State regulation of assisted reproductive technology (ART) has been occurring since the inception of earlier technological advances such as artificial insemination to aid human reproduction. I provide a brief overview of the current regulation of ART in the U.S. and the literature on state regulation. Unlike previous studies of ART regulation which use content analysis or case studies of individual state laws I estimate ART regulation for the entire U.S. by using a series of random effects logistic regression models for the time period 1995-2006. To my knowledge this is the first quantitative analysis of ART regulation. I test the hypothesis that the demand for ART is an important predictor of ART legislation in the U.S. Other hypotheses derived from the ART literature were also tested in the analysis. Results indicate that demand for ART is the most influential factor in predicting ART legislation from 1995-2006. Additionally, educational attainment of a state's population and the percentage of married couple households with children in each state may have a direct effect on the demand for ART and an indirect effect on ART regulation.

A configuração tradicional da família, composta pela família nuclear (pai/homem, mãe/mulher e filhos) vem sofrendo transmutações cada vez mais evidentes durante as últimas décadas. No Brasil, a luta pela normatização social e legislativa do casamento entre pessoas do mesmo sexo vem sendo travada e a vivência da parentalidade tem se tornado parte da luta de casais de mesmo sexo. Nesse sentido, um número crescente de famílias homoparentais passam a ser efetivamente formadas. As Novas Tecnologias Reprodutivas (NTR), assim como a adoção, fazem parte dos meios que esses casais têm utilizado para a concretização do sonho da parentalidade. As NTR são um produto médico de consumo que, ao desvincular sexo e reprodução, coloca esta última como questão de escolha, possibilitando diferentes arranjos parentais via compra de intervenção tecnológica. Dentro desse contexto, o estudo centrou-se nas concepções dos casais de mesmo sexo sobre o uso de NTR na efetivação do projeto de parentalidade. O estudo de natureza qualitativa foi realizado com casais de mesmo sexo, tanto de homens como de mulheres, que tinham o plano de terem filhos ou que já os tivessem tido. Foram realizadas entrevistas semiestruturadas com um grupo de 26 pessoas composto por 12 casais e dois sujeitos (um homem e uma mulher), todos residentes na Região Metropolitana de São Paulo, Brasil, entre os anos de 2011 e 2012. Os resultados apontam que os laços biológicos se fazem preponderantes nos discursos dos casais de mulheres, bem como há uma maior tendência destas a utilizarem/quererem utilizar as NTR, principalmente a ROPA (Recepção de Óvulos da Parceira). Os casais de homens, mesmo quando apontam para o desejo de terem um filho geneticamente aparentado, optam pelo recurso da adoção, dentre outros motivos, pelo receio do vínculo que possa ser estabelecido, por meio da gestação, entre a mãe de aluguel e a criança. A análise produzida a partir dos dados empíricos contribui para o debate sobre a relação entre famílias homoparentais e uso de tecnologias médicas. Isso porque problematiza como as NTR incorporam mudanças fundamentais no parentesco contemporâneo ocidental, e como a medicina e a sociedade caminham juntas na construção de novos significados acerca da parentalidade, num movimento em que natureza e cultura imiscuem-se tornando-se cada vez mais difícil e contraprodutivo separá-las / Family\'s traditional configuration, composed by the nuclear family (father/man, mother/woman and children) has been passing through evident transmutations during the last decades. In Brazil, the fight for social and legal standardizations of same-sex marriage has been occurring and the experience of parenthood has become part of the fight of same-sex couples. In this sense, homoparental families begin to be effectively formed. New Reproductive Technologies (NRT), as adoption, make part of the resources that these couples have been using to fulfill their dream of parenthood. NRT are a medical consumer product, which unlinking sex and reproduction make reproduction a matter of choice, enabling different parenthood arrangements through purchase of technological intervention. In this context, the study focused the same-sex couples conceptions about the use of NRT in their parenthood´s project effectiveness. The qualitative study was developed with same-sex couples, both men and women, who had plans to have children or have already had them. Semi-structured interviews were conducted with 26 respondents, composed by 12 couples and two subjects, resident in the metropolitan area of São Paulo, Brazil, between 2011 and 2012. The results point out the preponderance of biological bond in female couples speeches and that there is a tendency of such couples to use/want to use NRT, mainly ROPA (Reception of Oocytes from Partner). Male couples, even when they show the desire to have a genetically related child, choose adoption, among other reasons, for the fear of the bond that may be established through pregnancy between the surrogate mother and the child. The analysis produced from empirical data contributes to the debate about the relationship between homoparental families and the use of medical technologies, once it discusses how NRT incorporate fundamental changes in occidental contemporary kinship and how medicine and society walk together building new meanings to parenthood in a process that nature and culture encroach up, turning increasingly difficult and counter-productive to separate them

