Daily Exposure to Environmental Volatile Organic Compounds Triggers Oxidative Damage: Evidence from a Large-Scale Survey in China.

Volatile organic compounds (VOCs) are ubiquitous environmental pollutants and have been implicated in adverse health outcomes. In this study, concentrations of 11 VOC metabolites (mVOCs) and three oxidative stress biomarkers (8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxo-7,8-dihydro-guanosine, and dityrosine) were determined in 205 urine samples collected from 12 cities across mainland China. Urinary ∑11mVOC concentrations ranged from 498 to 1660 ng/mL, with a geometric mean (GM) value of 1070 ng/mL. The factorial analysis revealed that cooking, solvents, and vehicle emissions were the three primary sources of VOC exposure. A significant regional variation was clearly found in ∑11mVOC concentrations across four regions in China, with high urine VOC concentrations found in North and South China (GM: 1450 and 1340 ng/mL). The multiple linear regression model revealed that most mVOCs were significantly positively correlated with three oxidative stress markers (ß range: 0.06-0.22). Mixture effect regression showed that isoprene, crotonaldehyde, acrolein, and benzene were the strongest contributors to oxidative stress. Approximately 80% of the participants have HQ values greater than 1.0 for 1,3-butadiene and benzene, suggesting that their exposure doses were close to potential adverse health effects. Our findings provide comprehensive information on human exposure and potential health risks of VOCs in China.

Interleukin-4 activates the PI3K/AKT signaling to promote apoptosis and inhibit the proliferation of granulosa cells.

The inflammatory microenvironment has been demonstrated to play a role in folliculogenesis, ovulation and premature ovarian failure (POF), as well as infertility. In this study, we aimed to explore the role of inflammation in modulating growth and apoptosis in granulosa cells (GCs), the main components of ovarian follicles. ELISA was used to analyze the levels of inflammatory factors (IL-1ß, IL-4, IL-6 and IL-10) in follicular fluid samples and GCs derived from POF patients and healthy normal individuals. CCK-8, flow cytometry and TUNEL assays were used to assess the effect of IL-4 on GC growth and apoptosis. Western blotting was used to examine the effect of IL-4 on the activation of PI3K/Akt, Erk1/2 and Jnk signaling. The results showed that IL-4, IL-1ß and IL-6 levels were increased in follicular fluid samples and GCs derived from POF patients compared with those from healthy individuals. GC growth was weakened when cells were treated with IL-4, while apoptosis was increased. In addition, IL-4 increased the level of p-Akt/Akt in GCs. In addition, LY294002, an inhibitor of PI3K, abolished the effect of IL-4 by inhibiting GC growth and promoting apoptosis. In summary, this study demonstrated that IL-4 levels were increased in POF samples and that IL-4 could inhibit GC growth and induce GC apoptosis by activating PI3K/Akt signaling.

Serum anti-Müllerian hormone levels are associated with early miscarriage in the IVF/ICSI fresh cycle.

BACKGROUND: Anti-Müllerian hormone (AMH) is used as a biomarker to estimate ovarian reserve. The relationship between AMH and early miscarriage of in vitro fertilization (IVF) is still inconclusive. This study aimed to explore whether serum AMH levels are associated with early miscarriage rates after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) with fresh embryo transfer (ET). METHODS: This retrospective cohort study included 2246 patients undergoing their first oocyte retrievals for IVF/ICSI with fresh embryos transferred to Tianjin Central Hospital of Gynecology Obstetrics between May 2018 and March 2020. The serum AMH levels of the patients were measured within 12 months before the IVF/ICSI cycles. All women were divided into a low-AMH group, medium-AMH group and high-AMH group. Binary logistic regression was applied to confirm whether the serum AMH level was associated with the risk of early miscarriage independent of potential confounders, such as age, body mass index (BMI), duration of infertility, main diagnosis, history of internal medicine diseases, number of oocytes retrieved and high-quality embryo rate. RESULTS: The early miscarriage rate was significantly lower in the medium-AMH group than in either the low-AMH or high-AMH group among young (< 35 years) women (P = 0.015). In women above 35 years of age, the early miscarriage rates in the three AMH groups were not significantly different. Young women with high serum AMH levels had a significantly higher risk of early miscarriage regardless of age or other potential confounders (adjusted odds ratio (OR) 2.382, 95% confidence interval (CI) 1.246 to 4.553, P = 0.009). The results remained similar after restricting the analysis to women without polycystic ovary syndrome (PCOS). CONCLUSIONS: With a high AMH level, young women had a higher risk of early miscarriage than women with a medium AMH level in their first IVF/ICSI treatment. In young women, serum AMH levels were independently associated with the risk of early miscarriage after IVF-ET treatment. Serum AMH levels might be a valuable marker to estimate the risk of early miscarriage. It is worth noting to the clinical value of AMH.

