Search Results (330)

Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. Although traditionally considered a disease of older men, the incidence of early-onset PCa (diagnosis < 55 years) is steadily rising. Advances in screening and therapy have significantly improved survival, creating a growing cohort of younger survivors for whom post-treatment quality of life—notably reproductive function—is paramount. Curative treatments such as radical prostatectomy, pelvic radiotherapy, androgen-deprivation therapy (ADT), and chemotherapy often cause irreversible infertility via multiple mechanisms, including surgical disruption of the ejaculatory tract, endocrine suppression of spermatogenesis, direct gonadotoxic injury to the testes, and oxidative sperm DNA damage. Despite these risks, fertility preservation is frequently overlooked in pre-treatment counseling, leaving many patients unaware of their options. This narrative review synthesizes current evidence on how PCa therapies impact male fertility, elucidates the molecular and physiological mechanisms of iatrogenic infertility, and evaluates both established and emerging strategies for fertility preservation and restoration. Key interventions covered include sperm cryopreservation, microsurgical testicular sperm extraction (TESE), and assisted reproductive technologies (ART). Psychosocial factors influencing decision-making, novel biomarkers predictive of post-treatment spermatogenic recovery, and long-term offspring outcomes are also examined. The review underscores the urgent need for timely, multidisciplinary fertility consultation as a routine component of PCa care. As PCa increasingly affects men in their reproductive years, proactively integrating preservation into standard oncologic practice should become a standard survivorship priority. Full article

Background: Previous research has linked hypertensive disorders of pregnancy (HDP) and long-term cardiovascular disease (CVD) with assisted reproductive technology (ART). It is not clear whether this reflects the background population cardiovascular profiles or whether ART independently increases the long-term risk for CVD and alters cardiovascular function. Furthermore, CVD has been associated with pathological cardiovascular function before and after the establishment of the disease. The aim of this study was to compare cardiac function in women attending for ART between those who had previous treatment and those who had not after controlling for demographic characteristics which have been shown to affect cardiovascular function. Methods: This was a prospective observational cohort study at a London fertility clinic. Women were consecutively enrolled between May 2021 and March 2022. Maternal demographics and cardiac function using transthoracic echocardiography were assessed before the current treatment cycle in the mid-luteal phase of the menstrual cycle. Maternal demographics included age, body mass index, smoking, race, and parity. Cardiovascular parameters included blood pressure and indices of left-ventricular systolic and diastolic function. Differences between cardiac variables after controlling for maternal demographics and history of previous ART were assessed by multivariate linear regression. Results: There were 232 healthy women who agreed to participate in the study; of those, 153 (58%) had undergone previous ART. After controlling for maternal demographic characteristics, previous assisted reproductive technology was not an independent predictor of cardiac function. Conclusions: Previous ART is not associated with significant changes in cardiac function. Full article

Immunological factors have gained growing recognition as key contributors to recurrent pregnancy loss (RPL) after in vitro fertilization (IVF), representing a major challenge in reproductive medicine. RPL affects approximately 1–2% of women trying to conceive naturally and up to 10–15% of those undergoing IVF, where overall success rates remain around 30–40% per cycle. An imbalance in maternal immunological tolerance toward the semi-allogeneic fetus during pregnancy may lead to miscarriage and implantation failure. IVF-related ovarian stimulation and embryo modification offer additional immunological complications that can exacerbate existing immune dysregulation. Recent advances in reproductive immunology have significantly deepened our understanding of the immune mechanisms underlying RPL following IVF, particularly highlighting the roles of regulatory T cells (T regs), natural killer cells, cytokine dysregulation, and disruptions in maternal–fetal immune tolerance. In order to better customize therapies, this evaluation incorporates recently discovered immunological biomarkers and groups patients according to unique immune profiles. Beyond conventional treatments like intralipid therapy and intravenous immunoglobulin, it also examines new immunomodulatory medications that target certain immune pathways, such as precision immunotherapies and novel cytokine modulators. We also discuss the debates over immunological diagnostics and therapies, such as intralipid therapy, intravenous immunoglobulin, corticosteroids, and anticoagulants. The heterogeneity of patient immune profiles combined with a lack of strong evidence highlights the imperative for precision medicine to improve therapeutic consistency. Novel indicators for tailored immunotherapy and emerging treatments that target particular immune pathways have encouraging opportunities to increase pregnancy success rates. Improving management approaches requires that future research prioritize large-scale clinical trials and the development of standardized immunological assessments. This review addresses the immunological factors in RPL during IVF, emphasizing underlying mechanisms, ongoing controversies, and novel therapeutic approaches to inform researchers and clinicians. Full article

