Association between systemic immune-inflammation index and post-stroke depression: a cross-sectional study of the national health and nutrition examination survey 2005-2020.

Background: Less research has linked the Systemic Immune Inflammatory Index (SII) with post-stroke depression (PSD). This study aims to look at any potential connections between SII and PSD. Methods: The National Health and Nutrition Examination Survey (NHANES), conducted in a population that embodied complete SII and stroke data from 2005 to 2020, was used to perform the current cross-sectional survey. A fitted smoothed curve was used to depict the nonlinear link between SII and PSD, and multiple linear regression analysis demonstrated a positive correlation between SII and PSD. Results: Multiple linear regression analysis showed that SII and PSD were markedly related [1.11(1.05, 1.17)]. Interaction tests showed that the association between SII and PSD was not statistically different between strata, and age, sex, BMI, income poverty ratio, education level, smoking status, diabetes mellitus, coronary heart disease, and heart failure did not have a significant effect on this positive association (p > 0.05 for interaction). In addition, a nonlinear association between SII and PSD was found using a two-stage linear regression model. Conclusion: The results of our research support the existence of a significant positive correlation between SII levels and PSD. Further prospective trials are required to comprehend SII, which is for the PSD thoroughly.

Causal associations between Helicobacter pylori infection and pregnancy and neonatal outcomes: a two-sample Mendelian randomization study.

Background: Observational studies have reported that Helicobacter pylori (H. pylori) infection is associated with a series of pregnancy and neonatal outcomes. However, the results have been inconsistent, and the causal effect is unknown. Methods: A two-sample Mendelian randomization (MR) study was performed using summary-level statistics for anti-H. pylori IgG levels from the Avon Longitudinal Study of Parents and Children Cohort. Outcome data for pregnancy (miscarriage, preeclampsia-eclampsia, gestational diabetes mellitus, placental abruption, premature rupture of membranes, postpartum hemorrhage) and neonates (birthweight, gestational age, and preterm birth) were sourced from genome-wide association meta-analysis as well as the FinnGen and Early Growth Genetics Consortium. Causal estimates were calculated by five methods including inverse variance weighted (IVW). The heterogeneity of instrumental variables was quantified by Cochran's Q test, while sensitivity analyses were performed via MR-Egger, MR-PRESSO, and leave-one-out tests. Results: IVW estimates suggested that genetically predicted anti-H. pylori IgG levels were significantly associated with increased risks of preeclampsia-eclampsia (odds ratio [OR] = 1.12, 95% confidence interval [CI] 1.01-1.24, P = 0.026) and premature rupture of membranes (OR = 1.17, 95% CI 1.05-1.30, P = 0.004). Similar results were obtained for preeclampsia-eclampsia from the MR-Egger method (OR = 1.32, 95% CI 1.06-1.64, P = 0.027) and for premature rupture of membranes from the weighted median method (OR = 1.22, 95% CI 1.06-1.41, P = 0.006). No significant causal effects were found for other outcomes. There was no obvious heterogeneity and horizontal pleiotropy across the MR analysis. Conclusion: Our two-sample MR study demonstrated a causal relationship of H. pylori infection with preeclampsia-eclampsia and premature rupture of membranes. The findings confirm the epidemiological evidence on the adverse impact of H. pylori in pregnancy. Further studies are needed to elucidate the pathophysiological mechanisms and assess the effectiveness of pre-pregnancy screening and preventive eradication.

Association between proliferative-to-secretory endometrial compaction and pregnancy outcomes after embryo transfer: a systematic review and meta-analysis.

