Storage trends, usage and disposition outcomes following egg freezing.

RESEARCH QUESTION: What happens to eggs after egg freezing? DESIGN: A retrospective cohort study was performed spanning 2012-2022. Data were obtained from seven assisted reproductive technology clinics in Victoria, Australia. Aggregated, de-identified data were collected on cycles that resulted in egg freezing and the following outcomes, including treatment involving thawed eggs and disposition outcomes of surplus eggs. RESULTS: The number of patients with eggs in storage grew rapidly from 144 in 2012 to 2015 in 2022. In 2022, 73% of patients had stored their eggs for <5 years, 25% for 5-10 years, and 2% for ≥10 years. Most thaw cycles (600/645, 93%) involved eggs that had been frozen for <5 years, of which 47% had been frozen for <6 months. Overall, the live birth rate per initiated thaw cycle was 12%. Across the study period, 2800 eggs from 286 patients were either discarded, donated or exported. Of the 128 patients who discarded their eggs, 32% had stored their eggs for <5 years, 32% for 5-10 years and 36% for >10 years. Of the 23 patients who donated their eggs to someone else, all but four had stored their eggs for <5 years. No eggs were donated to research over the study period. CONCLUSIONS: This study shows that very few patients have made the decision to use or relinquish their eggs. Strategies may be needed to address the prolonged storage of surplus eggs, and ensure that patients are supported to make decisions regarding the fate of their eggs which align with their preferences and values.

Disparities in integrating non-invasive prenatal testing into antenatal healthcare in Australia: a survey of healthcare professionals.

BACKGROUND: Non-invasive prenatal testing (NIPT) has been clinically available in Australia on a user-pays basis since 2012. There are numerous providers, with available tests ranging from targeted NIPT (only trisomies 21, 18, and 13 +/- sex chromosome aneuploidy) to genome-wide NIPT. While NIPT is being implemented in the public health care systems of other countries, in Australia, the implementation of NIPT has proceeded without public funding. The aim of this study was to investigate how NIPT has been integrated into antenatal care across Australia and reveal the successes and challenges in its implementation in this context. METHODS: An anonymous online survey was conducted from September to October 2022. Invitations to participate were sent to healthcare professionals (HCPs) involved in the provision of NIPT in Australia through professional society mailing lists and networks. Participants were asked questions on their knowledge of NIPT, delivery of NIPT, and post-test management of results. RESULTS: A total of 475 HCPs responded, comprising 232 (48.8%) obstetricians, 167 (35.2%) general practitioners, 32 (6.7%) midwives, and 44 (9.3%) genetic specialists. NIPT was most commonly offered as a first-tier test, with most HCPs (n = 279; 60.3%) offering it to patients as a choice between NIPT and combined first-trimester screening. Fifty-three percent (n = 245) of respondents always offered patients a choice between NIPT for the common autosomal trisomies and expanded (including genome-wide) NIPT. This choice was understood as supporting patient autonomy and informed consent. Cost was seen as a major barrier to access to NIPT, for both targeted and expanded tests. Equitable access, increasing time demands on HCPs, and staying up to date with advances were frequently reported as major challenges in delivering NIPT. CONCLUSIONS: Our findings demonstrate substantial variation in the clinical implementation of NIPT in Australia, including in the offers of expanded screening options. After a decade of clinical use, Australian clinicians still report ongoing challenges in the clinical and equitable provision of NIPT.

NIPT for adult-onset conditions: Australian NIPT users' views.

Noninvasive prenatal testing (NIPT) has become widely available in recent years. While initially used to screen for trisomies 21, 18, and 13, the test has expanded to include a range of other conditions and will likely expand further. This paper addresses the ethical issues that arise from one particularly controversial potential use of NIPT: screening for adult-onset conditions (AOCs). We report data from our quantitative survey of Australian NIPT users' views on the ethical issues raised by NIPT for AOCs. The survey ascertained support for NIPT for several traits and conditions including AOCs. Participants were then asked about their level of concern around implications of screening for AOCs for the future child and parent(s). Descriptive and comparative data analyses were conducted. In total, 109 respondents were included in data analysis. The majority of respondents expressed support for NIPT screening for preventable (70.9%) and nonpreventable AOCs (80.8%). Most respondents indicated concern around potential harmful impacts associated with NIPT for AOCs, including the psychological impact on the future child and on the parent(s). Despite this, the majority of participants thought that continuation of a pregnancy known to be predisposed to an AOC is ethically acceptable. The implications of these data are critically discussed and used to inform the normative claim that prospective parents should be given access to NIPT for AOCs. The study contributes to a body of research debating the ethical acceptability and regulation of various applications of NIPT as screening panels expand.

