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.:INHALTSVERZEICHNIS I ABKÜRZUNGSVERZEICHNIS VI 1 EINLEITUNG 1 2 LITERATURÜBERSICHT 2 2.1 Rosseunterdrückung bei Pferden 2 2.2 Sexualzyklus und Gravidität der Stute 3 2.2.1 Der Sexualzyklus der Stute 3 2.2.2 Die equine Gravidität 3 2.2.3 Endokrine Regulation des Sexualzyklus und der frühen Trächtigkeit 6 2.2.3.1 Luteolyse und maternale Trächtigkeitserkennung 7 2.2.4 Immunhistologische Untersuchungen des Endometriums im Zyklusverlauf und während der Gravidität 9 2.2.4.1 Östrogen- und Progesteronrezeptoren 9 2.2.4.2 Ki-67 Antigen 10 2.2.4.3 Cyclooxygenase 2 10 2.3 Sekretorische Aktivität des Uterus 11 2.3.1.1 Uterokalin 11 2.3.1.2 Uteroferrin 12 2.3.1.3 Uteroglobin 13 2.4 Pathologie des equinen Endometriums 14 2.4.1 Histopathologische Veränderungen 14 2.4.1.1 Endometrose 14 2.4.1.2 Endometritis 16 2.4.2 Zelluläre Infiltrationen 17 2.4.2.1 Neutrophile Granulozyten 17 2.4.2.2 Makrophagen 18 2.4.2.3 Lymphozyten und Plasmazellen 18 2.4.2.4 Mastzellen 19 2.4.2.5 Eosinophile Granulozyten 19 2.4.3 Endometriumbiopsie als diagnostisches Mittel 20 2.5 Rosseunterdrückung bei Pferden 22 2.5.1 Methoden zur Rosseunterdrückung 22 2.5.2 Intrauterine devices (IUDs) 23 2.5.2.1 Allgemeine Betrachtung 23 2.5.3 IUDs zur Rosseunterdrückung bei Pferden 24 2.6 Fazit aus der Literatur bezogen auf die initiale Fragestellung dieser Arbeit 30 3 TIERE, MATERIAL UND METHODEN 31 3.1 Tiergut, Material und Probenherkunft 31 3.2 Nähere Charakterisierung des Tiergutes 31 3.3 Methoden 32 3.3.1 Probenentnahme und Probenaufbereitung 32 3.3.2 Anfertigung und Färbung der Schnitte 34 3.3.3 Lichtmikroskopische Auswertung und Kategorisierung 34 3.4 Histologische Spezialfärbungen 36 3.4.1 Unna-Pappenheim-Färbung (Methylgrün-Pyronin-Färbung) zur Identifizierung von Plasmazellen 36 3.4.2 Panoptische Färbung nach Pappenheim (kombinierte May-Grünwald-Giemsa-Färbung) zur Identifizierung von neutrophilen und eosinophilen Granulozyten sowie Mastzellen 36 3.5 Immunhistologische Methoden 37 3.5.1 Immunhistologische Kontrollen 37 3.5.2 Auswertung der immunhistologischen Untersuchung 37 3.6 Statistische Untersuchung 39 4 ERGEBNISSE 40 4.1 Anamnestische Untersuchungsbefunde 40 4.1.1 Zusammensetzung der Gruppen 40 4.1.2 Altersverteilung 41 4.2 Histopathologische Untersuchungsbefunde am Endometrium 41 4.2.1 Prävalenz der Endometritis im Untersuchungsgut 42 4.2.2 Prävalenz der Endometrose im Untersuchungsgut 43 4.2.3 Prävalenz der Angiosklerose im Untersuchungsgut 44 4.2.4 Kategorisierung 45 4.3 Immunhistologische Untersuchungen der Cyclooxygenase 2 46 4.3.1 Ergebnisse im Gruppenvergleich 47 4.4 Immunhistologische Untersuchungen zum Nachweis der endometrial synthetisierten Proteine 48 4.4.1 Uteroferrin (UF) 48 4.4.1.1 Uteroferrin-Expression im luminalen Epithel und den Zellen der Ausführungsgänge 49 4.4.1.2 Uteroferrin-Expression in den Drüsenzellen 49 4.4.1.3 Gesamtscore der Uteroferrin-Expression 50 4.4.1.4 Ergebnisse im Gruppenvergleich 51 4.4.1.5 Graduelle Abweichung des Ssc in der Endometrose 53 4.4.2 Uterokalin (UK) 53 4.4.2.1 Uterokalin-Expression im luminalen Epithel und den Zellen der Ausführungsgänge 53 4.4.2.2 Uterokalin-Expression in den Drüsenzellen 54 4.4.2.3 Gesamtscore der Uterokalin-Expression 55 4.4.2.4 Ergebnisse im Gruppenvergleich 55 4.4.2.5 Graduelle Abweichung des Ssc in der Endometrose 56 4.4.3 Uteroglobin (UG) 57 4.4.3.1 Uteroglobin-Expression in den basalen Drüsenzellen (bDr) 58 4.4.3.2 Ergebnisse im Gruppenvergleich 59 4.4.3.3 Graduelle Abweichung des Ssc in der Endometrose 60 4.4.4 Zusammenfassung Proteinexpression 61 4.5 