In Vitro Fertilization-embryo Transfer Outcome Research Articles

Chinese medicine Jianpi Antai formula improves pregnancy outcomes of IVF-ET in infertile women.

To evaluate the efficacy and safety of Chinese medicine Jianpi Antai formula in infertile women undergoing in vitro fertilization-embryo transfer (IVF-ET). A total of 300 infertile women who underwent 2 frozen embryo transfer procedures at the Department of Reproductive Medicine, Sir Run Run Shaw Hospital were included in the study. They were randomly divided into study group and the control group according to a random number table. The study group received routine medication plus the Jianpi Antai formula during the period of embryo transfer, while the control group received routine medication only. The general condition, embryo implantation rate, clinical pregnancy rate, live birth rate, and the blood routine and liver and kidney function were evaluated and compared between two groups. There were 277 cases who completed the study, including 134 in the study group and 143 in the control group. The embryo implantation rate (68.7% vs. 55.9%, P<0.05), the clinical pregnancy rate (56.7% vs. 44.8%, P<0.05) and the live birth rate (50.7% vs. 37.8%, P<0.05) in the study group were all higher than those in the control group. Subgroup analysis revealed that in patients of advanced age (≥35 years), the embryo implantation rate, clinical pregnancy rate, and live birth rate in the study group were all higher than those in the control group (all P<0.05). In patients with decreased ovarian reserve function (anti-Müllerian hormone <1.68 ng/mL), the embryo implantation rate, clinical pregnancy rate, and live birth rate in the study group were all higher than those in the control group (all P<0.05). During the follow-up period, there were no abnormalities in the basic vital signs of both groups, and no adverse events were reported. Jianpi Antai formula can improve the embryo implantation rate in infertile women undergoing IVF-ET, reduce the embryo miscarriage rate, increase the live birth rate, improve the clinical outcomes, and has a high level of safety.

High progesterone levels on the day after HCG injection has no effect on clinical pregnancy outcomes in in vitro fertilization-embryo transfer.

This study investigates the potential impact of high progesterone (P) level on the day following human chorionic gonadotropin (HCG) injection on the clinical pregnancy outcomes of in vitro fertilization-embryo transfer (IVF-ET). Retrospective analysis was conducted on 6418 cycles of IVF-ET performed at Liuzhou Maternal and Child Health Hospital between August 2020 to December 2021. Excluding cycles with progesterone levels ≥1.5ng/ml on HCG injection, a total of 781 cycles were identified according to the standard, and they were divided into five groups according to the progesterone level on the day after HCG: Group A: progesterone level < 2.5 ng/ml (n = 128); Group B: 2.5 ng/ml ≤ progesterone level < 3.5 ng/ml (n = 174); Group C: 3.5 ng/ml ≤ progesterone level < 4.5 ng/ml (n = 153); Group D: 4.5 ng/ml ≤ progesterone level < 5.5 ng/ml (n = 132); Group E progesterone level ≥5.5 ng/ml(n=194). Comparative analyses of clinical data, including general clinical data, and clinical pregnancy outcomes such as clinical pregnancy rate, miscarriage rate, and live birth rate were performed among these groups. There were significant differences in estradiol levels on HCG injection, but there were no differences in available embryo rate, clinical pregnancy rate, miscarriage rate, and live birth rate. Binary logistic regression analysis showed that there was no significant correlation between P level on the day after HCG injection and the live birth rate. Under the condition of low P level on HCG injection, high progesterone levels on the day after HCG injection does not affect the clinical pregnancy outcomes of IVF-ET.

Male Hyperuricemia Is Associated with Poor Reproductive Outcomes of IVF-ET

Objective. To investigate the effect of male hyperuricemia on reproductive outcome of in vitro fertilization-embryo transfer (IVF-ET). Methods. Clinical data of 412 couples who underwent their first cycle of IVF-ET were analyzed. According to the serum uric acid (SUA) level of the male, they were divided into control group (SUA ≤ 416 μmol/L) and hyperuricemia group (SUA &gt; 416 μmol/L). The primary and secondary observation indices were pregnancy outcome after quality fresh embryo transfer and embryo outcome after IVF. Binary logistic regression was used to analyze the relationship between male SUA and related pregnancy outcomes. The ROC curve of the effect of male SUA on biochemical pregnancy loss rate (BPLR) after fresh embryo transplantation was drawn. Results. BPLR in hyperuricemia group increased significantly than that in control group (4.7% vs. 31.6%, P=0.012), and the clinical pregnancy rate and live birth rate were significantly lower (61.5% vs. 39.4%, P=0.038) (56.9% vs. 33.3%, P=0.027). Binary logistic regression analysis showed that BPLR after fresh embryo transfer was positively correlated with male SUA (B = 0.010, P=0.019, OR = 1.010, 95% CI (1.002, 1.018)). The area under receiver operating characteristic curve was 0.784, the specificity was 53.7%, and the sensitivity was 100.0%, P=0.010. Moreover, the total fertilization rate and 2PN fertilization rate in hyperuricemia group were significantly lower than those in control group (86.0% vs. 81.6%, P=0.001) (75.0% vs. 69.6%, P &lt;0.001). Conclusion. Male hyperuricemia is an independent risk factor for increasing BPLR after fresh embryo transfer and can also reduce the total fertilization rate and 2PN fertilization rate of IVF.

