Search

In vitro gametogenesis (IVG), the reconstitution of germ cell development in vitro, is an emerging stem cell-based technology with profound implications for reproductive science. Despite researchers' long-term goals for future clinical applications, little is currently known about the views of IVG held by the stakeholders potentially most affected by its introduction in humans. We conducted focus groups and interviews with 80 individuals with lived experience of infertility and/or LGBTQ+ family formation in the US, two intersecting groups of potential IVG users. Respondents expressed hope that IVG would lead to higher reproductive success than current assisted reproductive technology (ART), alleviate suffering associated with ART use, and promote greater social inclusion, while expressing concerns predominantly framed in terms of equity and safety. These findings underscore the importance of sustained engagement with stakeholders with relevant experience to anticipate the implications of IVG for research and clinical translation.

Background: Advanced maternal age is associated with decreased oocyte quantity and quality and in vitro fertilization (IVF) success rates. This study aimed to investigate whether melatonin supplementation can improve IVF outcomes in women of advanced maternal age by modulating cuproptosis and ferroptosis. Methods: This prospective cohort study included 161 women aged 35–45 years undergoing IVF-frozen embryo transfer cycles. Participants were assigned to either melatonin (n = 86, 2 mg daily for ≥ 8 weeks) or control (n = 75) groups. Cumulus cells were analyzed for cuproptosis and ferroptosis-related gene expression. Additional experiments were conducted on the HGL5 human granulosa cell line to assess mitochondrial function and metabolic reprogramming. Results: Melatonin supplementation significantly improved IVF outcomes in women aged ≥ 38 years, increasing clinical pregnancy rates (46.0% vs. 20.3%, P < 0.01), ongoing pregnancy rates (36.5% vs. 15.3%, P < 0.01), and live birth rates (33.3% vs. 15.3%, P < 0.05). In cumulus cells from patients, gene expression analysis revealed that melatonin modulated cuproptosis and ferroptosis-related genes, including ATP7B and GPX4, with more pronounced effects in the ≥ 38 years group. This suggests melatonin enhances cellular resilience against oxidative stress and metal-induced toxicity in the ovarian microenvironment. In vitro studies using HGL5 cells showed melatonin reduced oxidative stress markers, improved mitochondrial function, restored expression of glycolysis and TCA cycle-related genes and modulated cuproptosis and ferroptosis-related gene expression. These findings provide mechanistic insight into melatonin's protective effects against regulated cell death in ovarian cells, potentially explaining the improved IVF outcomes observed. Conclusions: Melatonin supplementation significantly improved IVF outcomes in women of advanced maternal age, particularly those ≥ 38 years old, likely by modulating cuproptosis and ferroptosis and enhancing mitochondrial function in cumulus and granulosa cells. These results suggest that melatonin could be a promising adjuvant therapy for improving IVF success rates in older women. [ABSTRACT FROM AUTHOR]

In response to the changing landscape of transnational surrogacy, the industry has introduced flexible business models requiring women to move within and across borders to act as surrogate mothers. However, knowledge about their experiences remain vague, particularly concerning women traveling abroad under illegal conditions. Building upon interviews with Thai surrogate mothers, I demonstrate how their im/mobility reveals critical insights into labor conditions and power relations and is formed within the global reproductive industry as well as the specific national context. I also argue that the women’s im/mobility and flexibility are central when making themselves bioavailable for the global surrogacy market. [ABSTRACT FROM AUTHOR]

Within the expanding bioeconomy of assisted reproduction, there are limitations to providing quality informed consent for egg donation when the long-term risks remain unknown. Based on ethnographic fieldwork in Barcelona with egg donors and in vitro fertilization (IVF) professionals, in this paper, we speak of "temporal choreography" to describe how clinical practices delimit and circumscribe the information that will be offered to egg donors by positioning them in an immediate present or "temporal stasis" in which future risks of egg donation are precluded, and consideration of possible future uses or distribution of eggs is truncated. These aspects intersect with the biographical temporality of egg donors, who are mostly young and economically precarious. This choreography is essential to the commercial success of the Spanish egg donation industry, which is the largest in Europe. This article engages with the emerging interest in temporality and IVF by questioning whose bodies are positioned to anticipate risks and fertility as an act of self-care and whose are encouraged to cast aside concerns about harms in favor of short-term monetary gains. [ABSTRACT FROM AUTHOR]

Discussions on the Anthropocene have called for increased attention to how the effects of human actions on the planet are accounted for. While much of this debate remains at a theoretical level, more studies on situated Anthropocene realities have been called for. Contributing to the latter, this article explores how experimental and clinical interventions are being accounted for in life science laboratories. Drawing on three research cases, genetically modified mosquitoes, laboratory-grown stem cell lines and assisted reproduction in the IVF clinic, the article traces how 'strategic naturalizing' is conducted to make sense of and justify human interventions on cells, bodies and ecosystems. Strategic naturalizing in laboratory work is situated, fluid, and also implicates the presence of the social scientist. Although naturalizing biotechnologies is not a new phenomenon, according to our observations scientists increasingly draw on notions of a planet profoundly transformed by human intervention as they conceptualize their own accountability. Consequently, we propose that strategic naturalizing is emerging as an elemental logic in the patchy local enactments of the Anthropocene and its concerns. In the context of experimental and clinical laboratory work, it is a key element in enacting good science and orienting the work towards making biotechnology acceptable in wider society. In studying this, the social scientist also is implicated in situated local enactments of the Anthropocene. [ABSTRACT FROM AUTHOR]

This review article focusses on child development and family relationships in families formed through third-party assisted reproductive technologies (ART). First, we provide an overview of the existing developmental research on families formed through sperm donation, egg donation, embryo donation, and surrogacy, respectively. We then consider some of the cross-cutting themes and issues in families following different types of ART, such as the role of openness and disclosure, and making donor connections, that relate to family relationships and children’s outcomes. Finally, we reflect on some of the conceptual and methodological limitations of the current research, including its dependence on relatively homogenous samples, and its relative inattention to culture. We conclude by outlining some of the new directions for research in this area. [ABSTRACT FROM AUTHOR]

BACKGROUND Monozygotic (MZ) twins are believed to arise from the fission of a single fertilized embryo at different stages. Monochorionic MZ twins, who share one chorion, originate from the splitting of the inner cell mass (ICM) within a single blastocyst. In the classic model for dichorionic MZ twins, the embryo splits before compaction, developing into two blastocysts. However, there are a growing number of ART cases where a single blastocyst transfer results in dichorionic MZ twins, indicating that embryo splitting may occur even after blastocyst formation. OBJECTIVE AND RATIONALE For monochorionic MZ twins, we conducted a comprehensive analysis of the cellular mechanisms involved in ICM splitting, drawing from both ART cases and animal experiments. In addition, we critically re-examine the classic early splitting model for dichorionic MZ twins. We explore cellular mechanisms leading to two separated blastocysts in ART, potentially causing dichorionic MZ twins. SEARCH METHODS Relevant studies including research articles, reviews, and conference papers were searched in the PubMed database. Cases of MZ twins from IVF clinics were found by using combinations of terms including 'monozygotic twins' with 'IVF case report', 'ART', 'single embryo transfer', or 'dichorionic'. The papers retrieved were categorized based on the implicated mechanisms or as those with unexplained mechanisms. Animal experiments relating to MZ twins were found using 'mouse embryo monozygotic twins', 'mouse 8-shaped hatching', 'zebrafish janus mutant', and 'nine-banded armadillo embryo', along with literature collected through day-to-day reading. The search was limited to articles in English, with no restrictions on publication date or species. OUTCOMES For monochorionic MZ twins, ART cases and mouse experiments demonstrate evidence that a looser ICM in blastocysts has an increased chance of ICM separation. Physical forces facilitated by blastocoel formation or 8-shaped hatching are exerted on the ICM, resulting in monochorionic MZ twins. For dichorionic MZ twins, the classic model resembles artificial cloning of mouse embryos in vitro , requiring strictly controlled splitting forces, re-joining prevention, and proper aggregation, which allows the formation of two separate human blastocysts under physiological circumstances. In contrast, ART procedures involving the transfer of a single blastocysts after atypical hatching or vitrified-warmed cycles might lead to blastocyst separation. Differences in morphology, molecular mechanisms, and timing across various animal model systems for MZ twinning can impede this research field. As discussed in future directions, recent developments of innovative in vitro models of human embryos may offer promising avenues for providing fundamental novel insights into the cellular mechanisms of MZ twinning during human embryogenesis. WIDER IMPLICATIONS Twin pregnancies pose high risks to both the fetuses and the mother. While single embryo transfer is commonly employed to prevent dizygotic twin pregnancies in ART, it cannot prevent the occurrence of MZ twins. Drawing from our understanding of the cellular mechanisms underlying monochorionic and dichorionic MZ twinning, along with insights into the genetic mechanisms, could enable improved prediction, prevention, and even intervention strategies during ART procedures. REGISTRAITON NUMBER N/A. [ABSTRACT FROM AUTHOR]

