Nomogram prediction for the prediction of clinical pregnancy in Freeze-thawed Embryo Transfer.

BACKGROUND: This study aimed to identify multiple endometrial receptivity related factors by applying non-invasive, repeatable multimodal ultrasound methods. Combined with basic clinical data, we further established a practical prediction model for early clinical outcomes in Freeze-thawed Embryo Transfer (FET). METHODS: Retrospective analysis of clinical data of infertility patients undergoing FET cycle in our Center from January 2017 to September 2019. Receiver operating characteristic (ROC) curve and decision curve analyses were performed by 500 bootstrap resamplings to assess the determination and clinical value of the nomogram, respectively. RESULTS: A total of 2457 FET cycles were included. We developed simple nomograms that predict the early clinical outcomes in FET cycles by using the parameters of age, BMI, type and number of embryos transferred, endometrial thickness, FI, RI, PI and number of endometrial and sub-endometrial blood flow. In the training cohort, the area under the ROC curve (AUC) showed statistical accuracy (AUC = 0.698), and similar results were shown in the subsequent validation cohort (AUC = 0.699). Decision curve analysis demonstrated the clinical value of this nomogram. CONCLUSIONS: Our nomogram can predict clinical outcomes and it can be used as a simple, affordable and widely implementable tool to provide guidance and treatment recommendations for FET patients.

Method for fabricating large-area gratings with a uniform duty cycle without a spatial beam modulator.

A fabrication method for large-area gratings with uniform duty without using a spatial beam modulator is introduced in this study. The inhomogeneity of gratings caused by flaws of the lens and stray light was solved by controlling exposure time within an appropriate range and selecting a suitable beam expansion aperture in the optical path. A model for representing this process was established by analyzing the effects of exposure and development time length, and experimental results exhibited good agreement with the simulation results. Finally, a grating with a period of 550 nm, a uniform duty cycle, and a diameter larger than 30 mm was achieved using a Mach-Zehnder interferometer optical path without a spatial beam modulator. The uniformity of this grating was observed via atomic force microscopy, and the results were highly desirable.

Patterning nanoscale crossed grating with high uniformity by using two-axis Lloyd's mirrors based interference lithography.

A two-axis Lloyd's mirrors interferometer based optical fabrication system was theoretically investigated and constructed for patterning high-uniformity nanoscale crossed grating structures over a large area with a high throughput. The current interferometer was configured with two reflected mirrors and a grating holder, which are placed edge by edge and orthogonal with each other. In such a manner, the two beams reflected from the two mirrors interfere with the incident beam, respectively, forming a crossed grating patterns with only one exposure. Differing from the conventional solution for elimination of unexpected interference between the two reflected beams, a systematical analysis, that is based on the proposed index indicating the non-orthogonality between the two beams at different incident angles, was conducted by using a spatial full polarization tracing method. Without polarization modulation to eliminate the additional interference, an optimal exposure condition with small non-orthogonality between reflected beams was found at a certain incident angle range, while the two required interferences to construct cross grating still remain high. A pattern period of ∼1 µm-level crossed grating structure could be obtained through balancing the structure area and the non-orthogonality. Finally, the exposure setup with orthogonal two-axis Lloyd's mirrors interferometer is established, and the crossed grating structure with the periods of 1076 nm along X-direction and 1091 nm along Y-direction was successfully fabricated on a silicon substrate via microfabrication technology over a large area of 400 mm2. The uniformity of crossed grating array over the whole area was evaluated by an atomic force microscope, and the standard deviations of structure periods along X- and Y-directions smaller than 0.3% are achieved. It is demonstrated that the orthogonal two-axis Lloyd's mirrors interferometer based on single-beam single-exposure scheme with non-orthogonality systematic analysis is an effective approach to fabricate crossed grating patterns of 1 µm-level period with high uniformity over a large area.

Holographic fabrication of an arrayed one-axis scale grating for a two-probe optical linear encoder.

We present a method for the fabrication of an arrayed one-axis scale grating for a two-probe optical linear encoder using a dual-beam interference lithography (IL) system with a compact diode laser source. We employ a multiple-exposure stitching method to form an arrayed scale grating. This allows a scale grating with small line spacing to be achieved over a large width. This stitched scale grating integrates well with a newly developed two-probe optical encoder, allowing the measurement results to be numerically connected. Since neither the gap width nor the grating phase of the two adjacent gratings must be controlled, the fabrication process is both simplified and made more robust. This flexible and cost-effective fabrication technique can benefit many precision measurement applications. Experiments are carried out to demonstrate the feasibility of this technology.

