Human Reproduction Research Articles

Study of Masanumasika Garbha Vikas Krama (Monthwise Devlopment during Pregnancy) in Context to Embryogenesis and Foetal Development

Sushruta Samhita is a significant Ayurvedic text on human anatomy and physiology. It provides detailed information on Garbha Vriddhi and Vikas Krama (Growth and Development) Various texts express different opinions regarding Garbha Utpatti (Fertilization) and Garbha Vriddhi. Acharyas have explained Garbhini Lakshana (Gravida symptoms) also. Which are helpful in early pregnancy diagnosis. Charaka has explained month wise symptoms in Garbhini during pregnancy. Now days, obstetrics is a fundamental field of study dealing with human reproduction, offering comprehensive information on fetal growth and development. Contemporary obstetrics has undergone extensive research and development. Neonatal mortality and fetal fatality are always the causes of concern. Samhitas provide pertinent resources on these topics. Acharyas have discussed about these in the reference of Garbhini. It takes a great deal of research and debate to comprehend the old Garbha Utpatti or Garbhavkranti notion. Examining both contemporary and Ayurvedic literature will aid in learning more about this. The goal of this study is to compare and clarify the concepts of embryogenesis from antiquity to the present

REPRODUÇÃO ASSISTIDA: DESAFIOS E AVANÇOS DAFERTILIZAÇÃO IN VITRO E INSEMINAÇÃO ARTIFICIAL COM PERSPECTIVAS ATUAIS E FUTURAS

Assisted human reproduction (AHR) is a set of medical techniques that enable human reproduction with assistance, contributing to cases of infertility, advanced age, same-sex couples, independent gestation, and family planning. The main techniques are artificial insemination and in vitro fertilization (IVF). This exploratory-descriptive study investigates the challenges faced by these couples, as well as recent advancements and future perspectives of these techniques. The analysis includes a review of recent literature, focusing on advancements such as improved ovarian stimulation protocols and embryo selection, as well as the impact of emerging technologies. The study also addresses the variable success rates, procedure costs, and ethical issues involved. It is expected that ongoing innovations will improve success rates, reduce risks, and enhance the accessibility of these treatments. Currently, the technique of intracytoplasmic sperm injection (ICSI) is widely used. Despite the challenges, AHR has enabled infertile couples to realize their dream of parenthood. With scientific and technological advancements, it is anticipated that AHR techniques will continue to evolve to benefit more and more couples wishing to have children.

Chronic psychosocial stress affects insulin-like growth factor 1 and its receptors in mouse ovaries.

Context Chronic psychosocial stress negatively affects folliculogenesis and oogenesis. Intraovarian mechanisms mediating these effects are poorly understood. Aims This work aimed to find out how chronic psychosocial stress affects ovarian IGF1 and its receptor (IGF1R), as well as Igf1 and Igf1r gene expression in cumulus-oocyte complexes (COCs). It also aimed to address possible protective effects of gonadotropin stimulation on IGF1 ovarian signalling. Methods Female CD1 mice experienced chronic psychosocial stress of 11-day isolation followed by overcrowding for 10days. To verify the model, blood corticosterone levels and the quality of oocytes were evaluated in stressed females. The levels of IGF1/IGF1R, blood IGF1 concentration, and expression of Igf1 /Igf1r in the ovaries were compared in stressed and unstressed females. Key results Psychosocial stress caused an elevation of corticosterone level, which was alleviated by gonadotropin treatment. The stressed mice showed a decreased IGF1 level in the ovaries and a decreased expression of Igf1 and Igf1r in COCs. In the unstressed females, gonadotropin injection decreased the expression of Igf1 and Igf1r ; in the stressed females, the same treatment increased Igf1r expression. Neither stress nor ovarian stimulation with gonadotropins affected the serum IGF1 level. Conclusions Psychosocial stress suppresses IGF1 signalling in the ovaries. Gonadotropin treatment modulates these effects differently in stressed and unstressed animals. Implications The results may have translational value for human reproduction. Ovarian IGF1 can be considered a candidate for further improvement of IVF results in women under conditions of chronic stress.

The ENDOMIX perspective: how everyday chemical mixtures impact human health and reproduction by targeting the immune system†.

