ObjectiveThe objective was to analyze the impact of the uterine artery pulsatility index (PI) on pregnancy outcomes by measuring uterine artery blood flow on the day of endometrial transformation in patients undergoing frozen–thawed embryo transfer (FET).MethodsThis was a case-control study. In total, 2,036 patients who underwent FET at the Third Affiliated Hospital of Zhengzhou University from October 2019 to September 2020 were included. The patients were divided into a clinical pregnancy group and a nonclinical pregnancy group according to pregnancy outcome. A multivariate logistic regression model was used to analyze the factors affecting the clinical pregnancy rate. The receiver operating characteristic (ROC) curve was used to determine the optimal mean PI cutoff value of 1.75. After 1:1 propensity score matching (PSM), 562 patients were included. For statistical description and analysis, the patients were divided into two groups: a group with a mean PI > 1.75 and a group with a mean PI ≤ 1.75.ResultsThe clinical pregnancy group included 1,218 cycles, and the nonclinical pregnancy group included 818 cycles. There were significant differences in female age (P<0.01), infertility type (P=0.04), baseline follicle-stimulating hormone level (P=0.04), anti-Müllerian hormone (AMH) level (P<0.01), antral follicle count (P<0.01), number of transferred embryos (P=0.045) and type of transferred embryo (P<0.01). There was no significant difference in the mean bilateral PI (1.98 ± 0.34 vs. 1.95 ± 0.35, P=0.10). The multivariate analysis results showed that maternal age (AOR=0.95, 95% CI=0.93-0.98, P<0.01), AMH level (AOR=1.00, 95% CI=1.00-1.01, P=0.045), number of transferred embryos (AOR=1.98, 95% CI=1.47-2.70, P<0.01), and type of transferred embryo (AOR=3.10, 95% CI=2.27-4.23, P<0.01) were independent factors influencing the clinical pregnancy rate. The mean PI (AOR=0.85, 95% CI=0.70-1.05; P=0.13) was not an independent factor influencing the clinical pregnancy rate. Participants were divided into two groups according to the mean PI cutoff value of 1.75, and there was no significant difference between the two groups (P > 0.05).ConclusionIn this study, we found that the uterine artery PI on the day of endometrial transformation in patients undergoing FET is not a good predictor of pregnancy outcomes.

In this multicenter, non-inferiority, randomized trial, we randomly assigned 992 women undergoing in-vitro fertilization (IVF) with a good prognosis (aged 20-40, >= 3 transferrable cleavage-stage embryos) to strategies of blastocyst-stage (n = 497) or cleavage-stage (n = 495) single embryo transfer. Primary outcome was cumulative live-birth rate after up to three transfers. Secondary outcomes were cumulative live-births after all embryo transfers within 1 year of randomization, pregnancy outcomes, obstetric-perinatal complications, and livebirths outcomes. Live-birth rates were 74.8% in blastocyst-stage group versus 66.3% in cleavage-stage group (relative risk 1.13, 95%CI:1.04-1.22; Pnon-inferiority < 0.001, P-superiority = 0.003) (1-year cumulative live birth rates of 75.7% versus 68.9%). Blastocyst transfer increased the risk of spontaneous preterm birth (4.6% vs 2.0%; P = 0.02) and neonatal hospitalization >3 days. Among good prognosis women, a strategy of single blastocyst transfer increases cumulative live-birth rates over single cleavage-stage transfer. Blastocyst transfer resulted in higher preterm birth rates. This information should be used to counsel patients on their choice between cleavage-stage and blastocyst-stage transfer (NCT03152643, https://clinicaltrials.gov/study/NCT03152643).