It is not controversial to state that parental age is increasing in several countries. But how to deal with this increase might be. Some Nordic countries have set an upper age limit for females seeking assisted reproduction in their national legislation, but none have done so for males. There are also recommendations in place that restrict access to publicly funded assisted reproduction for both females and males of advanced age in some Nordic countries. As recent data now show somatic and psychiatric health risks related to advanced paternal age, we ask if the time has come for countries to set an upper age limit for males seeking assisted reproduction like there already is for females, and summarize some of the risks and rewards involved in treating couples with advanced age in fertility clinics. [ABSTRACT FROM AUTHOR]

Ovum Pick Up (OPU) is a minimally invasive technique widely used in cattle and mares for oocyte retrieval, involving ultrasound-guided puncture of ovarian follicles. It has been demonstrated that this technique is safe for its repeated use in the same female without affecting her reproductive health, allowing for the retrieval of oocytes in individuals regardless of their reproductive status. The oocytes obtained through OPU can subsequently be used for in vitro embryo production (IVP) using assisted reproductive techniques (ARTs) or be cryopreserved in biobanks for their future use. Traditionally, the minimally invasive technique of choice performed in vivo in domestic and wild felines was LOPU (laparoscopic-guided ovum pick up). The present study was designed to explore if ultrasound-guided OPU in the domestic cat is safe and effective. In an initial series of ex vivo experiments (n = 92 ovaries, n = 434 oocytes), the effect of different aspiration pressures for oocyte collection was explored. These experiments identified 43 mmHg as the optimal aspiration pressure, resulting in the highest recovery rate and a favorable maturation and blastocyst rate. Subsequently, 16 grade I and II oocytes were retrieved by OPU and 101 oocytes were retrieved following ovariectomy and slicing. Sixteen oocytes obtained with each technique were subjected to in vitro maturation (IVM) and in vitro fertilization (IVF). A total of 14 presumptive zygotes were selected for in vitro culture (IVC) from each group (OPU and slicing), obtaining a cleavage rate of 57.1 % and 64.2 %, a morula rate of 28.5 % in both groups, and a blastocyst rate of 7.14 % and 14.2 % respectively. The hormonal stimulation protocol was well-tolerated, with no adverse effects observed. Moreover, no complications arose during the ovariectomy performed post-OPU. The use of this technique in domestic cats represents a significant step forward in terms of safety, replicability, and invasiveness, serving as a valuable model for its application in wild felids species. Additional research involving a greater number of animals is required to validate these encouraging findings. • This study presents the first successful ultrasound-guided ovum pick-up (OPU) in the domestic cat. • OPU is a minimally invasive technique that offers advantages in terms of invasiveness and safety compared to LOPU. • In vitro embryo production from OPU and slicing showed comparable cleavage, morula, and blastocyst rates. • This research provides a replicable model for potential application in wild felid species. [ABSTRACT FROM AUTHOR]

Background: Preimplantation genetic testing (PGT) allows for the evaluation of embryo genetic information prior to implantation, enabling the selection of normal embryos for transfer and ultimately leading to better pregnancy outcomes. In this study, we explored factors that influence clinical outcomes of patients undergoing PGT. The effects of blastocyst grading and biopsy dates on clinical outcomes were also analyzed. Methods: The clinical data and pregnancy outcomes of 428 PGT cycles performed in the Reproductive Medicine Department of the Northern Theater General Hospital between January 2017 and December 2022 were retrospectively analyzed. Multifactorial logistic regression analysis and nomograms were used to determine factors influencing pregnancy outcomes. The impact of D5 blastocysts (290 cycles) and D6 blastocysts (138 cycles) with different quality levels on clinical outcomes was also compared. Results: Multifactorial logistic regression analysis showed that age, BMI, endometrial thickness, and embryo quality of women affected PGT clinical outcomes. Women aged <40 years or with a body mass index (BMI) >18.5 and endometrial thickness>1.0 cm had a significantly higher pregnancy success rate. Compared to that of D6 blastocyst biopsy, D5 blastocyst biopsy was associated with a higher pregnancy success rate but a similar live birth rate. No significant differences were observed in the pregnancy and live birth rates of D5 and D6 high-quality blastocysts. Conclusion: To achieve better pregnancy outcomes after PGT, considering blastocyst grading and biopsy dates when transferring embryos is essential for improving pregnancy outcomes. Furthermore, patients should adjust their BMI, endometrial receptivity, and endometrial thickness and pattern. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the association between first trimester (≤ 12 weeks gestation) subchorionic hemorrhage (SCH), and maternal and neonatal outcomes in women who conceived with the help of assisted reproductive technique (ART). Methods: PubMed, Embase, Web of Science, and Scopus databases were searched for observational studies that specifically focused on women who achieved pregnancy via ART and investigated the relationship between early pregnancy (within 12 weeks of gestation) SCH and maternal and neonatal outcomes. Only studies with singleton pregnancies and reporting data on the comparator group (women without SCH) were included. Primary outcomes of interest included incidences of early (within 20 weeks of gestation) pregnancy loss, preterm delivery, caesarean section, and live birth rates. Pooled effect sizes were reported as odds ratio (OR) with 95% confidence intervals (CI). Results: Nine studies were included. All studies had a cohort design. In all studies, the primary assisted reproduction technique used was in-vitro fertilization (IVF). Compared to pregnancies without SCH, women with diagnosed early pregnancy SCH have a similar risk of preterm birth (< 37 weeks) (OR 1.01, 95% CI 0.83, 1.22), low birth weight (< 2500 g) (OR 1.01, 95% CI 0.59, 1.73) and fetal growth restriction (OR 1.57, 95% CI 0.62, 4.02). The gestational age (in weeks) (weighted mean difference (WMD) − 0.06, 95% CI − 0.18, 0.06) and the birth weight (in grams) (WMD − 16.5, 95% CI − 62.9, 29.8) were also similar in the two groups. The odds of early pregnancy loss (OR 1.39, 95% CI 0.97, 2.01), live birth (OR 0.77, 95% CI 0.55, 1.08) and caesarean delivery (OR 0.97, 95% CI 0.81, 1.16) were statistically similar in both groups. The risk of maternal adverse outcomes such as gestational diabetes (OR 0.98, 95% CI 0.74, 1.29), hypertensive disorder (OR 0.95, 95% CI 0.63, 1.43), premature rupture of membranes (PROM) (OR 1.36, 95% CI 0.90, 2.05) and placental abruption (OR 2.44, 95% CI 0.57, 10.5) was also similar in both the groups. There was no evidence of publication bias. Conclusion: The findings suggest that SCH may not significantly increase the risk of adverse maternal and perinatal outcomes in pregnancies conceived through ART, particularly IVF. Trial registration: PROSPERO registration number CRD42024533996 [ABSTRACT FROM AUTHOR]

Monika Piotrowska has defended a new account of reproduction. Her account seems able to answer the question of whether reproduction takes place, and who reproduces, when we employ biotechnologies that bear little to no resemblance to naturally occurring human sexual reproduction. Piotrowska's account also seems to increase our understanding of biological individuality and seems to be compatible with the theory of evolution via natural selection. In this paper, I do two things. First, I show that Piotrowska's account is found wanting, because it is extensionally inadequate. Second, I show that her criticism of James Grisemer's account of reproduction is mistaken. [ABSTRACT FROM AUTHOR]

Copyright of Die Gynäkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Die Gynäkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The prenatal maternal affective bond can be understood as the emotional relationship that a pregnant woman establishes with her unborn child. This prenatal relationship develops gradually during the entire pregnancy. To study the prenatal maternal affective bond, and the variables involved therein, over the entire gestation for women who achieved pregnancy through assisted reproduction techniques (ART). We conducted a longitudinal study in which we evaluated 49 women at the three gestational trimesters: after the ultrasound confirmation of heart beat (from the 6th – 7th week of pregnancy), around the 20th week of gestation, and as of week 34. This study reflects, among other issues, that the prenatal maternal affective bond is very high from the beginning of pregnancy and increases trimester-by-trimester, showing very high levels at the end of the pregnancy. While the small number of participants has limited the statistical power, the data obtained are a first approximation to the studied reality that allows us to identify variables on which to continue working in future studies. [ABSTRACT FROM AUTHOR]

