Tal como já tinha sido mostrado anteriormente, existe uma relação entre a espessura do endométrio e as taxas de gravidez, em mulheres que necessitam de recorrer a ciclos de procriação medicamente assistida. Apesar de alguns dados não serem significativos, é possível considerar que uma espessura fina do endométrio constitui um fator de risco para um insucesso da gravidez. Algumas melhorias previamente apontadas devem ser consideradas de forma a permitir um estudo com uma maior precisão, de destacar o maior número de casos em estudo e a medição da espessura no dia da transferência embrionária.
Adicionalmente, ao longo deste estudo foi notória a relevância da epigenética no desenvolvimento embrionário, nas técnicas desenvolvidas e, até mesmo, no desenvolvimento da espessura do endométrio, sendo aconselhado um estudo mais aprofundado a este nível. Com as bases lançadas nesta dissertação, sugere-se uma investigação que procure responder a todas as questões da fisiologia e origem da patologia. Assim, poderia estudar-se o mecanismo pelo qual as alterações epigenéticas nos recetores de estrogénio levam a uma diminuição do desenvolvimento do endométrio. Desta forma, poderia entender-se uma nova causa para um endométrio fino e mais tarde, desenvolverem-se novas estratégias para combater esta patologia, recorrendo aos conhecimentos sobre as alterações da metilação nestes recetores. Além disso, seria importante estudar outros casos da metilação do DNA em outros genes e outras modificações epigenéticas que possam estar envolvidas numa redução do crescimento do endométrio.
Assim, são importantes estudos futuros que abranjam estas áreas, dada a melhoria que podem trazer para o sucesso das técnicas de reprodução assistida e toda a importância clínica que estas acarretam.
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Bibliografia
Allen, V. M., Wilson, R. D., & Cheung, A. (2006). Pregnancy Outcomes After Assisted Reproductive Technology. Journal of Obstetrics and Gynaecology Canada, 28(3), 220– 233.
Amoako, A. A., Nafee, T. M., & Ola, B. (2017). Epigenetic influences during the periconception period and assisted reproduction. In Advances in Experimental Medicine
and Biology (Vol. 1014, pp. 15–39).
Amodio, N., D’Aquila, P., Passarino, G., Tassone, P., & Bellizzi, D. (2017). Epigenetic modifications in multiple myeloma: recent advances on the role of DNA and histone methylation. Expert Opinion on Therapeutic Targets, 21(1), 91–101.
Asghari, S., Valizadeh, A., Aghebati-Maleki, L., Nouri, M., & Yousefi, M. (2018). Endometriosis: Perspective, lights, and shadows of etiology. Biomedicine and
Pharmacotherapy, 106(February), 163–174.
Balaban, B., Brison, D., Calderón, G., Catt, J., Conaghan, J., Cowan, L., … Van Den Abbeel, E. (2011). Istanbul consensus workshop on embryo assessment: Proceedings of an expert meeting. Reproductive BioMedicine Online, 22(6), 632–646.
Best, D., Avenell, A., & Bhattacharya, S. (2017). How effective are weight-loss interventions for improving fertility in women and men who are overweight or obese? A systematic review and meta-analysis of the evidence. Human Reproduction Update, 23(6), 681–705. Bodri, D., Nair, S., Gill, A., Lamanna, G., Rahmati, M., Arian-Schad, M., … Ahuja, K. K. (2018). Shared motherhood IVF: high delivery rates in a large study of treatments for lesbian couples using partner-donated eggs. Reproductive BioMedicine Online, 36(2), 130–136.
Boyce, T. w. (2015). Population Health: Behavioral and Social Science Insights.
Bunkar, N., Pathak, N., Lohiya, N. K., & Mishra, P. K. (2016). Epigenetics: A key paradigm in reproductive health. Clinical and Experimental Reproductive Medicine, 43(2), 59–81. Canovas, S., & Ross, P. J. (2016). Epigenetics in preimplantation mammalian development.
Theriogenology, 86(1), 69–79.
Carlberg, C., & Molnár, F. (2018). Chromatin Remodelers and Organizers. In Human
epigenomics (pp. 103–120).
Carneiro, R. (2013). A realidade da Procriação Medicamente Assistida : - Técnicas
laboratoriais - Criopreservação de ovócitos : Que futuro nos centros ? A realidade da Procriação Medicamente Assistida : - Técnicas laboratoriais nos centros ? Universidade
do Porto.