Adverse obstetric and perinatal outcomes in 2333 singleton pregnancies conceived after different endometrial preparation protocols: a retrospective study in China.

BACKGROUP: Frozen-thawed embryo transfer is rising worldwide. One adverse effect of programmed frozen embryo transfer (FET) reported in some studies is an increased risk of adverse obstetric and perinatal outcomes. Meanwhile, body mass index (BMI) also has adverse effect on obstetric and perinatal outcomes. In this study, we investigated that the influence of different endometrial preparation protocols on obstetric and perinatal outcomes and the role of BMI in it. METHOD: This retrospective cohort study included 2333 singleton deliveries after frozen-thaw embryo transfer at our centre between 2014 and 2021, including 550 cycles with programmed FET, 1783 cycles with true natural cycle FET (tNC-FET). In further analysis according to BMI grouped by Asian criterion, group A (18.5 kg/m2 ≤ BMI < 24.00 kg/m2) included 1257 subjects, group B (24 kg/m2 ≤ BMI < 28.00 kg/m2) included 503 subjects and group C (BMI ≥ 28 kg/m2) included 573 subjects. Baseline characteristics of the two groups were compared and analyzed. Binary logistic regression analyses were performed to explore the association between obstetric and perinatal outcomes and endometrial preparation protocols. RESULTS: There were no significant differences in the placenta previa, gestational diabetes mellitus(GDM), preterm premature rupture of membranes (PPROM), cesarean section (CS) and macrosomia between the tNC-FET and programmed FET groups (P > 0.05). The programmed FET cycles were associated to a higher risk of pregnancy-induced hypertension (PIH) compared with the tNC-FET cycles (7.3% vs 4.4%, crude OR 1.71[1.16-2.54]; adjusted OR 1.845[1.03-3.30]). After dividing the patients into three groups according to the BMI, The programmed FET cycles were associated to a higher risk of PIH in group C (14.4% vs 6.2%, crude OR 2.55 [1.42-4.55]; adjusted OR 4.71 [1.77-12.55]) compared with the tNC-FET cycles. But there was no statistically significant difference in group A and group B. Programmed FET group compared with the tNC-FET group, the risk of PIH increase as the body mass index increase. CONCLUSION: This study showed a tendency toward increasing risk of PIH in programmed FET cycle compared with the tNC-FET cycle, and the risk of PIH increases as BMI increases. Increased risk of preterm birth and low birth weight is linked to increased risk of PIH.

Previous caesarean delivery and the presence of caesarean scar defects could affect pregnancy outcomes after in vitro fertilization frozen-thawed embryo transfer: a retrospective cohort study.

