Background: In 2011, 45% of the 6.1 million pregnancies in the United States were unintended. Of the unintended pregnancies, 50% were attributed to contraceptive failure or method non-adherence. Long-acting reversible contraceptives (LARCs) are birth control methods consisting of intrauterine devices (IUDs) and the birth control implants that are the most effective forms of reversible contraceptives. LARCs are 20 times more effective than other birth control methods; yet only 5.6% of women are choosing LARCs. Despite multiple pharmacological and non-pharmacological interventions prior to the procedure, 35% of women reported having moderate pain and 42% of women had severe pain associated during the IUD placement Purpose: The purpose of this quality improvement project was to identify health care providers’ knowledge and practice of pain management methods for IUD insertion in iparous women at a military medical treatment facility (MTF). Methods: This DNP quality improvement (QI) project used a quantitative descriptive methodology with a pretest-posttest design and educational intervention to identify the current practice and knowledge primary care providers have regarding appropriate pain management for iparous women when placing an IUD. Results: The providers’ responses reflect a self-efficacy represented by a knowledge increase in the areas of the limited benefit of premedication with either oral analgesics or cervical softening agents, placing an IUD based on the patient’s menstrual cycle, incorporating the use of a local analgesic, and the connection between counseling and patient satisfaction. Limited provider knowledge can be suggested by the varied responses regarding the topic of a CPG. Self-efficacy stayed stable for the areas of post-procedural NSAID use and having the time for counseling regarding expected pain during the procedure. Conclusion: Improving provider knowledge, skill, and counseling techniques can help decrease the expected and perceived pain for iparous women having an IUD placed leading to an increase of women having IUDs placed. An ultimate goal is to increase IUD use and retention, leading to decreased unintended pregnancy rates, lower maternal and newborn mortality, and improving patient satisfaction when having an IUD placed.

Endometriosis is a chronic disease that is thought to potentially begin at menarche and progress through a woman’s reproductive years. Adolescents with endometriosis present with dysmenorrhea and chronic pelvic pain. Endometriosis can be treated with medical and surgical management. Levonorgestrel intrauterine devices (LNG-IUD) are an effective option for medical management in adolescents. The primary objective of this study was to determine the rate of IUD insertion after laparoscopy for endometriosis in adolescents. The secondary objective was to compare the characteristics of the adolescent population with and without an IUD placed at the time of surgery. The medical records of 109 adolescent patients </= 21 years old were retrospectively reviewed for patient demographic information and surgical information. In our cohort, 36% of patients had an IUD placed at the time of laparoscopic surgery for endometriosis. Patients with an IUD placed at the time of surgery had a significantly higher BMI than patients who did not have an IUD placed (p = 0.004). The most reported symptoms were dysmenorrhea (77.1%) and chronic pelvic pain (94.5%). Patients with an IUD placed had higher rates of excision of endometriosis while patients who did not have an IUD placed had higher rates of ablation of endometriosis (p = 0.003, p = 0.05). Dysmenorrhea and pelvic pain are commonly reported by adolescent patients with endometriosis. LNG-IUDs are often placed at time of excision of endometriosis surgery for adolescents and further studies are warranted to see if they are effective in the long term postoperative medical management of adolescents who have completed surgery.

Tanto no campo da Saúde Pública, como no da Demografia, não tem sido dada a devida ênfase ao estudo da mortalidade intra-uterina. Vários são os fatores que têm contribuído para essa aparente falta de interesse por este aspecto da reprodução humana, relacionados com as próprias características do fenômeno, com as disposições legais em matéria de registro e com o alto custo das investigações apropriadas para sua mensuração. Entretanto, minuciosos estudos médicos têm estimado que a mortalidade intra-uterina total - todas as perdas, reconhecidas ou não - pode alcançar o nível biológico de 630 mortes fetais por mil gestações. Estudos populacionais de tipo prospectivo - acompanhamento de gestações - têm conseguido estimar o nível de mortalidade intra-uterina reconhecível - perdas reconhecidas após a primeira amenorréia - em 260 mortes fetais por mil gestações e, os de tipo retrospectivo - história de gestações - indicam que o nível de mortalidade intra-uterina aparente - perdas reconhecidas após a segunda amenorréia - é da ordem de 160 mortes fetais por mil gestações. O objetivo geral deste trabalho consistiu em caracterizar a mortalidade intra-uterina experimentada por um grupo de mulheres grávidas residentes no Município de São Paulo, compreendendo os objetivos específicos de estimar o seu nível e estabelecer as suas relações com alguns fatores biológicos e sócio-demográficos. Mediante a análise das informaç5es derivadas de uma pesquisa de acompanhamento de uma amostra de gestantes residentes em oito sub-distritos e dois distritos periféricos - Brasilândia, Santo Amaro, Jabaquara, Nossa Senhora do Ó, Tucuruvi, Butantã, Santa Cecília, Sé, Itaquera e Jaraguá - do Município de São Paulo, realizada no período compreendido entre novembro de 1987 e fevereiro de 1989, importantes conclusões puderam ser extraídas. No que diz respeito à estimação do nível de mortalidade intra-uterina, com as informac6es da história retrospectiva das gestações, o valor encontrado da taxa de 164 mortes fetais por mil gestações é perfeitamente condizente com a magnitude da taxa de mortalidade fetal aparente, que a literatura destaca ser possível