Endocrine disruptor chemicals (EDCs) are natural and synthetic compounds found ubiquitously in the environment that interfere with the hormonal-immune axis, potentially impacting human health and reproduction. Exposure to EDCs has been associated with numerous health risks, such as neurodevelopmental disorders, metabolic syndrome, thyroid dysfunction, infertility, and cancers. Nevertheless, the current approach to establishing causality between EDCs and disease outcomes has limitations. Epidemiological and experimental research on EDCs faces challenges in accurately assessing chemical exposure and interpreting non-monotonic dose response curves. In addition, most studies have focused on single chemicals or simple mixtures, overlooking complex real-life exposures and EDC mechanistic insights, in particular regarding their impact on the immune system. The ENDOMIX project, funded by the EU's Horizon Health Program, addresses these challenges by integrating epidemiological, risk assessment, and immunotoxicology methodologies. This systemic approach comprises the triangulation of human cohort, in vitro, and in vivo data to determine the combined effects of EDC mixtures. The present review presents and discusses current literature regarding human reproduction in the context of immunotolerance and EDC mode of action. It further underscores the ENDOMIX perspective to elucidate the impact of EDCs on immune-reproductive health.

Current Issues of Cryopreservation and Storage of Human Reproductive Biomaterial

With the development of assisted reproductive technologies (ART), contracts covering cryopreservation and the storage of germ cells, as well reproductive organ tissues and embryos are beginning to find wide practical application. Parties to such contracts are faced with questions not currently set out in the current legislation of the Russian Federation. This aim of this article is to identify legal models capable of resolving the most pressing issues arising from these contracts. It is proposed that the following types of biomaterial be reviewed as a continuation of the human body: reproductive biomaterial extracted from the human body in the aims of subsequent reintroduction, and capable of fulfilling that biological function for which it is designated; as well as material aimed at restoration or improvement of organ function. Any intervention upon such biomaterial should be qualified as intervention upon human health. Thus any medical organization found to be in violation of its obligation to preserve health must compensate for any damage caused to a patient’s reproductive health - as set out in the rules of chapter 59 of the Civil Code of the Russian Federation. The author suggests the notion of “abandoned biomaterial” be incorporated in Russian legislation. “Abandoned biomaterial” presupposes the termination of the rights of a person to this biomaterial and enables the medical organization, while ensuring its preservation, to utilize such biomaterial or to use it for research purposes. This would ensure the protection of human rights and legitimate the interests of the contracting party in the event of any violation of the terms of the contract by the client. The author also proposes legal models for the resolution of conflicts related to the plurality of contractual parties, as well as to postmortem human reproduction.

Exploring the black box of human reproduction: endometrial organoids and assembloids - generation, implantation modeling, and future clinical perspectives

One of the critical processes in human reproduction that is still poorly understood is implantation. The implantation of an early human embryo is considered a significant limitation of successful pregnancy. Therefore, researchers are trying to develop an ideal model of endometrium in vitro that can mimic the endometrial micro-environment in vivo as much as possible. The ultimate goal of endometrial modeling is to study the molecular interactions at the embryo-maternal interface and to use this model as an in vitro diagnostic tool for infertility. Significant progress has been made over the years in generating such models. The first experiments of endometrial modeling involved animal models, which are undoubtedly valuable, but at the same time, their dissimilarities with human tissue represent a significant obstacle to further research. This fact led researchers to develop basic monolayer coculture systems using uterine cells obtained from biopsies and, later on, complex and multilayer coculture models. With successful tissue engineering methods and various cultivation systems, it is possible to form endometrial two-dimensional (2D) models to three-dimensional (3D) organoids and novel assembloids that can recapitulate many aspects of endometrial tissue architecture and cell composition. These organoids have already helped to provide new insight into the embryo-endometrium interplay. The main aim of this paper is a comprehensive review of past and current approaches to endometrial model generation, their feasibility, and potential clinical application for infertility treatment.

Antioxidants in Male and Animal Reproduction: Applications and Critical Issues

The Special Issue “Antioxidants in Male Human and Animal Reproduction: In Vitro and In Vivo Studies”, published by Antioxidants and led by us (https://www [...]