Immunhistologische Ergebnisse zum Nachweis von Steroidhormonrezeptoren 62 4.5.1 Östrogenrezeptoren 62 4.5.1.1 Östrogenrezeptor-Expression im luminalen Epithel (LE) und den Ausführungsgängen (AS) 62 4.5.1.2 Östrogenrezeptor-Expression in den Drüsenzellen (DZ) 63 4.5.1.3 Östrogenrezeptor-Expression in den Stromazellen (SZ) 63 4.5.1.4 Ergebnisse im Gruppenvergleich 65 4.5.2 Progesteronrezeptoren 65 4.5.2.1 Progesteronrezeptor-Expression im luminalen Epithel (LE) und den Ausführungsgängen (AS) 66 4.5.2.2 Progesteronrezeptor-Expression in den Drüsenzellen (DZ) 66 4.5.2.3 Progesteronrezeptor-Expression in den Stromazellen (SZ) 66 4.5.2.4 Ergebnisse im Gruppenvergleich 67 4.6 Ki-67 Antigenexpression 67 4.7 Vergleichende histomorphologische und immunhistologische Untersuchung des Endometriums hinsichtlich des Auftretens von Entzündungszellen 68 4.7.1 T-Lymphozyten 68 4.7.1.2 Ergebnisse im Gruppenvergleich 69 4.7.2 B-Lymphozyten 70 4.7.2.1 Ergebnisse im Gruppenvergleich 71 4.7.3 Plasmazellen 72 4.7.3.1 Ergebnisse im Gruppenvergleich 73 4.7.4 Makrophagen 74 4.7.4.1 Ergebnisse im Gruppenvergleich 74 4.7.5 Neutrophile Granulozyten 76 4.7.5.1 Ergebnisse im Gruppenvergleich 77 4.7.6 Eosinophile Granulozyten 78 4.7.6.1 Ergebnisse im Gruppenvergleich 78 4.7.7 Mastzellen 79 4.7.7.1 Ergebnisse im Gruppenvergleich 80 4.7.8 Zusammenfassung der Ergebnisse hinsichtlich der Auszählung der Entzündungszellpopulationen 81 5 DISKUSSION 83 5.1 Ziel der Arbeit 83 5.2 Kritische Beurteilung des Untersuchungsmaterials und der Untersuchungsmethoden 83 5.3 Abschließende Betrachtung der Resultate 84 5.3.1 KB-Stuten 84 5.3.2 IUD-Stuten 86 6 ZUSAMMENFASSUNG 93 7 SUMMARY 95 8 LITERATURVERZEICHNIS 97 9 ANHANG 122 9.1 Charakterisierung des Tiergutes 122 9.2 Immunhistologie 123 9.2.1 Verfahrensschritte der immunhistologischen Untersuchungen 123 9.2.2 Besondere Verfahren 124 9.2.3 Antigennachweis mittels monoklonaler AK nach der Peroxidase-anti-Peroxidase-Methode (PAP) 124 9.2.4 Antigennachweis mittels polyklonaler AK nach der Peroxidase-anti-Peroxidase-Methode (PAP) 124 9.2.5 Standard zur Nachbehandlung 125 9.2.6 Verwendete Antikörper und Seren 126 9.2.7 Lösungen und Puffer 127 10 DANKSAGUNG 129

Background: The appetite-stimulating hormone ghrelin is a fundamental regulator of human energy metabolism. A series of studies support the notion that long-term appetite and weight regulation may be already programmed in early life and it could be demonstrated that the intrauterine environment affects the ghrelin system of the offspring. Animal studies have also shown that intrauterine programming of orexigenic systems persists even until adolescence/adulthood. Methods: We hypothesized that plasma ghrelin concentrations in adulthood may be associated with the intrauterine exposure to cigarette smoke. We examined this hypothesis in a sample of 19-year-olds followed up since birth in the framework of the Mannheim Study of Children at Risk, an ongoing epidemiological cohort study of the long-term outcome of early risk factors. Results: As a main finding, we found that ghrelin plasma concentrations in young adults who had been exposed to cigarette smoke in utero were significantly higher than in those without prenatal smoke exposure. Moreover, individuals with intrauterine nicotine exposure showed a significantly higher prevalence of own smoking habits and lower educational status compared to those in the group without exposure. Conclusion: Smoking during pregnancy may be considered as an adverse intrauterine influence that may alter the endocrine-metabolic status of the offspring even until early adulthood.