STUDY QUESTION: Does the change in endometrial thickness (EMT) from the end of the follicular/estrogen phase to the day of embryo transfer (ET) determine subsequent pregnancy outcomes? SUMMARY ANSWER: Endometrial compaction from the late-proliferative to secretory phase is not associated with live birth rate (LBR) and other pregnancy outcomes. WHAT IS KNOWN ALREADY: Endometrial compaction has been suggested to be indicative of endometrial responsiveness to progesterone, and its association with ET outcome has been investigated but is controversial. STUDY DESIGN, SIZE, DURATION: A systematic review with meta-analysis was carried out. PubMed, EMBASE, and Web of Science were searched to identify relevant studies from inception to 18 November 2022. The reference lists of included studies were also manually screened for any additional publications. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cohort studies comparing ET pregnancy outcomes between patients with and without endometrial compaction were included. A review of the studies for inclusion, data extraction, and quality assessment was performed by two independent reviewers. The effect size was synthesized as odds ratio (OR) with 95% CI using a random-effects model. Heterogeneity and publication bias were assessed by the I2 statistic and Egger's test, respectively. The primary outcome was LBR. Secondary outcomes included biochemical pregnancy rate (BPR), clinical pregnancy rate (CPR), miscarriage rate (MR), ongoing pregnancy rate (OPR), and ectopic pregnancy rate (EPR). MAIN RESULTS AND THE ROLE OF CHANCE: Seventeen cohort studies involving 18 973 ET cycles fulfilled the eligibility criteria. The pooled results revealed that there were no significant differences between endometrial compaction and non-compaction groups in LBR (crude OR (cOR) = 0.95, 95% CI 0.87-1.04; I2 = 0%; adjusted OR (aOR) = 1.02, 95% CI 0.87-1.19, I2 = 79%), BPR (cOR = 0.93, 95% CI 0.81-1.06; I2 = 0%; aOR = 0.88, 95% CI 0.75-1.03, I2 = 0%), CPR (cOR = 0.98, 95% CI 0.81-1.18; I2 = 70%; aOR = 0.86, 95% CI 0.72-1.02, I2 = 13%), MR (cOR = 1.09, 95% CI 0.90-1.32; I2 = 0%; aOR = 0.91, 95% CI 0.64-1.31; I2 = 0%), and EPR (cOR = 0.70, 95% CI 0.31-1.61; I2 = 61%). The OPR was marginally higher in crude analysis (cOR = 1.48, 95% CI 1.01-2.16; I2 = 81%) among women with compacted endometrium, but was not evident in adjusted results (aOR = 1.36, 95% CI 0.86-2.14; I2 = 84%). Consistently, the pooled estimate of LBR remained comparable in further subgroup and sensitivity analyses according to the degree of compaction (0%, 5%, 10%, 15%, or 20%), type of ET (fresh, frozen, or euploid only), and endometrial preparation protocol (natural or artificial). No publication bias was observed based on Egger's test. LIMITATIONS, REASONS FOR CAUTION: Although the number of included studies is sufficient, data on certain measures, such as EPR, are limited. The inherent bias and residual confounding were also inevitable owing to the observational study design. Furthermore, inconsistent definitions of pregnancy outcomes may affect the accuracy of our pooled analysis. WIDER IMPLICATIONS OF THE FINDINGS: Given the lack of prognostic value, assessing endometrial compaction or repeated EMT measurement on the day of ET may not be necessary or warranted. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by Natural Science Foundation of Jiangxi Province (20224BAB216025), National Natural Science Foundation of China (82260315), and Central Funds Guiding the Local Science and Technology Development (20221ZDG020071). The authors have no conflicts of interest to declare. REGISTRATION NUMBER: CRD42022384539 (PROSPERO).

Anti-proliferation and apoptosis induced via the mTOR/PGC-1α signaling pathway in trophoblast cells of miscarriage.

Miscarriage is a common complication during early pregnancy and affects approximately 10%-15% of all pregnant women. Several studies have reported that the abnormal expression of mitochondrial oxidative stress-related genes might be involved in the occurrence and progression of miscarriage. The present study attempted to uncover the role of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) in miscarriage chorionic villous tissue. The hypothesis that PGC-1α is crucial for glycolysis and oxidative phosphorylation during early pregnancy was tested. The results showed that the mRNA and protein levels of PGC-1α were significantly increased in the miscarriage chorionic villous tissues compared with the artificial selective abortion group, and that the expression was regulated by mTOR in knockdown and overexpression of mTOR in HTR8 cell lines. PGC-1α also promoted mitochondrion oxidative phosphorylation but inhibited glycolysis process. In addition, PGC-1α could drive ROS production, reduce mitochondrial membrane potential and block NADPH synthesis, resulting in cell cycle arrest and cell apoptosis, eventually leading to miscarriage. These results suggested that the aberrant expression of PGC-1α is involved in the etiology of early miscarriage, providing new perspectives regarding the mechanisms of miscarriage and a potential therapeutic target for miscarriage.

Transcriptomic responses of cumulus granulosa cells to SARS-CoV-2 infection during controlled ovarian stimulation.