Chan, J. M., Sukumar, A. I., Ramalingam, M., Ranbir Singh, S. S., & Abdullah, M. F. (2018). The impact of endometrial thickness (EMT) on the day of human chorionic gonadotropin (hCG) administration on pregnancy outcomes: a 5-year retrospective cohort analysis in Malaysia. Fertil Res Pract, 4, 5.
Choux, C., Carmignac, V., Bruno, C., Sagot, P., Vaiman, D., & Fauque, P. (2015). The placenta: phenotypic and epigenetic modifications induced by Assisted Reproductive Technologies throughout pregnancy. Clinical Epigenetics, 7(1).
Chronopoulou, E., & Harper, J. C. (2015). IVF culture media: Past, present and future. Human
Reproduction Update, 21(1), 39–55.
Cito, G., Coccia, M. E., Dabizzi, S., Morselli, S., Della Camera, P. A., Cocci, A., … Natali, A. (2018). Relevance of testicular histopathology on prediction of sperm retrieval rates in case of non-obstructive and obstructive azoospermia. Urologia Journal,
39156031875894.
45
regulation of ATP-dependent chromatin-remodelling complexes. Nature Reviews
Molecular Cell Biology, 18(7), 407–422.
Cunningham, J. (2017). Infertility: A primer for primary care providers. Journal of the
American Academy of Physician Assistants, 30(9), 19–25.
Devi SS, G., Pandiyan, N., & Pandiyan, R. (2016). Does the endometrial thickness really matter in Assisted Reproductive Technology Cycles - A Retrospective analysis. Chettinad Health
City Medical Journal, (2277).
El Hajj, N., Haertle, L., Dittrich, M., Denk, S., Lehnen, H., Hahn, T., … Haaf, T. (2017). DNA methylation signatures in cord blood of ICSI children. Human Reproduction, 32(8), 1761– 1769.
Eniola, W., Adetola, A., & Abayomi, T. (2012). A review of Female Infertility; important etiological factors and management. Journal of Microbiology and Biotechnology Research
Scholars Research Library J. Microbiol. Biotech. Res, 2(3), 379–385. Retrieved from
http://scholarsresearchlibrary.com/archive.html
Ghosh, J., Coutifaris, C., Sapienza, C., & Mainigi, M. (2017). Global DNA methylation levels are altered by modifiable clinical manipulations in assisted reproductive technologies.
Clinical Epigenetics, 9(1), 14.
Giacinti, L., Claudio, P. P., Lopez, M., & Giordano, A. (2006). Epigenetic information and estrogen receptor alpha expression in breast cancer. The Oncologist, 11(1), 1–8.
Greally, J. M. (2018). A user’s guide to the ambiguous word “epigenetics.” Nature Reviews
Molecular Cell Biology, 19(4), 207–208.
Grimstad, F. W., & Decherney, A. (2017). A Review of the Epigenetic Contributions to Endometriosis. Clinical Obstetrics and Gynecology, 60(3), 467–476.
Guo, X. Y., Liu, X. M., Jin, L., Wang, T. T., Ullah, K., Sheng, J. Z., & Huang, H. F. (2017). Cardiovascular and metabolic profiles of offspring conceived by assisted reproductive technologies: a systematic review and meta-analysis. Fertility and Sterility, 107(3), 622– 631.e5.
Gupta, A., Desai, A., & Bhatt, S. (2017). Imaging of the Endometrium : Physiologic Changes and Diseases. RadioGraphics, 37, 2206–2207. https://doi.org/10.1148/rg.2017170008 Harada, T. (2014). Endometriosis: Pathogenesis and treatment. Nature Reviews Endocrinology,
10(5), 261–275.
Harper, J. C., Aittomäki, K., Borry, P., Cornel, M. C., de Wert, G., Dondorp, W., … Macek, M. (2017). Recent developments in genetics and medically assisted reproduction: from research to clinical applications. European Journal of Human Genetics.
Harper, J., Geraedts, J., Borry, P., Cornel, M. C., Dondorp, W. J., Gianaroli, L., … Macek, M. (2014). Current issues in medically assisted reproduction and genetics in Europe: Research, clinical practice, ethics, legal issues and policy. Human Reproduction, 29(8), 1603–1609.
