ChatGPT: a reliable fertility decision-making tool?

The internet is the primary source of infertility-related information for most people who are experiencing fertility issues. Although no longer shrouded in stigma, the privacy of interacting only with a computer provides a sense of safety when engaging with sensitive content and allows for diverse and geographically dispersed communities to connect and share their experiences. It also provides businesses with a virtual marketplace for their products. The introduction of ChatGPT, a conversational language model developed by OpenAI to understand and generate human-like text in response to user input, in November 2022, and other emerging generative artificial intelligence (AI) language models, has changed and will continue to change the way we interact with large volumes of digital information. When it comes to its application in health information seeking, specifically in relation to fertility in this case, is ChatGPT a friend or foe in helping people make well-informed decisions? Furthermore, if deemed useful, how can we ensure this technology supports fertility-related decision-making? After conducting a study into the quality of the information provided by ChatGPT to people seeking information on fertility, we explore the potential benefits and pitfalls of using generative AI as a tool to support decision-making.

Australian intended parents' decision-making and characteristics and outcomes of surrogacy arrangements completed in Australia and overseas.

Markets for international surrogacy often arise in jurisdictions with limited regulations regarding assisted reproductive technologies. In some countries, like Australia, regulated domestic surrogacy services are often sidestepped for international providers. This study describes how Australian intended parents decide where to pursue surrogacy and compares the characteristics and outcomes of arrangements completed within and outside of Australia. The findings show that, although intended parents preferred undergoing surrogacy in Australia, perceiving the process as too long and complicated was a common reason to pursue an international arrangement. Multiple embryo transfer, anonymous gamete donation, and a lack of counselling were common in international surrogacy arrangements. When compared to surrogacy arrangements completed in Australia, where single embryo transfer is mandatory for surrogacy cycles, the rates of multiple birth, preterm birth and neonatal intensive care in international surrogacy were higher. These findings raise concerns about the health and welfare of international surrogacy participants, particularly the surrogates and children. In lieu of any international instrument regulating surrogacy, improving access to surrogacy at a domestic level would reduce the number of people engaging with international arrangements and in turn, reduce the potential for harm.

Offspring physiology following the use of IVM, IVF and ICSI: a systematic review and meta-analysis of animal studies.

BACKGROUND: Since the birth of the first baby using IVF technology in 1978, over 10 million children have been conceived via ART. Although most aspects of ARTs were developed in animal models, the introduction of these technologies into clinical practice was performed without comprehensive assessment of their long-term safety. The monitoring of these technologies over time has revealed differences in the physiology of babies produced using ARTs, yet due to the pathology of those presenting for treatment, it is challenging to separate the cause of infertility from the effect of treatments offered. The use of systematic review and meta-analysis to investigate the impacts of the predominant ART interventions used clinically in human populations on animals produced in healthy fertile populations offers an alternative approach to understanding the long-term safety of reproductive technologies. OBJECTIVE AND RATIONALE: This systematic review and meta-analysis aimed to examine the evidence available from animal studies on physiological outcomes in the offspring conceived after IVF, IVM or ICSI, compared to in vivo fertilization, and to provide an overview on the landscape of research in this area. SEARCH METHODS: PubMed, Embase and Commonwealth Agricultural Bureaux (CAB) Abstracts were searched for relevant studies published until 27 August 2021. Search terms relating to assisted reproductive technology, postnatal outcomes and mammalian animal models were used. Studies that compared postnatal outcomes between in vitro-conceived (IVF, ICSI or IVM) and in vivo-conceived mammalian animal models were included. In vivo conception included mating, artificial insemination, or either of these followed by embryo transfer to a recipient animal with or without in vitro culture. Outcomes included birth weight, gestation length, cardiovascular, metabolic and behavioural characteristics and lifespan. OUTCOMES: A total of 61 studies in five different species (bovine, equine, murine, ovine and non-human primate) met the inclusion criteria. The bovine model was the most frequently used in IVM studies (32/40), while the murine model was mostly used in IVF (17/20) and ICSI (6/8) investigations. Despite considerable heterogeneity, these studies suggest that the use of IVF or maturation results in offspring with higher birthweights and a longer length of gestation, with most of this evidence coming from studies in cattle. These techniques may also impair glucose and lipid metabolism in male mice. The findings on cardiovascular outcomes and behaviour outcomes were inconsistent across studies. WIDER IMPLICATIONS: Conception via in vitro or in vivo means appears to have an influence on measurable outcomes of offspring physiology, manifesting differently across the species studied. Importantly, it can be noted that these measurable differences are noticeable in healthy, fertile animal populations. Thus, common ART interventions may have long-term consequences for those conceived through these techniques, regardless of the pathology underpinning diagnosed infertility. However, due to heterogeneous methods, results and measured outcomes, highlighted in this review, it is difficult to draw firm conclusions. Optimizing animal and human studies that investigate the safety of new reproductive technologies will provide insight into safeguarding the introduction of novel interventions into the clinical setting. Cautiously prescribing the use of ARTs clinically may also be considered to reduce the chance of promoting adverse outcomes in children conceived before long-term safety is confidently documented.

Endometrial scratching in Australia, New Zealand and the United Kingdom (UK): a follow-up survey.