BACKGROUND: Due to various iatrogenic and social factors, the global caesarean delivery (CD) rate has risen sharply in the past 30 years. It is more complicated and dangerous for women with a scarred uterus to experience pregnancy again than for women with a previous vaginal delivery (VD). In this study we investigated the impact of previous caesarean delivery (CD) and caesarean scar defects (CSDs) on pregnancy outcomes after in vitro fertilization frozen-thawed embryo transfer (IVF-FET). METHODS: We conducted a retrospective cohort study that included 1122 women aged < 40 years who had a history of only one parturition (after 28 weeks of pregnancy) and who underwent their first FET cycle between January 2014 and January 2020. Patients were divided into the CD group, VD group, and CSD group. Thereafter, according to the number of transferred embryos, the CD, VD, and CSD groups were divided into the single embryo transfer (SET) group and the double embryo transfer (DET) group. Outcome measures in this study were live birth, clinical pregnancy, multiple pregnancy, ectopic pregnancy, pregnancy loss, pregnancy complications, preterm birth, and neonatal birth weight. Multivariate logistic regression was performed to evaluate the relationship between pregnancy outcomes and CD. RESULTS: In SET patients, the clinical pregnancy and live birth rates were decreased in the CSD group compared with the VD and CD groups. In DET patients, the clinical pregnancy and live birth rates were significantly lower in theCSD group than in the CD and VD groups. After adjustment for confounders, previous CD and CSD were associated with a significantly lower clinical pregnancy rate and live birth rate than previous VD in the total sample. This effect was observed in DET patients, but not in SET patients. Additionally, DET patients with previous CD had a significantly higher multiple pregnancy rate (AOR = 0.47, 95% CI = 0.29, 0.75, P = 0.002) than those with previous VD, but no significant associations were observed in CSD and multiple pregnancies (AOR = 0.55, 95% CI = 0.23, 1.34, P = 0.192) between DET patients with CD and those with VD after adjusting for potential confounders. CONCLUSIONS: Our study showed that during an FET cycle, previous CD and the presence of a CSD could negatively affect pregnancy outcomes especially in DET patients.

New AMH cutoff values for warning of decreased ovarian response based on MCL characteristics in young women: a retrospective study using a propensity score-matching analysis.

BACKGROUND: Menstrual cycle length (MCL) and ovarian response varies widely among women of childbearing age. They are provided with anti-Mu¨llerian hormone (AMH) cutoffs for "normal" and "weakened" ovarian responses, which give an early warning of the onset of decreased ovarian response. METHODS: This was a retrospective study in women aged 21 to 35 years with MCLs of 21-35 days receiving in vitro fertilization (IVF) treatment at Center for Reproductive Medicine from October 2018 to October 2021. Intergroup variables were balanced using propensity score matching based on age and BMI, and each case patient (patients with MCLs of 21-25 days) was matched with three control patients (patients with MCLs of 26-35 days). A receiver operating characteristic curve was used to calculate the AMH cutoff values. RESULTS: We included 135 patients with MCLs of 21-25 days and 405 matched control patients with MCLs of 26-35 days who received IVF treatment. The case group had significantly fewer retrieved oocytes, lower AMH values and higher initial and total Gonadotropin (Gn) levels during controlled ovarian hyperstimulation than the control group. The ovarian response began to decrease when AMH was < 3.5 ng/ml in the case group and < 2.7 ng/ml in the control group. CONCLUSION: In young women with MCLs of 21-35 days, short MCL was negatively correlated with AMH values and the number of oocytes retrieved. In patients with MCLs of 21-25 days and 26-35 days, the AMH cutoff values corresponding to the onset of decreased ovarian response were 3.5 ng/ml and 2.7 ng/ml, respectively.

Hysteroscopic resection of type 3 fibroids could improve the pregnancy outcomes in infertile women: a case-control study.

BACKGROUND: Type 3 fibroids are a special subtype of intramural fibroids that are likely to affect the pregnancy outcomes of assisted reproductive techniques. Hysteroscopic resection is a treatment for type 3 fibroids, but there has few study of its efficacy to date. In this study we evaluated the effect of hysteroscopic resection of type 3 fibroids on the pregnancy outcomes in infertile women. METHODS: This retrospective case-control study was conducted from January 1, 2014 to June 30, 2021. Patients who underwent IVF-ICSI in our unit were divided into a type 3 fibroid group and a hysteroscopic myomectomy group. The inclusion criteria for the type 3 fibroid group and the hysteroscopic myomectomy group were as follows: 1) age ≤ 40 years; 2) fibroid diameter or total fibroid diameter > 2.0 cm. The following exclusion criteria were used: 1) oocyte donor treatment cycles and 2) presence of chromosomal abnormalities; 3) history of other uterine surgery; 4) presence of intracavitary lesions, including submucosal fibroids; 5) single fibroid > 5.0 cm; 6) cervical fibroids; 7) unclear ultrasound description of fibroids; 8) preimplantation genetic testing was performed and 9) congenital or acquired uterine malformations. The control group in our study was selected from patients who were treated with IVF only because of fallopian tube factors. According to the age of the type 3 fibroid group and hysteroscopic myomectomy group, random sampling was carried out in the patients between 25 and 47 years of age to determine a control group. The outcomes measured included the average transfer times to live birth, cumulative clinical pregnancy rate, and cumulative live birth rate. RESULTS: A total of 302 cycles were enrolled in our study, including 125 cycles with type 3 fibroids, 122 cycles with hysteroscopic myomectomy, and 139 cycles of control patients. The average transfer times to live birth were significantly higher in the type 3 fibroid group than in the other two groups. The frequency of cumulative live births in the type 3 fibroid group was significantly lower than that in the control group. Compared with the control group, the hysteroscopic myomectomy patients had no statistically significant differences in the cumulative clinical pregnancy rate and cumulative live birth rate. CONCLUSIONS: Type 3 fibroids significantly reduced the cumulative live birth rate of IVF patients. Ultrasound-guided hysteroscopic myomectomy can be used as a treatment for type 3 fibroids and could improve the pregnancy outcomes in infertile women.

