Bioethics and law for what and whom? Discussions about the Regulation of assisted reproductive techniques in ColombiaThe recent concern for the normative regulation of assisted reproduction techniques (ART), raises discussions about how to manage the embryos, how many times to use a sample, how to define parenthood, and other issues. However, it has not been questioned who would be favouredwith these regulations and what is their contribution to social equity and development for an entire country. Considering that the urgency to guarantee the sexual and reproductive rights —theoretical framework invoked to require ART— should be aimed at reaching a fair society.The proposed analysis will be undertaken considering the case of applying the ART for surrogate mothers in Colombia. The paper presents the context in which it is intended to apply the normative regulation, alongside the review of some conceptual and empirical contributions by Michael Sandel concerning trends in surrogate motherhood among «developed» and «third world» countries. This should allow considering the profiles of fertility in Colombia as a sign of inequality in our country.Subsequently, we will approach the current legal discussion in Colombia concerning surrogate motherhood, from the only case of surrogate motherhood resolved by the Colombian Constitutional Court and the bill projects presented in the Colombian Congress to regulate this issue. Finally,we will present some reflections and discussion on the normative regulation of the ART and surrogate gestation, and the law as a transmission belt of varied interests, that is, that it ought to lead to common good, solidarity and cooperation, and not simply function as a regulator that ensures the fulfilment of contracts. / Las recientes preocupaciones por la regulación normativa de las técnicas de reproducción humana asistida (TRHA) suscitan especialmente discusiones sobre cómo administrar los embriones, cuántas veces usar una muestra, cómo definir la filiación, entre otros. Sin embargo, no se ha cuestionado directamente a quienes estaría amparándose con estas regulaciones y cuál sería su contribución a la equidad social y al desarrollo de todo un país, pues la urgencia de salvaguardar los derechos sexuales y reproductivos —marco teórico invocado para exigir la regulación de las TRHA— debe apuntar necesariamente a la consecución de una sociedad menos desigual.El análisis propuesto será abordado a partir del caso de la aplicación de las TRHA para la maternidad subrogada en Colombia. En el artículo se presenta inicialmente el contexto en el cual se pretende la regulación de la maternidad sustitutiva, revisando algunos aportes conceptuales y empíricos de Michael Sandel sobre las tendencias de la maternidad subrogada entre los países «desarrollados» y los del «tercer mundo», para luego ver los perfiles de fecundidad en Colombia, como una muestra de la inequidad existente en el país.Posteriormente, se hará una aproximación al debate jurídico existente en el país, a partir del único caso de maternidad sustitutiva resuelto por la Corte Constitucional Colombiana y los proyectos de ley que han sido presentados en el país como intentos de regulación de esta materia. Finalmente, se llevarán a cabo algunas reflexiones y discusiones sobre la regulación normativa de las TRHA y la gestación sustitutiva, para que el derecho opere como verdadera correa de transmisión de variados intereses sociales1, es decir, que conduzca más bien hacia el bien común, la solidaridad y la cooperación, y no actúe como un simple regulador que asegure el cumplimiento de los contratos.

Objetivo: Avaliar se o uso de Ibuprofeno associado a lorazepam, ou isoladamente, reduz a dor máxima associada à raspagem endometrial. Adicionalmente, analisou-se se reduz a dor logo após o procedimento e a rejeição a um novo procedimento. Material e Métodos: Estudo controlado, duplo-cego, com alocação aleatória de mulheres em três grupos paralelos, na proporção de 1:1:1. Foram convidadas a participar desta pesquisa mulheres com idade >=18 anos em tratamento para infertilidade no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo e que realizaram raspagem endometrial para aumentar as chances de gravidez. Foram inclusas 150 mulheres. As mulheres de todos os grupos receberam dois comprimidos: um grupo recebeu Ibuprofeno 600 mg + Lorazepam 1mg (I+L); outro grupo, Ibuprofeno 600 mg + placebo (I+P); e o último grupo recebeu dois placebos (P+P). A injúria endometrial foi realizada aproximadamente uma hora após essas intervenções. O principal parâmetro avaliado foi a dor máxima durante o procedimento, mensurado por meio de uma escala visual analógica (EVA) de 100 mm e outra escala verbal numérica (EVN) de 11 pontos (0 a 10). Os desfechos secundários foram a dor logo após a procedimento aplicando EVA e EVN e a aceitação de um novo procedimento avaliado por uma escala de Likert de cinco pontos sobre a afirmação \"Eu repetiria este procedimento\". Os valores obtidos entre os grupos foram comparados por meio de ANOVA e Kruskal-Wallis e por ?