Endometrial scratching is a common IVF add-on. In 2015, a survey in Australia, New Zealand and the United Kingdom (UK) reported that 83% of fertility specialists recommended endometrial scratching for IVF. Several large trials have since been published reporting no clear evidence for improved live birth rates following endometrial scratching before IVF. An online survey was undertaken to ascertain the current practices and views across Australia, New Zealand, and the UK. A total of 121 eligible responses were received between October and December 2020 (fertility specialists (n = 61), embryologists (n = 26) and fertility nurses (n = 24)). Among fertility specialists, 34% currently offer endometrial scratching, mostly in the case of recurrent implantation failure. Most respondents were neutral or did not believe endometrial scratching improved pregnancy and live birth rates (>90%), except for in women with recurrent implantation failure (29% believed it can increase pregnancy and live birth rates in this group). More than half of respondents viewed reducing psychological distress as a benefit of endometrial scratching (55%). Among fertility specialists not offering endometrial scratching, 51% previously offered it but no longer do. The decline in use over the last five years likely reflects a response to recent evidence reporting no benefit from the procedure.

Experiences of surrogates and intended parents of surrogacy arrangements: a systematic review.

This review reports on the experiences of surrogates and intended parents of surrogacy arrangements. The findings from 47 studies, conducted across 12 countries and investigating predominately gestational surrogacy in a commercial setting, were analysed thematically, and are reported in a narrative summary. The findings reveal that the experiences of both parties of surrogacy arrangements are largely satisfactory and frequently involve positive relationships forming between one another, which they hope to maintain after birth. Some surrogacy participants experience challenges, particularly when the surrogate and intended parents reside in different countries. Intended parents face legal hurdles when returning home after an international arrangement. Concerningly, multiple reports of clinical practices in India have been published, in which commercial surrogacy was accessed by foreign intended parents, which infringed on surrogates' autonomy during the pregnancy. Intended parents turn to these international destinations when they face barriers to accessing surrogacy in their home country, such as the prohibition of commercial surrogacy. Looking beyond the altruistic and commercial dichotomy may alleviate some of the barriers to domestic surrogacy. Collaboration between professional fertility organizations to develop best practice guidelines can support clinics in providing international surrogacy services that minimize the risk of harm to those accessing care.

The quality of information about elective oocyte cryopreservation (EOC) on Australian fertility clinic websites.

BACKGROUND: The number of women who undergo elective oocyte cryopreservation (EOC) in the hope of preserving their fertility is increasing. Fertility clinic websites often serve as the first point of contact for women contemplating EOC. There are no guidelines for Australian fertility clinics regarding how information about procedures should be presented. AIM: To assess the quality of information presented on EOC on Australian fertility clinic websites. MATERIALS AND METHODS: A desktop audit was conducted of the websites of Australian fertility clinics offering EOC (n = 21) and the information provided about EOC was recorded. To allow comparison, a scoring matrix used in a study of the quality of EOC information on clinic websites in the USA was used to assess the quality of the information. The possible range of scores on this measure is 0-13. RESULTS: The mean information quality score for all clinic websites was 4.3 (range 2-8). More than half of the clinic websites (57%) had scores classified as 'poor', indicating that women are not receiving the information they need to make well-informed choices. CONCLUSION: Providing information on clinic websites that is transparent and scientifically accurate, that states the risks involved in the procedure, and its full cost is essential to allow women to make informed decisions. The scoring matrix used in this study to assess the quality of information relating to EOC can guide best practice for clinics in advertising EOC to prospective customers.

A variant of human growth differentiation factor-9 that improves oocyte developmental competence.

Growth differentiation factor-9 (GDF9) and bone morphogenetic protein-15 (BMP15) are co-expressed exclusively in oocytes throughout most of folliculogenesis and play central roles in controlling ovarian physiology. Although both growth factors exist as homodimers, recent evidence indicates that GDF9 and BMP15 can also heterodimerize to form the potent growth factor cumulin. Within the cumulin complex, BMP15 "activates" latent GDF9, enabling potent signaling in granulosa cells via type I receptors (i.e. activin receptor-like kinase-4/5 (ALK4/5)) and SMAD2/3 transcription factors. In the cumulin heterodimer, two distinct type I receptor interfaces are formed compared with homodimeric GDF9 and BMP15. Previous studies have highlighted the potential of cumulin to improve treatment of female infertility, but, as a noncovalent heterodimer, cumulin is difficult to produce and purify without contaminating GDF9 and BMP15 homodimers. In this study we addressed this challenge by focusing on the cumulin interface formed by the helix of the GDF9 chain and the fingers of the BMP15 chain. We demonstrate that unique BMP15 finger residues at this site (Arg301, Gly304, His307, and Met369) enable potent activation of the SMAD2/3 pathway. Incorporating these BMP15 residues into latent GDF9 generated a highly potent growth factor, called hereafter Super-GDF9. Super-GDF9 was >1000-fold more potent than WT human GDF9 and 4-fold more potent than cumulin in SMAD2/3-responsive transcriptional assays in granulosa cells. Our demonstration that Super-GDF9 can effectively promote mouse cumulus cell expansion and improve oocyte quality in vitro represents a potential solution to the current challenges of producing and purifying intact cumulin.

Appendix F: Quinn's Advantage Embryo Freeze Kit.

Despite a large focus on the use of vitrification to cryopreserve embryos in recent years, there are still arguments for the use of slow freezing for the cleavage-stage embryo. Having said this, there are lessons to be learned from the process of vitrification that could be applied to slow freezing to improve post-thaw survival and ultimately clinical pregnancy rates. Specifically, increasing the concentration of sucrose in the freezing solution from 0.1 to 0.2 M and subsequently increasing the sucrose concentrations in thawing solutions could prove beneficial. The use of vitrification warming solutions in the thawing of slow-frozen embryos may also be an option that not only improves survival but also streamlines product purchasing and protocols within the laboratory.