Objective:To investigate the impact of the progesterone concentration on human chorionic gonadotropin (hCG) trigger day in fresh cycles versus thawed transfer cycles (the freeze-all strategy) with an antagonist protocol, and to compare the differences in clinical outcomes.Methods:This retrospective cohort study included a total of 2 165 cycles conducted at Henan Provincial People′s Hospital with cleavage-stage embryo (at least one top-quality) transfer between January 2017 and December 2023, with serum progesterone levels on hCG trigger day all≤6.34 nmol/L (i.e. 2 ng/ml). Multivariate logsitic regression analysis and curve fitting were performed based on different serum progesterone levels on hCG trigger day [≤3.17 nmol/L (i.e. 1 ng/ml) or 1-2 ng/ml].Results:Multivariate regression analysis, by using cycle type (either fresh or frozen-thawed cycle) as the exposure variable, showed that the clinical pregnancy rate (≤1 ng/ml: OR=0.93, 95% CI: 0.75-1.14; 1-2 ng/ml: OR=1.05, 95% CI: 0.58-1.87) and live birth rate (≤1 ng/ml: OR=0.90, 95% CI: 0.71-1.13; 1-2 ng/ml: OR=1.53, 95% CI: 0.79-3.00) had no statistically significant differences in group of progesterone concentration ≤1 ng/ml or in group of 1-2 ng/ml. Using serum progesterone levels on hCG trigger day as a continuous variable for curve fitting analysis, the clinical pregnancy rate in fresh or thawed cycles showed no significant changes with increasing progesterone levels. Conclusions:In the antagonist protocol with cleavage-stage embryo transfer (at least one top-quality), when the serum progesterone level on hCG day is ≤2 ng/ml, there are no significant differences in clinical outcomes between thawed cycles and fresh cycles, including clinical pregnancy rate and live birth rate. Transferred in fresh cycles or choosing the freeze-all strategy could be selected based on the actual situation of the patients.

Objective:To analyze the clinical characteristics and genetic basis of a male patient with primary infertility caused by Acephalic spermatozoa syndrome.Methods:A patient who had presented at the Henan Provincial People′s Hospital on October 1, 2022 was selected as the study subject. Clinical data and results of laboratory exams and sperm electron microscopy were collected. The patient was subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing and pathogenicity analysis.Results:WES revealed that the patient has harbored compound heterozygous variants of the PMFBP1 gene, namely c. 853del (p.Ala285Leufs*24) and c. 1276A>T (p.Lys426X), which were both unreported previously. Sanger sequencing suggested that the c. 853del (p.Ala285Leufs*24) variant has derived from his deceased mother, whilst the c. 1276A>T (p.Lys426X) variant has derived from his father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+ PM2_Supporting+ PP4). Conclusion:The compound heterozygous variants of the PMFBP1 gene probably underlay the Acephalic spermatozoa syndrome in this patient. The discovery of the novel variants has also enriched the mutational spectrum of Acephalic spermatozoa syndrome.

The solute carrier family 12(SLC12)of cation-chloride cotransporters(CCCs)comprises potassium chlo-ride cotransporters(KCCs,e.g.KCC1,KCC2,KCC3,and KCC4)-mediated Cl-extrusion,and sodium po-tassium chloride cotransporters(N[K]CCs,NKCC1,NKCC2,and NCC)-mediated Cl-loading.The CCCs play vital roles in cell volume regulation and ion homeostasis.Gain-of-function or loss-of-function of these ion transporters can cause diseases in many tissues.In recent years,there have been considerable ad-vances in our understanding of CCCs'control mechanisms in cell volume regulations,with many tech-niques developed in studying the functions and activities of CCCs.Classic approaches to directly measure CCC activity involve assays that measure the transport of potassium substitutes through the CCCs.These techniques include the ammonium pulse technique,radioactive or nonradioactive rubidium ion uptake-assay,and thallium ion-uptake assay.CCCs'activity can also be indirectly observed by measuring y-aminobutyric acid(GABA)activity with patch-clamp electrophysiology and intracellular chloride con-centration with sensitive microelectrodes,radiotracer 36Cl-,and fluorescent dyes.Other techniques include directly looking at kinase regulatory sites phosphorylation,flame photometry,22Na+uptake assay,structural biology,molecular modeling,and high-throughput drug screening.This review sum-marizes the role of CCCs in genetic disorders and cell volume regulation,current methods applied in studying CCCs biology,and compounds developed that directly or indirectly target the CCCs for disease treatments.