#139 : Outcomes of IVF-ET in Overweight/Obese and Normal-Weight Women with PCOS

Background and Aims: Overweight/obese women with polycystic ovary syndrome (PCOS) have poorer pregnancy outcomes, compared to normal-weight women. Body mass index (BMI) is a risk factor of in vitro fertilization-embryo transfer (IVF-ET). This study is to compare the outcomes of IVF-ET between the overweight/obese and normal-weight women with PCOS. Method: We performed a retrospective cohort study in a large reproductive center of a university hospital. The participants were the women with PCOS who underwent IVF-ET. We compared live birth, miscarriage and other clinical outcomes between the women with BMI ≥25 (overweight/obese group) and 18≤BMI&lt;25 (normal-weight group). Results: We included 3733 women with PCOS who underwent the first IVF-ET cycle from Jan 2016 to Dec 2020. 1693 of them were overweight/obese and had longer stimulation days and more doses of gonadotropins, while less numbers of oocytes retrieved and good quality embryos. Live birth rates were significantly lower in overweight/obese women, compared with normal-weight women (29.8% vs. 36.2%, OR 0.8 (0.7, 0.9)). Clinical pregnancy rates were significantly lower (38.5% vs. 43.0%, OR 0.8 (0.7, 0.9)). Miscarriage rates were significantly higher in overweight/obese women, compared with normal-weight women (21.5% vs. 14.6%, OR 1.6 (1.2, 2.1)). Multivariate logistic regression analysis showed BMI was an independent risk factor. Conclusion: Overweight/obese women with PCOS had poorer outcomes of IVF-ET, compared to normal-weight women with PCOS.

Acupuncture for in vitro fertilization-embryo transfer: an overview of systematic reviews.

To evaluate the report quality, methodological quality and evidence quality of the systematic reviews and meta-analyses (SRs/MAs) of acupuncture for in vitro fertilization-embryo transfer (IVF-ET). The SRs/MAs of acupuncture for IVF-ET were searched electronically from databases of CNKI, Wanfang, VIP, SinoMed, PubMed, Embase, Cochrane Library, from inception of each database to September 27th, 2022. Two reviewers independently screened the literature and extracted the data. Using PRISMA statement, the AMSTAR 2 scale and the GRADE system, the report quality, methodological quality and evidence quality of the included SRs/MAs were assessed. A total of 28 SRs/MAs were included, with PRISMA scores ranging from 8.5 points to 27 points. The problems of report quality focused on protocol and registration, retrieval, risk of bias in studies, additional analysis, limitations and funding. The methodological quality of included studies was generally low, reflecting on items 2, 3, 7, 10, 12 and 16. A total of 85 outcome indexes were included in the GRADE system for evidence grade evaluation. Most of the evidences were low or very low in quality. The reasons for the downgrade were related to study limitations, inconsistency, imprecision and publication bias. Acupuncture therapy improves the outcomes of IVF-ET, but the methodological quality and evidence quality of related SRs/MAs are low. It is recommended to conduct more high-quality studies in the future to provide more reliable evidences.

DNA Methylation of Window of Implantation Genes in Cervical Secretions Predicts Ongoing Pregnancy in Infertility Treatment

