Background Optimal luteal phase support after fresh transfer remains a clinical challenge in GnRH antagonist IVF/ICSI cycles triggered with dual trigger. HCG/GnRha supports may improve outcomes, but its safety and ideal application remain uncertain. To investigate the effectiveness and safety of strengthened luteal phase support in fresh embryo transfer cycles following GnRH antagonist protocols with dual trigger, and further to identify patients who best most as well as clinical indicators. Methods This retrospective cohort study included all fresh embryo transfer cycles after dual-trigger oocyte retrieval between January 2020 and May 2024 at a single center. Patients were grouped based on LPS strategy: routine support (RT) or strengthened support (ST) using hCG (S-hCG), GnRHa (S-GnRHa), or both (S-Double). Pregnancy and neonatal outcomes and safety profiles were compared before and after propensity score matching. Subgroup analyses and mid-luteal estradiol ratio (E2 ratio) assessment were performed. Results ST was associated with significantly higher clinical pregnancy (48.2% vs 37.1%) and live birth rates (43.2% vs 34.3%) than RT (P < 0.001) without additional risks including OHSS, birth defects and maternal complications. Subgroup analyses showed benefits across diverse populations, including women ≥ 35 years, those with diminished ovarian reserve, and patients receiving suboptimal embryos. Among ST regimens, hCG supplementation achieved the best outcomes, and patients with a low mid-luteal E2 ratio (< 0.15) derived the greatest benefit. Conclusions Enhanced luteal support improves pregnancy outcomes in antagonist-dual trigger cycles. hCG appears most effective, but individualized strategies using biomarkers such as E2 ratio merit further investigation. Trial registration: Not applicable.

集落刺激因子(colony stimulating factor,CSF)是促进髓系祖细胞增殖、分化的一组生长因子,包括巨噬细胞集落刺激因子(macrophage colony stimulating factor,M-CSF/CSF1)、粒细胞巨噬细胞集落刺激因子(granulocyte-macrophage colony stimulating factor,GM-CSF/CSF2)、粒细胞集落刺激因子(granulocyte colony stimulating factor,G-CSF/CSF3)、多重集落刺激因子(multi-CSF/IL3)等,重组上市的商品化产品则称之为相应的形成细胞刺激因子.骨髓、间质细胞、成纤维细胞、单核细胞和巨噬细胞均可产生CSF,重组的GM-CSF、G-CSF、M-CSF在血液系统疾病和防治肿瘤放化疗不良作用等领域应用已经超过30年[1].CSF 与其受体(CSF-receptor,CSF-R)结合后发挥作用.已有研究发现,除髓系祖细胞、髓系白血病细胞、成熟的中性粒细胞、血小板、单核细胞、淋巴细胞和一些T细胞和B细胞膜上表达特异性的CSF-R外,子宫内膜上皮细胞、胎盘细胞、滋养细胞和黄素化的卵巢颗粒细胞等许多非造血组织细胞亦可表达CSF-R.

1病历摘要 患者,31岁.因婚后未避孕未孕4年,体外受精(IVF)失败2次,于2019年1月5日就诊于四川大学华西第二医院生殖医学科.患者20岁时出现痛经,疼痛程度逐渐加重,8年前诊断为“子宫腺肌病”,给予去氧孕烯-炔雌醇(妈富隆)治疗,月经期间服用布洛芬.患者于2014年结婚,婚后性生活正常,未避孕一直未孕.2017年7月15日曾就诊于本院,此前在院外先后进行了生殖激素测定和丈夫精液检查(报告丢失),对所带子宫输卵管造影片进行阅片后发现,子宫腔显影良好,双侧输卵管连续显影,弥散差,提示双侧输卵管通畅,怀疑粘连.