Objective:To explore whether the duration of oral estrogen treatment before progesterone application affects neonatal outcome in single frozen-thawed embryo transfer (FET) with artificial cycles.Methods:It was a retrospective cohort study. Patients who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), receiving single frozen blastocyst transfer with artificial cycle and delivering a single live birth in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University between January 2015 and December 2019 were included. All FET cycles were divided into four groups according to the estrogen treatment duration before progesterone application, ≤12 d ( n=306), 13-15 d ( n=620), 16-18 d ( n=471), and ≥19 d ( n=275). Primary outcome was the incidence of small for gestational age (SGA). Secondary outcomes were the incidence of preterm birth, low birth weight, macrosomia and large for gestational age (LGA). Results:A total of 1 672 single blastocyst transfer cycles were included. The incidence of SGA among the four groups was 7.8% (24/306), 4.8% (30/620), 5.7% (27/471), and 7.6% (21/275), respectively, with no statistically significant difference ( P=0.204). The results of multiple logistic regression analysis showed that the duration of estrogen used before progesterone application did not affect the incidence of SGA in singleton offspring (with ≤12 d as the reference, 13-15 d: a OR=1.37, 95% CI: 0.70-2.70, P=0.361; 16-18 d: a OR=0.74, 95% CI: 0.40-1.36, P=0.336; ≥19 d: a OR=0.81, 95% CI: 0.44-1.49, P=0.501). There were no significant differences in neonatal preterm birth rate ( P=0.204), low birth weight ( P=0.582), incidences of macrosomia ( P=0.201) and LGA infants ( P=0.335) among the four groups. Conclusion:In artificial FET cycle, the duration of oral estrogen treatment before progesterone application does not affect the outcome of singleton offspring after single blastocyst transfer.

Objective:To investigate whether there are differences in clinical pregnancy and perinatal outcomes among different protocols for artificial insemination by donor (AID) in female patients aged ≤35 years.Methods:This retrospective cohort study analyzed clinical data of patients who underwent AID at the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University from January 1, 2016 to January 31, 2021. Based on ovulation induction therapy, patients were divided into 4 groups: natural cycle (NC) group, letrozole (LE)/clomiphene (CC) group, gonadotropin (Gn) group and LE/CC combined with Gn (LE/CC+Gn) group. The clinical outcomes, incidence of complications, and offspring health were compared among these groups, and logistic regression analysis was employed to investigate the effects of different protocols on the clinical and perinatal outcomes of AID cycles.Results:In NC group, LE/CC group, Gn group and LE/CC+Gn group, the cycle cancellation rate [0.5% (11/2 147), 1.1% (12/1 045), 1.6% (9/549), 3.2% (9/315), P<0.001], the clinical pregnancy rate [31.5% (673/2 136), 35.8% (370/1 033), 42.8% (231/540), 38.2% (117/306), P<0.001], the multiple pregnancy rate [0.7% (5/673), 3.2% (12/370), 3.5% (8/231), 6.8% (8/117), P<0.001], the abortion rate [12.8% (86/673), 9.2% (34/370), 5.2% (12/231), 8.5% (10/117), P=0.008] and the live birth rate [27.2% (581/2 136), 31.4% (324/1 033), 40.0% (216/540), 34.3% (105/306), P<0.001] were statistically significant, while the differences among the four groups in the ectopic pregnancy rate, the preterm birth rate, and the overdue birth rate were not statistically significant (all P>0.05). After adjusting for confounding factors, the differences were not statistically significant in all indicators compared with the NC group (all P>0.05), except for the miscarriage rate in the LE/CC+Gn group, which was significantly higher than that in the NC group (a OR=2.141, 95% CI: 1.12-4.09; P=0.021). For patients who have been using the same treatment protocol, the cumulative pregnancy rate and the cumulative live birth rate in the NC group and the LE/CC group increased with the increase of assisted reproductive cycles, and the difference was statistically significant (all P<0.001). Regardless of whether confounding factors were adjusted, there were no statistically significant differences in neonatal mortality rate, low birth weight rate, normal birth weight rate, macrosomia rate, and male-to-female ratio among the groups (all P>0.05). Conclusion:In AID cycles with female patients aged ≤35 years, stimulated cycles had similar pregnancy outcomes to natural cycles and did not increase the risk of adverse neonatal outcomes or multiple pregnancies. Choosing the LE/CC stimulation protocol can improve the cumulative pregnancy rate of patients with abnormal ovarian follicle development or ovulation function.

Gut microbiota plays a vital role in human intestinal homeostasis, correlating strongly with the progression of numerous diseases. Recent researches provide powerful evidence that the connections exist between gut microbiota and renal anaemia. Gut microbiota may have an impact on renal anaemia by regulating the hypoxia-inducible factor (HIF) signalling, iron metabolism and inflammatory state. Because of this relationship, there may be potential treatments for renal anaemia. In this review, we will first provide an overview of current research progression on anaemia in chronic kidney disease and then introduce the relations among gut microbiota, HIF, and renal anaemia to explore the possible treatment options.

