Diminished ovarian reserve (DOR) is a major cause of female infertility, characterized by a complex and multifactorial etiology involving aging, genetic predisposition, environmental factors, and immune mechanisms. Therapeutic options for DOR remain limited, with no currently established treatments demonstrating consistently robust efficacy. Recent advances in regenerative medicine—including the use of mesenchymal stem cells and their derivatives, platelet-rich plasma and in vitro activation—have opened promising new avenues for ovarian function restoration. This review offers a comprehensive summary of research progress in DOR treatment over the past five years, covering hormonal therapies, assisted reproductive technologies, nutritional supplementation and lifestyle modifications, Traditional Chinese Medicine, targeted therapies, and regenerative medicine approaches, with the aim of providing guidance for clinical management of DOR.

Prokineticin 2 (PK2) is a secretory protein containing multiple cysteines with various biological functions, participating in numerous physiological processes in the body. Abnormal expression of PK2 and its signaling pathways can lead to diseases in various systems of the body, including the nervous system, digestive system, immune system, reproductive system, and others. This article will focus on a comprehensive review of the physiological functions of PK2 and its role in reproductive system diseases, aiming to provide theoretical support for the prevention and treatment of infertility and pregnancy-related disorders.

Male reproductive aging is characterized by degenerative changes in the structure and function of the testes. Testicular aging involves alterations in various types of cells, among which lysosomal dysfunction in Sertoli cells is particularly critical. Recent studies have shown that abnormal lysosomal acidification leads to impaired phagosome degradation, which fails to maintain normal nutrient cycling and thereby exacerbates damage to the testicular microenvironment. In addition, endoplasmic reticulum stress, mitochondrial dysfunction, and epigenetic changes are also important factors contributing to reproductive aging. Therefore, molecular intervention strategies targeting lysosomal dysfunction, mitochondrial oxidative stress, and endoplasmic reticulum stress, such as the use of lysosomal activators like ML-SA1 and antioxidants, may offer new therapeutic directions for alleviating male reproductive aging. Future research should further explore the interactions between these mechanisms and potential intervention targets to improve reproductive health and quality of life in middle-aged and older men.

Objective:To establish a day 4 embryo evaluation protocol by analyzing embryonic characteristics affecting blastocyst formation, and validate its clinical effectiveness.Methods:This retrospective cohort study included clinical data from 1 037 patients who underwent fresh in vitro fertilization and embryo transfer (IVF-ET) on day 4 in Center for Reproductive Medicine of Xingtai Meihe Reproductive and Genetic Hospital between January 2018 and April 2024. Morphological assessments were performed at (92±2) h post-fertilization. After excluding 1 326 embryos selected for fresh transfer, 2 723 embryos underwent blastocyst culture. To address selection bias in transferred embryos, the scoring system was primarily based on high-quality blastocyst formation rates. Multivariate binary regression analysis evaluated how day 4 developmental stage, fragmentation rate, stage-specific cleavage patterns, multinucleation/vacuolization affected transferable blastocyst formation rate and high-quality blastocyst rate. Regression coefficients determined parameter weights for high-quality blastocyst formation, establishing a day 4 embryo scoring protocol that compared outcomes across different grades. The scoring system was validated by comparing transferable blastocyst formation rate, high-quality blastocyst rate, and implantation rate among different day 4 embryo grades. All embryos were further rescored according to three previously reported evaluation schemes [Feil 2008, Gemma 2015, and European Society of Human Reproduction and Embryology (ESHRE) 2011]. The predictive values of these three day 4 scoring systems and the day 4 scoring system established in this study were compared using the area under the curve (AUC) receiver operating characteristic (ROC) curve in predicting the formation rate of transferable blastocyst, the formation rate of high-quality blastocyst, and implantation rate. Results:In the prediction of high-quality blastocyst formation, early blastocyst showed the highest influence weight compared to embryos with the ratio of blastomere numbers on day 4 to those on day 3 (BNR) <1.2 ( B=3.398, OR=29.915, P<0.001), followed by fragmentation <10% versus ≥50% ( B=1.263, OR=3.535, P<0.001), a stage-specific cleavage pattern ( B=0.903, OR=2.467, P=0.005), and absence of multinucleation or vacuoles ( B=0.797, OR=2.218, P=0.007). Using the newly developed day 4 scoring system, embryos were graded A, B, C, D, E. Transferable blastocyst formation rates were 88.57% (279/315), 76.99% (241/313), 56.11% (280/499), 40.27% (238/591) and 14.22% (143/1 005), respectively; high-quality blastocyst rates were 51.42% (162/315), 35.46% (111/313), 20.04% (100/499), 9.47% (56/591) and 3.98% (40/1 005). All inter-group differences were statistically significant (all P<0.005). Implantation rates for transferred embryos of grades A-E declined sequentially: 63.18% (381/603), 56.19% (322/573), 38.29% (54/141), 26.53% (13/49) and 9.67% (3/31). The day 4 embryo scoring system proposed in this study demonstrated significantly higher predictive efficacy for transferable blastocyst formation rate (AUC=0.812), high-quality blastocyst formation rate (AUC=0.804), and implantation rate (AUC=0.603) compared with Feil 2008 (AUC=0.797, P<0.001; AUC=0.781, P<0.001; AUC=0.585, P<0.001), Gemma 2015 (AUC=0.773, P<0.001; AUC=0.771, P<0.001; AUC=0.542, P=0.006), and ESHRE 2011 (AUC=0.710, P<0.001; AUC=0.745, P<0.001; AUC=0.592, P<0.001). We also observed the presence of pseudo-compacted embryo, whose transferable blastocyst formation rate [38.28% (49/128)] and high-quality blastocyst formation rate [7.03% (9/128)] were similar to those of cleavage-stage embryos with a BNR≥1.2. Conclusion:The established day 4 morphological assessment system reliably predicts the potential to transferable blastocyst and high-quality blastocyst, and effectively forecasts implantation rates.