². Resultados: Cento e cinquenta mulheres aceitaram participar do estudo, sendo randomizadas 50 em cada grupo. Essas mulheres receberam a intervenção proposta (I+L, I+P ou P+P) e foram submetidas à injúria endometrial, aproximadamente uma hora após a administração da intervenção. Não se observou diferença significativa entre os grupos na dor máxima durante o procedimento, mensurada por EVA, EVN, ou pela média entre essas medidas EVA/EVN. Também não se verificou diferença significativa entre os grupos na dor mensurada logo após o procedimento ou na aceitação de um novo procedimento. Conclusões: Durante o procedimento de injúria endometrial não houve diferença na quantificação da dor entre os grupos estudados. O uso de Ibuprofeno isolado ou associado ao Lorazepam não foi eficaz em reduzir o nível da dor ou mudar a aceitação do procedimento, quando comparado com placebo. / Objectives: To assess whether the use of Ibuprofen associated with lorazepam or alone reduces the maximum pain associated with endometrial scraping. Additionally, we will evaluate if it reduces pain soon after the procedure and the rejection to a new procedure. Materials and Methods: A double-blind controlled study with random allocation of women in three parallel groups, at a ratio of 1: 1: 1. Women who were >= 18 years old who underwent infertility treatment at HC-FMRP-USP and who underwent endometrial scaling to increase their chances of pregnancy were invited to participate in this study. 150 women were included in the study Women of all groups received two tablets: one group received Ibuprofen 600 mg + lorazepam 1mg (I + L); the other group ibuprofen 600 mg + placebo (I + P); and the last group received two 2 placebos (P + P). The endometrial injury was performed approximately one hour after the use of these interventions. The main parameter evaluated was the maximum pain during the procedure, measured by a visual analogue scale (EVA) of 100 mm and a numerical verbal scale (EVN) of 11 points (0 to 10). Secondary outcomes were pain right after the procedure using EVA and EVN and acceptance of a new procedure rated by a 5-point Likert scale on the statement \"I would repeat this procedure.\" The values obtained between the groups were compared by ANOVA and Kruskal-Wallis and by ?². Results: One hundred and fifty women accepted to participate in the study, and 50 women in each group were randomized. These women received the proposed intervention (I + L, I + P or P + P) and were submitted to endometrial injury approximately one hour after the intervention. There was no significant difference between the groups in the maximum pain during the procedure measured by VAS, EVN, or by the mean between these VAS/EVN measures. We also did not observe a significant difference between the groups in the pain measured immediately after the procedure or in the acceptance of a new procedure. Conclusions: During the endometrial injury procedure, no difference was observed in the quantification of pain between the groups studied. Use of ibuprofen alone or in combination with lorazepam was not effective in reducing the level of pain or changing the acceptability of the procedure when compared to placebo.

Objetivo:Comparar a eficácia dos meios de cultivo HTF (Human Tubal Fluid) e TCM 199 (Tissue Culture Medium) na maturação in vitro. Métodos:Estudo experimental controlado e randomizado no qual foram avaliadas as taxas de maturação oocitária, fertilização, clivagem e produção de embriões de boa qualidade em 23 ciclos não estimulados de maturação oocitária, com 119 oócitos coletados, de 13 mulheres com Síndrome dos Ovários Policísticos. Os oócitos de cada paciente foram transferidos randomicamente para cada um dos meios de cultivo sendo que, 61 (51%) foram colocados no meio TCM 199 e 58 (49%) no meio HTF. Os dois meios de cultivo receberam suplementação hormonal. Resultados:Diferenças significativas foram encontradas entre os meios de cultivo TCM 199 e HTF em relação à taxa de maturação oocitária (82% vs. 56.9%, p = 0.005), taxa de fertilização (70% vs. 39.4%, p = 0.007) e taxade produção de embriões de boa qualidade (81.3% vs. 41.7%, p= 0.023). Conclusão:O meio de cultivo HTF embora seja utilizado para manutenção de embriões em técnicas de fertilização assistida e em procedimentos de maturação in vitrocom ciclos estimulados, não é o meio mais apropriado paramaturação de oócitos obtidos de mulheres com Síndrome dos Ovários policísticosem ciclos não estimulados. / Objective:Compare oocytes human culture in human tubal fluid (HTF) and Tissue Culture Medium (TCM 199) invitromaturation cycles. Methods:Randomized controlled trial which oocyte maturation, fertilization, cleavage rates and embryo quality in 23 in vitromaturation cycles no stimulation were evaluated, resulting in 119 oocytes retrieved from 13 patients withpolycystic ovarian syndrome. The oocytes from each patient were assigned randomly to the two culture media, 61 (51%) to the TCM 199 and 58 (49%) to the HTF using the same hormonal supplementation. Results:Significant differences were observed between TCM 199 and HTF regarding maturation rate (82% vs. 56.9%, p = 0.005), fertilization rate (70% vs. 39.4%, p = 0.007) rates and embryo quality (81.3% vs. 41.7%, p= 0.023). Conclusion:The HTF medium, although widely employed for oocyte fertilization and embryo maintenance in IVF techniques, is not an appropriated medium to maturation oocytes obtained from PCOS patients innon - stimulated cycles.