A configuração tradicional da família, composta pela família nuclear (pai/homem, mãe/mulher e filhos) vem sofrendo transmutações cada vez mais evidentes durante as últimas décadas. No Brasil, a luta pela normatização social e legislativa do casamento entre pessoas do mesmo sexo vem sendo travada e a vivência da parentalidade tem se tornado parte da luta de casais de mesmo sexo. Nesse sentido, um número crescente de famílias homoparentais passam a ser efetivamente formadas. As Novas Tecnologias Reprodutivas (NTR), assim como a adoção, fazem parte dos meios que esses casais têm utilizado para a concretização do sonho da parentalidade. As NTR são um produto médico de consumo que, ao desvincular sexo e reprodução, coloca esta última como questão de escolha, possibilitando diferentes arranjos parentais via compra de intervenção tecnológica. Dentro desse contexto, o estudo centrou-se nas concepções dos casais de mesmo sexo sobre o uso de NTR na efetivação do projeto de parentalidade. O estudo de natureza qualitativa foi realizado com casais de mesmo sexo, tanto de homens como de mulheres, que tinham o plano de terem filhos ou que já os tivessem tido. Foram realizadas entrevistas semiestruturadas com um grupo de 26 pessoas composto por 12 casais e dois sujeitos (um homem e uma mulher), todos residentes na Região Metropolitana de São Paulo, Brasil, entre os anos de 2011 e 2012. Os resultados apontam que os laços biológicos se fazem preponderantes nos discursos dos casais de mulheres, bem como há uma maior tendência destas a utilizarem/quererem utilizar as NTR, principalmente a ROPA (Recepção de Óvulos da Parceira). Os casais de homens, mesmo quando apontam para o desejo de terem um filho geneticamente aparentado, optam pelo recurso da adoção, dentre outros motivos, pelo receio do vínculo que possa ser estabelecido, por meio da gestação, entre a mãe de aluguel e a criança. A análise produzida a partir dos dados empíricos contribui para o debate sobre a relação entre famílias homoparentais e uso de tecnologias médicas. Isso porque problematiza como as NTR incorporam mudanças fundamentais no parentesco contemporâneo ocidental, e como a medicina e a sociedade caminham juntas na construção de novos significados acerca da parentalidade, num movimento em que natureza e cultura imiscuem-se tornando-se cada vez mais difícil e contraprodutivo separá-las / Family\'s traditional configuration, composed by the nuclear family (father/man, mother/woman and children) has been passing through evident transmutations during the last decades. In Brazil, the fight for social and legal standardizations of same-sex marriage has been occurring and the experience of parenthood has become part of the fight of same-sex couples. In this sense, homoparental families begin to be effectively formed. New Reproductive Technologies (NRT), as adoption, make part of the resources that these couples have been using to fulfill their dream of parenthood. NRT are a medical consumer product, which unlinking sex and reproduction make reproduction a matter of choice, enabling different parenthood arrangements through purchase of technological intervention. In this context, the study focused the same-sex couples conceptions about the use of NRT in their parenthood´s project effectiveness. The qualitative study was developed with same-sex couples, both men and women, who had plans to have children or have already had them. Semi-structured interviews were conducted with 26 respondents, composed by 12 couples and two subjects, resident in the metropolitan area of São Paulo, Brazil, between 2011 and 2012. The results point out the preponderance of biological bond in female couples speeches and that there is a tendency of such couples to use/want to use NRT, mainly ROPA (Reception of Oocytes from Partner). Male couples, even when they show the desire to have a genetically related child, choose adoption, among other reasons, for the fear of the bond that may be established through pregnancy between the surrogate mother and the child. The analysis produced from empirical data contributes to the debate about the relationship between homoparental families and the use of medical technologies, once it discusses how NRT incorporate fundamental changes in occidental contemporary kinship and how medicine and society walk together building new meanings to parenthood in a process that nature and culture encroach up, turning increasingly difficult and counter-productive to separate them

Thesis (MScMedSc)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: CHAPTER 1 A review of the application of traditional semen parameters for the investigation and diagnosis of male infertility and the role of predictive values in assisted reproductive techniques (ART) is presented. The importance of sperm morphology, with special emphasis on sperm morphology evaluation, is discussed. Also presented is an overview of the physiology of sperm DNA, the process of spermatogenesis, as well as the contribution of the spermatozoon to the embryo. The different causes of sperm DNA damage and techniques to determine DNA damage in spermatozoa are described. A survey is presented of the correlation of sperm DNA with sperm morphology. CHAPTER 2 All the materials and methods applicable to this study are described. Sperm morphology assessment and two different sperm DNA tests, the