STUDY QUESTION:Is the preconception 1-h plasma glucose level during the oral glucose tolerance test (OGTT) more strongly associated with subsequent gestational diabetes mellitus than the fasting or 2-h glucose levels in women with PMOS/PCOS undergoing IVF treatment? SUMMARY ANSWER:Preconception 1-h plasma glucose showed a stronger and more consistent association with gestational diabetes mellitus than the fasting or 2-h glucose levels in women with PMOS/PCOS undergoing IVF treatment. WHAT IS KNOWN ALREADY:Women with PMOS/PCOS have an increased risk of gestational diabetes mellitus. International guidelines recommend a preconception OGTT in women with PMOS/PCOS without pre-existing diabetes because of the risk of hyperglycaemia and pregnancy complications. However, the comparative predictive value of different preconception OGTT time points, particularly 1-h glucose, remains unclear. STUDY DESIGN, SIZE, DURATION:This was a multi-centre retrospective cohort study including 2571 women with PMOS/PCOS who underwent their first IVF treatment at three reproductive medicine centres in China and had a preconception 75-g OGTT between March 2018 and December 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS:Women with PMOS/PCOS who completed a preconception 75-g OGTT before initiation of the IVF treatment were included. The primary outcome was GDM diagnosed at 24-28 weeks of gestation. Generalized linear mixed-effects models were used to assess associations between OGTT glucose levels and GDM, adjusting for age, BMI, infertility duration, hormonal profiles, and treatment protocols. Stratified analyses by BMI and PMOS/PCOS phenotype were conducted, and multiple imputation was applied for missing data. MAIN RESULTS AND THE ROLE OF CHANCE:Preconception fasting (aOR 1.97 [1.49-2.61]), 1-h (aOR 1.23 [1.13-1.34]) and 2-h glucose (aOR 1.30 [1.17-1.45]) were all significantly associated with GDM (all P < 0.001). Within the diabetic range, only the 1-h glucose measurement of ≥11.6 mmol/l remained a significant indicator. The association of 1-h glucose with GDM was significant in normal-weight and obese women but not in overweight women. The associations were consistent across PMOS/PCOS phenotypes. LIMITATIONS, REASONS FOR CAUTION:The retrospective design may have introduced residual confounding and limits causal inference. Missing data required imputation, and subgroup analyses may have limited statistical power. WIDER IMPLICATIONS OF THE FINDINGS:These findings suggest that preconception 1-h glucose may provide additional value for identifying women who are a higher risk of GDM among normal-weight and obese women with PMOS/PCOS undergoing IVF treatment, and support its consideration in preconception metabolic assessments. FUNDING:This work was supported by the National Natural Science Foundation of China (82522038, 82471670 and 82401908), the Natural Science Foundation of Fujian Province (2025J011428), and the "Yongjiang Science and Technology Innovation 2035" Key Research and Development Program (2025Z151). DISCLOSURES:The authors declared no competing interests. TRIAL REGISTRATION NUMBER:N/A.

Polycystic ovary syndrome (PCOS) is widely acknowledged as the prevailing reproductive endocrine disorder accompanied by numerous metabolic dysfunctions. However, there has been a lack of systematic examination regarding the amino acids profile in PCOS. There is a dearth of evidence in regard to the examination of connections between amino acid metabolites found in follicular fluid (FF) and the quality of embryos during in vitro fertilization (IVF). Our objective was to assess amino acid signatures associated with PCOS, as well as identify potential amino acid markers for evaluating embryo quality in PCOS. The cohort study consisted of 143 women who were undergoing lVF/ICSl. Among these, 79 patients who had been diagnosed with PCOS, while the remaining 64 patients did not have PCOS. The concentrations of 30 amino acids present in FF were accurately determined through the use of high-performance liquid chromatography-tandem mass spectrometry. We use the spearman correlation was used to calculate correlations. Odds ratio (ORs) and 95

