驅動卵巢纖維化的關鍵分子路徑包括轉化生長因子-β (TGF-β)/Smad訊號路徑、Wnt/β-catenin路徑和PI3K/Akt通路，

這些路徑調控纖維母細胞活化、細胞外基質重塑和組織硬化。

纖維化卵巢間質的特徵是I型和III型膠原蛋白、纖維連接蛋白和透明質酸含量升高，從而破壞正常的卵泡發生和類固醇生成。卵巢纖維化也與多囊性卵巢症候群、卵巢早衰和子宮內膜異位症等生殖系統疾病相關，

目前治療策略集中在吡非尼酮等抗纖維化藥物、TGF-β抑制劑和氧化壓力調節，以及乾細胞療法等新興療法。

. 2026 Jan 7;32(1):gaaf058.

doi: 10.1093/molehr/gaaf058.

Molecular mechanisms of ovarian fibrosis

Ovarian fibrosis is increasingly recognized as a pivotal factor contributing to ovarian ageing, dysfunction, and female infertility. It results from chronic or repetitive ovarian injury, such as that caused by repeated ovulation, which induces inflammation and excessive extracellular matrix (ECM) deposition, predominantly by activated fibroblasts and myofibroblasts. The key molecular pathways driving ovarian fibrosis include transforming growth factor-beta (TGF-β)/Smad signalling, Wnt/β-catenin, and PI3K/Akt pathways, which orchestrate fibroblast activation, ECM remodelling, and tissue stiffening. Elevated collagen types I and III, fibronectin, and hyaluronan characterize the fibrotic ovarian stroma, disrupting normal folliculogenesis and steroidogenesis. Ovarian fibrosis is also implicated in reproductive pathologies such as polycystic ovary syndrome, premature ovarian insufficiency and endometriosis, and may contribute to an increased risk of ovarian cancer, although definitive causal links require further elucidation. Current therapeutic strategies remain largely experimental, focusing on antifibrotic agents such as pirfenidone, TGF-β inhibitors, and modulation of oxidative stress, alongside emerging interventions such as stem cell therapies, which are offer potential avenues for intervention in the ovary. This review synthesizes current insights into the cellular and molecular mechanisms driving ovarian fibrosis, its association with reproductive disorders, and emerging therapeutic strategies. It underscores key knowledge gaps and emphasizes the need for future research focused on fibroblast activation, inflammatory signalling, and immune-ECM interactions to facilitate the development of targeted, long-term interventions aimed at preventing or reversing ovarian fibrosis and preserving female fertility. 

 

1. 精索靜脈曲張影響15%的男性族群。
2. 精索靜脈曲張合併低睪固酮水平的患者在接受精索靜脈曲張修復術後，總睪固酮水平平均升高約80至100 ng/dL。
3. 精索靜脈曲張切除術可能在無需藥物的情況下顯著改善睪固酮水平

. 2026 Jul;126(1):3-8.

doi: 10.1016/j.fertnstert.2026.03.011.

Varicocele and low testosterone

Varicoceles are estimated to affect 15% of the general male population. The association between varicocele and infertility has been well established, as reflected by impaired spermatogenesis. However, it is also crucial to consider the role of testes in testosterone production and the effects of testosterone deficiency on overall male health. Patients with varicocele and low testosterone have been found to have an average increase of approximately 80 to 100 ng/dL in total testosterone levels after varicocele repair. In combination with other interventions, such as weight loss, varicocelectomy may provide sufficient improvements in testosterone levels without requiring medications. Further research is warranted to better define predictors of postvaricocelectomy improvements, such as age, baseline testosterone levels, and varicocele grade, and to clarify the clinical significance of postoperative testosterone increases.

