997, h-index: 227)
European Heart J. - Cardiovascular Imaging     Hybrid Journal   (Followers: 8, 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: 7, SJR: 0.152, h-index: 31)
European J. of Cardio-Thoracic Surgery     Hybrid Journal   (Followers: 8, SJR: 1.568, h-index: 104)
European J. of Intl. Law     Hybrid Journal   (Followers: 180, 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: 23, SJR: 1.284, h-index: 64)
European Review of Agricultural Economics     Hybrid Journal   (Followers: 11, SJR: 1.549, h-index: 42)
European Review of Economic History     Hybrid Journal   (Followers: 29, SJR: 0.628, h-index: 24)
European Sociological Review     Hybrid Journal   (Followers: 41, 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: 10, SJR: 1.687, h-index: 115)
Fems Microbiology Letters     Hybrid Journal   (Followers: 22, SJR: 1.126, h-index: 118)
Fems Microbiology Reviews     Hybrid Journal   (Followers: 27, SJR: 7.587, h-index: 150)
Fems Yeast Research     Hybrid Journal   (Followers: 14, SJR: 1.213, h-index: 66)
Foreign Policy Analysis     Hybrid Journal   (Followers: 23, SJR: 0.859, h-index: 10)
Forestry: An Intl. J. of Forest Research     Hybrid Journal   (Followers: 15, 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: 32, SJR: 0.123, h-index: 10)
French Studies     Hybrid Journal   (Followers: 20, 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: 14, SJR: 3.22, h-index: 39)
Geophysical J. Intl.     Hybrid Journal   (Followers: 35, SJR: 1.839, h-index: 119)
German History     Hybrid Journal   (Followers: 27, SJR: 0.437, h-index: 13)
GigaScience     Open Access   (Followers: 3)
Global Summitry     Hybrid Journal   (Followers: 1)
Glycobiology     Hybrid Journal   (Followers: 14, SJR: 1.692, h-index: 101)
Health and Social Work     Hybrid Journal   (Followers: 55, SJR: 0.505, h-index: 40)
Health Education Research     Hybrid Journal   (Followers: 14, SJR: 0.814, h-index: 80)
Health Policy and Planning     Hybrid Journal   (Followers: 23, SJR: 1.628, h-index: 66)
Health Promotion Intl.     Hybrid Journal   (Followers: 21, SJR: 0.664, h-index: 60)
History Workshop J.     Hybrid Journal   (Followers: 30, SJR: 0.313, h-index: 20)
Holocaust and Genocide Studies     Hybrid Journal   (Followers: 27, SJR: 0.115, h-index: 13)
Human Molecular Genetics     Hybrid Journal   (Followers: 9, SJR: 4.288, h-index: 233)
Human Reproduction     Hybrid Journal   (Followers: 80, SJR: 2.271, h-index: 179)
Human Reproduction Update     Hybrid Journal   (Followers: 19, SJR: 4.678, h-index: 128)
Human Rights Law Review     Hybrid Journal   (Followers: 64, SJR: 0.7, h-index: 21)
ICES J. of Marine Science: J. du Conseil     Hybrid Journal   (Followers: 55, SJR: 1.233, h-index: 88)
ICSID Review     Hybrid Journal   (Followers: 12)
ILAR J.     Hybrid Journal   (Followers: 2, 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: 1, 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: 9, SJR: 1.37, h-index: 81)
Industrial Law J.     Hybrid Journal   (Followers: 33, SJR: 0.184, h-index: 15)
Information and Inference     Free  
Integrative and Comparative Biology     Hybrid Journal   (Followers: 8, SJR: 1.911, h-index: 90)
Interacting with Computers     Hybrid Journal   (Followers: 11, SJR: 0.529, h-index: 59)
Interactive CardioVascular and Thoracic Surgery     Hybrid Journal   (Followers: 5, SJR: 0.743, h-index: 35)
Intl. Affairs     Hybrid Journal   (Followers: 53, SJR: 1.264, h-index: 53)
Intl. Data Privacy Law     Hybrid Journal   (Followers: 31)
Intl. Health     Hybrid Journal   (Followers: 5, SJR: 0.835, h-index: 15)
Intl. Immunology     Hybrid Journal   (Followers: 3, SJR: 1.613, h-index: 111)
Intl. J. for Quality in Health Care     Hybrid Journal   (Followers: 34, SJR: 1.593, h-index: 69)
Intl. J. of Constitutional Law     Hybrid Journal   (Followers: 63, SJR: 0.613, h-index: 19)
Intl. J. of Epidemiology     Hybrid Journal   (Followers: 172, SJR: 4.381, h-index: 145)
Intl. J. of Law and Information Technology     Hybrid Journal   (Followers: 5, SJR: 0.247, h-index: 8)
Intl. J. of Law, Policy and the Family     Hybrid Journal   (Followers: 29, 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: 3, SJR: 1.69, h-index: 79)
Intl. J. of Public Opinion Research     Hybrid Journal   (Followers: 9, SJR: 0.906, h-index: 33)
Intl. J. of Refugee Law     Hybrid Journal   (Followers: 35, 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. Political Sociology     Hybrid Journal   (Followers: 34, SJR: 1.339, h-index: 19)
Intl. Relations of the Asia-Pacific     Hybrid Journal   (Followers: 20, 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: 40, SJR: 2.184, h-index: 68)
Intl. Studies Review     Hybrid Journal   (Followers: 18, 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: 48, SJR: 0.286, h-index: 34)
J. of Analytical Toxicology     Hybrid Journal   (Followers: 14, SJR: 1.038, h-index: 60)
J. of Antimicrobial Chemotherapy     Hybrid Journal   (Followers: 14, SJR: 2.157, h-index: 149)
J. of Antitrust Enforcement     Hybrid Journal   (Followers: 1)
J. of Applied Poultry Research     Hybrid Journal   (Followers: 4, SJR: 0.563, h-index: 43)
J. of Biochemistry     Hybrid Journal   (Followers: 42, 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: 36, 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: 13, SJR: 0.196, h-index: 15)
J. of Consumer Research     Full-text available via subscription   (Followers: 43, SJR: 4.896, h-index: 121)
J. of Crohn's and Colitis     Hybrid Journal   (Followers: 10, SJR: 1.543, h-index: 37)
J. of Cybersecurity     Hybrid Journal   (Followers: 3)
J. of Deaf Studies and Deaf Education     Hybrid Journal   (Followers: 10, SJR: 0.69, h-index: 36)
J. of Design History     Hybrid Journal   (Followers: 18, 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: 24, SJR: 2.909, h-index: 69)
J. of Environmental Law     Hybrid Journal   (Followers: 24, SJR: 0.457, h-index: 20)
J. of European Competition Law & Practice     Hybrid Journal   (Followers: 21)
J. of Experimental Botany     Hybrid Journal   (Followers: 14, SJR: 2.798, h-index: 163)
J. of Financial Econometrics     Hybrid Journal   (Followers: 23, SJR: 1.314, h-index: 27)
J. of Global Security Studies     Hybrid Journal   (Followers: 4)
J. of Heredity     Hybrid Journal   (Followers: 4, SJR: 1.024, h-index: 76)
J. of Hindu Studies     Hybrid Journal   (Followers: 8, SJR: 0.186, h-index: 3)
J. of Hip Preservation Surgery     Open Access  
J. of Human Rights Practice     Hybrid Journal   (Followers: 20, SJR: 0.399, h-index: 10)
J. of Infectious Diseases     Hybrid Journal   (Followers: 41, 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]   [80 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  [370 journals]
  • Human induced pluripotent stem cells and male infertility: an overview of
           current progress and perspectives
    • Authors: Fang F; Li Z, Zhao Q, et al.