Objective:To investigate the effects of individual versus connected microdroplet culture modes in time-lapse (TL) incubators on embryo development parameters and pregnancy outcomes in patients undergoing whole embryo culture to blastocyst stage.Methods:Using a retrospective cohort study, clinical data from 3 507 fresh blastocyst transfer cycles were analyzed. These cycles involved patients who underwent assisted reproductive technology treatment with whole embryo culture to blastocyst stage at the Reproductive Medical Center of Northwest Women's and Children's Hospital between January 2019 and December 2023. Based on different culture modes, patients were divided into two groups, connected group ( n=2 446, using connected microdroplet culture) and individual group ( n=1 061, using individual microdroplet culture). Baseline characteristics, embryo development parameters, pregnancy outcomes, and neonatal outcomes were compared between the two groups. Generalized linear models (GLM) were used to adjust for confounding factors and analyze the effect of culture mode. Results:Embryo development assessment showed the day 3 (D3) high-quality embryo rate in the connected group [60.12% (12 136/20 187)] was significantly lower than that in the individual group [63.62% (4 705/7 395), P<0.001], whereas the high-quality blastocyst formation rate [34.93% (7 052/20 187)] and the available blastocyst formation rate [56.07% (11 319/20 187)] were both significantly higher than those in the individual group [33.08% (2 446/7 395), P=0.004; 51.45% (3 805/7 395), P<0.001], with statistically significant differences. The implantation rate [67.40% (1 774/2 632)], the clinical pregnancy rate [70.20% (1 717/2 446)], and the live birth rate [60.66% (1 469/2 446)] in the connected group were all significantly higher than those in the individual group [63.40% (724/1 142), P=0.017; 66.73% (708/1 061), P=0.041; 55.89% (593/1 061), P=0.021], with statistically significant differences. Neonatal outcomes showed no statistically significant difference between the two groups (all P>0.05). After adjusting for confounding factors using GLM, connected culture was an independent influencing factor for D3 high-quality embryo rate (a MD=-0.017, 95% CI: -0.034-0.000, P=0.046), high-quality blastocyst formation rate (a MD=-0.020, 95% CI: 0.002-0.037, P=0.026), available blastocyst formation rate (a MD=0.032, 95% CI: 0.015-0.048, P<0.001), live birth rate (a OR=1.182, 95% CI: 1.006-1.388, P=0.042). However, it had no effect on D3 available embryo rate, clinical pregnancy rate, or early miscarriage rate (all P>0.05). Conclusion:In TL incubator systems, individual and connected microdroplet culture modes exert different effects at various stages of embryo development. Individual microdroplet culture can significantly enhance cleavage-stage embryo quality, whereas the connected microdroplet culture was more beneficial for enhancing the blastocyst formation rate and quality, ultimately improving the live birth rate without increasing neonatal risks.