estimar em estudos desse tipo. As informações prospectivas, computadas de forma direta, revelam um nível de mortalidade fetal de 58 mortes fetais por mil gestações, cujo baixo valor pode ser atribuído à natureza direta da medida - que não corrige o viés de seleção - devendo-se levar também em consideração a captação domiciliar das gestantes, sem qualquer limitação da duração da gravidez. Não obstante, quando as informações prospectivas são computadas em forma de Tábuas de mortalidade intra-uterina, consegue-se corrigir o viés de seleção, obtendo-se uma taxa de mortalidade fetal reconhecível de 236 por mil gestações, cifra absolutamente compatível com as estimativas efetuadas pelos estudos mais precisos de mortalidade fetal. Quanto ao estabelecimento de relações da mortalidade intrauterina com os fatores sócio-demográficos: cor, nível de instrução e estado conjugal, as informações analisadas parecem revelar indícios da existência de: - Um diferencial de mortalidade intra-uterina por cor; o maior nível corresponde às mulheres pretas, o intermediário às pardas e o menor às brancas. - Uma correlação negativa entre a mortalidade fetal e o nível de instrução; à medida que este aumenta, diminui o risco de experimentar perdas fetais. - Um diferencial de, mortalidade fetal por estado conjugal; as solteiras têm maior risco que as casadas e as unidas consensualmente, mais que as casadas com vínculo institucional. No que diz respeito ao estabelecimento de relações da mortalidade intra-uterina com os fatores biológicos: idade da mãe, ordem da gestação e história genética anterior, a análise permitiu constatar que: - Existe uma correlação positiva entre a mortalidade fetal e a idade da mãe, à medida que esta avança, aquela se eleva. - Existe também uma correlação positiva entre a mortalidade fetal e a ordem da gestação, quanto maior a ordem, maior o número de perdas. O fator que maior peso tem na determinação do risco de mortalidade fetal, é a história genésica anterior. / Both in the field of Public Health and in the Demography one, the proper emphasis has not been given to the study of intrauterine mortality. Many are the factors that have contributed to this apparent lack of interest to this aspect of human reproduction, they are related to the phenomenon own characteristics, to the legal dispositions in terms of register and to the high costs of appropriate investigations for its measurement. Nevertheless, precise medical studies have estimated that total intrauterine mortality - all the losses, recognized or not - may reach the biological level of 630 fetal deaths per thousand pregnancies. Populational studies of prospective type - follow up pregnancies - have been able to estimate the recognizable intrauterine mortality level recognized lesses after the first amenorrhea - in 260 fetal deaths per thousand pregnancies and of retrospective type - pregnancies history - indicated that the apparent intrauterine mortality level - recognized lesses after the second amenorrhea - is about 160 fetal deaths per thousand pregnancies. The main objective of this work consisted in characterize the intrauterine mortality experimented by a group of pregnant women resident in the Municipality of São Paulo, comprising the specific objectives of to estimate its level and stablish its relations with some biological and social demographic factors. It was possible to make important conclusions through the analysis of the informations derived from a follow up survey of a sample of pregnant women, living in eight subdistricts and two peripheric districts - Brasilândia, Santo Amaro, Jabaquara, Nossa Senhora do Ó, Tucuruvi, Butantã, Santa Cecília, Sé, Itaquera e Jaraguá from São Paulo Municipality, held in the period between November 1987 and February 1989. Concerning the estimation of intrauterine mortality level with the informations from the pregnancies retrospective history, the value found is about 164 fetal deaths per thousand pregnancies, that it\'s perfectly suitable with the magnitude of the apparent fetal mortality rate, which a literature emphasizes to be possible to estimate in this kind of studies. The prospective informations, computed in a direct way, reveal a level of intrauterine mortality of 58 fetal deaths per thousand pregnancies, which low value can be attributed to its direct nature that doesn\'t correct the bias of selection -, being also important to consider the pregnants domiciliary captation, without any kind of restriction in relation to the duration of the pregnancy. However, when the prospective informations are computed in the form of intrauterine mortality life tables, it\'s possible to correct the bias of selecting, achieving a rate of fetal mortality of 236 per thousand pregnancies, a result totally compatible to the estimations made by the most precise studies of fetal mortality. Regarding the stablishment of relationships of intrauterine mortality with the sociodemographic factor: race, instruction level and conjugal situation, the analised informations scem to reveal indications of the existence of: - A differential of intrauterine mortality by race, being the level represented by non white women higher than the represented by white ones. - A negative correlation between fetal mortality and instruction level, when this improves the risk of fetal losses decreases. - A differential of intrauterine mortality by conjugal situation, single women and those consesually joined more than women married with institutional links. In relation to the establishment of relationships of the intrauterine mortality with the biological factors: mother\'s age, pregnancy order and previous reproductive history, the analysis allowed to comprove that: - There is a positive correlation between fetal mortality and mother\'s age, in proportion that this increases, that improves. - There is also a positive correlation between intrauterine mortality and the pregnancy order, highest the order highest the number of lesses. - The most important factor in the determination of the risk of intrauterine mortality is the previous reproductive history.

