Reproduction & fertility最新文献

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Abstract: Oocyte in vitro maturation (IVM) is an evolving component of assisted reproductive technology (ART) that offers a less invasive and cost-effective alternative to conventional controlled ovarian stimulation. It is particularly beneficial for patients at risk of ovarian hyperstimulation syndrome (OHSS), those with polycystic ovary syndrome (PCOS), and individuals requiring urgent fertility preservation. Despite these advantages, clinical uptake has remained limited owing to concerns about the developmental competence and quality of IVM-derived oocytes. To address this, we conducted a comprehensive literature search of PubMed, Embase, and Web of Science for articles published between January 2000 and June 2025, using combinations of keywords related to IVM, oocyte maturation, culture protocols, oocyte quality, and clinical outcomes. Recent progress in the field has led to the development of biphasic culture systems, pre-IVM priming strategies, and the incorporation of regulatory factors such as C-type natriuretic peptide (CNP) and oocyte-secreted factors, all of which have contributed to improved oocyte maturation and embryo development. Nonetheless, variability in outcomes persists due to differences in patient selection, stimulation protocols, and laboratory practice. Continued optimisation of IVM culture systems and a deeper understanding of oocyte maturation mechanisms will be essential for enhancing clinical efficacy. Future research should prioritise standardisation, patient-tailored protocols, and systematic long-term outcome data to support wider adoption of IVM. This review provides a comprehensive overview of recent advances and ongoing challenges in human oocyte IVM, offering perspectives on future directions for clinical translation and improved ART outcomes.

Lay summary: IVM is a fertility treatment that allows immature eggs to mature in the laboratory rather than within the body. This approach can be safer, simpler, and more affordable than traditional IVF, especially for women with polycystic ovary syndrome (PCOS), those at risk of ovarian hyperstimulation, or those who need to preserve their fertility quickly, such as cancer patients. Although IVM holds great promise, it is not yet widely used because its success rates are not as high as those of conventional methods. This review looks at the latest scientific progress to improve IVM, including better laboratory techniques, the use of natural hormones and growth factors, and new ways to support egg development outside the body. These advancements have helped improve the quality of eggs and embryos, but challenges remain. Differences in patient types, medications used, and lab practices can affect how well IVM works. More research is needed to make IVM more consistent and effective so it can become a routine fertility option for a broader population.

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Abstract: Ovarian tissue transplantation is vital for preserving fertility in female cancer survivors. Since the first human ovarian tissue transplantation in 2000 and the first live birth in 2004, it has received much more attention. However, the research scale, core research teams, and publication quality have not been systematically documented. This lack of foundational data hinders researchers' ability to assess the maturity and prevailing trends within the domain, potentially leading to duplicated efforts and suboptimal resource allocation. Our study addresses this gap by analyzing ovarian tissue transplantation research from 2000 to 2023 to map academic performance and collaboration networks. Key findings reveal Belgium and the USA as leading contributors, with robust international collaboration driving progress. The Université Catholique Louvain emerged as the most productive institution, while Dolmans M.M. stood out as a pivotal researcher. Human Reproduction ranked as the top journal for disseminating OTT advancements. Research trends highlight sustained focus on 'tissue cryopreservation', 'activation', and 'live-birth' through 2023, with disease indications shifting from 'breast cancer' and 'chemotherapy' toward 'infertility', 'leukemia', and 'premature ovarian failure'. This study offers crucial insights and understanding for collaborative work among researchers in the field of ovarian tissue transplantation, as well as recommendations for pioneering authors and journal submissions.