Window of implantation (WOI) genes have been comprehensively identified at the single cell level. DNA methylation changes in cervical secretions are associated with in vitro fertilization embryo transfer (IVF-ET) outcomes. Using a machine learning (ML) approach, we aimed to determine which methylation changes in WOI genes from cervical secretions best predict ongoing pregnancy during embryo transfer. A total of 2708 promoter probes were extracted from mid-secretory phase cervical secretion methylomic profiles for 158 WOI genes, and 152 differentially methylated probes (DMPs) were selected. Fifteen DMPs in 14 genes (BMP2, CTSA, DEFB1, GRN, MTF1, SERPINE1, SERPINE2, SFRP1, STAT3, TAGLN2, TCF4, THBS1, ZBTB20, ZNF292) were identified as the most relevant to ongoing pregnancy status. These 15 DMPs yielded accuracy rates of 83.53%, 85.26%, 85.78%, and 76.44%, and areas under the receiver operating characteristic curves (AUCs) of 0.90, 0.91, 0.89, and 0.86 for prediction by random forest (RF), naïve Bayes (NB), support vector machine (SVM), and k-nearest neighbors (KNN), respectively. SERPINE1, SERPINE2, and TAGLN2 maintained their methylation difference trends in an independent set of cervical secretion samples, resulting in accuracy rates of 71.46%, 80.06%, 80.72%, and 80.68%, and AUCs of 0.79, 0.84, 0.83, and 0.82 for prediction by RF, NB, SVM, and KNN, respectively. Our findings demonstrate that methylation changes in WOI genes detected noninvasively from cervical secretions are potential markers for predicting IVF-ET outcomes. Further studies of cervical secretion of DNA methylation markers may provide a novel approach for precision embryo transfer.

Impact of vaccination against COVID-19 on the outcomes of in vitro fertilization-embryo transfer: a retrospective cohort study.

Vaccination against coronavirus disease 2019 (COVID-19) has become the primary approach in the fight against the spread of COVID-19. Studies have shown that vaccination against COVID-19 has adverse effects, particularly on human reproductive health, despite the fact that vaccination rates are still on the rise. However, few studies have reported whether vaccination affects the outcome of in vitro fertilization-embryo transfer (IVF-ET) or not. In this study, we compared the outcome of IVF-ET and the development of follicles and embryos between vaccinated and unvaccinated groups. A single-center retrospective cohort study of 10,541 in vitro fertilization (IVF) cycles was conducted from June 2020 to August 2021. 835 IVF cycles with a history of vaccination against COVID-19 and 1670 IVF cycles that served as negative controls were selected and analyzed utilizing the Matchlt package of R software (http://www.R-project.org/) and the nearest neighbor matching algorithm for propensity-matched analysis at a 1:2 ratio. The number of oocytes collected in the vaccinated group and the unvaccinated group were 8.00 (0, 40.00) and 9.00 (0, 77.00) (P = 0.073) and the good-quality embryo rates of the two groups were 0.56±0.32 and 0.56±0.31 averagely (P = 0.964). Clinical pregnancy rates for the vaccinated group and unvaccinated group were 42.4% (155/366) and 40.2% (328/816) (P = 0.486) and biochemical pregnancy rates were 7.1% (26/366) and 8.7% (71/816) (P = 0.355). Two other factors were analyzed in this study; vaccination among different genders and different types (inactivated vaccine or recombinant adenovirus vaccine) showed no statistically significant effect on the above outcomes. In our findings, vaccination against COVID-19 showed no statistically significant effect on the outcomes of IVF-ET and the development of follicles and embryos, nor did the gender of the vaccinated person or the formulation of vaccines showed significant effects.

The impact of sleep on in vitro fertilization embryo transfer outcomes: a prospective study

To prospectively examine the association between sleep quality before embryo transfer with pregnancy outcomes in a population with infertility. Prospective observational cohort study. Center for Reproductive Medicine, Shandong University. From 7,847 women who enrolled from July 2019 to July 2020, 3,183 were eligible. Information about sleep, including sleep quality, sleep duration, and sleep chronology, were collected before embryo transfer using an integrated questionnaire. Sleep quality is quantified by the Pittsburgh Sleep Quality Index (PSQI) with a cut-point of 5 (PSQI >5 identifying poor sleep vs. PSQI ≤5 identifying good sleep). Average weekly sleep duration was calculated and divided into 5 groups (≤7, 7-8, 8-9, 9-10, and >10 h/d). In defining sleep chronotype, women with a sleep midpoint earlier than 2:30 AM were defined as morningness type, whereas those with a sleep midpoint later than 3:30 AM were defined as eveningness type, and the remainder were defined as an intermediate type. Rate of clinical pregnancy and live birth. Compared with those reporting poor sleep quality, those reporting good sleep quality showed higher clinical pregnancy (69.3% vs. 65.1%) and live birth rates (50.5% vs. 45.7%). After adjusting for confounding factors, women who self-reported good sleep had a higher probability of acquiring clinical pregnancy (RR, 1.07; 95% confidence interval, 1.01-1.13) and of live birth (RR, 1.12; 95% confidence interval, 1.02-1.23). Women with the morningness chronotype had the lowest rates of clinical pregnancy and live birth and had the highest rate of miscarriage. Sleep duration was found to have no significant association with any outcomes. In the stratified analyses, the positive associations of good sleep quality with clinical pregnancy and live birth existed only among women younger than 35 years old or who had undergone fresh embryo transfer. Good sleep quality was positively associated with outcomes in invitro fertilization embryo transfer (IVF-ET), particularly with clinical pregnancy and live birth. Poor sleep quality may be a risk factor for adverse IVF-ET outcomes for women <35 years old. Treating sleep disorders and providing sleep behavior guidance to patients receiving IVF-ET may improve pregnancy outcomes.

