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.

corifollitropin alfa (CFA) + intra-nasal GnRH agonist  (CFA flare)

VS

corifollitropin alfa (CFA) +GnRH antagonist

前者CFA flare方案是可取代傳統的卵巢刺激方案，用於治療卵巢反應不良的患者。

此方案顯著減輕了患者的負擔，減少了FSH注射次數，且無需注射GnRH拮抗劑。

CFA flare protocol is a novel alternative to conventional ovarian stimulation regimens that are used for ‘poor responder’ patients. It significantly reduces the patient burden, with less injections of FSH and no injections of GnRH antagonist. The ovarian response is similar to that achieved with a conventional GnRH antagonist cycle, 

An injection-lite approach to ovarian stimulation in poor responder patients using corifollitropin alfa and nasal GnRH agonist

Can the unique pharmacokinetic and pharmacodynamic profiles of corifollitropin alfa (CFA) in combination with an intra-nasal GnRH agonist (CFA flare) provide adequate ovarian stimulation for poor-responder patients while minimising the burden of injections?

Methods

Twenty women aged between 31 and 41 years of age who were identified as potential poor responders to ovarian stimulation according to the POSEIDON criteria and who were attending the Fertility and Research Centre, Royal Hospital for Women and City Fertility, Sydney for IVF treatment were randomised to receive either the flare or the antagonist cycle. Serum FSH, LH, and E2 concentrations were measured daily for 5 days post-initiation of CFA during the early follicular phase.

Results

The number of injections given to women in the CFA flare arm (4) was significantly less than those in the CFA antagonist arm (11), (p = 0.001).

Two days after the initiation of CFA, serum FSH concentrations were 27 versus 11 IU/L (flare versus antagonist) (p = 0.022), and mean serum E2 concentrations were 349 versus 157 pmol/L (p = 0.039), and on day 7, were 3000 versus 1850 pmol/L.

The CFA flare stimulation protocol resulted in higher concentrations of FSH in the early period of follicular stimulation. There was an equivalent rise in serum E2 in both groups. The CFA flare protocol was non-inferior to the CFA antagonist protocol and may have been less burdensome to patients as fewer injections were needed.

Conclusion

The CFA flare protocol is a novel alternative to conventional ovarian stimulation regimens that are used for ‘poor responder’ patients. It significantly reduces the patient burden, with less injections of FSH and no injections of GnRH antagonist. The ovarian response is similar to that achieved with a conventional GnRH antagonist cycle, but this requires further evaluation in a larger study.

用1 mM N-乙醯半胱氨酸（NAC）處理的卵母細胞與其他實驗組相比，卵裂率較高。

Oocytes treated with 1 mM N-acetylcysteine (NAC)  showed higher cleavage rates compared to the other experimental groups

Effect of in vitro maturation medium supplementation with N-acetylcysteine on the developmental competence of sheep oocytes

The present study aimed to evaluate the effect of N-acetylcysteine (NAC) on in vitro maturation (IVM) and in vitro embryo production in sheep. Cumulus–oocyte complexes (COCs) were collected and matured in vitro in a control medium or supplemented with different concentrations of NAC (1, 1.5 and 2.0 mM). After maturation, a subset of oocytes was used for morphological assessment and chromatin configuration analysis, as well as for evaluating intracellular levels of reactive oxygen species (ROS), glutathione (GSH), mitochondrial activity and DNA fragmentation using the TUNEL assay. Another subgroup of oocytes was subjected to in vitro fertilization (IVF), and the presumed zygotes were cultured in in vitro culture (IVC) medium to assess cleavage rates. Data were statistically analysed, considering significance at P < 0.05. The concentration of 1 mM NAC resulted in lower ROS levels compared to the control and 1.5 mM groups, in addition to reducing DNA fragmentation. No significant differences (P > 0.05) were observed in GSH levels or mitochondrial activity between treated and control groups. Furthermore, oocytes treated with 1 mM NAC showed higher cleavage rates compared to the other experimental groups. In conclusion, supplementation with 1 mM NAC improves oocyte quality and early embryonic development, as demonstrated by reduced oxidative stress and DNA fragmentation, resulting in increased cleavage rates.

• 嵌合體胚胎的著床率和活產率顯著低於整倍體胚胎，
• 一旦著床發生兩組的生化懷孕流失率和流產率相當，顯示著床是嵌合體胚胎存活的主要限制因素。
• 節段性嵌合體的預後優於全染色體嵌合體。

Meta-Analysis

 

. 2025 Aug;42(8):2469-2481.

doi: 10.1007/s10815-025-03575-6. Epub 2025 Jul 10.

Live birth and other reproductive outcomes of mosaic and euploid embryos: a systematic review and meta-analysis

Advances in preimplantation genetic testing for aneuploidy (PGT-A) have improved embryo selection in assisted reproductive technologies (ART). However, the clinical significance of mosaic embryos remains uncertain. This systematic review and meta-analysis evaluates reproductive outcomes following mosaic embryo transfer compared to euploid embryos. Live birth rate was the primary outcome, while secondary outcomes included biochemical pregnancy, biochemical pregnancy loss, miscarriage, clinical pregnancy, ongoing pregnancy, and neonatal outcomes. Our findings indicate that mosaic embryos have significantly lower implantation and live birth rates than euploid embryos, reinforcing the superior reproductive potential of euploid embryos. However, once implantation occurs, biochemical pregnancy loss and miscarriage rates were comparable between groups, suggesting that implantation is the primary limiting factor in mosaic embryo viability. The type and extent of mosaicism may further influence reproductive outcomes, with segmental mosaicism showing better prognoses than whole-chromosome mosaicism. Additionally, a trend toward lower birth weight in mosaic embryos was observed, though neonatal health outcomes remained as favorable as euploid embryos. The heterogeneity in diagnostic and reporting criteria highlights the need for standardized classification of mosaicism to enhance prognostic accuracy. Further research is required to refine embryo selection strategies and improve clinical decision-making in ART.