1.  在OAT患者中，DGC法獲得的精子數量最多，速度、活力和SSFI也最佳。
2. AGF-2技術在正常精子症患者中是最有效的方法。 
3. DGC、AGF-2和上游處理後，精子DNA損傷顯著降低。
4. DGC對OAT患者最有益，
5. AGF-2和上游法更適合正常精子症患者。

. 2025 Nov 21;6(4):e250012.

doi: 10.1530/RAF-25-0012. Print 2025 Oct 1.

Sperm preparation techniques affect biological parameters, fertility indices, and DNA fragmentation in patients with oligo-astheno-teratozoospermia

Abstract: In normozoospermia, the albumin gradient filtration (AGF) and swim-up processing techniques are used to isolate spermatozoa with the highest biological parameters and specific sperm fertility indices (SSFI). In contrast, the highest number of sperm with the best motility rate, velocity, and SSFI, and the lowest DNA damage and nuclear fragmentation are isolated using the density gradient centrifugation (DGC) preparation technique in oligo-astheno-teratozoospermia (OAT) patients. The study aimed to evaluate the effect of DGC, AGF-1, AGF-2, and swim-up preparation techniques on biological parameters, including SSFI, chromatin integrity, and DNA fragmentation in patients with OAT and normozoospermia. One hundred men with normozoospermia and OAT participated in the study. Biological parameters (concentration, velocity, total motility, and normal morphology), SSFI (progressively motile sperm concentration-grade a (PMSCa), progressively motile sperm concentration-grade b (PMSCb), and sperm motility index, functional sperm concentration, motile sperm concentration), chromatin integrity, and DNA fragmentation were assessed before and after each processing method using SQA-V Gold sperm analyzer and specific staining, TUNEL, and COMET assays. In OAT patients, the highest number of sperm with the best velocity, motility, and SSFI was demonstrated in the DGC method. However, the AGF-2 technique was the most efficient method in normozoospermic patients. Sperm DNA damage significantly decreased following preparation with DGC, AGF-2, and swim-up techniques. Overall, the findings highlight that DGC is the most beneficial method for OAT patients, whereas AGF-2 and swim-up techniques are more suitable for normozoospermic individuals. These comparisons emphasize the need to tailor techniques according to patient-specific sperm profiles.

1.  菌叢失調——以乳酸桿菌屬減少和厭氧菌過度生長為特徵——與不良妊娠結局相關。
2. 慢性子宮內膜炎常伴隨乳桿菌屬減少和致病微生物（如加德納菌和埃希氏菌）定植，
3. 抗生素治療可能恢復菌叢平衡，並已被報告可提高胚胎著床率。
4. 反覆著床失敗通常與非乳酸桿菌主導的子宮內膜菌群有關，
5. 聯合使用抗生素和益生菌可部分恢復其正常狀態。
6. 多囊性卵巢症候群中，腸道菌叢失衡——以微生物多樣性低、短鏈脂肪酸產生菌減少和脂多醣產生革蘭氏陰性菌增加為特徵——與代謝和生殖功能障礙均相關。膳食纖維、益生菌和二甲雙胍可能有助於重建菌叢平衡。
7. 子宮內膜異位症和子宮肌腺症患者的生殖道菌叢多樣性往往較高，乳桿菌豐度降低，可能加劇發炎反應。
8. 妊娠期間，富含乳酸桿菌的陰道菌叢與較低的流產和早產風險有關。

Review

. 2026 Apr;125(4):574-582.

doi: 10.1016/j.fertnstert.2026.01.010. Epub 2026 Jan 21.