Macrophages play a vital role in endometrial receptivity and embryo implantation. However, it remains unclear if macrophages in peripheral blood is associated with pregnancy outcomes of frozen embryo transfer during implantation window. 50 patients preparing for the first time of frozen embryo transfer (FET) and 17 patients with recurrent implantation failure (RIF) from December 2022 to March 2023 were included in our present study. The percentages of peripheral macrophages and other immune cells (B-cell, T-cell, NK cell) were evaluated by flow cytometry. The concentrations of cytokines were verified with an IMMULITE 1000 Immunoassay System. FET patients were categorized into pregnant and nonpregnant groups according to clinical outcomes, respectively. The proportion of peripheral CD68+CD163+ M2 macrophages was increased in pregnant women than in nonpregnant women among the first time of FET patients. CD4+ T helper cells were positively correlated with M2-like macrophages in these women. The pregnancy rate of women with higher peripheral CD163 + M2-like monocytes increased compared with women with lower peripheral CD163 + M2-like monocytes in an independent cohort according to the cutoff value of CD163 + M2-like monocytes in ROC curve. Our findings revealed that peripheral CD163+ M2 macrophages in implantation window were associated with pregnancy outcomes. This indicated that the importance of peripheral M2 macrophages at the implantation site for pregnancy success.

Objective: A biological system's internal morphological structure or function can be changed as a result of the mechanical effect of focused ultrasound. Pulsed low-intensity focused ultrasound (LIFU) has mechanical effects that might induce follicle development with less damage to ovarian tissue. The potential development of LIFU as a non-invasive method for the treatment of female infertility is being considered, and this study sought to explore and confirm that LIFU can activate ovarian follicles. Results: We found a 50% increase in ovarian weight and in the number of mature follicles on the ultrasound-stimulated side with pulsed LIFU and intraperitoneal injection of 10 IU PMSG in 10-day-old rats. After ultrasound stimulation, the PCOS-like rats had a decrease in androgen levels, restoration of regular estrous cycle and increase in the number of mature follicles and corpora lutea, and the ratio of M1 and M2 type macrophages was altered in antral follicles of PCOS-like rats, consequently promoting further development and maturation of antral follicles. Conclusion:LIFU treatment could trigger actin changes in ovarian cells, which might disrupt the Hippo signal pathway to promote follicle formation, and the mechanical impact on the ovaries of PCOS-like rats improved antral follicle development.

Importance:Implantation failure remains a critical barrier to in vitro fertilization. Prednisone, as an immune-regulatory agent, is widely used to improve the probability of implantation and pregnancy, although the evidence for efficacy is inadequate. Objective:To determine the efficacy of 10 mg of prednisone compared with placebo on live birth among women with recurrent implantation failure. Design, Setting, and Participants:A double-blind, placebo-controlled, randomized clinical trial conducted at 8 fertility centers in China. Eligible women who had a history of 2 or more unsuccessful embryo transfer cycles, were younger than 38 years when oocytes were retrieved, and were planning to undergo frozen-thawed embryo transfer with the availability of good-quality embryos were enrolled from November 2018 to August 2020 (final follow-up August 2021). Interventions:Participants were randomized (1:1) to receive oral pills containing either 10 mg of prednisone (n = 357) or matching placebo (n = 358) once daily, from the day at which they started endometrial preparation for frozen-thawed embryo transfer through early pregnancy. Main Outcomes and Measures:The primary outcome was live birth, defined as the delivery of any number of neonates born at 28 or more weeks' gestation with signs of life. Results:Among 715 women randomized (mean age, 32 years), 714 (99.9%) had data available on live birth outcomes and were included in the primary analysis. Live birth occurred among 37.8% of women (135 of 357) in the prednisone group vs 38.8% of women (139 of 358) in the placebo group (absolute difference, -1.0% [95% CI, -8.1% to 6.1%]; relative ratio [RR], 0.97 [95% CI, 0.81 to 1.17]; P = .78). The rates of biochemical pregnancy loss were 17.3% in the prednisone group and 9.9% in the placebo group (absolute difference, 7.5% [95% CI, 0.6% to 14.3%]; RR, 1.75 [95% CI, 1.03 to 2.99]; P = .04). Of those in the prednisone group, preterm delivery occurred among 11.8% and of those in the placebo group, 5.5% of pregnancies (absolute difference, 6.3% [95% CI, 0.2% to 12.4%]; RR, 2.14 [95% CI, 1.00 to 4.58]; P = .04). There were no statistically significant between-group differences in the rates of biochemical pregnancy, clinical pregnancy, implantation, neonatal complications, congenital anomalies, other adverse events, or mean birthweights. Conclusions and Relevance:Among patients with recurrent implantation failure, treatment with prednisone did not improve live birth rate compared with placebo. Data suggested that the use of prednisone may increase the risk of preterm delivery and biochemical pregnancy loss. Our results challenge the value of prednisone use in clinical practice for the treatment of recurrent implantation failure. Trial Registration:Chinese Clinical Trial Registry Identifier: ChiCTR1800018783.