Cumulus granulosa cells (CGCs) play a crucial role in follicular development, but so far, no research has explored the impact of SARS-CoV-2 infection on ovarian function from the perspective of CGCs. In the present study, we compared the cycle outcomes between infected and uninfected female patients undergoing controlled ovarian stimulation, performed bulk RNA-sequencing of collected CGCs, and used bioinformatic methods to explore transcriptomic changes. The results showed that women with SARS-CoV-2 infection during stimulation had significantly lower number of oocytes retrieved and follicle-oocyte index, while subsequent fertilization and embryo development were similar. CGCs were not directly infected by SARS-CoV-2, but exhibited dramatic differences in gene expression (156 up-regulated and 65 down-regulated). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses demonstrated a high enrichment in antiviral, immune and inflammatory responses with necroptosis. In addition, the pathways related to telomere organization and double strand break repair were significantly affected by infection in gene set enrichment analysis. Further weighted gene co-expression network analysis identified a key module associated with ovarian response traits, which was mainly enriched as a decrease of leukocyte chemotaxis and migration in CGCs. For the first time, our study describes how SARS-CoV-2 infection indirectly affects CGCs at the transcriptional level, which may impair oocyte-CGC crosstalk and consequently lead to poor ovarian response during fertility treatment.

Pregnancy outcomes after frozen-thawed embryo transfer in women with COVID-19 history: A prospective cohort study.

The clinical effect of Coronavirus disease 2019 (COVID-19) on endometrial receptivity and embryo implantation remains unclear. Herein, we aim to investigate whether a COVID-19 history adversely affect female pregnancy outcomes after frozen-thawed embryo transfer (FET). This prospective cohort study enrolled 230 women who underwent FET cycles from December 2022 to April 2023 in an academic fertility center. Based on the history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection before FET, women were divided into the infected group (n = 136) and the control group (n = 94). The primary outcome was the clinical pregnancy rate per cycle. Multivariate logistic regression analysis was conducted to adjust for potential confounders, while subgroup analysis and restricted cubic splines were used to depict the effect of postinfection time interval on FET. The results showed that the clinical pregnancy rate was 59.6% in the infected group and 63.9% in the control group (p = 0.513). Similarly, the two groups were comparable in the rates of biochemical pregnancy (69.1% vs. 76.6%; p = 0.214) and embryo implantation (51.7% vs. 54.5%; p = 0.628). After adjustment, the nonsignificant association remained between prior infection and clinical pregnancy (OR = 0.78, 95% CI: 0.42-1.46). However, the odds for clinical pregnancy were significantly lower in the ≤30 days subgroup (OR = 0.15, 95% CI: 0.03-0.77), while no statistical significance was detected for 31-60 days and >60 days subgroups compared with the uninfected women. In conclusion, our findings suggested that SARS-CoV-2 infection in women had no significant effect on subsequent FET treatment overall, but pregnancy rates tended to be decreased if vitrified-thawed embryos were transferred within 30 days after infection. A 1-month postponement should be rationally recommended, while further studies with larger sample groups and longer follow-up periods are warranted for confirmation.

Reduced PATL2 Impairs the Proliferation of Ovarian Granulosa Cells by Decreasing ADM2 Expression in Patients with PCOS.

It is recognized that PCOS patients are often accompanied with aberrant follicular development, which is an important factor leading to infertility in patients. However, the relevant regulatory mechanisms of abnormal follicular development are not well understood. In the present study, by collecting human ovarian granulosa cells (GCs) from PCOS patients who underwent in vitro fertilization (IVF), we found that the proliferation ability of GCs in PCOS patients was significantly reduced. Surprisingly, PATL2 and adrenomedullin 2 (ADM2) were obviously decreased in the GCs of PCOS patients. To further explore the potential roles of PATL2 and ADM2 on GC, we transfected PATL2 siRNA into KGN cells to knock down the expression of PATL2. The results showed that the growth of GCs remarkably repressed after knocking down the PATL2, and ADM2 expression was also weakened. Subsequently, to study the relationship between PATL2 and ADM2, we constructed PATL2 mutant plasmid lacking the PAT construct and transfected it into KGN cells. The cells showed the normal PATL2 expression, but attenuated ADM2 expression and impaired proliferative ability of GCs. Finally, the rat PCOS model experiments further confirmed our findings in KGN cells. In conclusion, our study suggests that PATL2 promoted the proliferation of ovarian GCs by stabilizing the expression of ADM2 through "PAT" structure, which is beneficial to follicular development, whereas, in the ovary with polycystic lesions, reduction of PATL2 could result in the decreased expression of ADM2, subsequently weakened the proliferation ability of GCs and finally led to the occurrence of aberrant follicles.