What are future doctors learning about sex? An assessment of sexual health curricula across medical schools in the Northeastern United States.

Sexual health is an imperative area of study in medical school education, yet many medical schools do not offer a comprehensive curriculum nor is it standardized across the United States (US). This study aims to assess written curriculum materials from sexual health curricula in medical schools across the northeast region of the US and compare the current teachings to suggested standards. A compilation of academic resources including lecture materials and syllabi were systematically reviewed utilizing a standardized and validated rubric with variables assessed including: biological and psychological aspects of human sexual development, anatomy and physiology of the human sexual response cycle, sexual health in relation to human reproduction, and contraceptive options. We analyzed our data from the document analysis to look at the frequency of inclusion and exclusion of the sexual health topics included in our rubric. The outcomes of our data set were in line with our hypothesis that there is significant variance between sexual health curricula across institutions as well as an overall lack in material covering sexual health topics. The data show significant sex specific differences such that male-specific topics were covered more frequently than female-specific information. Additionally, only one of the 10 schools examined taught about vulvar conditions. There was also a paucity of information about sexuality in the post-partum period. The clinical implications of this study aim to highlight the discrepancy between an ideal sexual health curriculum and what is actually being taught in medical schools and help to guide future work of creating a comprehensive and standardized sexual medicine education in US. medical schools. The validity of this study was strengthened by analyzing direct curricula materials as opposed to previous use of subjective, self-reported questionnaires. However, the sample location being restricted to the Northeast was a limitation to generalize findings across the country. Future studies would aim to analyze medical school curricula across different regions in the US. This study shows that there is a lack of comprehensive and standardized sexual health curriculum in medical schools in the Northeastern US and serves as initial evidence for further investigation of this topic across American medical schools.

Sperm histone modifications may predict success in human assisted reproduction: a pilot study.

Currently, assisted reproduction clinics employ various sperm selection techniques to identify the best sperm for fertilization. However, these techniques may not assess crucial sperm traits that can substantially impact embryonic quality. To address this, we propose analyzing diverse histone modifications as potential markers of sperm functionality and success in assisted reproduction techniques. Cross-sectional pilot study including infertile male patients attending an infertility clinic in CABA, Argentina between April and August 2019 was performed. We used immunofluorescence techniques to evaluate post-translational modifications of histones in sperm and established correlations with in vitro fertilization outcome and embryo quality. Our findings indicate a negative correlation between H3K4me3 and H3K4me2 marks and fertilization rate and showed a positive correlation of this parameter with H3K9me mark. In addition, there was a positive correlation between H3K27me3 and good embryo quality. This pilot study proposes a non-invasive strategy to predict embryo quality by analyzing spermatozoa prior to fertilization. The assessment of histone post-translational modifications in sperm samples could provide useful information for the recognition of epigenetic marks that could predict the health of the embryo of an assisted fertilization treatment.