Background This study was designed to investigate the association between nutrients and female infertility.Methods A cross-sectional study on 18-45 years of age reproductive-age women was conducted using the data from the National Health and Nutrition Examination Surveys (NHANES) for the periods 2013-2014 and 2015-2016. Multivariate logistic regression analysis was performed to evaluate the association between nutrients and female infertility. Subgroup analysis was applied to the body mass index (BMI). Results were summarised using an odds ratio (OR) with a 95% confidence interval (CI).Results Of the total 1713 women, 204 women (11.91%) were infertile. The result demonstrated that higher intake of carbohydrate (OR: 0.46, 95% CI: 0.24-0.86, p = 0.018), vitamin A (OR: 0.44, 95% CI: 0.24-0.80, p = 0.009), vitamin C (OR: 0.48, 95% CI: 0.26-0.88, p = 0.020), magnesium (OR: 0.36, 95% CI: 0.17-0.76, p = 0.009), iron (OR: 0.43, 95% CI: 0.23-0.82, p = 0.012), lycopene (OR: 0.55, 95% CI: 0.33-0.91, p = 0.022), and total folate (OR: 0.38, 95% CI: 0.20-0.70, p = 0.003) were associated with a lower risk of female infertility. The subgroup analysis also reported that intakes of vitamin A, vitamin C, and lycopene were related to a lower risk of female infertility among women with a BMI being 18.5-24.9 kg/m(2). Among women with BMI > 24.9 kg/m(2), high intakes of magnesium, iron and total folate were associated with a decreased risk of female infertility.Conclusions The intake of several nutrients is associated with a decreased risk of female infertility. These findings provide insight into potentially modifiable lifestyle factors associated with female infertility.

This study was implemented to address the role of Roflumilast in polycystic ovary syndrome (PCOS) as well as to discuss its reaction mechanism in vivo and in vitro. In vivo, mice were administrated with 6 mg dehydroepiandrosterone (DHEA) per 100 g body weight and fed with 60% high fat diet to induce PCOS. The expression of phosphodiesterases 4 (PDE4) was assessed with RT-qPCR. The ovary pathology was observed by hematoxylin and eosin staining and follicles were counted. Enzyme-linked immunosorbent assay was adopted for the estimation of progesterone, testosterone and inflammatory factors and lipid accumulation was observed by Oil Red O staining. With the application of reverse transcription-quantitative PCR (RT-qPCR) and western blot, the messenger RNA (mRNA) and protein expressions of low-density lipoprotein receptor (LDLR) was resolved. In vitro, Cell counting kit-8 and flow cytometry analysis were applied for the assessment of cell proliferation and apoptosis. The proliferation- and apoptosis-related proteins were appraised with western blot. Additionally, the expressions of PDE-4 at both mRNA and protein levels were tested with RT-qPCR and western blot. Here, it was discovered that PDE4 was greatly elevated in PCOS mice and DHEA-induced ovarian granulosa cells (KGN). In PCOS mice, PDE4 was negative correlated with progesterone and had positive correlation with testosterone. Roflumilast could enhanced progesterone expression, increased the number of primary follicles, preantral follicles and antral follicles but reduced testosterone and decreased the number of cystic follicles in PCOS mice. It was also testified that Roflumilast could inhibit the release of inflammatory factors and lipid accumulation in PCOS mice. Besides, the proliferation of DHEA-induced KGN cells was enhanced while the apoptosis was declined by Roflumilast, accompanied by elevated contents of PCNA, Ki67 and antiapoptotic protein Bcl-2. Collectively, Roflumilast inhibited inflammation and lipid accumulation in PCOS mice to improve ovarian function and reduce DHEA-induced granulosa cell apoptosis.

