Fertility history and intentions of married women, China.

Objective: To estimate the proportion of married women in China who intend to become pregnant given the country's pronatalist population policy and to investigate fecundity, with an emphasis on the influence of socioeconomic factors. Methods: A nationally representative survey of 12 815 married women aged 20 to 49 years (mean: 36.8 years) was conducted during 2019 and 2020. All completed questionnaires, 10 115 gave blood samples and 11 710 underwent pelvic ultrasound examination. Fertility intention was the desire or intent to become pregnant combined with engagement in unprotected sexual intercourse. We defined infertility as the failure to achieve pregnancy after 12 months or more of unprotected intercourse. We considered an anti-Müllerian hormone level < 1.1 ng/mL and an antral follicular count < 7 as indicating an abnormal ovarian reserve. Findings: Fertility intentions were reported by 11.9% of women overall but by only 6.1% of current mothers (weighted percentages). Fertility intention was significantly less likely among women in metropolises (odds ratio, OR: 0.38; 95% confidence interval, CI: 0.31-0.45) and those with a higher educational level (OR: 0.74; 95% CI: 0.62-0.88). Overall, 18.0% had experienced infertility at any time and almost 30% had an abnormal ovarian reserve on assessment. An abnormal ovarian reserve and infertility were less likely in women in metropolises (P < 0.05) but more likely in obese women (P < 0.05). Conclusion: The willingness of Chinese married women to give birth remained low, even with relaxation of the one-child policy.

A Bayesian network model for prediction of low or failed fertilization in assisted reproductive technology based on a large clinical real-world data.

STUDY QUESTION: To construct prediction models based on the Bayesian network (BN) learning method for the probability of fertilization failure (including low fertilization rate [LRF] and total fertilization failure [TFF]) in assisted reproductive technology (ART) treatment. A BN model was developed to predict TFF/LFR. The model showed relatively high calibration in external validation, which could facilitate the identification of risk factors for fertilization disorders and improve the efficiency of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. WHAT IS KNOWN ALREADY: The prediction of TFF/LFR is very complex. Although some studies attempted to construct prediction models for TFF/LRF, most of the reported models were based on limited variables and traditional regression-based models, which are unsuitable for analyzing real-world clinical data. Therefore, none of the reported models have been widely used in routine clinical practice. To date, BN modeling analysis is a prominent and increasingly popular machine learning method that is powerful in dealing with dynamic and complex real-world data. STUDY DESIGN, SIZE, DURATION: A retrospective study was performed with 106,640 fresh embryo IVF/ICSI cycles from 2009 to 2019 in one of China's largest reproductive health centers. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 106, 640 cycles were included in this study, including 97,102 controls, 4,339 LFR cases, and 5,199 TFF cases. Twenty-four predictors were initially included, including 13 female-related variables, five male-related variables, and six variables related to IVF/ICSI treatment. BN modeling analysis with tenfold cross-validation was performed to construct the predictive model for TFF/LFR. The receiver operating characteristic (ROC) curves and the corresponding area under the curves (AUCs) were used to evaluate the performance of the BN model. MAIN RESULTS AND THE ROLE OF CHANCE: All twenty-four predictors were first organized into seven hierarchical layers in a theoretical BN model, according to prior knowledge from previous literature and clinical practice. A machine-learning BN model was generated based on real-world clinical data, containing a total of eighteen predictors, of which the infertility type, ART method, and number of retrieved oocytes directly influence the probabilities of LFR/TFF. The prediction accuracy of the BN model was 91.7%. The AUC of the TFF versus control groups was 0.779 (95% CI: 0.766-0.791), with a sensitivity of 71.2% and specificity of 70.1%; the AUC of of TFF versus LFR groups was 0.807 (95% CI: 0.790-0.824), with a sensitivity of 49.0% and specificity of 99.0%. LIMITATIONS, REASON FOR CAUTION: First, our study was based on clinical data from a single center, and the results of this study should be further verified by external data. In addition, some critical data (e.g., the detailed IVF laboratory parameters of the sperm and oocytes used for insemination) were not available in this study, which should be given full consideration when further improving the performance of the BN model. WIDER IMPLICATIONS OF THE FINDINGS: Based on extensive clinical real-world data, we developed a BN model to predict the probabilities of fertilization failures in ART, which provides new clues for clinical decision-making support for clinicians in formulating personalized treatment plans and further improving ART treatment outcomes. STUDY FUNDING/COMPETING INTEREST(S): Dr. Y. Wang was supported by grants from the Beijing Municipal Science & Technology Commission (Z191100006619086). We declare that there are no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Maternal and neonatal outcomes following blastocyst biopsy for PGT in single vitrified-warmed embryo transfer cycles.