Thesis (MScMedSc)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: Male factor infertility is a general term that describes couples in which an inability to conceive is associated with a problem identified in the male partner. Intrauterine insemination (IUI) together with ovulation induction has been shown to be an effective treatment method for male factor infertility. Oocyte production by the ovaries is stimulated by the use of fertility drugs. A prepared sperm sample is then injected into the uterus through the vagina using an IUI catheter which brings the oocytes and spermatozoa into close proximity. Semen preparation is an integral part of an IUI cycle. In a developing country, a simple inexpensive semen preparation method for IUI procedures, not necessitating a lot of equipment, is essential. An example of such a method, the Sep-D Kit (Surelife Sep-D Kit, Surelife Media Technologies Pty Ltd, Singapore) has been proposed as a possible preparation method. In a pilot study performed by the principal investigator (Roxanne Gentis), comparing the Sep-D Kit and standard swim-up preparation methods, it was found that the Sep-D Kit compared very well with the swim-up method regarding most pre- and post-preparation semen parameters. The Sep-D Kit method, however, still needed further testing to see whether or not pregnancy rates resulting from the method are comparable with that resulting from the standard swim-up method, as this ultimately is the required result of an IUI. The primary aim of this study was to compare the Sep-D Kit method to the standard swim-up method with regards to biochemical pregnancy outcome, post-preparation sperm count, motility, total motile count (TMC), morphology, DNA compaction and fragmentation (CMA3 and TUNEL). The secondary aim was to evaluate which variables, male and female, affect biochemical pregnancy outcome. The study took place at Drs Aevitas Fertility Clinic, Vincent Pallotti Hospital, Pinelands. The study was a prospective analytical study and was conducted from December 2010 until October 2012. A total of 473 IUI cycles were evaluated. Results showed that the Sep-D Kit semen preparation method was non-inferior to the standard swim-up method with regards to biochemical pregnancy rates, post-preparation count and TMC. The swim-up method produced samples with a significantly higher post-preparation motility compared to the Sep-D Kit method, however both methods still managed to produce similar biochemical pregnancy rates (10.39% for the swim-up group versus 11.57% for Sep-D Kit group). For the total cohort of cycles analysed the only female parameter which significantly predicted biochemical pregnancy outcome in this study was age. Sperm motility (post-preparation) was the only male parameter that significantly affected biochemical pregnancy outcome. The Sep-D Kit method is more cost effective and also time saving compared to the swim-up method. There is also no need for expensive laboratory equipment or a trained embryologist using the Sep-D Kit preparation method. The Sep-D Kit may therefore be used with confidence as a standard semen preparation method, and may be implemented in developing countries for use in routine IUI procedures. / AFRIKAANSE OPSOMMING: Manlike faktor infertiliteit is 'n algemene term wat gebruik word om paartjies te beskryf wat 'n onvermoë toon om swanger te raak as gevolg van 'n probleem wat geassosieer word met die man. Die kombinasie van intra-uteriene inseminasie (IUI) en ovulasie induksie kan doeltreffend gebruik word om manlike faktor infertiliteit te behandel. Vrugbaarheidsmiddels word gebruik om oösietproduksie in die die eierstokke te stimuleer en 'n voorbereide spermmonster word dan transvaginaal in die baarmoeder ingespuit om sodoende die spermatozoa en oösiete na-aan mekaar te bring. Semenvoorbereiding is 'n integrale deel van 'n IUI siklus en in 'n ontwikkelende land is 'n eenvoudige, goedkoop semenvoorbereidingsmetode – wat die gebruik van duur toerusting uitsluit – noodsaaklik. Die Sep-D Kit metode (Surelife Sep-D Kit, Surelife Media Technologies Pty Ltd, Singapore) is 'n voorbeeld van so 'n voorbereidingsmetode. 