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.

Predicting personalized cumulative live birth rate after a complete in vitro fertilization cycle: an analysis of 32,306 treatment cycles in China.

BACKGROUND: The cumulative live birth rate (CLBR) has been regarded as a key measure of in vitro fertilization (IVF) success after a complete treatment cycle. Women undergoing IVF face great psychological pressure and financial burden. A predictive model to estimate CLBR is needed in clinical practice for patient counselling and shaping expectations. METHODS: This retrospective study included 32,306 complete cycles derived from 29,023 couples undergoing IVF treatment from 2014 to 2020 at a university-affiliated fertility center in China. Three predictive models of CLBR were developed based on three phases of a complete cycle: pre-treatment, post-stimulation, and post-treatment. The non-linear relationship was treated with restricted cubic splines. Subjects from 2014 to 2018 were randomly divided into a training set and a test set at a ratio of 7:3 for model derivation and internal validation, while subjects from 2019 to 2020 were used for temporal validation. RESULTS: Predictors of pre-treatment model included female age (non-linear relationship), antral follicle count (non-linear relationship), body mass index, number of previous IVF attempts, number of previous embryo transfer failure, type of infertility, tubal factor, male factor, and scarred uterus. Predictors of post-stimulation model included female age (non-linear relationship), number of oocytes retrieved (non-linear relationship), number of previous IVF attempts, number of previous embryo transfer failure, type of infertility, scarred uterus, stimulation protocol, as well as endometrial thickness, progesterone and luteinizing hormone on trigger day. Predictors of post-treatment model included female age (non-linear relationship), number of oocytes retrieved (non-linear relationship), cumulative Day-3 embryos live-birth capacity (non-linear relationship), number of previous IVF attempts, scarred uterus, stimulation protocol, as well as endometrial thickness, progesterone and luteinizing hormone on trigger day. The C index of the three models were 0.7559, 0.7744, and 0.8270, respectively. All models were well calibrated (p = 0.687, p = 0.468, p = 0.549). In internal validation, the C index of the three models were 0.7422, 0.7722, 0.8234, respectively; and the calibration P values were all greater than 0.05. In temporal validation, the C index were 0.7430, 0.7722, 0.8234 respectively; however, the calibration P values were less than 0.05. CONCLUSIONS: This study provides three IVF models to predict CLBR according to information from different treatment stage, and these models have been converted into an online calculator ( https://h5.eheren.com/hcyc/pc/index.html#/home ). Internal validation and temporal validation verified the good discrimination of the predictive models. However, temporal validation suggested low accuracy of the predictive models, which might be attributed to time-associated amelioration of IVF practice.

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.

Increased blastomere number is associated with higher live birth rate in day 3 embryo transfer.

PURPOSE: To study the relationship between blastomere number and pregnancy outcomes of day 3 embryo transfers. METHODS: This retrospective cohort study included 2237 fresh single day 3 embryo transfer cycles from October 2013 to November 2020. Patients were divided into six groups according to the blastomere number on day 3: ≤ 6-cell (n = 100), 7-cell (n = 207), 8-cell (n = 1522), 9-cell (n = 187), 10-cell (n = 91) and ≥ 11-cell (n = 130). Generalized estimating equation analysis based on multivariate logistic regression model was performed to adjust for potential confounders. RESULTS: The live birth rate (LBR) was 19.0%, 27.1%, 38.9%, 32.1%, 44.0% and 53.8% for the ≤ 6-cell, 7-cell, 8-cell, 9-cell, 10-cell and ≥ 11-cell groups, respectively (P < 0.001). Specifically, the ≤ 6-cell group was associated with reduced LBR compared with the 8-cell group (aOR 0.50, 95% CI 0.29-0.86; P = 0.013). Conversely, the odds of live birth were significantly increased in patients transferred with 10-cell embryos (aOR 1.62, 95% CI 1.03-2.53; P = 0.035) and ≥ 11-cell embryos (aOR 2.14, 95% CI 1.47-3.11; P < 0.001) when using the 8-cell embryo group as reference. Similar trends were also observed in the rates of positive hCG test and clinical pregnancy, while no significant differences were detected in miscarriage risk. CONCLUSION: Increased blastomere number was associated with higher LBR in fresh single day 3 embryo transfer cycles. This finding questions the consensus on the reduced developmental potential of fast-cleaving embryos. Further large prospective studies are warranted for confirmation.