chromomycin A3 (CMA3) staining test and the terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labelling (TUNEL) assay, are discussed in detail. CHAPTER 3 Results obtained in this study are presented. Results include the prevalence of abnormal sperm DNA and association with sperm morphology, specifically in the p-pattern and g-pattern morphology groups. Further results include the correlation of sperm morphology and sperm DNA with fertilization in vitro, embryo quality and pregnancy outcome. The percentage CMA3 positive spermatozoa (abnormal DNA) and percentage TUNEL positive spermatozoa (abnormal DNA) had a significant negative association with normal sperm morphology. P-pattern and g-pattern morphology groups differed significantly from each other for both CMA3 and TUNEL. A significant positive association between CMA3 and TUNEL was observed. No association between the percentage normal sperm morphology, percentage CMA3 positive spermatozoa and percentage TUNEL positive spermatozoa and IUI pregnancy outcome was observed. A significant negative association between the percentage TUNEL positive spermatozoa and IVF/ICSI pregnancy outcome was established. The percentage CMA3 positive spermatozoa had a significant positive (unexpected) association with IVF/ICSI pregnancy outcome. There was no association between the three variables and IVF/ICSI fertilization rates. A significant positive association between the percentage normal sperm morphology and IVF/ICSI embryo quality was found. There was a significant positive association between the percentage CMA3 positive spermatozoa and IVF/ICSI embryo quality (unexpected). The percentage TUNEL positive spermatozoa and IVF/ICSI embryo quality was negatively associated. CHAPTER 4 Interpretation of the results and future perspectives are discussed. The CMA3 staining test and TUNEL assay has a limited ability to distinguish between the p-pattern and g-pattern morphology groups. P-pattern spermatozoa are more likely to possess poor chromatin packaging and show increased levels of DNA fragmentation, but some p-pattern patients also may have normal DNA and g-pattern patients abnormal DNA. It is recommended that a sperm DNA test should be implemented routinely in andrology laboratories for the clinical diagnosis of sperm DNA damage in patients. / AFRIKAANSE OPSOMMING: HOOFSTUK 1 'n Samevatting wat handel oor die toepassing van tradisionele semen parameters vir die evaluasie en diagnose van manlike infertiliteit, asook die rol van voorspellingswaardes in kunsmatige voortplantingstegnieke word voorgelê. Die belangrikheid van sperm morfologie, met die klem op sperm morfologie evaluering, word ook bespreek. 'n Oorsig van sperm DNS fisiologie, die proses van spermatogenese, sowel as die sperm se bydrae tot die embrio word hier aangebied. Die verskillende oorsake van sperm DNS skade en die tegnieke om sperm DNS skade vas te stel, asook die die korrelasie tussen sperm DNS en sperm morfologie word ook bespreek. HOOFSTUK 2 Alle materiale en metodes wat van toepassing is op hierdie studie word beskryf. Sperm morfologie evaluering en twee verskillende sperm DNS toetse, die chromomycin A3 (CMA3) kleuringstoets en die “terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labelling (TUNEL)" toets, word ook in meer besonderhede aangebied. HOOFSTUK 3 Resultate wat verkry is tydens hierdie studie word hier uiteengesit. Resultate behels die voorkomsyfer van abnormale DNS en die assosiasie met sperm morfologie, spesifiek in die p-patroon en g-patroon. Verdere resultate sluit die korrelasie van sperm morfologie en sperm DNS met bevrugting in vitro, embriokwaliteit en swangerskap uitkomste in. Die persentasie CMA3 positiewe sperme (abnormale DNS) en persentasie TUNEL positiewe sperme (abnormale DNS) het 'n betekenisvolle negatiewe assosiasie met normale sperm morfologie getoon. P-patroon en g-patroon morfologie groepe het betekenisvol van mekaar verskil vir beide CMA3 en TUNEL. 'n Betekenisvolle positiewe assosiasie is tussen CMA3 en TUNEL waargeneem. Geen assosiasie is tussen die persentasie normale sperm morfologie, persentasie CMA3 positiewe sperme en persentasie TUNEL positiewe sperme en IUI swangerskap uitkomste waargeneem nie. 'n Betekenisvolle negatiewe assosiasie is tussen die persentasie TUNEL positiewe sperme en IVB/ICSI swangerskap uitkomste vasgestel. Die persentasie CMA3 positiewe sperme het 'n betekenisvolle positiewe (onverwags) assosiasie met IVB/ICSI swangeskap uitkomste opgewys. Daar was geen assosiasie tussen die drie veranderlikes en IVB/ICSI bevrugting nie. 'n Betekenisvolle positiewe assosiasie is tussen die persentasie normale sperm morfologie en IVB/ICSI embryo kwaliteit waargeneem. Daar was 'n betekenisvolle positiewe assosiasie tussen die persentasie CMA3 positiewe sperme en IVB/ICSI embrio kwaliteit (onverwags). Die persentasie TUNEL positiewe sperme het 'n negatiewe assosiasie met IVB/ICSI embrio kwaliteit getoon. HOOFSTUK 4 Interpretasie van die resultate en toekomstige vooruitsigte is bespreek. Die CMA3 kleuringstoets en TUNEL toets het 'n beperkte vermoë om tussen die p-patroon en g-patroon morfologie groepe te onderskei. P-patroon spermatozoa sal heel waarskynlik oor swakker chromatien verpakking en meer DNS fragmentasie beskik. Sommige p-patroon pasiënte mag egter normale DNS toon, terwyl g-patroon pasiënte abnormale DNS het. Die implementering van 'n sperm DNS toets in andrologie laboratoriums, vir die kliniese diagnose van sperm DNS skade in pasiënte, word aanbeveel.