Ethical issues associated with prenatal screening using non-invasive prenatal testing for sex chromosome aneuploidy.

Prenatal screening for sex chromosome aneuploidies (SCAs) is increasingly available through expanded non-invasive prenatal testing (NIPT). NIPT for SCAs raises complex ethical issues for clinical providers, prospective parents and future children. This paper discusses the ethical issues that arise around NIPT for SCAs and current guidelines and protocols for management. The first section outlines current practice and the limitations of NIPT for SCAs. It then outlines key guidelines before discussing the ethical issues raised by this use of NIPT. We conclude that while screening for SCAs should be made available for people seeking to use NIPT, its implementation requires careful consideration of what, when and how information is provided to users.

Reproductive deliberation: Supporting autonomous decision making in prenatal genetic counseling.

As both the scope and popularity of non-invasive prenatal testing (NIPT) have expanded, debate has emerged about the extent to which this test enhances or undermines reproductive autonomy. Genetic counseling is crucial to support autonomy in the context of making complex and value-laden decisions about reproductive care following high-chance results from NIPT. Two models of post-test prenatal genetic counseling have been proposed; the first of these, non-directive counseling, is the predominant model, while shared decision making is an alternative model deriving from patient care for chronic conditions. In this paper, we argue that neither of these approaches is adequate for counseling after NIPT to support reproductive autonomy. Instead, then, we propose an alternative approach that we call reproductive deliberation. This approach to prenatal genetic counseling simultaneously recognizes the relationality of the counseling encounter and supports the decision making capacity and decisional responsibility of the pregnant person.

The revision of the French bioethics law and the questions it raises for the future of funding for egg freezing.

After two years of parliamentary discussion, Emmanuel Macron's government in France enacted the new bioethics law. What stands out in the revision of the bioethics law is the decision to offer partial reimbursement of the clinical procedure costs of 'non-medical' egg freezing, making France the first country in the world to do this. Our contention in this brief commentary is that the recent change in the French law presents an opportunity to reflect on the provision of public funding for egg freezing, including for what reasons funding is justifiable. The medical/non-medical distinction is used to distribute funding for egg freezing in many jurisdictions, worldwide. However, under the revised French bioethics law, this is the first instance where, for the purpose of determining eligibility for funding, the reason for egg freezing is irrelevant as public funding is available for both medical and non-medical egg freezing. This challenges the justification of using the medical/non-medical distinction within funding policies and prompts further consideration about whether this distinction is still relevant to funding decisions.

A major increase in oocyte cryopreservation cycles in the USA, Australia and New Zealand since 2010 is highlighted by younger women but a need for standardized data collection.

STUDY QUESTION: What are the cohort trends of women undergoing oocyte cryopreservation (OC)? SUMMARY ANSWER: There has been a dramatic increase in OC cycles undertaken each year since 2010, and the demographics of women accessing OC has shifted to a younger age group, but so far very few women have returned to use their cryopreserved oocytes in treatments. WHAT IS KNOWN ALREADY: Although OC, as a method of fertility preservation, is offered around the world, global data are lacking on who is accessing OC, who is returning to thaw oocytes and whether these trends are changing. STUDY DESIGN, SIZE, DURATION: A trinational retrospective cohort study was performed of 31 191 OC cycles and 972 oocyte thaw (OT) cycles undertaken in the USA (2010-2016) and 3673 OC and 517 OT cycles undertaken in Australia/New Zealand (Aus/NZ; 2010-2015). PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were obtained from the USA Society for Assisted Reproductive Technology (SART) national registry and the Australian and New Zealand Assisted Reproduction Database (ANZARD). De-identified data were requested on all autologous oocyte freeze-all cycles and all cycles where autologous oocytes were thawed to be used in a treatment cycle for the time periods of interest. MAIN RESULTS AND THE ROLE OF CHANCE: In both the USA and Aus/NZ, there has been a dramatic rise in the number of OC cycles performed each year (+880% in the USA from 2010 to 2016 and +311% in Aus/NZ from 2010 to 2015). Across both regions, most women undergoing OC were aged in their late 30s, but the average age decreased over time (USA: 36.7 years vs 34.7 years in 2010 and 2016, respectively). The number of women returning for thaw cycles was low (USA: 413 in 2016, Aus/NZ: 141 in 2015) and most thaw cycles (47%) across both regions involved oocytes that were frozen for <6 months. In the USA, a higher proportion of cycles resulted in a live birth when only thawed oocytes were used, compared to cycles that combined thawed oocytes with fresh oocytes (25% vs 11%, respectively; P < 0.001). Age at retrieval influenced live birth rate in the USA; 38% of thaw cycles started in women who stored oocytes when aged ≤35 years resulted in a live birth, whereas only 16% resulted in a live birth for women who stored oocytes when aged ≥36 years. Similar data were unobtainable from Aus/NZ. LIMITATIONS, REASONS FOR CAUTION: There were limitations associated with both the SART and ANZARD data outputs received. The format in which the ANZARD data were provided, and the inconsistencies seen amongst cycle reporting in the SART dataset, restricted data interpretation. For example, both datasets did not provide a clear indication as to why women were undergoing OC and it was not possible to accurately calculate duration of storage for thaw cycles in the USA. We also did not obtain details on embryo quality from either database and acknowledge that embryo quality and subsequent outcome (embryo freezing or discard) would be of interest, especially when considering the efficacy of OC. WIDER IMPLICATIONS OF THE FINDINGS: The data show that there is widespread demand for OC, and it is increasingly undertaken by younger women; however, the limitations encountered in the dataset support the need for a shift to a more uniform approach to data collection and presentation by large databases, worldwide. STUDY FUNDING/COMPETING INTEREST(S): This study received funding from the Fertility Society of Australia to support the ANZARD data extraction. M.J. is supported by an Australian Government Research Training Program Scholarship stipend. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Should the scope of NIPT be limited by a 'threshold of seriousness'?