Made available in DSpace on 2016-01-26T12:51:34Z (GMT). No. of bitstreams: 1 wagnervicensoto_dissert_parte1.pdf: 574820 bytes, checksum: 52b81a5827b47b0dd96036bb137bd216 (MD5) Previous issue date: 2004-06-01 / The oocyte donation and reception program is a technique in which female gametes from a woman (donor) are donated to other woman (recipient) in order to be fertilized with the respective recipient s husband spermatozoa. The present study analyzed fourteen patients who underwent 21 cycles of egg reception by this assisted reproductive medical technique at the Reproductive Medicine Institute (RMI) of São José do Rio Preto-SP, in the period from January 1998 to December 2002. The recipients age ranged between 29 to 49 years; the mean age 40 years. Ten patients (71.5%) did not report previous gestation, therefore considered women with primary infertility. In order to perform the indications to the oocyte reception we classified five patients (35.7%) as having premature menopause, five (35.7%) as ovarian failure, three (21.5%) as physiological menopause, and one (7.1%) as unsuccessful responder to previous treatments. Only six patients (42.9%) had not undergone previous infertility treatments. In 92.9% of the patients, the assisted reproductive technique used was the Intracytoplasmic Sperm Injection (ICSI). The number of embryos transferred per cycle was between two and four. A total of 21 cycles were performed with a rate of 52.4% of gestation per cycle and 71.5% gestation per patient. The rate of multiple gestations was 27.3%. Regarding the gestation evolutions, it was observed a rate of 36.4% of miscarriage and 63.6% of ongoing pregnancies, in which 9.1% had premature delivery, and 54.5% had full term delivery without intercurrences. The rate of home baby was 50%. The oocyte donation and reception program showed to be a successful technique, with excellent results, providing a feasible and ethic way of getting pregnant some selected patients who have otherwise been considered as having an infertility reserved diagnostic. / O programa de doação-recepção de oócítos é técnica pela qual os gametas femininos (oócitos) de uma mulher (doadora) são doados a outra (receptora) para que sejam fertilizados com espermatozóides dos respectivos maridos. Este estudo analisou quatorze pacientes submetidas a 21 ciclos de ovorecepção por técnica de reprodução medicamente assistida no Instituto de Medicina Reprodutiva (IMR) de São José do Rio Preto-SP, no período de janeiro de 1998 a dezembro de 2002. A idade das pacientes receptoras variou de 29 a 49 anos com média de 40 anos. Dez (71,5%) pacientes não referiram gestação anterior, sendo consideradas como infertilidade primária. Como indicações para realização de recepção de oócitos classificamos cinco (35,7%) pacientes como menopausa precoce, cinco (35,7%) como falência ovaríana, três (21,5%) como menopausa fisiológica e uma (7,1 %) como má respondedora. Apenas seis (42,9%) pacientes não haviam sido submetidas a tratamento anterior para infertilidade. Em 92,9% das pacientes foi utilizado a injeção intra-citoplasmática de espermatozóide (lCSl) como técnica de fertilização assistida. Foram transferidos por ciclo entre dois e quatro embriões. Dos 21 ciclos realizados obteve-se taxa de 52,4% de gestação por ciclo e de 71,5% de gestação por paciente. A taxa de gestação múltipla foi de 27,3%. Em relação à evolução das gestações observou-se taxa de abortamento de 36,4% e evolução da gestações em 63,6%, com 9,1% de parto prematuro e 54,5% gestações a termo sem íntercorrêncías. A taxa de "bebê em casa" foi de 50%. O programa de doação-recepção de oócitos mostrou-se técnica de excelentes resultados, representando uma forma viável e ética de se obter gestação em pacientes selecionadas que antes tinham diagnóstico reservado de infertilidade.