Effect of prior female SARS-CoV-2 infection on IVF outcomes: a prospective cohort study.

Introduction: The clinical impact of SARS-CoV-2 infection on human reproduction remains controversial. This prospective cohort study aimed to assess the effect of prior female SARS-CoV-2 infection on subsequent in vitro fertilization (IVF) outcomes. Materials and methods: A total of 451 women who underwent fresh IVF treatment between December 1, 2022 and April 30, 2023 were included from an academic fertility center. Participants were divided into the infected group if they had a prior COVID-19 history before cycle initiation (n = 252), while the control group were those uninfected (n = 199). The primary outcomes were the number of oocytes retrieved and clinical pregnancy rate after fresh embryo transfer. Multivariate linear and logistic regression analyses were conducted to control for potential confounders. Results: The number of oocytes retrieved (11.4 ± 8.3 vs. 11.6 ± 7.7; P = 0.457) and clinical pregnancy rate (70.3% vs. 73.7%; P = 0.590) were similar between infected and uninfected groups, with a fully adjusted ß coefficient of 0 (95% confidence interval [CI]: -0.14-0.13) and odds ratio of 0.64 (95% CI: 0.20-2.07), respectively. Consistently, the two groups were comparable in cycle characteristics as well as other laboratory and pregnancy parameters. In both subgroup analyses and restricted cubic splines, different post-infection time intervals to IVF cycle initiation showed no significant associations with treatment outcomes. Conclusion: Prior SARS-CoV-2 infection in females had no adverse influence on subsequent IVF treatment, regardless of the time interval following infection. Our findings provide reassurance for infected women planning for assisted reproduction. Additional prospective cohort studies with larger datasets and longer follow-up are required to confirm the conclusion.

Impact of inactivated COVID-19 vaccination on female ovarian reserve: a propensity score-matched retrospective cohort study.

Purpose: To explore the impact of inactivated COVID-19 vaccination on ovarian reserve as assessed by serum anti-Müllerian hormone (AMH) concentration. Methods: A total of 3160 women were included in this single-center retrospective cohort study between June 2021 and October 2022. Vaccination information were collected from official immunization records available in personal mobile apps. Serum AMH was qualified by electrochemiluminescence immunoassay and compared with previous measurement data within three years. Women were categorized to the vaccinated group if they received two doses of inactivated COVID-19 vaccines (Sinopharm or Sinovac) between AMH tests (n = 488), and to the control group if not vaccinated (n = 2672). Propensity score matching and multivariate linear regression were performed to control for potential confounders. The main outcome measures were the numeric AMH change and percentage AMH change between the two tests. Results: There were 474 women left in each group after matching all baseline characteristics. The mean interval from the first to second AMH measurement was 508.0 ± 250.2 and 507.5 ± 253.6 days for vaccinated and unvaccinated women, respectively (P = 0.680). Both groups had a significant AMH decrease in the second test compared with the first test (P = 0.001). However, the second AMH level remained comparable between groups (3.26 ± 2.80 vs. 3.24 ± 2.61 ng/mL, P = 0.757). Similarly, no significant differences were observed in numerical (-0.14 ± 1.32 vs. -0.20 ± 1.56 ng/mL, P = 0.945) and percentage (2.33 ± 58.65 vs. 0.35 ± 48.42%, P = 0.777) AMH changes. The results were consistent in sub-analyses for women aged <35 and ≥35 years. There were also no significant differences when vaccinated women were divided according to the time interval after vaccination: ≤30, 31-60, 61-90, and ≥91 days. Conclusion: Our study provides the first evidence that inactivated COVID-19 vaccination has no measurable detrimental effect on ovarian reserve, regardless of female age and vaccination interval. This reassuring finding adds to the safety evidence of COVID-19 vaccine in fertility, and should be useful to promote vaccine acceptance. Multicenter prospective cohort studies are needed to validate our conclusion.

Mutational analysis of minichromosome maintenance complex component (MCM) family genes in Chinese Han women with polycystic ovarian syndrome.