'n Loodsstudie, uitgevoer deur die hoofnavorser, (Roxanne Gentis), het gewys dat die Sep-D Kit en standaard opswem voorbereidingmetodes goed vergelyk ten opsigte van meeste semenparameters voor- en na voorbereiding. Dit is egter ook noodsaaklikheid vir verdere navorsing om vas te stel of swangerskapuitkoms na die gebruik van die twee semenvoorbereidingsmetodess vergelykbaar is, aangesien dit die uiteindelike, verlangde uitkoms van 'n IUI is. Die primêre doel van hierdie studie was om die Sep-D Kit metode te vergelyk met die standaard opswemmetode met betrekking tot biochemiese swangerskapuitkoms asook spermtelling, motiliteit, totale motiele spermtelling (TMS), morfologie, DNA kompaksie en fragmentering (CMA3 en TUNEL) na spermvoorbereiding. Die sekondêre doel was om te evalueer watter veranderlikes, manlik en vroulik, die bichemiese swangerskapuitkoms beïnvloed. Die studie is uitgevoer by die Drs Aevitas Fertiliteitskliniek, Vincent Pallotti Hospitaal, Pinelands. Die studie was prospektief analities en het gestrek vanaf Desember 2010 tot en met Oktober 2012. 'n Totaal van 473 IUI siklusse is evalueer en ontleed. Die resultate van die studie het getoon dat die Sep-D Kit semenvoorbereidingsmetode nie ondergeskik aan die opswemmetode was ten opsigte van biochemiese swangerskap, spermtelling en TMS na semenvoorbereiding nie, Spermmotiliteit was betekenisvol hoër vir die opswemmetode vergelykend met die Sep-D Kit, maar ten spite van die verskil was die biochemiese swangerskapsyfers in die twee groepe nie verskillend nie (10.39% in die opswem groep en 11.57% in Sep-D Kit groep). In die totale kohort siklusse wat ontleed is was dit net die ouderdom van die vrou wat 'n betekenisvolle effek op biochemiese swangerskapuitkoms gehad het. Die enigste manlike faktor wat 'n betekenisvolle effek op biochemiese swangerskapuitkoms gehad het was die motiliteit na semenvoorbereiding. Die Sep-D Kit metode is meer koste-effektief en tydbesparend as die standard opswemmetode. Die uitvoer van die Sep-D Kit metode vereis ook ook geen duur apparaat of 'n opgeleide embrioloog nie. Die Sep-D Kit metode kan dus met vertroue gebruik word as 'n standaard semenvoorbereidingsmetode en kan in ontwikkelende lande vir gebruik tydens roetine IUI prosedures geïmplementeer word.

The purpose of this research project is to develop a clinical practice guideline for contraceptive counseling to include long acting reversible contraceptive (LARC) recommendations for the adolescent population. LARCs, which include intrauterine devices and implants, are the top-tier contraceptive for nulliparous women yet they are only used in less than 6% of women under 19 years old. There is no LARC clinical practice guideline that addresses the adolescent’s unique developmental and psychosocial needs that arise. A clinical practice guideline with adolescent-specific recommendations will strengthen counseling especially for long-acting reversible contraceptives. The review of literature searched PubMed, CINHAL, National Guideline Clearinghouse, Google Scholar and the Cochrane Library using search terms "LARCs," and "contraceptive counseling." The search yielded over 35,000 results; titles and abstracts were reviewed using pre-determined inclusion and exclusion criteria. The final source documents included forty-eight applicable manuscripts, which were graded using the United States Preventative Task Force (USPSTF) scale. The evidence was then sorted by similar findings and practice recommendations. The findings were used to formulate practice statements, which were then input into the Bridge-wiz software. The program generated recommendations and assigned a strength rating, and the clinical practice guideline was written from these recommendations. Finally, four clinical experts were identified using snowball sampling; they each participated in the final appraisal using the AGREE II tool. Based on the analysis of the review of literature, fifteen evidenced-based recommendations emerged. The recommendation topics included: best-practices for recommending LARCs, using developmentally appropriate teaching, providing youth-friendly services, and eliminating potential barriers to LARC uptake in adolescents. There are fifteen practice recommendations that increase adolescent uptake of LARCs. Limitations for the project included the absence of an internal review committee to grade the evidence and assign a strength to each recommendation. The use of Bridge-wiz software and the USPSTF evidence scale minimized bias. Providers can facilitate use of LARCs among adolescents by using developmentally appropriate and comprehensive contraceptive counseling. If more adolescents chose a LARC as their primary form of contraception, then overall teenage pregnancies may decrease. Further research is needed to understand other barriers and possible interventions.