The association of serum phthalate metabolites with biomarkers of ovarian reserve in women of childbearing age.

Phthalates (PAEs) are widely used plasticizers drawing increasing concern due to reproductive toxicity. However, studies on serum PAEs metabolites (mPAEs) and their associations with human ovarian function remain very scarce. In this study, from April 2019 to August 2020, a total of 297 women of childbearing age were recruited in Tianjin, China. Eleven mPAEs were analyzed in serum samples and eight mPAEs were detected at frequencies > 65% with median concentrations of 0.43-15.3 ng/mL. In multinomial logistic analysis, an increase in serum mono (2-isobutyl) phthalate (miBP) was associated with decline in antral follicle count (AFC) (OR=1.26, 95% CI: 0.99, 1.61) and 5-mono-(2-ethyl-5-hydroxyhexyl) phthalate (mEHHP) was significantly associated with AFC increase (OR=1.43, 95% CI: 1.06, 1.92), which were aligned with the associations found between mPAEs and AMH through generalized linear regression. In multiple linear regression models, per 10% increase in serum mono (2-ethylhexyl) phthalate (mEHP), mono (2-ethyl-5-oxohexyl) phthalate (mEOHP) (oxo-mEHP), and principal component 1 featured for high concentrations of mono-n-butyl phthalate (mBP), miBP and mEHP were associated with 0.15 (95% CI: -0.29, -0.02), 0.01 (95% CI: -0.01, 0.00) and 0.01 (95% CI: -0.02, 0.00) ln-unit decrease in estradiol (E2) levels, respectively, while mono-[(2-carboxymethyl) hexyl] phthalate (mCMHP) (carboxymethyl-mEHP) was positively associated with 0.05 ln-unit increase of E2 (95% CI: 0.02, 0.08). The observed negative associations between mPAEs and the Anti-Müllerian hormone (AMH) also aligned with the change in AFC. Generalized linear regression also revealed nonlinear associations between mono-ethyl phthalate (mEP), mCMHP and follicle-stimulating hormone (FSH). Overall, serum mEHP and its metabolites were negatively associated with E2. miBP was negatively associated with AFC. The nonlinear associations between mPAEs and FSH, and AMH need further study.

Heterotopic cervical pregnancy: Case report and literature review.

Cervical pregnancy (CP) is a rare form of ectopic pregnancy (EP) in which the embryo implants and grows inside the endocervical canal. Heterotopic cervical pregnancy is an even rare form of EP, in which at least two embryos are simultaneously implanted in different sites and only one in the uterine cavity. Although many treatment approaches are available, the ideal management remains unclear. Here, we describe two cases of CP caused by assisted reproductive technologies (ART). One case underwent fertilization with intracytoplasmic sperm injection (ICSI) for male factor infertility, and the other was frozen-thawed embryo transfer (FET) following conventional in vitro fertilization (IVF). Both cases were successfully treated with ultrasound-guided cervical pregnancy aspiration, and intrauterine pregnancies were effectively protected. To the best of our knowledge, these two were rare case reports use aspiration without additional methods and intrauterine pregnancy achieved live birth.

Caesarean section defects may affect pregnancy outcomes after in vitro fertilization-embryo transfer: a retrospective study.