Heard, E., & Martienssen, R. A. (2014). Transgenerational epigenetic inheritance: Myths and mechanisms. Cell, 157(1), 95–109.
Holubekova, V., Mendelova, A., Jasek, K., Mersakova, S., Zubor, P., & Lasabova, Z. (2017). Epigenetic regulation by DNA methylation and miRNA molecules in cancer, 13, 2217– 2222.
Jiang, Z., Wang, Y., Lin, J., Xu, J., Ding, G., & Huang, H. (2017). Genetic and epigenetic risks of assisted reproduction. Best Practice and Research: Clinical Obstetrics and
Gynaecology, 44, 90–104.
Kamel, R. M. (2010). Management of the infertile couple : an evidence- based protocol.
Reproductive Biology and Endocrinology, 8(1), 21.
46
dysregulation of endometriosis susceptibility genes (Review). Molecular Medicine
Reports, 12(2), 1611–1616.
Kouhkan, A., Khamseh, M. E., Moini, A., Pirjani, R., Valojerdi, A. E., Arabipoor, A., … Baradaran, H. R. (2018). Predictive factors of gestational diabetes in pregnancies following assisted reproductive technology: a nested case–control study. Archives of
Gynecology and Obstetrics, 298(1), 199–206.
Laurentino, S., Borgmann, J., & Gromoll, J. (2016). On the origin of sperm epigenetic heterogeneity. Reproduction, 151(5), R71–R78.
Le, A. W., Wang, Z. H., Yuan, R., Shan, L. L., Xiao, T. H., Zhuo, R., & Shen, Y. (2013). Association of the estrogen receptor-β gene RsaI and AluI polymorphisms with human idiopathic thin endometrium. Genetics and Molecular Research, 12(4), 5978–5985. Leverrier-Penna, S., Mitchell, R. T., Becker, E., Lecante, L., Ben Maamar, M., Homer, N., …
Mazaud-Guittot, S. (2018). Ibuprofen is deleterious for the development of first trimester human fetal ovary ex vivo. Human Reproduction, 33(3), 482–493.
Lindheim, S. R., Glenn, T. L., Smith, M. C., & Gagneux, P. (2018). Ovulation Induction for the General Gynecologist. The Journal of Obstetrics and Gynecology of India.
Liu, K. E., Hartman, M., Hartman, A., Luo, Z.-C., & Mahutte, N. (2018). The impact of a thin endometrial lining on fresh and frozen–thaw IVF outcomes: an analysis of over 40 000 embryo transfers. Human Reproduction, 33(10), 1883–1888.
Llinàs-Arias, P., & Esteller, M. (2017). Epigenetic inactivation of tumour suppressor coding and non-coding genes in human cancer: an update. Open Biology, 7(9), 170152.
Luke, B. (2017). Pregnancy and birth outcomes in couples with infertility with and without assisted reproductive technology: with an emphasis on US population-based studies.
American Journal of Obstetrics and Gynecology, 217(3), 270–281.
Maekawa, R., Taketani, T., Mihara, Y., Sato, S., Okada, M., Tamura, I., … Sugino, N. (2017). Thin endometrium transcriptome analysis reveals a potential mechanism of implantation failure. Reproductive Medicine and Biology, 16(2), 206–227.
Mahajan, N., & Sharma, S. (2016). The endometrium in assisted reproductive technology: How thin is thin? Journal of Human Reproductive Sciences, 9(1), 3.
Marcho, C., Cui, W., & Mager, J. (2015). Epigenetic dynamics during preimplantation development. Reproduction, 150(3), R109–R120.
Menezo, Y., Dale, B., & Elder, K. (2017). Time to re-evaluate ART protocols in the light of advances in knowledge about methylation and epigenetics: an opinion paper. Human
Fertility, pp. 1–7.
Mukhtar, H. B., Shaman, A., Mirghani, H. O., & Almasalmah, A. A. (2017). The Outcome of Assisted Reproductive Techniques among Couples with Male Factors at Prince Khalid Bin Sultan Fertility Centre, Kingdom of Saudi Arabia. Open Access Macedonian Journal of
Medical Sciences.