Association between instantaneous heart rate sequence during the awake period and cardiovascular events: a study based on Sleep Heart Health Study.

BACKGROUND: Heart rate variability (HRV) has been reported to be associated with cardiovascular diseases (CVD), while few studies focused on the instantaneous heart rate (IHR). This study aimed to establish models to predict the occurrence of cardiovascular events based on the IHR sequence. METHODS: A total of 2977 participants with useful electrocardiogram (ECG) data and free of CVD events at baseline from the Sleep Heart Health Study (SHHS) database were included in this retrospective cohort study. All IHR indicators were measured during the awake period before sleep. The logistic regression, random forest, and XGBoost methods were used to develop the predictive models. The model performance was quantified by calculating the area under the curve (AUC). RESULTS: Of theses 2977 participants, 1460 (49.04%) participants had CVD events during the 15-year follow-up. Higher standard deviation of IHR (SDHR) (OR=0.906; 95% CI, 0.832-0.986), coefficient of variation of IHR (CVHR) (OR=0.910; 95% CI, 0.835-0.990), power in low frequency (LF) (OR=0.896; 95% CI, 0.822-0.975), power in high frequency (HF) (OR=0.872; 95% CI, 0.796-0.955), and total power (TP) (OR=0.887; 95% CI, 0.813-0.967) were associated with the lower risk of CVD events, while ratio of semi-minor axis and semi-major axis in Poincare plot (SDratio) (OR=1.105; 95% CI, 1.012-1.206) was related to the higher risk of CVD events. The AUCs of the logistic regression, random forest, and the XGBoost models were 0.734 (95% CI, 0.701-0.767), 0.794 (95% CI, 0.764-0.823) and 0.828 (95% CI, 0.801-0.855) in the testing set, respectively. CONCLUSIONS: IHR sequences were important predictors of cardiovascular events. The IHR indicators should be paid more attention to in future clinical researches on CVD.

ZAP70 interaction with 13 mRNAs as a potential immunotherapeutic target for endometrial cancer.

For advanced, refractory endometrial cancer (EC), it is advisable to find effective immunotherapeutic targets. In the present study, genes affecting the immune status of uterine corpus endometrial carcinoma (UCEC) samples within The Cancer Genome Atlas were explored by weighted correlation network analysis and differential gene expression analysis. The protein function and immune correlation of 14 key genes, including ζ-chain-associated protein kinase 70 (ZAP70), were analyzed. Based on the expression levels of key genes, the patients with UCEC were divided into two groups using consensus clustering, low expression (group 1) and high expression (group 2). Next, the functions of differentially expressed genes (DEGs) between the two groups were identified using Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes analysis and Gene Set Enrichment Analysis. The immune status of the patients in the two groups was evaluated using immune infiltration score and the expression levels of targets of immune checkpoint inhibitors. The role of ZAP70 in the prognosis of patients with UCEC and the differences in ZAP70 expression between EC tissues and healthy intimal tissues were determined by reverse transcription-quantitative PCR and immunohistochemistry. The present study found strong correlations between key genes, including ZAP70, LCK, FOXP3, TIGIT, CTLA4, ICOS, CD5, IL2RG, PDCD1, TNFRSF4, CD27, CCR7, GZMB, CXCL9. From the enrichment analyses, it was found that the functions of these DEGs were related to T cells. Patients in group 2 had stronger immune infiltration and higher immune checkpoints expression compared with those in group 1. ZAP70 was expressed at higher levels in EC tissues compared with in normal tissues, and may act as a protective factor in EC. In conclusion, ZAP70 interaction with 13 mRNAs may affect the immune status of patients with EC and may be a potential target for immunotherapy.

Corrigendum: Association between endometrial blood and clinical outcome in frozen single blastocyst transfer cycles.

[This corrects the article DOI: 10.3389/fphys.2023.1113853.].

Association between endometrial blood and clinical outcome in frozen single blastocyst transfer cycles.