Dissertation (PhD)--University of Stellenbosch, 2007. / ENGLISH ABSTRACT: Male fertility has for many years been defined in vitro as the ability of sperm to fertilize oocytes and to obtain early cleavage-stage embryos. Spermatozoa comprise of an extraordinary high percentage of polyunsaturated fatty acids in their plasma membrane. Due to an extremely low content of cytoplasm, sperm cells have a particularly low potential to scavenge reactive oxygen species (ROS), and are therefore highly sensitive to oxidative processes, which lead to sperm nucleus DNA damage/fragmentation. Normally, DNA fragmentation occurs in every ejaculate and can be induced by an excessive ROS production of active leukocytes or the spermatozoa themselves. Under distressed conditions, DNA fragmentation may also occur in the testis as a result of oxidative processes in the apoptotic cascade. These DNA fragmentations can be regarded as late signs of programmed cell death (apoptosis). Clinically, DNA fragmentation in spermatozoa results in significantly decreased implantation and pregnancy rates especially in patients with oligo- and/or teratozoospermia. The p-pattern normal sperm morphology has been shown to give poorer fertilization rates in vitro than the g- and n-patterns. In this study there is reported on the significant correlation found between the p-pattern normal sperm morphology and sperm DNA fragmentation as measured with the terminal deoxynucleotidyl transferase-mediated dUDP-biotin end labeling (TUNEL) assay. This finding further explains the lower fertility potential of patients presenting with p-pattern normal sperm morphology. In addition, this study explores the intricate relations between ROS in the semen, DNA fragmentation of the spermatozoa, as measured with the TUNEL assay and the sperm chromatin structure assay (SCSA ), spermatozoa apoptotic status and sperm parameters as measured with a standard semen analysis. Positive correlations were found between ROS and the apoptotic status of the sperm, as well as between sperm with non-fragmented DNA and sperm concentration and percentage motility. The results emphasize the importance of sperm selection especially when the treatment of choice is intracytoplasmic sperm injection (ICSI). An early sign of programmed cell death, also known as apoptosis, is the externalization of phosphatidylserine (PS) from the inner membrane leaflet to the outer leaflet. PS shows a high affinity to Annexin V. Apoptotic spermatozoa are able to fertilize oocytes, but embryo senescence may occur at the time when the paternal genes are activated. In this study there is reported on a novel method whereby spermatozoa can be separated on the basis of their apoptotic status through flow cytometry. Results showed that the normal sperm morphology, according to strict criteria, of the resultant nonapoptotic sperm fraction is significantly higher than that of the apoptotic counterpart. With refinement of this technique, it will be possible in future to use these separated non-apoptotic sperm cells during ICSI for fertilization. From the above it is apparent that the spermatozoon has to play a vital role in the development of the embryo from fertilization to implantation and pregnancy. It is, however, important to note that besides the gametes, there are other critical factors which contribute to a successful in vitro fertilization (IVF) cycle, among these are the in vitro culture conditions. In this regard, this study compared two sequential embryo culture systems. It was found that the more complex medium resulted in better day three embryo quality and a better blastocyst formation rate and pregnancy rate. These findings highlight the importance of a holistic