Lay summary: Ovarian tissue transplantation is the sole fertility preservation method for prepubertal girls and adult female patients whose anticancer therapy cannot be delayed. Since the first successful human live birth via ovarian tissue transplantation in 2004, this medical procedure has witnessed exponential growth, with more than 200 newborns worldwide having been delivered. This study presents an exhaustive bibliometric analysis that delineates the knowledge structure, authors' contributions, and research trends concerning ovarian tissue transplantation during the 21st century. We reveal that Belgium and the USA are in leading positions in terms of publications, citations, and academic influence. Keywords highlight the developmental trends in research types, ongoing foci, and disease indications for ovarian tissue transplantation. It offers crucial insights and understanding for collaborative work among researchers in the field of ovarian tissue transplantation, as well as recommendations for pioneering authors and journal submissions.

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Abstract: Using a large patient series, we aimed to evaluate, in a high-responder population, the effect of triggering oocyte maturation with human choriogonadotropin (hCG) or with a gonadotropin-releasing hormone agonist (GnRHa). We analyzed data from 683 intended fresh embryo transfer cycles (ETCs) and 534 frozen-thawed embryo transfer (FET) cycles. The rates of ovarian hyperstimulation syndrome (OHSS), and the embryological, clinical, and newborn outcomes were compared. Considering the type of oocyte maturation trigger and embryo destination, cycles were divided into five groups. Cycles using an hCG-trigger, with progesterone luteal support, had fresh embryo transfer or embryo freeze-all (FA). Cycles using GnRHa/agonist-trigger, with hCG, estrogen, and progesterone luteal support, had fresh embryo transfer or embryo FA. The fifth group consisted of agonist-trigger cycles, without luteal support, that underwent embryo FA. Severe OHSS only occurred in fresh ETC, with the agonist-trigger evidencing a non-significantly lower rate. The FA groups evidenced higher numbers of retrieved oocytes and blastocyst rates. In fresh ETC, the Ag-fresh-hCG group evidenced higher implantation and clinical pregnancy rates. No differences were observed in clinical outcomes after FET, but cumulative clinical outcomes showed higher clinical pregnancy and newborn rates in the Ag-fresh-hCG group. After multivariable logistic regression analysis, these differences were not observed. The present results thus suggest that, in high-responders, the use of a GnRHa-trigger with luteal hCG in a fresh ETC presents similar outcomes relative to the use of an hCG-trigger. Data also suggest that FA should be applied to all suspected OHSS cases.

Lay summary: Ovarian hyperstimulation syndrome (OHSS) is a complication of medically assisted reproduction treatments that may require hospitalization. In the presence of high risk to develop OHSS, embryo transfer can be canceled and embryos frozen to be used in a later cycle. Alternatively, a newer drug, an agonist, can be used for egg trigger in association with endometrium special preparation. Some characteristics make women more susceptible to develop OHSS. In this group of patients, we observed that the use of an agonist as egg trigger did not decrease pregnancy outcomes and that the option of freezing all embryos followed by embryo transfer in a later cycle abolished development of OHSS with hospitalization.

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Abstract: Endometriosis is a prevalent condition where tissue similar to the uterine lining grows outside the uterus, causing pain and infertility. Diagnosing endometriosis typically requires invasive procedures such as laparoscopy. MicroRNAs (miRNAs) have emerged as promising noninvasive biomarkers for various diseases, including endometriosis. However, studies have shown inconsistent miRNA expression patterns across populations. This study aims to validate circulating miRNAs as biomarkers for endometriosis in Indian women, addressing the limited validation data available for this population. This comprehensive review identified nine circulating miRNAs based on reproducibility and consistent expression patterns. Women with advanced-stage endometriosis (n = 12) and controls (n = 11) were recruited. Plasma samples were collected based on clinical symptoms, CA-125 levels, ultrasound, MRI findings, and laparoscopic confirmation. miRNA expression was quantified using qRT-PCR, and receiver operating characteristic (ROC) analysis was performed to assess diagnostic potential. Nine miRNAs (miR-451a, let-7b, miR-150-5p, miR-17-5p, miR-3613-5p, miR-20a-5p, miR-342-3p, miR-125b-5p, and miR-21-5p) were analyzed. Among them, miR-451a and miR-20a-5p exhibited significantly lower expression in endometriosis patients (n = 12) compared to controls (n = 11). ROC analysis demonstrated promising diagnostic potential for these miRNAs. miR-451a showed distinct trends compared to previous studies, while miR-20a-5p was consistent with earlier research. Although encouraging, these findings are based on a limited sample size. Larger multicenter studies across diverse populations using reliable reference genes are needed to fully assess the diagnostic value of these miRNAs as biomarkers for endometriosis.