PURPOSE: To investigate whether mutations in the minichromosome maintenance complex component (MCM) family genes were present in patients with polycystic ovary syndrome (PCOS) of Chinese descent. METHODS: A total of 365 Chinese patients with PCOS and 860 women without PCOS as control who underwent with assisted reproductive technology were enrolled. Genomic DNA was extracted from the peripheral blood of these patients for PCR and Sanger sequencing. The potential damage of these mutations/rare variants was analyzed through evolutionary conservation analysis and bioinformatic programs. RESULTS: Twenty-nine missense or nonsense mutations/rare variants in the MCM genes were identified in 365 patients with PCOS (7.9%, 29/365), all these mutations/rare variants were predicted to be 'disease causing' by SIFT and PolyPhen2 programs. Among those, four mutations were reported here for the first time, p.S7C (c.20C > G) in MCM2 (NM_004526.3), p.K350R (c.1049A > G) in MCM5 (NM_006739.3), p.K283N (c.849G > T) in MCM10 (NM_182751.2), and p.S1708F (c.5123C > T) in MCM3AP (NM_003906.4). All of these novel mutations were not found in our 860 control women, or also absent in public databases. In addition, the evolutionary conservation analysis results suggested that these novel mutations caused highly conserved amino acid substitutions among 10 vertebrate species. CONCLUSION: This study identified a high frequency of potential pathogenic rare variants/mutations in MCM family genes in Chinese women with PCOS, which further expands the genotype spectrum in PCOS.

Efficacy and Safety of the Chinese Herbal Compound TJAOA101 in Treating Diminished Ovarian Reserve: A Protocol for Multicenter, Prospective, and Pre-Post Study.

OBJECTIVE: Diminished ovarian reserve (DOR) can lead to early menopause, poor fecundity, and an increased risk of disorders such as osteoporosis, cardiovascular disease, and cognitive impairment, seriously affecting the physical and mental health of women. There is still no safe and effective strategy or method to combat DOR. We have developed a novel Chinese herbal formula, Tongji anti-ovarian aging 101 (TJAOA101), to treat DOR. However, its safety and efficacy need to be further validated. METHODS: In this prospective and pre-post clinical trial, 100 eligible patients aged 18-45 diagnosed with DOR will be recruited. All participants receive TJAOA101 twice a day for 3 months. Then, comparisons before and after treatment will be analyzed, and the outcomes, including anti-mullerian hormone (AMH) and follicle-stimulating hormone (FSH) levels and the antral follicle count (AFC), the recovery rate of menopause, and the Kupperman index (KMI), will be assessed at baseline, every month during medication (the intervention period), and 1, 3 months after medication (the follow-up period). Assessments for adverse events will be performed during the intervention and follow-up periods. CONCLUSION: A multicenter, prospective study will be conducted to further confirm the safety and efficacy of TJAOA101 in treating DOR and to provide new therapeutic strategies for improving the quality of life in DOR patients.

Effect of female coronavirus disease 2019 vaccination on assisted reproductive outcomes: a systematic review and meta-analysis.

IMPORTANCE: The effect of coronavirus disease 2019 (COVID-19) vaccination on fertility warrants clarification in women undergoing assisted reproductive treatment. OBJECTIVE: To study the association between female COVID-19 vaccination and outcomes of assisted reproductive treatment. DATA SOURCES: PubMed, Embase, the Web of Science, Cochrane Library, and medRxiv and bioRxiv were searched for eligible studies from December 1, 2019, to November 30, 2022, with no language restrictions. STUDY SELECTION AND SYNTHESIS: Observational studies comparing assisted reproductive outcomes between women with and without COVID-19 vaccination were included. The pooled estimates were calculated using the random-effects models as mean differences (MDs), standardized MDs, or odds ratios with 95% confidence intervals (CIs). Heterogeneity was evaluated using the I2 statistic. MAIN OUTCOMES: The number of oocytes retrieved and clinical pregnancy rate. RESULTS: Twenty-one cohort studies involving a total of 19,687 treatment cycles were included. In a comparison of the vaccinated vs. unvaccinated groups, the pooled MD for oocyte number was -0.06 (95% CI, -0.51 to 0.39; I2 = 0), and the pooled odds ratio for clinical pregnancy was 0.95 (95% CI, 0.85-1.05; I2 = 0). Similarly, there were no statistically significant adverse effects identified in other outcomes determined a priori, including 4 cycle characteristics, 6 laboratory parameters, and 3 pregnancy indicators. Most results were consistently unchanged in subgroup and sensitivity analyses, with no evidence of publication bias according to Egger's test. CONCLUSION AND RELEVANCE: Our work did not find significant differences in assisted reproductive outcomes between vaccinated and unvaccinated women. However, more data are warranted to confirm the safety of COVID-19 vaccination for assisted reproductive treatment and in female fertility in general.