BACKGROUND: Caesarean section rates are rising worldwide. One adverse effect of caesarean section reported in some studies is an increased risk of subfertility. Only a few studies have assessed the relationship between the previous mode of delivery and in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) reproductive outcomes. In this study, we primarily investigated the impact of a history of caesarean section with or without defects on IVF/ICSI-ET outcomes compared to a vaginal delivery history. METHODS: This retrospective study included 834 women who had a IVF or ICSI treatment at our centre between 2015 and 2019 with a delivery history. In total, 401 women with a previous vaginal delivery (VD) were assigned to the VD group, and 433 women with a history of delivery by caesarean section were included, among whom 359 had a caesarean scar (CS) without a defect and were assigned to the CS group and 74 had a caesarean section defect (CSD) and were assigned to the CSD group. Baseline characteristics of the three groups were compared and analysed. Binary logistic regression analyses were performed to explore the association between clinical outcomes and different delivery modes. RESULTS: There were no significant differences in the live birth rate, biochemical pregnancy rate, clinical pregnancy rate, mean implantation rate or abnormal pregnancy rate between the CS and VD groups However, the live birth rate and mean implantation rate in the CSD group were significantly lower than those in the VD group (21.6 vs 36.4%, adjusted OR 0.50 [0.27-0.9]; 0.25 ± 0.39 vs 0.35 ± 0.41, adjusted OR 0.90 [0.81-0.99]). Among women aged ≤ 35 years, the subgroup analyses showed that the live birth rate, biochemical pregnancy rate, clinical pregnancy rate, and mean implantation rate in the CSD group were all significantly lower than those in the VD group (21.4 vs 45.8%, adjusted OR 0.35[0.15 ~ 0.85]; 38.1 vs 59.8%, adjusted OR 0.52[0.24-0.82]; 31.0 vs 55.6%, adjusted OR 0.43[0.19-0.92]; 0.27 ± 0.43 vs 0.43 ± 0.43, adjusted OR 0.85[0.43 ± 0.43]). For women older than 35 years, there was no statistically significant difference in any pregnancy outcome among the three groups. CONCLUSIONS: This study suggested that the existence of a CS without a defect does not decrease the live birth rate after IVF or ICSI compared with a previous VD. However, the presence of a CSD in women, especially young women (age ≤ 35 years), significantly impaired the chances of subsequent pregnancy.

SIRT1 induces resistance to apoptosis in human granulosa cells by activating the ERK pathway and inhibiting NF-κB signaling with anti-inflammatory functions.

SIRT1, a member of the sirtuin family, has recently emerged as a vital molecule in controlling ovarian function. The aims of the present study were to investigate SIRT1 expression and analyze SIRT1-mediated apoptosis in human granulosa cells (GCs). Human ovarian tissues were subjected to immunohistochemistry for localization of SIRT1 expression. SIRT1 knockdown in a human ovarian GC tumor line (COV434) was achieved by small interfering RNA, and the relationship between apoptosis and SIRT1 was assessed by quantitative reverse transcription polymerase chain reaction and western blotting. We further detected SIRT1 expression in human luteinized GCs. Associations among SIRT1 knockdown, SIRT1 stimulation (resveratrol) and expression of ERK1/2 and apoptotic regulatory proteins were analyzed in cell lines and luteinized GCs. Resveratrol downregulated the levels of nuclear factor (NF)-κB/p65, but this inhibitory effect was attenuated by suppressing SIRT1 activity. The NF-κB/p65 inhibitor pyrrolidine dithiocarbamate achieved similar anti-apoptosis effects. These results suggest that SIRT1 might play an anti-apoptotic role in apoptosis processes in GCs, possibly by sensing and regulating the ERK1/2 pathway, which has important clinical implications. Thus, our study provides a mechanistic link, whereby activation of SIRT1 function might help to sustain human reproduction by maintaining GCs as well as oocytes, offering a novel approach for developing a new class of therapeutic anti-inflammatory agents.

Discs large homologue 1 (Dlg1) coordinates mouse oocyte polarisation during maturation.