      First page: 188
      Abstract: Recently, significant progress has been made in ART for the treatment of male infertility. However, current ART has failed to help infertile patients with non-obstructive azoospermia, unless donor sperm is used. In fact, most couples wish to have their own genetically related child. Human induced pluripotent stem cells (hiPSCs) can be generated from patients’ somatic cells and in vitro derivation of functional germ cells from patient-specific iPSCs may provide new therapeutic strategies for infertile couples. The overall developmental dynamics of human primordial germ cells are similar to that in mice, but accumulating evidence suggests that there are crucial differences between human and mouse PGC specification. Unlike mouse iPSCs (miPSCs) in naive state, hiPSCs exhibit a primed pluripotency which possess less potential for the germ cell fate. Based on research in mice, male germ cells at different stages have been derived from hiPSCs with different protocols, including spontaneous differentiation, overexpression of germ cell regulators, addition of cytokines, co-culture with gonadal cells in vitro and xeno-transplantation. The aim of this review is to summarize the current advances in derivation of male germ cells from hiPSCs and raise the perspectives of hiPSCs in medical application for male infertility, as well as in basic research for male germ cell development.
      PubDate: Fri, 05 Jan 2018 00:00:00 GMT
      DOI: 10.1093/humrep/dex369
  • Development of a new comprehensive and reliable endometrial receptivity
           map (ER Map/ER Grade) based on RT-qPCR gene expression analysis
    • Authors: Enciso M; Carrascosa J, Sarasa J, et al.
      First page: 220
      Abstract: STUDY QUESTIONIs it possible to determine the receptivity status of an endometrium by combined quantitative reverse transcription PCR (RT-qPCR) expression analysis of genes involved in endometrial proliferation and immunity'SUMMARY ANSWERThe new ER Map®/ER Grade® test can predict endometrial receptivity status by RT-qPCR using a new panel of genes involved in endometrial proliferation and the maternal immune response associated to embryonic implantation.WHAT IS KNOWN ALREADYThe human endometrium reaches a receptive status adequate for embryonic implantation around Days 19–21 of the menstrual cycle. During this period, known as the window of implantation (WOI), the endometrium shows a specific gene expression profile suitable for endometrial function evaluation. The number of molecular diagnostic tools currently available to characterize this process is very limited. In this study, a new system for human endometrial receptivity evaluation was optimized and presented for the first time.STUDY DESIGN, SIZE, DURATIONER Map®/ER Grade® validation was achieved on 312 endometrial samples including fertile women and patients undergoing fertility treatment between July 2014 and March 2016. Expression analyses of 184 genes involved in endometrial receptivity and immune response were performed. Samples were additionally tested with an independent endometrial receptivity test.PARTICIPANTS/MATERIALS, SETTING, METHODSA total of 96 fertile women and 120 assisted reproduction treatment (ART) patients participated in the study. Endometrial biopsy samples were obtained at LH + 2 and LH + 7 days in fertile subjects in a natural cycle and at the window of implantation (WOI) in patients in a hormone-replacement therapy (HRT) cycle. Total RNA was purified, quality-checked and reverse-transcribed. Gene expression was quantified by high-throughput RT-qPCR and statistically analyzed. Informative genes were selected and used to classify samples into four different groups of endometrial receptivity status.MAIN RESULTS AND THE ROLE OF CHANCESignificantly different gene expression levels were found in 85 out of 184 selected genes when comparing LH + 2 and LH + 7 samples (paired t-test, P < 0.05). Gene ontology analyses revealed that cell division and proliferation, cell signaling and response, extracellular organization and communication, immunological activity, vascular proliferation, blood pressure regulation and embryo implantation are the most over-represented biological terms in this group of genes. Principal component analysis and discriminant functional analysis showed that 40 of the differentially expressed genes allowed accurate classification of samples according to endometrial status (proliferative, pre-receptive, receptive and post-receptive) in both fertile and infertile groups.LARGE SCALE DATAN/A.LIMITATIONS, REASONS FOR CAUTIONTo evaluate the efficacy of this new tool to improve ART outcomes, further investigations such as non-selection studies and randomized controlled trials will also be required.WIDER IMPLICATIONS OF THE FINDINGSA new comprehensive system for human endometrial receptivity evaluation based on gene expression analysis has been developed. The identification of the optimal time for embryo transfer is essential to maximize the effectiveness of ART. This study is a new step in the field of personalized medicine in human reproduction which may help in the management of endometrial preparation for embryo transfer, increasing the chances of pregnancy for many couples.STUDY FUNDING/COMPETING INTEREST(S)The authors have no potential conflict of interest to declare. No external funding was obtained for this study.
      PubDate: Fri, 05 Jan 2018 00:00:00 GMT
      DOI: 10.1093/humrep/dex370
  • Adipose tissue-derived stem cells in a fibrin implant enhance
           neovascularization in a peritoneal grafting site: a potential way to
           improve ovarian tissue transplantation
    • Authors: Manavella D; Cacciottola L, Desmet C, et al.
      First page: 270
      Abstract: STUDY QUESTIONDo two different concentrations of human adipose tissue-derived stem cells (ASCs) embedded inside a fibrin scaffold have the potential to differentiate into vessels and aid vascularization in a peritoneal grafting site intended for ovarian tissue transplantation'SUMMARY ANSWERHuman ASCs in low and high concentrations differentiated into vessels when transplanted to mouse peritoneum inside a fibrin matrix, but only high ASC concentrations significantly increased human vessel area 14 days after transplantation.WHAT IS KNOWN ALREADYASCs have multilineage differentiation potential, including proangiogenic properties and have been used in tissue engineering to enhance vascularization in transplanted tissues. Fibrin has been studied and used as an ASC-compatible biomaterial.STUDY DESIGN, SIZE, DURATIONIn vivo experimental model using 22 severe combined immunodeficient mice. In total, 16 mice (eight per group) were intraperitoneally grafted with a fibrin scaffold loaded with two different human ASC concentrations (either 150 000 [L-ASC] or 1 500 000 [H-ASC] cells) and lithium phthalocyanine (LiPc) crystals as oxygen-sensitive probes. Six mice were grafted with an empty fibrin (EF) implant containing only LiPc and served as controls. Levels of partial pressure of oxygen (pO2) in implants were monitored in vivo by electron paramagnetic resonance oximetry (EPR). ASC identification, proliferation, and host and human vascularization were analyzed by immunohistochemistry (IHC). All analyses were performed on post-grafting Days 3, 7 and 14.PARTICIPANTS/MATERIALS, SETTING, METHODSProspective experimental study conducted at the Gynecology Research Unit, Université Catholique de Louvain. All materials were used to perform pO2 measurements (EPR oximetry), as well as histological (hematoxylin–eosin staining) and IHC (anti-human vimentin, anti-human Ki67, anti-mouse and human double CD34) analyses.MAIN RESULTS AND THE ROLE OF CHANCEA significant increase in pO2 in implants was observed in all groups between Days 3 and 7 (P < 0.001). ASC-loaded implants displayed a tendency towards increased pO2 levels from Days 7 to 14, not observed in EF implants. ASC-loaded implants showed differentiation into human CD34-positive vessels. Total CD34-positive endothelial area was correlated to pO2 values obtained by EPR oximetry (r = 0.6506, P = 0.0019). In the H-ASC group, a greater human CD34-positive vascular surface area was found compared to the L-ASC group 14 days after transplantation (P < 0.0049).LARGE SCALE DATAN/A.LIMITATIONS REASONS FOR CAUTIONAs demonstrated by our results, ASCs transplanted inside a fibrin matrix can differentiate into CD34-positive human vessels. However, other possible mechanisms involved in ASC angiogenic behavior remain to be investigated.WIDER IMPLICATIONS OF THE FINDINGSHigh concentrations of ASCs loaded inside a fibrin scaffold could serve as a substrate to prepare a peritoneal grafting site over 14 days, in order to enhance vascularization once human ovarian tissue is grafted. Our proposed preparation of the grafting site would not only benefit ovarian tissue transplantation, but also other experimental avascular grafting procedures.STUDY FUNDING/COMPETING INTEREST(S)This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (FNRS-PDR Convention T.0077.14, Télévie Grant no. 7.6515.16F awarded to DDM and Grant 5/4/150/5 awarded to M.M.D. [CAA is FRS-FNRS research associate]), Fonds Spéciaux de Recherche, and Fondation St Luc, Foundation Against Cancer, and donations from the Ferrero family. None of the authors have any competing interests to declare.
      PubDate: Wed, 03 Jan 2018 00:00:00 GMT
      DOI: 10.1093/humrep/dex374
  • Fertility preservation in women harboring deleterious BRCA mutations:
           ready for prime time'
    • Authors: Peccatori F; Mangili G, Bergamini A, et al.