Impact of inactivated SARS-CoV-2 vaccination on embryo ploidy: a retrospective cohort study of 133 PGT-A cycles in China.

BACKGROUND: Unsubstantiated concerns have been raised on the potential correlation between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and infertility, leading to vaccine hesitancy in reproductive-aged population. Herein, we aim to evaluate the impact of inactivated SARS-CoV-2 vaccination on embryo ploidy, which is a critical indicator for embryo quality and pregnancy chance. METHODS: This was a retrospective cohort study of 133 patients who underwent preimplantation genetic testing for aneuploidy (PGT-A) cycles with next-generation sequencing technology from June 1st 2021 to March 17th 2022 at a tertiary-care medical center in China. Women fully vaccinated with two doses of Sinopharm or Sinovac inactivated vaccines (n = 66) were compared with unvaccinated women (n = 67). The primary outcome was the euploidy rate per cycle. Multivariate linear and logistic regression analyses were performed to adjust for potential confounders. RESULTS: The euploidy rate was similar between vaccinated and unvaccinated groups (23.2 ± 24.6% vs. 22.6 ± 25.9%, P = 0.768), with an adjusted ß of 0.01 (95% confidence interval [CI]: -0.08-0.10). After frozen-thawed single euploid blastocyst transfer, the two groups were also comparable in clinical pregnancy rate (75.0% vs. 60.0%, P = 0.289), with an adjusted odds ratio of 6.21 (95% CI: 0.76-50.88). No significant associations were observed between vaccination and cycle characteristics or other laboratory and pregnancy outcomes. CONCLUSIONS: Inactivated SARS-CoV-2 vaccination had no detrimental impact on embryo ploidy during in vitro fertilization treatment. Our finding provides further reassurance for vaccinated women who are planning to conceive. Future prospective cohort studies with larger datasets and longer follow-up are needed to confirm the conclusion.

A novel heterozygous variant in PANX1 is associated with oocyte death and female infertility.

PURPOSE: Oocyte death is a severe clinical phenotype that causes female infertility and recurrent in vitro fertilization and intracytoplasmic sperm injection failure. We aimed to identify pathogenic variants in a female infertility patient with oocyte death phenotype. METHODS: Sanger sequencing was performed to screen PANX1 variants in the affected patient. Western blot analysis was used to check the effect of the variant on PANX1 glycosylation pattern in vitro. RESULTS: We identified a novel PANX1 variant (NM_015368.4 c.86G > A, (p. Arg29Gln)) associated with the phenotype of oocyte death in a non-consanguineous family. This variant displayed an autosomal dominant inheritance pattern with reduced penetrance. Western blot analysis confirmed that the missense mutation of PANX1 (c.86G > A) altered the glycosylation pattern in HeLa cells. Moreover, the mutation effects on the function of PANX1 were weaker than recently reported variants. CONCLUSION: Our findings expand the inheritance pattern of PANX1 variants to an autosomal dominant mode with reduced penetrance and enrich the variational spectrum of PANX1. These results help us to better understand the genetic basis of female infertility with oocyte death.

Construction of lncRNA-related competing endogenous RNA network and identification of hub genes in recurrent implantation failure.

BACKGROUND: The mechanism of recurrent implantation failure (RIF) is unclear at present and poor endometrial receptivity may be one of the leading reasons. This study aims to construct a competing endogenous RNA (ceRNA) network and identify potential hub genes underlying the development of RIF. METHODS: Weighted gene co-expression network analysis was performed based on differentially expressed mRNAs (DEMs) and lncRNAs (DELs) from the GSE111974 dataset. Functional enrichment analyses of gene modules were conducted using Gene Ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway. A lncRNA-miRNA-mRNA ceRNA regulatory network was constructed according to predictive interaction derived from the LncRNADisease, miRTarBase, miRDB and TargetScan databases. Topological analysis determined the key genes with the highest centroid and their expressions were further verified using public datasets and quantitative real-time polymerase chain reaction. RESULTS: A total of 1500 DEMs and 3 DELs were significantly up-regulated, whereas 1022 DEMs and 4 DELs were significantly down-regulated in the RIF group compared with the control group. Six functional co-expression modules were enriched in various biological processes, such as cell adhesion, regulation of cell motility and cellular response to vascular endothelial growth factor stimulus. Five hub genes were identified in the ceRNA network, of which GJA1 was down-regulated whereas TET2, MAP2K6, LRRC1 and TRPM6 were up-regulated in RIF endometrium. CONCLUSIONS: We constructed a lncRNA-associated ceRNA network and identified five novel hub genes in RIF. This finding could be helpful to understand the molecular mechanism for RIF pathogenesis, and may provide novel insights for its early diagnosis and treatment.