Introdução: O comprimento telomérico é estudado em vários processos da relação saúdedoença, tais quais estresse oxidativo, processo inflamatório e estresse crônico e parece ser modulado por fatores genéticos e ambientais, além de estar associado a doenças como aterosclerose, doença de Alzheimer, insuficiência cardíaca e disqueratose congênita. Nosso estudo buscou entender a relação entre os telômeros de recém-nascidos e a gestação sob condições adversas. Objetivo: avaliar o impacto da exposição a diferentes ambientes intrauterinos sobre o comprimento de telômeros dos recém-nascidos. Métodos: o comprimento telomérico foi avaliado através do método de qPCR (Razão T/S) de células da mucosa oral de uma amostra conveniência de 239 pares de mãe e recémnascido, divididos nos seguintes grupos de mães: diabéticas (DM) (n=39), hipertensas (HAS) (n=16), tabagistas (n=52), controle (n=99) e mães que tiveram filhos pequenos para a idade gestacional (PIG) (n=33). Resultados: Em todos os grupos observamos uma correlação fraca entre o comprimento telomérico da mãe e da criança (r= 0,229) (p<0,001). Não houve diferença significativa no comprimento telomérico entre os grupos DM, HAS, PIG, Tabaco e Controle. Entretanto, dentro do grupo Tabaco houve diferença significativa numa relação dose-resposta inversa, de maior consumo de cigarro e comprimento telomérico menor, tanto para a mãe (p=0,020) quanto para o recém-nascido (p=0,033). Conclusão: os achados deste estudo sugerem que o uso do tabaco na gestação pode exercer influência negativa sobre o comprimento dos telômeros tanto da mãe quanto do seu filho. / Background: Telomere lenght has been studied in several health-disease processes, such as oxidative stress, inflammatory process and chronic stress. It seems to be influenced by genetic and environmental issues, and it is associated with diseases such as atherosclerosis, Alzheimer's disease, heart failure and congenital dyskeratosis. Our study searched to understand the relationship between newborns telomeres and adverse intrauterine conditions. Objective: to evaluate the impact of exposure to different intrauterine environments on the telomere length of newborns. Methods: the telomere length was evaluated by qPCR (T/S ratio) on oral mucosa cells of a convenience sample of 239 pairs of mother and newborn, divided according to the following groups of mothers: diabetic (DM) (n = 39), hypertensive (HAS) (n = 16), tobacco (n = 52), controls (n = 99) and mothers who had small children for gestational age (SGA) (n = 33). Results: In all groups we observed a weak correlation between the telomere of the mother and the son (r= 0.229) (p <0.001). There was no significant difference in telomere size between DM, HAS, SGAG, Tobacco and Control groups. However, in the Tobacco group there was a significant difference in an inverse dose-response relationship: higher cigarette consumption and lower telomere length, both for the mother (p = 0.020) and for the newborn (p = 0.033). Conclusion: the findings of this study suggest that tobacco use during gestation may induce a negative influence on the telomere length of both the mother and her child.

Background: This thesis is based on a randomised controlled trial comparing the effectiveness of intrauterine insemination (IUI) plus Controlled Ovarian Hyperstimulation (COH) versus in vitro fertilisation (IVF) as the first line treatment option for couples with unexplained subfertility. Subfertility of a couple is classed as unexplained when they fail to conceive after one year of regular unprotected intercourse and when all the standard investigations for ovulation, tubal patency and semen analysis have been found to be normal. It affects 30-40% of couples. The age-old methods of treating these couples have included the empirical use of clomiphene or gonadotrophins to correct any possible subtle defects in ovulation with or without IUI (to overcome any existing cervical barrier to natural conception) or IVF. However, the best treatment options for these couples have yet to be determined. The matter has been made even more controversial by the issue of NICE (National Institute for Health and Care Excellence) guidelines in the UK that suggest IUI be abandoned completely for these women in favour of IVF after 2 years of expectant management. A systematic review of the available literature comparing IUI + COH versus IVF for unexplained subfertility revealed limited numbers of available studies and high clinical and statistical heterogeneity among them. An online survey was also conducted among fertility specialists to establish the general consensus regarding management of such couples. The results revealed a lack of agreement among fertility specialists with regards to the first line treatment of couples with unexplained subfertility. The mixed 8 response to this survey demonstrated the ongoing dilemma among practitioners, much of which was due to the lack of robust evidence. A randomised controlled trial was then designed to examine the effectiveness of COH with gonadotrophins + IUI versus IVF as the first line approach to the treatment of unexplained subfertility (Figure 1). This was the first UK-based randomised controlled trial comparing these two first-line management options for unexplained subfertility.