Objective:To investigate the effect of laparoscopic ovarian cystectomy on anti-Mullerian hormone (AMH) level, ovarian response to gonadotropin stimulation and pregnancy rate for in vitro fertilization (IVF) patients with benign ovarian cysts.Methods:Patients with benign ovarian cysts who were admitted for cystectomy and had undergone IVF treatment were enrolled in the study. There were 373 participants with ovarian cysts underwent laparoscopic ovarian cystectomy in the experimental group. According to duration of post-surgery, there were four sub-groups: 1 year post-surgery (1Y POST), 2 years post-surgery (2Y POST), 4 years post-surgery (4Y POST) and ≥5 years post-surgery (≥5Y POST) in the experimental group. According to histopathologic types of ovarian cysts, there were two sub-groups: ovarian endometriotic cysts and ovarian non-endometriotic cysts. Two hundreds and three patients with no history of ovarian cysts and ovarian surgery were in the control group. The level of AMH and basic concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), estradiol (E 2) were measured. Antral follicle counts (AFC) were calculated. There were other study variables: total dose of gonadotropins, duration of ovarian stimulation, the number of oocyte retrieved, the number of embryo obtained, blastocyst transfer rate and pregnancy rate. Results:The control group was matched as closely as possible to the experimental group, including age, body mass index and menstrual cycle (all P>0.05). Compared to the women in control group, the women in ovarian endometriotic cystectomy sub-group had significantly higher levels of basal FSH and basal P, lower level of AMH (all P<0.05); the women in ovarian endometriotic cysts sub-group had significantly higher dose of gonadotropins (all P<0.05); the women in ovarian endometriotic cysts ≥5Y POST sub-group had significantly lower number of oocyte retrieved, lower number of embryo obtained, lower blastocyst transfer rate, and lower pregnancy rate (all P<0.05). Compared to the women in control group, the women in ovarian non-endometriotic cysts sub-group had a significantly higher level of basal FSH and basal P (all P<0.05). The women in ovarian non-endometriotic cysts sub-group had lower level of AMH, higher dose of gonadotropins, lower number of oocyte retrieved, lower number of embryo obtained, lower rate of blastocyst transfer and lower rate of pregnancy than the control group but there were no statistically significant differences among them (all P>0.05). The women with unilateral ovarian endometriotic cysts had significantly lower number of oocyte retrieved on the side of surgery than another side ( P<0.05). Conclusions:In short term laparoscopic ovarian cystectomy has no significant effect on ovarian reserve. But with long-term follow-up ovarian reserve, ovarian response to gonadotropin stimulation and pregnancy rate are decreased. The effect of laparoscopic ovarian cystectomy in benign cysts on ovarian is associated with whether or not it is the surgical side.

OBJECTIVE To investigate the situation of pharmaceutical pr eparations in medical institutions （hereinafter refer to hospital preparations ），and to promote the sustained and healthy development of hospital preparations. METHODS Under the organization of National Pharmacy Administration & Quality Control Center ，internet survey was adopted to statistically analyze the data of hospital preparations in 2019 that was completed and reported by the secondary general hospitals and above in provinces （cities，districts）and Xinjiang Production and Construction Corps. RESULTS Among the 4 639 hospitals，9.36％ had drug approval numbers and 8.15％ had preparation laboratories. The average ratio of the number of hospital preparations in production to the number of preparations approved was 0.72，and that of 41.52％ hospital was concentrated in 1-0.9. Self-produced by hospital was the main production mode of hospital preparations ；the higher hospital level was ，the higher the proportion of self-production combined with commissioned processing ，while the lower the proportion of commissioned processing only. In hospitals with preparation approval numbers ，the proportion of owning TCM preparations was the highest （73.66％），followed by common chemical preparations （69.93％）. From perspective of annual output value of hospital preparations ，tertiary hospitals were higher than secondary hospitals ，and private hospitals were higher than public hospitals ；it was related to the production mode ，varieties of hospital preparations and the establishment of the preparation laboratories. There was a trend that the development of hospital preparations in C entral China ，North China and South China was better than that in the Northeast China ，Northwest China and Southwest China. CONCLUSIONS At present ，hospital preparations in China are mainly made in medical institutions ， com and the types are relatively limited. The regional developmentis unbalanced and the scale of hospital preparations is reduced.It is suggested that medical institutions should pay attention to the innovation of hospital preparations ，especially to deve lopment of characteristic preparations with definite curative effect ，so as to give full play to their role of “shortage make-up ”. Great importance also should be paid to the policy support of dispensing and the establishment of regional dispensing centers.