Oxidative stress (OS) is associated with poor oocyte quality and in vitro fertilization and embryo transfer (IVF-ET) outcomes for patients with polycystic ovary syndrome (PCOS). Growth hormone (GH) can function to reduce OS in some types of cells. Therefore, this prospective randomized study investigated whether GH can significantly improve OS and oocyte quality in women with PCOS. This study enrolled 109 and 50 patients with and without PCOS (controls), respectively. The patients with PCOS were randomly assigned to receive treatment with GH (PCOS-T) or not (PCOS-C). The primary outcome included markers of OS in serum and FF, and secondary outcomes were mitochondrial function in granulosa cells (GCs) and IVF-ET outcomes. The PCOS groups showed higher basal serum total oxidant status (TOS) and OS index (OSI) levels. The follicle fluid (FF) TOS and OSI and GC apoptosis rate were significantly higher, whereas the GC mitochondrial membrane potential (MMP) was significantly lower in the PCOS-C group than in the PCOS-T and non-PCOS control groups (P < 0.05). Significantly more oocytes were fertilised and cleavage stage embryos were produced in the PCOS-T group than in the PCOS-C group (P < 0.05). GH also improved the rates of implantation and clinical pregnancy, but not significantly (P > 0.05). This study showed that GH alleviated the TOS and OSI level in FF and improved GC mitochondrial dysfunction and oocyte quality in patients with PCOS.Clinical Trial Registration Number: This project was prospectively registered on the Chinese Clinical Trial Registry on October 20, 2018. (ChiCTR1800019437) ( https://www.chictr.org.cn/edit.aspx?pid=28663&htm=4 ).

子宫内膜癌(endometrial cancer, EC)是常见的妇科恶性肿瘤.2017年,以子宫内膜癌为主要表现的子宫体恶性肿瘤的全球新发病例超过 40 万,年发病率达到9.6/10 万[1].疾病报告体系建立完善国家新发病例的年发病率更高,达到15～27/10 万,14 ％发生于绝经前, 5 ％的患者确诊年龄低于40岁[2].美国的一项大型研究显示,子宫内膜增生年发生率为132.57/10 万,其中的子宫内膜非典型增生(endometrial atypical hyperplasia,EAH)年发生率为18.63/10 万,35岁前诊断者占2.6 ％,40 岁前患者占7.3 ％[3].80 ％的Ⅰ型 EC 与子宫内膜增生有关联,一项跨时15 年共 306 例 EAH 随访结果显示, 29.1 ％发展成为 EC[4].

Ambient air pollution has been a major concern in China due to its effect on population health. Exposure to ambient air pollution has negative impact on animal reproduction and fertility, however, its effect on human reproduction has been inconclusive. We conducted a retrospective study on in vitro fertilization (IVF) patients from Chengdu, Sichuan Province in western China, a city with persistent ambient air pollution. We analyzed the medical records of 1139 patients who underwent first conventional IVF cycles during 2014-2019. The relationship between six atmospheric pollutants (PM2.5, PM10, O3, NO2, SO2, CO) and IVF pregnancy outcomes were assessed by 1) stratification of maternal age into three groups (<35, 35-39, ≥40 years), and by 2) averaging pollutant concentration during different exposure windows. The results indicate that the association between ambient air pollution and IVF pregnancy outcomes (biochemical pregnancy and clinical pregnancy) is more significant for women in <35 years age group. Concentrations of PM2.5, PM10, NO2, SO2 and CO are negatively associated with the odds of biochemical pregnancy and clinical pregnancy, and concentration of CO in particular is associated with the largest reduction in odds. Conversely, O3 concentration is positively associated with biochemical pregnancy and clinical pregnancy. Moreover, pollutant concentration during long-term exposure window is associated with larger magnitude of change in the odds of biochemical pregnancy and clinical pregnancy. Findings from this study suggest that exposure to ambient air pollution during any period within the IVF treatment timeline would influence IVF pregnancy outcomes, and such influence is more pronounced in younger women (<35 years).

