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It is recognised that the environment to which the fetus is exposed in utero, after implantation, can program longer term health outcomes and alter the possibility of disease onset later in life. It is becoming evident that the environment, to which the pre-implantation embryo is exposed, can also affect the ability of the embryo to form a viable pregnancy as well as altering fetal growth. Despite this understanding, little is known about the mechanism by which the environment can ‘program’ the pre-implantation embryo. Using model stress systems, either ammonium or DMO in the culture medium, this thesis addressed the hypothesis that suboptimal environmental conditions may alter mitochondrial homeostasis and function and/or epigenetic parameters and these are the possible mechanisms responsible for the altered fetal outcomes seen. While common measures of embryo quality such as on time blastocyst development were not affected by either stress, more in-depth investigations found several striking differences. Exposure to DMO significantly decreased blastocyst cell number and allocation to the inner cell mass and trophectoderm, as well as increased blastocyst apoptosis. After exposure to DMO, blastocysts were transferred to pseudopregnant recipients, and both the ability of the embryos to implant and develop into a fetus was impaired as well as fetal weights and crown rump length were significantly reduced indicative of altered growth. Similar results have also been demonstrated after pre-implantation embryos are exposed to ammonium in vitro. Exposure to ammonium during pre-implantation embryo development also altered placental gene expression and function, indicating a possible mechanism of the observed reduced fetal growth parameters. Interestingly, the pre-implantation embryo appears to be the most vulnerable to an environmental stress during the pre-compaction stage, in particular the zygote to 2-cell transition, as exposure to either stress during this stage alone shows similar perturbations to if the stress was present for the entire pre-implantation developmental period. At this early stage of embryo development, mitochondria are the sole energy generators and are therefore critical for embryo function. This study determined that either ammonium or DMO stress exposure, during the first cleavage division, significantly perturbed mitochondrial distribution, membrane potential and ATP/ADP levels. Removal of the stress did not allow these effects to be completely reversed, implicating mitochondrial perturbations as a possible mechanism behind altered embryo programming. During pre-implantation embryo development there are also significant epigenetic changes which are vital for re-programming the embryonic genome. Both in vitro stresses significantly altered DNA de-methylation at the 2-cell stage and reduced blastocyst gene expression levels of DNA methyltransferases (Dnmt3a and Dnmt3b), which are responsible for de novo methylation. Together these data highlight the importance of pre-implantation embryo development as a critical period of growth in which the presence of environmental stress can have an impact on metabolic homeostasis and critical epigenetic events that may be responsible for the downstream effects seen on fetal growth. These results are not only important for assisted reproductive therapy, where the presence of an in vitro laboratory stress can potentially alter embryo programming, but are also important for in vivo embryo development where the health and wellbeing of the mother can also potentially influence the in utero environment and thus the long-term health outcomes of her child. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1522143 / Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2010

O Brasil é o país que mais realiza aspiração folicular de oócitos guiada por ultrasonografia (OPU) para fins de produção in vitro de embriões bovinos. Com isso é possível aumentar consideravelmente o número de progênies por fêmea por ano. O objetivo desse trabalho foi identificar polimorfismos em genes envolvidos na foliculogênese e associar alterações gênicas com o número de folículos pré-antrais recrutados em bovinos, estimados pelo número de oócitos recuperados por OPU. Dados de aspiração folicular feitas a campo em fêmeas Nelore (Bos taurus indicus) foram obtidos de duas empresas diferentes, sendo que 30 fêmeas foram utilizadas para a prospecção de polimorfismos de nucleotídeos únicos (SNPs), 218 para estudos populacionais e dados de 193 fêmeas foram utilizados para a análise de efeitos das variações genéticas com o número de oócitos viáveis colhidos por OPU. Vinte fêmeas da raça Holandesa (Bos taurus taurus) foram genotipadas para a identificação de alelos taurinos ou zebuínos específicos. Regiões dos genes Gdf9, Fgf8, Fgf10 e BmprII foram amplificadas por meio da reação em cadeia da polimerase (PCR) e seqüenciadas para prospecção de SNPs. Quatro polimorfismos foram genotipados