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There is emerging evidence that after infertility and assisted conception women are at increased risk of early parenting difficulties. The aims of this study were to characterize postpartum psychological functioning of women conceiving through assisted reproductive technology (ART) and to identify factors that may be associated with early parenting difficulties defined as: postpartum psychological distress, low maternal confidence and admission to residential early parenting services. (For complete abstract open document)

The focus of this thesis is the current policy situation in relation to assisted reproductive technologies (ART) in Aotearoa/New Zealand. I explore how government policies (and lack of policy) have shaped access to ART. I also explore the policy initiatives of funding agencies, the National Ethics Committee on Assisted Human Reproduction (NECAHR), managers, healthcare professionals, and interest groups. My investigation into ART policy issues critically examines the various formal mechanisms and policies used to regulate and control ART in Aotearoa/New Zealand. Drawing on my analysis of policy-focused documents and material from in-depth interviews with key actors in the policy debate, I demonstrate how the ad hoc and contingent approach to ART developments, practices, funding, and access has contributed to inconsistent and inequitable access to ART services. I argue that the lack of an ART-specific policy organisation contributes to fragmented, and possibly discriminatory, policy decisions. I examine how the use of restrictive access criteria to manage the increasing demand for publicly funded ART services disadvantages certain groups wishing to use these services. By investigating the influence of rationing strategies on the allocation of resources and regulation of access, I provide some appreciation of the 'messy reality' of policy creation, interpretation, and implementation. I argue that the criteria used to limit access to public ART services obscure the use of social judgements and provider discretion. Likewise, they succeed in limiting publicly funded ART treatments to those who conform most effectively to the normative definition of family. My analysis of the ART policy discourse identifies silences and gaps in relation to specific ART practices, particularly the use of ART by Maori. I highlight the invisibility and marginalisation of Maori within the ART policy debate. After examining the broader issues concerning Maori access to health services, I explore how these may affect Maori using ART services to overcome infertility. I argue that the gathering of information about the utilisation of ART services is crucial for the accurate identification of the needs of Maori. It is also fundamental for effective monitoring of state health policy decisions and outcomes.

Abstract The effectiveness of intrauterine insemination (IUI) combined with controlled ovarian hyperstimulation (COH) in the treatment of subfertility was investigated in the present study. For this purpose the prognostic factors associated with success of clomiphene citrate (CC)/human menopausal gonadotrophin (HMG)/IUI were identified in 811 treatment cycles. Furthermore, a long gonadotrophin-releasing hormone agonist (GnRHa)/HMG stimulation protocol was compared with a standard CC/HMG protocol. In addition, the usefulness of alternative insemination techniques including fallopian tube sperm perfusion (FSP) and intrafollicular insemination (IFI) was investigated. Finally, the obstetric and perinatal outcome of pregnancies after COH/IUI was examined and compared with those of matched spontaneous and in vitro fertilization(IVF) pregnancies. Female age, duration of infertility, aetiology of infertility, number of large preovulatory follicles and number of the treatment cycle were predictive as regards pregnancy after CC/HMG/IUI. The highest pregnancy rate (PR) was obtained in women of < 40 years of age with infertility duration ≤ 6 years, who did not suffer from endometriosis. A multifollicular ovarian response to CC/HMG resulted in better treatment success than a monofollicular response, indicating the necessity of COH combined with IUI. A significantly higher PR was achieved in the first treatment cycles compared with the others, and 97% of the pregnancies were obtained in the first four treatment cycles. The PR per cycle did not differ significantly between a long GnRHa/HMG and a standard CC/HMG protocol, but the average medication expense of GnRHa/HMG stimulation was four times the cost of CC/HMG stimulation. Therefore, the routine use of a long GnRHa/HMG protocol in IUI treatment remains questionable. The FSP procedure was easy to perform by using a paediatric Foley catheter. The success rate in couples with either FSP or standard IUI did not differ significantly, although there was a trend towards a lower PR in the FSP group. The FSP technique should not replace the simpler and less time-consuming IUI technique in routine use. The IFI technique was also simple to perform and convenient for patients. However, only one normal singleton intrauterine pregnancy resulted in 50 IFI-treated women, indicating that IFI is inefficacious for treating subfertility. The IUI parturients differed from average Finnish parturients in respect to higher maternal age, more frequent primiparity and a higher incidence of multiple pregnancies. The use of antenatal care services was significantly lower in IUI singleton pregnancies compared with IVF singletons, although there were no more complications in IVF pregnancies. The hospitalization and Caesarean section rates were generally high in all pregnancies. The mean birthweight of IUI singletons was significantly lower than that in spontaneous pregnancies, but comparable to that in IVF pregnancies. However, the incidence of preterm birth, low birth weight and other variables describing the outcome of infants were similar in IUI, IVF and spontaneous pregnancies. In summary, the IUI procedure itself does not seem to affect adversely the obstetric and perinatal outcome of pregnancy, and patient characteristics and multiplicity may be more important in this respect.