RESEARCH QUESTION: Does blastocyst biopsy for preimplantation genetic testing (PGT) increase the risk of adverse maternal and neonatal outcomes? STUDY DESIGN: Retrospective cohort study of 5097 single vitrified-warmed blastocyst transfer cycles from January 2016 to December 2018, with 2061 cycles in the biopsied group and 3036 cycles in the unbiopsied group enrolled in the analyses. Maternal and neonatal outcomes were compared between the two groups. RESULTS: The live birth rate in the biopsied group (41.1%) was significantly higher than that in the unbiopsied group (35.6%, adjusted odds ratio [aOR] 1.27, 95% confidence interval [CI] 1.05-1.54, P = 0.012) after adjusting for maternal age, maternal body mass index, gravidity, parity, infertility diagnosis, timing of blastocyst transfer, blastocyst quality, regimen of endometrial preparation, endometrial thickness before transfer and treatment year. The rates of total pregnancy loss (25.4% versus 32.2%, aOR 0.69, 95% CI 0.52-0.91, P = 0.008) and early miscarriage (12.1% versus 17.3%, aOR 0.56, 95% CI 0.38-0.83, P = 0.004) were significantly lower in the biopsied group than in the unbiopsied group. No significant differences were found in sex ratio or the risks of hypertensive disorders in pregnancy, diabetes in pregnancy, placenta previa, preterm premature rupture of membranes, low birthweight, very low birthweight, macrosomia, small for gestational age, large for gestational age or birth defects between the two groups. When the subgroup analyses were conducted based on different types of PGT, similar patterns were found for all types. CONCLUSION: Blastocyst biopsy might not increase the risks of adverse maternal and neonatal outcomes in the short term.

Age-specific random day serum antimüllerian hormone reference values for women of reproductive age in the general population: a large Chinese nationwide population-based survey.

BACKGROUND: Antimüllerian hormone, the most reliable biomarker of ovarian reserve, is widely used in various clinical situations. Antimüllerian hormone levels consistently decrease with age. However, there is no standard, age-specific reference values for antimüllerian hormone in women of reproductive age, which limits its application. OBJECTIVE: This study aimed to establish age-specific antimüllerian hormone percentile reference values for women of reproductive age. STUDY DESIGN: A nationwide, population-based cross-sectional survey was conducted between May 2019 and April 2021 in 15 provinces and municipalities in mainland China. A total of 10,053 eligible women aged 20 to 49 years were selected using a multistage stratified sampling procedure. Women who were pregnant, had undergone ovarian surgery, took hormone drugs in the past 3 months, or had an antimüllerian hormone outlier value were excluded from establishing antimüllerian hormone percentile reference values. Serum antimüllerian hormone concentrations were measured using ultrasensitive, 2-site enzyme-linked immunosorbent assays (Ansh Lab, Webster, TX) in the Reproductive Endocrinology Laboratory of Peking University Third Hospital. Generalized additive models for location scale and shape with the Box-Cox t original distribution were used to estimate the fitted antimüllerian hormone percentile reference values. RESULTS: A total of 9112 eligible women aged 21 to 49 years were included in the fitting model. The fitted 50th (2.5th-97.5th) percentiles of antimüllerian hormone values for women aged 21, 25, 30, 35, 40, 45, and 49 years were 4.83 (0.79-18.41), 4.47 (0.72-16.58), 3.67 (0.50-13.82), 2.59 (0.24-10.35), 1.35 (0.05-6.68), 0.33 (<0.01 to 3.40), and 0.04 (<0.01 to 1.77) ng/mL, respectively. The population-based decline rate of antimüllerian hormone accelerated with increasing age, especially age >35 years. The magnitude of the decline of the 25th antimüllerian hormone percentile curve was greater than that of the 75th percentile curve. CONCLUSION: This study established age-specific antimüllerian hormone percentile reference values for women of reproductive age based on a large representative sample of the general population and described antimüllerian hormone changes. These findings may facilitate antimüllerian hormone application in clinical practices.