Orientadores: Eliana Amaral, Maria Yolanda Makuch / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-11-07T13:33:28Z (GMT). No. of bitstreams: 1 Rossi_AndreadaSilveira_D.pdf: 2215950 bytes, checksum: c190d83a71722140f11b48daa634163e (MD5) Previous issue date: 2010 / Resumo: Objetivo: Identificar quais Serviços de Reprodução Assistida (SRA) e Serviços de Assistência Especializada em HIV e Aids (SAE) do Sistema de Saúde Pública do Brasil, que oferecem atendimento a pessoas vivendo com HIV com desejo reprodutivo e descrever as vivências, informações adquiridas e barreiras encontradas pelos gestores de programas, profissionais de saúde e usuários, relacionados a essa demanda. Metodologia: Estudo descritivo, de corte transversal através de entrevistas telefônicas com 69 gestores dos programas de saúde da mulher (PSM) e 69 de DST/Aids, estaduais e municipais associado a estudo de casos através de entrevistas semi-estruturadas com profissionais e usuários soropositivos de um serviço de reprodução assistida (SRA) e um serviço de atenção especializada em HIV/Aids (SAE) por região geográfica do país. Foi realizada análise descritiva dos dados quantitativos e análise temática do conteúdo para os dados qualitativos. Resultados: Foram realizadas 64 entrevistas com gestores dos PSM, sendo identificado apenas um SRA universitário que atendia casais soropositivos. Nas 63 entrevistas realizadas com gestores dos Programas de DST/Aids, constatou-se que 64% dos SAE estaduais e 73% dos municipais ofereciam orientação reprodutiva. As dificuldades relatadas pelos gestores para não oferecimento de apoio à reprodução incluíram falta de decisão política, de recursos humanos e financeiros. Nas entrevistas com os profissionais dos seis SAE visitados, foi observado que o foco dos atendimentos era na prevenção, principalmente através do uso do preservativo. A falta de encaminhamentos apropriados e a desatualização do conhecimento científico foram frequentes nos relatos dos profissionais dos serviços. A dificuldade em falar sobre o desejo reprodutivo nas consultas foi observada nas falas dos profissionais e também dos usuários. Para os últimos, isso esteve associado ao medo da discriminação e do preconceito. Entretanto, através da 47 entrevistas realizadas com usuários, o desejo de ter filhos foi vivenciado de maneira natural e expresso independentemente de se ter ou não parceiro fixo, mas, para aqueles que possuem parceiros fixos, o fato de não ter filhos da atual união pareceu aumentar a intenção reprodutiva. Conclusão: Os resultados sugerem a existência de demanda reprimida para reprodução de casais vivendo com HIV, a falta de aconselhamento reprodutivo nos SAE e de investimento em SRA que atenda a essa população, havendo um único SRA universitário no país que oferece esse tipo de atendimento. A falta de integração entre os vários setores sugere a ausência de políticas públicas voltadas para o aconselhamento reprodutivo e a necessidade de diretrizes nacionais específicas voltadas para a redução da transmissão do HIV durante todo o contexto reprodutivo / Abstract: Objective: To identify assisted reproductive services(ARS) and specialized HIV/AIDS services within the Brazilian public health system that provide care to people living with HIV who desire a child and describe the experience, the information, and the barriers encountered by program managers, healthcare professionals and users with respect to this demand. Methods: A descriptive, cross-sectional study in which 69 women's healthcare program managers and 69 STD/AIDS program managers at both state and municipal level were interviewed by telephone, in association with a case study conducted through semistructured interviews with professionals and users of one ARS service and one HIV/AIDS service in each geographical region of the country. Descriptive analysis of the quantitative data and thematic content analysis of the qualitative data were performed. Results: Sixty-four interviews were conducted with women's healthcare program managers. Only one university ARS provided care to seropositive couples. Of the 63 interviews carried out with STD/AIDS program managers, 64% of the state and 73% of the municipal HIV/AIDS services were found to offer reproductive counseling. The difficulties offered by managers as reasons for not providing reproductive support included a lack of political decision and of human and financial resources. At the six HIV/AIDS services the professionals revealed that the focus of consultations was on the prevention, lack of appropriate referrals and outdated scientific knowledge were frequently reported. Difficulty in discussing reproductive issues was perceived in the interviews with the professionals and also with the users. In the latter case, this was associated with a fear of discrimination and prejudice. Nevertheless, as shown in the 47 interviews conducted with users, the desire to have a child was experienced as a natural part of life and was expressed irrespective of whether the individual had a steady partner or not; however, in the former case, the fact of not having a child with the individual's current partner appeared to increase the desire for a child. Conclusion: These findings suggest the existence of a repressed demand for reproduction of PLWHA and lack of reproductive counseling was observed at all HIV/Aids specialized services, as well as investment in ART services to be provided to HIV-positive couples, based on the finding that only one university ART service in the country offers this type of care. Lack of integration between the various sectors suggests an absence of public policies on reproductive counseling and a need for specific national guidelines aimed at reducing HIV transmission within the whole context of reproduction / Doutorado / Ciencias Biomedicas / Doutor em Tocoginecologia