Objective Method Results Conclusion To explore the assisted reproductive outcomes of patients with atypical endometrial hyperplasia (AEH) and early‐stage endometrial cancer (EEC) who achieved complete remission after conservative treatment and to provide reference for clinical selection of appropriate conservative treatment.This retrospective cohort study included seven patients with EEC and 62 patients with AEH who underwent in vitro fertilization or intracytoplasmic sperm injection at the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University between August 2015 and October 2023. The authors divided the participants into two groups based on the type of fertility‐sparing treatment received: the oral medication group and the levonorgestrel‐releasing intrauterine system (LNG‐IUS) group. The primary outcome was the cumulative clinical pregnancy rate. Secondary outcomes included clinical pregnancy rate per transfer cycle, embryo utilization rate, and high‐quality embryo rate.The LNG‐IUS group had a significantly higher rate of usable embryos compared with the oral medication group (80.8% vs 91.1%, P = 0.005) and also had a thinner endometrial thickness on the day of embryo transfer. The cumulative clinical pregnancy rate was higher in the LNG‐IUS group compared with the medication group (46.7% vs 78.9%, P = 0.037), and the difference was statistically significant.For patients with AEH and EEC with fertility needs, the conservative treatment method of LNG‐IUS can achieve better assisted reproductive outcomes. [ABSTRACT FROM AUTHOR]

Assisted reproduction is a key aspect of modern animal breeding, providing valuable assistance in improving breeding programs. In this field, the administration of exogenous hormones, such as follicle-stimulating hormone (FSH), plays a crucial role in the induction of multiple ovulations. However, commercial FSH used in veterinary practice has been derived primarily from pituitary glands, obtained mostly from pigs for nearly four decades. Although these hormones have contributed significantly to the advancement of assisted reproductive techniques, they have certain limitations that warrant further improvements. These limitations include contamination with luteinizing hormone (LH), the potential risk of pathogen contamination, the potential to trigger an immune response in non-pig species, and the short half-life in circulation, requiring the implementation of complex 8-dose superovulation schedules. Our research team has developed and characterized a new variant of bovine follicle-stimulating hormone (bscrFSH) to address these limitations. The new hormone is produced recombinantly in CHO cell cultures, with a specific productivity of about 30 pg/cell/day. The bscrFSH can be purified to a high purity of 97 % using a single step of immobilized metal affinity chromatography (IMAC). N-glycan analysis of bscrFSH showed that approximately 74 % of the glycans corresponded to charged structures, including mono-, di-, tri-, and tetra-sialylated glycans. Superovulation trials conducted in cattle revealed that bscrFSH, administered at a total dose of about 0.5 μg per kg of body weight, using a decrescent schedule of 4 doses with 24-h intervals, resulted in an average yield of 8–12 transferable embryos per animal. Further research is required; however, the preliminary findings indicate that bscrFSH, currently packaged under the provisional brand name of Cebitropin B, holds potential as a commercial product for assisted reproduction in ruminants. • The bovine FSH variant (brscFSH) designed by the team is functional in inducing superovulation in cattle. • brscFSH can be produced at 30 pg/cell/day and purified to >95% purity using immobilized-metal affinity chromatography (IMAC). • brscFSH yields 8–12 transferable embryos on average at 0.5 μg/kg in a four-dose schedule over 12 hours. • Further studies are needed to assess brscFSH in two/single-dose schedules and in other species like sheep, goats, camelids, and mares. • brscFSH is now available for research use only on the Centro de Biotecnología y Biomedicina SpA website. [ABSTRACT FROM AUTHOR]

Surrogate motherhood raises a variety of ethical, legal, theological, and sociological questions. Discussions on this topic often become heated, particularly when considering the use of a woman's body to carry a pregnancy on behalf of another individual--married or unmarried, male or female--with an ovum that, in most cases, has no biological connection to her and is legally recognized as belonging to the commissioning party or parties post-birth. On one side, issues of self-determination, solidarity, and compassion are debated, while on the other, dignity, the sanctity of life, commodification, and exploitation are concerns. This article, without overlooking these significant issues, attempts an interreligious examination of surrogate motherhood to elucidate how the three major monotheistic religions, along with Hinduism and Buddhism, assess, interpret, and understand this practice. The aim is to highlight both converging and diverging positions across different views and to more fully comprehend the various theological and cultural dimensions that shape the contemporary bioethical understanding of this issue. [ABSTRACT FROM AUTHOR]

Background/Objectives: In this observational prospective cohort study, conducted at the Fertility Centre of the University Hospital, Duesseldorf Germany, the spontaneous reversal capacity and the effect of waiting time on an adverse vaginal microbiome profile in subfertile patients were investigated. Methods: Vaginal swabs of 76 patients were obtained before starting a fertility treatment using a commercially available test to perform a microbiome analysis. Patients with a favorable microbiome profile ("medium" or "high profile") according to the manufacturer's algorithm proceeded with the fertility treatment. Patients with an unfavorable microbiome profile ("low profile") postponed their fertility treatment and were sampled up to four times in each successive cycle or until a shift to a more favorable profile was detected. Results: Initially, 54/76 subjects had a high or medium profile and 23/76 had a low profile. Within 3 months, 75% of patients with an initial low profile shifted to a more favorable profile (7/23 dropouts). The presence of Lactobacillus crispatus in the initial sample was associated with a higher likelihood of a spontaneous shift to a more favorable profile. Conclusions: The vaginal microbiome is subject to strong fluctuations. Even an unfavorable microbiome profile can develop into a favorable microbiome profile within a few months without treatment. [ABSTRACT FROM AUTHOR]

Unerfüllter Kinderwunsch ist weltweit ein bedeutsames Problem. Die psychologischen Auswirkungen dieser Entwicklung werden meist unterschätzt, während der Mythos der „psychogenen Infertilität" hartnäckig persistiert. In diesem Beitrag wird zunächst eine Übersicht über grundlegende Fakten zur Thematik gegeben, bevor die psychologischen Auswirkungen sowohl der Diagnosestellung Infertilität als auch der therapeutischen Optionen aufgezeigt werden. Psychologische Aspekte der Familienbildung mit Hilfe Dritter und der weiteren Entwicklung nach Kindsgeburt bzw. ohne Kind werden skizziert, wie auch ein kurzer Einblick in allgemeine und spezifische Beratungsinhalte bei unerfülltem Kinderwunsch gegeben. Der Beitrag schließt mit Überlegungen zu möglichen psychologischen Konsequenzen der weiteren medizinischen Entwicklungen in diesem Bereich. Summary: The unfulfilled desire for children is a significant problem worldwide. The psychological effects of this development are usually underestimated, while the myth of "psychogenic infertility" stubbornly persists. This article first provides an overview of the basic facts on the subject before highlighting the psychological effects of both the diagnosis of infertility and the therapeutic options. Psychological aspects of "third-party" reproduction and further developments after childbirth or without a child are discussed, followed by a brief outline of the general and specific subject matter addressed in infertility counselling. The article concludes with reflections on the possible psychological consequences of further medical developments in this area. [ABSTRACT FROM AUTHOR]