      First page: 181
      Abstract: Fertility issues have become critical in the management and counseling of BRCA mutation carriers. In this setting four points deserve consideration. (1) Women in general lose their ability to conceive at a mean age of 41 years, thus the suggested policy of prophylactic bilateral salpingo-oophorectomy at age 40 for BRCA mutation carriers does not affect the chances of natural pregnancy. Conversely, if the procedure is chosen at 35 years old, oocyte cryopreservation prior to surgery should be considered. (2) Some evidence suggests that ovarian reserve may actually be partly reduced in BRCA mutations carriers and that the mutation may affect ovarian responsiveness to stimulation. However, these findings are still controversial. (3) Breast cancer is not rare before the age of 40 and fertility preservation after diagnosis can be requested in a significant proportion of BRCA mutation carriers. Thus, a policy of oocyte cryopreservation in young healthy carriers deserves consideration. The procedure could be considered at a young age and in an elective setting, when ovarian stimulation may yield more oocytes of better quality. (4) Preimplantation genetic diagnosis (PGD) could be considered in BRCA mutations carriers, particularly when good quality oocytes have been stored at a young age. Based on the current knowledge, a univocal approach cannot be recommended; in depth patient counseling is warranted.
      PubDate: Fri, 01 Dec 2017 00:00:00 GMT
      DOI: 10.1093/humrep/dex356
  • Birthweight of singletons born after cleavage-stage or blastocyst transfer
           in fresh and warming cycles
    • Authors: De Vos A; Santos-Ribeiro S, Van Landuyt L, et al.
      First page: 196
      Abstract: STUDY QUESTIONDoes extended culture to the blastocyst stage affect singleton birthweight after either fresh or vitrified-warmed embryo transfer'SUMMARY ANSWERSingleton birthweight z-scores did not vary significantly after a fresh blastocyst transfer, whereas the additional effect of vitrification remains inconclusive.WHAT IS KNOWN ALREADYObservational studies have associated extended culture with an increased risk of preterm birth and low birthweight. On the contrary, in terms of birthweight and gestational age, singletons born after vitrification have been associated with a better perinatal outcome when compared to those born following a fresh transfer.STUDY DESIGN, SIZE, DURATIONOur post-hoc cohort analysis on neonatal outcomes included 447 liveborn singletons was derived from a recent retrospective analysis on cumulative live birth rates after cleavage-stage and blastocyst transfers. These babies were born following a fresh single cleavage-stage transfer (FCT Day 3, n = 113), fresh single blastocyst transfer (FBT Day 5, n = 218), vitrified-warmed cleavage-stage transfer (VCT Day 3, n = 58) or vitrified-warmed blastocyst transfer (VBT Day 5, n = 58).PARTICIPANTS/MATERIALS, SETTING, METHODSSingleton birthweight was the primary outcome measure. Gestational age and gender of the newborn were accounted for by using birthweight z-scores in a multivariable linear regression analysis, adjusting for other confounders (maternal age, BMI, parity and smoking behaviour). Vanishing twins were excluded from the analysis.MAIN RESULTS AND THE ROLE OF CHANCEA significantly lower z-score was observed after blastocyst transfer compared to cleavage-stage transfer in the vitrified-warmed Day 5 group (P = 0.013), a difference not observed in the fresh transfer groups (P = 0.32). Following multivariable regression analysis [adjusted regression coefficient (95% confidence interval)], the FCT and FBT groups showed no significant influence on the birthweight z-scores after fresh transfer [−0.19 (−0.44; 0.05)], but the transfer of vitrified blastocysts (VBT) was associated with a lower birthweight [−0.52 (−0.90; −0.15)] compared with the transfer of vitrified cleavage-stage embryos (VCT).LIMITATIONS, REASONS FOR CAUTIONThe present cohort was relatively small, especially in the vitrified-warmed subgroups. Pregnancy-associated factors possibly influencing birthweight (such as diabetes, hypertension, pre-eclampsia) were also not accounted for in the analysis.WIDER IMPLICATIONS OF THE FINDINGSDifferent ART procedures, including extended culture and vitrification, may hold potential safety issues. These results require further confirmation in future larger studies.STUDY FUNDING/COMPETING INTEREST(S)None.TRIAL REGISTRATION NUMBERN/A.
      PubDate: Fri, 01 Dec 2017 00:00:00 GMT
      DOI: 10.1093/humrep/dex361
  • Medical treatment or surgery for colorectal endometriosis' Results of
           a shared decision-making approach
    • Authors: Vercellini P; Frattaruolo M, Rosati R, et al.
      First page: 202
      Abstract: STUDY QUESTIONWhat is the degree of patient satisfaction in women with symptomatic colorectal endometriosis who choose medical or surgical treatment after a shared decision-making (SDM) process'SUMMARY ANSWERThe degree of satisfaction with treatment was high both in women who chose medical treatment with a low-dose oral contraceptive (OCP) or a progestin, and in those who chose to undergo surgical resection of bowel endometriosis.WHAT IS KNOWN ALREADYHormonal therapies and surgery for colorectal endometriosis have been investigated in non-comparative studies with inconsistent results.STUDY DESIGN, SIZE, DURATIONParallel cohort study conducted on 87 women referring to our centre with an indication to surgery for colorectal endometriosis. A standardised SDM process was adopted, allowing women to choose their preferred treatment. Median follow-up was 40 [18–60] months in the medical therapy group and 45 [30–67] in the surgery group.PARTICIPANTS/MATERIALS, SETTING, METHODSPatients with endometriosis infiltrating the proximal rectum, the rectosigmoid junction, and the sigmoid, not causing severe sub-occlusive symptoms were enroled. A total of 50 patients chose treatment with an OCP (n = 12) or a progestin (n = 38), whereas 37 women confirmed their previous indication to surgery. Patient satisfaction was graded according to a 5-category scale. Variations in bowel and pain symptoms were measured by means of a 0–10 numeric rating scale. Constipation was assessed with the Knowles–Eccersley–Scott Symptom Questionnaire (KESS), health-related quality of life with the Short Form-12 questionnaire (SF-12), psychological status with the Hospital Anxiety and Depression scale (HADS) and sexual functioning with the Female Sexual Function Index (FSFI).MAIN RESULTS AND THE ROLE OF CHANCESix women in the medical therapy group requested surgery because of drug inefficacy (n = 3) or intolerance (n = 3). Seven major complications were observed in the surgery group (19%). At 12-month follow-up, 39 (78%) women in the medical therapy group were satisfied with their treatment, compared with 28 (76%) in the surgery group (adjusted odds ratio (OR), 1.37; 95% confidence interval (CI), 0.45–4.15; intention-to-treat analysis). Corresponding figures at final follow-up assessment were 72% in the former group and 65% in the latter one (adjusted OR, 1.74; 95% CI, 0.62–4.85). The 60-month cumulative proportion of dissatisfaction-free participants was 71% in the medical therapy group compared with 61% in the surgery group (P = 0.61); the Hazard incidence rate ratio was 1.21 (95% CI, 0.57–2.62). Intestinal complaints were ameliorated by both treatments. Significant between-group differences in favour of medical treatment were observed at 12-month follow-up in diarrhoea, dysmenorrhoea, non-menstrual pelvic pain and SF-12 physical component scores. The total HADS score improved significantly in both groups, whereas the total FSFI score improved only in women who chose medical therapy.LIMITATIONS REASONS FOR CAUTIONAs treatments were not randomly assigned, selection bias and confounding are likely. The small sample size exposes to the risk of type II errors.WIDER IMPLICATIONS OF THE FINDINGSWhen adequately informed and empowered through a SDM process, most patients with non-occlusive colorectal endometriosis who had already received a surgical indication, preferred medical therapy. The possibility of choosing the preferred treatment may allow maximisation of the potential effect of the interventions.STUDY FUNDING/COMPETING INTEREST(S)This study was financed by Italian fiscal contribution ‘5 × 1000’—Ministero dell’Istruzione, dell’Università e della Ricerca—devolved to Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy. P.V., M.P.F., R.R., D.D., A.R., P.M., O.D.G. and M.C. declare that they have no conflicts of interest. E.S. received grants from Ferring and Serono.