perspective towards the complexity of the factors involved in affecting embryo quality and pregnancy outcome. / AFRIKAANSE OPSOMMING: Manlike fertiliteit is vir baie jare gedefinieer as die in vitro vermoë van ‘n spermsel om ‘n eiersel te bevrug om sodoende embrios te verkry. Die spermsel se plasmamembraan bestaan uit ‘n hoë persentasie poli-onversadigde vetsure. As gevolg van die klein hoeveelhede sitoplasma van die spermsel het dit ‘n beperkte weerstand teen reaktiewe suurstof spesies (ROS) en is gevolglik baie sensitief vir oksidasie. Oksidasie lei tot DNS skade/fragmentasie. DNS fragmentasie kom in spermselle van alle ejakulate voor en is gewoonlik die gevolg van ROS produksie deur die leukosiete in die semen of vanaf die spermselle self. Onder sekere omstandighede kan DNS fragmentasie ook voorkom in die testis waar dit deel vorm van apoptose. Hierdie tipe DNS skade word gesien as laat tekens van geprogrammeerde seldood (apoptose). In oligo- en/of teratozoospermiese mans lei DNS fragmentasie tot verlaagde implantasie- en swangerskapssyfers. Die p-patroon normale sperm morfologie groep gee laer in vitro bevrugting en swangerskapsyfers as die g- en n-patrone. In hierdie studie doen ons verslag oor die statisties betekenisvolle korrelasie wat gevind is tussen die p-patroon normale sperm morfologie en DNS fragmentasie soos gemeet met die ‘terminal deoxynucleotidyl transferase-mediated dUDP-biotin end labeling’ of te wel TUNEL toets. Hierdie bevinding is ‘n verdere verklaring vir die laer fertiliteits potensiaal van pasiënte wat voordoen met p-patroon sperm morfologie. ‘n Verdere doel van die studie was om die moontlike verband tussen ROS in die semen, spermatozoa DNS fragmentasie, apoptotiese status van die sperms en die motiliteits parameters van die spermatozoa te bepaal. ‘n Positiewe korrelasie is gevind tussen ROS en sperm apoptotiese status. Sperms met ongeframenteerde DNS is ook positief gekorreleer met sperm konsentrasie en motiliteit. Die resultate beklemtoon die belangrikheid van spermseleksie veral in pasiënte waar die keuse van behandeling intrasitoplasmiese sperm inspuiting (ICSI) is. ‘n Vroeë teken van apoptose is die eksternalisering van ‘phosphatidylserine’ (PS) vanaf die interne oppervlakte van die plasmamembraan na die eksterne oppervlak. PS het ‘n hoë affiniteit vir Annexin V. Apoptotiese sperms het die vermoë om ‘n oösiet te bevrug, maar kan lei tot die staking van embrio deling wanneer die vaderlike gene ‘n rol begin speel in embrio ontwikkeling. In hierdie studie het ons ‘n nuwe metode ontwikkel waarvolgens die spermatozoa in die ejakulaat op grond van hul apoptotiese status geskei kan word in apoptotiese en nie-apoptotiese fraksies. Die normale sperm morfologie van die nie-apoptotiese fraksie is betekenisvol beter as dié van die apoptotiese fraksie. Verdere verfyning van die tegniek kan daartoe lei dat dit in die toekoms toegepas kan word om vir nie-apoptotiese sperms te selekteer veral voor die uitvoering van ICSI. Uit die bogenoemde is dit duidelik dat die spermsel ‘n baie belangrike rol in die ontwikkeling van ‘n embrio, vanaf bevrugting tot implantasie en swangerskap, speel. Dit is egter ook belangrik om in gedagte te hou dat daar ander bydraende faktore tot ‘n suksesvolle in vitro swangerskap is, soos laboratorium toestande en embrio kultuursisteem. Om hierdie rede is daar ook twee kultuurmedia in hierdie studie vergelyk. Daar is bevind dat die meer komplekse medium beter kwaliteit embrios op dag drie lewer, asook meer blastosiste en ‘n hoër swangerskapsyfer. Dit is dus duidelik dat dit uiters belangrik is om ‘n holistiese perspektief te hê op die komplekse faktore wat ‘n invloed mag hê op bevrugting, embrio kwaliteit asook die swangerskapsyfer.