por meio de restrição enzimática de DNA, (PCR-RFLP; genes: Gdf9, Fgf8, Lhr e DNA mitocondrial-mtDNA) ou PCR em tempo real utilizando sondas específicas para cada alelo (BmprII). A avaliação de efeitos dos marcadores sobre a característica foi realizada por análise de variância utilizando modelos mistos com dados repetidos, em que o número de oócitos viáveis foi considerado variável dependente, as fêmeas foram consideradas variável aleatória, e local de aspiração, ano de aspiração e o SNP foram efeitos fixos. O mesmo modelo foi utilizado para estimar efeito médio de substituição alélica, em que o marcador foi substituído por uma co-variável numérica. A diferença entre médias de quadrados mínimos foram estimadas por meio de contrastes e a significância avaliada por teste t. Os efeitos ou as diferenças entre as médias foram consideradas significativas quando P<0,05. Foram identificados 19 SNPs sendo que 10 polimórficos entre as fêmeas Nelore, 04 causadores de substituição de aminoácidos na proteína. Entre os marcadores nucleares genotipados (Gdf9, A318C; Fgf8, C1027G; BmprII, A40048G; Lhr C62478T), todos apresentaram equilíbrio de segregação alélica dentro do marcador e genotípica entre os marcadores (P>0,05). Os SNPs nos genes Gdf9, BmprII e Lhr genotipados em fêmeas Nelore e Holandesas apresentaram-se fixados na segunda raça. Foram identificados efeitos dos polimorfismos dos genes Gdf9, Fgf8, BmprII e Lhr (P<0,05), entretanto os variantes de mtDNA não foram significativos. As diferenças entre médias confirmaram os resultados da ANOVA. Para os polimorfismos no gene Gdf9, BmprII e Lhr, observou-se a tendência de os indivíduos heterozigotos terem menores médias de oócitos viáveis quando comparados aos homozigotos, já o polimorfismo no gene Fgf8, observou-se a tendência de interação aditiva entre os alelos, em que foi estimado um efeito médio de 1,13±0,01 oócitos viáveis por troca de alelo C por G. Conclui-se que variações genéticas são causas de variabilidade do número de folículos presentes nos ovários, estimados por OPU. / Brazil is the country with the biggest number of ovum pick up (OPU) collection for bovine in vitro embryo production. This strategy is used to increase the number of calves born per cow per year. The objective of this work was to identify polymorphisms in genes related in folliculogenesis and associate some of the resulted gene variants with the number of pre antral follicle recruited in bovines, estimated by the number of oocytes collected by OPU. Records of open filed OPUs performed in Nelore cows (Bos taurus indicus) were obtained from two independent enterprises, and 30 females were used for single nucleotide polymorphism (SNP) prospection, 218 females for genotype and allelic population analysis and 193 females used for identification of genetic variation effects over the number of viable oocytes collected by OPU. Twenty Holstein cows (Bos taurus taurus) were also genotyped for identification of taurine and zebuine specific alleles. Segments of genes Gdf9, Fgf8, Fgf10 and BmprII were amplified by polymerase chain reaction (PCR) and sequenced for SNP prospection. Four polymorphisms were genotyped by means of enzymatic DNA digestion (PCR-RFLP, genes: Gdf9, Fgf8, Lhr and mitochondrial DNA - mtDNA) or real time PCR using allelic specific probes (Gene: BmprII). Genetic marker effect over the analyzed characteristic was realized by analysis of variance using mixed models with repeated data, in which the number of viable oocytes were set as dependent variable, the females were considered random variable, OPU place, OPU year and SNP were fixed effects. The same model was used for average allelic substitution effect estimation, where the genetic marker class was changed by a numeric covariant. The least square means (LSM) differences were estimated by contrasts and the significance evaluated by t test. Fixed effects or LSMs differences were considered significant when P<0.05. Nineteen SNPs were identified, from which ten were polymorphic among Nelore cows, four were expected to cause amino acid changes in protein. Among the nuclear genome markers genotyped (Gdf9, A318C; Fgf8, C1027G; BmprII, A40048G; Lhr C62478T, all resulted in allelic segregation equilibrium within marker and genotypic segregation equilibrium between markers (P>0.05). The SNPs in genes Gdf9, BmprII and Lhr genotyped in Nelore and Holstein cows were fixed in the last breed. SNPs in genes Gdf9, Fgf8, BmprII and Lhr affected the characteristic (P<0.05), however the mtDNA variants did not. The LSMs differences confirmed the ANOVA results. Heterozygote females for SNPs in genes Gdf9, BmprII and Lhr tend to have smaller LSMs than homozygous ones. On the other hand, there is indication of additive allelic interaction between alleles of SNP in gene Fgf8, for which an average allele substitution was estimated in 1.13±0.01 viable oocytes for a C/G change. We concluded that genetic variations were responsible for variable number of follicles present in ovaries, estimated by OPU.