Objective: To investigate the clinical efficacy of blastocyst culture supernatant transfer in hormone replacement freeze-thaw embryo transfer (FET) cycles. Methods: The present study was a prospective double-blind randomized controlled study. Patients who met the inclusion criteria for the first hormone replacement freeze-thaw single blastocyst transfer proposed from September 2017 to December 2020 were randomly grouped at the endometrial transformation day of the secretory phase (P + 0). Patients in Group A (the experimental group) received the blastocyst culture supernatant at P + 2 and a single blastocyst at P + 5. Patients in Group B (the control group) received the embryo culture at P + 2 and a single blastocyst at P + 5. The clinical outcomes were compared between the two groups. Results: A total of 288 cycles were included in the present study, with 144 cycles in each group. The clinical pregnancy rate and live birth rate were higher in group A than in group B (54.9% vs 45.8%, and 50% vs 39.6%, respectively), and the differences were more pronounced in patients with the age of >= 35 years (51.7% vs 37.5%, and 44.8% vs 32.1%, respectively), but the differences were not statistically significant. Conclusion: Blastocyst culture supernatant transfer in hormone replacement FET cycles could improve the pregnancy outcomes.

Objective:To compare the clinical efficacy of transdermal estradiol patch and oral estradiol valerate in hormone replacement frozen-thawed embryo transfer cycle.Methods:Clinical data of 363 patients undergoing hormone replacement frozen-thawed embryos transfer from June 2018 to December 2019 were retrospectively analyzed. Patients in group A received transdermal estradiol patch. Patients in group B received estradiol valerate orally. The clinical outcomes of the two groups were compared.Results:The clinical pregnancy rate was 55.7% (113/203) in group A and 58.4% (87/149) in group B, with no significant difference between the two groups ( P=0.663). There were no significant differences in human chorionic gonadotropin (hCG) positive rate [63.5%(129/203) vs. 65.8% (98/149)], early abortion rate [10.6% (12/113) vs. 9.2% (8/87)] and ectopic pregnancy rate [1.8% (2/113) vs. 4.6% (4/87)] between the two groups (all P>0.05). The serum estradiol level in group B [(271.6±73.8) ng/L] was significantly higher than that in group A [(209.5±65.9) ng/L] on the day of endometrial conversion of progesterone ( P=0.008). Conclusion:The clinical effect of the transdermal estradiol patch is the same as that of oral estradiol valerate in hormone replacement frozen-thawed embryo transfer cycle. It is recommended for patients with chronic liver and kidney disease, high risk factors for thrombosis, dyslipidemia.

Background To determine the small nucleolar RNA (snoRNA) expression profiles in the endometrium during the implantation phase and identify their potential biological functions. Methods We used RNA sequencing to analyze the expression changes of snoRNAs in the endometrium of women during the implantation phase of the natural cycle and in the GnRH antagonist stimulation protocol. The expression of snoRNA ENST00000391318 was manipulated in endometrial cells by lentivirus. CCK-8, clone formation, flow cytometry, scratch and Transwell assays were used to detect the effects of ENST00000391318 on the proliferation, apoptosis, migration and invasion of endometrial cells. RNA pulldown and luciferase reporter gene experiments were used to detect the binding of ENST00000391318 to miRNA. Results Endometrial SNORNA ENST00000391318 was upregulated in the GnRH antagonist stimulation protocol. SNORNA ENST00000391318 overexpression inhibited cell proliferation and the cell cycle in Ishikawa cells, and SNORNA ENST00000391318 knockdown promoted cell proliferation and the cell cycle in Ishikawa cells. SNORNA ENST00000391318 overexpression inhibited cell migration and invasion in Ishikawa cells. SNORNA ENST00000391318 inhibited the expression of endometrium receptivity factor. miRNA-3928-5p is a target of SNORNA ENST00000391318 in Ishikawa cells. SNORNA ENST00000391318 regulates the expression of CDH11 through interaction with miRNA-3928-5p in Ishikawa cells. Conclusions The ENST00000391318/miR-3928-5p/CDH11 signaling pathway can regulate the receptivity of the endometrium for patients in the GnRH antagonist stimulation protocol. SNORNA ENST00000391318 downregulates the function of miR-3928-5p through a ceRNA mechanism to upregulate the expression of CDH11. SNORNA ENST00000391318 downregulates the receptivity of the endometrium by upregulating the expression of CDH11.