Thesis (DMed (Obstetrics and Gynaecology))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: Chapter 1 is a literature review investigating the incidence of cancer in children and young adults. It describes the most important treatment options including chemotherapy, radiotherapy and surgery and the effect of treatment on future endocrine development and fertility. Different primary cancer sites are discussed in more detail. Chapter 2 is a literature review on the effects of cancer surgery in women and the options for fertility sparing. Cervical cancer and pre-cancer are discussed in detail with options for more conservative surgery in selected patients. A summary of the available published cases of trachelectomy with pregnancy outcomes is included. Other gynaecological cancers requiring surgery are also discussed with reference to conservative options. Chapter 3 is a literature review about the medical (pharmacological) options for protection of ovarian function in patients undergoing oncotherapy. The role of gonadotrophin releasing hormone analogues and hormonal contraceptives in ovarian suppression is discussed in detail. Chapter 4 This chapter examines germ cell physiology with reference to cryopreservation. It includes two major parts. Part 1 is the description of germ cell- and follicle physiology, the principles of cryobiology followed by a review of oocyte cryopreservation and ovarian tissue preservation. Both slow freezing and vitrification techniques are described. The second part of chapter 4 is a report on a randomised controlled evaluation of two different slow freezing cryopreservation protocols. This experimental study compared ultrastructural changes in fresh and previously cryopreserved ovarian cortical tissue after equilibration and thawing using two different cryoprotectants. This is the first randomised investigation into DMSO and PROH as cryoprotectants. Chapter 5 is an investigation into cryopreservation of ovarian tissue as a strategy to protect hormonal function and fertility against gonadotoxic treatment. This chapter consists of two parts. The first part is a thorough literature review of all the published work about grafting of previously cryopreserved ovarian tissue. The largest case series found from a single institution was five patients. Another report of six patients included patients from various sites in Denmark. Part 2 is a description of a cohort of patients followed up after re-implantation of previously cryopreserved ovarian cortical tissue. Follow-up hormone levels of 13 individual cases are described in detail. This is the largest case series ever reported. The experimental study described in Chapter 4 and the clinical study described in Chapter 5 was approved by the ethical research committee of the Faculty of Health Sciences, Stellenbosch University, project number N05/10/182. Chapter 6 provides an integrated overview of the incidence and treatment of cancer in young women and how its negative effects may be prevented or mitigated. Aspects of chemotherapy, radiotherapy and surgery are evaluated where it may affect future reproductive health. The role of oocyte and ovarian tissue cryopreservation is discussed. Guidelines are provided for clinicians. / AFRIKAANSE OPSOMMING: Hoofstuk 1 Hierdie is ‘n literatuuroorsig wat die insidensie van kanker in kinders en jong volwassenes ondersoek. Dit sluit die mees belangrike behandelingsopsies in, naamlik chemoterapie, radioterapie en chirurgie en die effek wat behandeling mag hê op toekomstige endokriene ontwikkeling en fertiliteit. ‘n Verskeidenheid kanker tipes word in meer detail beskryf. Hoofstuk 2 Hoofstuk 2 is ‘n literatuuroorsig oor die effekte van kankerchirurgie in vroue en die geleenthede tot beskerming van fertiliteit. Servikale kanker en voorlopers van servikale kanker word bespreek en die opsies vir konserwatiewe chirurgie in uitgesoekte pasiënte word gegee. ‘n Opsomming van die inligting wat beskikbaar is oor tragelektomie en swangerskap uitkomste word ingesluit. Ander ginekologiese kankers wat chirurgie mag benodig, word ook bespreek met verwysing na konserwatiewe hantering. Hoofstuk 3 ‘n Literatuuroorsig oor die mediese (farmakologiese) opsies vir die beskerming van ovariële funksie in pasiënte wat behandeling ontvang vir kanker. Die rol van gonadotropien-vrystellingshormoon-analoë en hormonale kontrasepsie vir ovariële onderdrukking word in detail bespreek. Hoofstuk 4 Hierdie hoofstuk ondersoek kiemselfisiologie met verwysing na vriesbewaring. Dit is verdeel in twee dele. Deel 1 is ‘n beskrywing van kiemsel- en follikelfisiologie en die beginsels van vriesbiologie. Dit word gevolg deur ‘n oorsig van oösiet vriesbewaring en ovariële weefselbewaring. Stadige bevriesing en vitrifikasie- metodes word bespreek. Die tweede deel van hoofstuk 4 is ‘n verslag oor ‘n gerandomiseerde, gekontroleerde evaluasie van twee stadige bevriesingsmetodes. Hierdie eksperimentele studie het die ultrastrukturele veranderinge vergelyk in vars en voorheen bevrore ovariële kortikale weefsel na ekwilibrasie en ontdooiing met twee verskillende vriesbeskermers. Dit is die eerste gerandomiseerde studie oor DMSO en PROH as vriesbeskermers. Hoofstuk 5 Hierdie hoofstuk handel oor ‘n ondersoek na vriesbewaring van ovariële weefsel as ‘n benadering tot beskerming van hormonale funksie en fertiliteit teen gonadotoksiese behandeling. Die