Research report submitted in accordance with the requirements for the Degree Master of Science in Medicine( Bioethics and Health Law. Faculty of Health Sciences, University of the Witwatersrand Steve Biko Centre for Bioethics, 2014 / It is every normal parent’s wish to have a happy child free of ailments and suffering. However, not all children are born free of diseases and suffering. Some are born with severe disabilities and others are born with congenital genetic problems that have less chances of cure or no cure at all. These unfortunate circumstances make parents of such children with severe medical conditions desperate and devastated to the extent that they try anything possible in attempting to improve quality of life of their sick children. No parent wants to see his or her child suffering. However, a more pressing situation is when parents decide to have a second child whose purpose is to save the life of the sick first child by donating stem cells from cord blood or bone marrow. This second child is sometimes referred to as the “Saviour sibling” and is born for the purpose of saving the life of the sick older child of the family. ‘Saviour sibling is the media name for a child who is conceived, gestated, and delivered in order to provide umbilical cord blood, or, even more contentious, bone marrow desperately needed by the parents’ older child’ (Mills 2005:2).Because there is no matching donor for the ill older child, a donor is created in the form of a second sibling, whose match is genetically guaranteed by IVF, preimplantation genetic diagnosis (PGD), and tissue typing (Boyle and Savulescu 2001). Given that children are already being created in other Countries such as the United States of America, France and Britain for the above-mentioned purpose, this research report will attempt to engage in the debate surrounding saviour siblings, the use of preimplantation genetic diagnosis (PGD) in creating these children, and the possibility of this technology being abused and misused for gender selection. Taking this into consideration, this research report will attempt to highlight what the South African laws and policies say about saviour siblings. Should parents with pressing issues as mentioned-above demand to have a “saviour child” of their own for the purpose of using him or her to save the life of another of their children in South Africa, on which grounds would it be rejected or accepted?

Orientador: Maria Yolanda Makuch / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-11-09T15:39:47Z (GMT). No. of bitstreams: 1 Filetto_JulianaNicolau_D.pdf: 899402 bytes, checksum: b505244b4e512938da35a1ca1479c305 (MD5) Previous issue date: 2009 / Resumo: Objetivo: Descrever as vivências de homens e mulheres ao estarem iniciando os procedimentos de fertilização in vitro (FIV) e em longo prazo após o fracasso da terapêutica. Metodologia: Para cumprir com os objetivos propostos foram feitos dois estudos qualitativos, ambos realizados no Ambulatório de Reprodução Humana do Departamento de Tocoginecologia da Faculdade de Ciências Médicas (UNICAMP). Para o primeiro estudo foi escolhida uma amostra proposital por variedade de tipos - casais sem filhos, com filhos e que a mulher tinha filhos de um relacionamento anterior - que tinham realizado a FIV sem sucesso quatro a sete anos antes de serem entrevistados. O número de participantes foi definido conforme o critério de saturação da informação. Foram conduzidas entrevistas semi-estruturadas utilizando-se um roteiro temático, as quais foram gravadas e transcritas. Para o segundo estudo foi realizada uma re-análise das entrevistas de casais sem filhos realizadas quatro a seis anos após o fracasso da FIV do estudo acima e de casais sem filhos, que estavam iniciando pela primeira vez ou repetindo os procedimentos da FIV de outro estudo. O número de entrevistas analisadas foi definido conforme o critério de saturação da informação. Resultados: No primeiro estudo, homens e mulheres consideraram a FIV como uma experiência válida, apesar de alguns terem vivenciado dificuldades no relacionamento conjugal após o fracasso, as quais foram sendo superadas em longo prazo. Em relação às etapas do procedimento, alguns participantes se referiram ao desenvolvimento folicular como uma etapa difícil e dolorida e alguns acreditavam que a medicação tinha causado mudanças permanentes no corpo das mulheres. Os homens referiram a etapa da coleta do sêmen como uma experiência desconfortável. Após o fracasso da FIV, a maioria dos casais considerou a possibilidade da adoção, porém poucos adotaram e outros participantes se dedicaram a novos projetos de vida que não fosse o de terem um filho. Casais sem filhos decidiram realizar novas tentativas de FIV em outros serviços devido a necessidade de continuarem tentando. No segundo estudo, ao se contrapor as vivências de homens e mulheres, iniciando os procedimentos e em longo prazo, os participantes falaram que a decisão tinha sido baseada principalmente na certeza de sucesso e algumas mulheres mencionaram a necessidade de serem iguais às "mulheres férteis". Nas entrevistas dos homens, tanto no início do procedimento como em