目的:探讨经阴道超声检测激素替代周期胚胎移植中内膜转化日子宫内膜厚度 、子宫内膜血流等参数对妊娠结局的评估价值.方法:选择100例于激素替代周期行冻融胚胎移植的不孕症患者,根据妊娠结果分为妊娠组(n=60)与未妊娠组(n=40).比较两组子宫内膜转化日的子宫内膜厚度、内膜血流搏动指数(pulsatility index,PI)、阻力指数(resistance index,RI)、收缩期峰值流速与舒张末期流速比值(systolic-diastolic ratio,S/D)等参数.结果:两组内膜转化日的雌二醇(estradiol,E2)、黄体生成素(luteinizing hormone,LH)、卵泡刺激素(follicle stimulation hormone,FSH)水平,优质胚胎数及子宫内膜厚度差异均无统计学意义.与未妊娠组比较,妊娠组内膜PI、RI、S/D等血流动力学参数明显降低(P<0.05).转化日子宫内膜厚度<8 mm者妊娠率低于子宫内膜厚度≥8 mm者(P<0.05).妊娠组转化日内膜S/D>3者的比例低于非妊娠组(P<0.05).结论:经阴道超声检测子宫内膜血流参数,有助于预测激素替代周期胚胎移植的妊娠结局.

To report a case of treating cornual pregnancy combined with intrauterine pregnancy following embryo transfer after bilateral salpingectomy with a laparoscopic approach. A 40-year-old pregnant woman who presented with minor vaginal bleeding at 5 weeks gestation. A cornual pregnancy with uterine pregnancy by ultrasonography at 7 weeks 4 days gestation was diagnosed. The cornual pregnancy was successfully removed via laparoscopy, and the uterine horn was repaired. The intrauterine single pregnancy progressed and a caesarean section was performed at 37 weeks gestation, resulting in the healthy male infant.

本文报道1例染色体核型分析正常的反复妊娠丢失夫妇,经过人全外显子测序及拷贝数变异检测,发现双方共同存在妊娠特异性糖蛋白编码基因的部分缺失;探讨了新的基因检测技术及平台对反复妊娠丢失诊断的价值.

Background Previous studies have demonstrated that progestin-primed ovarian stimulation (PPOS) protocol was a feasible and efficient method in in vitro fertilization (IVF) cycle. However, its application in women with advanced age has not been determined yet. The purpose of this study was to investigate its efficacy in women aged ≥40 years old. Methods This retrospective cohort study included patients with ages of ≥40 years old at the time of ovarian stimulation. The embryonic and clinical outcome of mild stimulation and PPOS were compared. Primary outcome was top-quality embryo rate on day 3, and secondary outcome was clinical pregnancy rate. Results Baseline characteristics of patients was similar in mild stimulation (122 cycles) and PPOS (47 cycles). No significant difference was found in the number of retrieved and mature oocytes and the fertilization and cleavage rates. Of interest, the rate of top-quality embryos was significantly higher in PPOS group (50.08% vs 33.29%, p = 0.015), with an increasing trend of viable embryo rate (73.55% vs 61.16%). A greater amount of gonadotropin was observed in PPOS group (2061.17 ± 1254.63 IU vs 1518.14 ± 547.25 IU, p < 0.05) in spite of comparable duration of stimulation. After FET cycle, no significant difference was found in the clinical pregnancy rates between mild stimulation (12.5%) and PPOS group (16.7%). Conclusions Higher percentage of top-quality embryos on Day 3 and comparable clinical pregnancy rate was obtained in PPOS protocol, which could be considered as a feasible ovarian stimulation protocol in women aged above 40 years old.