STUDY QUESTION How do individual religious, political, and social tolerance orientations influence the acceptance of ART among Spanish citizens? SUMMARY ANSWER Social tolerance and religiosity are predictive factors for the acceptance of ART, with more tolerant individuals and those with lower levels of religiosity being more accepting of ART; political conservatism mediates the relationship between social tolerance and acceptance of ART, particularly for left-leaning individuals. WHAT IS KNOWN ALREADY The rapid advancement of ART has raised questions about its societal acceptance, especially in the context of religious, political, and social beliefs. STUDY DESIGN, SIZE, DURATION The analysis utilized data from the combined Europe Values Study and World Values Survey, comprising cross-sectional national surveys from 1981 to 2021. Each country's population was surveyed a maximum of seven times and a minimum of two times during this period. This study uses the cross-sectional data of 2021. After filtering for Spanish citizens and deleting cases with missing key variables, a sample of 1030 valid responses from Spanish citizens was obtained. Quotas were set for sex, age, and educational level, following guidance from the Spanish Statistics Institute. PARTICIPANTS/MATERIALS, SETTING, METHODS The study surveyed participants' attitudes towards ART, their religious and political orientations, and collected demographic information. The sample consisted of 51.7% women, most respondents were married or in common-law partnerships, and 61.6% had children. Catholicism was the dominant religion (53.0%) and a majority had completed secondary education (66.2%), with half earning over 1400 euros per month. MAIN RESULTS AND THE ROLE OF CHANCE Using two linear models to test hypotheses, the study found that social tolerance and religiosity significantly predict acceptance of ART, with more tolerant and less religious individuals being more accepting. Political conservatism mediated the relationship between social tolerance and ART acceptance, particularly among left-leaning individuals. LIMITATIONS, REASONS FOR CAUTION This study is cross-sectional and based on self-reported data, which may have limitations. Additionally, the findings are based on a Spanish sample and may not be universally applicable. WIDER IMPLICATIONS OF THE FINDINGS The results have significant implications for policymakers and healthcare professionals in the field of reproductive technologies. They also contribute to public debates on ethical considerations surrounding ART. STUDY FUNDING/COMPETING INTEREST(S) This work was funded by the Mineco-FrontVida Program, Frontiers of Life, Social Change, and Changing Values Around the Beginning and End of Life (grant number PID2019-106882RB-I00), as part of the State Program for Knowledge Generation and Scientific and Technological Strengthening, and the State R&D Program Oriented to the Challenges of Society, 2019, Ministry of Science, Innovation, and Universities of Spain. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is there an elevated risk of cyanotic congenital heart defects (CCHD) among livebirths following infertility treatments? SUMMARY ANSWER In this population-based study of single livebirths, infertility treatment (either ART or non-ART) was associated with a higher prevalence of CCHD among livebirths. WHAT IS KNOWN ALREADY The use of infertility treatment has been on the rise over the past few decades. However, there are limited studies assessing the risk of major cardiac defects following infertility treatments. STUDY DESIGN, SIZE, DURATION A retrospective cohort study of livebirth data from the National Vital Statistics System (NVSS) was conducted, comprising of 9.6 million singleton livebirths among first-time mothers aged 15–49 years from 2016 to 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS Information on infertility treatment use and CCHD was obtained from the health and medical information section of birth certificates, which was completed by healthcare staff after reviewing medical records. Logistic regression models were used to estimate odds ratios (OR) and 95% CI. Entropy balancing weighting analysis and probabilistic bias analysis were also performed. MAIN RESULTS AND THE ROLE OF CHANCE The proportion of births following infertility treatment increased from 1.9% (27 116) to 3.1% (43 510) during the study period. Overall, there were 5287 cases of CCHD resulting in a prevalence of 0.6 per 1000 livebirths. The prevalence was 1.2 per 1000 live births among infertility treatment users (ART: 1.1 per 1000 livebirths; non-ART: 1.3 per 1000 livebirths) while that for naturally conceived births was 0.5 per 1000 livebirths. Compared to naturally conceived births, the use of any infertility treatment (OR: 2.06, 95% CI: 1.82–2.33), either ART (OR: 2.02, 95% CI: 1.73–2.36) or other infertility treatments (OR: 2.12, 95% CI: 1.74–2.33), was associated with higher odds of CCHD after adjusting for maternal and paternal age, race and ethnicity, and education, as well as maternal nativity, marital status, source of payment, smoking status, and pre-pregnancy measures of BMI, hypertension and diabetes. This association did not differ by the type of infertility treatment (ART versus other infertility treatments) (OR: 1.04, 95% CI: 0.82–1.33, P  = 0.712), and was robust to the presence of exposure and outcome misclassification bias and residual confounding. LIMITATIONS, REASONS FOR CAUTION The findings are only limited to livebirths. We did not have the capacity to examine termination data, but differential termination by mode of conception has not been supported by previous studies designed to consider it. Infertility treatment use was self-reported, leading to the potential for selection bias and misclassification for infertility treatment and CCHD. However, the association persisted when systematic bias as well as exposure and outcome misclassification bias were accounted for in the analyses. Information on the underlying etiology of infertility relating to either maternal, paternal, or both factors, data on specific types of ART and other infertility treatments, as well as information on subtypes of CCHD, were all not available. WIDER IMPLICATIONS OF THE FINDINGS In light of the increasing trend in the use of infertility treatment in the USA, and elsewhere, the finding of the current study holds significant importance for the clinical and public health of reproductive-aged individuals. The data show that the use of infertility treatment may expose offspring to elevated odds of severe congenital heart defects such as CCHD studied here. These findings cannot be interpreted causally. While our findings can assist in preconception counseling and prenatal care for pregnancies conceived by either ART or other infertility treatments, they also support some current recommendations that pregnancies resulting from infertility treatments undergo fetal echocardiography screening. STUDY FUNDING/COMPETING INTEREST(S) No funding was sought for the study. The authors declare that they have no conflict of interest. TRIAL REGISTRAION NUMBER N/A [ABSTRACT FROM AUTHOR]

Objective: The study aims to elucidate the impacts of different types of male chromosomal polymorphisms (MCPs) on various outcomes of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment. Methods: This retrospective cohort study included 1442 couples with normal karyotypes, 1442 couples with MCPs, 42 couples with male chromosomal rearrangements (MCRs), and 42 couples with MCRs combined with MCPs who underwent IVF/ICSI treatment at Peking University Third Hospital from 2015 to 2021. The semen quality, embryological outcomes, and clinical outcomes of different groups stratified by karyotypes were compared. Results: For couples undergoing IVF, male inv(9) was associated with a significantly lower sperm viability rate (29.41% vs 34.49%, P = 0.030), a lower progressive motility rate (25.13% vs 30.50%, P = 0.013), and a lower normal fertilization rate (52.41% vs 59.84%, P = 0.014). Male 9qh + was related to a lower sperm viability rate (27.56% vs 34.49%, P = 0.028). No MCPs were observed to compromise clinical outcomes in couples undergoing IVF. For couples undergoing ICSI, no MCPs exhibited an association with poorer semen quality and embryological outcomes. However, Yqh + and DGpstk+ were found to be significantly correlated with an increased likelihood of preterm birth (23.3% vs 9.2%, P = 0.003; 20.0% vs 9.2%, P = 0.041, respectively). In couples with MCRs, the presence of MCPs significantly reduced the sperm viability rate (19.99% vs 30.97%, P = 0.017) and progressive motility rate (8.07% vs 27.85%, P = 0.018). Conclusion: Our study provides detailed evidence for the impacts of various MCPs on IVF/ICSI outcomes, reveals the complexity and heterogeneity of these impacts, and highlights the adverse effects of male inv(9). Synopsis: The impact of different types of male chromosomal polymorphisms on assisted reproductive outcomes is highly heterogeneous, and the adverse effects of inv(9) require vigilance. [ABSTRACT FROM AUTHOR]

Assisted reproduction often involves biological contributions by third parties such as egg/sperm donors, mitochondrial DNA donors, and surrogate mothers. However, these arrangements are also characterised by a biological relationship between the child and at least one intending parent. For example, one or both intending parents might use their own eggs/sperm in surrogacy, or an intending mother might conceive using donor sperm or gestate a donor embryo. What happens when this relationship is absent, as in the case of 'double‐donor surrogacy' arrangements (DDS)? Here, a child is conceived using both donor eggs and sperm, carried by a surrogate, and raised by the commissioning parents. In this paper, I critically examine proposals to allow DDS in the United Kingdom, and the intentionalist justification for treating this practice distinctly (morally and legally speaking) from private adoption. I argue that the intentionalist approach cannot plausibly justify such a distinction and that other approaches to moral parenthood are also unlikely to succeed. [ABSTRACT FROM AUTHOR]

In China, neither reproduction and parenthood by lesbian couples nor their marital status are regulated or protected by law. In 2020, the first legal dispute in China involving a lesbian couple over custody of their joint baby was heard in court. This study examines the legal and ethical issues that lesbian couples confront when they decide to give birth to a child of their own. These challenges begin with regulatory restrictions on their lawful access to assisted reproductive technology and extend to gaps in the legal establishment of parenthood. We found that the lack of access to legitimate reproductive assistance for lesbian couples in China has caused them to make efforts to circumvent laws and regulations to have a child. However, the legislative gaps later led to ethical dilemmas when resolving disputes over parenthood. This study discusses different accounts of establishing and determining natural parenthood in China and concludes by pointing out the urgent need for change in legislative and sociocultural attitudes toward both assisted reproductive technology and same‐sex relationships, mapping the way forward for lesbian couples to obtain better protection of procreation and parenthood before their marriage is culturally accepted and finally legalized. [ABSTRACT FROM AUTHOR]