Background: The success of embryo transfer cycle depends mainly on the quality of embryo and endometrial receptivity. Ultrasound examination is still the most widely used non-invasive evaluation method for its advantages of convenience, non-invasiveness and repeatability. Ultrasound-measured endometrial blood flow is one of the important evaluation indicators of morphology. Aims: To investigate the effect of the number of endometrial blood flow branches on pregnancy outcome of frozen-thawed embryo transfer cycles which have undergoing hormone replacement therapy (HRT-FET). Material and methods: A retrospective cohort study was performed looking at a total of 1390 HRT-FET cycles from our reproductive medicine center between January 2017 to December 2021, which transferred one blastocyst frozen on day 5 with good quality in morphology. Associations between endometrial blood flow branches and pregnancy outcomes were evaluated with multivariable linear regression analysis. Results: The number of endometrial blood flow branches was independently associated with clinical pregnancy (OR 1.10; 95% CI 1.02-1.20). After adjusting for potential confounders, the effect size (odds ratio) was 1.09 (95% CI 1.00-1.19), and the results showed that the clinical pregnancy rate and live birth rate of T2 and T3 groups were significantly higher than those in group T1 (p < 0.05). Subgroup analysis showed that a consistent association between the endometrial blood flow branches and clinical pregnancy in all subgroups. Conclusion: Our study provided evidence for the influence of endometrial blood flow on pregnancy outcomes. There may be an independent association between the number of endometrial blood flow branches and pregnancy outcomes in frozen-thawed single blastocyst transfer cycles.

The relationship and optimal threshold of endometrial thickness with early clinical pregnancy in frozen embryo transfer cycles.

OBJECTIVE: To investigate the associations of endometrial thickness with pregnancy outcome in frozen embryo transfer (FET) cycles. METHODS: A retrospective cohort study was performed looking at 1627 FET cycles from the Reproductive Medicine Center of the study hospital between January 2017 and July 2018. Endometrial ultrasonographic characteristics were recorded on the embryo transfer day in FET cycles. RESULTS: A total of 1627 FET cycles were included. The endometrial thickness was independently associated with clinical pregnancy outcomes after adjusting for potential confounders (odds ratio 1.06; 95% confidence interval [CI] 1.01-1.12). A non-linear relationship was detected between endometrial thickness and pregnancy outcomes, whose point was 10.9 mm. The effect size of the left and right sides of the inflection point were 1.16 (95% CI 1.07-1.25) and 0.89 (95% CI 0.78-1.01), respectively. Subgroup analysis showed that the correlation between endometrial thickness and pregnancy outcome was consistent in all subgroups. CONCLUSION: The relationship between endometrial thickness and pregnancy outcome was non-linear and there is an inflection point. When endometrial thickness was less than 9.5 mm, it was positively related to clinical pregnancy rate. If it was beyond the inflection point, the pregnancy rate does not increase significantly.

Polarized holographic lithography system for high-uniformity microscale patterning with periodic tunability.

Periodic microscale array structures play an important role in diverse applications involving photonic crystals and diffraction gratings. A polarized holographic lithography system is proposed for patterning high-uniformity microscale two-dimensional crossed-grating structures with periodic tunability. Orthogonal two-axis Lloyd's mirror interference and polarization modulation produce three sub-beams, enabling the formation of two-dimensional crossed-grating patterns with wavelength-comparable periods by a single exposure. The two-dimensional-pattern period can also be flexibly tuned by adjusting the interferometer spatial positioning. Polarization states of three sub-beams, defining the uniformity of the interference fringes, are modulated at their initial-polarization states based on a strict full polarization tracing model in a three-dimensional space. A polarization modulation model is established considering two conditions of eliminating the unexpected interference and providing the desired identical interference intensities. The proposed system is a promising approach for fabricating high-uniformity two-dimensional crossed gratings with a relatively large grating period range of 500-1500 nm. Moreover, our rapid and stable approach for patterning period-tunable two-dimensional-array microstructures with high uniformity could be applicable to other multibeam interference lithography techniques.

[Influence of varicocele on sperm chromatin structure and sperm motility].

OBJECTIVE: To study the influence of varicocele on sperm chromatin structure and sperm motility. METHODS: Routine semen analysis and sperm chromatin structure assay (SCSA) were performed in a varicocele group (n=74) and a control group (n=89). RESULTS: Sperm concentration (41.4 +/- 38.7] x 10(6)/ml) grade a+b sperm percentage ([31.7 +/- 16.9]% and sperm viability ([62.8 +/- 22.2]%) in the varicocele group were evidently lower than those ([80.9 +/- 63.1] x 10(6)/ml, [46.8 +/- 20.5]%, [77.2 +/- 17.5])% in the control group (P < 0.05) and so were VCL, VSL and VAP ([37.4 +/- 12.5 microm/s, [23.4 +/- 7.8] microm/s, [26.5 +/- 8.2] microm/s) in the varicocele group than those ([42.4 +/- 10.7] microm/s, [27.3 +/- 7.3] microm/s, [30.7 +/- 7.8] microm/s) in the control (P < 0.05). MAD was increased (P < 0.01), and the COMP alphat of SCSA (23.2 +/-16.2) was obviously higher in the former than in the latter (14.1 +/- 11.8) (P < 0.05). CONCLUSION: Varicocele causes damage to sperm DNA and changes sperm motility, which may result in male infertility.