The cells within the male reproductive system have a molecular material basis for binding and retaining radionuclides. Radionuclides can cause ionizing radiation damage and genotoxicity to the cells of the male reproductive system through mechanisms such as thermal effects and oxidative stress, leading to corresponding changes in cell structure and function, even cell death, and inducing nuclear genetic material abnormalities or even mutagenesis, resulting in a high risk of genetic or epigenetic defects in offspring. Strengthening the protection, monitoring, and investigation of radionuclides in male reproduction will help prevent damage to the male reproductive system caused by radionuclides, thereby ensuring physical health, including male reproductive health.

Objective:To evaluate the therapeutic efficacy of the Wenyang Huazhuo Formula on spontaneous pregnancy outcomes in advanced-age infertile patients with spleen-kidney yang deficiency syndrome.Methods:A retrospective cohort study design was employed to gather clinical data from 303 advanced-age infertile patients with spleen-kidney yang deficiency syndrome who sought treatment at the Department of Reproductive Medicine in the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine between June 2019 and June 2023. Patients were categorized into two groups based on their treatment regiments: a basic treatment group (non-exposed group, n=151) and a group receiving basic treatment in conjunction with the Wenyang Huazhuo Formula (exposed group, n=152). The study compared and analyzed pregnancy outcomes, including time to pregnancy (TTP) within one year, ongoing pregnancy rate, and clinical pregnancy rate, between the two groups over a one-year follow-up period. Additionally, stratified analyses were performed based on age and anti-Müllerian hormone (AMH) levels to evaluate the impact of Wenyang Huazhuo Formula on pregnancy outcomes across different patient subgroups. Results:The TTP in the exposed group was significantly reduced compared with the non-exposed group ( HR=1.70, 95% CI: 1.12-2.57, P=0.013), suggesting a significant shortening of their TTP, and the ongoing pregnancy rate [28.29% (43/152)] and the clinical pregnancy rate [33.55% (51/152)] were significantly higher than those in the non-exposed group [13.91% (21/151), P=0.020; 21.85% (33/151), P=0.023], and the early abortion rate [15.69% (8/51)] was significantly reduced compared with the non-exposed group [36.36% (12/33), P=0.031]. Stratified analyses by age revealed that for patients aged 35-37 years, the exposed group exhibited a significantly shorter TTP ( HR=1.67, 95% CI: 1.03-2.70, P=0.038), while no significant difference in TTP was observed in the 38-44-year old patients ( HR=1.78, 95% CI: 0.77-4.10, P=0.174). Regarding the ongoing pregnancy rate, the exposed group showed a significant higher rate [31.31% (31/99)] than the non-exposed group [13.91% (15/112), P=0.022] among patients aged 35-37 years, whereas no significant difference was observed in the 38-44 years old group ( P=0.386). Stratified analysis based on AMH levels showed that both low AMH levels (<1.68 μg/L) and high AMH levels (≥1.68 μg/L) patients in the exposed group experienced a significant reduction in TTP compared with the non-exposed group ( HR=8.07, 95% CI: 1.04-62.52, P=0.046; HR=1.57, 95% CI: 1.01-2.43, P=0.044, respectively), along with a notable improvement in the ongoing pregnancy rate [13.64% (6/44) vs. 0% (0/29), P=0.038; 34.26% (37/108) vs.17.21% (21/122), P=0.028, respectively]. Further stratified analysis indicated that, compared with patients with low AMH levels, both the exposed group and the non-exposed group of patients with high AMH levels exhibited a significantly shorter TTP ( HR=1.91, 95% CI: 1.02-3.69, P=0.043; HR=9.48, 95% CI: 1.30-69.22, P=0.002, respectively), along with a significantly higher ongoing pregnancy rate ( P=0.014; P=0.008). Conclusion:The Wenyang Huazhuo Formula significantly shortens TTP, enhances both the clinical pregnancy rate and the ongoing pregnancy rate and reduces the early abortion rate in advanced-age infertile women diagnosed with spleen-kidney yang deficiency syndrome.

With the global trend of delaying childbearing, the decline in female fertility has emerged as a critical public health concern. While previous research predominantly focused on ovarian failure, recent studies have revealed that endometrial aging and impaired endometrial receptivity are closely associated, serving as significant contributors to reproductive failures such as embryo implantation failure and recurrent miscarriage. This review aims to explore the impact of age-related and pathological endometrial epithelial cell senescence on the impairment of endometrial receptivity, with a focus on key factors including the senescence-associated secretory phenotype, oxidative stress, cellular-level alterations (e.g., abnormalities in cilia proportion and function), and the endometrial microenvironment. By elucidating the molecular mechanisms and signaling pathways underlying endometrial epithelial senescence, this review seeks to advance the development of effective interventions, offering novel therapeutic strategies to enhance endometrial receptivity and improve fertility outcomes among advanced-age women.