Objetivo:Comparar a eficácia dos meios de cultivo HTF (Human Tubal Fluid) e TCM 199 (Tissue Culture Medium) na maturação in vitro. Métodos:Estudo experimental controlado e randomizado no qual foram avaliadas as taxas de maturação oocitária, fertilização, clivagem e produção de embriões de boa qualidade em 23 ciclos não estimulados de maturação oocitária, com 119 oócitos coletados, de 13 mulheres com Síndrome dos Ovários Policísticos. Os oócitos de cada paciente foram transferidos randomicamente para cada um dos meios de cultivo sendo que, 61 (51%) foram colocados no meio TCM 199 e 58 (49%) no meio HTF. Os dois meios de cultivo receberam suplementação hormonal. Resultados:Diferenças significativas foram encontradas entre os meios de cultivo TCM 199 e HTF em relação à taxa de maturação oocitária (82% vs. 56.9%, p = 0.005), taxa de fertilização (70% vs. 39.4%, p = 0.007) e taxade produção de embriões de boa qualidade (81.3% vs. 41.7%, p= 0.023). Conclusão:O meio de cultivo HTF embora seja utilizado para manutenção de embriões em técnicas de fertilização assistida e em procedimentos de maturação in vitrocom ciclos estimulados, não é o meio mais apropriado paramaturação de oócitos obtidos de mulheres com Síndrome dos Ovários policísticosem ciclos não estimulados. / Objective:Compare oocytes human culture in human tubal fluid (HTF) and Tissue Culture Medium (TCM 199) invitromaturation cycles. Methods:Randomized controlled trial which oocyte maturation, fertilization, cleavage rates and embryo quality in 23 in vitromaturation cycles no stimulation were evaluated, resulting in 119 oocytes retrieved from 13 patients withpolycystic ovarian syndrome. The oocytes from each patient were assigned randomly to the two culture media, 61 (51%) to the TCM 199 and 58 (49%) to the HTF using the same hormonal supplementation. Results:Significant differences were observed between TCM 199 and HTF regarding maturation rate (82% vs. 56.9%, p = 0.005), fertilization rate (70% vs. 39.4%, p = 0.007) rates and embryo quality (81.3% vs. 41.7%, p= 0.023). Conclusion:The HTF medium, although widely employed for oocyte fertilization and embryo maintenance in IVF techniques, is not an appropriated medium to maturation oocytes obtained from PCOS patients innon - stimulated cycles.

A partir de données en population, nous avons: 1) évalué le risque de cardiopathies congénitales (CC) chez les fœtus conçus par assistance médicale à la procréation (AMP); et 2) déterminé les effets de l’AMP sur la prise en charge prénatale et le devenir périnatal des fœtus porteurs de CC. Nous avons observé que l'AMP était associée à une augmentation de 40% du risque de CC sans anomalies chromosomiques associées (OR ajusté = 1,4 IC95% 1,1-1,7). Nous avons également retrouvé qu'il existait des associations variables selon la catégorie de CC et la méthode d'AMP considérées. Nous avons observé que l'AMP était associée à une multiplication par 2,4 du risque de tétralogie de Fallot (OR ajusté = 2,4 IC95% 1,5-3,7), alors que nous n’avons pas retrouvé d’association statistiquement significative pour les trois autres CC spécifiques étudiées. Dans notre population, l'exposition à l'AMP ne semblait pas modifier le recours au diagnostic prénatal et à l'interruption médicale de grossesse chez les fœtus porteurs de CC comparés aux fœtus porteurs de CC conçus spontanément. Nous avons par ailleurs observé que le risque de prématurité des fœtus porteurs de CC conçus par AMP était environ 5 fois plus élevé que celui des fœtus porteurs de CC conçus spontanément (OR ajusté = 5,0 IC95% 2,9-8,6). En nous basant sur une méthodologie d'analyses de cheminement, nous avons retrouvé que les grossesses multiples contribuaient pour environ 20% au risque plus élevé de tétralogie de Fallot associé à l'AMP que nous avons observé. Enfin, les grossesses multiples contribuaient pour environ 2/3 du risque de prématurité associé à l'AMP chez les fœtus porteurs de CC. / Using population-Based data, we: 1) assessed the risk of congenital heart defects (CHD) in assisted reproductive techniques (ART) conceived fetuses; and 2) evaluated the effects of ART on prenatal management and perinatal outcomes of fetuses with CHD. We observed that ART were associated with a 40% increased risk of CHD without associated chromosomal anomalies (adjusted OR = 1.4 95%CI 1.1-1.7). We also found varying associations between the different methods of ART and categories of CHD. We observed that ART were associated with 2.4-Higher odds of tetralogy of Fallot (adjusted OR = 2.4 95%CI 1.5-3.7), whereas no statistically significant association was found for the three other specific CHD included. In our population, ART exposure did not seem to modify prenatal diagnosis and termination of pregnancy for fetal anomaly in fetuses with CHD compared to fetuses with CHD conceived spontaneously. The risk for premature birth in fetuses with CHD conceived following ART was 5-Fold higher as compared to fetuses with CHD conceived spontaneously (adjusted OR = 5.0 95%CI 2.9-8.6). Using a path-Analysis method, we found that multiple pregnancies contributed for about 20% to the higher risk of tetralogy of Fallot associated with ART that we had found. Finally, multiple pregnancies contributed for the 2/3 of the risk of premature birth associated with ART in fetuses with CHD.