Sumário: O DIU TCu380A é um método contraceptivo de alta eficácia e taxa de continuidade. O ACOG recomenda que o mesmo seja oferecido como primeira linha de contracepção para adolescentes independente da paridade. A falta de conhecimento e informação apropriada pode ser um fator decisivo para a nãoescolha do método. Objetivos: avaliar o grau de conhecimento sobre o DIU e identificar os principais motivos para sua não-escolha como contraceptivo por adolescentes entre 13 e 19 anos. Materiais e Métodos: Estudo transversal, prospectivo, onde o fator em estudo é o conhecimento sobre DIU e o desfecho é prevalência da opção pelo uso DIU (reposta SIM a pergunta " usaria DIU "). A amostra foi de 38 pacientes que consultam nos ambulatórios ou são puérperas internadas na maternidade do HCPA. O instrumento foi um questionário para auto-preenchimento. Análise de dados foi realizada por SPPS 18 e InfoStat. Resultados: A média de idade das entrevistadas foi de 16,05 anos (DP 1,33). Para analisar as perguntas verdadeiro/falso sobre assertivas acerca do DIU, criou-se a variável identificada como conhecimento correto, que correspondia ao acerto das 7 questões Não se encontrou associação entre conhecimento correto e possibilidade de uso de DIU (variável "usaria DIU") (Teste Exato de Fischer, p = 0,4, poder de 99,5%). Nas análises individuais para cada uma das assertivas de verdadeiro ou falso e a variável “usaria DIU", apenas a assertiva "A pílula é um método mais seguro que o DIU" emergiu como marginalmente significativa (Yates, bi-caudal 0,08, poder 60%). Observou-se uma associação entre maior escolaridade e conhecimento correto sobre o DIU (p=0,03, teste exato de Fischer). O principal motivo de recusa para uso encontrado foi informação insuficiente (26,3%) e medo da colocação (10,5%). Conclusões: O conhecimento correto de que a pílula não é um método mais seguro que o DIU significativamente influencia o uso do DIU no futuro. O fato das demais assertivas não determinarem maior escolha pelo DIU demonstra que o fato de desconhecerem que estarão mais protegidas com o uso de um LARC limita o uso do DIU. É fundamental informar as equipes de saúde que o DIU é um método mais efetivo e que não existe nenhum impeditivo para seu uso em adolescentes. / Background: The TCu380A IUD is a contraceptive method with high efficacy and continuity. The ACOG recommends that it should be offered as the first line of contraception for adolescents, despite parity. Lack of knowledge and appropriate information about the method can be a decisive factor for nonchoice. Objectives: to evaluate the degree of knowledge about the IUD and to identify the main reasons for not choosing the contraceptive method for adolescents between 13 and 19 years of age. Material and Methods: A cross-sectional, prospective study which the objective was to evaluate the knowledge about IUDs and the outcome was the prevalence of IUD possible use. The sample consisted of 38 patients who were attended at Gynecology and Obstetrics clinic or were hospitalized at the maternity (puerperium period) of the hospital. The instrument was a self-completion questionnaire. Data analysis was performed by SPPS 18 and InfoStat. Results: The average age of the interviewers was 16.05 years (SD 1.33). To analyze the true / false assertive questions about the IUD, we created the variable identified as correct knowledge, which corresponded to the correctness of the 7 questions There was no association between correct knowledge and the possibility of using IUDs. (Fischer's Exact Test, p = 0.4, 99.5% power). In the individual analyzes for each of the assertions of true or false and the variable would use IUDs, only the assertive " The pill is a safer method than the IUD " emerged as marginallly significant (Yates, two-tailed p = 0.08, power 60%). There was an association between higher education and correct knowledge about the IUD (p = 0.03, Fischer's exact test). The main reason for the refusal to use IUD was insufficient information (26.3%) and fear of insertion (10.5%). Conclusions: The correct knowledge that the pill is not a safer method than the IUD significantly influences the possibilty of IUD use in the future. The fact that the other assertions do not determine a greater choice for the IUD demonstrates that lack of knowledge that they would be more protected with the use of a LARC limits the IUD use. It is critical to inform health teams that the IUD is a more effective method and that there is no impediment to expand its use in adolescents and reduce the rate of pregnancy in adolescence.