Identification of key genes in benign prostatic hyperplasia using bioinformatics analysis.

PURPOSE: This study aimed to identify differentially expressed genes (DEGs) and pathways in benign prostatic hyperplasia (BPH) by comprehensive bioinformatics analysis. METHODS: Data of the gene expression microarray (GSE6099) were downloaded from GEO database. DEGs were obtained by GEO2R. Functional and enrichment analyses of selected genes were performed using DAVID database. Protein-protein interaction network was constructed through STRING. Anterior gradient 2 (ARG2) and lumican (LUM) staining in paraffin-embedded specimens from BPH and normal prostate (NP) were detected by immunohistochemistry (IHC). Differences between groups were analyzed by the Student's t test. RESULTS: A total of 24 epithelial DEGs and 39 stromal DEGs were determined. The GO analysis results showed that epithelial DEGs between BPH and NP were enriched in biological processes of glucose metabolic process, glucose homeostasis and negative regulation of Rho protein signal transduction. For DEGs in stroma, enriched biological processes included response to ischemia, antigen processing and presentation, cartilage development, T cell costimulation and energy reserve metabolic process. ARG2, as one of the epithelial DEGs, was mainly located in epithelial cells of prostate. In addition, LUM is primarily expressed in the stroma. We further confirmed that compared with NP, the BPH have the lower ARG2 protein level (p = 0.029) and higher LUM protein level (p = 0.003) using IHC. CONCLUSIONS: Our study indicated that there are possible differentially expressed genes in epithelial and stromal cells, such as ARG2 and LUM, which may provide a novel insight for the pathogenesis of BPH.

Efficacy and safety of prostatic artery embolization for benign prostatic hyperplasia: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate the efficacy and safety of prostatic artery embolization (PAE) vs. transurethral resection of the prostate (TURP) in patients affected by benign prostatic hyperplasia (BPH). We also reviewed mean changes from baseline in PAE at selected follow-up points. METHODS: PubMed, Web of Science, and Embase were searched up to May 1, 2020. Randomized controlled trials on PAE were collected according to specific inclusion and exclusion criteria. Meta-analyses were performed using RevMan 5.3, STATA 14, and GraphPad Prism 8. Pooled patient-reported scores and functional outcomes were calculated by using a fixed or random-effect model. RESULTS: Eleven articles met our selection criteria and ten independent patient series were included in the final analysis. Pooled estimates suggested no significant difference between TURP and PAE for patient-reported outcomes including International Prostate Symptom Score (2.32 (- 0.44 to 5.09)) and quality of life (0.18 (- 0.41 to 0.77)) at 12 months. PAE was less effective regarding improvements in most functional outcomes such as maximum flow rate, prostate volume, and prostate-specific antigen. Moreover, PAE may be associated with relatively fewer complications, lower cost, and shorter hospitalization. After the PAE procedure, the overall weighted mean differences for all outcomes except sexual health scores were significantly improved from baseline during follow-up to 24 months. CONCLUSION: PAE is non-inferior to TURP with regard to improving patient-reported outcomes, though most functional parameters undergo more changes after TURP than after PAE. Moreover, PAE can significantly continue to relieve symptoms for 24 months without causing serious complications. KEY POINTS: • PAE is as effective as TURP in improving subjective symptom scores, with fewer complications and shorter hospitalization times. • PAE is inferior to TURP in the improvement of most functional outcomes. • Improvements due to PAE are durable during follow-up to 24 months.

Potential risks of SARS-CoV-2 infection on reproductive health.

The outbreak of 2019 novel coronavirus disease (COVID-19) has become a major pandemic threat worldwide. Such a public health emergency can greatly impact various aspects of people's health and lives. This paper focuses on its potential risks for reproductive health, including the reproductive system and its functioning, as well as gamete and embryo development, which could be affected by the virus itself, drug treatments, chemical disinfectants and psychological effects related to panic during the COVID-19 outbreak.