There have been leaps in both fields of epigenetics and reproductive technology. This has culminated in the production of bi-maternal mouse offspring through a few studies utilizing direct gene mutations as functional-imprints. While these genetic interventions result in positive results, it has yet to be described, in full, what mechanisms underlie the epigenetic barriers to human gynogenesis. Between maternal and paternal imprints, differences in methylation patterns of CpG island promoters, non-coding regions, microsatellites, transposons, and histones result in differences in higher order chromatin structure, which ultimately impacts expression of certain genes. While the necessary components of a minimal paternal epigenetic program are described, programming this imprint onto m2, a hypothetical, experimentally-produced maternal genome with a paternal epigenome is still not elucidated. Sequential timing of imprint acquisition and maintenance and the numerous regulatory factors associated with them illuminate how difficult potential assisted reproductive epigenetic interventions will be. Other processes like histone-protamine exchange which also plays a crucial factor in structural regulation of imprints, as well as signaling through and after fertilization, pose logistical problems to creating a gynogenote through epigenetic means. Lastly, ethics surrounding the introduction of dangerous mutations and epialleles into the human population add another wall of caution and hesitance in exploring human gynogenesis as a reproductive technology.

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.

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.

As an Assisted Reproductive Technology (ART) that has been available for over twenty years, the transfer of healthy eggs from a presumably fertile woman into the womb of a woman diagnosed as infertile has become a common part of the landscape of human reproduction in the United States. Yet the general societal acceptance of this practice commonly known as "egg donation" oversimplifies the complex medical, ethical, and societal issues ignited by its use. In light of the limited critical discussions presently occurring about egg transfer, I will interrogate some of the silences and more ambiguous issues invoked by its practice. By giving particular attention to the often ignored experiences of egg "donors," I will analyze the popularly used discourses around this ART. In doing so, I will investigate the ways in which egg donation complicates notions of altruism, autonomy, and exploitation as well as what consequences this has for women's reproductive freedoms as envisioned by many U.S. feminists.