Tanto no campo da Saúde Pública, como no da Demografia, não tem sido dada a devida ênfase ao estudo da mortalidade intra-uterina. Vários são os fatores que têm contribuído para essa aparente falta de interesse por este aspecto da reprodução humana, relacionados com as próprias características do fenômeno, com as disposições legais em matéria de registro e com o alto custo das investigações apropriadas para sua mensuração. Entretanto, minuciosos estudos médicos têm estimado que a mortalidade intra-uterina total - todas as perdas, reconhecidas ou não - pode alcançar o nível biológico de 630 mortes fetais por mil gestações. Estudos populacionais de tipo prospectivo - acompanhamento de gestações - têm conseguido estimar o nível de mortalidade intra-uterina reconhecível - perdas reconhecidas após a primeira amenorréia - em 260 mortes fetais por mil gestações e, os de tipo retrospectivo - história de gestações - indicam que o nível de mortalidade intra-uterina aparente - perdas reconhecidas após a segunda amenorréia - é da ordem de 160 mortes fetais por mil gestações. O objetivo geral deste trabalho consistiu em caracterizar a mortalidade intra-uterina experimentada por um grupo de mulheres grávidas residentes no Município de São Paulo, compreendendo os objetivos específicos de estimar o seu nível e estabelecer as suas relações com alguns fatores biológicos e sócio-demográficos. Mediante a análise das informaç5es derivadas de uma pesquisa de acompanhamento de uma amostra de gestantes residentes em oito sub-distritos e dois distritos periféricos - Brasilândia, Santo Amaro, Jabaquara, Nossa Senhora do Ó, Tucuruvi, Butantã, Santa Cecília, Sé, Itaquera e Jaraguá - do Município de São Paulo, realizada no período compreendido entre novembro de 1987 e fevereiro de 1989, importantes conclusões puderam ser extraídas. No que diz respeito à estimação do nível de mortalidade intra-uterina, com as informac6es da história retrospectiva das gestações, o valor encontrado da taxa de 164 mortes fetais por mil gestações é perfeitamente condizente com a magnitude da taxa de mortalidade fetal aparente, que a literatura destaca ser possível estimar em estudos desse tipo. As informações prospectivas, computadas de forma direta, revelam um nível de mortalidade fetal de 58 mortes fetais por mil gestações, cujo baixo valor pode ser atribuído à natureza direta da medida - que não corrige o viés de seleção - devendo-se levar também em consideração a captação domiciliar das gestantes, sem qualquer limitação da duração da gravidez. Não obstante, quando as informações prospectivas são computadas em forma de Tábuas de mortalidade intra-uterina, consegue-se corrigir o viés de seleção, obtendo-se uma taxa de mortalidade fetal reconhecível de 236 por mil gestações, cifra absolutamente compatível com as estimativas efetuadas pelos estudos mais precisos de mortalidade fetal. Quanto ao estabelecimento de relações da mortalidade intrauterina com os fatores sócio-demográficos: cor, nível de instrução e estado conjugal, as informações analisadas parecem revelar indícios da existência de: - Um diferencial de mortalidade intra-uterina por cor; o maior nível corresponde às mulheres pretas, o intermediário às pardas e o menor às brancas. - Uma correlação negativa entre a mortalidade fetal e o nível de instrução; à medida que este aumenta, diminui o risco de experimentar perdas fetais. - Um diferencial de, mortalidade fetal por estado conjugal; as solteiras têm maior risco que as casadas e as unidas consensualmente, mais que as casadas com vínculo institucional. No que diz respeito ao estabelecimento de relações da mortalidade intra-uterina com os fatores biológicos: idade da mãe, ordem da gestação e história genética anterior, a análise permitiu constatar que: - Existe uma correlação positiva entre a mortalidade fetal e a idade da mãe, à medida que esta avança, aquela se eleva. - Existe também uma correlação positiva entre a mortalidade fetal e a ordem da gestação, quanto maior a ordem, maior o número de perdas. O fator que maior peso tem na determinação do risco de mortalidade fetal, é a história genésica anterior. / Both in the field of Public Health and in the Demography one, the proper emphasis has not been given to the study of intrauterine mortality. Many are the factors that have contributed to this apparent lack of interest to this aspect of human reproduction, they are related to the phenomenon own characteristics, to the legal dispositions in terms of register and to the high costs of appropriate investigations for its measurement. Nevertheless, precise medical studies have estimated that total intrauterine mortality - all the losses, recognized or not - may reach the biological level of 630 fetal deaths per thousand pregnancies. Populational studies of prospective type - follow up pregnancies - have been able to estimate the recognizable intrauterine mortality level recognized lesses after the first amenorrhea - in 260 fetal deaths per thousand pregnancies and of retrospective type - pregnancies history - indicated that the apparent intrauterine mortality level - recognized lesses after the second amenorrhea - is about 160 fetal deaths per thousand pregnancies. The main objective of this work consisted in characterize the intrauterine mortality experimented by a group of pregnant women resident in the Municipality of São Paulo, comprising the specific objectives of to estimate its level and stablish its relations with some biological