STUDY OF THE ENDOMETRIAL GLANDULAR COMPONENT IN WOMEN WITH FERTILITY AND POST-COVID SYNDROME IN ANAMNESIS

The aim. To increase the effectiveness of the endometrial endometrial glandular component study in women with infertility and post-COVID syndrome. Materials and methods. A study was conducted at the State institution "Carpathian Human Reproduction Centre" of the Ministry of Health of Ukraine in the period from 2022 to the end of the first half-year of 2024. There were included 80 women in the experimental group and 40 women in the control group. The selection criterion for the study group was the presence of documented post-COVID syndrome (COVID-19 symptoms lasted longer than 12 weeks). The selection criterion for the control group was the absence of confirmed SARS-CoV-2 virus in the anamnesis. The following characteristics were common for both groups: diagnosed infertility, age – 25-42 years, written informed consent of the patient to participate in the study. The criteria for exclusion from the study for patients of both groups were: detection of human immunodeficiency virus, viral hepatitis, other sexually transmitted infections, tuberculosis of the genitourinary system, malignant diseases, mental disorders that make communication with person impossible or the awareness of written consent is questioned. General clinical and laboratory examinations and transvaginal sonographic examination of the pelvic organs were performed in the middle stage of proliferation and the middle stage of secretion according to the calendar calculation the menstrual cycle. A visually guided diagnostic office hysteroscopy was performed with the collection of biological material from the most changed areas (biopsies were collected in the middle stage of proliferation and the middle stage of secretion in different menstrual cycles). A routine staining of samples with hematoxylin-eosin, morphometry of the endometrial glandular component, optical determination of the number of glands and measurement of the diameter of the lumen of the studied glands, considering the possible measurement error, glandular-stromal ratio, functional activity of the glands, were performed. A histochemical PAS-reaction to identify the glycoproteins of gland secretions and immunohistochemical staining of the glandular epithelium to express the receptivity of the glands to estrogen and progesterone were carried out. The results. After conducting the PAS-reaction, a higher secretion was noted in the glands than in the stroma of the endometrium during the period of the implantation window in both cohorts. No statistically significant difference between the groups in the amount of glycogen of the middle proliferative phase in the glands (p=0.315) or stroma (p=0.486). Glycogen in this phase was visualized of very small granules and coarse granules, without their formation in clusters. A decrease in secretion was established in 16 (40%) patients of the control group and 49 (61.3%) women of the experimental group in the middle secretory phase, which was statistically significant (p=0.028). A decrease in the expression level of the progesterone receptor in the middle secretory phase was found to be significantly more pronounced in the experimental group than in the control group (р=0.044). Conclusions. In the middle secretory phase, a decrease in the secretion of glycogen by the endometrial glands and a decrease in the level of expression of the progesterone receptor in endometrial biopsies were detected by the routine histological, histochemical techniques and immunohistochemical stude in women with infertility and a history of post-COVID syndrome.

Their stories, our history: Ken Daniels

INTRODUCTION: This article forms part of the “Their stories, our history” series which provides information regarding some of the major contributors to the profession of social work in Aotearoa New Zealand. Ken Daniels is featured in this article. METHODS: A life history methodology is used to document some of the contributions made by Ken Daniels. Life history is a qualitative methodology where various forms of data are used to piece together a narrative. Interviews, documents, articles and other historical artifacts have all contributed to the development of this article. FINDINGS: Ken Daniels has pioneered a number of social work advances in the areas of mental health, social work education and the professionalisation of social work. He has also made outstanding contributions nationally and internationally in the field of assisted human reproduction through a time of rapid change. Using a calm, compassionate and determined approach, Ken has been able to navigate through the complexities of practice, policy and education. CONCLUSIONS: Ken Daniels has exemplified a practice which has centred a generalist social work approach, working in different ways and at different systems levels to achieve desired outcomes.

Fetal hypoxia exposure induced Hif1a activation and autophagy in adult ovary granulosa cells.

Environmental hypoxia adversely impacts the reproduction of humans and animals. Previously, we showed that fetal hypoxia exposure led to granulosa cell (GC) autophagic cell death via the Foxo1/Pi3k/Akt pathway. However, the upstream regulatory mechanisms underlying GC dysfunction remain largely unexplored. Here, we tested the hypothesis that fetal hypoxia exposure altered gene expression programs in adult GCs and impaired ovarian function. We established a fetal hypoxia model in which pregnant mice were maintained in a high-plateau hypoxic environment from gestation day (E) 0--16.5 to study the impact of hypoxia exposure on the ovarian development and subsequent fertility of offspring. Compared with the unexposed control, fetal hypoxia impaired fertility by disordering ovarian function. Specifically, fetal hypoxia caused mitochondrial dysfunction, oxidant stress and autophagy in GCs in the adult ovary. RNA-seq analysis revealed that 437 genes were differentially expressed in the adult GCs of exposed animals. Western blotting results also revealed that fetal exposure induced high levels of hypoxia-inducible factor 1-alpha (Hif1a) expression in adult GCs. We then treated GCs isolated from exposed mice with PX-478, a specific pharmacological inhibitor of Hif-1a, and found that autophagy and apoptosis were effectively alleviated. Finally, by using a human ovarian granulosa-like tumor cell line (KGN) to simulate hypoxia in vitro, we showed that Hif1a regulated autophagic cell death in GCs through the Pi3k/Akt pathway. Together, these findings suggest that fetal hypoxia exposure induced persistent Hif1a expression, which impaired mitochondrial function and led to autophagic cell death in the GCs of the adult ovary.