hoofstuk bestaan uit twee dele. Die eerste deel is ‘n deeglike oorsig van die literatuur oor al die beskikbare werk wat handel oor terugplasing van voorheen bevrore ovariële weefsel. Die grootste pasiëntreeks van ‘n enkel instelling was slegs vyf pasiënte. ‘n Ander beskrywing van ses pasiënte het pasiënte van verskeie eenhede in Denemarke ingesluit. Deel 2 is ‘n beskrywing van ‘n groep pasiënte wat opgevolg is na oorplanting van voorheen bevrore ovariële kortikale weefsel. Opvolg hormoonvlakke van 13 gevalle word in detail bespreek. Hierdie is die grootste pasiëntreeks wat tot nog toe beskryf is. Die eksperimentele studie wat in hoofstuk 4 beskryf word en die kliniese studie wat in hoofstuk 5 beskryf word, is goedgekeur deur die etiese navorsingskomitee van die Fakulteit Gesondheidswetenskappe van die Universiteit Stellenbosch met die projeknommer N05/10/182 Hoofstuk 6 Hierdie is ‘n geïntegreerde oorsig van die voorkoms en behandeling van kanker in jong vroue en hoe die negatiewe effekte daarvan voorkom of verminder kan word. Aspekte van chemoterapie, radioterapie en chirurgie word geëvalueer ten opsigte van die effek op toekomstige reproduktiewe gesondheid. Die rol van oösiet- en ovariële weefselvriesbewaring word bespreek. Riglyne vir klinici word gegee.

Thesis (DSc)--Stellenbosch University, 2012. / Please refer to full text for abstract.

Assisted reproductive technology (ART) uses advanced techniques such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) to combat human infertility. However, the success rate of ART is poor and can, at least in part, be attributed to detrimental (iatrogenic) damage incurred by gametes and embryos during laboratory treatment or manipulation, thus compromising their functional role and reducing the chances of fertilisation. The sperm plays two fundamental roles upon gamete fusion: (1) to deliver paternal genomic DNA of optimal integrity into the oocyte, and (2) to activate the oocyte to initiate embryogenesis. Protamine and phospholipase C zeta (PLCζ) are two critical sperm proteins fundamentally responsible for facilitating these two key roles, respectively. The essential role of these sperm proteins with regards to male fertility, and fertilisation outcome following ART treatment, has been widely reported. This thesis was predominantly designed to investigate the potential effects of cryopreservation and sperm immobilisation via polyvinylpyrrolidone (PVP) upon the abundance and localisation of protamine and PLCζ in mouse and human sperm, respectively. Deficiency of these proteins could lead to reduced sperm DNA integrity and oocyte activation ability, respectively. An immunofluorescent quantitative assay was first designed and optimised for the determination of protamine 1 (P1) and 2 (P2) levels in sperm. This assay demonstrated that the total levels of P1 and P2, but not the P1:P2 ratio, were significantly reduced (by approximately 50%) in mouse sperm following cryopreservation. This novel assay may represent a useful clinical tool to predict DNA integrity and help select sperm with the best quality DNA. Clinical screening of PLCζ was also carried out in the largest dataset reported to date and confirmed that total levels of PLCζ in human sperm varied significantly between samples (P ≤ 0.05). Cluster analysis led to the development of a PLCζ scoring system with significant potential as a clinical prognostic and diagnostic assay. Regression models also correlated fertilisation rate and PLCζ content in a total of 30 clinical samples. Collectively, these novel tools show significant promise as predictors of oocyte activation ability. Specific case studies involving vasectomy, oocyte activation deficiency (OAD), and globozoospermia, were identified and shown to be associated with significantly reduced levels of PLCζ (P ≤ 0.05). In two of these case studies, a single nucleotide polymorphism (SNP) was identified in the PLCζ promoter region, potentially indicating a novel mechanism for PLCζ expression in human sperm. Another case of OAD suggested the apparent deficiency of a crucial interacting factor in the oocyte, emphasising that OAD is not exclusively linked to sperm abnormalities. For the first time, efforts were made to assess whether PLCζ expression was linked to male age; total levels and the proportion of sperm exhibiting PLCζ were found not to differ significantly amongst a total of 46 males. Furthermore, in a pilot experiment, levels of PLCζ were significantly reduced (by 23% to 89%) in PVP-treated sperm from 9 controls and 3 infertile patients, with patient sperm showing higher susceptibility to the effects of PVP compared to controls. However, a more robust experiment featuring sperm from 16 fertile donors, failed to show any significant effect of PVP upon PLCζ. Collectively, data arising from this thesis generated a series of potential clinical tools to quantify protamine and PLCζ in sperm, provides strong evidence that levels of protamine are significantly reduced by cryopreservation, and has provided at least some evidence that PVP may cause detrimental effect upon the level of PLCζ in human sperm. Further work on the effects of vasectomy and the relative functional importance of the SNP detected in the PLCζ promoter are highly warranted. Further investigation and clinical translation of these findings may help to improve the success rate of ART.