[Application of single sperm sequencing for the preimplantation genetic testing of a Chinese family affected with Spinal muscular atrophy].

OBJECTIVE: To assess the value of single sperm sequencing in preimplantation genetic testing for monogenic disease (PGT-M). METHODS: A Chinese couple with two children whom had died of Spinal muscular atrophy (SMA) and attended the Jiangxi Provincial Maternal and Child Health Care Hospital in June 2020 was selected as the subject. Eleven single sperm samples were isolated by mechanical immobilization and subjected to whole genome amplification. Real-time PCR and Sanger sequencing were used to detect the SMN1 variants in the single sperm samples. Genomic DNA of the wife, her parents and the husband, as well as one single sperm sample harboring the SMN1 variant and two single sperm samples without the variant were used for the linkage analysis. Targeted capture and high-throughput sequencing were carried out to test 100 single nucleotide polymorphisms distributed within 2 Mb up- and downstream the variant site. The haplotypes linked with the SMN1 variants were determined by linkage analysis. Blastocyst embryos were harvested after fertilizing by intracytoplasmic sperm injection. Cells from the trophoblasts of each embryo were biopsied and subjected to whole genome amplification and targeted capture and high-throughput sequencing to determine their carrier status. Chromosomal aneuploidy of wild-type embryos was excluded. An euploid embryo of high quality was transferred. Amniotic fluid sample was taken at 18 weeks of gestation to confirm the status of the fetus. RESULTS: Genetic testing showed that the couple both had deletion of exons 7 ~ 8 of the SMN1 gene. The wife has inherited the deletion from her father, while the husband was de novo. The haplotypes of the husband were successfully constructed by single sperm sequencing. Preimplantation genetic testing has indicated that 5 embryos had harbored the heterozygous variant, 4 embryos were of the wild type, among which 3 were euploid. Prenatal diagnosis during the second trimester of pregnancy has confirmed that the fetus did not carry the deletion. CONCLUSION: By single sperm sequencing and PGT-M, the birth of further affected child has been successfully avoided.

Effect of COVID-19 vaccination on semen parameters: A systematic review and meta-analysis.

The aim of this study was to investigate the effect of coronavirus disease 2019 (COVID-19) vaccination on semen parameters through systematic review and meta-analysis. PubMed, EMBASE, Web of Science, and Cochrane Library were comprehensively searched by June 2022. Studies were considered eligible if they compared semen parameters before and after COVID-19 vaccination or between vaccinated and unvaccinated men, with no restrictions on vaccine types or doses. The effect size was calculated as mean difference (MD) with 95% confidence interval (CI) using a random-effects model. Subgroup and sensitivity analyses were conducted to assess the sources of heterogeneity measured by the I2 statistic, with publication bias evaluated by Egger's test. Twelve cohort studies involving 914 participants fulfilled the inclusion criteria. In a comparison of vaccinated versus unvaccinated group, the pooled data revealed no significant differences in semen volume (MD = 0.18 ml, 95% CI -0.02 to 0.38), sperm concentration (MD = 1.16 million/ml, 95% CI -1.34 to 3.66), total sperm motility (MD = -0.14%, 95% CI -2.84 to 2.56), progressive sperm motility (MD = -1.06%, 95% CI -2.88 to 0.77), total sperm count (MD = 5.92 million, 95% CI -10.22 to 22.05), total motile sperm count (MD = 2.18 million, 95% CI -1.28 to 5.63), total progressively motile sperm count (MD = -3.87 million, 95% CI -13.16 to 5.43), and sperm morphology (MD = 0.07%, 95% CI -0.84 to 0.97). The results also remained similar across messenger ribonucleic acid, viral-vector, and inactivated COVID-19 vaccines. Sensitivity analysis identified two individual studies that contributed to heterogeneity, while the effect size was not materially altered. No obvious publication bias was detected among included studies. Our finding suggested that COVID-19 vaccination had no detrimental impact on semen quality, which could be potentially helpful to reduce male vaccine hesitancy and increase vaccination coverage.