Clinical characteristics of severe late-onset ovarian hyperstimulation syndrome and its impact on the live birth outcome of IVF-ET

Objective: To investigate the correlation between different clinical features and live birth in patients with severe late-onset ovarian hyperstimulation syndrome (OHSS) after in vitro fertilization-embryo transfer (IVF-ET). Methods: The clinical information of 330 patients who were pregnant after IVF-ET and referred to medical treatments diagnosed as late-onset severe OHSS in Peking University Third Hospital from January 2016 to December 2020 was retrospectively analyzed. The patients were divided into live birth achieved group (n=287) and non-live birth achieved group (n=43) according to pregnancy outcomes, and live birth achieved group was further divided into two subgroups, full-term birth group (n=222) and early-term birth group (n=65) according to gestational week at delivery for better analysis. Single factor and multi-factor analysis were utilized to clarify the influencing factors of both live birth and early-term birth. Results: Among all the patients who received IVF-ET, the incidence of severe OHSS was 0.67% (673/100 758). Among 330 severe late-onset OHSS patients, 42.4% (140/330) had pleural effusion, the incidence of abnormal liver function was 69.4% (229/330), and the live birth rate was 87.0% (287/330). Among the 287 patients who achieved live birth, 55.4% (159/287) had no pleural effusion, 18.5% (53/287) had a small amount of pleural effusion, and 26.1% (75/287) had medium or massive pleural effusion; in the non-live birth achieved group, there were more patients without pleural effusion and less patients with a small amount of pleural effusion; the difference was statistically significant (χ2=6.213, P=0.045). The rate of selective fetal reduction in live birth achieved group was 16.0% (46/287), which was significantly higher than that in the non-live birth achieved group, which was 2.3% (1/43; χ2=5.749, P=0.017). Multivariate logistic regression analysis revealed that moderately abnormal liver function was an independent risk factor for live birth (OR=3.15, 95%CI: 1.60-6.19), while selective fetal reduction was an independent protective factor for live birth (OR=0.13, 95%CI: 0.02-0.96). Additionally, subgroup analysis suggested that twin birth was an independent risk factor for preterm birth (OR=8.54, 95%CI: 4.31-16.91). Conclusions: Moderate hepatic dysfunction may be associated with adverse pregnancy outcomes in patients with severe late-onset OHSS. Selective fetal reduction and singleton pregnancy are recommended to ameliorate live birth rate, full-term delivery rate, also the maternal and neonatal prognosis for patients with multiple pregnancies.

Novel pathogenic splicing variants in helicase for meiosis 1 (HFM1) are associated with diminished ovarian reserve and poor pregnancy outcomes.

Diminished ovarian reserve (DOR) is associated with compromised fertility that affects approximately 10% of couples. Gene mutations are implicated in the pathogenesis of DOR. Here, we aimed to assess the clinical and genetic characteristics of two sisters with impaired fertility history. The two sisters showed DOR and suffered from recurrent pregnancy loss (RPL) in natural pregnancy and in vitro fertilization-embryo transfer (IVF-ET). Whole exome sequencing (WES) was performed for the proband and pathogenic variants detected were validated by Sanger sequencing in all available family members. Minigene assay was performed to evaluate the impact of sequence variants on splicing effect. Two novel heterozygous variants on the HFM1 gene, c.1978-2A > C and c.2680 + 3_2680 + 4delAT, were observed in the two patients. The genotype of their parents was all heterozygous, while the unaffected sister and brother did not carry the variants. Both variants could produce alternative transcripts compared to wild-type counterparts, which might result in protein dysfunction. Our results demonstrated that the pathogenic splicing variants in HFM1 are associated with DOR in these two sisters. Mutations in HFM1 may contribute to RPL and poor IVF-ET outcomes because of descending quality and quantity of oocytes. The study enriched the genetic defect spectrum of DOR and understanding of the roles of HFM1 in female reproduction.