The reproductive tract microbiome and female fertility: dysbiosis, disease links, and emerging therapeutic strategies

The reproductive tract microbiome plays a pivotal role in female fertility, with Lactobacillus-dominated communities maintaining a protective, low-pH environment. Dysbiosis-characterized by a reduction in Lactobacillus species and overgrowth of anaerobes-is associated with adverse outcomes. Chronic endometritis frequently involves diminished Lactobacillus species and colonization by pathogenic microbes such as Gardnerella and Escherichia, and antibiotic treatment may restore eubiosis and has been reported to improve implantation rates. Recurrent implantation failure is often linked to non-Lactobacillus-dominated endometrial microbiota, which can be partially normalized through combined antibiotic and probiotic interventions. In polycystic ovary syndrome, gut dysbiosis-marked by low microbial diversity, reduced short-chain fatty acid-producing bacteria, and increased lipopolysaccharide-producing Gram-negative species-correlates with both metabolic and reproductive dysfunction. Dietary fiber, probiotics, and metformin may help reestablish microbial balance. Patients with endometriosis and adenomyosis tend to harbor high-diversity reproductive tract microbiota with decreased Lactobacillus abundance, potentially exacerbating inflammatory pathways. During pregnancy, a Lactobacillus-rich vaginal microbiota is associated with lower risks of miscarriage and preterm birth, whereas bacterial vaginosis-like, high-diversity communities are linked to increased risks. Emerging therapies-including antibiotics, vaginal probiotics, and vaginal microbiota transplantation-aim to restore eubiosis and improve reproductive outcomes. Collectively, this review highlights the impact of dysbiosis on fertility and summarizes emerging therapeutic strategies to optimize reproductive success.

 節段性嵌合體和染色體單體嵌合體胚胎的懷孕結局與整倍體胚胎的懷孕結局相當，

染色體三體嵌合體胚胎的懷孕結局則明顯較差

. 2026 May;125(5):786-796.

doi: 10.1016/j.fertnstert.2026.01.008. Epub 2026 Jan 21.

Impact of different types of embryonic mosaicism on pregnancy outcomes

Objective: Mosaic embryos can yield healthy live births, although pregnancy outcomes are inferior to those with euploid embryos. Pregnancy outcomes also vary significantly among mosaic embryos with different characteristics, yet current classifications lack sufficient granularity to reflect this heterogeneity. However, prevailing classification systems lack sufficient granularity to adequately reflect this heterogeneity. The objective of this study is to delineate pregnancy outcome differences among mosaic embryos categorized using a refined classification framework that provides greater resolution of mosaicism characteristics.

Subjects: A total of 434 cycles of mosaic embryo transfers and 868 cycles of euploid embryo transfers were included.

Exposure: The euploid or mosaic embryos transferred and the characteristics of mosaicism.

Main outcome measures: Clinical pregnancy rate, ongoing pregnancy rate, live birth rate, first-trimester pregnancy loss rate, incidence of maternal complications, and congenital anomalies.

Results: Generalized estimating equation (GEE) models were used to compare pregnancy outcomes between groups. Overall, mosaic embryos were associated with significantly inferior pregnancy outcomes than euploid embryos, driven primarily by high-level mosaic embryos. Compared with euploid embryos, the segmental mosaic embryos had similar pregnancy outcomes, whereas the chromosomal mosaic embryos had worse pregnancy outcomes, with lower clinical pregnancy rate (odds ratio [OR]=0.65; 95% confidence interval [CI]: 0.43-0.98), ongoing pregnancy rate (OR=0.56; 95%CI: 0.37-0.84), and live birth rate (OR=0.61; 95%CI: 0.41-0.92). Within chromosomal mosaic embryos, pregnancy outcomes did not differ significantly between monosomy mosaic and euploid embryos. In contrast, chromosomal trisomy mosaic embryos presented markedly worse outcomes than euploid embryos across all measures: biochemical pregnancy rate (OR=0.46; 95%CI: 0.25-0.83), clinical pregnancy rate (OR=0.48; 95%CI: 0.27-0.84), first-trimester pregnancy loss rate (OR=6.00; 95%CI: 1.99-18.11), ongoing pregnancy rate (OR=0.32; 95%CI: 0.18-0.58), and live birth rate (OR=0.35; 95%CI: 0.19-0.63). Finally, the incidence of maternal complications and congenital anomalies did not differ significantly between mosaic and euploid groups.