Rationale: During ultrasound prenatal screening, absence of the fetal nasal bone is used as a marker for common aneuploidies in singleton pregnancies. However, its application in multiple pregnancies is less sensitive and more challenging owing to difficulties in obtaining adequate views of the fetal face. Patient concerns: A 38-year-old woman with dichorionic-diamniotic (DCDA) pregnancy and a history of in vitro fertilization and embryo transfer was referred to our hospital with the absence of the nasal bone noted on ultrasound images obtained during the second trimester in 1 fetus. Diagnosis: Prenatal sonographic examination revealed the absence of the nasal bone in 1 fetus in the DCDA gestation. Amniocentesis performed on the dual amniotic sacs revealed normal karyotypes for each twin. The absence of the nasal bone was confirmed on a radiograph obtained postnatally in 1 infant. Interventions: The mother underwent routine outpatient care according to the gestational age and successfully delivered following lower-segment cesarean section. Outcomes: Two live infants were uneventfully delivered. Radiography confirmed the absence of the nasal bone in 1 of the newborns on postnatal day 3. The infants were followed up until 2 years and 9 months of age, which revealed normal appearance and eating and breathing functions. Lessons: Prenatal diagnosis of the absence of nasal bone in 1 fetus of DCDA pregnancy has rarely been reported. Although a fetus with the absence of the nasal bone in DCDA gestation poses a significant risk of aneuploidy, it is acceptable when the defect is an isolated anomaly after ruling out genetic abnormalities. Appropriate consultation should be provided for these patients.

Objective To determine the age at menarche and patterns of menstruation among school girls in China.Methods With multi-stage sampling,5 981 primary and middle school students from both urban and rural areas in eight provinces were investigated anonymously with the method of computer assisted self-interview (CASI).Results Menarche was attained at the age of (12.7 ± 0.0) years,(12.4 ± 0.0) years and (13.0 ± 0.0) years for urban and rural respectively (P＜0.01).The mean interval between menarche and regular cycle was (1.2 ± 0.0) years.Analysis on the menstrual cycle pattern according to the time post menarche showed that the proportion of participants with regular cycle were similar in different time post menarche (P=0.33);the proportion of participants with blood flow duration between 4-7 d and moderate blood flow were increased with time (P＜0.01);the incidence of dysmenorrhoea and degree of pain were increased with time (P＜0.01).Conclusion The age ofmenarche of urban was 0.6 year earlier than that of rural.The proportion of participants with regular cycle was similar after 1 year postmenarche.The duration and amount of menstrual blood flow become the pattem of adult women with time.The incidence of dysmenorrhoea and severe pain increased with time.

获得生育能力称之为生育力( fecundity ),一般以观察时间段的临床妊娠率或活产率来评价,也可将获得临床妊娠时间( time to pregnancy,TTP)的长短作为评价指标。女性在25岁后,随着年龄的增加,生育力逐渐下降,自然流产率、妊娠和分娩期并发症、围生儿病率和死亡率等同步上升,35岁后这些变化更为明显,因此通常将35岁以上的妇女定义为生育高龄妇女(advanced maternal age,AMA),超过45岁以上的妇女则定位为超高龄妇女( very advanced maternal age,vAMA)[1]。据测算,我国全面实施二孩政策后符合条件的1.4亿对夫妇中,女方年龄在35岁以上的约60%[2],其中新增9000万对夫妇中,40~49岁的约占50%。全面实施二孩政策,需要解决生得起、生得出、生得好3个问题[3]。科学精准的生育力评估后,对目标人群提出合理实用的生育方法建议,使有生育能力的夫妇选择恰当的方法尽早怀孕,对已经失去自然生育能力的夫妇做出放弃生育的建议,减少夫妇实现二孩生育的经济付出和时间消耗,在此基础上对怀孕后的母胎进行科学保健以实现优生。

The polycystic ovary syndrome (PCOS) is an endocrine disorder mainly associated with infertility. Abnormal regulation of relevant genes is required for follicular development in PCOS. In the current study, the expression of serum miRNAs of PCOS patients was explored using miRNA array followed by qRT-PCR assays. The circulating level of miR-592 was significantly down-regulated in PCOS patients in comparison with healthy controls. Furthermore, we found that miR-592 was inversely correlated with the level of luteinizing hormone/chorionic gonadotropin receptor (LHCGR). Computational analysis predicted that miR-592 interacts with the LHCGR mRNA via binding to a site located in the 3′UTR region. Using a luciferase-based reporter assay we found that miR-592 directly targeted the LHCGR. In KGN cell line, miR-592 overexpression inhibited cell viability and the transition of phase G1 to phase S. Knocking down of LHCGR inhibited cell viability and cell cycle progression in KGN cells, and LHCGR co-transfection reversed the inhibitory effect of miR-592. These results shed new light on the diagnosis and treatment of PCOS syndrome.