Statistical modelling of data from the embryo transfer process of In-Vitro Fertilization (IVF) treatments is motivated by the need to perform statistical inference for potential factors and to develop predictive models for these treatments. The biggest issue arising when modelling these treatments is that a number of embryos are transferred but unless all of the embryos get implanted or fail to implant then it is not possible to identify which of the embryos implanted. Little work has been done to address this partial observability of the outcome as it arises in this context. We adopt an Embryo-Uterus (EU) framework where a patient response has distinct uterine and embryo components. This framework is used to construct statistical models, expand them to allow for clustering effects and develop a package that will enable the fitting and prediction of these models in STATA. The capabilities of this package are demonstrated in two real datasets, aimed in investigating the effect of a new embryo prognostic variable and the effect of patient clustering in these treatments. In a simulation study EU models are shown to be capable of identifying a patient covariate either as a predictor of uterine receptivity or embryo viability. However a simulation case study shows that a considerable amount of information about the embryo covariate is lost due to the partial observability of the outcome. Further simulation work evaluating the performance of a number of proposed alternatives to the EU model shows that these alternatives are either biased or conservative. The partially observed cycles are finally considered as a missing data problem and two novel modelling approaches are developed which are able to handle the structure of these treatments. These novel models, based on multiple imputation and probability weighting, are compared to the EU model using simulation in terms of predictive accuracy and are found to have similar predictive accuracy to the EU model.

This randomized, double-blind, placebo-controlled study was conducted to compare the effectiveness of intravenous acetaminophen vs. oral acetaminophen or placebo as an adjunct to opioids on lowering post-operative pain scores, discharge time, need for opioids, and opioid-related side effects, as well as assessing for any effects pain treatment has on embryological and pregnancy outcomes. Secondary analysis included identifying risk factors in patients that cause them to have worsening pain or minor relief from traditional pain management. This study was conducted at a single academic fertility center at Massachusetts General Hospital in Boston with a patient population of 159 English-speaking women between 18-43 years old, undergoing oocyte retrieval as a part of In Vitro Fertilization procedure. Participants were randomly placed in one of three treatment groups to receive either 1000mg IV acetaminophen and PO placebo (Group A), IV placebo, and 1000mg PO acetaminophen (Group B), or IV and PO placebo (Group C) as pain control before oocyte retrieval procedure. The primary outcomes measured were patient-reported post-operative visual analogue scale pain scores in the recovery room at 10 minutes, 30 minutes, and discharge time. Using these values to measure the effectiveness of each treatment at improving post-operative pain. To assess the relationship, if any, between demographical or clinical factors and pain, we analyzed what factors were common in those experiencing high or low pain. We used the Visual Analog Scale (VAS) which has patients rank pain from 1-10. For this analysis, low pain is defined as those whose 10-minute post-operative pain score was less than 5 (VAS score <5/10) and high pain as those whose 10-minute postoperative pain score is 5 or greater (VAS score 5+/10). Results showed that mean post-operative pain scores were similar between the study groups at 10 minutes (A:2.3, B: 2.6, C:2.8, p=0.51). Timing of discharge was also similar (A:60.1 mins, B: 58.8 mins, C:57.6mins; p=0.76). Although not statistically significant, the mean post-operative opioid dose for patients in group A was less than half of that in Group B and C (0.24mg vs. 0.59mg vs. 0.58mg; p=0.34) and fewer required rescue pain medication in the recovery room (4% vs. 19% vs. 15% respectively; p=0.24). There was a trend towards decreased side effects of constipation in Group A compared to Groups B and C (15% vs. 31% vs. 33%, respectively; p=0.07). There were no differences in embryological or early pregnancy outcomes between study groups. An analysis of predictors of pain, patients with BMI >/=30kg/m2 (obese) were more likely to report high post-operative pain (p=0.009). Prior abdominal surgeries, including pelvic laparoscopy and laparotomy, were associated with low post-operative pain (p=0.069 and p=0.025, respectively). Those who reported having pre-operative pain greater than zero were more likely to report lower postoperative pain (p=0.002). There was no significant relationship between race/ethnicity, infertility diagnosis, and procedure length and pain. This study's findings showed no significant difference between post-operative pain scores or discharge times in women undergoing oocyte retrieval when given IV acetaminophen, PO acetaminophen, or a placebo. There were severe findings that suggested that IV acetaminophen may reduce the need for post-operative narcotics and lead to fewer opioid-related side effects, however these findings while large were statistically insignificant. The predictors of higher post-operative pain we found, including high BMI, no prior history of abdominal procedures, and lack of pre-operative pain, indicate that further investigation into these predictors could be beneficial. This information may allow physicians and anesthesiologists to optimize their pain control.