Exposure to benzyl butyl phthalate (BBP) leads to increased double-strand break formation and germline dysfunction in Caenorhabditis elegans.

Benzyl butyl phthalate (BBP), a plasticizer found in a wide range of consumer products including vinyl flooring, carpet backing, food packaging, personal care products, and children's toys, is an endocrine-disrupting chemical linked to impaired reproduction and development in humans. Despite evidence that BBP exposure perturbs the integrity of male and female gametes, its direct effect on early meiotic events is understudied. Here, using the nematode Caenorhabditis elegans, we show that BBP exposure elicits a non-monotonic dose response on the rate of X-chromosome nondisjunction measured using a high-throughput screening platform. From among the range of doses tested (1, 10, 100 and 500 μM BBP), we found that 10 μM BBP elicited the strongest effect on the germline, resulting in increased germ cell apoptosis and chromosome organization defects. Mass spectrometry analysis shows that C. elegans efficiently metabolizes BBP into its primary metabolites, monobutyl phthalate (MBP) and monobenzyl phthalate (MBzP), and that the levels of BBP, MBP, and MBzP detected in the worm are within the range detected in human biological samples. Exposure to 10 μM BBP leads to germlines with enlarged mitotic nuclei, altered meiotic progression, activation of a p53/CEP-1-dependent DNA damage checkpoint, increased double-strand break levels throughout the germline, chromosome morphology defects in oocytes at diakinesis, and increased oxidative stress. RNA sequencing analysis indicates that BBP exposure results in the altered expression of genes involved in xenobiotic metabolic processes, extracellular matrix organization, oocyte morphogenesis, meiotic cell cycle, and oxidoreduction. Taken together, we propose that C. elegans exposure to BBP leads to increased oxidative stress and double-strand break formation, thereby compromising germline genomic integrity and chromosome segregation.

Effect of body mass index on semen quality, sperm chromatin integrity and sperm DNA methylation

Obesity represents a growing problem due to its impacts on human health and reproduction. In this study, we analysed semen quality, sperm DNA integrity and gene-specific CpG methylation in 116 healthy men from normal population. The men were divided into three groups according to their body mass index (BMI), and their ejaculates were analysed using standard methods, sperm chromatin structure assay (SCSA), methylation next generation sequencing (NGS) and amplicon sequencing. The sperm methylation NGS revealed six significantly differentially methylated regions (DMRs). Using subsequent targeted amplicon sequencing in 116 men, two of the DMRs were proved as differentially methylated in sperm of men with normal BMI vs. BMI ≥ 25. The DMRs were located in the EPHA8 and ANKRD11 gene. Also, we detected a significant decline in the EPHA8, ANKRD11 and CFAP46 gene methylation in association with increasing BMI values. The genes EPHA8 and ANKRD11 are involved in the nervous system and brain development; the CFAP46 gene plays a role in a flagellar assembly and is associated with sperm motility. Significantly lower rates of motile and progressive motile sperm were observed in men with BMI ≥ 30. Our results show that excess body weight can modify CpG methylation of specific genes, affect sperm motility, and compromise sperm chromatin integrity. These factors can stand behind the observed reduced fertility in men with obesity. The methylation changes might be transmitted to their offspring through sperm, and become a basis for possible developmental and reproductive issues in the next generation.

Sexual and reproductive health: level of knowledge and source of information in adolescence.