Non-invasive prenatal testing (NIPT) has the potential to screen for a wider range of genetic conditions than is currently possible at an early stage of pregnancy and with minimal risks. As such, there have been calls to apply a 'threshold of seriousness' to limit the scope of conditions being tested. This approach is based on concerns about society at large and the potential impact on specific groups within it. In this paper, we argue that limiting the scope of NIPT using the criterion of 'seriousness' is arbitrary, potentially stigmatises certain disabilities over others and fails to respect reproductive autonomy. We contend that concerns about expanded NIPT are more appropriately addressed by the provision of adequate information, counselling and consent procedures. We recommend a decision-making process that helps healthcare providers support prospective parents to make informed decisions about the nature and scope of NIPT screening based on their own values and social context. In addition to addressing concerns about expanded NIPT screening, this process would help clinicians to obtain legally valid consent and discharge their duty of care (including the duty to inform) in the prenatal context.

Financing future fertility: Women's views on funding egg freezing.

Like other assisted reproductive technology (ART) procedures, the cost of egg freezing (EF) is significant, presenting a potential barrier to access. Given recent technological advancements and rising demand for EF, it is timely to reassess how EF is funded. An online cross-sectional survey was conducted in Victoria, Australia and was completed by 656 female individuals. Participants were asked their views on funding for both medical and non-medical EF. The median age of participants was 28 years (interquartile range 23-37 years) and most participants were employed (44% full-time, 28% part-time, 33% students). There was very high support for public funding for medical EF (n = 574, 87%), with 302 (46%) participants indicating support for the complete funding of medical EF through the public system. Views about funding for non-medical EF were more divided; 43 (6%) participants supported full public funding, 235 (36%) supported partial public funding, 150 (23%) supported coverage through private health insurance, and 204 (31%) indicated that non-medical EF should be self-funded. If faced with the decision of what to do with surplus eggs, a high proportion of participants indicated that they would consider donation (71% to research, 59% to a known recipient, 52% to a donor programme), indicating that eggs surplus to requirements could be a potential source of donor eggs. This study provides insights that could inform policy review, and suggests revisiting whether the medical/non-medical distinction is a fair criterion to allocate funding to ART.

Employer-Sponsored Egg Freezing: Carrot or Stick?

BackgroundSince 2014, many companies have followed the lead of Apple and Facebook and now offer financial support to female employees to access egg freezing. Australian companies may soon make similar offers. Employer-sponsored egg freezing (ESEF) has raised concerns and there is academic debate about whether ESEF promotes reproductive autonomy or reinforces the 'career vs. family' dichotomy. Despite the growing availability of ESEF and significant academic debate, little is known about how ESEF is perceived by the public. The aim of this study was to explore women's attitudes toward ESEF.MethodsWomen aged 18-60 years who resided in Victoria, Australia were invited to complete an online, cross-sectional survey investigating views toward egg freezing. Associations between participant demographics and their views about ESEF were assessed using multinominal logistic regression, adjusted for age and free text comments were analyzed using thematic analysis.ResultsThe survey was completed by 656 women, median age 28 years (range: 18-60 years). Opinions on the appropriateness of employers offering ESEF were divided (Appropriate: 278, 42%; Inappropriate: 177, 27%; Unsure: 201, 31%). There was significantly less support for ESEF among older participants and those employed part-time (p < 0.05). While some participants saw the potential for ESEF to increase women's reproductive and career options, others were concerned that ESEF could pressure women to delay childbearing and exacerbate existing inequities in access to ARTs.ConclusionsOur analysis revealed that while some women identified risks with ESEF, for many women ESEF is not viewed as theoretically wrong, but rather it may be acceptable under certain conditions; such as with protections around reproductive freedoms and assurances that ESEF is offered alongside other benefits that promote career building and family. We suggest that there may be a role for the State in ensuring that these conditions are met.