Submitted by Rosivalda Pereira (mrs.pereira@ufma.br) on 2017-08-21T18:59:25Z No. of bitstreams: 1 SilviaSousa.pdf: 2280503 bytes, checksum: a06b53b8d68a96973316e3b881bd15d6 (MD5) / Made available in DSpace on 2017-08-21T18:59:25Z (GMT). No. of bitstreams: 1 SilviaSousa.pdf: 2280503 bytes, checksum: a06b53b8d68a96973316e3b881bd15d6 (MD5) Previous issue date: 2017-02-22 / Introduction: Intrauterine growth restriction (IUGR) and preterm birth (PT) are considered to be public health problems in developing countries. The occurrence of catch-up favors the ability of these infants to obtain equivalent growth to that of infants born without IUGR and at term. Objective: To assess the influence of IUGR and of PT on the occurrence of catch-up in weight and BMI in schoolchildren from two birth cohorts from cities with contrasting socioeconomic conditions in the Northeast and Southeast of Brazil. Method: A total of 1,463 children were studied, from whom information was collected at birth and at school age in 1994 and 2004/2005 in Ribeirão Preto, SP (RP) and in 1997/1998 and 2005/2006 in São Luís, MA (SL). The response variable was defined as the difference in weight and BMI between the Z-score of the schoolchild and the Z-score at birth. A change in Z-score ≥ 0.67 was considered to be catch-up. The explanatory variable was divided into four categories: without IUGR and at term (NIUGR-T), only IUGR (IUGR-T), only PT (NIUGR-PT), and PT plus IUGR (IUGR-PT). Estimates of the relative risk for catch-up in weight were obtained by logistic regression in separate models for each city. Results: RP children had a greater proportion of both catch-up than SL children. In RP, 90.8% of IUGR-PT and 70.8% of NIUGR-PT (it was more frequent in pre-terms, restricted or not) caught up in weight at school age. In SL, the NIUGR-PT and IUGR-T caught up in a similar way. There was no difference between genders. Regarding marital status, in RP, no difference was found, however, in SL, the odds of catching up at 7 years old was 65% lower for those schoolchildren whose mothers did not have a partner. Having only one child, both in RP and in SL, increased almost twofold (OR=1.89 in RP and 1.83 in SL) the odds of the schoolchild catching up; and receiving up to 5 times the monthly minimum wage decreased by 50% the odds of catching up in SL, although no difference was found in RP. The head of the family’s occupation being unqualified manual labor or unemployed decreased by half the odds of catching up in both cities. Maternal age and education level were not associated to catchup in school age. Conclusion: In both cities, children born preterm with/without IUGR had a greater proportion of catch-up in weight and without IUGR and at term in BMI. / Introdução: A restrição de crescimento intrauterino (RCIU) e o nascimento pré-termo (PT) são considerados problemas de saúde pública nos países em desenvolvimento. A ocorrência de catch-up propicia que estes consigam equiparar seu crescimento ao das crianças nascidas sadias. Objetivo: Avaliar a influência da RCIU e do PT na ocorrência de catch-up de peso e IMC em escolares de duas coortes de nascimentos de cidades com condições socioeconômicas contrastantes. Método: Foram estudadas 1.463 crianças, cujas informações foram coletadas ao nascer e na idade escolar em 1994 e 2005/06 em Ribeirão Preto, SP (RP) e em 1997/98 e 2005/06 em São Luís, MA (SL). A variável resposta foi definida pela diferença entre o escore z do escolar e escore z ao nascimento do peso e IMC. Considerou-se como catch-up uma mudança de escore z de ≥ 0,67. A variável explanatória foi dividida em quatro categorias: sem RCIU e a termo (TNR), só RCIU (TR), só PT (PTNR) e PT com RCIU (PTR). Estimativas do risco relativo para catch-up de peso foram obtidas por regressão logística em modelos separados por cidade. Resultados: O fenômeno “catch-up” tanto de peso quanto de IMC foi mais evidente em RP para todas as categorias das chamadas condições de nascimento. Para ambas as cidades a maior incidência de catch-up de peso se deu para os PT e/ou com RCIU, já o de IMC para os TNR. Não houve diferença entre os sexos. Ter somente 1 filho, maior renda familiar e escolaridade materna além da ocupação do chefe mais qualificada aumentou a frequência do catch-up de peso e IMC em ambas as cidades. Conclusão: Não só condições biológicas ao nascer mas também as condições de vida, tais como, acesso aos serviços de saúde e melhor oferta de alimentos nas idades mais precoces da criança influenciam na ocorrência de catch-up de peso e IMC nas duas cidades estudadas.

Bakgrund: Det finns begränsad kunskap om hur mammor upplever att drabbas av HELLP syndrom och samtidigt mista sitt väntade barn. Ytterligare kunskap kan bidra till ökad förståelse och leda till bättre vård. Syfte: Att beskriva mammors upplevelser av att drabbas av HELLP syndrom och samtidigt mista sitt väntade barn. Metod: En kvalitativ fallstudie med djupintervjuer som analyserades genom kvalitativ innehållsanalys. Resultat: Studien påvisade det kaos och den overklighetskänsla mammorna upplevde då insjuknandet och händelserna skedde i snabb takt. Det fanns ingen tid för reflektion, tillståndet var livshotande och en katastrofkänsla uppstod. Temat overkligt kaos formades. De svårt sjuka mammorna klarade inte att delta vid första omvårdnaden av sitt döda barn men kunde under vårdtiden vara tillsammans med barnet vid flera tillfällen vilket gav känslor av både glädje och sorg. Mammorna upplevde restsymtom av HELLP syndrom ett halvår efter händelsen. Slutsatser: Det snabba insjuknandet och händelseförloppet resulterade i ett overkligt kaos för mammorna. Det är viktigt att vårdpersonalen är tydliga i sin kommunikation och hela tiden närvarande hos mamman. Barnmorskan har en central roll i att hjälpa mammorna att möta och vara nära sitt döda barn så mycket som möjligt.