To date, there is a lack of a structured national plan of sexual education in Italy, with large interregional differences and poor uniformity in the promotion and learning of sexual health. The aim of this study was to evaluate the level of knowledge on sexuality and reproductive function among adolescents before and after a sexual education program, considering gender differences in the results. A longitudinal and interventional study was conducted on high school students. Six sessions for each class were carried out by a multidisciplinary team. Anonymous questionnaires were administered to investigate basic knowledge of human sexuality and reproduction before and after intervention. Participants were high school students who completed the questionnaires. Outcomes included pre and posttest answers on the knowledge questionnaire in study population. We obtained data from 842 high school students (mean ± SD age, 16.11 ± 1.74years). The main informative sources on sexuality were social media in 37.9% of participants; family, school, and scientific material were the main source in 15.1%, 5.2%, and 4.4%, respectively. A total score of 12.6 ± 3.4 (range, 1-20) was obtained on the knowledge questionnaire; specifically, the score was higher in females than males (12.8 ± 3.4 vs 11.9 ± 3.4, P = .0001). In males and females, a statistically significant increase in level of knowledge was found after the multidisciplinary intervention (14.5 ± 3.6, P = .0001). The lack of sexual education programs in schools in Italy compels adolescents to refer to frequently unreliable sources, such as social media and peers, contributing to misinformation and adoption of risky sexual behaviors. This study is based on a large sample size and highlights the importance of sexual education programs. The main limitations are a greater representation of the female population and the inclusive nature of the school (ie, an artistic school), attracting students who identify with sexual minorities. Adolescents have limited knowledge about sexuality and reproduction, with a notable gender disparity; sexual education programs in schools, providing information from sexuality experts, led to a substantial increase in knowledge and a reduction in the gender gap.

Treatment motivation in adolescent girls with obesity

Background. The prevalence of obesity among children is increasing, which is a serious healthcare problem. In healthcare, the problem of motivation affects an important area that reflects its effectiveness – patient motivation for treatment. A decrease in treatment motivation reduces therapeutic effect, increases the complication rate of the underlying disease, reduces the quality of life of patients and increases treatment costs.The aim of the work. To identify the differences in treatment motivation in adolescent girls with obesity.Materials and methods. The pilot study was carried out at the clinic of the Scientific Centre for Family Health and Human Reproduction Problems. The study included 40 girls aged 14–16 years suffering from grade 1 obesity. To study treatment motivation, we used the following methods: J. Nuttin’s, D. McClelland’s, S.R. Panteleev’s, J.K. Collins’, method of the self-conception research, the “Type of Attitude Towards the Disease” method; attitude towards the disease.Results. The study showed that the adolescents who were admitted into hospital for the first time had higher treatment motivation during the study than the adolescents who were readmitted into hospital. The adolescents who were readmitted into hospital felt guilty remorse, anxious suspiciousness, and fear of failure. The dominant type of treatment motivation in both groups consisted of the following attitudes: achieving symptomatic improvement; receiving a “secondary gain” from the disease; other motivation (passive position).Conclusion. The obtained data from the study of treatment motivation in adolescent girls with obesity can be used to optimize the process of therapy of such patients in a hospital setting.

In Vitro Embryo Production: Overview

Reproductive biotechnologies, also known as assisted reproductive technologies (ART), have undergone significant development over time, reaching a remarkable level of evolution in the 20th century. Currently, several biotechnologies stand out, among which Artificial Insemination (AI), widely spread globally, Embryo Production (EP) both in vivo and in vitro for embryo transfer, Intracytoplasmic Sperm Injection (ICSI), sexing, among other innovations. In Vitro Production (IVP) of embryos has emerged as the biotechnology that has experienced the greatest development and evolution in recent decades, covering various fields such as research in assisted human reproduction, obtaining transgenic animals for biomedicine, preservation of endangered species and conservation of animals of high genetic value. This research aims to analyze the relevance of IVP, as well as the fundamental elements that make up this complex process. IVP of embryos involves several stages, from oocyte procurement, oocyte selection and in vitro maturation, sperm preparation, in vitro fertilization, to the culture of the resulting zygotes to blastocysts. These blastocysts, once transferable to recipients, culminate in the birth of a new being. However, this process has both advantages and disadvantages, which motivates continuous innovation in the field.

VPS34 Governs Oocyte Developmental Competence by Regulating Mito/Autophagy: A Novel Insight into the Significance of RAB7 Activity and Its Subcellular Location.