      PubDate: Fri, 08 Dec 2017 00:00:00 GMT
      DOI: 10.1093/humrep/dex364
  • Safety of ovarian tissue transplantation in patients with borderline
           ovarian tumors
    • Authors: Masciangelo R; Bosisio C, Donnez J, et al.
      First page: 212
      Abstract: STUDY QUESTIONIs transplantation of cryopreserved ovarian tissue from patients with borderline ovarian tumors (BOTs) a safe procedure'SUMMARY ANSWERBOT cells were found in frozen–thawed and xenografted ovarian tissue in 1 of 11 BOT patients.WHAT IS KNOWN ALREADYThe risk of reintroducing malignant cells upon ovarian tissue transplantation has been subject of debate for many years. Reimplantation of cryopreserved ovarian tissue from leukemia patients is unsafe, while results from studies of cryopreserved ovarian tissue from other forms of cancer, such as Hodgkin’s lymphoma, are reassuring.STUDY DESIGN, SIZE, DURATIONProspective experimental study conducted in an academic research unit using ovarian tissue from 11 patients undergoing cryopreservation for BOTs.PARTICIPANTS/MATERIALS, SETTING, METHODSHistology, immunohistochemistry (IHC) for mucin 1 (MUC1) and cytokeratin 7 (CK7) and molecular analysis by reverse transcription quantitative polymerase chain reaction (RT-qPCR) for CK7 and MUC1 were performed on frozen–thawed ovarian tissue from 11 patients. Long-term (5 months) xenografting of ovarian tissue in immunodeficient mice was performed. The xenografts were analyzed by histology, IHC and RT-qPCR, furthermore IHC for CD10, a marker of endometriosis, was performed on a selected sample.MAIN RESULTS AND THE ROLE OF CHANCEAnalysis by histology, IHC and RT-qPCR indicated 10 of the ovarian tissue samples were negative. Analysis of the xenograft samples indicated nine were negative for malignant cells but in two xenografts glandular lesions were detected by histology. In these two xenografts, CK7 and MUC1 markers were demonstrated by IHC and CK7 expression also by RT-qPCR. A BOT was confirmed in the xenograft in which the original ovarian tissue was positive, while in the other case IHC demonstrated expression of endometriosis marker CD10.LIMITATIONS, REASONS FOR CAUTIONCryopreserved ovarian fragments cannot be tested before transplantation, therefore the preimplantation analysis cannot guarantee that all cryopreserved fragments will be free of BOT cells.WIDER IMPLICATIONS OF THE FINDINGSBOT cells can be found in cryopreserved ovarian tissue from BOT patients, therefore preimplantation analysis is an absolute prerequisite. Endometriosis can also be detected in cryopreserved ovarian tissue and caution should also be exercised in this scenario.STUDY FUNDING/COMPETING INTEREST(S)This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (FNRS–PDR Convention T.0077.14, Télévie Grant 7.4590.16 awarded to Rossella Masciangelo, and Grant 5/4/150/5 awarded to Marie-Madeleine Dolmans), the Fonds Speciaux de Recherche, and the Foundation Against Cancer. None of the authors have any conflicting interests to declare.
      PubDate: Thu, 21 Dec 2017 00:00:00 GMT
      DOI: 10.1093/humrep/dex352
  • New application of dydrogesterone as a part of a progestin-primed ovarian
           stimulation protocol for IVF: a randomized controlled trial including 516
           first IVF/ICSI cycles
    • Authors: Yu S; Long H, Chang H, et al.
      First page: 229
      Abstract: STUDY QUESTIONCan dydrogesterone (DYG) be used as an alternative progestin in a progesterone primed ovarian stimulation (PPOS) protocol'SUMMARY ANSWERDYG can be used as an appropriate alternative progestin in a PPOS protocol.WHAT IS KNOWN ALREADYPPOS is a new ovarian stimulation regimen based on a freeze-all strategy that uses progestin as an alternative to a GnRH analog for suppressing a premature LH surge during the follicular phase. Medroxyprogesterone acetate (MPA) has been successfully used as an adjuvant to gonadotrophin in the PPOS protocol. However, the use of MPA may lead to stronger pituitary suppression and thus may require a higher dosage of hMG and a longer duration of ovarian stimulation than that of conventional ovarian stimulation protocol.STUDY DESIGN SIZE, DURATIONA prospective RCT including 516 patients was performed between November 2015 and November 2016. Computerized randomization was conducted to assign participants at a 1:1 ratio into two treatment groups: an hMG + DYG group (260 patients) or an hMG + MPA group (256 patients) followed by IVF or ICSI with the freeze-all strategy. One cycle per patient was included. The primary outcome of the trial was the number of oocytes retrieved. The sample size was chosen to detect a difference of two oocytes with a power of 90%.PARTICIPANTS/MATERIALS, SETTING, METHODSPatients under 36 years of age with normal ovarian reserve who were undergoing their first IVF/ICSI procedure due to tubal factor infertility were randomized into two groups based on the oral progestin protocol used: hMG co-treatment with DYG (hMG + DYG) or hMG co-treatment with MPA (hMG + MPA). The different progestin was simultaneously administered at the beginning of menstrual cycle 3 (MC3). Oocyte maturation was co-triggered by administration of a GnRH agonist and hCG. All viable embryos from both protocols were cryopreserved for later transfer. Only the first frozen embryo transfer (FET) cycle was included in our study. The embryological and clinical outcomes were measured.MAIN RESULTS AND THE ROLE OF CHANCEBasic characteristics, such as age, BMI and infertility duration, in both groups were comparable. There was no significant difference in the number (mean ± SD) of oocytes retrieved [10.8 ± 6.3 for the hMG + DYG group versus 11.1 ± 5.8 for the hMG + MPA group, P = 0.33] or the oocyte retrieval rate [74.3 ± 19.6% for the hMG + DYG group versus 75.0 ± 19.5% for the hMG + MPA group, P = 0.69] between the groups. The viable embryo rate per oocyte retrieved did not differ between the two groups [odds ratio (OR): 1.08, 95% CI: 0.97–1.21, P = 0.16]: 37.4% (1052/2815) for the hMG + DYG group versus 35.6% (1009/2837) for the hMG + MPA group. During the whole process of ovarian stimulation, the mean LH level in the hMG + DYG group was always higher than that in the hMG + MPA group (P < 0.001); however, no patient from either group experienced a premature LH surge. In addition, no patients experienced moderate or severe ovarian hyperstimulation syndrome during the ovarian stimulation. No significant difference was found in the clinical pregnancy rate of the first FET cycle between the two groups (OR: 0.82, 95% CI: 0.56–1.21, P = 0.33): 57.6% for the hMG + DYG group (125/217) versus 62.3% for the hMG + MPA group (132/212).LIMITATIONS REASONS FOR CAUTIONThe patients and physician were not blinded to the study. Further, a large proportion of patients were still pregnant at the end of the clinical trial, therefore live birth rates were not observed in the follow-up period. The dose-effectiveness of DYG administration was not addressed in the trial design.WIDER IMPLICATIONS OF THE FINDINGSDYG, which exhibits no or only weak inhibition of ovulation in normal dosage, can serve as an hMG adjuvant during ovarian stimulation. This finding suggests the possibility of a new application of DYG: as an appropriate alternative progestin for a PPOS protocol in IVF.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by The National Nature Science Foundation of China (Grant no. 81503603), Shanghai Three-year Plan on Promoting TCM Development (Grant no. ZY3-LCPT-2-2006) and the Natural Science Foundation of Shanghai (Grant nos. 15401932700 and 15ZR1424900). None of the authors declare any conflict of interest.TRIAL REGISTRATION ChiCTR-IPR-15007251.TRIAL REGISTRATION 22 October 2015.DATE OF FIRST PATIENT’S ENROLLMENT1 November 2015.
      PubDate: Fri, 29 Dec 2017 00:00:00 GMT
      DOI: 10.1093/humrep/dex367
  • Reduced live-birth rates after IVF/ICSI in women with previous unilateral
           oophorectomy: results of a multicentre cohort study
    • Authors: Lind T; Holte J, Olofsson J, et al.