Objective:To investigate the pregnancy outcomes in patients ≤35 years old with diminished ovarian reserve (DOR) undergoing intrauterine insemination (IUI).Methods:A retrospective cohort study was conducted by analyzing the clinical data of 6 229 IUI cycles performed in patients aged ≤35 years at the Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University between June 2016 and March 2024. Based on serum anti-Müllerian hormone (AMH) levels, the subjects were divided into two groups: patients with AMH <1.1 μg/L were classified as the DOR group (489 cycles), and patients with AMH ≥1.1 μg/L were classified as the normal ovarian reserve (NOR) group (5 740 cycles). Propensity score matching (PSM) was applied to control for confounding factors, after 1∶1 PSM matching, 486 cycles were included in each group. Clinical pregnancy rate, miscarriage rate, live birth rate, biochemical pregnancy rate, and ectopic pregnancy rate were compared between the two groups by generalized estimating equations.Results:The clinical pregnancy rate was 21.19% (103/486) in DOR group and 24.07% (117/486) in NOR group, with no statistically significant difference ( P=0.294). The live birth rate was 18.31% (89/486) in DOR group and 20.16% (98/486) in NOR group, also without significant difference ( P=0.469). Additionally, no significant differences were observed in miscarriage rate, biochemical pregnancy rate, or ectopic pregnancy rate between the two groups (all P>0.05). Conclusion:In patients aged ≤35 years with DOR, pregnancy outcomes from IUI are comparable to those in young patients with NOR.

Objective:To reveal the relationship between fat mass and obesity associated (FTO) protein and the occurrence of diseases in patients with polycystic ovary syndrome (PCOS) combined with metabolic syndrome (MS).Methods:A retrospective case-control study was conducted, and general clinical data and laboratory test indicators of 50 PCOS patients (PCOS group) and 54 healthy individuals (control group) were collected from December 2023 to October 2024. The PCOS group was divided into the PCOS without MS subgroup (PCOS+nMS subgroup, n=25) and the PCOS with MS subgroup (PCOS+MS subgroup, n=25) based on whether MS was present or not. The expression level of serum FTO protein was detected by enzyme-linked immunosorbent assay method. The clinical data and metabolic characteristics of PCOS patients were analyzed, as well as the correlation between serum FTO protein level and the occurrence of PCOS with MS. Receiver operating characteristic (ROC) curves were drew to analyze the predictive ability of serum FTO protein level for PCOS combined MS, and the correlation between serum FTO protein level and metabolic status of PCOS patients was evaluated through logistic regression model. Results:The level of serum FTO protein in the PCOS group [57.42 (45.87, 68.53) μg/L], and PCOS+nMS subgroup [48.41 (37.84, 64.30) μg/L] was all significantly higher than that in the control [45.70 (36.41, 52.86) μg/L, P<0.001; adjusted P=0.016]. The expression level of serum FTO protein in PCOS+MS subgroup [60.31 (50.99, 72.28) μg/L] was significantly higher than that in PCOS+nMS subgroup (adjusted P=0.013) and the control (adjusted P<0.001). The serum FTO protein expression level in the PCOS group was significantly positively correlated with body mass index, waist circumference, systolic blood pressure,diastolic blood pressure, low density lipoprotein cholesterol, homeostasis model to assess insulin resistance index (all P<0.05). The expression level of serum FTO protein had a certain predictive value for PCOS, with an area under the curve (AUC) value of 0.725 (95% CI: 0.627-0.824) and a better predictive value for the occurrence of MS in PCOS, with an AUC value of 0.869 (95% CI: 0.762-0.976) as shown by the ROC curve. Multivariate logistic regression analysis indicated that in PCOS patients, the expression level of serum FTO protein had a significant positive effect on the coexistence of MS, ( OR=1.092,95% CI: 1.010-1.180, P=0.026). Conclusion:PCOS patients have higher serum FTO protein levels than healthy women, and PCOS patients with MS have higher serum FTO protein levels than those without MS. The serum FTO protein level has a good predictive value for the occurrence of PCOS and PCOS complicated with MS, and is an independent risk factor for the occurrence of MS in PCOS.