Objective To evaluate the optimal waiting period for frozen-thawed embryo transfer (FET) after hysteroscopic polypectomy (HSC-P). Design Retrospective cohort. Setting University-affiliated hospital. Patient(s) All patients included in this research underwent hysteroscopy before the first FET cycle after whole embryo freezing. A total of 206 patients had undergone HSC-P, and 3681 patients without endometrial polyps were defined as the controls. Intervention(s) HSC-P. Main outcome measure(s) The HSC-P group was divided into three subgroups based on the time interval between HSC-P and the start of an FET cycle. Subgroup 1 consisted of patients who underwent FET after their next menses, subgroup 2 after two menstrual cycles, and subgroup 3 after three or more menstrual cycles. Demographics, baseline in vitro fertilization (IVF) characteristics, and pregnancy outcomes, especially perinatal outcomes after FET were compared among the groups. Results There were 137 patients in subgroup 1, 40 in subgroup 2, and 29 in subgroup 3. There were no differences in the baseline characteristics of the three groups. IVF-related data and FET-related data, such as endometrial thickness and ET no. Of embryoes, were similar among the three subgroups. The three subgroups showed no significant differences in implantation rate, biochemical pregnancy rate, abortion rate, clinical pregnancy rate or live birth rate. Besides, There was no significant difference in perinatal outcomes including very preterm delivery, preterm delivery, low birth weight, macrosomia, small for gestational age, large for gestational age, birth weight(g), birth-height(cm)and Apgar Scores. Conclusion(s) Compared with FET after their next menses, FET after two or more menstrual cycles after HSC-P does not necessarily produce superior outcomes.

Objective To assess whether women of advanced age (≥35 years) with polycystic ovary syndrome (PCOS) have the same cumulative live birth rate (CLBR) as their age-matched controls with tubal factor infertility and to determine the influencing factors on the CLBRs of aged women. Design A retrospective cohort study. Setting and Population A total of 160 women of advanced age (≥35 years) with PCOS and 1073 women with tubal factor infertility were included in our study. All patients underwent their first fresh cycles and subsequent frozen cycles within in one year in our centre from 2015 to 2020. Methods To determine independent influencing factors on the CLBRs of these aged patients, a multivariable Cox regression model of CLBR according to the transfer cycle type was constructed. Main outcome measure(s): CLBRs. Result The Cox regression model of the CLBRs indicated that there was no significant difference between the PCOS group and the tubal infertility group in terms of advanced age (HR, 0.95; 95% CI, 0.71-1.27, P=0.732). The CLBR significantly decreased for women of advanced reproductive age up to 37 years of age (HR, 0.46; 95% CI, 0.39-0.56, P<0.001). The CLBR increased by 63% when more than ten oocytes were retrieved (HR, 1.63; 95% CI, 1.34-1.98, P<0.001). Patients with an AMH level above 32.13pmol/l were likely to have a 72%(HR, 1.72; 95% CI, 1.08-2.73, = 0.023) and 34% (HR, 1.34; 95% CI, 1.07-1.68, P=0.010)improvement in CLBR compared to those with an AMH below 7.85pmol/l and 7.85-32.12pmol/l, respectively. Conclusion Despite the higher number of oocytes retrieved in PCOS patients, the reproductive window is not extended for PCOS patients compared with tubal factor infertility patients. Age, AMH and the number of oocytes retrieved play crucial roles in the CLBRs of patients of advanced age (≥35 years).

