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  • 1. Altmäe, Signe
    et al.
    Esteban, Francisco J
    Stavreus-Evers, Anneli
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Simón, Carlos
    Giudice, Linda
    Lessey, Bruce A
    Horcajadas, Jose A
    Macklon, Nick S
    D'Hooghe, Thomas
    Campoy, Cristina
    Fauser, Bart C
    Salamonsen, Lois A
    Salumets, Andres
    Guidelines for the design, analysis and interpretation of 'omics' data: focus on human endometrium2013Ingår i: Human Reproduction Update, ISSN 1355-4786, E-ISSN 1460-2369, Vol. 20, nr 1, s. 12-28Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    BACKGROUND 'Omics' high-throughput analyses, including genomics, epigenomics, transcriptomics, proteomics and metabolomics, are widely applied in human endometrial studies. Analysis of endometrial transcriptome patterns in physiological and pathophysiological conditions has been to date the most commonly applied 'omics' technique in human endometrium. As the technologies improve, proteomics holds the next big promise for this field. The 'omics' technologies have undoubtedly advanced our knowledge of human endometrium in relation to fertility and different diseases. Nevertheless, the challenges arising from the vast amount of data generated and the broad variation of 'omics' profiling according to different environments and stimuli make it difficult to assess the validity, reproducibility and interpretation of such 'omics' data. With the expansion of 'omics' analyses in the study of the endometrium, there is a growing need to develop guidelines for the design of studies, and the analysis and interpretation of 'omics' data.

    METHODS Systematic review of the literature in PubMed, and references from relevant articles were investigated up to March 2013.

    RESULTS The current review aims to provide guidelines for future 'omics' studies on human endometrium, together with a summary of the status and trends, promise and shortcomings in the high-throughput technologies. In addition, the approaches presented here can be adapted to other areas of high-throughput 'omics' studies.

    CONCLUSION A highly rigorous approach to future studies, based on the guidelines provided here, is a prerequisite for obtaining data on biological systems which can be shared among researchers worldwide and will ultimately be of clinical benefit.

  • 2.
    Altmäe, Signe
    et al.
    Division of Obstetrics and Gynaecology, Dept of Clinical Science, Karolinska University Hospital Huddinge, Sweden.
    Hovatta, O.
    Division of Obstetrics and Gynaecology, Dept of Clinical Science, Karolinska University Hospital Huddinge, Sweden.
    Stavreus-Evers, Anneli
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Salumets, A.
    Competence Centre on Reproductive Medicine and Biology, Tartu, Estonia.
    Genetic predictors of controlled ovarian hyperstimulation: where do we stand today?2011Ingår i: Human Reproduction Update, ISSN 1355-4786, E-ISSN 1460-2369, Vol. 17, nr 6, s. 813-828Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    BACKGROUND

    Nowadays, the use of IVF has improved the prospects of infertility treatment. The expected outcome of IVF depends greatly on the effectiveness of controlled ovarian hyperstimulation (COH), where exogenous gonadotrophins are used to induce folliculogenesis. The response to stimulation varies substantially among women and is difficult to predict. Several predictive markers of COH outcome have been proposed (e.g. maternal age and ovarian reserve), but the search for optimal predictors is ongoing. Pharmacogenetic studies demonstrate the effects of individual genetic variability on COH outcome and the potential for customizing therapy based on the patient's genome.

    METHODS

    MEDLINE, EMBASE, DARE, CINAHL and the Cochrane Library, and references from relevant articles were investigated up to February 2011 regarding any common genetic variation and COH/IVF outcome.

    RESULTS

    Several polymorphisms in genes involved in FSH signalling, estrogen biosynthesis, folliculogenesis, folate metabolism and other aspects influence the response to exogenous gonadotrophin administration, resulting in differences in COH and IVF outcomes. Nevertheless, the most studied polymorphism FSHR Asn680Ser is practically the only genetic marker, together with ESR1 PvuII T/C, that could be applied in clinical tests.

    CONCLUSIONS

    Although data are accumulating with evidence suggesting that the ovarian response to COH is mediated by various polymorphisms, the optimal biomarkers and the efficacy of the tests still remain to be evaluated.