Conclusion: Segmental and chromosomal monosomy mosaic embryos have pregnancy outcomes comparable with those of euploid embryos, whereas chromosomal trisomy mosaic embryos are associated with significantly poorer outcomes.

 子宮內膜容受性分析 (ERA) 顯示，無論是一般不孕症族群或是有胚胎移植失敗史的患者，ERA 都無法優化 EET 週期中的生殖結果

. 2023 Oct 23:14:1251699.

doi: 10.3389/fendo.2023.1251699. eCollection 2023.

Does endometrial receptivity array improve reproductive outcomes in euploid embryo transfer cycles? a systematic review

Besides chromosomal normality, endometrial receptivity is an important factor in determining successful pregnancies. Endometrial receptivity array (ERA), a promising endometrial receptivity test, was speculated to improve the reproductive outcomes. However, its effectiveness is controversial in clinical practice. Therefore, we conducted this review to investigate its role in in vitro fertilization (IVF) treatment. To eliminate the interference of embryo quality, we only analyzed studies that originally reported the reproductive outcomes of patients who underwent ERA-guided euploid embryo transfer (EET). Unexpectedly, it revealed that ERA could not optimize the reproductive outcomes in EET cycles, no matter in general infertile population or in patients with a history of previous failed embryo transfers.

 endometrial receptivity analysis (ERA)子宮內膜容受性分析 

ERA接受性( receptivity)與否

----與年紀無明顯關聯

. 2026 Apr;43(4):1169-1177.

doi: 10.1007/s10815-026-03824-2. Epub 2026 Feb 9.

Endometrial aging and uterine receptivity: endometrial receptivity analysis (ERA) outcomes in female patients of diverse age groups

Purpose: To assess whether the endometrial receptivity analysis (ERA) captures receptivity changes attributed to endometrial aging and whether it may be useful for older patients undergoing fertility treatment.

Methods: Retrospective cohort study of patients who underwent ERA testing at an academic center (01/2019-05/2024). The ERA inferred transcriptomic levels of canonical receptivity markers from biopsies obtained at standard timing. Demographic and treatment-related variables were analyzed by age group. The proportion of non-receptive ERA results (pre- and post-receptive combined) was compared using Fisher's exact test. Univariable and multivariable logistic regression assessed associations between predictors and non-receptive ERA.

Results: Of 210 patients, 205 were included. Age distribution was < 35 (n = 35, 17%), 35-37 (n = 58, 28.3%), 38-40 (n = 53, 25.8%), and ≥ 41 (n = 59, 28.8%). Overall, 166 (81.0%) ERAs were receptive, 33 (16.1%) pre-receptive, and 6 (2.9%) post-receptive. BMI, infertility diagnosis, and prior implantation or miscarriage history did not differ by age. Non-receptive ERA proportions were 20% (< 35), 17.2% (35-37), 17.0% (38-40), and 22.0% (≥ 41) (p = 0.52). In multivariable analysis adjusting for BMI and number of prior failed euploid transfers, age was not associated with non-receptive ERA (aOR 0.98, 95% CI 0.34-2.30, p = 0.97).

Conclusion: Uterine age was not associated with increased odds of non-receptive ERA, suggesting that the test does not capture age-related changes in endometrial receptivity. Although endometrial aging is implicated in reduced embryo transfer success, the ERA should not be ordered solely on the basis of uterine age. The ERA may not reliably detect age-related endometrial differences in the window of implantation at a clinical level.

空卵泡症候群 (EFS) ------ 一種罕見的體外受精併發症，指在取卵過程中未取出卵子。

ZP3 基因中一種新的雜合突變 (p.Ser173Cys, c.518C > G)----與空卵泡綜合症相關

Empty follicle syndrome (EFS) ------ a rare IVF complication where no eggs are retrieved during an egg collection procedure,

Novel heterozygous mutation (p.Ser173Cys, c.518C > G) in the ZP3 gene

----associated with EFS

A novel mutation in ZP3 causes empty follicle syndrome and abnormal zona pellucida formation

• Genetics
• Published: 02 November 2020

• Volume 38, pages 251–259 (2021)
• Cite this article

Save article

Journal of Assisted Reproduction and GeneticsAims and scopeSubmit manuscript

Purpose

To identify disease-causing genes involved in female infertility.