Background: We evaluated whether heat shock protein HSP70 plays a protective role in the embryos of Kunming mice subjected to chronic unpredictable mild stress.Methods: Female mice were stimulated for 4 weeks with nine stressors and then divided into mild, moderate and severe stress groups. Superovulation was induced with a gonadotropin preparation (PMSG/HCG) and HSP70 expression in 2-cell embryos and day 4 embryos was detected by immunofluorescence (IF) and real-time polymerase chain reaction (RT-PCR).Results: In the mild stress group, ovarian response and oocyte development potential were similar to those of the control group, while the HSP70 mRNA levels of the embryos were significantly higher (P < 0.05). In the severe stress group, ovarian response and oocyte development potential decreased compared with the control group (P < 0.05), while the HSP70 mRNA levels were similar. The results of the moderate stress group were intermediate among the three groups. Furthermore, HSP70 mRNA levels of the embryos were shown to be positively associated with parameters of oocyte and embryo development potential (P < 0.05).Conclusions: HSP70 overexpression may play a protective role in the embryos of the mild or moderate stress mice stimulated by chronic unpredictable mild stress.

目的 探讨短效曲普瑞林长方案中不同卵泡大小停用促性腺激素释放激素激动剂(GnRH-a)方案的临床效果.方法 回顾性分析2012年11月-2013年1月期间,行体外受精/卵胞浆单精子注射助孕,年龄＜40岁妇女,排除卵巢储备功能低下、多囊卵巢综合征以及既往有卵巢手术和卵巢反应不良史者,共收集358个周期的临床资料,根据停用GnRH-a时主导卵泡大小分为＜14mm和≥14mm两组.结果 早期停用GnRH-a组患者控制性促排卵(COH)中促性腺激素用量及使用时间高于晚期停用GnRH-a组(P＜0.05);但两组患者HCG日雌二醇、孕酮、早发孕酮峰发生率及获卵数、优胚数、胚胎种植率、临床妊娠率、早期流产率和活产率等临床结局差异无统计学意义(P＞0.05).结论 对于接受短效GnRH-a长方案患者,COH过程中表现为卵巢慢反应者早期停用GnRH-a可有效维持垂体降调节,且不影响临床妊娠结局.

Background: Recent studies have indicated the use of gonadotropin-releasing hormone antagonists (GnRH-ant) as an adjuvant treatment to prevent premature luteinization (PL) and improve the clinical outcomes in patients undergoing controlled ovarian stimulation (COS) with intrauterine insemination (IUI). However, the results of these studies are conflicting.Methods: We conducted a systematic review and meta-analysis of randomized trials aiming to compare the clinical efficacy of GnRH-ant in COS/IUI cycles. Twelve studies were identified that met inclusion criteria and comprised 2,577 cycles assigned to COS/IUI combined GnRH-ant or COS/IUI alone.Results: Meta-analysis results suggested that GnRH-ant can significantly increase the clinical pregnancy rate (CPR) (OR = 1.42; 95% CI, 1.13-1.78) and decrease the PL rate (OR = 0.22, 95% CI, 0.16-0.30) in COS/IUI cycles. Subgroup analysis results suggested statistically significant improvement in the CPR in non-PCOS patients (OR = 1.54; 95% CI, 1.03-2.31) but not in the PCOS population (OR = 1.65; 95% CI, 0.93-2.94) and multiple mature follicle cycles (OR = 1.87; 95% CI, 0.27-12.66). There were no difference in the miscarriage and multiple pregnancy rates between the groups.Conclusion: This meta-analysis suggested that GnRH-ant can reduce the incidence of PL and increase the CPR when used in COS/IUI cycles, and it was especially useful for non-PCOS patients. However, evidence to support its use in PCOS patients is still insufficient