Effect of inactivated COVID-19 vaccination on pregnancy outcomes following frozen-thawed embryo transfer: A retrospective cohort study.

OBJECTIVE: To investigate the effect of inactivated coronavirus disease 2019 (COVID-19) vaccination on frozen-thawed embryo transfer (FET) outcomes. METHODS: This retrospective cohort study enrolled 1,210 patients undergoing FET cycles in a single university-affiliated hospital between July 1, 2021, and May 1, 2022. Of them, 387 women with two full doses of inactivated SARS-CoV-2 vaccines (CoronaVac or BBIBP-CorV) after oocyte retrieval were assigned to the vaccinated group, while 823 were unvaccinated as controls. Propensity score matching and multiple regression analysis were applied to control for baseline and cycle characteristics (19 covariates in total). RESULTS: There were 265 patients in each group after matching. The rates of clinical pregnancy (58.5% vs. 60.8%; P = 0.595) and live birth (44.4% vs. 48.8%; P = 0.693) were similar between vaccinated and unvaccinated patients, with adjusted odds ratios of 0.89 (95% confidence interval [CI] 0.61-1.29) and 1.31 (95% CI 0.37-4.56), respectively. Consistently, no significant differences were found in serum human chorionic gonadotropin levels as well as biochemical pregnancy, biochemical pregnancy loss, and embryo implantation rates. Based on the time interval from vaccination to FET, vaccinated patients were further subdivided into two categories of ≤2 months and >2 months, and the outcomes remained comparable. CONCLUSION: Our study showed that inactivated COVID-19 vaccination in women did not have measurable detrimental impact on implantation performance and live birth outcome during FET treatment cycles. This finding denies the impairment of endometrial receptivity and trophoblast function by vaccine-induced antibodies at the clinical level.

Indentification of novel MSTO1 compound heterozygous mutations in a Chinese family with recessive cerebellar atrophy and ataxia.

Misato mitochondrial distribution and morphology regulator 1 (MSTO1) is a nuclear-encoded cytoplasmic protein involved in mitochondrial fusion and distribution. Its disruption causes an extremely rare mitochondrial disorder characterized by early-onset myopathy and cerebellar ataxia. The genotype-phenotype correlation in the MSTO1 gene is rarely studied before 2017, and only 25 mutations have been described in the patients. Here, we reported two siblings with progressive cerebellar atrophy and ataxia in a Chinese family. Two compound heterozygous mutations in the MSTO1 gene, a novel missense mutation c.571C>T (p.Arg191Trp), and a reported frameshift mutation c.1259delG (p.Gly420ValfsTer2) were identified in the patients by whole exome sequencing. in vitro experiments found both of the mutations lead to reduced protein abundance and link to decreased mtDNA content. Except for ataxia and delayed motor, both of the siblings also have low birth weights, learning difficulties, and dysarthria. Our report enriched the genotype and phenotype spectrums of the MSTO1-related disorder and supported the recessive inheritance of the disease.

Autophagy markers are dysregulated in the endometrial tissues of patients with unexplained repeated implantation failure.

Endometrium decidualization is a complex biological process, which includes the interplay of transcription factors, cytokines, cell cycle regulators, and other signaling pathways. However, the underlying molecular mechanisms of this process are not fully elucidated to date. In this study, we aimed to investigate the possible association between autophagy and recurrent implantation failure (RIF). A total of 81 genes were downregulated and 231 genes were upregulated in the RIF group compared with the control group, and the differences were statistically significant (p < 0.05). Further, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway were analyzed, and we found that some autophagy markers, for example, LC3-II, LAMP2, and HIF-1α were significantly increased, whereas P62 was drastically downregulated in the RIF group. Similar results were observed in proteins level; and the autophagy puncta were also markedly enhanced in the endometrial tissues of RIF patients. Autophagy is closely associated with the RIF occurs and may be involved in the pathogenesis of RIF.

Mapping separase-mediated cleavage in situ.