Methods

Whole-exome sequencing and Sanger DNA sequencing were used to identify the mutations in disease-causing genes. We performed subcellular protein localization, western immunoblotting analysis, and co-immunoprecipitation analysis to evaluate the effects of the mutation.

Results

We investigated 17 families with female infertility. Whole-exome and Sanger DNA sequencing were used to characterize the disease gene in the patients, and we identified a novel heterozygous mutation (p.Ser173Cys, c.518C > G) in the ZP3 gene in a patient with empty follicle syndrome. When we performed co-immunoprecipitation analysis, we found that the S173C mutation affected interactions between ZP3 and ZP2.

Conclusions

We identified a novel mutation in the ZP3 gene in a Chinese family with female infertility. Our findings thus expand the mutational and phenotypical spectrum of the ZP3 gene, and they will be helpful in precisely diagnosing this aspect of female infertility.

比較了體外成熟的牛和鼠的生殖泡卵母細胞，包括

卵丘-卵母細胞複合體（COCs）、

去卵丘卵母細胞（DOs）

與卵丘細胞共培養的去卵丘卵母細胞（DOs + CCs）

DOs + CCs使小鼠的大部分參數恢復到類似COCs的水平，

但僅使牛的部分參數恢復到COCs的水平。

在體外成熟過程中，卵丘-卵母細胞通訊受到物種特異性的調節，

牛卵母細胞是依賴完整卵支持的轉化性人類體外成熟研究的更合適的模型。

Journal Article

Species-specific differences in cumulus support during final oocyte maturation in mice and cattle 

Reproduction, Volume 172, Issue 2, August 2026, xaag093,

In brief: Cumulus support is more critical for bovine than murine oocytes during in-vitro maturation (IVM), affecting transzonal projection maintenance, organelle remodeling, molecular signatures, and meiotic progression. These species-specific differences support the bovine oocyte as the more informative experimental model for translational human IVM.

Abstract: Cumulus–oocyte communication is a key regulator of oocyte maturation; however, comparative studies across species relevant to the choice of models for human in-vitro maturation (IVM) remain insufficient. We compared bovine and murine germinal vesicle oocytes matured in vitro as cumulus–oocyte complexes (COCs), denuded oocytes (DOs), or DOs cocultured with cumulus cells (DOs + CCs) to define species-specific dependence on cumulus support. Structural, organelle, molecular markers, transzonal projections (TZPs), connexin 37/43 expression, mitochondrial redistribution, lipid droplet remodeling, BAX/BCL2 ratios, DNMT3A/Dnmt3a expression, and maturation rate. In both species, IVM of COCs reduced TZP signal, but the decline was greater in cattle. Denudation revealed a marked divergence: bovine DOs showed near-complete TZP loss, retention of immature-like mitochondrial organization, impaired lipid remodeling, altered BAX/BCL2 and DNMT3A expression, and reduced maturation, whereas murine DOs preserved TZP features, underwent mitochondrial redistribution comparable to COCs, and maintained maturation rates. Cumulus coculture restored most parameters to COC-like levels in mice but only partially in cattle. Lipid remodeling also differed by species, with increased droplet number in bovine oocytes and fewer but larger droplets in murine oocytes. Bovine oocyte maturation was the highest in hormone-supplemented media in COCs and decreased after denudation, whereas mouse oocyte maturation was similar in COCs and DOs regardless of the hormone presence in culture media. These findings show that cumulus–oocyte communication is regulated in a species-specific manner during IVM and identify the bovine oocyte as a more appropriate model for translational human IVM studies that depend on intact cumulus support.