Philosophiae Doctor - PhD / Infertility is currently a serious problem that is escalating, not only in South Africa, but also worldwide. In Cape Town, a culturally diverse, urban community of approximately 1000 couples are referred to the Groote Schuur Hospital Infertility Clinic annually. Although infertility is primarily regarded as a medical condition, the treatments have emotional effects on infertile couples due to the recurring highs and lows that often accompany treatments. This study aimed to qualitatively explore and understand the emotional and psychological experiences of infertility and its treatments (specifically In Vitro Fertilisation and Embryo Transfer). Social constructionism is based on the premise that realities are not constructed in a vacuum but rather undergo a process whereby the subjective and inter-subjective experiences over time and through cultural processes come to be regarded as truths. These truths become internalised and function as lenses through which we see ourselves, compose and invent ourselves accordingly, making sense of what would otherwise have been chaotic and meaningless experiences. Additional aims were to examine women's experiences of infertility care whilst undergoing treatment and describe their experiences of coping with infertility and In Vitro Fertilisation and Embryo Transfer (IVF-ET). Semi-structured, in-depth individual interviews were conducted with 21 women presenting with primary infertility at a fertility clinic. This study utilised an ethnographic case study design. The results of the study suggested that women perceived themselves as not conforming to a dominant belief system that promotes motherhood as the most important role for women. The women described their 'failure' to fulfill socio-cultural expectations as emotionally turbulent. Some of the psychological responses to infertility included feelings of disappointment, shock, denial, devastation, anger, frustration, sadness, inadequacy, poor self-image and self-esteem. The women's personal accounts of their experiences of In Vitro Fertilisation and Embryo Transfer (IVF-ET) revealed that they found the treatment to be highly stressful, with emotional bouts of anxiety, nervousness, excitement and optimism. A psychological synopsis of infertility and IVF-ET is infertility and IVF-ET presents. The findings in this study suggest the need for the incorporation of 6 presented. This diagrammatic representation shows the intensity of the emotional rollercoaster that psychosocial intervention into infertility management. Greater attention to the psychological and emotional repercussions of infertility treatment could lead to a more personalised approach which, in turn, would optimise patient satisfaction and also prepare couples for the demands of the program by informing them about better ways of coping.

Ghanaian women experiencing infertility problem, have been seeking invitro fertilisation treatment in the quest for motherhood, however there is a dearth in the nursing studies researching this phenomenon. It appears that the concept and meanings of infertility is inadequately explored from the perspective of women experiences following unsuccessful invitro fertilisation treatment. In particular, it is vital to be knowledgeable about the challenges women encounter when undergoing IVF treatment and following unsuccessful procedure. The study sought to gain a deeper knowledge and to understand the meanings women struggling with infertility and its treatment experience and how invitro fertilisation treatment failure affects women in their everyday life. To unearth the women perception and meaning attributed to their experiences of unsuccessful infertility treatment, Heidegger's philosophy of phenomenology underpinned this study. A semistructured opening question and further probing questions were used to gather information which was reduced to sub-themes and main themes which captured the participant's lived experiences of unsuccessful invitro fertilisation treatment. I adopted van Manen's (1990) six steps of research activities as a structure to unravel the participants' phenomenological conversations. Applying Heidegger's concept of the three modes of existence (Existenze): authenticity, inauthenticity and undifferentiatedness, four major themes were identified: 1. Seeking wholistic and authentic care- authenticity 2. Facing up to the Angst- inauthenticity 3. The vulnerable self - inauthenticity 4. Living with infertility (being-in-the-world-of-motherless) - undifferentiatedness The participants' phenomenological conversations and their stories have revealed a range of challenges Ghanaian women who seek invitro fertilisation treatment go through. The study contribute significantly by giving insight to the painful experiences Ghanaian women go through when seeking invitro fertilisation treatment and has given a voice to how assisted reproductive technologies are currently experienced in the Ghanaian context. From the women's narrative, it appeared that their emotional and informational needs were not being met and were not being cared for as expected. The findings provide some direction regarding the needs of women experiencing infertility for information, support and advocacy in their pursuit of assisted reproductive technology services in Ghana. There is a critical need to simplify invitro fertilisation treatment and provision of safe, affordable procedure so that the average Ghanaian women can access it.