  • 3.
    Sergentanis, Theodoros N.
    et al.
    Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Greece.
    Diamantaras, Andreas-Antonios
    Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Greece.
    Perlepe, Christina
    Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Greece.
    Kanavidis, Prodromos
    Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Greece.
    Skalkidou, Alkistis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Petridou, Eleni Th.
    Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Greece.
    IVF and breast cancer: a systematic review and meta-analysis2014Ingår i: Human Reproduction Update, ISSN 1355-4786, E-ISSN 1460-2369, Vol. 20, nr 1, s. 106-123Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    BACKGROUND

    The effects of controlled ovarian hyperstimulation (COH) for IVF in terms of breast cancer risk remain controversial, despite the hormone-dependent nature of the latter.

    METHODS

    Eligible studies up to 15 February 2013 were identified and pooled effect estimates for relative risk (RR) were calculated separately for the investigations using the general population and those using infertile women, as a reference group. Fixed- or random-effects models were implemented and subgroup analyses were performed, as appropriate.

    RESULTS

    Eight cohort studies were synthesized, yielding a total cohort size of 1 554 332 women among whom 14 961 incident breast cancer cases occurred, encompassing 576 incident breast cancer cases among women exposed to IVF. No significant association between IVF and breast cancer was observed either in the group of studies treating the general population (RR = 0.91, 95% confidence interval (CI): 0.74–1.11) or infertile women (RR = 1.02, 95% CI: 0.88–1.18), as a reference group. Of note were the marginal associations, protective for pregnant and/or parous women after IVF (pooled effect estimate = 0.86, 95% CI: 0.73–1.01) and adverse for women <30 years at first IVF treatment (pooled effect estimate = 1.64, 95% CI: 0.96–2.80).

    CONCLUSIONS

    At present, COH for IVF does not seem to impart increased breast cancer risk. Longer follow-up periods, comparisons versus infertile women, subgroup analyses aiming to trace vulnerable subgroups, adjustment for various confounders and larger informative data sets are needed before conclusive statements for the safety of the procedure are reached.

  • 4.
    Siristatidis, Charalampos
    et al.
    Assisted Reproduction Unit, 3rd Department of Obstetrics and Gynecology, University of Athens, Attikon Hospital, Chaidari, Greece.
    Sergentanis, Theodoros N.
    Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Greece.
    Kanavidis, Prodromos
    Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Greece.
    Trivella, Marialena
    UK Cochrane Centre, National Institute of Health Research, Oxford University Hospitals, UK.
    Sotiraki, Marianthi
    Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Greece.
    Mavromatis, Ioannis
    Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Greece.
    Psaltopoulou, Theodora
    Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Greece.
    Skalkidou, Alkistis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Petridou, Eleni Th
    Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Greece.
    Controlled ovarian hyperstimulation for IVF: impact on ovarian, endometrial and cervical cancer-a systematic review and meta-analysis2013Ingår i: Human Reproduction Update, ISSN 1355-4786, E-ISSN 1460-2369, Vol. 19, nr 2, s. 105-123Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    BACKGROUND: In response to the ongoing debate on the long-term effects of assisted reproduction technologies, such as IVF, we systematically reviewed and meta-analyzed available evidence on the association between controlled ovarian hyperstimulation for IVF and risk of ovarian, endometrial and cervical cancer. METHODS: Eligible studies were identified and pooled effect estimates for relative risk (RR) were calculated by cancer type among two reference groups (general population or infertile women), through fixed-or random-effects models as appropriate. RESULTS: Nine cohort studies were synthesized, corresponding to a total size of 109 969 women exposed to IVF, among whom 76 incident cases of ovarian, 18 of endometrial and 207 cases of cervical cancer were studied. The synthesis of studies with general population as the reference group pointed to a statistically significant positive association between IVF and increased risk for ovarian (RR = 1.50, 95% confidence interval (CI): 1.17-1.92) and endometrial (RR = 2.04, 95% CI: 1.22-3.43), but not cervical (RR = 0.86, 95% CI: 0.49-1.49)cancers. On the contrary, when infertile women were used as the reference group, no significant associations with ovarian, endometrial or cervical cancer types were noted (RR=1.26, 95% CI: 0.62-2.55 RR=0.45, 95% CI: 0.18-1.14 and RR= 5.70, 95% CI: 0.28-117.20, respectively). CONCLUSIONS: IVF does not seem to be associated with elevated cervical cancer risk, nor with ovarian or endometrial cancer when the confounding effect of infertility was neutralized in studies allowing such comparisons. Of note, only one study provided follow-up longer than 10 years for the group exposed to IVF. Future cohort studies should preferably use infertile women as the reference group, rely on IVF-registered valid exposure data, adjust for a variety of meaningful confounders and adopt relatively longer follow-up periods before sound conclusions are drawn.

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