and social demographic factors. It was possible to make important conclusions through the analysis of the informations derived from a follow up survey of a sample of pregnant women, living in eight subdistricts and two peripheric districts - Brasilândia, Santo Amaro, Jabaquara, Nossa Senhora do Ó, Tucuruvi, Butantã, Santa Cecília, Sé, Itaquera e Jaraguá from São Paulo Municipality, held in the period between November 1987 and February 1989. Concerning the estimation of intrauterine mortality level with the informations from the pregnancies retrospective history, the value found is about 164 fetal deaths per thousand pregnancies, that it\'s perfectly suitable with the magnitude of the apparent fetal mortality rate, which a literature emphasizes to be possible to estimate in this kind of studies. The prospective informations, computed in a direct way, reveal a level of intrauterine mortality of 58 fetal deaths per thousand pregnancies, which low value can be attributed to its direct nature that doesn\'t correct the bias of selection -, being also important to consider the pregnants domiciliary captation, without any kind of restriction in relation to the duration of the pregnancy. However, when the prospective informations are computed in the form of intrauterine mortality life tables, it\'s possible to correct the bias of selecting, achieving a rate of fetal mortality of 236 per thousand pregnancies, a result totally compatible to the estimations made by the most precise studies of fetal mortality. Regarding the stablishment of relationships of intrauterine mortality with the sociodemographic factor: race, instruction level and conjugal situation, the analised informations scem to reveal indications of the existence of: - A differential of intrauterine mortality by race, being the level represented by non white women higher than the represented by white ones. - A negative correlation between fetal mortality and instruction level, when this improves the risk of fetal losses decreases. - A differential of intrauterine mortality by conjugal situation, single women and those consesually joined more than women married with institutional links. In relation to the establishment of relationships of the intrauterine mortality with the biological factors: mother\'s age, pregnancy order and previous reproductive history, the analysis allowed to comprove that: - There is a positive correlation between fetal mortality and mother\'s age, in proportion that this increases, that improves. - There is also a positive correlation between intrauterine mortality and the pregnancy order, highest the order highest the number of lesses. - The most important factor in the determination of the risk of intrauterine mortality is the previous reproductive history.

Problem: Primary HSV-2 infection during pregnancy is associated with adverse pregnancy outcomes. However the mechanisms underlying these outcomes remain largely unknown. In this study we developed and characterized a mouse model of primary HSV-2 infection during early pregnancy and examined its effects on pregnancy and fetal outcomes. Methods of Study: C57BL/6 female mice positive for vaginal plugs were infected intravaginally (IVAG) with 10^3/10^4/10^5 PFU/mouse of HSV-2 (333) or saline (control) on gestational day (GD) 5. For comparison, female mice in diestrus stage were infected with HSV-2 at the same doses. Survival, pathology scores and vaginal viral shedding were measured post-infection. Systemic viral dissemination was examined by real-time PCR. Vaginal tissue, implantation sites, placenta and fetuses were examined by histology. Maternal serum (GD 13) and amniotic fluid (GD 8) was collected for multiplex cytokine analysis. Results: The minimum viral inoculation dose for infection in pregnant mice was 10^3 PFU of HSV-2, compared to 100-fold higher dose required to infect diestrus mice (10^5 PFU). There was a dose-dependent increase in implantation failure and number of resorptions with increasing dose of viral inoculum in pregnant mice at GD 8. In the 10^3 PFU group, although vaginal viral shedding was observed in all mice, 75% survived the infection, while all the mice in 10^4 and 10^5 PFU groups succumbed to infection by GD 13-15. There was evidence of abnormal placental morphology and necrotic fetal tissues in HSV-2 infected, pregnant mice compared to controls. Presence of HSV-2 DNA was measured in the vaginal tract, uterus (mated non-pregnant mice), and implantations of infected mated mice. HSV-2 DNA was also present in the spleen of the GD 13 time point group. Conclusions: These results indicate a 100-fold increase in susceptibility to HSV-2 infection during early pregnancy. At higher inoculation doses, IVAG HSV-2 infection spread systemically resulting in poor pregnancy outcomes and maternal mortality, especially in later gestation. At lower inoculation dose, the infection was localized in the reproductive tract and implantation sites, resulting in increased inflammation and adverse outcomes. This model will help to understand pathological mechanisms underlying adverse outcomes following primary HSV-2 infection in pregnancy. / Thesis / Master of Science (MSc)