凍胚植入

Letrozole (LE)-induced ovulation vs hormone replacement treatment (HRT) 

----Letrozole誘導排卵可能可達到較高懷孕率

. 2025 May 8;42(6):1907–1915. doi: 10.1007/s10815-025-03500-x

Letrozole-stimulated cycles versus hormone replacement treatment cycles for frozen embryo transfer in women with polycystic ovary syndrome: a prospective randomized controlled trial

Purpose

This study aimed to compare the pregnancy outcomes of letrozole (LE)-induced ovulation and hormone replacement treatment (HRT) in endometrial preparation for frozen embryo transfer (FET) in women with polycystic ovary syndrome (PCOS).

Methods

A randomized controlled trial involved 200 patients with PCOS from December 2017 to December 2022. Participants, who underwent FET with one or two good-quality blastocysts or cleavage-stage embryos, were randomly assigned to the LE group or HRT group in a 1:1 ratio. The primary outcome was the clinical pregnancy rate. Secondary outcomes included biochemical pregnancy, implantation, ectopic pregnancy, miscarriage, multiple pregnancy, and live birth rates.

Results

The clinical pregnancy rate was 66.0% in the LE group compared to 53.0% in the HRT group (absolute difference, 13.0% [95% CI, − 0.5 to 26.5%]; RR, 1.25 [95% CI, 0.98 to 1.57]; P = 0.061). The biochemical pregnancy rate was higher in the LE group (71.0% vs 57.0%; absolute difference, 14.0% [95% CI, 0.8 to 27.2%]; RR, 1.25 [95% CI, 1.01 to 1.54]; P = 0.039). No significant differences were observed for the other secondary outcomes. The LE group showed higher biochemical pregnancy and live birth rates in the normal weight and normal androgen subgroups. Pregnancy outcomes were similar in the overweight and hyperandrogenic subgroups.

Conclusion

There were no statistically significant differences in clinical pregnancy rates between the LE and HRT cycles for FET in women with PCOS. However, the LE protocol may be a preferable option to HRT for women with normal weight or normal androgen levels. 

植入管內外管分批置入 vs 植入管內外管同時置入 

----先放外管再植入內管可達到較高懷孕率

 

Steps forward in embryo transfer technique: a retrospective study comparing direct versus afterload catheters at different time frames

Purpose

To assess whether embryo transfer (ET) technique can influence the clinical pregnancy rate (CPR) and its correlation with the embryo transfer difficulty.

Design

This single center retrospective cohort analysis of fresh and frozen single blastocyst transfers performed between January 2016 and December 2021 included fresh and frozen single blastocyst transfers performed during the study timeframe. Direct technique was the only one used from January 2016 to September 2017. From September 2017 to March 2019, the choice between the two techniques was given by randomization, due to a clinical trial recruitment. From April 2019, only the afterload technique was used. Preimplantation genetic testing cycles and gamete donation procedures and cycles performed with external gametes or embryos were excluded. CPR was the primary outcome, while difficult transfer rate the secondary one. Univariate and multivariate logistic regressions were performed.

Results

During the period, 8,189 transfers were performed. CPR of the afterload group resulted significantly higher compared to the direct group (44.69% versus 41.65%, OR 1.13, 95% CI 1.02–1.25, p = 0.017) and the rate of difficult transfers two-thirds lower (9.06% versus 26.85%, OR 0.27, 95% CI 0.24–0.31, p < 0.001).

Conclusion

Our study demonstrated that CPR is significantly affected by the ET technique. In particular, with the afterload protocol, both CPR and easy transfer rates increased.

 胚胎移植前子宮內注射 hCG 並不能提高活產率

Intrauterine human chorionic gonadotropin administration before embryo transfer (IHABT): an individual participant data meta-analysis of randomized controlled trials Open Access

Intrauterine administration of hCG has been considered as a promising IVF add-on before embryo transfer to improve fertility outcomes. A Cochrane review and four more recent systematic reviews all showed improved clinical pregnancy rates and/or live birth rates following intrauterine administration of hCG, however, a high unexplained heterogeneity was also present.

OBJECTIVE AND RATIONALE

To investigate the effectiveness and safety of intrauterine administration of hCG before embryo transfer in participants undergoing IVF. Individual participant data meta-analysis (IPD-MA) is recognized as the gold standard for evidence synthesis due to its ability to harmonize the data and to investigate treatment–covariate interactions. In addition, with recent experiences of guideline development and systematic review production raising increasing concerns about the trustworthiness of randomized controlled trials (RCTs) in women’s health research, an IPD-MA provides a unique opportunity to summarize the best available and most trustworthy evidence on this topic.

OUTCOMES

We detected 28 RCTs, of which 7 RCTs with IPD involving 2244 participants were included. All seven RCTs with IPD met trustworthiness criteria and six RCTs had overall low risk of bias. All RCTs without IPD did not meet trustworthiness criteria. IPD-MA showed intrauterine administration of hCG before embryo transfer did not improve live birth rates (7 RCTs, 2244 participants, odds ratio [OR] 0.99, 95% CI 0.83–1.19) or clinical pregnancy rates (7 RCTs, 2244 participants, OR 1.04, 95% CI 0.83–1.31). Studies without IPD showed different results from those with IPD for live birth (1.99, 0.72–5.50, P for interaction <0.001) and clinical pregnancy (1.87 (1.48–2.35), 17 RCTs without IPD, 3152 participants, P for interaction 0.005).