The typical outcome measure in infertility treatment is the (cumulative) healthy live birth rate per patient or per cycle. This means that those who end the treatment trajectory with a healthy baby in their arms are considered to be successful and those who do not are considered to have failed. In this article, we argue that by adopting the healthy live birth standard as the outcome measure that defines a successful fertility treatment, it becomes an interpretative self‐fulfilling prophecy: those who achieve the goal consider themselves successful and those who do not consider themselves failures. This is regardless of the fact that having children is only one out of many ways to alleviate the suffering related to infertility and that stopping fertility treatment can also be a positive decision to move on to other goals, rather than a form of "giving up," "dropping out," "nonadherence," or failure. We suggest that those seeking fertility treatment would be served better by an alternative outcome measure, which can be equally self‐fulfilling, according to which a successful treatment is one in which people leave the clinic released from the suffering that accompanied their status as infertile when they first entered the clinic. This new outcome measure still implies that walking out with a healthy baby is a positive outcome. What changes is that walking out without a baby can also be a positive outcome, rather than being marked exclusively as a failure. [ABSTRACT FROM AUTHOR]

Abstract Background Advanced maternal age is associated with decreased oocyte quantity and quality and in vitro fertilization (IVF) success rates. This study aimed to investigate whether melatonin supplementation can improve IVF outcomes in women of advanced maternal age by modulating cuproptosis and ferroptosis. Methods This prospective cohort study included 161 women aged 35–45 years undergoing IVF-frozen embryo transfer cycles. Participants were assigned to either melatonin (n = 86, 2 mg daily for ≥ 8 weeks) or control (n = 75) groups. Cumulus cells were analyzed for cuproptosis and ferroptosis-related gene expression. Additional experiments were conducted on the HGL5 human granulosa cell line to assess mitochondrial function and metabolic reprogramming. Results Melatonin supplementation significantly improved IVF outcomes in women aged ≥ 38 years, increasing clinical pregnancy rates (46.0% vs. 20.3%, P

Background: Infertility along with fertility treatments has been reported to have a devastating effect on the well-being of the individuals involved as well as their relationship. So far, the studies exploring the impact on the relationship have mainly focused on heterosexual couples facing infertility and undergoing treatment. There is, therefore, a lack of data on the potential role of sexual orientation, gamete origin, as well as treatment success on the risk of separation after fertility treatment. The purpose of this study was, thus, to explore whether sexual orientation, donation treatment, and fertility success affected the relationship well-being and to explore various separation-related aspects. Methods: We have performed a prospective cohort study of heterosexual and homosexual couples undergoing fertility treatment with autologous and donated gametes in Sweden and followed them for up to 10 years after receiving fertility treatment. In the current follow-up study, 660 individuals have been included. Results: Almost 39% of lesbian couples participating reported having separated as opposed to 11–17% of heterosexual couples undergoing treatment with own or donated gametes. Neither background factors nor treatment success protected against separation. By using the relationship satisfaction ENRICH tool, we were able to demonstrate that dissatisfaction of one of the lesbian spouses or heterosexual spouses undergoing oocyte donation increased significantly the risk of separation 8–10 years after treatment commencement. Conclusion: The findings can be used by fertility clinics to provide relationship tools to the treated couples in order to help them nurture their relationship and decrease the risk of separation in the long run.

Objective To explore the effectiveness of intraovarian injection of platelet-rich plasma(PRP) in the treatment of patients with diminished ovarian reserve(DOR), aiming to provide new diagnostic and therapeutic ideas for the treatment. Methods A total of 22 patients with DOR who underwent autologous PRP ovarian injection at the Reproductive Medical and Genetic Center of Qinzhou Maternal and Child Health Hospital from January 2021 to December 2023 were collected. Among them, 12 patients underwent assisted reproductive technology for pregnancy. The patient′s anti-Müllerian hormone (AMH), antral follicle count (AFC), basal follicle-stimulating hormone (FSH), basal luteinizing hormone (LH) and basal estradiol (E2) levels were observed. Results The levels of AMH, AFC, basal FSH, basal LH and basal E2 in 22 patients improved after treatment compared with those before treatment. Of the 12 patients who received assisted reproduction, 2 had IVF cycle canceled due to poor ovarian reaction. Ten patients obtained embryos, of which 5 obtained high-quality embryos. Conclusion Intraovarian injection of autologous PRP can effectively improve ovarian reserve function in patients with DOR.

This piece analyzes the way in which women that froze, are considering freezing or are freezing their eggs in Spain think critically about broader reproductive politics in Spain and about assisted reproduction. Drawing partially on previous studies around egg freezing, Thomas Lemke has suggested that cryopreservation practices represent a "politics of suspension" characterized by both reversibility and disposition, and concomitant with broader political inaction (Lemke in Sci Technol Hum Values 48(4):1–27, 2021). Drawing on feminist literature, and on how some of these women think about motherhood, it is relevant to emphasize this 'suspension of politics' that takes place along with a "politics of suspension," meaning that certain matters (such as reproduction and its postponement) are only to be dealt with privately and individually, through marketized fertility preservation programs in this case. Some of the women interviewed describe these programs as useful tools within a problematic context: technologies that give time in a context that leaves them on their own to figure out motherhood (or its absence) in the midst of uncertainty and loneliness. This paper shows their critical views on these matters, while reflecting on how their experiences and desires become increasingly imbricated with the fertility industry in the making of their reproductive biographies (Perler and Schurr in Body Soc 27(3): 3–27, 2021). [ABSTRACT FROM AUTHOR]

Abstract Damage from ice and potential toxicity of ice-inhibiting cryoprotective agents (CPAs) are key issues in assisted reproduction of humans, domestic and research animals, and endangered species using cryopreserved oocytes and embryos. The nature of ice formed in bovine oocytes (similar in size to oocytes of humans and most other mammals) after rapid cooling and during rapid warming was examined using synchrotron-based time-resolved x-ray diffraction. Using cooling rates, warming rates and CPA concentrations of current practice, oocytes show no ice after cooling but always develop large ice fractions—consistent with crystallization of most free water—during warming, so most ice-related damage must occur during warming. The detailed behavior of ice at warming depended on the nature of ice formed during cooling. Increasing cooling rates allows oocytes soaked as in current practice to remain essentially ice free during both cooling and warming. Much larger convective warming rates are demonstrated and will allow routine ice-free cryopreservation with smaller CPA concentrations. These results clarify the roles of cooling, warming, and CPA concentration in generating ice in oocytes and establish the structure and grain size of ice formed. Ice formation can be eliminated as a factor affecting post-warming oocyte viability and development in many species, improving outcomes and allowing other deleterious effects of the cryopreservation cycle to be independently studied.

Abstract Background This study was designed to evaluate pregnancy outcomes between morulae transferred on day 4 (D4) and blastocysts transferred on day 5 (D5). Methods From September 2017 to September 2020, 1963 fresh transfer cycles underwent early follicular phase extra-long protocol for assisted conception in our fertility center were divided into D4 (324 cases) and D5 (1639 cases) groups, and the general situation and other differences of patients in both groups were compared. To compare the differences in pregnancy outcomes, the D4 and D5 groups were further divided into groups A and B based on single and double embryo transfers. Furthermore, the cohort was divided into two groups: those with live births (1116 cases) and those without (847 cases), enabling a deeper evaluation of the effects of D4 or D5 transplantation on assisted reproductive outcomes. Results In single embryo transfer, there was no significant difference between groups D4A and D5A (P > 0.05). In double embryo transfer, group D4B had a lower newborn birthweight and a larger proportion of low birthweight infants (P 0.05). Conclusion When factors such as working life and hospital holidays are being considered, D4 morula transfer may be a good alternative to D5 blastocyst transfer. Given the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) success rate and risk of twin pregnancy, D4 morula transfer requires an adapted decision between single and double embryo transfer, although a single blastocyst transfer is recommended for the D5 transfer in order to decrease the twin pregnancy rate. In addition, age, endometrial thickness and other factors need to be taken into account to personalize the IVF program and optimize pregnancy outcomes.

The large amount of excess adipose tissue affects negatively every single step of the assisted reproductive treatment process – from the controlled ovarian hyperstimulation (COH) to obstetric complications and health consequences for the fetus. A number of scientific data show correlation between impaired clinical pregnancy rates (CPR) and obese patients maintaining high body mass index (BMI). The debate whether high proportion of body fat negatively affects oocyte quality or only impacts endometrial receptivity remains open.