Healthy pregnancy requires a tightly regulated materno-fetal dialogue for processes such as embryo implantation, endometrial decidualisation (in the mouse), placentation and maternal adaptation to occur. Disruption of placental development as well as maternal adaptation can lead to fetal intrauterine growth restriction (IUGR) which increases the risk of late miscarriage/stillbirth (e.g. 53% of preterm stillbirth and 26% of term stillbirth are found to be IUGR). Furthermore, IUGR is a risk factor for neurodevelopmental conditions in childhood and for a spectrum of related adult health disorders such as cardiovascular disease and type II diabetes, often termed metabolic syndrome. Despite these pregnancy disorders being common (e.g. 1 in 200 pregnancies results in stillbirth in the UK) the molecular lesion(s) underlying their pathophysiology are poorly understood and in particular those with placental and/or maternal aetiologies most frequently remain unexplained. Here we investigate the hypothesis that poly(A)-binding protein 4 (PABP4) is required for healthy pregnancy in mice. PABP4 is an RNA-binding protein and a member of the PABP family which are central regulators of mRNA translation and stability. Using all four permutations of wild-type and knock-out crosses, we find that maternal PABP4-deficiency results in a reduced litter size and IUGR. The number of implantations at e8.5 were not reduced in Pabp4-/- females, implying that the reduced litter size was not a consequence of decreased ovulation, fertilisation or implantation frequency. Further longitudinal analysis (at e13.5, e15.5 and e18.5) reveals that fetal death primarily occurred between e18.5 and birth, suggesting these mice may provide a unique opportunity to inform on the maternal causes of stillbirth. The onset of IUGR, which was found to be symmetrical in nature, was established by e15.5 preceding the majority of fetal death. During pregnancy, a materno-fetal dialogue directs and responds to changes in gene expression to give rise to the placenta and adapt the maternal physiology. Defects in these processes may result in reduced growth and/or fetal death and were examined in Pabp4-/- mice to shed light on the mechanistic basis of these related phenotypes. Fetal to placental (F:P) weight ratio, whose changes can be indicative of placental insufficiency or placental adaptation in an attempt to aid fetal growth, was found to be increased in Pabp4-/- dams at e15.5 and e18.5 due to the presence of IUGR fetuses with placentas of normal weight. Consistent with this observation, placental volume was unchanged at e18.5. Total placental weight and volume alone fails to discriminate potential differences in the individual placental zones which include the labyrinth zone, where materno-fetal gas and nutrient exchange occur; the junctional zone, which has endocrine functions including those that promote maternal adaptation; and the decidua basalis, derived from the maternal endometrium and is the site of trophoblast invasion and maternal vascular remodelling in early pregnancy. Therefore, volumetric analysis of these zones and the maternal blood spaces, which transcend the decidua basalis and junctional zone, was undertaken. This showed no change in the maternal blood spaces or the labyrinth, the latter being the zone whose size is most frequently altered in IUGR. Critically however, the size of the maternally-derived decidua basalis was increased with a concurrent decrease in the size of the junctional zone. These morphological changes may play a causative role either through directly affecting placental function and/or by the reduced junctional zone failing to promote appropriate maternal adaptation. Alternatively, they may reflect compensatory adaptations to a primary defect elsewhere in the mother. Complementing these morphological studies, functional studies were undertaken: remodelling of maternal vasculature and the resistance index of vessels delivering blood to the fetus were assessed; as was delivery of nutrients to the fetus (measured by fetal glucose); and systemic maternal adaptations (maternal hormonal profile, circulating glucose levels and organ weights). Uterine, umbilical and decidual spiral arteries were examined, but displayed no apparent differences suggestive of normal blood supply to the fetus. However fetal blood glucose was reduced suggesting a reduced delivery of nutrients important for fetal growth. This was not due to lower circulating maternal blood glucose levels, and mRNA levels of the placental glucose transporters Glut-1 and Glut-3 were not reduced but upregulated, suggestive of an attempt to compensate for reduced fetal glucose. Furthermore, upregulation of at least one system A amino acid transporter mRNA, Snat-2, was observed. The maternal physiological state of PABP4-deficient dams showed deviations in some organ weights (e.g. spleen weight is reduced at e13.5 and e15.5) and the levels of some circulating hormones (e.g. estradiol is deceased whereas progesterone is increased at e18.5). However, future work will be required to determine which, if any, of these changes are primary defects rather than downstream consequences and to identify which mis-regulated mRNAs/pathways within in the materno-fetal dialogue underlie the phenotype. Taken together, my results suggest that the regulation of mRNA translation/stability by PABP4 is critical to achieving the correct pattern of gene expression within the materno-fetal dialogue to enable appropriate placentation and maternal adaptation. Furthermore, my results suggest that Pabp4-/- mice provide a unique opportunity to further understand the maternal causes of a spectrum of related pregnancy complications including IUGR, late miscarriage and stillbirth.