Lay summary: Endometriosis is a common condition where tissue similar to the uterine lining grows outside the uterus, causing pain and infertility. Diagnosing it usually requires invasive procedures such as laparoscopy. We focused on microRNAs (miRNAs), small molecules in plasma that could offer a noninvasive way to diagnose endometriosis. After reviewing 45 research articles, we identified 102 miRNAs that were elevated and 197 that were reduced in endometriosis patients. From these, we selected nine promising miRNAs for validation in the Indian population. We collected blood samples from 12 women with endometriosis and 11 healthy controls. Our analysis showed significant differences in miRNA expression, with miR-451a and miR-20a-5p showing strong potential to distinguish between endometriosis patients and healthy individuals. These findings suggest that miRNAs could improve the diagnosis of endometriosis in a less invasive manner. In conclusion, our research highlights the potential of miRNAs in advancing endometriosis diagnosis and management.

Abstract: Dietary zinc deficiency disrupts fertility in vivo by impairing oocyte and embryo development near ovulation. Acute treatment of newborn ovaries with a strong intracellular chelator (TPEN), which preferentially binds zinc, disrupts follicular development. However, the chronic effects of transition metal chelation on preantral follicle development are not known. In this study, the effect of the extracellular transition metal chelator, diethylenetriaminepentaacetic acid (DTPA), was used to examine more prolonged effects on preantral follicle development. Preantral granulosa cell-oocyte complexes from 14-day-old mice were cultured under control, chelated (DTPA), or rescue (DTPA + ZnSO4) conditions for up to 10 days. Preantral follicles cultured in DTPA alone showed impaired growth, disrupted nucleolar morphology, and impaired meiotic progression. The granulosa cells in DTPA-treated follicles underwent apoptosis at a higher rate than controls, had fewer physical connections to the oocyte, and reduced activation of pSMAD2 signaling. Moreover, Lhcgr and Ar transcripts were higher in cumulus cells, and Figla was lower in oocytes from DTPA-treated follicles. These data support a role for transition metals in general, and zinc in particular, in proper development of preantral ovarian follicles. The loss of somatic support cells explains some or all of the growth and developmental deficits seen in the DTPA-treated oocytes. DTPA preferentially binds zinc. Therefore, these results support growing evidence that a proper supply of transition metals, including zinc, is essential for optimal ovarian function.

Lay summary: The roles the mineral zinc plays in the ovary are not yet clear. The present study used follicles from mouse ovaries that were grown in the lab for up to 10 days. Follicles are round structures that contain a large egg cell at the center, surrounded by smaller cells called granulosa cells. Follicles were either grown with adequate zinc or insufficient zinc levels. The findings show that follicles require sufficient zinc to form connections between the egg and granulosa cells, which are essential for growth of both the egg and the granulosa cells. When there is insufficient zinc, loss of these connections leads to more granulosa cells dying and smaller follicles. These results show that zinc is important for growth of ovarian follicles, which could be important for treating infertility by supplying adequate levels of zinc in the diet.