目的:探讨microRNA-29b (miRNA-29b)在卵巢癌细胞中的表达差异及其对卵巢癌细胞增殖和侵袭能力的影响.方法:采用real-time PCR技术检测人卵巢癌上皮细胞系SKOV-3及正常人卵巢上皮细胞系IOSE80中miRNA-29b的表达水平;采用转染技术上调SKOV-3细胞中miRNA-29b的表达水平;采用CCK-8法检测SKOV-3细胞增殖能力;采用Transwell法检测SKOV-3细胞的侵袭能力;采用Western印迹法检测SKOV-3细胞中蛋白表达水平.结果:与IOSE80细胞相比,人卵巢癌上皮细胞系SKOV-3细胞miRNA-29b的表达下降(P＜0.05).转染miRNA-29b mimic后SKOV-3细胞中miRNA-29b的表达水平增加;从第4天开始,转染miRNA-29b的SKOV3细胞增殖能力下降(P＜0.05).转染miRNA-29b减少了通过聚碳酸酯膜的SKOV3细胞数量,抑制了SKOV3细胞的侵袭能力(P＜0.05);转染miRNA-29b mimic后,卵巢癌细胞SKOV3中抑制凋亡蛋白Bcl-2和侵袭相关蛋白MMP-9的表达均降低,与阴性对照组相比差异有统计学意义(P＜0.05).结论:miRNA-29b可通过抑制凋亡相关蛋白Bcl-2和侵袭相关蛋白MMP-9的表达来抑制卵巢癌细胞的增殖和侵袭.

To compare Crinone vaginal progesterone gel with intramuscularly injected progesterone for luteal phase support in progesterone-supplemented frozen-thawed embryo transfer (FET) cycles, a randomized prospective study of patients qualified for FET was conducted between September 2010 and January 2013 at a hospital in Shanghai, China. From the day of transformation into secretory phase endometrium (day 0), Crinone vaginal gel (90 mg/d) was administered to patients in the Gel Group, while progesterone (40 mg/d) was injected intramuscularly in patients in the Inj Group (n = 750 per group). All patients received oral dydrogesterone (20 mg/d) and estradiol valerate (4–8 mg/d). Day 3 embryos with the highest pre-frozen scores were transferred to patients in the two groups and the clinical outcomes compared. This study comprised 1,500 cycles (750 in each group). Twenty-nine cycles in the Gel Group and 24 in the Inj Group were withdrawn. There were no significant differences between groups in age, endometrial thickness, endometrial preparation time or number of embryos transferred. No significant differences were observed between the Gel Group and Inj Group in the rates of live birth (32.6% vs. 31.7%, P = 0.71), clinical pregnancy (40.1% vs. 40.6%, P = 0.831), implantation (25.8% vs. 25.3%, P = 0.772), abortion (16.3% vs. 18.3%, P = 0.514) or ectopic pregnancy (2.8% vs. 4.4%, P = 0.288). Multivariate logistic regression analysis revealed that the odds ratios (95% confidence intervals) for the rates of live birth, clinical pregnancy, abortion and ectopic pregnancy (Gel Group relative to Inj Group) were 1.036 (0.829–1.295), 0.971 (0.785–1.200), 0.919 (0.595–1.420) and 0.649 (0.261–1.614), respectively. Our study revealed that using Crinone vaginal gel in FET cycles achieved similar pregnancy outcomes to intramuscular progesterone, indicating that vaginal gel is a viable alternative to intramuscular injection. Trial Registration Chinese Clinical Trial Registry ChiCTR-TRC-14004565

目的: 探讨新鲜胚胎移植周期黄体酮阴道缓释凝胶作为黄体支持的临床效果。方法: 回顾性分析接受IVF/ICSI助孕的行新鲜胚胎移植患者的临床资料, 统计分析3 193个周期采用黄体酮阴道缓释凝胶行黄体支持(A组)者的临床妊娠率和活产率, 并与肌肉注射黄体酮行黄体支持的813个周期(B组)进行比较, 同时进一步按长、短、拮抗剂方案进行分层分析。结果: 活产率A组为34.3%, B组为34.9%, 组间无统计学差异(P>0.05), 临床妊娠率和流产率组间也均无统计学差异(P>0.05)。活产率分层分析显示, 长方案A组为40.0%, B组为40.3%;短方案A组为25.9%, B组为28.3%, 拮抗剂方案A组为28.3%, B组为28.8%, 两两比较均无统计学差异(P>0.05), 临床妊娠率和流产率也均无统计学差异(P>0.05)。结论: 作为IVF/ICSI-ET周期的黄体支持, 黄体酮阴道缓释凝胶临床效果与肌肉注射黄体酮相同, 阴道凝胶给药是一种可行的替代肌肉注射的黄体支持方式。