Assisted reproductive technology (ART) is an infertility treatment used to assist women to become pregnant. Although the procedure is safe, there are gaps in understanding the association between treatment and adverse pregnancy outcomes (e.g., stillbirth) in the United States. The purpose of this study was to investigate the relationship between stillbirth delivery and ART. The 2 research questions addressed the association between methods of conception (ART versus non-ART) and the delivery of a stillbirth, and the association between multiple gestation pregnancy and risk of stillbirths. Retrospective cohort data from the States Monitoring ART collaborative were analyzed using Pearson's chi squared tests and log binominal regression models. Findings indicated that from 2006 to 2011, the average stillbirth rates were lower among ART-conceived pregnancies than non-ART conceived pregnancies. After controlling for confounding factors, ART-conceived pregnancies did not show increased risks of stillbirths compared to non-ART conceived pregnancies regardless of plurality. This lower risk of stillbirth was particularly significant during early pregnancies, before 28 weeks of gestation. Findings may be used to improve understanding of the use of ART treatment and its associated pregnancy outcomes. Findings may also be used to prevent stillbirths and to improve prenatal care, early stillbirth detection, and effective clinical management of fetal and maternal conditions during pregnancy.

I denna studie undersöks professionellas erfarenheter, möjligheter och utmaningar de upplevt i sitt arbete med den psykosociala utredningar med samkönade par i en IVF-process. Studien har queerteorin som teoretisk utgångspunkt tillsammans med de teoretiska begreppen heteronormativitet, homofobi och bemötande. Studien har en kvalitativ ansats och datainsamlingen har gjorts genom semistrukturerade intervjuer med fem deltagare, som alla har kunskap inom beteendevetenskap. Materialet har analyserats genom en tematisk analys och sammanställdes i sju teman; Lika för alla, Att bemöta samkönade par på deras villkor, Ifrågasättande av heteronormen, Förändringen av lagar och föreskrifter, Samkönade par är mer genomtänkta och pratar öppet, Öppenhet hos de professionella samt Egenreflektion. Resultatet visar att professionella inom IVF-behandlingen har stor erfarenhet av att arbeta med samkönade par. Utmaningarna som de sett i sitt arbete är kopplade till heteronormativiteten i samhället, samt hur lagar och föreskrifter tidigare varit utformade. De möjligheter de sett är att en IVF-process är mer självklar för samkönade par, vilket gör dem mer öppna och genomtänkta, något som underlättar för professionella i sitt arbete. Även öppenhet hos de professionella för att öka sin kunskap och egenreflektion kring sina egna tankar och värderingar var möjligheter som framkom i studien. Slutsatsen som kan göras av studien är att den tidigare forskningen inte stämmer överens med det deltagarna lyft under samtliga intervjuer, de motsäger varandra. Det är något som delvis kan förklaras med att studien har ett professionellt perspektiv och den tidigare forskningen har ett klientperspektiv.

Bakgrund: Var tionde par i Sverige drabbas av ofrivillig barnlöshet. När en kvinna inte lyckats bli gravid under 12 månader med oskyddat samlag kan en fertilitetsutredning påbörjas. Att som kvinna leva med ofrivillig barnlöshet kan påverka hälsan både psykiskt men även fysiskt vilket kan resultera i ett lidande hos kvinnorna. Allmänsjuksköterskan behöver ha kunskap om kvinnornas situation och se dessa kvinnors individuella livsvärld för att kunna främja hälsa, förebygga sjukdom, återställa hälsa, lindra lidande. Syfte: Syftet var att belysa kvinnors upplevelse av ofrivillig barnlöshet. Metod: En kvalitativ litteraturstudie som baserades på fem självbiografier. En manifest innehållsanalys med induktiv ansats genomfördes. Resultat: Analysprocessen av de fem självbiografierna ledde till två huvudkategorier: Ett lidande your flera perspektiv med tre underkategorier som handlar om kvinnors upplevelse av ett lidande på olika plan exempelvis sorg, utanförskap samt sjukvårdens bemötande. Meningen med livet med två underkategorier som handlar om hoppet att bli mamma och förlikning, livet kan vara bra ändå. Slutsats: Resultatet i studien visade att kvinnor som lever med ofrivillig barnlöshet ofta drabbas av någon slags ohälsa vilket gör att dessa kvinnor behöver emotionellt stöd för att hantera exempelvis sorgeprocessen och att det är stor vikt att sjuksköterskor ska ha kunskap och ha en förståelse för kvinnor med ofrivillig barnlöshet för att ge den bästa personcentrerade vården kvinnorna har rätt till.