Background/Objectives: Although biallelic pathogenic variants in different DNAH gene family members have been associated with infertility, the role of DNAH12 in this disorder is still incompletely understood. To date, few patients have been shown to have infertility due to biallelic variants in this gene. Here, we report two more unrelated patients with infertility who carry homozygous variants in DNAH12. Methods: This study included two male patients with primary infertility and oligoasthenoteratozoospermia (OAT). Patient 1 was a 32-year-old with 1.5 years of infertility and no chronic illnesses or prior assisted reproductive technologies (ARTs). Patient 2 was a 49-year-old with 24 years of infertility, a history of varicocelectomy, and the occasional use of PRN analgesics for bone pain. Using genome sequencing, we identified two homozygous variants: c.3757C>A, p. Pro1253Thr, and c.11086-1G>A, p.?, in patients 1 and 2, respectively. Results: Our findings add supportive evidence that DNAH12 is a gene implicated in rare cases of male infertility. The identification of these homozygous variants in two additional patients supports the association between DNAH12 variants and reproductive dysfunction. Conclusions: This study highlights the need for further research on the role of DNAH12, including functional studies to clarify the mechanisms contributing to infertility. Full article

The incidence of sperm DNA fragmentation (SDF) in the ejaculate has garnered increasing attention in recent years due to its negative impact on reproductive outcomes. SDF involves two primary types of damage to the canonical double helix of DNA: single-strand breaks and double-strand breaks. Both of these can occur throughout the entire process of gametogenesis. Determining the precise causes of elevated SDF remains challenging, as it is influenced by a wide range of physiological processes and environmental factors. This review comprehensively explores the mechanisms underlying SDF, with a particular emphasis on the critical role of deoxyribonucleases (DNases) across different stages of male gamete development, as well as their relevance in assisted reproductive technologies (ART). Full article

Sperm membrane potential (Em) hyperpolarization during capacitation is a functional hallmark of fertilizing ability and has been proposed as a predictive biomarker for conventional in vitro fertilization (IVF) success. However, it is unclear whether Em remains stable across ejaculates over time and can reliably guide assisted reproductive technology (ART) decisions in advance. Thus, we aimed to evaluate the temporal consistency of human sperm Em within individuals and assess its utility as a prognostic marker when measured days or weeks prior to IVF procedures. Em was assessed in capacitated and non-capacitated sperm from normospermic donors at three time points over 28 days, using a fluorometric assay. Capacitated values were compared to a −48.6 mV threshold previously associated with successful fertilization. Intra-donor Em variability and coefficients of variation (CV) were analyzed statistically. Our results showed that Em values exhibited significant intra-donor variability over time (p = 0.007), with approximately half of the donors crossing the −48.6 mV functional threshold across sessions. Capacitated sperm samples showed significantly greater variability than non-capacitated ones, with several donors exceeding a 30% CV cutoff. No consistent correlation was found between CV and mean Em values. While Em remains a promising functional marker when assessed on the day of IVF, its temporal variability undermines its reliability as a predictive tool for ART decisions made in advance. These findings underscore the importance of timing in functional sperm assessments and call for further studies to identify the physiological factors influencing Em stability. Full article

This study explored psychological distress and gender differences among couples diagnosed with unexplained infertility (UI) and undergoing evaluation for assisted reproductive treatment at the AOUP Santa Chiara Hospital in Pisa, Italy. A total of 21 heterosexual couples (N = 42) completed the Perceived Stress Scale (PSS), Depression Anxiety Stress Scale (DASS-21), Defeat Scale (DS), and Core-Fertility Quality of Life questionnaire (Core-FertiQol). Women reported significantly higher levels of anxiety and stress compared to men, as confirmed both by DASS-21 and PSS scores. No significant gender differences emerged either in depressive symptoms or defeat. In the Core-FertiQol, women scored higher in the Mind–Body component. Within-couple comparisons mirrored between-gender findings, with women showing higher distress. Despite elevated distress levels, women also demonstrated relatively preserved quality of life, possibly reflecting more adaptive coping strategies. The study provides preliminary support for the development of mindfulness-based interventions tailored to couples coping with UI. Further research with larger samples is needed to clarify gender-specific mechanisms and inform integrated psychological care in fertility settings. Full article