Thesis (Ph. D.)--University of Washington, 1997. / Vita. Includes bibliographical references (leaves 75-85).

Orientador: Luis Guillermo Bahamondes / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-14T21:06:45Z (GMT). No. of bitstreams: 1 Canteiro_Renata_M.pdf: 1520573 bytes, checksum: 430ed31c6f7893af060873188cd2b55a (MD5) Previous issue date: 2009 / Resumo: Introdução e objetivos: O dispositivo intrauterino (DIU), apesar de ser um método contraceptivo altamente eficaz e adequado para a maioria das mulheres, nem sempre é recomendado para mulheres nuligestas. Alguns artigos apontaram para taxas de expulsão e gravidez aumentadas neste grupo de mulheres e outros sugeriram a adoção de DIU menores para nuligestas. Esta discussão tem se tornado mais evidente devido ao grande número de gravidezes indesejadas entre adolescentes (as quais, em sua maioria, são nuligestas), evidenciando a necessidade de métodos contraceptivos adequados a este perfil de usuárias. Restam dúvidas sobre a necessidade de novos DIU menores ou de formatos diferentes. Além disso, a avaliação do comprimento da cavidade uterina com o ultrassom, método mais moderno e preciso que o histerômetro, pode orientar para a necessidade de modelos de DIU diferenciados para nuligestas. O objetivo deste trabalho foi avaliar o comprimento da cavidade uterina em mulheres nuligestas e com gestação prévia através da histerometria e do ultrassom. Sujeitos e métodos: Foram avaliadas 570 mulheres (17 a 52 anos) distribuídas em 260 nuligestas e 310 com gestação prévia. Resultados: A diferença entre os valores médios obtidos pela histerometria e pelo ultrassom foi de 0,28cm. O comprimento da cavidade uterina em nuligestas e mulheres com gestação prévia foi 3,84 ± 0,03 e 4,25 ± 0,03, respectivamente, (p < 0,001) pela histerometria e 3,70 ± 0,03 e 3,84 ± 0,03 (média ± EPM), respectivamente pelo ultrassom (p = 0,006). Conclusões: O comprimento da cavidade uterina, avaliado por ambas as técnicas, foi maior entre as mulheres com gestação prévia que entre nuligestas. Esta foi em média maior que 3,6cm, que é o comprimento da maioria dos DIU disponíveis atualmente (TCu 380A) e o sistema liberador de levonorgestrel (LNG-IUS; 3,2cm). Entretanto, um terço das mulheres apresentou valores abaixo dessa medida. Isto permite especular que há poucas razões para o desenvolvimento de novos DIU com comprimento menor, embora exista a possibilidade de um terço das mulheres não se ajustar ao tamanho atual. / Abstract: Introduction and objectives: Due to the controversies about the necessity of new shorter intrauterine devices (IUDs) for nulliparous women in order to reduce expulsion rate, the length of the endometrial cavity was measured in women with different parities by uterine sound and ultrasound. Materials and methods: We evaluated 570 women (17 to 52 years old) distributed on 260 nulliparous and 310 parous. Results: The difference between mean values obtained by the uterine sound and by ultrasound was 0.28 cm. The length of the endometrial cavity on nulliparous and parous women was 3.84 ± 0.03 and 4.25 ± 0.03, respectively (p < 0.001) when assessed by the uterine sound and 3.70 ± 0.03 and 3.84 ± 0.03 (mean ± SEM), respectively when assessed by ultrasound (p = 0.006). Conclusions: The endometrial cavity length evaluated by the two techniques showed a mean value greater than 3.6 cm which is the length of the most worldwide available IUD (TCu380A) and the levonorgestrel-releasing intrauterine system (LNG-IUS). This allows us to speculate that there is no rationale to develop new IUDs with shorter length, because the actual models are fitted to most of the women, including nulliparous. / Mestrado / Ciencias Biomedicas / Mestre em Tocoginecologia