Abstract: Adenomyosis is an estrogen-dependent disease featuring chronic inflammation. This study was undertaken to investigate whether vagal tone is reduced in patients with adenomyosis compared with healthy women. We recruited 75 patients with adenomyosis, as diagnosed by a combination of ultrasound and gynecological examination, and 75 healthy women without adenomyosis, endometriosis, or other uterine disorders per ultrasound examination. All recruited subjects received an electrocardiogram evaluation, and their heart rate variability was assessed. In addition, lesional stiffness for patients with adenomyosis and myometrial stiffness for healthy controls were measured by ultrasound elastography. Severity of dysmenorrhea and the amount of menstrual blood loss were also evaluated. Patients with adenomyosis exhibited statistically significant sympatho-vagal imbalance, featuring domination of the sympathetic branch of the autonomic nervous system over the parasympathetic branch, as evidenced by reduced vagal tone and increased sympathetic activity. In addition, lesional stiffness, a proxy for the extent of lesional fibrosis, was found to be negatively associated with vagal tone. Patients with adenomyosis have reduced vagal tone. In addition, reduced vagal tone is likely attributable to increased lesional stiffness, a proxy for the extent of lesional fibrosis, which correlated with the severity of dysmenorrhea and the amount of menstrual blood loss. This raises the prospect of employing vagus nerve stimulation as a possible therapeutics approach. Future human studies are needed to determine whether vagus nerve stimulation can have any therapeutic effects.

Lay summary: Adenomyosis is a condition in which the inner lining of the uterus is found in the muscular wall of the uterus (called the myometrium). It is a common gynecological disease affecting mostly women of reproductive age. We found that patients with adenomyosis exhibited significant imbalance between the 'flight-or-fight' system and the 'rest-and-digest' system (sympatho-vagal imbalance), featuring reduced vagal tone (dampened calm-down system) and increased sympathetic activity (more anxiety and restlessness). In addition, we found that the stiffness of adenomyotic lesions, which can be viewed as a proxy for the 'age' of the lesions, was negatively associated with vagal tone. This reduced vagal tone may suggest that perhaps some vagal stimulating procedures, which are safe and non-invasive, can be used to boost vagal tone to achieve therapeutic purposes.

Abstract: The objective of the study was to i) characterize the aerobic and microaerophilic vaginal microbiota of collared peccaries (Pecari tajacu) across reproductive stages and ii) correlate microbiota findings with progesterone levels and vaginal cytology at each reproductive stage. Samples were collected for progesterone assessment (serum concentration), vaginal cytology, and microbial analysis (after isolation followed by MALDI-TOF identification) from four young pubescent, four non-pregnant, and three pregnant females. Microbial composition varied according to the reproductive stage: young pubescent females predominantly harbored Alcaligenes faecalis (Proteobacteria; 33.3%), non-pregnant females primarily hosted Bacillus badius and Staphylococcus microti (Firmicutes; 85.7%), and pregnant females had more Bacillus cereus and Mammaliicoccus sciuri (Firmicutes; 54.5%). No significant correlation (P > 0.05) was found between microbial proportions and progesterone levels or vaginal cytology. Although no differences were detected in the proportions of different vaginal bacterial populations, there was great qualitative diversity of species of microorganisms among females at different reproductive stages. While the small sample size may have limited our ability to detect more subtle quantitative differences, these findings provide foundational insights into the reproductive microbiota of collared peccaries, with potential implications for their conservation and management.

Lay summary: Despite the importance of reproductive microbiomes in animal conservation, there is still a lack of knowledge in many wild species. The present study characterized for the first time the composition of the aerobic and microaerophilic microbiota (bacteria that can survive in the presence of oxygen or in low-oxygen conditions, respectively) of the vaginal tract from collared peccaries (pig-like mammals from Central and South America commonly known as musk hogs) at different reproductive stages. Although no differences were detected in the proportions of different vaginal bacterial populations, there was great qualitative diversity of species of microorganisms among females at different reproductive stages. These findings provide foundational insights into the reproductive microbiota of collared peccaries, with potential implications for their conservation and management.

