In Vitro Fertilization-embryo Transfer Research Articles

Potential innate immunity-related markers of endometrial receptivity and recurrent implantation failure (RIF)

The successful implantation of the embryo into a receptive endometrium is essential for the establishment of a viable pregnancy while recurrent implantation failure (RIF) is a real challenge in assisted reproduction. The maternal innate immune system, specifically the Toll-like receptors (TLRs), are involved in maintaining immunity in the female reproductive tract (FRT) required for fertility. In this study, we aimed to investigate the importance of innate immunity-related gene expression in the regulation of human fertility and as a prediction of potential outcome of in vitro fertilization - embryo transfer (IVF-ET), thus, we assessed the gene expression levels of TLR signalling molecules using quantitative real-time PCR between endometrial biopsies of healthy fertile women, and the patients experiencing RIF. Interestingly, our results showed that, TRIB2 and TLR9 genes were differentially expressed between the endometrial biopsies of healthy women and those with RIF. However, comparing expression levels of same genes between pre-receptive and receptive healthy endometrial biopsies showed different genes (ICAM1, NFKBIA, VCAM1, LIF, VEGFB, TLR5) had significantly altered expression, suggesting their involvement in endometrial receptivity. Thus, further investigations will enable us to better understand the role of these genes in the biology of FRT and as a possible target for the improvement of infertility treatments and/or development of non-hormonal contraception.

Integrated Analysis of Hub Genes and MicroRNAs in Human Placental Tissues from In Vitro Fertilization-Embryo Transfer.

ObjectiveSupraphysiological hormone exposure, in vitro culture and embryo transfer throughout the in vitro fertilization-embryo transfer (IVF-ET) procedures may affect placental development. The present study aimed to identify differences in genomic expression profiles between IVF-ET and naturally conceived placentals and to use this as a basis for understanding the underlying effects of IVF-ET on placental function.MethodsFull-term human placental tissues were subjected to next-generation sequencing to determine differentially expressed miRNAs (DEmiRs) and genes (DEGs) between uncomplicated IVF-ET assisted and naturally conceived pregnancies. Gene ontology (GO) enrichment analysis and transcription factor enrichment analysis were used for DEmiRs. MiRNA-mRNA interaction and protein-protein interaction (PPI) networks were constructed. In addition, hub genes were obtained by using the STRING database and Cytoscape. DEGs were analyzed using GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Differentially expressed miRNAs were validated through qRT-PCR.ResultsCompared against natural pregnancies, 12 DEmiRs and 258 DEGs were identified in IVF-ET placental tissues. In a validation cohort, it was confirmed that hsa-miR-204-5p, hsa-miR-1269a, and hsa-miR-941 were downregulation, while hsa-miR-4286, hsa-miR-31-5p and hsa-miR-125b-5p were upregulation in IVF-ET placentas. Functional analysis suggested that these differentially expressed genes were significantly enriched in angiogenesis, pregnancy, PI3K-Akt and Ras signaling pathways. The miRNA-mRNA regulatory network revealed the contribution of 10 miRNAs and 109 mRNAs while EGFR was the most highly connected gene among ten hub genes in the PPI network.ConclusionEven in uncomplicated IVF-ET pregnancies, differences exist in the placental transcriptome relative to natural pregnancies. Many of the differentially expressed genes in IVF-ET are involved in essential placental functions, and moreover, they provide a ready resource of molecular markers to assess the association between placental function and safety in IVF-ET offspring.

Is It Possible to Expand Oocyte Donors by Decreasing Number of Oocytes for Own Use? Insights From a Large Single-Center Study.