Anastomotic stricture indexes for endoscopic balloon dilation after esophageal atresia repair: a single-center study.

We investigated changes in anastomotic stricture indexes (SIs) and stricture diameter (SD) between before and 6 months after the first dilatation in children with anastomotic stricture after esophageal atresia (EA) repair and identified predictors of medium-term dilatation success (success for at least 3 months). We retrospectively reviewed the records and measurement indexes of patients who underwent post-EA repair endoscopic balloon dilatation between November 2017 and August 2019 in our hospital. We identified diagnostic and performance indicators that predicted medium-term dilatation success by univariate and multivariate analyses and receiver operator characteristic (ROC) curve analysis. Sixty patients (34 boys and 26 girls) showed post-EA repair anastomotic stricture. Paired sample t-tests showed that SD (P < 0.001), upper pouch SI (U-SI, P < 0.001), lower pouch SI (L-SI, P < 0.001), upper pouch esophageal anastomotic SI (U-EASI, P < 0.001) and lower pouch EASI (L-EASI, P < 0.001) were significantly better at 6 months after than before the first dilatation. Logistic regression analysis showed that dilatation number (P = 0.002) and U-SI at 6 months after the first dilatation (P = 0.019) significantly predicted medium-term dilatation success. ROC curve analysis revealed that combining U-SI (cut-off value = 55.6%) and dilatation number (cut-off value = 10) had good accuracy in predicting medium-term dilatation success 6 months after the first dilatation (area under the curve-ROC: 0.95). In conclusion, endoscopic balloon dilatation significantly improved SD and SIs in children with post-EA repair anastomotic stricture. Dilatation number and U-SI at 6 months after the first dilatation were useful in predicting medium-term dilatation success and could represent a supplementary method to improve judgment regarding whether further dilatation is needed 6 months after the first dilatation.

The ability of different imputation methods for missing values in mental measurement questionnaires.

BACKGROUND: Incomplete data are of particular important influence in mental measurement questionnaires. Most experts, however, mostly focus on clinical trials and cohort studies and generally pay less attention to this deficiency. We aim is to compare the accuracy of four common methods for handling items missing from different psychology questionnaires according to the items non-response rates. METHOD: All data were drawn from the previous studies including the self-acceptance scale (SAQ), the activities of daily living scale (ADL) and self-esteem scale (RSES). SAQ and ADL dataset, simulation group, were used to compare and assess the ability of four imputation methods which are direct deletion, mode imputation, Hot-deck (HD) imputation and multiple imputation (MI) by absolute deviation, the root mean square error and average relative error in missing proportions of 5, 10, 15 and 20%. RSES dataset, validation group, was used to test the application of imputation methods. All analyses were finished by SAS 9.4. RESULTS: The biases obtained by MI are the smallest under various missing proportions. HD imputation approach performed the lowest absolute deviation of standard deviation values. But they got the similar results and the performances of them are obviously better than direct deletion and mode imputation. In a real world situation, the respondents' average score in complete data set was 28.22 ± 4.63, which are not much different from imputed datasets. The direction of the influence of the five factors on self-esteem was consistent, although there were some differences in the size and range of OR values in logistic regression model. CONCLUSION: MI shows the best performance while it demands slightly more data analytic capacity and skills of programming. And HD could be considered to impute missing values in psychological investigation when MI cannot be performed due to limited circumstances.

Focusing on the premature death of redeployed miners in China: an analysis of cause-of-death information from non-communicable diseases.