Glutamine and norepinephrine in follicular fluid synergistically enhance the antioxidant capacity of human granulosa cells and the outcome of IVF-ET

An increasing number of studies demonstrate that changes in neurotransmitters metabolic levels in follicular fluid are directly related to oocyte maturation, fertilization, the quality of embryo and pregnancy rates. However, the relationship between the intra-follicular neurotransmitters and the function of granulosa cells (GCs), and the outcome of in vitro fertilization-embryo transfer (IVF-ET) is not clear. Human follicular fluid and cumulus GCs were harvested from large follicles obtained from patients undergoing IVF. Neurotransmitters and steroid hormones in follicular fluid were measured through liquid chromatography-tandem mass spectrometry (LC–MS/MS) and high-performance liquid chromatography-mass spectrometry (HPLC–MS/MS). Based on the content of glutamine (Gln) in follicular fluid, the samples were divided into two groups: high Gln level group and low Gln level group. The expression of proliferation-, steroidogenesis- and antioxidant-related genes in GCs was detected by qRT-PCR. In vitro, KGN cells were used to further verify the effects of Gln and NE on GCs function. Primary and secondary outcomes were the number of mature and retrieved oocytes, and the ratio of high-quality embryos, respectively. Gln (46.75 ± 7.74 μg/mL) and norepinephrine (NE, 0.20 ± 0.07 μg/mL) were abundant neurotransmitters in follicular fluid, and exhibited a significantly positive correlation (R = 0.5869, P < 0.005). In high Gln level group, the expression of proliferation, steroidogenesis and antioxidant-related genes in GCs were higher than those in low Gln level group, and the contents of estriol and E2 in follicular fluid were more abundant. Moreover, the concentrations of Gln and NE in follicular fluid showed significantly positive correlation with IDH1 expression in GCs (R = 0.3822, R = 0.4009, P < 0.05). Importantly, a significantly positive correlation was observed between IDH1 expression in GCs and the ratio of higher-quality/cleaved embryos (R = 0.4480, P < 0.05). In vitro studies further demonstrated that Gln and NE played synergistically function in improving GCs proliferation and E2 production by upregulating IDH1 expression. These data demonstrate that Gln and NE in follicular fluid might play significant positive roles in GCs function, and may be potential predictors for selecting optimal quality oocytes and evaluating the quality of embryonic development.

Serum antiphospholipid antibody status may not be associated with the pregnancy outcomes of patients undergoing in vitro fertilization.

Antiphospholipid syndrome (APS) is an autoimmune disease that is associated with recurrent pregnancy loss. It is still controversial whether the presence of antiphospholipid antibodies (aPL) in the serum of patients with in vitro fertilization-embryo transfer (IVF-ET) has a negative effect on the outcomes. In view of the discrepancies, a meta-analysis of the published data was performed to explore the relationship of aPL and IVF-ET outcomes. We searched for all published articles indexed in PubMed, Web of Science, and Cochrane Library, which were retrieved up to April, 2021. A total of 921 studies were yielded, of which 6 finally met the inclusion criteria. We carried out the meta-analysis by pooling results of these studies with Review Manager 5.3 software. The effect index was measured with 95% confidence intervals (CIs) of the relative risks (RRs). Six eligible studies were included in this meta-analysis, involving 3214 patients. Our results showed that positive aPL was not associated with decreased clinical pregnancy rate (RR 0.97; 95% CI 0.91-1.04). There was no correlation between positive aPL and increased miscarriage risk (RR 1.22; 95% CI 0.94-1.58). Only 5 of the 6 studies referred to live birth rate, but still no association was found between them (RR 0.95; 95% CI 0.81-1.11). The results showed that the presence of positive aPL neither decreased clinical pregnancy rate and live birth rate, nor increased miscarriage rate in women undergoing IVF, which is differed from the opinion of clinical practice. More prospective studies with high quality and larger sample size are needed to evaluate the relationship between positive aPL and outcomes of IVF-ET.

Influencing Factors of Pregnancy Outcome of in vitro Fertilization-Embryo Transfer

To analyze the effect of factors relevant to blastocyst transfer on the pregnancy outcome of in vitro fertilization-embryo transfer (IVF-ET). The clinical data of 790 pregnant women who underwent IVF-ET in our hospital from July 2015 to July 2020 were retrospectively analyzed. The pregnancy outcome of blastocysts transferred on day 5 (D5, n=705) and those transferred on day 6 (D6, n=85) were compared. According to the pregnancy outcome, the cases were divided into a live birth group ( n=322) and a non-live birth group ( n=468), and multivariate logistic regression was conducted to study the effect of factors relevant to blastocyst transfer on the live birth outcome of IVF-ET. In the D5 group, the biochemical pregnancy rate, clinical pregnancy rate and live birth rate of blastocyst transfer were 69.93%, 64.96%, and 41.84%, respectively, which were significantly higher than those of the D6 group at 50.59%, 45.88%, and 30.59%, respectively. The difference was statistically significant ( P<0.05). There was no statistically significant difference in the miscarriage rate between the D5 group and the D6 group ( P>0.05). Multivariate logistic analysis revealed that age>35 years, years of infertility>5 years, endometrium thickness<9 mm on the day of blastocyst transfer, trophoblast cell rating of C, blastocyst transfer performed on D6, and multiparity were all risk factors for non-live birth outcome of IVF-ET ( P<0.05). The adverse pregnancy outcomes of IVF-ET were found to be associated with age, duration of infertility, endometrial thickness on the day of to blastocyst transfer, trophoblast cell rating, and blastocyst transfer performed after how many days of embryo development, and multiparity, which should be closely monitored, and effective measures should be adopted accordingly to prevent adverse outcomes of pregnancy.