Asynchronous nuclear and cytoplasmic maturation in human oocytes is believed to cause morphological anomalies after controlled ovarian hyperstimulation. Vacuolar protein sorting 34 (VPS34) is renowned for its pivotal role in regulating autophagy and endocytic trafficking. To investigate its impact on oocyte development, oocyte-specific knockout mice (ZcKO) are generated, and these mice are completely found infertile, with embryonic development halted at 2- to 4-cell stage. This infertility is related with a disruption on autophagic/mitophagic flux in ZcKO oocytes, leading to subsequent failure of zygotic genome activation (ZGA) in derived 2-cell embryos. The findings further elucidated the regulation of VPS34 on the activity and subcellular translocation of RAS-related GTP-binding protein 7 (RAB7), which is critical not only for the maturation of late endosomes and lysosomes, but also for initiating mitophagy via retrograde trafficking. VPS34 binds directly with RAB7 and facilitates its activity conversion through TBC1 domain family member 5 (TBC1D5). Consistent with the cytoplasmic vacuolation observed in ZcKO oocytes, defects in multiple vesicle trafficking systems are also identified in vacuolated human oocytes. Furthermore, activating VPS34 with corynoxin B (CB) treatment improved oocyte quality in aged mice. Hence, VPS34 activation may represent a novel approach to enhance oocyte quality in human artificial reproduction.

Recommendations from the 2024 Australian evidence-based guideline for unexplained infertility: ADAPTE process from the ESHRE evidence-based guideline on unexplained infertility.

The 2024 Australian evidence-based guideline for unexplained infertility provides clinicians with evidence-based recommendations for the optimal diagnostic workup for infertile couples to establish the diagnosis of unexplained infertility and optimal therapeutic approach to treat couples diagnosed with unexplained infertility in the Australian health care setting. The guideline recommendations were adapted for the Australian context from the rigorous, comprehensive European Society of Human Reproduction and Embryology (ESHRE) 2023 Evidence-based guideline: unexplained infertility, using the ADAPTE process and have been approved by the Australian National Health and Medical Research Council. The guideline includes 40 evidence-based recommendations, 21 practice points and three research recommendations addressing: definition - defining infertility and frequency of intercourse, infertility and age, female and male factor infertility; diagnosis - ovulation, ovarian reserve, tubal factor, uterine factor, laparoscopy, cervical/vaginal factor, male factor, additional testing for systemic conditions; and treatment - expectant management, active treatment, mechanical-surgical procedures, alternative therapeutic approaches, quality of life. CHANGES IN ASSESSMENT AND MANAGEMENT RESULTING FROM THE GUIDELINE: This guideline refines the definition of unexplained infertility and addresses basic diagnostic procedures for infertility assessment not considered in previous guidelines on unexplained infertility. For therapeutic approaches, consideration of evidence quality, efficacy, safety and, in the Australian setting, feasibility, acceptability, cost, implementation and ultimately recommendation strength were integrated across multidisciplinary expertise and consumer perspectives in adapting recommendations to the Australian context by using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework, which had not been used in past guidelines on unexplained infertility to formulate recommendations. The Australian process also included an established data integrity check to ensure evidence could be trusted to guide practice. Practice points were added and expanded to consider the Australian setting. No evidence-based recommendations were underpinned by high quality evidence, with most having low or very low quality evidence. In this context, research recommendations were made including those for the Australian context. The full guideline and technical report are publicly available online and can be accessed at https://www.monash.edu/medicine/mchri/infertility and are supported by extensive translation resources, including the free patient ASKFertility mobile application (https://www.askfertility.org/).

Mortality risk predicts global, local, and individual patterns of human reproduction

BackgroundHuman reproductive dynamics in the post-industrial world are typically explained by economic, technological, and social factors including the prevalence of contraception and increasing numbers of women in higher education and the workforce. These factors have been targeted by multiple world governments as part of family policies, yet those policies have had limited success. The current work adopts a life history perspective from evolutionary biology: like most species, human populations may respond to safer environments marked by lower morbidity and mortality by slowing their reproduction and reducing their number of offspring. We test this association on three levels of analysis using global, local, and individual data from publicly available databases.ResultsData from over 200 world nations, 3,000 U.S. counties and 2,800 individuals confirm an association between human reproductive outcomes and local mortality risk. Lower local mortality risk predicts “slower” reproduction in humans (lower adolescent fertility, lower total fertility rates, later age of childbearing) on all levels of analyses, even while controlling for socioeconomic variables (female employment, education, contraception).ConclusionsThe association between extrinsic mortality risk and reproductive outcomes, suggested by life history theory and previously supported by both animal and human data, is now supported by novel evidence in humans. Social and health policies governing human reproduction, whether they seek to boost or constrain fertility, may benefit from incorporating a focus on mortality risk.