Abstract Background: Women with polycystic ovary syndrome (PCOS) have a higher ovarian reserve and 9 number of oocytes retrieved than women with tubal infertility. To assess whether women of 10 advanced age (≥35 years) with PCOS have the same cumulative live birth rate (CLBR) as their age-11 matched controls with tubal factor infertility and to determine the influencing factors on the CLBRs 12 of aged women. 13 Methods: A total of 190 women of advanced age (≥35 years) with PCOS and 627 women with tubal 14 factor infertility were included in our study. All patients underwent their first fresh cycles and 15 subsequent frozen cycles in our centre from 2007 to 2018. To determine independent influencing 16 factors on the CLBRs of these aged patients, a multivariable Cox regression model of CLBR 17 according to the transfer cycle type was constructed. 18 Results: The Cox regression model of the CLBRs indicated that there was no significant difference 19 between the PCOS group and the tubal infertility group in terms of advanced age (HR, 0.96; 95% CI, 20 0.77~1.20). The CLBR significantly decreased for women of advanced reproductive age up to 37 21 years of age (HR, 0.65; 95% CI, 0.53~0.80). The CLBR increased by 31% when more than ten 22 oocytes were retrieved (HR, 1.31; 95% CI, 1.08~1.59). In addition to age and the number of oocytes, 23 the addition of recombinant LH was an independent factor that increased the CLBRs of the women of 24 advanced age (HR, 1.25; 95% CI, 1.03~1.53). 25 Conclusions: Despite the higher number of oocytes retrieved in PCOS patients, the reproductive 26 window is not extended for PCOS patients compared with tubal factor infertility patients. Age, the 27 number of oocytes retrieved and supplementation with LH play crucial roles in the CLBRs of 28 patients of advanced age (≥35 years).

Heart failure (HF) is a major comorbidity in patients with end-stage renal disease (ESRD). The pathogenesis of HF in patients on renal replacement therapy represents the confluence of several traditional and nontraditional vascular risk factors, unique to the milieu of chronic kidney disease and the dialysis modality [1]. The purpose of this report is to describe the efficacy and safety of sacubitril/valsartan for an ESRD patient on hemodialysis therapy conmbined with heart failure with reduced ejection fraction (HFrEF). A 35-year-old woman was undergoing hemodialysis due to ESRD and suffering from heart failure with reduced ejection fraction. Because of worsening heart failure and hypertension, she was prescribed with sacubitril/valsartan at a dose of 50 mg twice a day, spironolactone at a dose of 20 mg three times a day and metoprolol at a dose of 23.75 mg once daily. There was a symptomatic improvement with the heart failure and reduction in NT-proBNP level, accompanied by a decrease of blood pressure after using sacubitric/valsartan. In conclusion, it is safe and effective to take sacubitril/valsartan in this hemodialysis patient with severe heart failure.

目的:观察沙库巴曲/缬沙坦(SV)治疗对维持性血液透析(MHD)高血压患者的疗效及安全性.方法:采用自身对照研究,选取郑州大学第一附属医院血液净化中心MHD合并高血压接受SV治疗的患者31例,包括难治性高血压患者21例.其中11例将血管紧张素Ⅱ受体拮抗剂(ARB)换为SV.分析治疗前后血压、血常规、血生化等相关指标变化.结果:31例患者治疗后4周、12周透析前收缩压较治疗前下降,治疗后1周、4周、12周透析中收缩压与透析后收缩压均较治疗前下降,治疗后12周透析前舒张压较治疗前下降,治疗后1周、4周、12周透析中舒张压与透析后舒张压均较治疗前下降(P＜0.05).治疗后患者服用其他降压药限定日剂量下降[2.49±1.58 vs 3.42±1.81,P＜0.05].将ARB换为SV的11例患者在治疗后1周、4周、12周透析前、透析中、透析后血压同样较治疗前降低.用药期间未发现与SV相关的不良反应.结论:SV联合使用可有效控制MHD患者高血压,且安全性较好.

自1978年第一例试管婴儿诞生至今,辅助生殖技术迅速发展.1983年,首例通过冻融胚胎移植技术(FET)妊娠成功.FET作为体外受精-胚胎移植的一项重要补充,在辅助生殖技术中发挥着越来越多的作用.FET增加了每单次采卵后的累计妊娠率,同时也降低了卵巢过度刺激综合征的发生率.某些在采卵周期由于客观原因不能进行移植的患者,可以将胚胎冷冻保存,至合适的时机再进行胚胎复苏移植.