Early pregnancy loss: Do Per- and polyfluoroalkyl substances matter?

Per- and poly-fluorinated substances (PFASs) with endocrine disrupting effect can efficiently transfer across the blood-follicle barrier. However, it is still controversial and attracting extensive public concern that whether PFASs can affect the human fertility potential. Therefore, we aimed to analyze the associations of women's exposure to PFASs with pregnancy loss, the relevant processes of fertilization, zygote implantation, and embryo development by using a prospective cohort study. The women undergoing in vitro fertilization-embryo transfer (IVF-ET) treatment were recruited in Beijing City (Beijing Center) and Yantai City (Yantai Center) in China during 2015-2017. A total of 305 women were recruited before the IVF-ET treatment. Twelve PFASs were measured in their serum samples collected in the day before the IVF-ET treatment, as well as in the human chorionic gonadotropin (hCG) day. The three IVF-ET outcomes were included, i.e. hCG test negative, clinical pregnancy failure (CPF), and preclinical spontaneous abortion. Nine serum PFASs had detection rate of >70% in Beijing and Yantai centers. The exposure patterns to PFASs between these two centers were overall different. For Beijing Center, we only found a positive association of perflurodecanoic acid (PFDA) with the risk of CPF [RR=2.28 (95%CI: 1.02-5.11)], but there is a reverse trend in Yantai Center with [RR=0.45 (95%CI: 0.23-0.85)]. However, the serum concentration of PFDA in Beijing Center was relatively lower than that of Yantai Center. Other significant associations of the detected PFASs with the IVF-ET outcomes, or with the relevant clinical processes, were not found. The multi-pollutant regression model of the Bayesian kernel machine regression suggested that there were no joint effects between various PFASs on the concerned outcomes. Overall, we suggest that most PFAS were not associated with early pregnancy loss at the current exposure levels. As for the PFDA, there may exist susceptibility of different populations.

The Microbial Composition of Lower Genital Tract May Affect the Outcome of in vitro Fertilization-Embryo Transfer.

Objective: This work was conducted in order to study the effect of the lower genital tract (vaginal and cervical canal) microbiota on pregnancy outcomes of reproductive-aged women receiving embryo transfer.Study design: A total of 150 reproductive-aged patients who received the first fresh in vitro fertilization-embryo transfer (IVF-ET) were included in the study. Samples from the vagina and cervical site of each patient were collected separately using sterile swabs before ET. Genomic DNA was pyrosequenced for the V3–V4 regions of the 16S ribosomal RNA gene. Further bioinformatics analysis was performed using QIIME and R package. Pregnancy outcomes were followed and analyzed to compare differences in microbial composition.Results: The cervical microbiota had a higher Shannon index than the vaginal microbiota, and the microbial composition was different between the two sites. However, the Sorenson index between the two sites within the same individual was 0.370 (0.309–0.400). A total of 89 patients achieved clinical pregnancy after ET, while 61 failed. The Shannon indices and the microbial community of both vaginal and cervical microbiota between pregnant and non-pregnant groups were not significantly different. The relative abundance of Lactobacillus in the vagina and cervical canal did not differ between the two groups. Linear discriminant analysis, random forest analysis, and receiver-operating characteristic curve analysis showed that Bifidobacterium, Prevotella, and Lactobacillus iners in the vagina, as well as Solanum torvum, Fusobacterium, and Streptococcus in the cervix, may be negatively associated with clinical pregnancy after IVF.Conclusion: The cervical microbiota was more diverse than the vaginal microbiota, but because of anatomical continuity, there was a correlation between the two sites. The microbial composition of the vagina and cervical canal may influence the outcome of IVF-ET, but more samples are needed to verify this conclusion.