BackgroundCurrently, in China, only women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles can donate oocytes to others, but at least 15 oocytes must be kept for their own treatment. Thus, the aim of this study was to determine whether oocyte donation compromises the cumulative live birth rate (CLBR) of donors and whether it is possible to expand oocyte donors’ crowd.MethodsThis was a retrospective cohort study from August 2015 to July 2017 including a total of 2,144 patients, in which 830 IVF–embryo transfer (IVF-ET) patients were eligible for oocyte donation and 1,314 patients met all other oocyte donation criteria but had fewer oocytes retrieved (10–17 oocytes). All 830 patients were advised to donate approximately three to five oocytes to others and were eventually divided into two groups: the oocyte donation group (those who donated) and the control group (those who declined). The basic patient parameters and CLBR, as well as the number of supernumerary embryos after achieving live birth, were compared. These two factors were also compared in all patients (2,144) with oocyte ≥10.ResultsIn 830 IVF-ET patients who were eligible for oocyte donation, only the oocyte number was significantly different between two groups, and the donation group had more than the control group (25.49 ± 5.76 vs. 22.88 ± 5.11, respectively; p = 0.09). No significant differences were found between the two groups in other factors. The results indicate that the live birth rate in the donation group was higher than that in the control group (81.31% vs. 82.95%, p = 0.371), without significance. In addition, CLBR can still reach as high as 73% when the oocyte number for own use was 10. Supernumerary embryos also increased as the oocyte number increased in all patients (oocyte ≥10).ConclusionsCurrently, oocyte donation did not compromise CLBR, and oocyte donation can decrease the waste of embryos. In addition, in patients with 10 oocytes retrieved, the CLBR was still good (73%). Thus, it is possible to expand oocyte donors if the number of oocyte kept for own use was decreased from 15 to 10 after enough communication with patients.

Effects of Hochuekkito, a traditional Japanese medicine (Kampo), on reproduction of aging female mice.

PurposeTo determine the potentials of Hochuekkito (HET) treatment for aging infertility.MethodsMice at 36 weeks of age were fed without (control, n = 40) or with low (100 mg/kg/day, n = 24) and high (1000 mg/kg/day, n = 38) doses of HET for 12 weeks. Aging animals at 48 weeks of age were used for in vitro fertilization‐embryo transfer (IVF‐ET), and their ovaries were subjected to histological and quantitative inflammation analyses.ResultsHET administration decreased transcript levels of ovarian inflammatory markers, interleukin 6 (IL‐6), IL‐1β, tumor necrosis factor (TNF)‐α, and interferon‐gamma (IFN‐γ) but suppressed ovulation rates and the number of ovulated oocytes in aging mice. Furthermore, HET treatment decreased the rates of oocytes maturation and fertilization and the cumulus‐cell expression of TNF‐α‐induced protein 6 and epidermal growth factor receptor. After IVF‐ET, no improvement of declined live offspring rate by aging was achieved by HET administration, although there were no adverse effects on embryo development and implantation as well as gross morphology and bodyweight of pups.ConclusionPresent study indicated HET treatment interfered with ovulation and fertilization in aging mice without affecting ovarian follicle development. No improvement on the age‐associated decline of live offspring rate and follicle development was achieved after HET treatment.

The Mechanism of Traditional Chinese Medicine Based on Semi-Targeted Metabolomics to Improve IVF Outcomes in Senile Patients.

Objective To identify the biological function and metabolic pathway of differential metabolites in follicular fluid of senile patients with kidney qi deficiency undergoing in vitro fertilization-embryo transfer (IVF-ET) and observe the effect of kidney-invigorating herbs on IVF outcomes in senile patients. Methods A total of 95 women undergoing IVF treatment were recruited and divided into three groups, including 34 cases in the treatment group (the senile patients with kidney qi deficiency after the intervention of Chinese medicine), 31 cases in the experiment group (the senile patients with kidney qi deficiency of no intervention of Chinese medicine), and 30 cases in the control group (young women with infertility due to male factor). The three groups of women were treated with long protocol ovarian hyperstimulation; the treatment group was given Qi-Zi-Yu-Si decoction on the day of HCG downregulation. Their IVF clinical outcomes were observed. The metabolites changes of kidney qi deficiency syndrome were analyzed in follicular fluid metabolomics using liquid chromatography-mass spectrometry (UPLC-MS/MS). Results The syndrome score of kidney qi deficiency syndrome in the treatment group was significantly improved after treatment (P < 0.01). Compared with the experiment group, the available embryo rate and implantation rate were increased, and the difference was statistically significant (P < 0.05). Progesterone, indoleacrylic acid, 2-propenyl 1-(1-propenylsulfinyl) propyl disulfide, N-acetyltryptophan, decanoylcarnitine, 20a-dihydroprogesterone, testosterone acetate, eicosatrienoic acid, 1H-indole-3-carboxaldehyde, choline, phosphorylcholine, and tryptophan were downregulated in the treatment group. Through pathway analysis, glycerophospholipid metabolism and steroid hormone biosynthesis were regulated in senile patients with kidney qi deficiency after Qi-Zi-Yu-Si decoction intervention. Conclusion Qi-Zi-Yu-Si decoction can effectively improve the IVF outcome and clinical symptoms of senile patients. Follicular fluid metabolites were significantly changed in senile infertile women with kidney qi deficiency, and the mechanism by which kidney-invigorating herbs improve IVF treatment outcomes may be related to glycerophospholipid metabolism and steroid hormone biosynthesis. This study was registered in the Chinese Clinical Trials Registry Platform (ChiCTR1800014422).