Objective:To explore the effectiveness, safety and cost between urinary follicle stimulating hormone (uFSH) and recombinant follicle stimulating hormone (rFSH) in controlled ovarian stimulation (COS) in China.Methods:Data were collected from 16 reproductive centers in China covering oocytes collection time from May 1, 2015 to June 30, 2018. Eligible patients were over 18 years old, adopting COS with uFSH (uFSH group) or rFSH (rFSH group) as start gonadotropins (Gn), and using in vitro fertilization (IVF) and (or) intracytoplasmic sperm injection for fertilisation, excluding frozen embryo recovery cycle. Generalised estimating equation was used to address the violation of independency assumption between cycles due to multiple IVF cycles for one person and clustering nature of cycles carried out within one center. Controlling variables included age, body mass index, anti-Müllerian hormone level, cause of infertility, ovulation protocol, type of fertilisation, number of embryos transferred, number of days of Gn use.Results:Totally 102 061 cycles met eligibility criteria and were included in the analyses. In terms of effectiveness, after controlling relevant unbalanced baseline characteristics, compared with rFSH group, the high oocyte retrieval (>15 oocytes was considered high retrieval) rate of uFSH group significantly decreased in gonadotropin-releasing hormone agonist protocol ( OR=0.642, P<0.01) and in gonadotropin-releasing hormone antagonist protocol ( OR=0.556, P=0.001), but the clinical pregnancy rate per transfer cycle and the live birth rate per transfer cycle significantly increased ( OR=1.179, OR=1.169, both P<0.01) in both agonist and antagonist protocols. For safety, multiple analysis result demonstrated that in the agonist protocol, compared with rFSH group, the incidence of moderate to severe ovarian hyperstimulation syndrome of uFSH group significantly decreased ( OR=0.644, P=0.002). The differences in ectopic pregnancy rate and multiple pregnancy rate between the uFSH and rFSH groups were not significant ( P=0.890, P=0.470) in all patients. In terms of cost, compared with rFSH group, the uFSH group had lower total Gn costs for each patient ( P<0.01). Conclusion:For patients who underwent COS, uFSH has better safety, and economic profiles over rFSH in China.

Objective:To explore the clinical outcomes of top-quality blastocysts transfer developed from cleavage embryos with different grading and determine whether the cleavage stage embryo morphology grading should be taken into consideration when transferring the embryo at the blastocyst stage.Methods:A number of 3 059 cycles were included with single top-quality blastocyst transfer dating from January 2017 to May 2021 in Henan Provincial People′s Hospital. According to the number of cleavage sphere and degree of fragmentation, all cleavage stage embryos were divided into three groups: top D3 embryo (8 cells, ≤5% fragments)-TB group, suboptimal D3 embryo (8 cells, 5%0.05); and the early abortion rate were 10.74%, 12.54% and 12.62%, respectively ( P>0.05). After adjusting for confounders, logistic regression showed that no significant associations were found between cleavage stage embryo morphology grading and clinical pregnancy rate (suboptimal D3 embryo-TB group: OR=1.02, 95% CI: 0.76-1.38, P=0.879; normal D3 embryo-TB group: OR=0.84, 95% CI: 0.61-1.14, P=0.262) and early abortion rate (suboptimal D3 embryo-TB group: OR=1.18, 95% CI: 0.77-1.82, P=0.445; normal D3 embryo-TB group: OR=1.26, 95% CI: 0.81-1.98, P=0.309). The results of threshold effect analysis showed that when a single top-quality blastocysts was transferred, the effect of age on the clinical pregnancy rate showed a curve relationship, when the age was≥33 years old, the clinical pregnancy rate decreased significantly with age increased ( OR=0.89, 95% CI: 0.83-0.95, P=0.007); and there was no significant change in early abortion rate ( OR=1.01, 95% CI: 0.97-1.06, P=0.628). Conclusions:Cleavage stage embryo grading is not found to correlate with clinical outcomes in single top-quality blastcyst tranfer. Therefore, when considering blastocyst transfer, its morphology at blastocyst stage is more relevant. The effect of age on pregnancy outcomes of single blastocyst transfer should be considered.

