Reproduction & fertility最新文献

Lay summary: Endometriosis is a chronic condition where tissue resembling the uterine lining grows elsewhere in the pelvis, often causing pain, infertility, and inflammation. For decades, textbooks and research papers have described the rectovaginal septum (RVS), the thin layer between the vagina and rectum, as a common site of deep endometriosis. Yet this belief has never been conclusively proven. In our study of 161 patients, combining advanced ultrasound, meticulous keyhole surgery, and tissue analysis, we found no evidence of endometriosis within the RVS. Instead, all lesions were located in surrounding structures, including the uterosacral ligaments, the rectouterine pouch, or the bowel. These findings challenge a long-standing anatomical misconception and call for the retirement of outdated terminology. Clarifying where endometriosis truly occurs is critical for improving diagnosis, surgery, and communication in women's health. Our study overturns decades of dogma by showing that 'rectovaginal septum endometriosis' may be a myth.

Abstract: This retrospective study investigated factors associated with abnormal endometrial peristaltic waves (EPWs) and evaluated the impact of Atosiban intervention on clinical outcomes in frozen-thawed embryo transfer (FET) cycles. A total of 7,554 infertile women undergoing FET cycles were assessed using one-minute transvaginal ultrasound examinations 1 day before transfer to determine peristaltic frequency and direction. Logistic regression identified maternal reproductive history and cycle characteristics as parameters associated with abnormal EPWs. Among women with abnormal EPWs (n = 515), Atosiban was administered before embryo transfer, while controls (n = 7,039) did not. After propensity score matching (approximately 1:2), 505 treated cycles were compared with 993 control cycles. Overall, pregnancy outcomes were comparable between groups, although Atosiban administration was associated with a modest improvement in clinical pregnancy rate (58.6 vs 53.3%; P = 0.049). Subgroup analysis by embryo stage revealed that this benefit was mainly observed in cleavage-stage (day 3) embryo transfers (50.2 vs 41.4%; P = 0.025), with no significant effect in blastocyst (day 5/6) transfers. These findings suggest that abnormal EPWs are influenced by multiple clinical factors, and Atosiban intervention may improve pregnancy outcomes, particularly in cleavage-stage embryo transfer cycles.

Lay summary: A successful pregnancy after frozen embryo transfer cycles depends on proper coordination between the embryo and the uterus. In some cases, the uterus shows abnormal movements - called abnormal EPWs - which may make it harder for implantation. In this study, we analyzed medical data from over 7,500 women who had frozen embryo transfers. About 500 of them showed abnormal EPWs during an ultrasound check before embryo transfer. These women received a medication (Atosiban) that helps relax the uterus. We found that abnormal uterine movements can be caused by several factors. After receiving treatment, women with abnormal movements had pregnancy chances similar to those without the problem. The benefit was even greater when embryos were transferred at an early stage (day 3 embryos). This suggests that detecting and treating abnormal uterine movements could improve the chances of pregnancy for some women undergoing IVF, especially those receiving early-stage embryos.

Abstract: As men age, their reproductive capacity changes. Although males do not have a defined 'biological clock', evidence suggests that paternal age plays a pivotal role in male reproduction and offspring health. Epigenetic mechanisms, which influence how genes are expressed in all cells, are important in gametogenesis and can be influenced by endogenous factors such as diet, toxin exposure, stress, and age. Hence, an altered paternal environment can generate epigenetic modifications that can be passed onto the offspring via the ejaculate. In humans, more couples in developed countries are delaying parenthood and are relying on assisted reproductive techniques. Although research has focused on maternal age, growing evidence shows that advanced paternal age (APA) can influence the epigenetic pathways in embryos and offspring. There are several known epigenetic mechanisms that may link APA to downstream fitness effects in offspring: DNA methylation, histone post-translational modifications, chromatin remodelling, and small noncoding RNA (sncRNA) expression. Sperm RNAs were once considered residual products of sperm maturation. Now, small RNAs have emerged as key players in male fertility. sncRNA expression tightly regulates the sperm cell cycle and maturation, and embryo development. Despite their importance in epigenetic inheritance, the relationship between paternal age, sncRNA expression, and reproductive outcomes is unclear. Given the role of sncRNA expression in gametogenesis and embryogenesis, understanding how age influences sncRNA expression could provide insights into the underlying factors of failed natural and assisted fertility. This review explores the links between paternal age, sperm epigenetics, reproduction, and offspring health, with a focus on sncRNA expression.