Purpose - The purpose of the present study is to compare intrauterine msemination (IUI) pregnancy rates (PR) as a function of diagnosis and ovulation protocol utilizing an extended semen transport time. This allowed clients to conveniently collect IUI specimens in the comfort and privacy of their home. A single IUI per treatment cycle was performed. Basic Procedures - Three-hundred-ten consecutive infertilty couples having unexplained, male factor, ovulatory dysfunction, endometriosis, tubal factor or combined diagnostic factors receiving a total of 584 cycles of IUI were included. Ovulation protocols included LH surge, clomiphene citrate (CC)-hCG, CC-gonadotropins(Gn)-hCG, Gn-hCG or leuprolide acetate (L)-Gn-hCG followed 36-42 hours by a single IUI. Pregnancy rates per cycle (fecundity) and per couple (fertility) as a function of diagnosis, ovulation protocol and cycle number were evaluated. In each cycle the couples processed the specimen by adding sperm washing medium at room temperature to the specimen 30 min following collection and allowed it to incubate for two hours prior to IUI during transport. Main Findings - Overall, fecundity was 11.8% (69/584) and fertility was 22.3% (69/310); respectively by diagnosis was: unexplained 22.6%,38.8%; male factor 18.8%,42.9%; ovulatory dysfunction 12.4,22.6%; endometriosis 5.3%,11.1%; tubal factor 7.6%,13.3%; and combined factors 9.7%, 20.0%. Unexplained vs endometriosis (P < 0.0001, P < 0.005), tubal factor (fecundity P < 0.008) and ovulatory dysfunction (fecundity P < 0.027) was statistically different. Male factor vs endometriosis (P < 0.011, P < 0.036) was significantly different. Ovulatory dysfunction vs endometriosis was significantly different (fecundity P < 0.027). Pregnancies by ovulation protocol: LH surge 4.5%,10.5%; CC-hCG 9.4%,14.9%; CC-Gn-hCG 13.7%,23.7%; Gn-hCG 17.5%,45.3%; L-Gn-hCG 3.5%,6.7%. For Gn-hCG vs L-Gn-hCG (P < 0.009, P < 0.030) and LH surge (fecundity P < 0.033). CC-Gn-hCG vs CC-hCG (fertility P < 0.050) and L-Gn-hCG (P < 0.033, P < 0.034). Gn-hCG vs CC-hCG (fecundity P < 0.043). Conclusions - We conclude that IUI is effective when utilizing an extended transport time allowing most couples to collect the specimen at home and is most effective when utilizing Gn-hCG therapy. Based on our analysis, endometriosis, tubal factor and combined diagnostic categories should proceed earlier to higher level assisted reproductive technologies.

Intrauterine Bälle („small uterine device“; IUDs) sind aus Glas, Plastik oder Metall und wer-den vaginal in den Uterus eingeführt. Bei Stuten werden IUDs im Turniersport zur Unterdrü-ckung der unerwünschten Verhaltensänderungen während der Rosse eingesetzt. Der Einsatz ist einfach, günstig und minimal invasiv. Der Effekt wird durch eine Verlängerung der primären lutealen Phase erzielt, wobei jedoch der exakte Ablauf des Wirkmechanismus bisher ungeklärt ist. Hypothesen wie eine Scheinträchtigkeit, ein Placeboeffekt bei den Besitzern und eine chronische Endometritis werden in der Literatur diskutiert. Für die Untersuchung wurden 30 Stuten in vier Gruppen (G) eingeteilt: G1: KB (künstlich besamt) und tragend (n=8); G2: KB, nicht-tragend (zyklisch; n=7); G3: IUD, verlängerte luteale Phase (n=7) IUD-P (IUD-Positiv); G4: IUD, reguläre luteale Phase (n=8) IUD-N (IUD-Negativ). Die Uterusbiospien wurden am Tag 15 post ovulationem entnommen. Das Ziel der Studie war, mittels immunhistologischer Untersuchungen die Expression des Enzyms Cyclooxygenase 2 (COX2), verschiedener uteriner Proteine (Uteroglobin, Uterofer-rin, Uterokalin), Hormonrezeptoren (Östrogen-, Progesteronrezeptor) und des Proliferations-markers Ki-67 Antigen in endometrialen Biopsien bei IUD-Stuten darzustellen sowie die erhobenen Befunde mit den Ergebnissen am equinen Endometrium künstlich besamter Stuten zu vergleichen. Weiter wurde in den Endometriumbioptaten das Auftreten von Entzündungszellen analysiert (neutrophile und eosinophile Granulozyten, Mastzellen, Lymphozyten, Plasmazellen und Makrophagen). Die statistische Auswertung erfolgte mittels SPSS (SPSS