Objective:To explore the related factors of poor ovarian response (POR) in patients receiving controlled ovarian stimulation (COS) and to establish the nomogram for predicting POR in patients who received in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI).Methods:In this retrospective research, clinical data of 17 164 cycles of patients who received IVF/ICSI treatment at Henan Provincial People′s Hospital from September 1st, 2016 to September 1st, 2020 were analyzed. Independent correlative factors affecting the occurrence of POR were screened by logistic regression, which were the model enrollment variables in the prediction model. Totally 13 266 cycles with well-record of enrollment variables were screened, and these data were randomly divided into model group (9 896 patients) and validation group (3 370 patients) according to 3∶1. The nomogram was established according to the regression coefficient of the relevant variables. The prediction accuracy of the nomogram was evaluated by calculating area under the receiver operating characteristic curve (AUC).Results:Multivariate logistic regression analysis showed age, infertility type, body mass index, anti-Müllerian hormone, basal follicle stimulating hormone, basal estrogen, antral follicle number, previous times of POR, history of ovarian surgery, ovulation stimulation protocol and average amount of gonadotropin were independent correlative factors affecting the occurrence of POR (all P<0.05). In the model group, according to the above factors, the prediction model and nomogram of POR risk were constructed and the validation group verified the model. The AUC of the model group was 0.893 (95% CI: 0.885-0.900), and the AUC of the validation group was 0.890 (95% CI: 0.878-0.903). Conclusion:The influencing factors of POR after COS in patients treated by IVF/ICSI are screened, and the nomogram for predicting POR established in this study is proved to be effective, simple, intuitive and clear in predicting the occurrence of POR.

OBJECTIVE: To explore the clinical feature and gene variant for two cases of primary male infertility caused by severe asthenospermia and to analyze the etiology of the disease. METHODS: Genomic DNA of peripheral blood samples of patients and their parents was extracted and gene variant analysis of the patients was conducted by using whole exome sequencing. Suspected pathogenic variant was verified by Sanger sequencing and pathogenic analysis. RESULTS: Whole exome sequencing showed that the DNAH1 gene of patient 1 had two heterozygous variants of c.2016T>G(p.Y672X) and c.6017T>G (p.V2006G). The DNAH1 gene of patient 2 had a homozygous variant of c.2610G>A(p.W870X), which were inherited from his father and mother, respectively. According to American College of Medical Genetics and Genomics standards and guidelines, the c.2016T>G (p.Y672X) and c.2610G>A (p.W870X) varaints of DNAH1 gene were predicted to be pathogenic (PVS1+PM2+PM3+PP3). CONCLUSION The two patients of multiple morphological abnormalities of the sperm flagella may be caused by DNAH1 gene variant, which has resulted in primary male infertility.
Dyneins/genetics* ; Genomics ; Humans ; Infertility, Male/genetics* ; Male ; Mutation ; Sperm Tail/pathology* ; Whole Exome Sequencing

Objective:To assess the nutritional status of elderly patients with dementia in a memory clinic and to identify patients with malnutrition and patients at risk for malnutrition.Methods:A total of 510 elderly dementia patients were recruited from a memory clinic of the First Affiliated Hospital of Chongqing Medical University.All subjects were assessed with the mini-nutritional assessment short-form(MNA-SF), mini-mental state examination(MMSE), activities of daily living scale(ADL)and neuropsychiatric inventory(NPI). Logistic regression was used to explore potential risk factors and to establish a prediction model.Results:13.33%(68/510)of participants were classified as being malnourished, 52.94%(270/510)as being at risk for malnutrition and 33.73%(172/510)as well nourished.A Logistic regression model for predicting malnutrition identified dysphagia, irritability, physical self-maintenance scale(PSMS), appetite and eating disorders as important influencing factors( OR=4.334, 1.096, 1.121, 1.213, all P<0.05), and MMSE score, family history of dementia and age were important influencing factors for predicting malnutrition/at risk for malnutrition( OR=0.923, 0.517, 1.045, all P<0.05). Conclusions:The incidence of malnutrition and the risk of malnutrition in elderly patients with dementia in the memory clinic are high, and there are many related influencing factors.Early detection and intervention can delay or avoid malnutrition.