Cracked open: exploring attitudes on access to egg freezing.

Egg freezing (EF) technology has improved significantly over the last decade, giving women more choice over their reproductive futures. Despite this advance, EF brings forth contentious ethical and regulatory issues. Policies controlling access to EF vary around the world and there is a lack of consensus about who should have access and what criteria are relevant in making these decisions. This study aimed to identify views of women about access to EF for both "medical" and "non-medical" risks to infertility. An online survey was administered to women aged between 18 and 60 years in Victoria, Australia between April and May 2018. A total of 1,066 individuals initiated the survey. The median age of the participants was 28 years and 81% were <40 years old. Almost all participants (98%) supported access to medical EF in situations where treatments (e.g. chemotherapy) or illnesses threaten fertility. Support for access to EF for non-medical indications was lower; 75% supported EF for "lack of suitable partner", followed by "financial insecurity to raise a child" (72%) and "career/educational advancement" (65%). Older respondents (aged ≥40 years) were less likely than their younger counterparts to support all indications for non-medical EF. Our findings indicate broad support for EF. However, the variation in support between indications for non-medical EF suggests that individuals do not think about access to EF simply in terms of medical necessity. To reflect public views, future policy may need to consider access to EF beyond the medical/non-medical distinction.

Comparison of reorganization of the somatosensory system in rats that sustained forelimb removal as neonates and as adults.

Studies of sensory pathways in several species indicate that the extent and form of reorganization resulting from deafferentation early in life vs. adulthood are not the same. The reasons for such differences are not well understood. To gain further insight into age-dependent mechanisms of reorganization, this study compared the consequences of neonatal vs. adult forelimb amputation in rats at multiple levels of the sensory pathway, including primary somatosensory cortex, brainstem, and dorsal root ganglia. At the cortical level, the average area of the functional forelimb-stump representation from rats amputated as adults was significantly smaller (P < 0.05) than that of neonatally amputated rats (4.3 +/- 1.3 mm(2) vs. 6.6 +/- 1.5 mm(2), respectively). At the brainstem level, neonatally amputated rat cuneate neurons possessed the following responsivities: 20% stump responsive, 40% responsive to both stump and hindlimb, 30% responsive to another body region, and 10% unresponsive. In contrast, cuneate neurons of adult amputated rats were 70% stump responsive, 2% responsive to both stump and hindlimb, and 30% unresponsive. A significantly (P < 0.001) greater percentage of the C(6)-C(8) dorsal root ganglia neurons of adult amputated rats were unresponsive to peripheral stimulation vs. neurons from neonatally amputated rats (48% vs. 16%, respectively). These results indicate that the reorganization that occurs in response to forelimb amputation at birth vs. adulthood is distinctly different at each of these levels of the dorsal column-medial lemniscal pathway. Possible mechanisms to account for these differences are considered.

gammadelta T-cell receptors: functional correlations.

The gammadelta T-cell receptors (TCRs) are limited in their diversity, suggesting that their natural ligands may be few in number. Ligands for gammadeltaTCRs that have thus far been determined are predominantly of host rather than foreign origin. Correlations have been noted between the Vgamma and/or Vdelta genes a gammadelta T cell expresses and its functional role. The reason for these correlations is not yet known, but several different mechanisms are conceivable. One possibility is that interactions between particular TCR-V domains and ligands determine function or functional development. However, a recent study showed that at least for one ligand, receptor specificity is determined by the complementarity-determining region 3 (CDR3) component of the TCR-delta chain, regardless of the Vgamma and/or Vdelta. To determine what is required in the TCR for other specificities and to test whether recognition of certain ligands is connected to cell function, more gammadeltaTCR ligands must be defined. The use of recombinant soluble versions of gammadeltaTCRs appears to be a promising approach to finding new ligands, and recent results using this method are reviewed.