Master of Science in Medicine (by research) / Assisted reproductive technologies (ARTs) are very efficient in producing embryos, however many of these embryos have poor viability. No more than 50% of IVF embryos complete preimplantation development (Hardy et al. 2001). The poor viability is manifested as a reduced rate of cell proliferation and increased rates of apoptosis in the early embryo, resulting in high rates of embryo mortality (Hardy et al. 2001). The reduced viability occurs as a response to a range of cellular stressors that are a consequence of embryo culture (Hardy et al. 2001). The stress of culture disrupts some survival signalling pathways, metabolism of substrates and induces redox stress (Hardy et al. 2001). The cellular stress sensor p53 is expressed in the early embryo but is normally kept at very low levels (Li et al. 2005). This latency may be breached in IVF embryos following culture of zygotes in vitro for 96 hours, resulting in the up-regulation and nuclear accumulation of p53 (Li et al. 2005). Activation of the p53 stress-sensing pathway in the early mouse embryo by culture in vitro causes a marked loss of their developmental competence (Li et al. 2005). This study aimed to establish whether benefits could be obtained by culturing mice IVF embryos in the presence of p53 protein inhibitors. IVF zygotes were cultured individually in 10µl drops of 1.25, 2.5, 5 or 10µM Pifithrin-a (PFTa) in 0.05% DMSO for 96 hours. On day 5 the development stage was assessed. Embryos reaching the blastocyst stage were fixed and stained with Hoechst 33342 for total cell count and the proportion of nuclei with normal and abnormal morphology. There was an increase in the blastocyst rate, total cell count and the proportion of nuclei in a blastocyst with normal nuclei in 10µM-treated embryos. This study also aimed to determine whether benefits could be obtained by incubating mouse IVF sperm with p53 protein inhibitors during IVF. IVF sperm was treated with 1.25, 2.5, 5 or 10µM of PFTa in 0.05% DMSO during incubation with oocytes for 6 hours. Resulting zygotes were cultured for 96 hours individually in 10µl drops of MODHTFM. On day 5 the development stage was assessed. Embryos reaching the blastocyst stage were fixed and stained with Hoechst 33342 for total cell count and the proportion of nuclei with normal and abnormal morphology. There was a reduction in the proportion of fragmented nuclei in blastocysts derived from 1.25 and 10µM-treated sperm. 10µM treated sperm increased the total cell count, the proportion of normal nuclei in a blastocyst and the blastocyst development rate. IVF sperm incubated with 1.25µM PFTa during insemination of oocytes increased the fertilisation rate. Another aim of this study was to establish whether p53 siRNA could inhibit p53 mRNA in mice IVF embryos and if so, whether this would improve embryo viability in culture. IVF zygotes were transfected with 15nM p53 small inhibiting RNA (siRNA) and 0.8% Oligofectamine Reagent immediately, 24 h, 48 h and 72 h after IVF then cultured individually in 10µl drops of MOD-HTFM for a total of 96 hours. On day 5 the blastocyst rate was assessed and immunofluorescence performed probing for p53. There was no significant reduction in p53 expression and no improvement in blastocyst rate at any of the transfection times. However, there was a decrease in the proportion of nuclei which expressed p53 when p53 siRNA was transfected 72 hours after IVF. Also, it was determined that siRNA was efficiently being delivered into the preimplantation embryo with Oligofectamine Reagent. Lastly, this study aimed to determine whether mice sperm with p53 gene deletions have a selective advantage in fertilising the oocyte compared to their wild-type counterparts. p53+/- males were mated with p53+/+ females and the resulting zygotes genotyped after 24 hours of culture. More than 50% of offspring had a p53+/+ genotype. There was no selective advantage for p53 null sperm to fertilise the oocyte, there was actually a disadvantage. The selective disadvantage for p53 null sperm to fertilise the F1 hybrid oocyte in IVF compared to its wild-type counterparts may imply that p53 null sperm are not as viable and may have a survival disadvantage. The reduction in fertility of p53 null sperm in vitro infers that p53 function may be important for the fertility of the mouse sperm in vitro. The results of this thesis could establish means of improving human embryo viability in ART, some examples being P53 protein inhibition in preimplantation embryos during culture prior to transfer to the uterus, or P53 protein inhibition in IVF sperm. The use of the new technology, p53 siRNA was not effective in inhibiting p53 expression, although the build-up experiments determined that siRNA is efficiently delivered into the preimplantation embryo with Oligofectamine Reagent. The demonstration that p53 null sperm has a selective disadvantage in fertilising the oocyte compared to their wild-type counterparts does not indicate a positive selection pressure for naturally occurring mutations to this gene. And so, there is no concern regarding the genetic and epigenetic risks to progeny arising from assisted reproductive technologies with respect to sperm.

In the last 30 years, in vitro fertilization (IVF) has created a significant amount of controversy around the world. Within the U.S., policy movement has been limited, occurring primarily at the state level, which has created a fragmented system of rules to manage the technology. However, there appear to be indications that how the issue is presented, and which actors are chosen to be represented in legislation, may impact the passage of policy, thereby also providing a reason for why little policy movement has occurred. In this study, pieces of federal, California and Georgia legislation were examined for the occurrence of differing frames, as identified by the actors presented, in order to determine whether different frames occurred in passed legislation than those found in failed legislation. It was determined that, while actors did not differ significantly between passed and failed legislation, there were some slight differences between actors used at the federal level, as well between the different state levels. Even further, the presentation of actors and their interests did appear to differ slightly between passed and failed legislation.