Mouse oocyte meiotic division requires the establishment of asymmetries in the oocyte before division, indicating the presence of polarity-establishing molecules. During mouse oocyte maturation proper orientation and positioning of the meiotic spindle at the oocyte cortex, as well as polarity in the oocyte cytoplasm and its oolemma, are necessary for the formation of functional haploid oocytes. Discs large homologue 1 (Dlg1) protein is a conserved protein that regulates cell polarity. In the present study, we found that Dlg1 was expressed at different stages of oocyte development. The localisation of Dlg1 during mouse oocyte maturation and its relationship with the cytoskeleton were analysed. Our data show that at the germinal vesicle stage, Dlg1 was present in the cytoplasm, prominently surrounding the germinal vesicle membrane. During maturation, Dlg1 became highly polarised by associating with the spindle and formed characteristic crescent-shaped accumulations under the cortex. Addition of nocodazole or cytochalasin B into the culture medium at different stages changed the localisation of Dlg1, indicating that the organisation of Dlg1 is a complex multi-step process and is dependent on microtubules and microfilaments. More importantly, we found that silencing of Dlg1 compromised the G2-M transition.

[Establishment of a novel HLA genotyping method for preimplantation genetic diagnonis using multiple displacement amplification-polymerase chain reaction-sequencing based technique].

OBJECTIVE: To establish a novel HLA genotyping method for preimplantation genetic diagnonis (PGD) using multiple displacement amplification-polymerase chain reaction-sequencing based technique (MDA-PCR-SBT). METHODS: Peripheral blood samples and 76 1PN, 2PN, 3PN discarded embryos from 9 couples were collected. The alleles of HLA-A, B, DR loci were detected from the MDA product with the PCR-SBT method. The HLA genotypes of the parental peripheral blood samples were analyzed with the same protocol. The genotypes of specific HLA region were evaluated for distinguishing the segregation of haplotypes among the family members, and primary HLA matching was performed between the embryos. RESULTS: The 76 embryos were subjected to MDA and 74 (97.4%) were successfully amplified. For the 34 embryos from the single blastomere group, the amplification rate was 94.1%, and for the 40 embryos in the two blastomeres group, the rate was 100%. The dropout rates for DQ allele and DR allele were 1.3% and 0, respectively. The positive rate for MDA in the single blastomere group was 100%, with the dropout rates for DQ allele and DR allele being 1.5% and 0, respectively. The positive rate of MDA for the two blastomere group was 100%, with the dropout rates for both DQ and DR alleles being 0. The recombination rate of fetal HLA was 20.2% (30/148). Due to the improper classification and abnormal fertilized embryos, the proportion of matched embryos HLA was 20.3% (15/74),which was lower than the theoretical value of 25%. CONCLUSION: PGD with HLA matching can facilitate creation of a HLA-identical donor (saviour child) for umbilical cord blood or bone marrow stem cells for its affected sibling with a genetic disease. Therefore, preimplantation HLA matching may provide a tool for couples desiring to conceive a potential donor progeny for transplantation for its sibling with a life-threatening disorder.

The impact of coronavirus disease 2019 on frozen-thawed embryo transfer outcomes.

Background: Coronavirus disease 2019 (COVID-19) has raised concerns about its potential effects on human fertility, particularly among individuals undergoing assisted reproductive therapy (ART). However, the impact of COVID-19 on female reproductive and assisted reproductive outcomes is unclear. In this study, we aimed to evaluate the effects of COVID-19 on pregnancy outcomes during frozen-thawed embryo transfer (FET) cycles. Methods: This retrospective cohort study included 327 enrolled patients who underwent FET cycles at a single reproductive centre. The study group consisted of patients treated between 1 January 2023 and 31 March 2023 who recently recovered from COVID-19. The embryos for transfer were generated prior to COVID-19 infection. The control group consisted of patients treated between 1 January 2021 and 31 March 2021 who were not infected and did not receive a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Demographic and cycle characteristics and outcomes were compared. Results: A total of 160 recovered women and 167 controls were included. The primary outcome-the live birth rate-was similar between the two groups (43.8% vs. 43.1%, P > 0.05). The secondary outcomes, such as the implantation rates (41.2% vs. 39.3%), biochemical pregnancy rates (56.3% vs. 56.3%), clinical pregnancy rates (52.5% vs. 52.1%), early abortion rates (8.3% vs. 12.6%) and ongoing pregnancy rates (46.9% vs. 44.3%), were also similar (P < 0.05). According to a logistic regression model, the live birth rate did not decrease after SARS-CoV-2 infection after adjusting for confounding factors (adjusted OR (95% CI) = 0.953 (0.597∼1.523)). Regardless of stratification by age or the number of embryos transferred, the differences remained nonsignificant. Subgroup logistic regression demonstrated that the time interval from infection to transplant had no significant influence on the live birth rate. Conclusions: SARS-CoV-2 infection after oocyte retrieval had no detrimental effect on subsequent FET outcomes.