Software-GmbH München). Hinsichtlich der Altersverteilung sind die Stuten der Gruppe 1 (KB/tragend) jünger als Tiere der Gruppe 2 (KB/nicht-tragend). Ein entsprechendes Ergebnis kann für die Stuten der Grup-pe 3 (IUD-P) im Vergleich zu den Tieren der Gruppe 4 (IUD-N) erhoben werden. Darüber hinaus sind Angiopathien bei den Pferden der Gruppe 1 bzw. 3 geringer ausgeprägt als bei den Stuten der Gruppe 2 bzw. 4. Immunhistologisch sind die endometrialen Drüsenzellen der Tiere aus Gruppe 1 durch eine maximale Uterokalin-(UK)-Expression gekennzeichnet, wohingegen Uteroferrin (UF) ledig-lich schwach exprimiert wird. Eine COX2-Expression kann bei diesen Stuten nicht beobachtet werden. Im Vergleich zu den graviden Pferden (Gruppe 1) zeigen künstlich besamte, nicht-tragende Stuten (Gruppe 2) zwar eine ausgeprägte UF- und COX2-Expression, UK wird dagegen lediglich gering exprimiert. Die KB-tragenden (Gruppe 1) und nicht-tragenden (Gruppe 2) Tiere sind somit durch eine ihrem Reproduktionszyklus entsprechende Expression der genannten Marker gekennzeichnet. Die IUD-Stuten (Gruppe 3 und 4) dagegen zeigen eine variable COX2, UF- und UK-Expression. Keine statistisch signifikanten Unterschiede sind zwischen allen Gruppen in der UG- und der Ki-67 Antigen-Expression nachweisbar. Stuten mit einer verlängerten lutealen Phase (Gruppe 1 und 3) und hohen Progesteronwerten im Serum besitzen eine geringere ER- und PR-Expression als die Versuchstiere mit einer regulären lutealen Phase (Gruppe 2 und 4) und einer Östrogendominanz. Die Auszählung der Entzündungszellen zeigt keine statistisch signifikanten Unterschiede hinsichtlich der Anzahl von neutrophilen und eosinophilen Granulozyten, Mastzellen, Plasmazellen sowie Lymphozyten zwischen den Gruppen. Im Stratum compactum ist die Zahl der Makrophagen in Gruppe 1 (tragend) signifikant höher als in Gruppe 2 (zyklisch), ebenfalls zeigt sich ein Anstieg dieser Zellen von der Gruppe 4 zu 3, allerdings ist diese Erhöhung nicht statistisch signifikant. Ein Placeboeffekt bei den Besitzern kann nahezu ausgeschlossen werden, da die Expression der Proteine (UF, UK) und COX2 in den IUD-Stuten, im Vergleich zu den KB-Stuten, signi-fikante Unterschiede aufweist. Da im eigenen Untersuchungsgut zwischen den tragenden Stuten (Gruppe 1) und den IUD-Stuten der Gruppe 3 (vlP)/“Scheinträchtigkeit“ ein signifikant unterschiedliches Expressionsverhalten hinsichtlich des Enzyms COX2 und des Proteins UF besteht, kann die Hypothese einer Scheinträchtigkeit ebenso als unwahrscheinlich eingestuft werden. Bei keiner der IUD-Stuten konnte eine chronische Endometritis nachgewiesen werden, somit ist auch diese Hypothese als Ursache des IUD-Effektes eher unwahrscheinlich. Die erhöhte Anzahl an Makrophagen in der Gruppe 3 könnte jedoch hinweisend auf einen lokalen Effekt der IUDs im Sinne einer Fremdkörperreaktion sein. Da hinsichtlich des Auftretens einer Endometritis zwischen resistenten und empfänglichen Tieren unterschieden wird, könnte somit die erhöhte Anzahl an Makrophagen in der Gruppe 3 möglicherweise als Hinweis auf „Endometritis empfängliche Stuten“ gewertet werden und dies eine Ursache für die variierende Wirksamkeit der Rosseunterdrückung mittels IUDs darstellen. Die eigenen Untersuchungen zeigen ferner, dass die IUD-Stuten mit verlängerter lutealer Phase (IUD-positive Wirkung, Gruppe 3) jünger sind im Vergleich zu den Tieren, die trotz IUD eine Luteolyse (IUD-negative Wirkung, Gruppe 4) aufweisen. Zudem weisen die IUD-P Tiere geringere An-giopathien auf. Möglicherweise sind zudem das Alter und die Perfusion des Uterus bedeutend für die Wirksamkeit der IUDs in Equiden. Abschließend kann somit der Wirkmechanismus der IUDs auch mittels der durchgeführten Untersuchungen nicht endgültig geklärt werden. Unter Berücksichtigung der erhobenen Be-funde sollten zukünftige Studien insbesondere Untersuchungen zu Entzündungsmediatoren, wie z.B. Zytokine, beinhalten.