[Investigation of semen quality of 18-35 year old Chinese army men].

OBJECTIVE: To investigate the semen quality of the Chinese army men. METHODS: Ten-item sperm quality analyses were made by manual methods and the computer assisted sperm analysis system in 1054 young Chinese army men. The subjects were divided into 4 age groups (18-20 yrs., 21-25 yrs., 26-30 yrs and 31-35 yrs.), and the results of the analyses were compared. RESULTS: Among the 1 054 young males investigated, the semen volume was (2.6 +/- 1.4) ml, sperm density (55.9 +/- 46.5) x 10(6)/ml, sperm grade a + b motility (47.1 +/- 19.0)%, sperm viability (70.6 +/- 22.1)%, morphologically normal sperm (84.7 +/- 10.2)%, and acrosomal integrity (86.1 +/- 7.2)%. As for the percentages of the quality indexes that met WHO standards, the sperm volume was 73.5%, liquefaction time 91.1%, pH 93.0%, grade a + b motility 45.5%, viability 86.7%, sperm density 80.4%, morphologically normal sperm 98.2%, and the sperm total number 78.0%. Those who accorded with all the WHO standards accounted for 40.2%. CONCLUSION: The semen quality of the 18-35 year old army men was better than previously reported in the similar literature. And that of the 26-30 yrs. group was the best among all the age groups.

[Long-term exposure to low intensity microwave radiation affects male reproductivity].

OBJECTIVE: To evaluate the effect of Long-term exposure to low intensity microwave radiation on male reproductivity. METHODS: A total of 289 married male radar operators were included in the radar group and 148 married men unexposed to microwave radiation were enrolled as controls. Questionnaires were used and the intensity of microwave radiation in different working areas was detected. RESULTS: The rate of sexual dysfunction was 43.6% in the radar group and 24.4% in the control group (P < 0.01). The natural pregnancy rate was 53.6% within 1 year of marriage and 46.4% after 1 year of marriage in the radar group, as compared with 81.1% and 18.9% in the control group (P < 0.01). CONCLUSION: Long-term exposure to low intensity microwave radiation evidently increased the sexual dysfunction rate and decreased natural pregnancy rate in men.

[Evaluation of radiation damage to the sperm DNA of radar operators].

OBJECTIVE: To evaluate the inflicted by radar electromagnetic radiation to the sperm DNA of radar operators. METHODS: Sperm concentration, viability, motility, sperm abnormality were determined by routine sperm analysis and sperm chromatin structure assay (SCSA) in the highly exposed group(n = 88), lowly exposed group(n = 143) and control group(n = 39). RESULTS: Sperm motility, viability of the highly exposed group reduced compared with that of the lowly exposed group and control group, while sperm abnormality increased. The COMP alpha reduction of the highly exposed group indicated that the highly exposed group had a medium fertility potential. The multifactor variable analysis showed that daily working time was a dangerous factor in sperm abnormality and abstinence time was a dangerous factor in the parameter of SCSA. CONCLUSIONS: Radar radiation inflicts damage to male reproduction system and it is important to take protective measures.

[Analysis of correlation between parameters of sperm chromatin structure assay and semen routine analysis].

OBJECTIVES: To analysis the correlation between parameters of sperm chromatin structure assay(SCSA) and semen routine analysis, and to discuss the reliable methods of semen quality evaluation. METHODS: Five hundred and eleven semen samples were detected to analyse the mutiple-parameter correlation between results of SCSA (COMP alpha t) and semen routine analysis. RESULTS: The parameters that have low-level positive correlation(r: 0.10-0.30) with denatured sperm percentage(COMP alpha t) were viscosity, ejaculation interval, abnormal sperm ratio, concentration of grade c sperm; those having low-level negative correlation(r: -0.30(-)-0.10) were VDL, VSL and VAP; those having mid-level positive correlation (r: 0.30-0.70) were sperm concentration, percentage of grade d sperm; those having mid-level negative correlation (r: -0.70(-)-0.30) were MAD, percentage of grade a sperm and survival rate. CONCLUSIONS: Flow cytometry can be used to evaluate the percentage of denatured or injured sperm rapidly, correctly and simply. The result (COMP alpha t) correlates partly with semen parameters, and it is not a conclusively parameter compared with routine semen analysis. It is important to use SCSA to evaluate productivity under the above situation.