Co-occurrence of phthalate and non-phthalate plasticizers in dust and hand wipes: A comparison of levels across various sources.

E-waste dismantlers' occupational exposure to plasticizers, particularly non-phthalate (NPAE) plasticizers, is poorly understood. This study monitored 11 phthalates (PAEs) and 16 NPAEs in dust and hand wipe samples from Central China e-waste workplace and ordinary homes. Concentrations of plasticizers in dust from e-waste dismantling workshops (median: 217 µg/g) were significantly lower than that from ordinary homes (462 µg/g; p < 0.01), however, the trend was similar but not significant in hand wipes from these two scenarios (50.2 vs. 72.3 µg/m2; p = 0.139). PAEs were still the dominant plasticizers, which is, on average, 5.46 and 3.58-fold higher than NPAEs. In all samples, di-(2ethylhexyl) phthalate (65.4%) and tri-octyl trimellitate (44.9%) were the most common PAE and NPAE plasticizers. Increasing dust concentrations of di-iso-nonyl ester 1,2-cyclohexane dicarboxylic acid, citrates and sebacates were significantly associated with their levels in worker's hand wipe, by contrast, this trend was not found in general population. Dust ingestion was the main channel, followed by hand-to-mouth contact, all participants' daily plasticizer intakes (median: 154 ng/kg bw/day) are within safety limits. Our work highlights knowledge gaps about co-exposure to PAEs and NPAEs by multiple pathways in occupational e-waste workers, which could provide baseline data in the future.

Dysregulation of steroid metabolome in follicular fluid links phthalate exposure to diminished ovarian reserve of childbearing-age women.

The widespread use of phthalates (PAEs) has drawn increasing attention due to their endocrine disruption and reproductive toxicity, while the steroid metabolome is essential for follicular development. However, the mechanism by which PAE exposure affects ovarian reserve through the steroid metabolome remains unclear. This study recruited 264 childbearing-age women in Tianjin (China) from April 2019 to August 2020 in a cross-sectional design. Target metabolome analysis of 16 steroids was performed in follicular fluid (FF) to compare diminished ovarian reserve (DOR) against normal ovarian reserve (NOR) women and differential steroids were identified using binary logistic analyses. Further analysis of eleven PAE metabolites (mPAEs) in FF was conducted, and the retrieved oocyte number (RON) representing ovarian reserve was counted. Multiple linear regression and quantile-based g-computation (qgcomp) models were used to associate individual mPAEs and mPAE mixture with the DOR-related differential steroids in FF. Mediation analysis was used to discuss the mediating effect of DOR-related steroids on the association between mPAEs and RON. Androstenedione (A4), corticosterone (CORT), cortisol (COR) and cortisone were significantly down-regulated in FF from women with DOR. Nine mPAEs with detection frequencies greater than 60% and median concentrations of 0.02-4.86 ng/mL were incorporated into statistical models. Negative associations with COR and CORT were found for mono-ethyl phthalate (mEP), mono-(2-ethyl-5-oxohexyl) phthalate (mEOHP), and mono-2-ethylhexyl phthalate (mEHP). A positive association with cortisone was found for mEOHP, mEHP, monobutyl phthalate (mBP), and mono (2-isobutyl) phthalate (miBP). The qgcomp and mediation analyses revealed that mEP and mEOHP not only significantly contributed to the decline of COR and CORT in the mixed exposure but also indirectly reduced RON through the mediating effects of COR and CORT. In conclusion, PAE exposure may decrease ovarian reserve by downregulating COR and CORT.

Serum organophosphate flame retardants and plasticizers in Chinese females of childbearing age: Association with serum reproductive and thyroid hormones.