Per- and polyfluoroalkyl substances (PFASs) comprise a diverse array of synthetic chemicals that resist environmental degradation. They are increasingly recognised as endocrine-disrupting compounds (EDCs). These chemicals, found in non-stick cookware, food packaging, and industrial waste, accumulate in human tissues and fluids, raising substantial concerns regarding their impact on female reproductive health. Epidemiological studies have demonstrated associations between PFAS exposure and reduced fertility; nevertheless, the underlying molecular pathways remain inadequately understood. This narrative review investigates the multifaceted effects of PFASs on ovarian physiology, including its disruption of the hypothalamic–pituitary–ovarian (HPO) axis, alteration of anti-Müllerian hormone (AMH) levels, folliculogenesis, and gonadotropin receptor signalling. Significant attention is directed towards the emerging association between PFASs and polycystic ovarian syndrome (PCOS), wherein PFAS-induced hormonal disruption may exacerbate metabolic issues and elevated androgen levels. Furthermore, we analyse the current data regarding PFAS exposure in women undergoing treatment based on assisted reproductive technologies (ARTs), specifically in vitro fertilisation (IVF), highlighting possible associations with diminished oocyte quality, suboptimal embryo development, and implantation failure. We examine potential epigenetic and transgenerational alterations that may influence women’s reproductive capabilities over time. This study underscores the urgent need for further research and regulatory actions to tackle PFAS-related reproductive toxicity, particularly in vulnerable populations, such as women of reproductive age and those receiving fertility treatments. Full article

The increasing use of assisted reproductive technologies (ARTs) globally, such as intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF), has highlighted the pressing need to determine the modifiable factors affecting the success of implantation and the outcomes of early pregnancy. Scientific interest in the role of nutrition in fertility is growing, but outside of celiac disease, little is known about gluten, a dietary protein with immunogenic and inflammatory properties. With an emphasis on ART results, this narrative review summarizes the most recent data regarding the possible effects of gluten consumption on reproductive health, focusing primarily on individuals with celiac disease (CD) and non-celiac gluten sensitivity (NCGS). In addition to discussing potential molecular processes connecting gluten-induced inflammation, increased gut permeability, autoimmune, and decreased endometrial receptivity, we further explore the documented link between CD and infertility and investigate new information on NCGS. These findings are tentative and based on scant low-quality evidence, although some case reports and small clinical studies have indicated that avoiding gluten may help some people undergoing ART, especially those with immune-mediated diseases or infertility that cannot be explained. There is currently no robust prospective evidence confirming that gluten restriction improves infertility outcomes. Therefore, before gluten elimination is advised in this situation, more carefully planned extensive research is required to generate reliable scientific proof. Beyond traditional celiac disease, we suggest that gluten sensitivity might be an underappreciated factor in ART failure that merits more research. A gluten-free diet may serve as a low-risk supplementary option for appropriately selected patients, pending the results of more extensive controlled studies. Full article