      First page: 238
      Abstract: STUDY QUESTIONIs there a reduced live-birth rate (LBR) after IVF/ICSI treatment in women with a previous unilateral oophorectomy (UO)'SUMMARY ANSWERA significantly reduced LBR after IVF/ICSI was found in women with previous UO when compared with women with intact ovaries in this large multicentre cohort, both crudely and after adjustment for age, BMI, fertility centre and calendar period and regardless of whether the analysis was based on transfer of embryos in the fresh cycle only or on cumulative results including transfers using frozen-thawed embryos.WHAT IS KNOWN ALREADYSimilar pregnancy rates after IVF/ICSI have been previously reported in case-control studies and small cohort studies of women with previous UO versus women without ovarian surgery. In all previous studies multiple embryos were transferred. No study has previously evaluated LBR in a large cohort of women with a history of UO.STUDY DESIGN, SIZE, DURATIONThis research was a multicentre cohort study, including five reproductive medicine centres in Sweden: Carl von Linné Clinic (A), Karolinska University Hospital (B), Uppsala University Hospital (C), Linköping University Hospital (D) and Örebro University Hospital (E). The women underwent IVF/ICSI between January 1999 and November 2015. Single embryo transfer (SET) was performed in approximately 70% of all treatments, without any significant difference between UO exposed women versus controls (68% versus 71%), respectively (P = 0.32), and a maximum of two embryos were transferred in the remaining cases. The dataset included all consecutive treatments and fresh and frozen-thawed cycles.PARTICIPANTS/MATERIALS, SETTING, METHODSThe exposed cohort included 154 women with UO who underwent 301 IVF/ICSI cycles and the unexposed control cohort consisted of 22 693 women who underwent 41 545 IVF/ICSI cycles. Overall, at the five centres (A–E), the exposed cohort underwent 151, 34, 35, 41 and 40 treatments, respectively, and they were compared with controls of the same centre (18 484, 8371, 5575, 4670 and 4445, respectively).The primary outcome was LBR, which was analysed per started cycle, per ovum pick-up (OPU) and per embryo transfer (ET). Secondary outcomes included the numbers of oocytes retrieved and supernumerary embryos obtained, the Ovarian Sensitivity Index (OSI), embryo quality scores and cumulative pregnancy rates. We used a Generalized Estimating Equation (GEE) model for statistical analysis in order to account for repeated treatments.MAIN RESULTS AND THE ROLE OF CHANCEThe exposed (UO) and control women's groups were comparable with regard to age and performance of IVF or ICSI. Significant differences in LBR, both crude and age-adjusted, were observed between the UO and control groups: LBR per started cycle (18.6% versus 25.4%, P = 0.007 and P = 0.014, respectively), LBR/OPU (20.3% versus 27.1%, P = 0.012 and P = 0.015, respectively) and LBR/ET (23.0% versus 29.7%, P = 0.022 and P = 0.025, respectively). The differences in LBR remained significant after inclusion of both fresh and frozen-thawed transfers (both crude and age-adjusted data): LBR/OPU (26.1% versus 34.4%, P = 0.005 and P = 0.006, respectively) and LBR/ET (28.3% versus 37.1%, P = 0.006 and P = 0.006, respectively). The crude cancellation rate was significantly higher among women with a history of UO than in controls (18.9% versus 14.5%, P = 0.034 and age-adjusted, P = 0.178). In a multivariate GEE model, the cumulative odds ratios for LBR (fresh and frozen-thawed)/OPU (OR 0.70, 95% CI 0.52–0.94, P = 0.016) and LBR (fresh and frozen-thawed)/ET (OR 0.68, 95% CI 0.51–0.92, P = 0.012) were approximately 30% lower in the group of women with UO when adjusted for age, BMI, reproductive centre, calendar period and number of embryos transferred when appropriate. The OSI was significantly lower in women with a history of UO than in controls (3.6 versus 6.0) and the difference was significant for both crude and age-adjusted data (P = <0.001 for both). Significantly fewer oocytes were retrieved in treatments of women with UO than in controls (7.2 versus 9.9, P = <0.001, respectively).LIMITATIONS, REASONS FOR CAUTIONDue to the nature of the topic, this is a retrospective analysis, with all its inherent limitations. Furthermore, the cause for UO was not possible to obtain in all cases. A diagnosis of endometriosis was also more common in the UO group, i.e. a selection bias in terms of poorer patient characteristics in the UO group cannot be completely ruled out. However, adjustment for all known confounders did not affect the general results.WIDER IMPLICATIONS OF THE FINDINGSTo date, this is the largest cohort investigated and the first study indicating an association of achieving reduced live birth after IVF/ICSI in women with previous UO. These findings are novel and contradict the earlier notion that IVF/ICSI treatment is not affected, or is only marginally affected by previous UO.STUDY FUNDING/COMPETI...
      PubDate: Mon, 04 Dec 2017 00:00:00 GMT
      DOI: 10.1093/humrep/dex358
  • Surrogacy families headed by gay men: relationships with surrogates and
           egg donors, fathers’ decisions over disclosure and children’s views on
           their surrogacy origins
    • Authors: Carone N; Baiocco R, Manzi D, et al.
      First page: 248
      Abstract: STUDY QUESTIONHow do gay father families experience surrogacy in terms of their relationships with surrogates and egg donors, fathers’ disclosure decisions and children’s views on their surrogacy origins'SUMMARY ANSWERMore families had a relationship with the surrogate than the egg donor, and almost all had started to disclose to their children, the majority of whom expressed limited interest in their surrogacy conception.WHAT IS KNOWN ALREADYGay fathers tend to report greater contact with the surrogate than the egg donor and to disclose only the use of a surrogate (omitting discussion of the egg donor and the respective fathers’ genetic relatedness). Children’s views on their surrogacy conception to gay fathers are not known.STUDY DESIGN, SIZE, DURATIONThirty-one children and 80 fathers were interviewed as part of a larger in-depth investigation of 40 Italian gay father surrogacy families. Multiple strategies were used to recruit participants.PARTICIPANTS/MATERIALS, SETTING, METHODSChildren were aged 6–12 years and had been born to gay fathers through gestational surrogacy. Semi-structured interviews were conducted in participants’ homes with each family member, separately. Fathers’ interviews were presented from the perspective of the father who identified as being most involved with the child on a day-to-day basis. Qualitative content analysis was performed and quotations illustrating the findings were reported. Where appropriate, comparisons were conducted using χ2 or Fisher’s exact tests.MAIN RESULTS AND THE ROLE OF CHANCEA total of 31 children in 24 families were interviewed. Most families reported a harmonious relationship with the surrogate (n = 20, 57.1%) and a distant relationship with the donor (n = 10, 66.7%) (χ2(1) = 23.33, P < 0.001). Before the child was aged 4 years, almost all families (n = 34, 85%) had started to disclose their use of a surrogate, with 16 families (n = 16, 40%) also disclosing their use of a donated egg, and only 4 (10%) disclosing which father’s sperm had been used. Of the 31 children interviewed, most (n = 17, 54.8%) showed a clear understanding of their conception. About 19 (61.3%) expressed limited interest in their conception, 11 (35.5%) felt positive and 1 child (3.2%) was unsure how he felt. Children differed in their feelings towards their surrogate and egg donor (Fisher’s exact test, P = 0.002). Of the 31 children who were aware of the surrogate, the majority felt grateful towards her (n = 22, 71%), while of the 25 children who were also aware of the egg donation, 11 (44%) showed limited interest in their donor.LIMITATIONS, REASONS FOR CAUTIONThe sample’s convenience nature and the gay father families’ high income limited the representativeness of the findings. Further, some children belonged to the same family, and this could have biased the results, as these children may have had similar experiences.WIDER IMPLICATIONS OF THE FINDINGSPrior to this study, the voice of children conceived by gay fathers through surrogacy had not been heard. Future research on factors influencing children’s desired contact with—or interest in—the surrogate and/or egg donor and their feelings when contact is not possible will be important in preparing families for such events.STUDY FUNDING/COMPETING INTEREST(S)Support was obtained from a Sapienza Starting Grant for Research to the first author (grant number AR11715C77EB56B2). None of the authors has any conflict of interest.