<p>Uvod: Infertilitet pogađa 10-15% parova reproduktivnog doba. Vanetesna oplodnja (VTO) je najefikasniji vid tret-mana infertiliteta, ali uprkos značajnom napretku stopa uspeha VTO u proseku iznosi oko 30% po ciklusu. Glavnim razlogom neuspeha smatra se neadekvatan kvalitet embriona, dok se pretpostavlja da u 10-20% slučajeva razlog neuspeha leži u neadekvatnoj receptivnosti uterusa. Na osnovu inicijalnih istraživanja histeroskopija, koja predstvalja zlatni standard u dijagnostici i tretmanu patologije kavuma uterusa, se često izvodi u svakodnevnoj kliničkoj praksi kako bi se povećala uspe&scaron;nost VTO. Uprkos &scaron;irokoj primeni i dalje ne postoji dovoljno kvalitetnih dokaza o realnoj ulozi histeroskopije na ishod VTO kako kod patolo&scaron;kih stanja kavuma tako i rutinski, pre prvog ili rekurentnog poku&scaron;aja VTO. Cilj disertacije bio je da se utvrdi uticaj sprovođenja histeroskopije na ishod VTO, ustanovi učestalost prethodno neprepoznate patologije kavuma uterusa, kao i da se ispitaju stavovi pacijenata o primeni rutinske histeroskopije pred VTO. Materijal i metode: Istraživanje je sprovedeno u Kliničkom centru Vojvodine, u formi prospektivne studije u dve sukcesivne etape od 01.01.2015. do 01.04.2017. U prvoj etapi poređen je ishod VTO kod pacijentkinja kojima pred postupak VTO nije sprovedena histeroskopija (Grupa A), pacijentkinja kod kojih je dobijen uredan nalaz histeroskopije pred postupak VTO (Grupa B) i pacijentkinja gde je pred postupak VTO dobijen patolo&scaron;ki nalaz kavuma na histeroskopiji koji je u istom aktu tertian (Grupa C). Druga etapa istraživanja predstavljala je randomiziranu kontrolisanu studiju (RCT &ndash; randomised controlled trial). Nakon verifikacije urednog ultrazvučnog nalaza pred prvi postupak VTO, pacijentkinje su randomizirane u Grupu A2 kojima pred postupak VTO nije sprovedena histeroskopija i Grupu B2 kojima je pred postupak VTO sprovedena rutinska histeroskopija. Statistička analiza sprovedena je upotrebom odgovarajućeg softvera (JMP Ver. 9). Poređeni su podaci o osnovnim karakteristikama pacijenata, toka i ishoda ciklusa VTO. Primarni parametar ishoda bila je stopa kliničke trudnoće po embriotransferu. Pored analize ishoda primarno konstruisanih grupa, urađena je analiza i naknadno konstruisanih subgrupa, kao i predikcioni model uspeha VTO baziran na logističkoj regresiji. Rezultati: Studija je uključila 253 pacijentkinje (52 pacijentkinja iz Grupe A, 50 iz Grupe B, 50 iz Grupe C, 51 iz Grupe A2 i 50 iz Grupe B2). Nije postojala statistički značajna razlika u karakteristikama pacijentkinja, parametrima ovarijalne rezerve, broju dobijenih jajnih ćelija ni drugim parametrima toka postupka VTO među posmatranim grupama. U prvoj etapi istraživanja dobijena je statistički značajno (p=0,013) veća stopa kliničkih trudnoća kod pacijentkinja kojima je pred postupak VTO sprovedena histeroskopija - 50 % za Grupu B i 42% za grupu C u odnosu na 30,77% kod pacijentkinja bez histeroskopije (Grupa A), bez statistički značajne razlike među histeroskopskim grupama. U drugoj etapi istraživanja stopa kliničkih trudnoća prilikom upotrebe rutinske histeroskopije pred prvu VTO (Grupa B2) iznosila je 46% naspram 31,37% kod pacijentkinja bez histeroskopije pred prvu VTO (Grupa A2), iako uočena razlika nije dostigla statističku značajnost (p =0,089), uz relativan rizik (RR) za ostvarivanje kliničke trudnoće nakon primene histeoskopije uiznosio od 1,47 (95% CI 0,88-2,43) (p=0,13). Analizon subgrupa kod 100 pacijentkinja sa rutinski sprovedenom histeroskopijom pred VTO i 103 pacijentkinje bez histeroskopije pred VTO, dobijena je statistički značajnao veća stopa kliničkih trudnoća (48% naspram 31,07%, istim redom), uz RR od 1,54 (95% CI 1,08-2,20) (p=0,013), kao i stopa tekućih trudnoća od RR 1,49 (CI 1,01-2,19) (p= 0,039). Analiza ukupnog uticaja izvođenja histeroskopije pred VTO dobila je statistički značanjno veću stopu kliničkih trudnoća po ET za grupu histeroskopije uz RR 1,48 (CI 1,06-2,07) (p=0,017). Histeroskopijom je nakon urednog ultrazvučnog nalaza ustanovljeno postojanje patolo&scaron;kog nalaza kod 34,65% pacijenata i to 22,7% major patologije i 11,88% minor patologije kavuma. Nije postojala statistički značajna razlika u uspehu VTO u odnosu na sam nalaz histeroskopije. 