The efficacy of in vitro fertilization (IVF) is significantly hindered by early embryonic developmental failure and oocyte maturation arrest. Recent findings in reproductive genetics have identified several oocyte-specific genes—TUBB8, KIF11, and CKAP5—as essential regulators of meiotic spindle formation and cytoskeletal dynamics. Mutations in these genes can lead to significant meiotic defects, fertilization failure, and embryo arrest. The links between genotype and phenotype, along with the underlying biological mechanisms, remain inadequately characterized despite the increasing number of identified variations. This systematic review was conducted in accordance with PRISMA 2020 guidelines. Relevant papers were retrieved from the PubMed and Embase databases using combinations of the keywords “TUBB8,” “KIF11,” “CKAP5,” “oocyte maturation arrest,” “embryonic arrest,” and “IVF failure.” Studies were included if they contained clinical, genomic, and functional data on TUBB8, KIF11, or CKAP5 mutations in women undergoing IVF. Molecular data, including gene variant classifications, inheritance models, in vitro tests (such as microtubule network analysis in HeLa cells), and assisted reproductive technology (ART) outcomes, were obtained. Eighteen trials including 35 women with primary infertility were included. Over fifty different variants were identified, the majority of which can be attributed to TUBB8 mutations. TUBB8 disrupted α/β-tubulin heterodimer assembly due to homozygous missense mutations, hence hindering meiotic spindle formation and leading to early embryo fragmentation or the creation of many pronuclei and cleavage failure. KIF11 mutations resulted in spindle disorganization and chromosomal misalignment via disrupting tubulin acetylation and microtubule transport. Mutations in CKAP5 impaired bipolar spindle assembly and microtubule stabilization. In vitro validation studies showed cytoskeletal disturbances, protein instability, and dominant negative effects in transfected animals. Donor egg IVF was the sole effective treatment; however, no viable pregnancies were documented in patients with pathogenic mutations of TUBB8 or KIF11. TUBB8, KIF11, and CKAP5 are essential for safeguarding oocyte meiotic competence and early embryonic development at the molecular level. Genetic differences in these genes disrupt microtubule dynamics and spindle assembly, resulting in various aspects of oocyte maturation and fertilization. Functional validation underscores the necessity of routine genetic screening for women experiencing unresolved IVF failure, as it substantiates their causal role in infertility. Future therapeutic avenues in ART may be enhanced by tailored counseling and innovative rescue methodologies like as gene therapy. Full article

The significant decline in amphibians worldwide is demanding the development of reliable techniques to save species and their genetic diversity. Considerable efforts are currently in progress to develop assisted reproductive technologies (ARTs), focusing mainly on sperm cryopreservation and in vitro fertilization (IVF). In Xenopus, a simple and efficient transgenesis method based on the intracytoplasmic injection (ICSI) of cryoconserved sperm was developed several decades ago, allowing for quick generation of large numbers of transgenic animals, for biological research. Such a methodology could be critical for the recovery of species and their genetic diversity, contributing to amphibian conservation. However, this approach raised the question of whether the sperm preservation method used with ICSI is compatible with long-term storage. To address this question, animals were generated by ICSI using a twenty-year-old cryopreserved sperm preparation. Their development, behavior, and reproduction ability were compared with those of animals obtained using a recently frozen sperm preparation and those of animals obtained via IVF using fresh semen. Although lower than with IVF, we showed that fertilization rates using ICSI after 20 years of cryopreservation are similar to those of a recent preparation, with viable offspring leading to normal F2 generation. This pioneering achievement is proof of concept for long-term sperm cryopreservation using simple and readily available technologies for the conservation of endangered amphibians. Full article

Standard semen parameters remain the cornerstone of male infertility evaluation, though they often poorly reflect the likelihood of success in assisted reproductive technology (ART). This study evaluates sperm DNA fragmentation (SDF) as a diagnostic tool for male infertility and predictive biomarker for ART success. Semen samples were collected from 20 fertile donors and 40 infertile patients with abnormal semen parameters. A fraction of each sample was used for SDF assessment via TUNEL assay and flow cytometry, while the remaining portion was processed for conventional semen analysis and ART. Infertile patients exhibited higher SDF levels (32.77 ± 13.61%) compared to donors (22.19 ± 8.37%; p < 0.01), a difference that remained statistically significant across all subgroups stratified by semen parameters. Additionally, significant correlations were obtained between the percentage of SDF and sperm count (r = −0.4036), motility (r = −0.6377), and morphology (r = −0.2783). Regarding ART outcomes, patients with low-quality embryos exhibited higher SDF levels compared to those with high-quality embryos (30.02 ± 12.52% vs. 23.16 ± 8.41%; p = 0.0036). Receiver operating characteristic (ROC) curve analysis revealed an area under the curve (AUC) above 0.7 for the classification of male infertility as well as the assessment of embryo quality. Overall, our results support the utility of SDF as both a diagnostic biomarker for male infertility and a predictive indicator of embryo quality in ART, particularly in the presence of an oocyte-related female factor. Full article