BackgroundPer- and polyfuoroalkyl substances (PFAS) are categorized as persistent organic pollutants and commonly detected in humans, and their toxicity has attracted widespread attention. However, few studies have reported comparison of PFAS levels and potential factors between women pregnant using assisted reproduction technology (ART) and women pregnant naturally. ObjectiveTo analyze and compare serum concentrations and sociodemographic determinants of PFAS in pregnant women conceiving through ART and conceiving naturally from Shanghai. MethodsBased on the China National Birth Cohort (CNBC) in Shanghai from 2017 to 2019, 333 pregnant women conceiving through ART and 689 pregnant women conceiving naturally were recruited during the same period as study subjects. The concentrations of 32 PFAS were measured in early-pregnancy serum of all pregnant women, and four PFAS with the highest co-exposure levels in both groups were included in the subsequent analysis. Multiple linear regression models were performed to evaluate the associations of sociodemographic factors with serum PFAS concentrations in the two groups respectively. Beta coefficients and 95% confidence intervals (CI) were exponentiated to calculate the ratio of the geometric mean (GM) of PFAS concentrations after each unit change in the independent variable.ResultsPerfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), 6∶2 chlorinated polyfluoroethersulfonic acid (6∶2 Cl-PFESA), and perfluorohexanesulfonic acid (PFHxS) were four major PFAS in serum of pregnant women conceiving through ART and conceiving naturally, and the concentrations of PFOA, PFOS, and 6∶2 Cl-PFESA were higher in pregnant women conceiving through ART than in pregnant women conceiving naturally (P 300000 CNY had lower serum concentrations of PFOA [GM ratio (95%CI): 0.82 (0.72, 0.95) and 0.89 (0.81, 0.97), respectively] and PFHxS [GM ratio (95%CI): 0.66 (0.51, 0.86) and 0.77 (0.66, 0.90), respectively] than those women whose household annual income

BackgroundPesticide exposure may impact the reproductive health of women undergoing assisted reproductive technology (ART). However, data on pesticide exposure levels in women undergoing ART in China are scarce, and current research on influencing factors is limited. ObjectiveTo evaluate the preconceptional pesticide exposure levels and identify potential determinants among women undergoing ART. MethodsThis study was designed as a cross-sectional survey and recruited 508 women undergoing ART from July 2017 to December 2018 at the fertility clinic of the International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Gas chromatography/liquid chromatography-tandem mass spectrometry was used to determine the metabolite concentrations of organophosphate pesticides (OPs), pyrethroid pesticides (PYRs), and neonicotinoid pesticides (NEOs) in urine. The sum of molar concentrations of the three pesticide classes (∑2OPs, ∑2PYRs, and ∑2NEOs) were calculated. A questionnaire was used to collect demographic characteristics, dietary habits, and behavioral information. Multiple linear regression was employed to analyze the associations of demographic characteristics, dietary habits, and behavioral variables with the concentrations of pesticide metabolites in urine among the participants. ResultsThe median creatinine-adjusted concentrations of ∑2OPs, ∑2PYRs, and ∑2NEOs in this study were 419.77, 2.95, and 20.36 nmol·g−1, respectively. The multiple linear regression results showed that the urinary concentration of ∑2OPs was 42.88% higher in the participants with daily vegetable intake than in those who consumed vegetables ≤3 d per week (P

Abstract Purpose The study aimed to investigate the potential influence of COVID-19 infection on embryo implantation and early development in women undergoing frozen embryo transfer (FET), with a specific focus on infections occurring at different periods around FET. Methods A retrospective analysis was performed on women who had undergone FET during a period marked by a significant surge in COVID-19 infection in Shanghai. All enrolled women experienced their first documented COVID-19 infection around the time of FET, ensuring that infections did not occur prior to oocyte retrieval. Participants were categorized into six groups based on the timing of infection: uninfected, ≥ 60 days,

Abstract The aim of our study was to evaluate if the response to follicular GnRH agonist (GnRHa) trigger be used to predict intracycle ovarian response in GnRH antagonist cycles among women undergoing fertility preservation IVF. We conducted a prospective study of 146 GnRH antagonist oocyte pickup (OPU) cycles to evaluate GnRHa stimulation test (GAST). On day 2 of the cycle, basal E2 were measured, followed by injection of 0.2 mg GnRHa as part of the initial ovarian stimulation. 12 h later blood sampling was repeated (GAST E3). E2 response was used as test parameter. The major outcome was the number of mature cryopreserved oocytes. We found a linear correlation between both GAST E3 level and GAST E3/E2 ratio and number of M2 oocytes. ROC curve analysis of GAST E3, GAST E3/E2 ratio, AFC and day 3 FSH for > 15 M2 and 15 M2 oocytes, AUC value of 0.8. Patients with GAST E3 ≤ 384 pmol/l has 58.6% risk to obtain 708 pmol/l have 66% chance for freezing > 15 oocytes. The response to single GnRHa administration during GnRH antagonist cycle can be used as biomarker of ovarian reserve. This simple, widely available marker, which reflect the estradiol response of small follicles, might predict the response of the specific cycle, and can potentially be used to adjust the treatment dose. Trial registration number: 0304-20-ASF.

Objective: To explore the use of weekly continuous dosing of corifollitropin α in DuoStim cycles. Design: Pilot-matched case-control study. Setting: Private fertility center. Patient(s): Cases were defined as DuoStim cycles performed from November 2022 to May 2023 receiving weekly continuous dosing of corifollitropin α (n = 15). Controls were chosen from a database comprising DuoStim cycles conducted at our institution during the years 2021/2022. Matching was done on a 1-to-1 basis, based on antimüllerian hormone values (±0.4 pmol/L) and age (n = 15). Intervention(s): Injections of corifollitropin α once every 8 days, along with uninterrupted oral administration of micronized progesterone 200 mg/d (for luteinizing hormone surge prevention) throughout the follicular and luteal phases for ovarian stimulation. Oocyte retrieval. Main outcome measure(s): Total number of cumulus-oocyte complexes and metaphase II oocytes obtained in follicular + luteal phase stimulation. Secondary outcomes evaluated fertilization rates, number of blastocysts, days of stimulation, number of injectables required, and gonadotropin cost. Result(s): The study group achieved similar total oocyte and MII yield vs. daily follicle-stimulating hormone protocol (13.3 ± 6.9 vs. 11.8 ± 6.1 and 10.4 ± 6.3 vs. 9.2 ± 4.6, respectively). All secondary outcomes showed no significant differences. The study group experienced a significant reduction of injections to complete a DuoStim cycle (4.5 ± 1.4 vs. 35.2 ± 12.2; mean deviation -30.7; 95% confidence interval, −37.5– to −23.9)]. Conclusion(s): Corifollitropin α on a weekly basis throughout a DuoStim cycle yields an equivalent number of oocytes as standard daily follicle-stimulating hormone administration while drastically reducing the number of required injections. Trial registration number: NCT05815719. EudraCT: 2022-003177-32.

Blastocyst vitrification has significantly improved embryo transfer methods, leading to higher implantation success rates and better pregnancy outcomes in subsequent frozen embryo transfer cycles. This study aimed to simulate the transcriptional changes caused by vitrifying human blastocysts using mouse blastocysts as a model and to further investigate these changes' effects. Utilizing a human vitrification protocol, we implanted both vitrified and fresh embryos into mice. We observed the implantation success rates and performed transcriptomic analysis on the blastocysts. To validate the results from messenger RNA sequencing, we conducted reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) to measure the expression levels of specific genes. Based on mRNA profiling, we predicted the microRNAs responsible for the regulation and used qPCR basic microRNA assays for validation. Our observations revealed a higher implantation success rate for vitrified embryos than fresh embryos. Transcriptomic analysis showed that vitrified–warmed blastocysts exhibited differentially expressed genes (DEGs) primarily associated with thermogenesis, chemical carcinogenesis-reactive oxygen species, oxidative phosphorylation, immune response, and MAPK-related signaling pathways. RT-qPCR confirmed increased expression of genes such as Cdk6 and Nfat2, and decreased expression of genes such as Dkk3 and Mapk10. Additionally, gene-microRNA interaction predictions and microRNA expression analysis identified twelve microRNAs with expression patterns consistent with the predicted results, suggesting potential roles in uterine epithelial cell adhesion, trophectoderm development, invasive capacity, and immune responses. Our findings suggest that vitrification induces transcriptomic changes in mouse blastocysts, and even small changes in gene expression can enhance implantation success. These results highlight the importance of understanding the molecular mechanisms underlying vitrification to optimize embryo transfer techniques and improve pregnancy outcomes. [ABSTRACT FROM AUTHOR]