      PubDate: Mon, 11 Dec 2017 00:00:00 GMT
      DOI: 10.1093/humrep/dex362
  • Human-specific subcellular compartmentalization of P-element induced wimpy
           testis-like (PIWIL) granules during germ cell development and
    • Authors: Gomes Fernandes M; He N, Wang F, et al.
      First page: 258
      Abstract: STUDY QUESTIONWhat is the dynamics of expression of P-element induced wimpy testis-like (PIWIL) proteins in the germline during human fetal development and spermatogenesis'SUMMARY ANSWERPIWIL1, PIWIL2, PIWIL3 and PIWIL4 were expressed in a sex-specific fashion in human germ cells (GC) during development and adulthood. PIWILs showed a mutually exclusive pattern of subcellular localization. PIWILs were present in the intermitochondrial cement and a single large granule in meiotic GC and their expression was different from that observed in mice, highlighting species-differences.WHAT IS KNOWN ALREADYIn mice, PIWIL proteins play prominent roles in male infertility. PIWIL mouse mutants show either post-meiotic arrest at the round spermatid stage (PIWIL1) or arrest at the zygotene-pachytene stage of meiosis I (PIWIL2 and PIWIL4) in males, while females remain fertile. Recent studies have reported a robust piRNA pool in human fetal ovary.STUDY DESIGN, SIZE, DURATIONThis is a qualitative analysis of PIWILs expression in paraffin-embedded fetal human male (N = 8), female gonads (N = 6) and adult testes (N = 5), and bioinformatics analysis of online available single-cell transcriptomics data of human fetal germ cells (n = 242).PARTICIPANTS/MATERIALS, SETTING, METHODSHuman fetal gonads from elective abortion without medical indication and adult testes biopsies were donated for research with informed consent. Samples were fixed, paraffin-embedded and analyzed by immunofluorescence to study the temporal and cellular localization of PIWIL1, PIWIL2, PIWIL3 and PIWIL4.MAIN RESULTS AND THE ROLE OF CHANCEPIWIL1, PIWIL2 and PIWIL4 showed a mutually exclusive pattern of subcellular localization, particularly in female oocytes. To our surprise, PIWIL1 immunostaining revealed the presence of a single dense paranuclear body, resembling the chromatoid body of haploid spermatocytes, in meiotic oocytes. Moreover, in contrast to mice, PIWIL4, but not PIWIL2, localized to the intermitochondrial cement. PIWIL3 was not expressed in GC during development. The upregulation of PIWIL transcripts correlated with the transcription of markers associated with piRNAs biogenesis like the TDRDs and HENMT1 in fetal GC.LARGE SCALE DATANon-applicable.LIMITATIONS, REASONS FOR CAUTIONThis study is limited by the restricted number of samples and consequently stages analyzed.WIDER IMPLICATIONS OF THE FINDINGSIn the germline, PIWILs ensure the integrity of the human genome protecting it from ‘parasitic sequences’. This study offers novel insights on the expression dynamics of PIWILs during the window of epigenetic remodeling and meiosis, and highlights important differences between humans and mice, which may prove particularly important to understand causes of infertility and improve both diagnosis and treatment in humans.STUDY FUNDING/COMPETING INTEREST(S)M.G.F. was funded by Fundação para a Ciência e Tecnologia (FCT) [SFRH/BD/78689/2011]; N.H. by China Scholarship Council (CSC) [No. 201307040026] and F.W. by Medical Personnel Training Abroad Project of Henan Province [No. 2015022] and S.M.C.d.S.L. by the Netherlands Organization of Scientific Research (NWO) [ASPASIA 015.007.037] and the Interuniversity Attraction Poles-Phase VII [IUAP/PAI P7/14]. The authors have no conflicts of interest to declare.
      PubDate: Mon, 11 Dec 2017 00:00:00 GMT
      DOI: 10.1093/humrep/dex365
  • Endometrial stromal cell attachment and matrix homeostasis in abdominal
           wall endometriomas
    • Authors: Itoh H; Mogami H, Bou Nemer L, et al.
      First page: 280
      Abstract: STUDY QUESTIONHow does progesterone alter matrix remodeling in abdominal wall endometriomas compared with normal endometrium'SUMMARY ANSWERProgesterone may prevent attachment of endometrial cells to the abdominal wall, but does not ameliorate abnormal stromal cell responses of abdominal wall endometriomas.WHAT IS KNOWN ALREADYMenstruation is a tightly orchestrated physiologic event in which steroid hormones and inflammatory cells cooperatively initiate shedding of the endometrium. Abdominal wall endometriomas represent a unique form of endometriosis in which endometrial cells inoculate fascia or dermis at the time of obstetrical or gynecologic surgery. Invasion of endometrium into ectopic sites requires matrix metalloproteinases (MMPs) for tissue remodeling but endometrium is not shed externally.STUDY DESIGN SIZE, DURATIONObservational study in 14 cases and 19 controls.PARTICIPANTS /MATERIALS, SETTING, METHODSTissues and stromal cells isolated from 14 abdominal wall endometriomas were compared with 19 normal cycling endometrium using immunohistochemistry, quantitative PCR, gelatin zymography and cell attachment assays. P values < 0.05 were considered significant and experiments were repeated in at least three different cell preps to provide scientific rigor to the conclusions.MAIN RESULTS AND THE ROLE OF CHANCEThe results indicate that MMP2 and MMP9 are not increased by TGFβ1 in endometrioma stromal cells. Although progesterone prevents attachment of endometrioma cells to matrix components of the abdominal wall, it does not ameliorate these abnormal stromal cell responses to TGFβ1.LARGE SCALE DATAN/A.LIMITATIONS REASONS FOR CAUTIONEndometriomas were collected from women identified pre-operatively. Not all endometriomas were collected. Stromal cells from normal endometrium were from different patients, not women undergoing endometrioma resection.WIDER IMPLICATIONS OF THE FINDINGSThis work provides insight into the mechanisms by which progesterone may prevent abdominal wall endometriomas but, once established, are refractory to progesterone treatment.STUDY FUNDING/COMPETING INTEREST(S)Tissue acquisition was supported by NIH P01HD087150.
      Authors have no competing interests.
      PubDate: Thu, 28 Dec 2017 00:00:00 GMT
      DOI: 10.1093/humrep/dex371
  • The direct and indirect effects of kisspeptin-54 on granulosa lutein cell
    • Authors: Owens L; Abbara A, Lerner A, et al.