Nalaboff, K. M., Pellerito, J. S., & Ben-Levi, E. (2001). Imaging the Endometrium: Disease and Normal Variants. RadioGraphics, 21(6), 1409–1424.
Oliveto, S., Mancino, M., Manfrini, N., & Biffo, S. (2017). Role of microRNAs in translation regulation and cancer. World Journal of Biological Chemistry, 8(1), 45.
Palermo, G. D., O’Neill, C. L., Chow, S., Cheung, S., Parrella, A., Pereira, N., & Rosenwaks, Z. (2017). Intracytoplasmic sperm injection: State of the Art in Humans. Reproduction
(Cambridge, England), REP-17-0374.
Pandian, Z., Gibreel, A., Bhattacharya, S., Pandian, Z., Gibreel, A., & Bhattacharya, S. (2015). In vitro fertilisation for unexplained subfertility ( Review ) In vitro fertilisation for unexplained subfertility. Cochrane Database of Systematic Reviews (Online), 11(11), CD003357.
47
Pedri, S., Lico, D., Cello, A. Di, D’Alessandro, P., Vaiarelli, A., Alviggi, E., … Venturella, R. (2016). Thin endometrium in patient undergoing Assisted Reproductive Technology: pathogenesis and treatment. Current Trends in Clinical Embriology, 3(1).
Peeraer, K., Debrock, S., De Loecker, P., Tomassetti, C., Laenen, A., Welkenhuysen, M., … D’Hooghe, T. M. (2015). Low-dose human menopausal gonadotrophin versus clomiphene citrate in subfertile couples treated with intrauterine insemination: A randomized controlled trial. Human Reproduction, 30(5), 1079–1088.
Pfeifer, S., Butts, S., Fossum, G., Gracia, C., La Barbera, A., Mersereau, J., … Vernon, M. (2017). Optimizing natural fertility: a committee opinion. Fertility and Sterility, 107(1), 52–58.
Punab, M., Poolamets, O., Paju, P., Vihljajev, V., Pomm, K., Ladva, R., … Laan, M. (2017). Causes of male infertility: A 9-year prospective monocentre study on 1737 patients with reduced total sperm counts. Human Reproduction, 32(1), 18–31.
Rajender, S., Avery, K., & Agarwal, A. (2011). Epigenetics, spermatogenesis and male infertility. Mutation Research - Reviews in Mutation Research, 727(3), 62–71.
Richter, K. S., Bugge, K. R., Bromer, J. G., & Levy, M. J. (2007). Relationship between endometrial thickness and embryo implantation, based on 1,294 cycles of in vitro fertilization with transfer of two blastocyst-stage embryos. Fertility and Sterility, 87(1), 53–59.
Rienzi, L., Gracia, C., Maggiulli, R., LaBarbera, A. R., Kaser, D. J., Ubaldi, F. M., … Racowsky, C. (2016). Oocyte, embryo and blastocyst cryopreservation in ART: systematic review and meta-analysis comparing slow-freezing versus vitrification to produce evidence for the development of global guidance. Human Reproduction Update, 23(2), 139–155.
Shi, D.-Q., Ali, I., Tang, J., & Yang, W.-C. (2017). New Insights into 5hmC DNA Modification: Generation, Distribution and Function. Frontiers in Genetics, 8.
Sinha, P., Pandey, K., & Srivastava, A. (2017). Factors determining successful intrauterine insemination, 6(9), 3887–3891.
Sirard, M. A. (2017). The influence of in vitro fertilization and embryo culture on the embryo epigenetic constituents and the possible consequences in the bovine model. Journal of
Developmental Origins of Health and Disease, 8(4), 411–417.
Štiavnická, M., Abril-Parreño, L., Nevoral, J., Králíčková, M., & García-Álvarez, O. (2017). Non-Invasive Approaches to Epigenetic-Based Sperm Selection. Medical Science
Monitor, 23, 4677–4683.
Stuppia, L., Franzago, M., Ballerini, P., Gatta, V., & Antonucci, I. (2015). Epigenetics and male reproduction: The consequences of paternal lifestyle on fertility, embryo development, and children lifetime health. Clinical Epigenetics, 7(1).
Sunderam, S., Kissin, D. M., Crawford, S. B., Folger, S. G., Jamieson, D. J., Warner, L., & Barfield, W. D. (2017). Assisted Reproductive Technology Surveillance — United States, 2014. MMWR. Surveillance Summaries, 66(6), 1–24.