The Mediterranean Diet, characterized by high consumption of plant-based foods, olive oil, moderate intake of fish and poultry, and low consumption of red meat and processed foods, has been suggested to improve assisted reproductive technology (ART) outcomes. This narrative review aimed to summarize and synthesize the evidence from observational studies on the associations between preconception adherence to the Mediterranean Diet and ART outcomes. PubMed/MEDLINE, Embase, ScienceDirect, Google Scholar, and Web of Science databases were searched to identify relevant studies. Seven observational studies (n = 2321 women undergoing ART) were included. Adherence to the Mediterranean Diet was assessed using food frequency questionnaires with 6–195 items. Three studies found that higher Mediterranean Diet scores were associated with improved clinical pregnancy rates (OR 1.4, 95% CI 1.0–1.9; RR 1.98, 95% CI 1.05–3.78) or live birth rates (RR 2.64, 95% CI 1.37–5.07). Two studies showed a positive effect on embryo yield (p = 0.028) and ovarian response. However, two studies reported no significant associations with ultimate ART success, and four studies found no effects on oocyte and embryo number or quality. The heterogeneity in study designs, Mediterranean Diet assessment methods, and ART protocols limited the strength of conclusions. Evidence for the effects of greater adherence to the Mediterranean Diet on ART outcomes is limited but promising. Future research should focus on conducting randomized controlled trials with standardized Mediterranean Diet assessment methods to establish causal relationships between Mediterranean Diet adherence and ART outcomes, and to elucidate potential mechanisms of action. [ABSTRACT FROM AUTHOR]

Damage from ice and potential toxicity of ice-inhibiting cryoprotective agents (CPAs) are key issues in assisted reproduction of humans, domestic and research animals, and endangered species using cryopreserved oocytes and embryos. The nature of ice formed in bovine oocytes (similar in size to oocytes of humans and most other mammals) after rapid cooling and during rapid warming was examined using synchrotron-based time-resolved x-ray diffraction. Using cooling rates, warming rates and CPA concentrations of current practice, oocytes show no ice after cooling but always develop large ice fractions—consistent with crystallization of most free water—during warming, so most ice-related damage must occur during warming. The detailed behavior of ice at warming depended on the nature of ice formed during cooling. Increasing cooling rates allows oocytes soaked as in current practice to remain essentially ice free during both cooling and warming. Much larger convective warming rates are demonstrated and will allow routine ice-free cryopreservation with smaller CPA concentrations. These results clarify the roles of cooling, warming, and CPA concentration in generating ice in oocytes and establish the structure and grain size of ice formed. Ice formation can be eliminated as a factor affecting post-warming oocyte viability and development in many species, improving outcomes and allowing other deleterious effects of the cryopreservation cycle to be independently studied. [ABSTRACT FROM AUTHOR]

Objective: To investigate fetal growth trajectories and risks of small and large for gestational age (SGA and LGA), and macrosomia in pregnancies after fresh and frozen embryo transfer (ET), and natural conception (NC). Design: Longitudinal population‐based cohort study. Setting: Swedish national registers. Population: A total of 196 008 singleton pregnancies between 2013 and 2017. Methods: Of all singleton pregnancies resulting in live births in the Swedish Pregnancy Register, 10 970 fresh ET, 6520 frozen ET, and 178 518 NC pregnancies with ultrasound data were included. A general least squares model was used to examine the effect of fresh or frozen ET on fetal growth while adjusting for confounders. Main Outcome Measures: Fetal growth velocity. SGA, LGA and macrosomia. Results: At 120 days, fetal weights were lower in fresh ET pregnancies compared with NC pregnancies. Thereafter fresh ET as well as FET fetuses had higher fetal weights than NC fetuses, with no differences between themselves until the second trimester. From 210 days, FET fetuses were heavier than fresh ET fetuses, whereas fresh ET fetuses had lower fetal weights than NC fetuses from 245 days. After fresh ET, SGA was more frequent, whereas LGA and macrosomia were less frequent, than after FET. Conclusions: This study gives new insights into the differences in fetal growth dynamics between fresh and frozen ET and NC pregnancies. Clinically relevant differences in proportions of SGA, LGA and macrosomia were observed. Linked article: This article is commented on by Paolo Ivo Cavoretto pp. 1238–1239 in this issue. To view this mini commentary visit https://doi.org/10.1111/1471‐0528.17810. [ABSTRACT FROM AUTHOR]

The use of hormonal contraception can be considered to aid in the timing of assisted reproductive technology cycles, reduce the risk of ovarian cysts at in vitro fertilization cycle initiation, and optimize visualization before hysteroscopy. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the current practice and views on (expanded) carrier screening ((E)CS) among healthcare professionals in medically assisted reproductive (MAR) practices in Europe? SUMMARY ANSWER The findings show a limited support for ECS with less than half of the respondents affiliated to centres offering ECS, and substantial variation in practice between centres in Europe. WHAT IS KNOWN ALREADY The availability of next-generation sequencing, which enables testing for large groups of genes simultaneously, has facilitated the introduction and expansion of ECS strategies, currently offered particularly in the private sector in the context of assisted reproduction. STUDY DESIGN, SIZE, DURATION A cross-sectional survey evaluating practice and current views among professionals working in MAR practice in different European countries was designed using the online SurveyMonkey tool. The web-based questionnaire included questions on general information regarding the current practice of (E)CS in MAR and questions on what is offered, to whom the test is offered, and how it is offered. It consisted mostly of multiple-choice questions with comment boxes, but also included open questions on the respondents' attitudes/concerns relevant to (E)CS practice, and room to upload requested files (e.g. guidelines and gene panels). In total, 338 responses were collected from 8 February 2022 to 11 April 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS The online survey was launched with an invitation email from the ESHRE central office (n = 4889 emails delivered) and the European Society of Human Genetics (ESHG) central office (n = 1790 emails delivered) sent to the ESHRE and ESHG members, and by social media posts. The survey was addressed to European MAR centres or gamete banks and to centres located in non-European countries participating in the European IVF-monitoring Consortium. Two reminder emails were sent. After exclusion of 39 incomplete responses received (e.g. only background information), 299 respondents from 40 different countries were included for analyses. MAIN RESULTS AND THE ROLE OF CHANCE Overall, 42.5% (127/299) of respondents were affiliated to centres offering ECS. The perceived responsibility to enable prospective parents to make informed reproductive decisions and preventing suffering/burden for parents were the main reasons to offer ECS. A single ECS panel is offered by nearly 45% (39/87 received answers) of the centres offering ECS, 25.3% (22/87) of those centres offer a selection of ECS panels, and 29.9% (26/87) offer whole exome sequencing and a large in silico panel. Different ranges of panel sizes and conditions were included in the ECS panel(s) offered. Most of the respondents (81.8%; 72/88 received answers) indicated that the panels they offer are universal and target the entire population. Pathogenic variants (89.7%; 70/78 received answers), and to a lesser extent, likely pathogenic variants (64.1%%; 50/78 received answers), were included in the ECS report for individuals and couples undergoing MAR with their own gametes. According to 87.9% (80/91 received answers) of the respondents, patients have to pay to undergo an ECS test. Most respondents (76.2%; 61/80 received answers) reported that counselling is provided before and after the ECS test. Preimplantation genetic testing, the use of donor gametes, and prenatal diagnostic testing were the three main reproductive options discussed with identified carrier couples. The main reason, according to the respondents, for not offering ECS in their centre, was the lack of professional recommendations supporting ECS (52.5%; 73/139 received answers) and the high cost for couples or reimbursement not being available (49.6%; 69/139). The challenges and moral dilemmas encountered by the respondents revolved mainly around the content of the offer, including the variants classification and the heterogeneity of the panels, the counselling, and the cost of the test. LIMITATIONS, REASONS FOR CAUTION Although the total number of respondents was acceptable, the completion rate of the survey was suboptimal. In addition, the heterogeneity of answers to open-ended questions and the ambiguity of some of the answers, along with incomplete responses, posed a challenge in interpreting survey results. It is also plausible that some questions were not easily understood by the respondents. For this reason, response and non-response bias are acknowledged as further limitations of the survey. WIDER IMPLICATIONS OF THE FINDINGS The results of this survey could aid in identifying potential challenges or areas for improvement in the current practice of ECS in the MAR field and contribute to the discussion on how to address them. The results underline the need to stimulate a more knowledge-based debate on the complexity and the pros and cons of a possible implementation of ECS in MAR. STUDY FUNDING/COMPETING INTEREST(S) All costs relating to the development process were covered from European Society of Human Reproduction and Embryology and European Society of Human Genetics funds. There was no external funding of the development process or manuscript production. A.C. is full-time employee of Juno Genetics. L.H. declared receiving a research grant during the past 36 months from the Netherlands Organisation for Health Research and Development. She has also participated in a Health Council report of the Netherlands on preconception carrier screening and collaborated with the VSOP Dutch Genetic Alliance (patient umbrella organization on rare and genetic disorders). L.H. and C.v.E. are affiliated with Amsterdam University Medical Centre, a hospital that offers ECS in a non-commercial setting. R.V. received honoraria for presentations from Merck Academy and is unpaid board member of the executive committee of the Spanish Fertility Society. The other authors had nothing to disclose. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions Commercial products currently available for sperm selection utilizing hyaluronic acid (HA) binding prior to intracytoplasmic sperm injection (ICSI) are widely used but have some disadvantages. To potentially circumvent these limitations, we compared ICSI using a self‐made hyaluronic acid (smHA) reagent with ICSI using SpermSlow.The binding of the reagents to spermatozoa on plastic‐ or glass‐bottom dishes was quantitated using spermatozoa that were isolated by density‐gradient centrifugation and swim‐up procedures (N = 10/group). Additionally, we investigated the relationship between the HA reagent used prior to ICSI and clinical outcomes after assisted reproduction with HA‐ICSI (N = 81).The smHA reagent exhibited extremely stable binding to human spermatozoa. The binding time of spermatozoa was significantly longer in the smHA reagent than in SpermSlow on both plastic and glass dishes (plastic: 60.0 ± 0.0 min vs. 2.7 ± 5.9 min, P < 0.001; glass: 60.0 ± 0.0 min vs. 2.5 ± 1.8 min, P < 0.001). There were no significant differences in the normal fertilization rate between HA‐ICSI with the smHA reagent (128/160, 80.0%) and HA‐ICSI with SpermSlow (171/231, 74.0%, P = 0.184). The frequency of the blastocyst development from the HA‐ICSI‐derived zygote was significantly higher with the smHA reagent (74/101, 73.3%) than with SpermSlow (76/131, 58.0%, P = 0.019). The rates of biochemical pregnancy, clinical pregnancy, fetal heart movement, live birth, and miscarriage were not significantly different between HA‐ICSI with the smHA reagent and HA‐ICSI with SpermSlow.The blastulation rate was higher for HA‐ICSI with the smHA reagent as compared with SpermSlow. Clinical outcomes, excluding blastulation, after HA‐ICSI were the same using smHA reagent and using SpermSlow. Spermatozoa binding to the smHA reagent was not attenuated over a 60‐min time course. In conclusion, this reagent may shorten and simplify HA‐ICSI procedures because smHA can be used with any dish material, making it easier to observe the spindle or assess intracytoplasmic morphology. [ABSTRACT FROM AUTHOR]