Lay summary: Unlike women, men do not have a clear biological clock. However, research shows that a man's age can affect his fertility and the health of his children. As men get older, the way genes are turned on and off in sperm changes and these changes can be passed on to their children. Lifestyle factors such as diet, stress, and exposure to toxins can affect how genes are controlled. Much research has focused on the effects of maternal age, but there is growing evidence that advanced paternal age (APA) can influence fertility and embryo development. A key area of interest is small sperm molecules that influence early development. Once thought to be mere by-products of sperm development, these molecules are now known to play crucial roles in sperm function and embryo development. This review examines how a father's age affects these small sperm molecules and their role in fertility and offspring health.

Abstract: This prospective cohort study aimed to assess whether a history of embryonic chromosomal abnormality affects subsequent pregnancy outcomes in women with unexplained recurrent pregnancy loss. A total of 233 women with unexplained recurrent pregnancy loss who conceived naturally were included. Participants were categorized according to the chromosomal status of prior miscarriages. A multivariate logistic regression model was constructed to predict live birth based on these categories and observed pregnancy outcomes. Among the 233 included women, 171 (73.4%) had a live birth, while 62 (26.6%) experienced early pregnancy loss. Among women with one abnormal chromosomal miscarriage (n = 110), 94 (85.5%) had a live birth, accounting for 40.3% of the total cohort. In contrast, in the one normal chromosomal miscarriage group (n = 77), 47 (61.0%) achieved live birth, representing 20.2% of the total. The model identified a history of one chromosomally abnormal miscarriage (odds ratio = 3.88, 95% confidence interval: 1.87-8.06) and history of two chromosomally abnormal miscarriages (odds ratio = 8.93, 95% confidence interval: 1.07-74.55) as significant predictors of live birth. The predictive model achieved an area under the curve of 0.73 in the training dataset and 0.75 in the testing dataset. A history of embryonic chromosomal miscarriage may reflect improved pregnancy prospects and inform clinical counseling in unexplained recurrent pregnancy loss.

Lay summary: Women with unexplained recurrent miscarriage often wonder whether their history will affect future natural pregnancies. Chromosomal abnormalities in embryos are a leading cause of miscarriage, but the impact of such a history on later outcomes has remained unclear. We studied 233 women with repeated unexplained losses and assessed their subsequent pregnancy results. Overall, 73.4% achieved a live birth, while 26.6% had another early miscarriage. Interestingly, among women who had one chromosomal abnormal miscarriage, 85.5% subsequently achieved a live birth. In contrast, the live birth rate was lower in the group who had a normal chromosomal miscarriage; only 61.0% went on to achieve a live birth. These results suggest that a history of abnormal chromosomal miscarriage may indicate better chances of future pregnancy and help guide clinical care.

Abstract: Artificial vaginas (AVs) are tools used to collect semen from domestic and exotic species for artificial insemination and managed breeding programs. AVs differ widely in their shape, size, component parts, and material composition to fit species-specific applications. The quality of semen collected with AVs is inconsistent within and across species. This review examines peer-reviewed published literature on features of AVs used on non-human vertebrate taxa and assesses AV composition changes over time. Google Scholar, PubMed, and Web of Science databases were used to search for the term 'AV' from 1914 to 2024. After screening the abstracts and methods sections, 778 articles were included in the analysis. AVs were categorized based on AV material, shape, elasticity, and design augmentations. Over the past century, perissodactyls and artiodactyls have been the most studied orders for AV semen collection. Most AVs are made of rubber/latex or plastic, tube-shaped, and have a rigid outer shell and semi-elastic inner liner made of rubber/latex. AV materials, shapes, and elasticity have not changed substantially over time. Most commercially available AVs do not differ substantially from AVs developed originally for use with bulls and stallions, with few examples of species-specific AV compositions. As AVs are an increasingly important tool for semen collection, particularly among exotic species, future studies could consider how to reflect the genital variation of taxa within the shape, material, and design augmentations of AVs.

Lay summary: AVs are devices used to collect semen from trained animals in human care for breeding programs. AVs have been developed for many bird and mammalian species. We examined the published literature to assess how AV compositions have changed across species since their initial use in 1914. We extracted data from the literature on AV materials, shapes, elasticities, and unique design features. Most AVs consisted of semi-elastic tube-shaped devices constructed of multiple materials. The most common design feature was a warmed bladder. AV compositions have not changed substantially over time or species, indicating opportunities for innovations such as incorporating anatomical features to improve semen quality.