Serum zinc concentration and risk of adverse outcomes to in vitro fertilization and embryo transfer: A prospective cohort study in northern China

Zinc (Zn) plays an important role in female reproductive health. Few studies have currently assessed the effects of female Zn level on the outcome of in vitro fertilization-embryo transfer (IVF-ET). This study investigated the association between serum Zn concentration and IVF-ET outcomes, and the potential effects of some lifestyles on this association. A prospective cohort study design was adopted, and 305 women undergoing IVF-ET were recruited from two cities, Beijing and Shandong, in northern China. Fasting blood specimens were obtained on the day prior to the first treatment cycle. A questionnaire was used to collect demographic characteristics and lifestyle information. Serum Zn concentration was measured using inductively coupled plasma-mass spectrometry. Female serum Zn levels in Beijing center were found to be significantly higher than those in Shandong center. Women who failed to achieve clinical pregnancy had significantly lower Zn concentrations among Shandong subjects, but not in Beijing or the total participants in both centers. For Beijing participants, no statistically significant associations were found between Zn concentrations and the failure risk of IVF-ET [adjusted relative risk (aRR) = 0.65, 95% confidence interval (CI): 0.37–1.15]. For Shandong participants, lower Zn concentrations (< 610.3 ng/mL) were associated with a 66% increased risk of IVF-ET failure (aRR = 1.66, 95% CI: 1.10–2.51). Also, significantly positive correlations were observed between Zn concentrations and the habitual consumption of two food types, including fresh vegetables and beans or bean products, but this was not the case in Beijing. It was concluded that the effect of serum Zn concentrations on IVF-ET outcome may vary by the geographic location. Lower Zn levels might be a risk factor for IVF-ET failure among Shandong women, which can be addressed by adjusting the food intakes. These findings have implications for human infertility treatment and public health problem addressing.

Association between serum oestradiol level on the hCG administration day and neonatal birthweight after IVF-ET among 3659 singleton live births

Oestradiol, an important hormone in follicular development and endometrial receptivity, is closely related to clinical outcomes of fresh in vitro fertilization-embryo transfer (IVF-ET) cycles. A supraphysiologic E2 level is inevitable during controlled ovarian hyper-stimulation (COH), and its effect on the outcome of IVF-ET is controversial. The aim of this retrospective study is to evaluate the association between elevated serum oestradiol (E2) levels on the day of human chorionic gonadotrophin (hCG) administration and neonatal birthweight after IVF-ET cycles. The data of 3659 infertile patients with fresh IVF-ET cycles were analysed retrospectively between August 2009 and February 2017 in First Hospital of Zhengzhou University. Patients were categorized by serum E2 levels on the day of hCG administration into six groups: group 1 (serum E2 levels ≤ 1000 pg/mL, n = 230), group 2 (serum E2 levels between 1001 and 2000 pg/mL, n = 524), group 3 (serum E2 levels between 2001 and 3000 pg/mL, n = 783), group 4 (serum E2 levels between 3001 and 4000 pg/mL, n = 721), group 5 (serum E2 levels between 4001 and 5000 pg/mL, n = 548 ), and group 6 (serum E2 levels > 5000 pg/mL, n = 852). Univariate linear regression was used to evaluate the independent correlation between each factor and outcome index. Multiple logistic regression was used to adjust for confounding factors. The LBW rates were as follows: 3.0% (group 1), 2.9% (group 2), 1.9% (group 3), 2.9% (group 4), 2.9% (group 5), and 2.0% (group 6) (P = 0.629), respectively. There were no statistically significant differences in the incidences of neonatal LBW among the six groups. We did not detect an association between peak serum E2 level during ovarian stimulation and neonatal birthweight after IVF-ET. The results of this retrospective cohort study showed that serum E2 peak levels during ovarian stimulation were not associated with birth weight during IVF cycles. In addition, no association was found between higher E2 levels and increased LBW risk. Our observations suggest that the hyper-oestrogenic milieu during COS does not seem to have adverse effects on the birthweight of offspring after IVF. Although this study provides some reference, the obstetric-related factors were not included due to historical reasons. The impact of the high estrogen environment during COS on the birth weight of IVF offspring still needs future research.

The Analysis of Anxiety and Depression in Different Stages of in vitro Fertilization-Embryo Transfer in Couples in China.