Organophosphate flame retardants (OPFRs) are extensively used as flame retardants and plasticizers, but their endocrine disrupting potentials have raised concerns. However, the impacts of OPFR exposures on reproductive and thyroid hormones in females remains unclear. In this study, serum concentrations of OPFRs were investigated, and levels of reproductive and thyroid hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, anti-Müllerian hormone, prolactin (PRL), testosterone (T), and thyroid stimulating hormone, were analyzed in childbearing-age females undergoing in-vitro fertilization treatment from Tianjin, a coastal city in China (n = 319). Tris (2-chloroethyl) phosphate (TCEP) was the predominant OPFR, with a median concentration of 0.33 ng/mL and a detection frequency of 96.6%. In the whole population, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tris(2-chloroisopropyl) phosphate (TCIPP) were positively associated with T (p < 0.05), while triethyl phosphate (TEP) was negatively associated with LH (p < 0.05) and LH/FSH (p < 0.01). Particularly, TCIPP was negatively associated with PRL in the younger subgroup (age≤30, p < 0.05). Moreover, TCIPP was negatively associated with diagnostic antral follicle counting (AFC) in the mediation analysis by a dominating direct effect (p < 0.01). In conclusion, serum levels of OPFRs were significantly associated with reproductive and thyroid hormone levels and a risk of decreased ovarian reserve in childbearing-age females, with age and body mass index being significant influencing factors.

[Applications and prospect of multiple displacement amplification in preimplantation genetic diagnosis].

Multiple displacement amplification (MDA) is a new technology for whole genome amplification (WGA), which can generate large amount of high-quality DNA and features high amplification efficiency and fidelity. MDA combined with conventional PCR techniques has been successfully applied for preimplantation genetic diagnosis, which has broaden latter's clinical applications.

Germline specification from pluripotent stem cells.

Reproduction is a key event in life guaranteeing the propagation and evolution of a species. Infertility caused by abnormal germ cell development is a topic of extensive concern. Herein, in vitro germline specification studies provide a modeling platform to investigate gametogenesis. The differentiation of pluripotent stem cells (PSCs) into germ cells has been studied for more than 30 years, and there have been many astonishing breakthroughs in the last decade. Fertile sperm and oocytes can be obtained from mouse embryonic stem cells (ESCs) through a primordial germ cell (PGC)-based method. Moreover, human PGC-like cells (PGCLCs) can be derived with a similar strategy as that used for mouse PGCLC derivation. In this review, we describe the reconstitution of PGCs and the subsequent meiosis, as well as the signaling pathways and factors involved in these processes.

COVID-19 vaccine hesitancy and associated factors among infertile couples undergoing assisted reproductive treatment.

Although periconception vaccination is important to maternal and neonatal health, little is known about the COVID-19 vaccine hesitancy among infertile couples seeking fertility treatment. Thus, we conducted this survey among infertile patients in a reproductive medicine center, between September 2021 and December 2021, to estimate the prevalence of COVID-19 vaccine hesitancy and its influencing factors. Information was collected through face-to-face interviews among volunteers. Among the 987 included interviewees, 17.33% reported hesitancy in primary vaccination, 25.63% reported hesitancy in booster vaccination, and 32.32% delayed the primary vaccination. Hesitancy in primary vaccination was associated with unexplained infertility (OR: 1.77, 95% CI: 1.05-2.98), ongoing IVF treatment (OR: 2.17, 95% CI: 1.22-3.89), concerns for vaccine safety (OR: 4.13, 95% CI: 2.66-6.42), effectiveness (OR: 1.62, 95% CI: 1.15-2.28), and influence on pregnancy (OR: 2.80, 95% CI: 1.68-4.67). These factors were also associated with hesitancy in booster vaccination. Delay of the primary vaccination was inversely associated with a college or above degree (OR: 0.49, 95% CI: 0.27-0.87), previous history of influenza vaccination (OR: 0.67, 95% CI: 0.46-0.98), and was positively associated with concerns for the influence on pregnancy (OR: 7.78, 95% CI: 5.01-12.07). It is necessary to carry out targeted education program by health professionals to publicize the benefits of periconception vaccination, and to reduce the resistance to COVID-19 vaccine among infertile couples.