      First page: 292
      Abstract: STUDY QUESTIONWhat are the in vivo and in vitro actions of kisspeptin-54 on the expression of genes involved in ovarian reproductive function, steroidogenesis and ovarian hyperstimulation syndrome (OHSS) in granulosa lutein (GL) cells when compared with traditional triggers of oocyte maturation'SUMMARY ANSWERThe use of kisspeptin-54 as an oocyte maturation trigger augmented expression of genes involved in ovarian steroidogenesis in human GL cells including, FSH receptor (FSHR), LH/hCG receptor (LHCGR), steroid acute regulatory protein (STAR), aromatase, estrogen receptors alpha and beta (ESR1, ESR2), 3-beta-hydroxysteroid dehydrogenase type 2 (3BHSD2) and inhibin A (INHBA), when compared to traditional maturation triggers, but did not alter markers of OHSS.WHAT IS KNOWN ALREADYhCG is the most widely used trigger of oocyte maturation, but is associated with an increased risk of OHSS. The use of GnRH agonists to trigger oocyte maturation is a safer alternative to hCG. More recently, kisspeptin-54 has emerged as a novel therapeutic option that safely triggers oocyte maturation even in women at high risk of OHSS. Kisspeptin indirectly stimulates gonadotropin secretion by acting on hypothalamic GnRH neurons. Kisspeptin and its receptor are also expressed in the human ovary, but there is limited data on the direct action of kisspeptin on the ovary.STUDY DESIGN SIZE, DURATIONForty-eight women undergoing IVF treatment for infertility consented to kisspeptin-54 triggering and/or granulosa cell collection and were included in the study. Twelve women received hCG, 12 received GnRH agonist and 24 received kisspeptin-54 to trigger oocyte maturation. In the kisspeptin-54 group, 12 received one injection of kisseptin-54 (9.6 nmol/kg) and 12 received two injections of kisspeptin-54 at a 10 h interval (9.6 nmol/kg × 2).PARTICIPANTS/MATERIALS, SETTING, METHODSFollicular fluid was aspirated and pooled from follicles during the retrieval of oocytes for IVF/ICSI. GL cells were isolated and either RNA extracted immediately or cultured in vitro ± kisspeptin or hCG.MAIN RESULTS AND THE ROLE OF CHANCEGL cells from women who had received kisspeptin-54 had a 14-fold and 8-fold higher gene expression of FSHR and a 2-fold (ns) and 2.5-fold (P < 0.05) higher expression of LHCGR than GL cells from women who had received hCG or GnRH agonist, respectively. CYP19A1 expression was 3.6-fold (P < 0.05) and 4.5-fold (P < 0.05) higher, STAR expression was 3.4-fold (P < 0.01) and 1.8-fold (P < 0.05) higher, HSD3B2 expression was 7.5- (P < 0.01) and 2.5-fold higher (P < 0.05), INHBA was 2.5-fold (P < 0.01) and 2.5-fold (P < 0.01) higher in GL cells from women who had received kisspeptin-54 than hCG or GnRHa, respectively. ESR1 (P < 0.05) and ESR2 (P < 0.05) both showed 3-fold higher expression in cells from kisspeptin treated than GnRHa treated women. Markers of vascular permeability and oocyte growth factors were unchanged (VEGFA, SERPINF1, CDH5, amphiregulin, epiregulin). Gene expression of kisspeptin receptor was unchanged. Whereas treating GL cells in vitro with hCG induced steroidogenic gene expression, kisspeptin-54 had no significant direct effects on either OHSS genes or steroidogenic genes.LIMITATIONS REASONS FOR CAUTIONMost women in the study had PCOS, which may limit applicability to other patient groups. For the analysis of the in vitro effects of kisspeptin-54, it is important to note that GL cells had already been exposed in vivo to an alternate maturation trigger.WIDER IMPLICATIONS OF THE FINDINGSThe profile of serum gonadotropins seen with kisspeptin administration compared to other triggers more closely resemble that of the natural cycle as compared with hCG. Thus, kisspeptin could potentially permit an ovarian environment augmented for steroidogenesis, in particular progesterone synthesis, which is required for embryo implantation.STUDY FUNDING/COMPETING INTEREST(S)Dr Owens is supported by an Imperial College London PhD Scholarship. Dr Abbara is supported by an National Institute of Health Research Academic Clinical Lectureship. The authors do not have any conflict of interest to declare.TRIAL REGISTRATION NCT01667406.
      PubDate: Fri, 01 Dec 2017 00:00:00 GMT
      DOI: 10.1093/humrep/dex357
  • Aromatase inhibitor use during ovarian stimulation suppresses growth of
           uterine endometrial cancer in xenograft mouse model
    • Authors: Kawahara T; Okamoto N, Takae S, et al.
      First page: 303
      Abstract: STUDY QUESTIONCould aromatase inhibitors (AI) be used to reduce risks of uterine endometrial cancer growth or recurrence during ovarian stimulation'SUMMARY ANSWERIn a xenograft mouse model of endometrial cancer, concomitant AI administration suppressed the growth of endometrial cancer during ovarian stimulation.WHAT IS KNOWN ALREADYRecurrence and mortality rates of estrogen receptor-positive early breast cancer are reduced by long-term AI administration. Concomitant AI use for ovarian stimulation in patients with breast cancer is recommended for reducing estrogen-related potential risks. However, the efficacy of concomitant AI use for estrogen receptor-positive endometrial cancer have not been demonstrated conclusively by clinical or experimental animal studies.STUDY DESIGN, SIZE, DURATIONForty nude mice xenografted with uterine endometrial cancer cells were allocated to four groups. Group 1: no ovarian stimulation (control). Group 2: ovarian stimulation. Group 3: AI administration + ovarian stimulation. Group 4: ovariectomy and ovarian stimulation. Tumor growth was evaluated during the 6-week treatment period.PARTICIPANTS/MATERIALS, SETTING, METHODSIshikawa 3-H-12 uterine endometrial cancer cells (estrogen and progesterone receptors-positive) were transplanted into 6-week-old BALB/cSlc-nu/nu nude mice, followed by interventions 2 weeks later.MAIN RESULTS AND THE ROLE OF CHANCECompared to ovarian stimulation alone (Group 2), significant suppressions of tumor growth were observed in other three groups (Groups 1, 3 and 4, all at P < 0.05) and correlated with estrogen levels. AI administration had no apparent impact on embryo development.LIMITATIONS, REASONS FOR CAUTIONIn this study, we examined the growth of endometrial cancer tumors using one endometrial cancer cell line. Clinical endometrial cancer or hyperplasia cells can have diverse origins and AI may not be effective against other cancer cell types.WIDER IMPLICATIONS OF THE FINDINGSConcomitant AI use may provide a chance for safer childbirth by for patients with endometrial cancer or hyperplasia.STUDY FUNDING/CONPETING INTEREST(S)This study was supported by the Graduate Student Aid from the St. Marianna University School of Medicine. The authors declare no competing interests.
      PubDate: Thu, 28 Dec 2017 00:00:00 GMT
      DOI: 10.1093/humrep/dex368
  • Maternal age at birth and daughters’ subsequent childlessness
    • Authors: Basso O; Weinberg C, D’Aloisio A, et al.
      First page: 311
      Abstract: STUDY QUESTIONDoes maternal age at a daughter’s birth predict her subsequent probability of lifelong childlessness'SUMMARY ANSWERIn this study population, women born to older mothers were more likely to be childless.WHAT IS KNOWN ALREADYAlthough maternal age at childbearing is increasing in many countries, there is limited evidence on whether being born to older parents may influence offspring fertility.STUDY DESIGN SIZE AND DURATIONThis analysis included 43 135 women from the US-based Sister Study, a cohort study of 50 884 sisters of women with breast cancer recruited between 2003 and 2009.PARTICIPANTS/MATERIALS, SETTING, METHODSParticipants had no breast cancer at baseline. Women were included in the analytic sample if they were born between 1930 and 1964 and were at least 44 years old at enrolment. Median age when reproductive history was last ascertained was 63.8 years. We estimated relative risks (RR) and 95% CI of lifelong childlessness as a function of maternal age at birth, using multivariable log-binomial models, including total number of siblings, birth order, socioeconomic indicators of the family of origin, race and birth cohort. We examined the association in different subgroups and in a sibling-matched analysis including 802 sister pairs discordant for childlessness.MAIN RESULTS AND ROLE OF CHANCECompared with women born to 20–24-year-old mothers, those born to mothers aged 25–29, 30–34 and ≥35 years were more likely to be childless [RR (95% CI): 1.21 (1.14–1.29), 1.30 (1.22–1.39) and 1.40 (1.31–1.50), respectively]. The association was consistent in strata defined by birth cohort, number of siblings, birth order, and participant’s educational level, as well as within sister pairs. Overall, we found weak evidence for an independent contribution of paternal age at birth to the daughter’s probability of childlessness.LIMITATIONS REASONS FOR CAUTIONAll participants had at least one sister, and all information was self-reported. We had no knowledge of whether childlessness was intentional and found only a modest association between maternal age at birth and self-reported indicators of infertility. Still, the association with childlessness was highly consistent.WIDER IMPLICATIONS OF THE FINDINGGiven the widespread tendency to delay childbearing, evaluating the influence of maternal age at birth on offspring fertility is a public health priority.STUDY FUNDING/COMPETING INTERESTSThis research was supported in part by the Intramural Research Programme of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005). The authors report no conflict of interest.
      PubDate: Mon, 04 Dec 2017 00:00:00 GMT
      DOI: 10.1093/humrep/dex350
  • Gestational age-specific perinatal mortality rates for assisted
           reproductive technology (ART) and other births
    • Authors: Chughtai A; Wang A, Hilder L, et al.