[Detection of DNA damage of human sperm using single cell electrophoresis].

OBJECTIVES: To detect the sperm DNA damage and to evaluate its significance in male reproductive using single cell gel electrophoresis (SCGE). METHODS: Four hundred and eighteen sperm samples were analysed using the computer assisted analysis system and SCGE. The sperms samples were divided into five grades according to the extent of the sperm nuclear DNA damage. RESULTS: 1. When the sperm density is less than 20 x 10(6)/ml, the occurence of grade II and III are increased significantly; 2. In the unmotile grade d sperm the occurence of grade I comet amounts was 5.39%, the occurence of grade II and III was remarkably increased. There was a evidently variance between the grade d and grade a + b sperm. CONCLUSIONS: SCGE can be used to detect the sperm DNA breakage and to evaluate the sperm quality and damage.

[Study on sperm quality of the soldiers influenced by reinforced training].

OBJECTIVES: To investigate the correlation between abnormal sperm parameters and reproductive hormones and reinforced training. METHODS: Epidemic investigation were done between two different groups by determining endocrine hormone and standard clinical sperm analysis. RESULTS: Comparison between reinforced training group and non-training group showed decreased sperm velocity but no change on sperm moving form, increased teratism sperm percentage but no change on sperm number, decreased plasma testosterone but no change on LH. CONCLUSIONS: Reinforced training has correlation with weak part of sperm parameter analysis and reproductive hormones.

[The effect of overtraining on human sperm chromatin structure].

OBJECTIVE: To identify the effects of overtraining on human sperm DNA. METHODS: Molecular epidemiological investigation of 249 men from different groups (training and non-training) was carried out by using flow cytometer to detect the integrity and damage of in situ DNA of sperm nucleus, and sperm chromatin structure assay was performed. RESULTS: The average COMPalpha(t) in training group was 11.02% while that in control group was 5.90% (P < 0.01). COMPalpha(t) was significantly correlated with sperm activity (r = 0.41, P < 0.05). CONCLUSION: Overtraining could induce sperm DNA injury and affect sperm activity, thus to decrease the potentiality of reproduction.

[A cross-sectional study on nonionizing radiation to male fertility].

OBJECTIVE: To investigate the relationship between microwave radiation and male reproductivity. METHODS: After filling out questionnaire and body check, we carried out molecular epidemiological studies, using single cell gel electrophoresis (SCGE) and sperm automatic analysis among people working on radar. RESULTS: Quality of semen and semi-clinical injury of sperm among the people working on radar had changed when radar electromagnetic wave frequency distance, intensity, lasting time and protection shield were changing. Dose-response relationship was noticed and the increase of sperm dysmorphia played a principal role. The results between exposed group and control group showed significant difference (P < 0.01). CONCLUSION: People working on radar who suffered from non-ionization for long time and had bad radar shield protection would show semi-clinical injury on sperm and bad semen quality. However, it did not affect the male reproductive function. It was necessary to reinforce the protection of non-ionization and to improve male reproductive health care of people working on radar.

[Study on sperm quality of males living in cold area].

OBJECTIVE: To investigate the effects on male reproductive function working under cold area. METHODS: After on site investigation, advanced molecular lab analysis-single-cell gel electrophoresis (SCGE) and sperm chromatin structure assay (SCSA) which are combined with semen routine analysis were used to evaluate semen quality and sperm sub-clinical injury. RESULTS: Semen routine analysis showed that the semen parameters of the males working in cold area were within normal range, but level I comet cell percentage in SCGE increased significantly, which was 4.4%, compared to the contrast group (1.9%) with significant difference. During sperm chromatin structure assay parameters, comp alpha t increased, with an average value of 22.26%. The two kinds of results both showed single and double strand breakages in sperm. CONCLUSION: Long-term exposure to cold could induce sperm DNA injury, but not affect sperm quality. The results suggested that it was important to reinforce the reproductive care in males working in cold areas.