In order to identify and describe the effectiveness of transdermal testosterone pretreatment on poor ovarian responders, MEDLINE, EMBASE, the Cochrane library and the Chinese biomedical database were searched for randomized controlled trials (RCTs). Three RCTs, which compared the outcomes of female pretreatment with transdermal testosterone prior to in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) with those of control groups, were included in the present review. The three RCTs enrolled a total of 221 randomized subjects. The meta-analysis revealed that females who received transdermal testosterone treatment prior to their IVF/ICSI cycle had a two-fold increase in live birth rate [risk ratio (RR)=2.01, 95% confidence interval (CI) 1.03-3.91], clinical pregnancy rate (RR=2.09, 95% CI 1.14-3.81) and a significantly more oocyte retrieved [mean difference (MD)=1.36, 95% CI 0.82-1.90]. The current findings provide evidence that pretreatment with transdermal testosterone may improve the clinical outcomes for poor ovarian responders undergoing IVF/ICSI. However, the results should be interpreted with caution due to the small sample size of the studies used and the heterogeneities. Further good quality RCTs would be needed to reach further conclusions.

Polycystic ovary syndrome (PCOS) patients undergoing controlled ovarian stimulation and intrauterine insemination (COS/IUI) often face the risk of premature luteinization, which may result in lower pregnancy rate and higher miscarriage rate. This review was performed to identify if adjuvant treatment with GnRH antagonist (GnRH-ant) could effectively improve the clinical outcome of patients with PCOS undergoing COS/IUI. A literature search was conducted on the PubMed, EMBASE and Cochrane library databases. Two randomized controlled trials were included in this review, enrolling a total of 333 cycles. The patients who received GnRH-ant treatment had lower progesterone levels on the hCG day and a reduced premature luteinization rate. However, the rates of live birth, clinical pregnancy and miscarriage did not significantly differ between the GnRH-ant supplementation group and control group. In conclusion, although the existing randomized controlled trials indicate that GnRH-ant can effectively decrease the premature luteinizaton rate, evidence to support its use to improve clinical pregnancy outcomes in PCOS patients undergoing COS/IUI treatment is insufficient.

OBJECTIVE The study aimed to explore the method for in vitro expansion of CD4+CD25+regulatory T cells(CD4+CD25+Treg) by co-culturing mouse allogeneic bone marrow-derived dendritic cells( BMDC) with CD4+T cells.METHODS Mouse allogeneic imBMDC were co-cultured with CD4+T cells and the ability of the co-culturing in the in vitro expansion of CD4+CD25+Treg was evaluated by determining the changes in cell proliferation rate and in percentage of CD4+CD25+Treg cells among the CD4+T population. Fluorescent quantitative RT-PCR was used to measure the expression of FOXP3gene in in vitro-expanded CD4+CD25+Treg cells, and cell proliferation inhibition experiments were utilized to determine the functional activities of CD4+CD25+Treg cells. RESULTS The rate of cell proliferation increased by 5.26 ± 0.286 times on the7th day of the co-culturing; CD4+CD25+Treg cells accounted for 33.77 ± 3.69% of the CD4+T cells, which was significantly higher than the proportion of CD4+CD25+Treg cells in freshly isolated mouse spleen cells(P﹤0.05). No statistically significant difference was observed in the expression of FOXP3 gene between in vitro-expaneded and freshly isolated CD4+CD25+Treg cells(P﹥ 0.05). Co-culturing of lymphocytes demonstrated that in vitro-expaneded CD4+CD25+Treg had stronger inhibitory effect on cell proliferation than freshly isolated CD4+CD25+Treg cells. CONCLUSION Co-culturing of mouse allogeneic BMDCs with CD4+T cells can effectively induce the expanded CD4+CD25+Treg cells and maintain the functional activities of immune cells.

Background Obesity may exert a negative effect on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment. However, the effect of obesity on the endometrium remains unknown. This study was designed to assess the effect of isolated body mass index (BMI) on endometrial blood supply in non-polycystic ovary syndrome (PCOS) women during ICSI by power Doppler Ultrasound. Methods An observational prospective study was carried out. A total of 206 patients without PCOS were divided into 4 groups based on Chinese BMI classification (kg/m(2): underweight (BMI < 18.5), normal weight (18.5 less than or equal to BMI < 24), overweight (24 less than or equal to BMI < 28), and obese (BMI greater than or equal to 28). Endometrial thickness, endometrial pattern, endometrial spiral arterial resistance index (RI) and pulsatility index (PI) values and systolic/diastolic ratio (S/D) were assessed on the day of human chorionic gonadotropin administration. Results Obese patients required more doses of gonadotrophin and longer stimulation duration than the normal weight patients (P < 0.05). Endometrial thickness and pattern were not statistically different between the 4 BMI subgroups (P > 0.05). Subendometrial blood flow was detected in 165 (80.1%) patients and spiral arterial PI was significantly higher in the obese group than in the normal weight and underweight groups (P < 0.05). All parameters of ICSI outcome were comparable, including pregnancy and miscarriage rates. Conclusions Obesity (BMI greater than or equal to 28 kg/m(2)) appears to exert a negative effect on endometrial and subendometrial blood flow based on the Chinese standard of obesity; however, it seems to have no significant effect on ICSI outcomes in non-PCOS women.