囊胚培養並非適用於所有患者的萬能策略。雖然延長培養時間可能提高多胚胎患者的胚胎選擇率和治療效率，但對於胚胎數量有限、高齡產婦或卵巢反應不良的患者，也可能增加失去存活胚胎的風險。因此，最佳移植策略應根據患者的預後、胚胎數量、先前體外受精史、治療目標以及實驗室的胚胎培養和冷凍保存能力進行個別化製定。

The Blastocyst Era: Is Blastocyst Transfer the Best Strategy for Every Patient?

Jing Wang, M.D., Ph.D.1 ∙ Ben W. Mol, M.D., Ph.D.2 ∙ Han Zhao, M.D., Ph.D.1

Taken together, current evidence suggests that blastocyst culture is not a one-size-fits-all strategy. Although extended culture may improve embryo selection and treatment efficiency in patients with multiple embryos, it may also increase the risk of losing viable embryos in those with limited embryo numbers, advanced maternal age, or poor ovarian response. The optimal transfer strategy should therefore be individualized according to patient prognosis, embryo availability, previous IVF history, treatment goals, and the laboratory's capabilities in embryo culture and cryopreservation, with patients with a strong ovarian response and many embryos probably benefiting from blastocyst culture. More level 1 evidence beyond women with good prognosis is needed. An important next step is an individual participant data (IPD) meta-analysis to identify patient characteristics that can guide personalized decisions between blastocyst and cleavage-stage transfer.

 雖然 NIPT 在 ART 受孕妊娠的特異性很高，但其在檢測常見胎兒染色體非整倍體（21,18,13)(特別是 21 三體綜合徵）方面的敏感性低於自然受孕妊娠。

Noninvasive prenatal testing as a prenatal screening test in pregnancies following assisted reproductive technologies: a diagnostic test accuracy systematic review and meta-analysis

Importance

The accuracy of the noninvasive prenatal testing (NIPT) for common trisomies remains unclear in pregnancies following assisted reproductive technology (ART), and the adoption of NIPT as a prenatal screening test in ART pregnancies has been cautious because of the absence of clear recommendations.

Objective

To estimate the accuracy of NIPT for screening for common chromosomal abnormalities compared with conventional karyotype or microarray testing in ART pregnancies.

Data sources

A comprehensive search of the following: PubMed, Scopus, and Embase.

Study selection and synthesis

A systematic review and meta-analysis was conducted, and cross-sectional and cohort studies of antenatal women who conceived following ART and opted for prenatal testing with NIPT were included.

Main outcomes

Pooled sensitivity and specificity of NIPT for common chromosomal abnormalities (trisomy 21, 18, and 13).

Results

We identified a total of 548 records through electronic searches and finally included 13 studies for quantitative synthesis. The pooled sensitivity and specificity for combined abnormalities in singleton ART pregnancies were 88.2% (95% confidence interval, [CI] 61.0%–97.3%) and 99.6% (95% CI 98.4%–99.9%), respectively. Similarly, for twin ART pregnancies, the pooled sensitivity and specificity for combined abnormalities were 88.2% (95% CI 66.4%–96.6%) and 99.8% (95% CI 99.6%–99.9%), respectively. The pooled sensitivity and specificity for trisomy 21 in singleton ART pregnancies were 87.2% (95% CI 59.0%–97.0%) and 99.7% (95% CI 98.8%–99.9%), respectively, whereas in ART twin pregnancies, the pooled sensitivity was 86.9% (95% CI 63.4%–96.2%) and the specificity was 99.8% (95% CI 99.6%–99.9%).

Conclusion and relevance

Although the specificity of NIPT is high in ART-conceived pregnancies, its sensitivity in the detection of common fetal chromosomal aneuploidy, in particular trisomy 21, is substantially lower than in naturally conceived pregnancies.