This dissertation consists of two separately published articles and one book chapter linked together by their investigation of the legal regulation of reproductive and genetic technologies. In "Fragmenting the Body" I explore how law is to understand the relationship between the person and the body, and the body and its parts in the context of the instrumental uses to which reproductive and genetic material can be put. Drawing on feminist and postmodernist theories, the article critiques the liberal legal conception of personhood and argues in favour of an embodied account of personhood as central to the legal metaphors and categories we should use in analyzing novel social and material arrangements. "Public Bodies, Private Parts: Genetics in a Post-Keynesian Era" analyzes the use of the new genetics and the role of geneticization in the privatization orientation of the Canadian state from 1990-2002. The chapter defines and explores the relationships among genetics, geneticization and privatization, and demonstrates how a new discourse of health is central to the privatization agenda. The chapter examines three policy/legal initiatives of the Canadian government regulating the new genetics and demonstrates how law operates to further the values and objectives of privatization. Finally, the chapter addresses the gendered impact of the relationship between the new genetics and privatization. In "Beyond Conception: Legal Determinations of Filiation in the Context of Assisted Reproductive Technologies" I argue that legal determinations of filiation are normative ideological constructions about how societal relations between children and parents should be ordered. They are based on particular understandings of the relationship between social and biological facts and operate to create asymmetrical relationships between the categories of maternity and paternity. I suggest that developments in reproductive and genetic filiation offer the potential for an expanded understanding of relatedness which does not take the two-parent -one of each sex--model of the family as its normative form.

Orientador: Anaglória Pontes / Coorientador: Maria Teresinha de Oliveira Cardoso. / Banca: Paulo Sérgio França / Banca: Adriano Bueno Tavares / Resumo: A histerossonografia (HSN) foi descrita pela primeira vez há três décadas. A infusão de solução salina na cavidade uterina favorece sua exploração e proporciona excelente visualização da anatomia e do interior da cavidade do útero melhor do que com ultrassonografia transvaginal convencional (USG). Para verificar o papel atual da HSN na avaliação da cavidade uterina de mulheres com sangramento uterino anormal (SUA) e assintomática, foi realizado revisão bibliográfica de estudos que compararam a HSN com a USG ou histeroscopia diagnóstica ambulatorial (HTDx). Para isso, pesquisou-se estudos relevantes em bases de dados eletrônicas Medline/PubMed, SciELO/LILACS. A HSN é procedimento ambulatorial, "não invasivo", de melhor custo-benefício, com melhor sensibilidade e especificidade na identificação de anomalias uterinas, causando desconforto mínimo e com baixo índice de complicações. Foi objeto de revisões, não existindo mais dúvidas quanto a sua acurácia. Pode-se concluir que a HSN é ferramenta útil na propedêutica de avaliação da cavidade uterina de mulheres sintomáticas com SUA, infertilidade e perdas gestacionais repetidas, falhas de implantação embrionária em programas com técnicas de reprodução assistida (TRA) / fertilização in vitro (FIV) e naquelas com qualquer alteração uterina intra ou extracavitária na USG. Portanto, está indicada como método de avaliação inicial da cavidade uterina antes de indicar HTDx / Abstract: Sonohysterography (HSN) was firstly described three decades ago. The saline solution infusion into the uterine cavity favors its use and provides excellent visualization of the anatomy and the inner cavity of the uterus better than the conventional transvaginal sonography (USG). To check the current role of HSN in the uterine cavity assessment in women with abnormal uterine bleeding (AUB) and asymptomatic, a literature review comparing HSN with USG and/or ambulatory diagnostic hysteroscopy (HTDx) was carried out. To this end, relevant studies were researched in electronic databases Medline/PubMed, SciELO/LILACS. The HSN is an ambulatory procedure, non-invasive, better cost-benefit, better sensitivity and specificity to identify uterine abnormalities, causing minimal discomfort and low complications rate. It was subject to revision which there is no more doubt about its accuracy. It can be concluded that the HSN is a useful tool in the propedeutics to assess uterine cavity of symptomatic patients with SUA, infertility, recurrent miscarriages, and embryonic implantation failures in assisted reproduction treatment (ART) / in vitro fertilization (FIV) and in any other intra and extra uterine cavity alteration. Hence, USG is indicated as an initial method of assessment of the uterine cavity previously to HTDx / Mestre