This article reads the uptake of facial-matching algorithms by fertility clinics in Spain through the lens of ‘the fertility fix’: a software fix to the social reconfiguration of kinship and a fixed capital investment made by competing fertility companies and firms. ‘The fertility fix’ is proposed as a critical, ethical lens through which to situate algorithmic facial-matching in assisted reproduction in the context of the racial politics of the face and phenotype and the spatial politics of market expansion. While an ‘infertility crisis’ is often mentioned when explaining the growth of the assisted reproductive technologies (ARTs) industry, the use of donated reproductive cells is tied up in societal, ecological and economic shifts. Combining Software Studies analysis with Marxist Feminist and trans*feminist perspectives on shifting re/production dynamics, the article details the role of computational technologies in promoting certain ideas and beliefs about family and fixing certain territories of capital flow. [ABSTRACT FROM AUTHOR]

Background: This study was designed to evaluate pregnancy outcomes between morulae transferred on day 4 (D4) and blastocysts transferred on day 5 (D5). Methods: From September 2017 to September 2020, 1963 fresh transfer cycles underwent early follicular phase extra-long protocol for assisted conception in our fertility center were divided into D4 (324 cases) and D5 (1639 cases) groups, and the general situation and other differences of patients in both groups were compared. To compare the differences in pregnancy outcomes, the D4 and D5 groups were further divided into groups A and B based on single and double embryo transfers. Furthermore, the cohort was divided into two groups: those with live births (1116 cases) and those without (847 cases), enabling a deeper evaluation of the effects of D4 or D5 transplantation on assisted reproductive outcomes. Results: In single embryo transfer, there was no significant difference between groups D4A and D5A (P > 0.05). In double embryo transfer, group D4B had a lower newborn birthweight and a larger proportion of low birthweight infants (P < 0.05). The preterm delivery rate, twin delivery rate, cesarean delivery rate, and percentage of low birthweight infants were lower in the D5A group than in the D5B group (P < 0.05). Analysis of factors influencing live birth outcomes further confirmed the absence of a significant difference between D4 and D5 transplantation in achieving live birth (P > 0.05). Conclusion: When factors such as working life and hospital holidays are being considered, D4 morula transfer may be a good alternative to D5 blastocyst transfer. Given the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) success rate and risk of twin pregnancy, D4 morula transfer requires an adapted decision between single and double embryo transfer, although a single blastocyst transfer is recommended for the D5 transfer in order to decrease the twin pregnancy rate. In addition, age, endometrial thickness and other factors need to be taken into account to personalize the IVF program and optimize pregnancy outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND Girls with Turner syndrome (TS) lack a partial or complete sex chromosome, which causes an accelerated decline of their ovarian reserve. Girls have to deal with several dilemmas related to their fertility, while only a limited number of them are referred to a fertility specialist and counselled about options of family planning on time. OBJECTIVE AND RATIONALE This scoping review provides an update of the literature on fertility in girls with TS throughout their lifespan and aims to propose a clinical practice guideline on fertility in TS. SEARCH METHODS Databases of PubMed, Embase, and Web of science were searched using the following key terms: Turner syndrome, fertility, puberty, pregnancy, sex-hormones, karyotype, fertility preservation, assisted reproductive techniques, and counselling, alongside relevant subject headings and synonymous terms. English language articles published since 2007 were critically reviewed. Pregnancies after using donated oocytes and data about girls with TS with Y-chromosomal content were excluded. OUTCOMES This search identified 1269 studies of which 120 were extracted for the review. The prevalence of natural conception ranged from 15% to 48% in women with 45,X/46,XX, 1% to 3% in women with 45,X, and 4% to 9% in women with other TS karyotypes. When assessing a girl's fertility potential, it was crucial to determine the karyotype in two cell lines, because hidden mosaicism may exist. In addition to karyotype, assessment of anti-Müllerian hormone (AMH) played a significant role in estimating ovarian function. Girls with AMH above the detection limit were most likely to experience spontaneous thelarche, menarche, and ongoing ovarian function during the reproductive lifespan. Fertility preservation became more routine practice: vitrification of oocytes was reported in 58 girls with TS and a median of five oocytes were preserved per stimulation. Ovarian tissue cryopreservation has demonstrated the presence of follicles in approximately 30% of girls with TS, mostly in girls with mosaic-TS, spontaneous puberty, and AMH above the detection limit. Although girls and their parents appreciated receiving counselling on fertility in TS, only one in ten girls with TS received specialized counselling. Unfamiliarity with fertility preservation techniques or uncertainties regarding the eligibility of a girl for fertility preservation constituted barriers for healthcare professionals when discussing fertility with girls with TS. WIDER IMPLICATIONS There currently is a high demand for fertility preservation techniques in girls with TS. A reliable prognostic model to determine which girls with TS might benefit from fertility preservation is lacking. Only a minority of these girls received comprehensive fertility counselling on the full spectrum of fertility, including uncertainties of fertility preservation, pregnancy risks, and alternatives, such as adoption. Fertility preservation could be a viable option for girls with TS. However, the question remains whether enough oocytes can be obtained for a realistic prospect of a live birth. It is important that girls and parents are empowered with the necessary information to make a well-informed decision. [ABSTRACT FROM AUTHOR]

Accurate assessment of embryo development is of paramount importance for the success of Assisted Reproductive Technologies (ART). Traditional methods predominantly rely on subjective embryo morphological evaluations, lacking objectivity and real-time capabilities. Time-lapse Technology (TLT) offers a more stable incubation environment, facilitating dynamic monitoring of embryo development, analysis, and modeling of dynamic parameters during different developmental stages for predicting embryo implantation potential. However, dynamic parameters often require manual annotations, introducing subjective bias and exhibiting significant disparities in data modeling capabilities, deviating from real-world scenarios, especially in the analysis of chromosomal ploidy. With the continuous advancement of Artificial Intelligence (AI), the integration of TLT and AI holds promise in reducing manual annotation time in TLT, enhancing embryo implantation rates, and chromosomal ploidy prediction. This review aims to explore the application of TLT combined with AI in morphological and dynamic parameters for assessing embryo implantation potential and chromosomal ploidy. [ABSTRACT FROM AUTHOR]