      First page: 320
      Abstract: STUDY QUESTIONIs perinatal mortality rate higher among births born following assisted reproductive technology (ART) compared to non-ART births'SUMMARY ANSWEROverall perinatal mortality rates in ART births was higher compared to non-ART births, but gestational age-specific perinatal mortality rate of ART births was lower for very preterm and moderate to late preterm births.WHAT IS KNOWN ALREADYBirths born following ART are reported to have higher risk of adverse perinatal outcomes compared to non-ART births.STUDY DESIGN, SIZE, DURATIONThis population-based retrospective cohort study included 407 368 babies (391 952 non-ART and 15 416 ART)—393 491 singletons and 10 877 twins or high order multiples.PARTICIPANTS/MATERIALS, SETTING, METHODSAll births (≥20 weeks of gestation and/or ≥400 g of birthweight) in five states and territories in Australia during the period 2007–2009 were included in the study, using National Perinatal Data Collection (NPDC). Primary outcome measures were rates of stillbirth, neonatal and perinatal deaths. Adjusted odds ratio (AOR) and 95% confidence interval (CI) were used to estimate the likelihood of perinatal death.MAIN RESULTS AND THE ROLE OF CHANCERates of multiple birth and low birthweight were significantly higher in ART group compared to the non-ART group (P < 0.01). Overall perinatal mortality rate was significantly higher for ART births (16.5 per 1000 births, 95% CI 14.5–18.6), compared to non-ART births (11.3 per 1000 births, 95% CI 11.0–11.6) (AOR 1.45, 95% CI 1.26–1.68). However, gestational age-specific perinatal mortality rate of ART births (including both singletons and multiples) was lower for very preterm (<32 weeks’ gestation) and moderate to late preterm births (32–36 weeks’ gestation) (AOR 0.61, 95% CI 0.53–0.70 and AOR 0.61, 95% CI 0.53–0.70, respectively) compared to non-ART births. Congenital abnormality and spontaneous preterm were the most common causes of neonatal deaths in both ART and non-ART group.LIMITATIONS, REASONS FOR CAUTIONDue to different cut-off limit for perinatal period in Australia, the results of this study should be interpreted with cautions for other countries. Australian definition of perinatal period commences at 20 completed weeks (140 days) of gestation and ends 27 completed days after birth which is different from the definition by World Health Organisation (commences at 22 completed weeks (154 days) of gestation and ends seven completed days after birth) and by Centers for Disease Control and Prevention (includes infant deaths under age 7 days and fetal deaths at 28 weeks of gestation or more).WIDER IMPLICATIONS OF THE FINDINGSPreterm birth is the single most important contributing factor to increased risk of perinatal mortality among ART singletons compared to non-ART singletons. Further research on reducing early preterm delivery, with the aim of reducing the perinatal mortality among ART births is needed. Couples who access ART treatment should be fully informed regarding the risk of preterm birth and subsequent risk of perinatal death.STUDY FUNDING/COMPETING INTEREST(S)There was no funding associated with this study. No conflict of interest was declared.
      PubDate: Mon, 13 Nov 2017 00:00:00 GMT
      DOI: 10.1093/humrep/dex340
  • New intronic Fibroblast Growth Factor Receptor 1 (FGFR1) mutation leading
           to disrupted splicing and Kallmann syndrome
    • Authors: Känsäkoski J; Vaaralahti K, Raivio T.
      First page: 328
      Abstract: Congenital hypogonadotropic hypogonadism (CHH), which can present with a defective sense of smell (Kallmann syndrome, KS), is a clinically and genetically heterogeneous disorder. Over 31 genes have been associated with CHH, but most of the patients still lack a molecular genetic diagnosis. Some cases may be explained by mutations that disrupt the splicing of already established CHH genes but that are unrecognized either because they are located deep in introns or are not predicted to disrupt splicing. Here we identified a patient with a previously unreported Fibroblast Growth Factor Receptor 1 (FGFR1) mutation, c.1664-9T>G, that leads to the skipping of exon 13 of FGFR1. Notably, the mutation was not predicted to cause a significant alteration in the splicing motif but in vitro analysis confirmed the pathogenicity of the mutation. Our results thus reveal a new splicing-affecting mutation in FGFR1 and suggest that all new sequence variants located close to exon/intron boundaries should be experimentally investigated for pathogenicity, rather than relying solely on computer prediction programs.
      PubDate: Fri, 08 Dec 2017 00:00:00 GMT
      DOI: 10.1093/humrep/dex363
  • The epigenetic control of transposable elements and imprinted genes in
           newborns is affected by the mode of conception: ART versus spontaneous
           conception without underlying infertility
    • Authors: Choux C; Binquet C, Carmignac V, et al.
      First page: 331
      Abstract: STUDY QUESTIONDo assisted reproductive technologies alter DNA methylation and/or transcription of transposable elements and imprinted genes in cord blood and placenta'SUMMARY ANSWERAfter ART, DNA methylation and/or transcription changes of some transposable elements and imprinted genes were found in placenta samples while transcription modifications for some transposable elements were also discovered in cord blood.WHAT IS KNOWN ALREADYRecent studies have confirmed the increased risk of placenta-related adverse pregnancy outcomes and the excess of imprinted disorders with abnormal methylation patterns after ART, which raises the issue of a potential ART-induced epigenetic risk.STUDY DESIGN, SIZE, DURATIONA total of 51 IVF/ICSI (15 conventional and 36 ICSI) singleton pregnancies were prospectively included from January 2013 to April 2015 and compared to 48 spontaneously conceived singleton pregnancies.PARTICIPANTS/MATERIALS, SETTING, METHODSThe DNA methylation and transcription of three imprinted loci (H19/IGF2, KCNQ1OT1 and SNURF DMRs) and four transposon families (LINE-1, ERVFRD, AluYa5 and ERVW) in cord blood and placenta obtained at birth were assessed by pyrosequencing and quantitative RT-PCR, respectively. All data were adjusted for gestational age at delivery, sex of the newborn, parity and maternal age.MAIN RESULTS AND THE ROLE OF CHANCEDNA methylation levels of H19/IGF2, KCNQ1OT1, LINE-1Hs and ERVFRD-1 were significantly lower in IVF/ICSI placentas than in control placentas, while there was no difference for cord blood. Moreover, the expression of ERVFRD-1 and LINE-1 ORF2 in cord blood and ERVFRD-1 in placenta was lower in the IVF/ICSI group than in controls. The expression of ERVFRD-1 in placenta correlated positively with birth weight and placenta weight, but only in the control group, thus pointing to the potential deregulation of syncytin function after ART.LARGE SCALE DATAN/A.LIMITATIONS, REASONS FOR CAUTIONThe control group of fertile couples having conceived within 1 year prevented us from deciphering the distinct roles of ART and infertility.WIDER IMPLICATIONS OF THE FINDINGSThese novel findings of ERVFRD (syncytin-2) expression correlating with birth weight and placenta weight suggest that more research on syncytins and pregnancy-associated diseases could lead to them being used as biomarkers or even as therapeutic targets. The epigenetic modifications in placenta for sequences involved in foetal development raise the question of their potential effects on pregnancy and future life. These results should encourage us to analyse the exact causes and consequences of epigenetic changes and strive to minimize these variations in the interests of epigenetic safety after ART.STUDY FUNDING/COMPETING INTEREST(S)The study was funded by a grant from Besançon and Dijon University Hospitals. The authors have no conflicts of interest to declare.
      PubDate: Mon, 11 Dec 2017 00:00:00 GMT
      DOI: 10.1093/humrep/dex366
  • Clinical trial registry alone is not adequate: on the perception of
           possible endpoint switching and P-hacking
    • Authors: Hill M; Connell M, Patounakis G.
      First page: 341
      PubDate: Wed, 29 Nov 2017 00:00:00 GMT
      DOI: 10.1093/humrep/dex359
  • Reply: Clinical trial registry alone is not adequate: on the perception of
           possible endpoint switching and P-hacking
    • Authors: Abbara A; Clarke S, Islam R, et al.
      First page: 342
      PubDate: Wed, 29 Nov 2017 00:00:00 GMT
      DOI: 10.1093/humrep/dex360
  • Corrigendum: COMPI Fertility Problem Stress Scales is a brief, valid and
           reliable tool for assessing stress in patients seeking treatment
    • Authors: Sobral M; Costa M, Schmidt L, et al.
      First page: 345
      PubDate: Thu, 28 Dec 2017 00:00:00 GMT
      DOI: 10.1093/humrep/dex373
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