Purpose: To compare the clinical result of mini-dose GnRH-a long protocol with short protocol in older patients undergoing IVF.Materials and methods: This was a retrospective study. Four hundred and sixty-one women aged above 35-year-old in first cycle were assigned to two groups: GnRH-a short protocol (n = 359); and mini-dose GnRH-a long protocol (n = 102). Both groups were divided based on their age, into groups over and under 38 years old. Primary outcome include live birth rate per started cycle. Other clinical outcomes were good-quality embryo rate, clinical pregnancy rate.Results: Patients treated with mini-dose GnRH-a protocol and those treated with short protocol showed similar live birth rate. In the mini-dose long protocol group aged 35-38 years old, patients showed significantly thicker endometrium at the day of hCG administration, higher number of good embryos obtained and higher good-quality embryo rate (56.3% versus 46.5%) compared with short protocol. The implantation rate and clinical pregnancy rate were higher versus short protocol group, but this result was not statistically significant.Conclusion(s): Mini-dose GnRH-a long protocol for older women is at least as effective as short protocol, especially in patients aged 35-38 years, with a better good-quality embryo rate and higher number of good embryos obtained, therefore mini-dose GnRH-a long protocol can be considered as an alternative protocol for patients above 35 years age.

CONTEXT Identifying novel molecular markers for assessing endometrial receptivity is necessary for understanding human implantation and may help in improving the clinical outcome of in vitro fertilization. OBJECTIVE We aimed to compare the gene expression profiles of the pre-receptive vs receptive phases of the natural cycle in human endometrial biopsies. DESIGN The design of this study was detecting the global gene expression profile of human endometrial receptivity by RNA-Seq. SETTING This study was conducted at a university reproductive center. PARTICIPANTS Twelve women with normal menstrual cycles participated in the study. INTERVENTION Study interventions included endometrial biopsies. MAIN OUTCOME MEASURES The endometrial transcriptomes were determined by RNA-Seq, and the expression of selected differentially expressed genes (DEGs) was validated by quantitative RT-PCR. RESULTS A total of 2372 DEGs were identified by RNA-Seq. Of these genes, 1099 were up-regulated at LH+7 versus LH+2, whereas 1273 were down-regulated. Nineteen selected genes were confirmed by quantitative RT-PCR. We first demonstrated that metallothionein (MT) family members, MT1E, F, G, H, M, X, and 2A, and four novel transcripts, HAP1, ZCCHC12, MRAP2, and OVGP1, which were not previously linked to endometrial physiology, showed significant expression changes during implantation. Mineral absorption was the most enriched pathway for up-regulated genes, and cell cycle was enriched for down-regulated genes. Gene co-expression network analysis identified five core regulatory factors (GLI2, CDC25A, TLR9, MT1G, and SLC5A1) that are involved in endometrial receptivity during implantation. Examination of the promoter regions of the DEGs identified AP2 and SP1 binding sites, suggesting a potential regulatory role in endometrial gene expression for these two transcription factors. CONCLUSIONS This study provides the first RNA-Seq-based transcriptome comparison of pre-receptive and receptive human endometria. Many novel candidate genes, which have not been previously studied in human endometrium, may have functional significance during implantation and serve as molecular markers for endometrial receptivity.

子宫内膜自然杀伤(uNK)细胞是胚胎植入前内膜和早孕期蜕膜中数量最多的一类免疫细胞.母体的uNK细胞与胎儿的滋养层细胞相邻且相互作用.uNK细胞分泌一系列细胞因子和血管生长因子,调控滋养层细胞入侵并参与子宫螺旋动脉的重塑.uNK细胞数量的增多与反复种植失败(RIF)、复发性流产(RSA)有关.但仍需更多的研究阐明uNK细胞在胚胎种植过程中的具体作用、对内膜容受性的影响,以此作为临床治疗的依据.