Szyf, M. (2016). The elusive role of 5′-hydroxymethylcytosine. Epigenomics, 8(11), 1539– 1551.
Talbert, P. B., & Henikoff, S. (2017). Histone variants on the move: Substrates for chromatin dynamics. Nature Reviews Molecular Cell Biology, 18(2), 115–126.
Uysal, F., Akkoyunlu, G., & Ozturk, S. (2015). Dynamic expression of DNA methyltransferases (DNMTs) in oocytes and early embryos. Biochimie, 116, 103–113. Uysal, F., Akkoyunlu, G., & Ozturk, S. (2016). DNA methyltransferases exhibit dynamic
expression during spermatogenesis. Reproductive BioMedicine Online, 33(6), 690–702. Vaegter, K. K., Lakic, T. G., Olovsson, M., Berglund, L., Brodin, T., & Holte, J. (2017). Which
48
factors are most predictive for live birth after in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) treatments? Analysis of 100 prospectively recorded variables in 8,400 IVF/ICSI single-embryo transfers. Fertility and Sterility, 107(3), 641–648.e2. Van Montfoort, A. P. A., Hanssen, L. L. P., De Sutter, P., Viville, S., Geraedts, J. P. M., & De
Boer, P. (2012). Assisted reproduction treatment and epigenetic inheritance. Human
Reproduction Update, 18(2), 171–197.
Ventura-Juncá, P., Irarrázaval, I., Rolle, A. J., Gutiérrez, J. I., Moreno, R. D., & Santos, M. J. (2015). In vitro fertilization (IVF) in mammals: Epigenetic and developmental alterations. Scientific and bioethical implications for IVF in humans. Biological Research, 48(1). Whidden, L., Martel, J., Rahimi, S., Chaillet, J. R., Chan, D., & Trasler, J. M. (2016).
Compromised oocyte quality and assisted reproduction contribute to sex-specific effects on offspring outcomes and epigenetic patterning. Human Molecular Genetics, 25(21), 4649–4660.
Wiweko, B., Anggraheni, U., Elvira, S. D., & Lubis, H. P. (2017). Distribution of stress level among infertility patients. Middle East Fertility Society Journal, 22(2), 145–148.
World Health Organization. (2010). WHO laboratory manual for the Examination and
processing of human semen. World Health Organization.
Wu, M.-H., Su, P.-F., Chen, K.-Y., Tie, T.-H., Ke, H.-C., Chen, H., … Ou, H.-T. (2018). Heart rate variability among women undergoing in vitro fertilization treatment: Its predictive ability for pregnancy. PLOS ONE.
Yang, W., Zhang, T., Li, Z., Ren, X., Huang, B., Zhu, G., & Jin, L. (2018). Combined analysis of endometrial thickness and pattern in predicting clinical outcomes of frozen embryo transfer cycles with morphological good-quality blastocyst. Medicine (United States),
97(2).
Yuan, R., & Le, A. W. (2012). A study on the estrogen receptor α gene polymorphism and its expression in thin endometrium of unknown etiology. Gynecologic and Obstetric
Investigation, 74(1), 13–20.
Yuan, X., Saravelos, S. H., Wang, Q., Xu, Y., Li, T. C., & Zhou, C. (2016). Endometrial thickness as a predictor of pregnancy outcomes in 10787 fresh IVF–ICSI cycles.
Reproductive BioMedicine Online, 33(2), 197–205.
Zegers-Hochschild, F., Adamson, G. D., de Mouzon, J., Ishihara, O., Mansour, R., Nygren, K., … Vanderpoel, S. (2009). International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology, 2009*. Fertility and Sterility, 92(5), 1520–1524.
Zhang, T., Li, Z., Ren, X., Huang, B., Zhu, G., Yang, W., & Jin, L. (2018). Endometrial thickness as a predictor of the reproductive outcomes in fresh and frozen embryo transfer cycles. Medicine, 97(4), e9689.
Zheng, H., Zhou, X., Li, D. K., Yang, F., Pan, H., Li, T., … Yuan, W. (2017). Genome-wide alteration in DNA hydroxymethylation in the sperm from bisphenol A-exposed men. PLoS
ONE, 12(6).