Separase is a protease that performs critical functions in the maintenance of genetic homeostasis. Among them, the cleavage of the meiotic cohesin during meiosis is a key step in producing gametes in eukaryotes. However, the exact chromosomal localization of this proteolytic cleavage was not addressed due to the lack of experimental tools. To this end, we developed a method based on monoclonal antibodies capable of recognizing the predicted neo-epitopes produced by separase-mediated proteolysis in the RAD21 and REC8 cohesin subunits. To validate the epigenomic strategy of mapping cohesin proteolysis, anti-RAD21 neo-epitopes antibodies were used in ChIP-On-ChEPseq analysis of human cells undergoing mitotic anaphase. Second, a similar analysis applied for mapping of REC8 cleavage in germline cells in Macaque showed a correlation with a subset of alpha-satellites and other repeats, directly demonstrating that the site-specific mei-cohesin proteolysis hotspots are coincident but not identical with centromeres. The sequences for the corresponding immunoglobulin genes show a convergence of antibodies with close specificity. This approach could be potentially used to investigate cohesin ring opening events in other chromosomal locations, if applied to single cells.

Identification of a novel ESR1 mutation in a Chinese PCOS woman with estrogen insensitivity in IVF treatment.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex reproductive disorder, that affects approximately 5-10% of women of reproductive age. The disease is complex because its evolution may be impacted by genetic, lifestyle and environmental factors. Previous studies have emphasized the important roles of estrogen receptors in the pathogenesis of PCOS. OBJECTIVE: To use whole exome sequencing (WES) to assess possible pathogenic factors in a PCOS patient who exhibited estrogen insensitivity during hormone replacement therapy (HRT) treatment. METHODS: Genome sequencing and variant filtering via WES were performed in a patient with PCOS. DNA extraction from 364 unrelated female controls without PCOS was followed by PCR amplification, Sanger sequencing and sequence alignment. Evolutionary conservation analysis, protein structural modelling and in silico prediction were applied to analyse the potential pathogenicity of the novel ESR1 mutation. RESULT(S): During the controlled ovarian hyperstimulation (COH) period of an IVF cycle, the patient experienced markedly prolonged ovarian stimulation due to a poor response to gonadotropins (Gn) and elevated serum FSH. A novel heterozygous ESR1 mutation, c.619G > A/p.A207T, leading to the replacement of a highly conserved alanine with a threonine, was identified in this patient, via WES analysis. This novel variant was not identified in 364 unrelated female controls without PCOS, or in the Exome Aggregation Consortium (ExAC) or 1000 Genome Project. CONCLUSION(S): We identified a novel heterozygous ESR1 mutation in a Han Chinese PCOS woman exhibiting clinical signs of estrogen insensitivity. This study may provide new strategies for IVF therapy, especially for patients who exhibit estrogen insensitivity during IVF cycle.

Retrospective analysis of GnRH-a prolonged protocol for in vitro fertilization in 18,272 cycles in China.

BACKGROUND: This large-cohort, retrospective study investigates the relationship between the number of oocytes retrieved and the clinical outcomes for patients receiving the GnRH-a prolonged protocol (mGnRH-a protocol) for fertilization in vitro or intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) treatment. RESULTS: We categorized 18,272 cycles into three groups by the number of oocytes retrieved (1-8, 9-17, and ≥ 18) during IVF with the GnRH-a prolonged protocol at the Reproductive Medical Center of Jiangxi Maternal and Child Health Hospital from January 2014 to December 2018 (excluding oocyte donation cycles), analyzing the associations among oocyte number and live birth rates (LBRs) or cumulative LBRs (CLBRs), as well as the rate of moderate-to-severe ovarian hyperstimulation syndrome (OHSS). We defined the primary outcome as LBR and the secondary outcome to include the rate of patients at high risk for OHSS. The LBR (with fresh ET) per cycle of oocyte pick-up increased as the number of retrieved oocytes increased from 1 to ~ 8, plateaued between 9 ~ 17, and steadily decreased thereafter. However, the CLBR per cycle continued to increase as the oocyte number increased, as did the incidence of moderate-to-severe OHSS. CONCLUSIONS: Our results show a strong relationship between the number of oocytes retrieved and the CLBR following IVF treatment. The balance between treatment success and the risk of complications, especially OHSS, should be investigated further. We recommend a fresh-ET strategy for the GnRH-a prolonged protocol because the endometrial receptivity in the fresh cycles was better than those in the frozen cycles.