longo prazo, foi observado que a decisão tinha sido mais influenciada pelo desejo das parceiras pela gravidez. Em relação às etapas da FIV, as mulheres que estavam iniciando o procedimento, referiram as injeções de hormônios como preocupante, e em longo prazo, as consideraram doloridas e algumas, semelhante ao resultado do primeiro estudo, também acreditavam que a medicação tinha causado mudanças permanentes em seus corpos. Os homens, em geral, falaram da preocupação com a possível repercussão dos medicamentos na saúde da parceira. Algumas mulheres, tanto iniciando como em longo prazo, tinham a percepção de que a coleta do sêmen não tinha incomodado os parceiros. A mesma percepção foi mencionada pela maioria dos homens iniciando os procedimentos, embora a lembrança que prevaleceu em longo prazo foi a de ter sido uma experiência tensa e constrangedora. Conclusão: Homens e mulheres, devido à esperança pela gravidez, tendem a não se incomodarem com as exigências dos procedimentos, o que não ocorreu após o fracasso da FIV. Em longo prazo, homens e mulheres consideraram os procedimentos da FIV como uma experiência positiva e foram capazes de se dedicarem a outros projetos de vida, os quais foram considerados satisfatórios, exceto para os casais sem filhos. / Abstract: Objective: To describe the life experience of men and women at the beginning and after unsuccessful in vitro fertilization (IVF) procedures. Methods: Two qualitative studies were conducted to achieve the proposed aims, at the Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas (UNICAMP). Participants for the first study were chosen using a purposive sampling per variety of types - couples without children, couples who already had children and wished to have another child, and couples in which the women had children from a previous relationship - that had experienced unsuccessful IVF four to seven years before the interviews. The number of interviews carried out was defined according to the criteria of information saturation. Semi-structured interviews were conducted using a thematic script, which were tape-recorded and transcribed. The second study was based on the re-analysis of the interviews of couples without children interviewed four to six years after an unsuccessful IVF from the study above and couples without children interviewed at the beginning of the procedures the first time they were participating or when repeating IVF from a previously conducted study. The number of interviews carried out was defined according to the criteria of information saturation. Results: In the first study, men and women considered IVF a positive experience, even though some couples recalled difficulties in their relationship after unsuccessful IVF, however they felt that their marital relationship had not been permanently affected. Regarding the stages of the procedure, some participants recalled follicular development as a difficult and painful stage in the treatment and some believed that the medication used during that phase had resulted in body changes, in some cases considered permanent. The men referred to semen collection as an uncomfortable experience. The majority of the couples had considered adoption, but only a few couples actually adopted and others participants had focused on new life projects other than having children. Couples who had no children recalled they had pursued treatment in other clinics due to the necessity to keep trying. In the second study, comparing men and women's life experiences at the beginning of the procedures and in the long-term, all participants recalled that their decision to undergo IVF had been based principally on the certainty of success, and some women referred to their need to be like "a fertile women". In men's interviews, at the beginning of procedures and in the long-term, it was observed that the decision to participate in IVF procedures had been mainly based on woman's desire of pregnancy. Regarding the stages of the procedures, women who were beginning the procedures referred the hormone injections as preoccupying and in the long term they remembered as painful stage and some, similar to the results of the first study, believed that had resulted in permanent body changes. Men, in general, referred to worries about the possible repercussion of the medicines used during this stage in their partner's health. Some women in the beginning and in long-term, had the perception that semen collection was not a stressful experience for the partners. A similar perception was mentioned by the majority of men beginning the procedures, although in the long term their recollection was of a stressful and embarrassing experience. Conclusion: Men and women due the hope for the pregnancy tend not to be bothered with the requirements of the procedures, different of what happened after IVF failure. In long-term, men and women, considered IVF procedures as a positive experience and were able to focus on other life projects, which were considered satisfactory, except for the couples without child. / Doutorado / Ciencias Biomedicas / Doutor em Tocoginecologia

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