Abstract: The long-term in vitro culture (LIVC) of cumulus-oocyte complexes (COCs) derived from early antral follicles (EAFs) has shown significant potential in producing meiotically competent oocytes in adult ewes. However, the effectiveness of this approach in prepubertal ewes remains unexplored. This study aimed to evaluate the efficiency of the LIVC system in prepubertal ewes, addressing the challenge of limited EAF availability in adults. Both adult and prepubertal ewe ovaries were used to isolate COCs from EAFs (350-450 µm), which were then cultured in TCM199 supplemented with 0.15 μg/mL Zn++, 10-4 IU/mL FSH, 10 ng/mL estradiol, 50 ng/mL testosterone, 50 ng/mL progesterone, and 5 μM cilostamide. After five days of LIVC, a group of COCs underwent in vitro maturation, while others were evaluated for LIVC effectiveness, including morphology, oocyte diameter, chromatin configuration, gap junction communication, meiotic competence, intracellular reactive oxygen species (ROS) levels, mitochondrial activity, and distribution. Results showed a significant increase in oocyte diameter (116.3 vs. 113.4 µm, p < 0.01), higher COC morphological integrity (61.8% vs. 42.6%), and active gap junction communication in adults compared to prepubertal ewes. Moreover, prepubertal ewes exhibited a higher mitochondrial activity, along with spontaneous meiosis resumption (26.7% vs. 0%) after LIVC and a lower rate of meiosis resumption (21.0% vs. 59.4%) following in vitro maturation. No significant differences in ROS levels or mitochondrial distribution were observed between groups. In conclusion, COCs isolated from EAFs of prepubertal ewes showed restricted development during LIVC, highlighting significant age-related differences in optimizing fertility preservation techniques for prepubertal animals.

Lay summary: Fertility preservation in adult livestock can be achieved by culturing growing oocytes from early antral follicles, a stage characterized by a small fluid-filled cavity. Still, its effectiveness in prepubertal animals remains uncertain. This study compared the quality and growth of oocytes from adult and prepubertal sheep. After five days in culture, oocytes from adult sheep showed better growth, structure, and cell-to-cell communication. In contrast, those from prepubertal sheep grew less but showed higher energy activity and early signs of maturation. These findings reveal clear age-related differences and suggest that current methods may need adjustments for younger animals. This work supports the development of better fertility preservation strategies for immature livestock.

Abstract: This study evaluated the effects of low-dose equine chorionic gonadotropin (eCG) supplementation on follicular dynamics, ovulation, corpus luteum (CL) development, luteal hemodynamics, and angiogenesis-related gene expression in indigenous White Lamphun cows under a short-duration estrous synchronization protocol. Twenty multiparous cows were randomly allocated into two groups: a control group (n = 10) and an eCG-treated group (n = 10) receiving 200 IU eCG intramuscularly at CIDR removal (day 0). Daily B-mode ultrasonography revealed significantly faster dominant follicle growth and larger preovulatory follicle (POF) diameters in the eCG group (P < 0.05). CL development assessed on days 4 and 11 post-ovulation (CL 4 and CL 11) showed greater CL diameter, area, and volume in the eCG group (P < 0.01 and P < 0.001, respectively). Color Doppler imaging indicated improved luteal hemodynamics, with a higher colored area/total CL area ratio on both CL 4 (P < 0.05) and CL 11 (P < 0.01). Plasma progesterone (P4) concentrations were significantly elevated at CL 11 (P < 0.05), while preovulatory estradiol (E2) levels were also higher in the eCG group (P < 0.05). Gene expression analysis of luteal tissues on CL 11 revealed significant upregulation of NOTCH4, JAG1, and CD300LG (P < 0.05), whereas NOS3 and MMP9 did not differ significantly between groups (P > 0.05). These results indicate that low-dose eCG enhances follicular development, CL function, and luteal angiogenesis, providing a promising strategy to improve fertility in Bos indicus cattle.

Lay summary: This study tested whether a small dose of equine chorionic gonadotropin (eCG), a hormone naturally produced during pregnancy in horses, can enhance ovarian function in native Thai cattle. We added eCG to a short estrous synchronization program, a hormone-based protocol used to align the timing of ovulation among cows within a few days, and evaluated key reproductive processes: egg release (ovulation), development of the CL, a temporary gland formed after ovulation that secretes progesterone (P4), a hormone essential for establishing and maintaining early pregnancy, and blood flow to the CL. We also measured hormone levels and the activity of genes involved in forming new blood vessels. Cows that received eCG showed stronger ovarian activity, including larger preovulatory follicles, more robust CL development, better ovarian blood flow, and higher P4 levels. Genes related to vascular growth were also more active. These findings indicate that low-dose eCG supports CL function and ovarian physiology and may help improve the efficiency of breeding management in local cattle.