Mixed and single effects of endocrine disrupting chemicals in follicular fluid on likelihood of diminished ovarian reserve: A case-control study.

Endocrine-disrupting chemicals (EDCs) are a group of the most widely spread pollutants. Their impacts on reproductive health have become public concerns. Diminished ovarian reserve (DOR) is a disorder of ovarian function. Associations between EDC and DOR have been inconsistent. Very little research investigated the joint effects of multiple EDCs. Here, we performed a case-control study among 64 DOR women and 86 controls. Twenty-one EDC chemicals were assessed in follicular fluid, including parabens, phenols, phthalates and poly-fluoroalkyl substances. Both mixed and single effects of EDCs on DOR were evaluated and validated with a Bayesian kernel machine and logistic regressions. We found that the likelihood of DOR significantly increased with rising levels of the 21-EDC mixture, with an odds ratio (OR) and 95% confidence interval (CI) of 2.12 (1.17-3.83) for the 75th percentile compared to its median level. The overall effect was higher than effects of each subgroup. BP4, MECPP, and PFHxA were driving the association to the mixture, and their single effects were validated, with individual ORs of 8.25 (95%CI:3.45-12.21), 1.92 (95%CI:1.02-4.09), and 1.84 (95%CI:1.08-3.86), respectively. In conclusion, we provided new pollutant markers for DOR and emphasized the importance of the effects of EDC mixtures on female reproductive health.

Synthetic Phenolic Antioxidants and Their Metabolites in Follicular Fluid and Association with Diminished Ovarian Reserve: A Case-Control Study.

BACKGROUND: Diminished/decreased ovarian reserve (DOR) is a disorder of ovarian function, which severely affects women's reproductive health. Accumulating evidence has found that adverse environmental factors can affect ovarian function. However, whether synthetic phenolic antioxidants (SPAs) exposure is associated with DOR is still unknown. OBJECTIVES: We explored whether concentrations of SPAs and their metabolites are associated with DOR. METHODS: A case-control study was conducted from January 2019 to January 2020 in China. One hundred eighty-one women 20-44 years of age, with (case group, n=63) and without DOR (control group, n=118) were included in our study. The follicular fluid concentrations of typical SPAs and their metabolites were measured, including butylated hydroxyanisole (BHA), tert-butylhydroquinone (TBHQ), butylated hydroxytoluene (BHT), and five BHT metabolites [3,5-di-tert-butyl-4-hydroxy-benzylalcohol (BHT-OH), 3,5-di-tert-butyl-4-hydroxybenzaldehyde (BHT-CHO), 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHT-COOH), 2,6-di-tert-butyl-1,4-benzoquinone (BHT-Q), and 2,6-di-tert-butyl-4-hydroxy-4-methylcyclohexa-2,5-dien-1-one (BHT-quinol)]. Information about serum basal concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH) and the basal antral follicle count (AFC) was collected. RESULTS: The measured frequencies of BHA, TBHQ, BHT, BHT-OH, BHT-CHO, BHT-COOH, BHT-Q, and BHT-quinol in follicular fluid were 1.7%, 2.2%, 40.3%, 46.4%, 57.5%, 100%, 64.6%, and 49.2%, respectively. The concentrations of BHT-CHO (0.49 ng/mL vs. 0.12 ng/mL, p=0.041), BHT-COOH (0.45 ng/mL vs. 0.28 ng/mL, p<0.001), BHT-Q (0.70 ng/mL vs. 0.13 ng/mL, p<0.001), and the sum of five BHT metabolites (Σ5metabolites; 1.79 ng/mL vs. 1.0 ng/mL, p<0.001) in the case group were significantly higher than those in the control group. The risk of DOR was further analyzed according to the tertiles of chemical concentration. Compared with the low levels of BHT metabolites, the adjusted odds ratios (ORs) for DOR were significantly increased in the high levels of BHT-CHO [OR=3.19, 95% confidence interval (CI): 1.22, 8.31, p=0.018], BHT-COOH [OR=4.73 (95% CI: 1.63, 13.71), p=0.004], and BHT-Q [OR=4.48 (95% CI: 1.69, 11.86), p=0.003] after adjusting for age, body mass index, education, infertility type, triglycerides, and total cholesterol. Moreover, compared with the low level of Σ5metabolites, increased adjusted ORs for DOR were found both in the middle level [OR=4.11 (95% CI: 1.44, 11.75), p=0.008] and high level [OR=5.51 (95% CI: 1.81, 16.77), p=0.003], showing an obvious dose-response relationship (pTrend=0.003). CONCLUSION: In this study, we report the measured frequency and concentrations of BHA, TBHQ, BHT, and their metabolites in follicular fluid. Moreover, we found the concentrations of BHT metabolites, especially BHT-CHO, BHT-COOH, and BHT-Q, are positively associated with the increased risk of DOR. https://doi.org/10.1289/EHP11309.