BackgroundThis study aimed to examine the differences in anxiety and depression between infertile Chinese couples in diverse stages of in vitro fertilization-embryo transfer (IVF-ET) and their relationship with the IVF-ET outcomes.MethodsFrom February 2016 to December 2018, a total of 247 couples that were undergoing IVF-ET were randomly selected for this study. On the day they started their treatment (T1), the day human chorionic gonadotropin was administered (T2), and 4 days after the embryo transfer (T3), self-designed questionnaires, the Self-Rating Anxiety Scale, and the Self-Rating Depression Scale were completed to investigate anxiety and depression in different stages.ResultsAge had an effect on the anxiety and depression in women. Male infertility type and the cause of infertility had an effect on the anxiety and depression in men. The incidence of anxiety in women in the T1, T2, and T3 stages was 29.96%, 44.94%, and 17.81%, respectively. The anxiety scores of women were 46.14 ± 8.37, 50.83 ± 8.50, and 44.09 ± 8.17, respectively, which were significantly higher than those of men (p < 0.05). The anxiety score in stage T2 was the highest in women, and the depression score of women in stage T1 was the highest. The incidence of anxiety in men in the T1, T2, and T3 stages was 20.65%, 8.50%, and 6.07%, respectively. The incidence of anxiety was not significantly different in diverse stages (p > 0.05), and the same result was obtained for the incidence of depression. The anxiety and depression scores of the infertile couples in different stages were not related to the outcome of IVF-ET.ConclusionThe incidence of anxiety and depression in infertile couples in diverse stages of IVF-ET is different, especially in women, and the anxiety and depression of infertile couples in the process of IVF-ET may not be related to the outcome of assisted pregnancy.

Bisphenol A promotes autophagy in ovarian granulosa cells by inducing AMPK/mTOR/ULK1 signalling pathway

BackgroundBisphenol A (BPA) is a widespread endocrine-disrupting chemical with estrogen like effects, which could interfere with the human reproductive system by disrupting the normal function of granulosa cells (GCs) leading to abnormal ovarian function. However, the mechanism of its toxicity on human GCs has not been clearly described thus far. Methods106 normogonadotropic infertile women undergoing their first in-vitro fertilization-embryo transfer (IVF-ET) cycle were recruited. Urinary BPA level and the early outcomes of IVF-ET were analysed. Patients were divided to low and high BPA exposure groups using the median urinary BPA concentration as the cut-off value. In-vivo and in-vitro studies were conducted using mice and human granulosa cell line (KGN cells). Female Kunming mice approximately 6–8 weeks of age were poisoned with BPA at different dosages (1, 10 or 100 μg/kg) by oral gavage once daily for 2 weeks, while KGN cells were exposed to BPA at the concentration of 1, 10 or 100 nM for 24 h, 48 h or 72 h. BPA-induced ovarian morphologic changes were analysed by histopathology investigation. Cell viability and apoptosis were evaluated using CCK-8, TUNEL and flowcytometric, respectively. Hormone levels were determined using ELISA and the molecular mechanism studies were conducted using immunofluorescence, RT-PCR and western blots. ResultsThe oocyte retrieval rate, maturation rate and embryo implantation rate significantly decreased with the higher level of urinary BPA concentration. Peak E2 level was lower in high BPA group, but no statistical significance could be observed. In BPA treated mice, cystic dilation of the follicles with a decreased number of GCs could be observed histopathologically. Decreased E2, P4 and AMH level and GCs autophagy could be detected both in-vivo and in-vitro with the activation of AMPK/mTOR/ULK1 signalling pathway. As being confirmed in KGN cells, phosphorylated AMPK and ULK1 increased while phosphorylated mTOR decreased, and by inhibition autophagy using knockdown of AMPK or 3-MA, adverse effects of BPA exposure in-vitro could be reversed. ConclusionBPA exposure might abnormally influence human ovarian functions leading to abnormal folliculogenesis by activation of autophagy in GCs through AMPK/mTOR/ULK1 pathway.

Association between exposure of light rare earth elements and outcomes of in vitro fertilization-embryo transfer in North China

The adverse health effects of rare earth elements (REEs) on reproductive health remain a subject of debate, and few clinical observations are available. This study investigated the association between light REEs (LREEs) exposure and the outcome of in vitro fertilization–embryo transfer (IVF-ET). We recruited a total of 305 women undergoing IVF-ET in Beijing City and Shandong Province of northern China. Their demographic information and lifestyle characteristics were collected using questionnaires at enrollment. Fasting blood samples were collected on the day before the IVF-ET treatment cycle began. Serum concentrations of the LREEs of concern were analyzed using inductively coupled plasma-mass spectrometry, and four LREEs were measured with a high detection rate, including lanthanum (La), cerium (Ce), praseodymium (Pr), and neodymium (Nd). We found that a higher serum La concentration was associated with a 30% increased likelihood of clinical pregnancy failure [relative risk (RR) = 1.30, 95% confidence interval (CI): 1.00–1.67] and a 230% increased likelihood of preclinical spontaneous abortion (RR = 3.30, 95% CI: 1.57–6.94). There was a negative correlation between serum La concentration and the number of good-quality oocytes. For the other LREEs, no statistically significant associations were observed. We concluded that a high serum La concentration may have an adverse effect on IVF-ET outcomes.