BACKGROUND: Reducing premature deaths is an important step towards achieving the World Health Organization's sustainable development goal. Redeployed miners are more prone to disease or premature death due to the special occupational characteristics. Our aims were to describe the deaths of redeployed miners, assess the losses due to premature death and identify their main health problems. All the records of individuals were obtained from Fuxin Mining Area Social Security Administration Center. Year of life lost (YLL) and average year of life lost were used to assess the loss due to premature death. YLL rates per 1000 individuals were considered to compare deaths from different populations. RESULTS: Circulatory system diseases contributed the most years of life lost in the causes of death, followed by neoplasms. But average year of life lost in neoplasms was 6.85, higher than circulatory system diseases, 5.63. Cerebrovascular disease and ischemic heart disease were the main causes of death in circulatory system diseases. And average years of life lost in cerebrovascular disease and ischemic heart disease were 5.85 and 5.62, higher than those in other circulatory system diseases. Lung cancer was the principal cause of death in neoplasms. Average year of life lost in liver cancer was 7.92, the highest in neoplasms. CONCLUSIONS: For redeployed miners, YLL rates per 1000 individuals in cerebrovascular disease, ischemic heart disease and lung cancer were higher than those in other populations, especially in men. It is important to attach importance to the health of redeployed miners, take appropriate measures to reduce premature death and achieve the sustainable development goal. Our findings also contribute to a certain theoretical reference for other countries that face or will face the same problem.

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.

The adenosine A2A receptor in human sperm: its role in sperm motility and association with in vitro fertilization outcomes.

Background: The involvement of ATP and cAMP in sperm function has been extensively documented, but the understanding of the role of adenosine and adenosine receptors remains incomplete. This study aimed to examine the presence of adenosine A2A receptor (A2AR) and study the functional role of A2AR in human sperm. Methods: The presence and localization of A2AR in human sperm were examined by western blotting and immunofluorescence assays. The functional role of A2AR in sperm was assessed by incubating human sperm with an A2AR agonist (regadenoson) and an A2AR antagonist (SCH58261). The sperm level of A2AR was examined by western blotting in normozoospermic and asthenozoospermic men to evaluate the association of A2AR with sperm motility and in vitro fertilization (IVF) outcomes. Results: A2AR with a molecular weight of 43 kDa was detected in the tail of human sperm. SCH58261 decreased the motility, penetration ability, intracellular Ca2+ concentration, and CatSper current of human sperm. Although regadenoson did not affect these sperm parameters, it alleviated the adverse effects of SCH58261 on these parameters. In addition, the mean level of A2AR in sperm from asthenozoospermic men was lower than that in sperm from normozoospermic men. The sperm level of A2AR was positively correlated with progressive motility. Furthermore, the fertilization rate during IVF was lower in men with decreased sperm level of A2AR than in men with normal sperm level of A2AR. Conclusions: These results indicate that A2AR is important for human sperm motility and is associated with IVF outcome.

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.

Factors affecting cumulative live birth rate after the 1st oocyte retrieved in polycystic ovary syndrome patients in women during IVF/ICSI-ET.

BACKGROUND: The factors affecting the cumulative live birth rate (CLBR) of PCOS (Polycystic ovary syndrom) patients who received in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) needs more research for a better outcome. METHODS: Here we carried out a retrospective analysis of 1380 PCOS patients who received IVF/ICSI-ET for the first time from January 2014 to December 2016. We divided them into cumulative live birth group (group A) and non-cumulative live birth group (group B) according to whether there were live births. RESULTS: The conservative cumulative live birth rate was 63.48%. There were 876 cumulative live births (group A) and 504 non-cumulative live births (group B) according to whether the patients had live births or not. Competition analysis showed that duration of infertility, primary/secondary type of infertility, stimulation protocols, starting dose of gonadotrophins and oocyte retrieved numbers were significantly correlated with CLBR. The Cox proportional risk regression model of PCOS patients showed that stimulation protocols had a significant impact on CLBR. Patients in the GnRH (Gonadotropin-releasing hormone)-antagonist protocol group and the mild stimulation protocol had lower CLBR than those in the prolonged GnRH-agonist protocol, which was statistically significant. PCOS patients with the starting dose of gonadotrophins greater than 112.5u had lower CLBR than those with less than 100u, which was statistically significant. Women with 11-15 oocytes and 16-20 oocytes had higher CLBR than women with 1-9 oocytes, which was statistically significant. CONCLUSIONS: When we used Prolonged GnRH-agonist protocol, or the first starting dose of gonadotrophins was 100u-112.5u, or the number of oocytes obtained was 11-15 and 16-20, the CLBR of PCOS patients increased significantly after the 1st oocyte collection.

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.

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.

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.

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.