Assisted reproduction technology (ART) has advanced significantly over the past four decades, leading to improved pregnancy outcomes and a reduction in complications, particularly those associated with multiple pregnancies. These improvements largely stem from advances in understanding embryonic physiology, which has enabled better culture conditions. As a result, embryologists can now efficiently culture embryos to the blastocyst stage and successfully cryopreserve them for future use. However, while incubators aim to replicate the maternal environment of the oviduct and uterus, embryos in vitro are cultured in static conditions, unlike the dynamic, constantly changing environment they experience in vivo. Key factors such as pH, temperature, osmolality, and gas concentrations are crucial for establishing optimal embryo development and implantation potential. Moreover, the vitrification procedure for gametes or embryos can introduce oxidative stress, as well as osmotic shock and cryoprotectant toxicity, which may affect embryo viability and increase the risk of birth defects. Since the first successful ART birth in 1978, over 10 million babies have been conceived through these techniques. Although most of these children are healthy, concerns exist about potential birth defects or changes linked to the handling of gametes and embryos. The preimplantation period is marked by significant epigenetic reprogramming, which can be influenced by ART procedures such as ovarian stimulation, in vitro fertilization, embryo culture, and cryopreservation. However, the long-term health implications for offspring remain uncertain. Epigenetic reprogramming during early embryogenesis is essential for proper embryo development and can be changed by ART-related conditions. These concerns have raised questions about the possible connection between ART and a higher risk of birth defects or other changes in children born through these methods. Therefore, we conducted a scoping review following PRISMA-ScR guidelines to map evidence on ART-related risks, including epigenetic and birth defect outcomes. Full article

Purpose: Cancer treatments can result in subfertility or infertility in female adult childhood cancer survivors (ACCSs). While ACCSs may utilize assisted reproductive technology (ART) or other family-building options, the limited evidence describing their experiences remains a hindrance to developing and implementing appropriate patient-centered supports. The study’s aim is to describe the challenges female ACCSs experienced while navigating ART and family-building options, to inform improvements in clinical practice in a western Canadian province. Methods: In this qualitative Interpretive Description study, interviews were conducted with 15 female ACCSs and data were analyzed using an interpretive thematic approach and constant comparative techniques. Results: ACCSs’ narratives suggest they experienced five prominent challenges while navigating ART and family-building options, including (1) confronting unexpected, impaired fertility, (2) grieving loss and redefining identity, (3) encountering unsupportive healthcare, (4) exploring alternative paths of adoption and international family-building, and (5) facing financial strain. Conclusions: This exploratory study provides initial insights into the significant and multifaceted challenges female ACCSs experience related to family building and highlights gaps in healthcare services. Further research is warranted to articulate these challenges across contexts and the development and implementation of mitigating approaches. Implications for Cancer Survivors: The integration of comprehensive informational, psychosocial, and financial supports into existing cancer survivor and family-building services is vital to meeting female ACCSs’ unmet needs. Full article

One of the critical challenges in assisted reproductive technology (ART) is the inadequacy of effective regulation of reactive oxygen species. Simultaneously, the endogenous antioxidant defense system plays a significant role in combating oxidative stress across various physiological stages of embryonic development. However, these intrinsic defense systems alone are insufficient as they rely on exogenous antioxidants that interact synergistically to enhance and sustain antioxidant capacity. Considering the principal role of antioxidants in mitigating oxidative stress in oocyte growth, identifying reliable and non-toxic antioxidants is an essential prerequisite for effective therapeutic applications. Thus, owing to the need to explore exogenous antioxidants, we attempted to summarize and analyze the literature data defining the potential use of curcumin in mitigating oxidative stress to promote oocyte maturation through in vivo and in vitro model studies. Recent studies demonstrated the protective role of curcumin against oxidative stress and the inflammatory response, primarily through the upregulation of key antioxidant enzymes (including SOD, CAT and GPx), a reduction in oxidative stress markers (e.g., ROS, MDA) and by suppressing the pro-inflammatory signaling pathways (such as NF-kB, JAK/STAT) while activating the NRF2/HO-1 pathway to further enhance the cellular antioxidant defense. Advancing curcumin as a therapeutic agent necessitates a thorough understanding of curcumin’s molecular mechanisms and targeted pharmacological effectiveness to treat female infertility, and despite the progress in enhancing curcumin’s bioavailability, the optimal dosing strategies still need to be defined. Future studies are required to develop strategies to augment antioxidant defense mechanisms (modeling in vivo and in vitro studies) using curcumin with a specific emphasis on curcumin’s role in improving mitochondrial activity. This approach is expected to represent a significant advancement in the field of medicine, offering novel therapeutic possibilities. Full article