98,67% pacijenata podržalo je rutinsku upotrebu histeroskopije pred prvi postupak VTO, dok je 83% pacijenata podržavlo rutinsku upotrebu histeroskopije pred svaki postupak VTO. U finalnom predikcionom modelu se uz AUC od 0,748 jedino postojanje visokokvalitetnog embriona uz odnos &scaron;ansi (OR) 7,91 (95% CI 1,80-56,06; p=0,0047), transfer blastociste uz OR 3,80 (95% CI 1,90-7,98; p=0,0001) i izvođenje histeroskopije pred VTO uz OR 2,13 (95% CI 1,14-4,08, p=0,0169) pokazalo statistički značajnim prediktorima trudnoće. Diskusija: Studija je dobila pozitivan uticaj histeroskopije na ishod postupka VTO, iskazan pre svega povećanjem stope kliničkih trudnoća nakon sprovođenja histeroskopije (bilo da je na histeroskopiji nađen uredan ili patolo&scaron;ki nalaz). Dodatna prednost histeroskopije predstavljala je i i detekcija prethodno nepropoznate patologije kavuma. Umeren efekat na ukupno pobolj&scaron;anje stope kliničkih trudnoća prilikom rutinskog sprovođenja histeroskopije pred prvu VTO, koji je statističku značajnost dostigao tek analizom subgrupa u skladu je sa nalazima novijih dobro dizajniranih studija koji donekle limitiraju nekritičku upotrebu histeroskopije. Biolo&scaron;ko obja&scaron;njenje potencijalnog pozitivnog uticaja histeroskopije najverovatnije leži u detekciji i tretmanu prethodno nepropoznate patologije kavuma, olak&scaron;avanju procedure embriotransfera, kao i humoralnim i molekularnim promenama koje nastaju u endometrijumu kao posledica odgovarajuće histeroskopske traume a koji su u dosa&scaron;anjim istraživanjima apostrofirani kao faktori koji mogu povećati receptivnost uterusa. Zaključak: Histeroskopija je efikasna, bezbedna i visoko prihvatljiva procedura koja dovodi do povećanja uspeha VTO u standardnim kliničkim indikacijama (prethodnog neuspelog postupka VTO i sumnje na patolo&scaron;ki nalaz kavuma uterusa) bilo da se na samoj histeroskopiji nađe uredan ili patolo&scaron;ki nalaz. Rutinska primena histeroskopije pred prvi postupak VTO se na osnovu rezultata studije ne može smatrati apsolutno opravdanom usled statistički nedovoljno značajnog povećanja stope kliničke trudnoće. Uzev&scaron;i u obzir visoku prihvatljivost od strane pacijenata i najverovatniji pozitivan efekat na stopu trudnoće primena rutinske histeroskopije pred prvu VTO bila bi opravdana ukoliko se implementira koncept ambulantne histeroskopije.</p> / <p>Introduction: Infertility affects 10-15% of all couples. In vitro fertilisation (IVF) is the most effective method of infertility treatment, but despite a significant improvement, success rate of IVF is still around 30% per cycle. The main reason for the IVF failure is inadequate embryo quality, but in 10-20% of cases the cause of IVF failure lies in impaired uterine receptivity. Based on earlier studies hysteroscopy, gold standard in the diagnosis and treatment of uterine cavity pathology, is often performed to increase IVF success. Despite its wide use, there is lack of high quality evidence regarding real contribution of hysteroscopy on IVF outcome in situations of uterine cavity pathology or routinely prior to first IVF or after recurrent implantation failure. The aim of this dissertation was to determine the influence of performing hysteroscopy on IVF outcome, as well as the incidence of previously unrecognized uterine pathology, and to examine patient&#39;s attitudes about performing routine hysteroscopy prior to IVF. Material and methods: The research was conducted in a prospective manner in two successive stages at Clinical Center of Vojvodina from 01.01.2015. until 01.04.2017. During first stage of the study IVF outcome was compared between patients who did not have a hysteroscopy prior to IVF (group A), patients with normal hysteroscopic finding prior to the IVF (Group B) and patients with abnormal hysteroscopic findings prior to IVF which was treated at the same time (Group C). The second stage of the study was a randomized controlled trial (RCT). After verification of normal ultrasound findings prior to the first IVF, patients were randomized to group A2 in who me hysteroscopy was not performed and group B2 who had routine hysteroscopy prior to first IVF. Statistical analysis was carried out using the appropriate statistical software (JMP Ver. 9). Patient characteristics, course and outcome of IVF cycle were compared between groups. The primary outcome was clinical