To characterize the clinical features of a female patient with isolated follicle-stimulating hormone (FSH) deficiency and to investigate the underlying mechanisms of FSH inactivation. The proband was a 29-year-old woman with primary amenorrhea, impaired pubertal development, and infertility. Subsequently, reproductive endocrine was screened. DNA sequencing was conducted for the identification of FSHβ mutation. RT-PCR, western blots, in vitro immunometric assay, and bioassay were performed to confirm the impact of the mutation on FSH expression and biological activity. Molecular model consisting of FSHα and mutant FSHβ subunit was built for the structural analysis of FSH protein. The evaluation of reproductive endocrine revealed undetectable basal and GnRH-stimulated serum FSH. Sequencing of the FSHβ gene identified a homozygous nonsense mutation at codon 97 (Arg97X). RT-PCR and western blot analysis revealed the mutation Arg97X did not affect FSHβ mRNA and protein expression. But in vitro immunometric assay and bioassay demonstrated the production of normal bioactive FSH protein was disturbed by the mutation Arg97X. Structural analysis showed the surface structure of the resulting mutant FSH presented with lock-and-key, mosaic binding pattern, while the native structure was an encircling binding mode. The mutation Arg97X could disturb structural stability of the resulting FSH protein consisting of FSHα and mutant FSHβ subunit, which may lead to FSH deficiency.

Objective To compare the pregnancy outcome of patients with PCOS who has been receiving ovulation induction by HMG combined with different doses of LE, and to summarize the best dosage of LE in the combined ovulation induction scheme.MethodThis is a prospective and randomized cotrolled study. 142 PCOS patients who showed no dominant follicular after the ovulation of LE were randomly included by using the random number table, and were divided into group LE 2.5 mg (n=70) and group LE 5.0 mg (n=72). The number of dominant follicles, E2 level on the day of HCG injection, endometrial thickness on the day of HCG injection, HMG usage and clinical outcome related indicators were copared.ResultsThere is no signiifcant difference in age, duration of infertility, BMI, D3 FSH, D3 E2 and D3 endometrial thicknessbetween the two groups(P>0.05). During the process of ovulation induction, there is no signiifcant difference in the number of 14-18mm follicles, the rate of ovulation , endometrial thickness on the day of HCG injection, the rate of biochemical pregnancy, the rate of multiple pregnancy, the rate of miscarriage, the rate of cancelled cycle and the rate of OHSS between the two groups (P>0.05).≥18mm follicles, E2 levels on the day of HCG injection, dosage of HMG and the days of using HMG is higher in group LE 5.0 mg than group LE 2.5 mg, and the difference is statistically signiifcant(P<0.05). Compared to group LE 2.5 mg, group LE 5.0 mg shows an increasing trend in the rate of clinical pregnancy, although the difference is not statistically signiifcant(P>0.05).Conclusions PCOS patients who showed no dominant follicular after the ovulation of LE only should receive ovulation induction by HMG combined LE, and the appropriate choice of the dosage of LE should be 5.0 mg/d rather than 2.5 mg/d.

目的 探讨孕酮(P)撤退出血对无排卵多囊卵巢综合征(PCOS)患者来曲唑(LE)促排卵周期妊娠结局的影响.方法 该研究为单中心前瞻性随机对照研究.利用随机数字表法,将纳入的169例无排卵PCOS患者,随机分为实验组(84例)及对照组(85例).其中,实验组患者未经P撤退出血,直接接受LE促排卵治疗.对照组患者P撤退出血后再接受LE促排卵治疗.比较两组患者促排卵治疗过程中优势卵泡数目、hCG日E2水平、hCG日子宫内膜厚度、Gn用量及临床结局相关指标的差异.结果 两组患者年龄、不孕年限、BMI、促排卵治疗前FSH及E2水平、促排卵治疗前的内膜厚度比较,差异无统计学意义(P＞0.05);促排卵治疗过程中,两组患者14～18 mm卵泡数、≥18 mm卵泡数、hCG日E2水平、排卵率、生化妊娠率、流产率、取消周期率(OHSS发生率、卵巢反应不良发生率)比较,差异无统计学意义(P＞0.05);实验组促排卵治疗前的LH水平、促排卵过程中hCG日内膜厚度、Gn用量、Gn使用天数均高于对照组,差异有统计学意义(P＜0.05);与对照组相比,实验组临床妊娠率呈增高趋势,差异无统计学意义(P＞0.05).结论 P撤退出血可"削薄"无排卵PCOS患者接受LE促排卵治疗hCG日的子宫内膜厚度,使临床妊娠率呈下降趋势.处于基础状态的无排卵PCOS患者,可不经P撤退出血,直接及接受LE促排卵治疗.