Association between maternal MTHFR C677T/A1298C combination polymorphisms and IVF/ICSI outcomes: a retrospective cohort study.

STUDY QUESTION: What are the roles of maternal 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C combination polymorphisms on the embryological and clinical outcomes of IVF/ICSI? SUMMARY ANSWER: Our study reveals for the first time that the oocyte maturation potential gradually decreases with a reduction of maternal MTHFR activity determined by combined C677T/A1298C polymorphisms, while embryo quality was worse in women with intermediate MTHFR activity. WHAT IS KNOWN ALREADY: Although many previous studies have explored the association between MTHFR polymorphisms and IVF/ICSI outcomes, the results remain contradictory due to inadequate samples, no adjustment for potential confounders and/or the study of C677T and A1298C separately. Few studies have systematically investigated the exact role of MTHFR activity determined by combined C677T/A1298C polymorphisms on the embryological and clinical outcomes of IVF/ICSI. STUDY DESIGN SIZE DURATION: This is a retrospective cohort study investigating 1160 women who were referred for MTHFR genotyping and IVF/ICSI treatment at Peking University Third Hospital from May 2017 to May 2020. PARTICIPANTS/MATERIALS SETTING METHODS: Women who were referred for MTHFR genotyping and their first IVF/ICSI treatment at our hospital were included and those undergoing preimplantation genetic testing cycles were excluded. The included women were divided into different cohorts according to their C677T, A1298C and combined C677T/A1298C genotypes. The embryological outcomes, including oocytes retrieved, metaphase II oocytes, oocyte maturation rate, normal fertilization rate and transplantable embryo rate, were evaluated by generalized linear regression models. The clinical outcomes, including biochemical pregnancy rate, clinical pregnancy rate and live birth rate, were evaluated by log-binomial regression models. All outcomes were adjusted for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Women with the combined 677TT/1298AA genotype (hereafter abbreviated as TT/AA, as with other combined genotypes), whose enzyme activity was the lowest, had a lower oocyte maturation rate compared with those with the wild-type genotype (P = 0.007). Moreover, the oocyte maturation rate decreased linearly with the decline in MTHFR enzyme activity determined by combined C677T/A1298C genotypes (P-trend = 0.001). The combined CC/AC, CC/CC&CT/AA and CT/AC genotypes with intermediate enzyme activity were associated with a lower transplantable embryo rate (P = 0.013, 0.030 and 0.039, respectively). The differences in clinical outcomes between women with wild-type genotype and combined C677T/A1298C variant genotypes were not significant. LIMITATIONS REASONS FOR CAUTION: Our study population had comparable embryological outcomes but worse clinical outcomes than other women undergoing IVF/ICSI treatment at our hospital. Therefore, the results related to the clinical outcomes should be generalized with caution. In addition, we did not detect the folate concentration of each patient during pregnancy. However, this might not have much influence on our results because almost all of our study participants took sufficient folic acid around pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: We provide a holistic view of the effect of MTHFR C677T and A1298C polymorphisms on the IVF/ICSI outcomes, which can contribute to providing reasonable folic acid supplementation suggestions for women with different MTHFR genotypes, especially for those with a low oocyte maturation rate and/or low embryo quality. STUDY FUNDING/COMPETING INTERESTS: This work was funded by the National Natural Science Foundation of China (31871447, and 82101677), the National Key Research and Development Program (2019YFA0801400) and the Natural Science Foundation of Beijing Municipality (7202226). The authors declare that they have no competing interests. TRIAL REGISTRATION NUMBER: N/A.