pregnancy rate (CPR) per embryotransfer. In addition to analyzing the IVF outcomes in primarily defined groups, subgroup analysis was also performed, as well as IVF success pre-diction model based on logistic regression. Results: The study included 253 patients (52 patients in Group A, 50 in Group B, 50 in Group C, 51 in Group A2 and 50 in Group B2). There was no statistically significant difference in patient characteristics, ovarian reserve parameters, number of retrieved oocytes, or other relevant parameters of IVF course between the observed groups. In the first stage of the study there was statistically significant (p = 0.013) higher clinical pregnancy rate in patients who had a hysteroscopy before IVF - 50% for Group B and 42% for group C versus 30,77 % in patients without hysteroscopy before IVF (Group A), without statistically significant difference between hysteroscopic groups. In the second stage of the study, routine hysteroscopy prior to first IVF (Group B2) led to clinical pregnancy rate 46% versus 31.37% in patients without hysteroscopy prior to first IVF (Group A2), although without statistical significance (p = 0.089. Relative risk (RR) for achieving clinical pregnancy after performing hysteroscopy was 1.47 (95% CI 0.88-2.43) (p = 0.13). Subgroup analysis of 100 patients with routinely performed hysteroscopy before IVF and 103 patients without hysteroscopy prior to the IVF showed statistically significant higher rates of clinical pregnancies (48% versus 31.07%, in the same order), with RR of 1.54 (95% CI 1.08-2.20), (p = 0.013), and for ongoing pregnancies RR was 1.49 (95% CI 1.01-2.19) (p = 0.039). Overall effect of performing hysteroscopy prior to IVF resulted in a statistically significant increase in the clinical pregnancy with RR 1.48 (95% CI 1.06-2.07) (p = 0.017). After normal ultrasound finding hysteroscopy revealed 34.65% of pathological finding, 22.7% of major and 11.88% of minor pathology of the cavity). There was no statistically significant difference in IVF outcome based on hysteroscopy findings. 98.67% of patients supported the routine use of hysteroscopy before the first IVF procedure, while 83% of patients supported the routine use of the hysteroscopy before every IVF procedure. In the final prediction model, with the AUC of 0.748, only the presence of high quality embryos with odds ratio (OR) 7,91 (95% CI 1,80-56,06; p=0,0047), blastocyst transfer with OR 3,80 (95% CI 1,90-7,98; p=0,0001) and performing hysteroscopy prior to IVF with OR 2,13 (95% CI 1,14-4,08, p=0,0169) proved to be statistically significant predictors of pregnancy. Discussion: The study shoved a positive influence of hysteroscopy on the IVF outcome by increasing clinical pregnancy rate after performing hysteroscopy (whether hysteroscopy revealed normal or pathological finding). Additional benefit of hysteroscopy was detection of previously unrecognized uterine pathology. A moderate effect on the overall improvement in clinical pregnancy rate with use of routine hysteroscopy, which reached statistical significance only by subgroup analysis, is in line with findings of recent well designed studies that somewhat limit the noncritical use of hysteroscopy. A biological explanation of the potential positive effect of hysteroscopy is most likely due to detection and treatment of the previously unrecognized uterine pathology, facilitating embryotransfer procedure, as well as the humoral and molecular changes that occur in the endometrium as a consequence of the hysteroscopic trauma. Those changes were hypothesized as factors that can increase uterine receptivity by numerous research. Conclusion: Hysteroscopy is an effective, safe and highly acceptable procedure that increases IVF success when performed for accepted clinical indications (previous IVF failures, pathological findings of uterine cavity), whether hysteroscopy reveals normal or pathological finding. The routine use of hysteroscopy prior to first IVF based on this study can not be considered justified since increase in clinical pregnancy rate did not reach statistical significance. Given the high acceptance of this concept by the patients and moderate but probable positive effect on IVF outcome, implementation of routine hysteroscopy prior to first VTO would be justified only in office hysteroscopy setting.</p>