Abstract: Uterine rupture is a major complication of caesarean section (CS) associated with high fetal and maternal morbidity. The objective is to develop an in vivo model of uterine healing and rupture after CS in order to analyse histological phenomena controlling scarring tissue development and potential causes of defects. Eighteen pregnant primiparous female rabbits were bred naturally. At caesarean, after 28 days of gestation, foetuses were either extracted through a longitudinal incision in one of the uterine horns ('CS horn') or via a short incision at the tip of the contralateral horn ('control horn'). The uterine horns were sutured in a single layer, all by the same surgeon. They were mated again 14 days later and euthanised at G28. Genital tracts were collected for histological, biomechanical and polarimetric analyses. Macroscopically, 2/18 presented a dehiscence and 1/18 a spontaneous rupture. The mean thickness of the scarred area was significantly lower, 0.9 mm (0.7-1.4), than the non-scarred area on CS horns 2.2 (1.6-2.3) or control horns 2 (1.5-2.3) (P < 0.0001). The scar zone was statistically more fibrous (P < 0.0001), containing fewer vessels (P = 0.03), oestrogen receptors (P < 0.001) and progesterone receptors (P < 0.0001). After balloon inflation, rupture occurred in the scar zone in 8 out of 17 cases (47%). Polarimetry revealed that the scar zone was statistically inhomogeneous (73%). Multifactorial analysis identified groups with poor uterine healing and less resistance to rupture (balloon inflation), mostly in cases of thin myometrium in the scar, and a group with strong resistance to rupture and correct healing characteristics.

Lay summary: CS rates are rising across the world. When a CS is carried out, it can lead to scarring on the uterus that can affect its resistance to pressure. During the next pregnancy, the uterus can tear, increasing risks to the mother and baby. We carried out CSs in rabbits, allowing us to analyse the scar on the uterus, the healing and tissue resistance. The scarred part of the uterus was statistically thinner, more fibrous and contained fewer vessels and hormone receptors than the area without scarring. Under similar conditions, poor healing was observed in some animals, reducing resistance in following pregnancies. These results suggest that individual and genetic factors have an effect on healing after a CS. This study may improve our knowledge and management of care for patients who have a CS in order to reduce complications.

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Abstract: Intending parents on the African continent have limited access to quality services for infertility treatment. South Africa is the primary provider of fertility care on the continent, but because specialist training is only available in three public (teaching) hospitals, supported through partnerships with private institutions, there is a shortage of medical staff and waiting times for admission to training programmes can be years. We draw on data from our qualitative research study on assisted reproduction, generated from clinic visits, informal interviews, participation in science meetings, and formal interviews with 117 patients, gamete donors, clinicians, reproductive scientists and others to explore access to and motivation for training. Trainees' reasons for embarking on this specialisation included: concern with limited access to gynaecological and fertility care on the continent; lack of skilled fertility specialists and embryologists; and lack of options for assisted reproduction available to low-income intending parents. Trainee fellows expressed commitment to low-cost IVF models to address the lack of affordable and accessible reproductive health care. Fertility specialists often shared this concern and emphasised the need for trained professionals to expand services. In general, interviewees felt that infertility care and assisted reproduction were regarded as of lesser importance to other reproductive and health problems, despite the extent of infertility and the demand for assisted reproduction technology (ART) on the continent.

Lay summary: Countries across the African continent have the highest infertility rate in the world, yet access to diagnosis of cause, treatment and assisted reproductive technology is sparse. Assisted reproduction clinics now operate in several countries, particularly Ghana, Nigeria, Kenya and South Africa. Most support is in the private health system, and few women and men have access to low-cost assisted reproduction services at public hospitals. While clinics, biobanking services and laboratories are sparse, so too is training. We draw on data from a large study on assisted reproduction in South Africa to explore the provision of training. Most training is provided in South Africa, and people from other countries can access this. However, few teaching hospitals provide training, and people face long delays, sometimes years, before they can enrol. The limited opportunities for training seriously impact the capacity of countries to meet the health needs and support the reproductive hopes of many of their populations.