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Abstract: Human KGN cells are a widely studied cellular model for human granulosa cell tumors (GCTs), as well as for non-tumorous human granulosa cells. Such studies are typically performed at oxygen (O2) levels that are equivalent to the atmospheric concentration for practical reasons. However, in most tissues of the human body, as well as in tumors, much lower O2 levels exist. Hypoxic conditions can regulate the phenotype and the behavior of cells in a cell-type-specific way. However, how they may impact KGN cells was not well known. The aim of this study was therefore to evaluate the consequences of a defined hypoxic condition (1% O2; 10 days) in KGN cells. Compared to cells cultured in atmospheric conditions, hypoxia reduced the numbers and increased the size of KGN cells but did not alter cell velocity in cell migration studies. Hypoxia affected the cellular proteome of KGN cells (57 more and 75 less abundant proteins). The associated pathways indicate, among others, metabolic adaptations and mitochondrial changes evoked by hypoxia. The cellular responses may be related, in part, to the increased nuclear expression of hypoxia-inducible factor 1α (HIF1α). The results provide a detailed picture of hypoxia-induced changes in KGN cells and are a resource for future studies. If transferable to the in situ situation, they shed light on how variable O2 levels within the GCT microenvironment may regulate tumor cells and thereby may contribute to tumor cell heterogeneity.

Lay summary: Human cells can be isolated from the body and kept alive in incubators, in which, mainly for practical reasons, the oxygen (O2) levels typically correspond to the surrounding atmosphere. This does not reflect the conditions within the human body, where much lower O2 levels exist. This study shows the importance of low O2 levels on the cellular make-up and behavior of KGN cells, which are accepted models for a group of ovarian tumors (GCTs), as well as normal, non-tumorous granulosa cells (from which GCTs originate). We found that when KGN cells were exposed to low O2 levels, cell numbers and cell size, as well as cellular proteins and RNA, changed. The experiments, revealing adaptations associated with hypoxia, may contribute to a better understanding of the normal ovary and ovarian tumors.

Abstract: The effectiveness of GnRH antagonist protocol remains controversial due to inconsistent conclusions and inadequate subgroup analyses. The aim of this study was to provide some references for clinicians when choosing GnRH antagonist protocol for patients. A retrospective cohort study analyzed 1845 infertility patients aged 20-50 years who underwent IVF/ICSI treatment. They used the GnRH agonist or GnRH antagonist protocol at the Assisted Reproduction Center of Wuhan Union Hospital from June 2023 to June 2024. One-to-one PSM was used to match the population characteristics. The difference of cumulative live birthrates (CLBR) was analyzed by multivariate logistic regression. Endometrial tissues were obtained and the endometrial receptivity was determined by detecting the expression of mesenchymal-epithelial transition (MET), decidualization markers and cell implantation in vitro. There was a significantly higher CLBR in GnRH agonist compared with GnRH antagonist protocol (81.54 versus 73.07%, P<0.05). The GnRH agonist also had significantly higher clinical pregnancy rate (CPR) and live birth rate (LBR) per fresh ET cycle compared to the GnRH antagonist. Multivariate logistic regression analysis showed that ovarian stimulation protocol was an independent risk factor for CLBR. Age and endometrial thickness were significantly correlated with CLBR. Furthermore, GnRH antagonist reduces endometrial receptivity mainly by hindering the formation of MET in stromal cells and affecting endometrial decidualization. The GnRH antagonist protocol may be associated with inferior LBR per fresh ET cycle and CLBR per cycle compared with GnRH agonist protocol, likely due to its negative impact on endometrial receptivity.

Lay summary: Doctors aren't sure how well one of the methods used for IVF treatment-the GnRH antagonist method-works. It uses drugs to temporarily block brain signals to the ovaries, controlling egg maturation and preventing early egg release (critical for IVF success). It isn't known how effective this method at achieving pregnancy or live birth. We analysed previous data and lab tests to guide doctors using this method. Results showed another common method-the GnRH agonist method (using drugs that first boost, then lower brain signals to ovaries to control eggs)-had much higher pregnancy rates and live birth rates per fresh embryo transfer cycle than the GnRH antagonist one. Data showed three key factors affected the cumulative live birth rate: the ovarian stimulation plan used, the patient's age, and the thickness of their womb lining (where embryos attach). Overall, the GnRH antagonist method may lead to lower live birth rates (per transfer and per cycle) than the agonist one-most likely because it makes the womb lining less able to support embryos.