Objective To assess the validity of HLA active specific immunotherapy for infertility.Methods This study was conducted in 98 URSA patients who were given intradermal injection of their husbands' leukomonocyte once two weeks.The injection sites were divided into 6~8 areas.Then they came to the secondary therapy course after six weeks.One or two more therapy courses should be used in these patients who got negative results of HLA-DR antibody testing and pregnant patients.Results 32 patients of primary infertility and 15 patients of secondary infertility were HLA-DR antibody positive after one course of HLA active therapy,and the effective rate was82% and 88% respectively.15 patients of primary infertility and 11 patients of secondary infertility got the positive results of HLA-DR antibody after two courses of HLA active therapy,and the effective rate was 79% and 85%.HLA-DR antibody of 32 patients of primary infertility and 2 patients of secondary infertility changed to positive after three courses of HLA active therapy,and the effective rate was 43% and 67% respectively.45 patients were pregnant after HLA active immunotherapy,and the achievement ratio was 46%.Conclusion HLA active specific immunotherapy may increase the pregnancy rate of infertility patients with negative HLA-DR antibody.HLA-DR antibody can be a useful marker for the diagnosis and immunotherapy of infertility.

Objective To investigate the effect of different in vitro fertilization ( IVF) treatment protocols on infertile women with adenomyosis. Methods Sixty-four infertile women with adenomyosis who had IVF treatment cycles from January 2006 to June 2009 were retrospectively analyzed. According to administration of long course gonadotropin-releasing hormone agonist ( GnRH-a) and the start time of gonadotropin ( Gn) ,all participants were divided into three groups:the first group with ultra-long term protocol,the second group with long or short term protocol after administration of long course GnRH-a and the third group with routine long term protocol. Results There were no differences among the three groups with regard to days of Gn administration,amounts of Gn administration,numbers of retrieved oocytes,prevalence of poor response and miscarriage ( P > 0. 05). The cancelation rates of the three groups were 20. 0% 、7. 7% and 30. 0% respectively. There were significant differences in cancelation rates among the groups ( χ2 = 5. 74,P < 0. 05) ,and the cancelation rate in the second group was significantly lower than the other groups ( χ2 = 7. 21,P < 0. 05). The ongoing pregnancy rates of the groups were 23. 0% 、37. 0% and 15. 3% respectively. There were significant differences in ongoing pregnancy rates among three groups ( χ2 =11. 31,P <0. 05) ,and the ongoing pregnancy rate in the second group was significantly higher than the other groups ( χ2 =8. 52,P <0. 05). Conclusion Compared with the ultra-long term and routine long term protocol of IVF treatment in infertile woman with adenomyosis,the ongoing pregnancy rate might be higher and the cancelation rate might be lower in the long or short term protocol after administration of long course GnRH-a.

目的探讨激光透明带切割技术对常规体外受精-胚胎移植(IVF-ET)冻融胚胎移植后妊娠率和植入率的影响。方法因输卵管因素不孕行常规IVF-ET患者共145个冻融周期胚胎纳入研究,实验组76个冻融周期的胚胎复苏后采用激光透明带切割技术进行辅助孵化;对照组69个冻融周期的胚胎复苏后未进行辅助孵化,均培养0.5~3 h后移植。比较两组冻融胚胎移植后的妊娠率和植入率。结果对照组妊娠率14.49%,植入率5.85%;实验组妊娠率30.26%,植入率11.57%,均高于对照组(P<0.05)。结论应用激光透明带切割技术可以提高冻融胚胎移植后妊娠率和植入率。