Η ενδομήτρια καθυστέρηση ανάπτυξης ορίζεται ως παθολογική μείωση του ρυθμού εμβρυικής ανάπτυξης που καταλήγει σε ένα έμβρυο το οποίο δεν έχει την αναμενόμενη ανάπτυξη σύμφωνα με την ηλικία κύησης και το οποίο διατρέχει κίνδυνο αυξημένης περιγεννητικής νοσηρότητας και θνησιμότητας. Ενδομήτρια καθυστέρηση ανάπτυξης είναι η ανικανότητα του εμβρύου να διατηρήσει τον αναμενόμενο ρυθμό ανάπτυξης ανεξάρτητα αν το βάρος του είναι κάτω από τη 10η εκατοστιαία θέση. Όταν η ανάπτυξη του εμβρύου είναι κάτω από την 5η εκατοστιαία θέση τότε ίσως να μπορεί να θεωρηθεί πραγματική ενδομήτρια καθυστέρηση ανάπτυξης. Σύμφωνα με το αμερικανικό κολέγιο γυναικολόγων και μαιευτήρων American College of Obstetricians and Gynecologists (ACOG) η ενδομήτρια καθυστέρηση ανάπτυξης ορίζεται ως το έμβρυο που αποτυγχάνει να έχει τον αναμενόμενο ρυθμό ανάπτυξης. Πολλές φορές οι όροι ενδομήτρια καθυστέρηση ανάπτυξης (IUGR) και μικρό για την ηλικία κύησης (SGA) συγχέονται και για αυτό το λόγο διευκρινίζεται ότι ο όρος μικρό για την ηλικία κύησης (SGA) αναφέρεται σε έμβρυο του οποίου το εκτιμώμενο βάρος είναι κάτω από τη 10η εκατοστιαία θέση. Από το σύνολο των μικρών για την ηλικία κύησης (SGA) εμβρύων το 40% είναι υγιή, 20% είναι μικρά εξαιτίας χρωμοσωμικών και περιβαλλοντικών παραγόντων και 40% διατρέχουν ιδιαίτερα αυξημένο κίνδυνο ενδομήτριου θανάτου και σχετίζονται με ενδομήτρια καθυστέρηση ανάπτυξης. Η ενδομήτρια καθυστέρηση ανάπτυξης είναι μια πολυσυστηματική διαταραχή και διακρίνεται σε: Α) Συμμετρική. Όταν η ανάπτυξη της κεφαλής και της κοιλιάς επιβραδύνονται συμμετρικά. Είναι λιγότερο συχνή, 20%-30%. Β) Ασύμμετρη. Δυσανάλογη ελάττωση του μεγέθους της κοιλιάς σε σχέση με αυτό της κεφαλής. Είναι περισσότερο συχνή, 70%-80%, και οφείλεται συνήθως σε μητροπλακουντιακή ανεπάρκεια και συμβαίνει μετά την 28η εβδομάδα. Στη φάση αυτή γίνεται η μεγαλύτερη εναπόθεση λίπους. Η ενδομήτρια καθυστέρηση ανάπτυξης αποτελεί κύριο πρόβλημα στην περιγεννητική ιατρική, είναι η ΔΕΥΤΕΡΗ αιτία θανάτου μετά την προωρότητα. 52% των ανεξήγητων ξαφνικών θανάτων των εμβρύων συσχετίζονται με ανάπτυξη IUGR. 10% των περιπτώσεων περιγεννητικής θνησιμότητας στην Ευρώπη είναι αποτέλεσμα μη διαγνωσμένης IUGR. Η επίπτωση της ενδομήτριας καθυστέρησης ανάπτυξης είναι 8% στον γενικό πληθυσμό. / Intrauterine growth restriction (IUGR) is the failure of the fetus to achieve his/her intrinsic growth potential and is associated with significantly increased perinatal morbidity and mortality. IUGR affects 10% of pregnancies and perinatal mortality rates are 4-8 times higher for infants with this disorder. Intrauterine growth restriction is not a specific disease entity with a unique pathophysiology, but the result of suboptimal intrauterine growth conditions in conjunction with a variety of disorders from genetic to metabolic, vascular, coagulative, autoimmune, as well as infectious. Newborns with intrauterine growth restriction (IUGR) present reduced fat mass and undergo adaptational changes of endocrine/metabolic mechanisms as a result of intrauterine malnutrition. Recently, it was shown that fat-secreted adipokines such as visfatin, a novel adipokine improving glucose tolerance through insulin-mimetic effects, and vaspin , profoundly influence insulin sensitivity and energy metabolism.