Coping strategies mediate the association between stigma and fertility quality of life in infertile women undergoing in vitro fertilization-embryo transfer

BackgroundThe mediating role of coping strategies and its relationship with psychological well-being and quality of life has been considered in the literature. However, there is little research to explore the mechanism of coping strategies on stigma and fertility quality of life (FertiQoL) in infertile women undergoing In Vitro Fertilization Embryo Transfer (IVF-ET). The aim of this study was to examine the mediating effect of coping strategies on the relationship between stigma and fertility quality of life (FertiQoL) in Chinese infertile women undergoing In Vitro Fertilization Embryo Transfer (IVF-ET).MethodsIn this cross-sectional study, a total of 768 infertile women undergoing IVF-ET were recruited from Assisted Reproductive Center of Shaanxi Province, China. The personal information, infertility stigma scale, coping strategy scale and FertiQoL scale were measured using a set of questionnaires. The multiple mediator model was performed using AMOS 21.0.ResultsThe model showed a significant negative direct effect between stigma on FertiQoL. There were significantly negative indirect effects of stigma on FertiQoL through active-avoidance, active-confronting and passive-avoidance, respectively. The meaning-based coping played a positive intermediary role. The model explained 69.4% of the variance in FertiQoL.ConclusionActive-avoidance coping strategy is the most important mediator factor between stigma and FertiQoL in infertile women undergoing IVF-ET treatment. Meaning-based coping strategy plays a positive mediating role between stigma and FertiQoL.

Multifactor Prediction of Embryo Transfer Outcomes Based on a Machine Learning Algorithm.

In vitro fertilization-embryo transfer (IVF-ET) technology make it possible for infertile couples to conceive a baby successfully. Nevertheless, IVF-ET does not guarantee success. Frozen embryo transfer (FET) is an important supplement to IVF-ET. Many factors are correlated with the outcome of FET which is unpredictable. Machine learning is a field of study that predict various outcomes by defining data attributes and using relevant data and calculation algorithms. Machine learning algorithm has been widely used in clinical research. The present study focuses on making predictions of early pregnancy outcomes in FET through clinical characters, including age, body mass index (BMI), endometrial thickness (EMT) on the day of progesterone treatment, good-quality embryo rate (GQR), and type of infertility (primary or secondary), serum estradiol level (E2) on the day of embryo transfer, and serum progesterone level (P) on the day of embryo transfer. We applied four representative machine learning algorithms, including logistic regression (LR), conditional inference tree, random forest (RF) and support vector machine (SVM) to build prediction models and identify the predictive factors. We found no significant difference among the models in the sensitivity, specificity, positive predictive rate, negative predictive rate or accuracy in predicting the pregnancy outcome of FET. For example, the positive/negative predictive rate of the SVM (gamma = 1, cost = 100, 10-fold cross validation) is 0.56 and 0.55. This approach could provide a reference for couples considering FET. The prediction accuracy of the present study is limited, which suggests that there may be some other more effective predictors to be developed in future work.

Clinical Application of Noninvasive Prenatal Testing for Pregnant Women with Assisted Reproductive Pregnancy.

ObjectiveThis paper analyzes the clinical significance of noninvasive prenatal testing (NIPT) for fetal chromosome aneuploidy in the screening of in vitro fertilization–embryo transfer (IVF) pregnancies.MethodsThe study subjects consisted of 3163 IVF-pregnant women who underwent NIPT at the Women’s Hospital, School of Medicine, Zhejiang University and Taizhou Hospital, Zhejiang Province from February 2015 to June 2019. Fetal or neonatal karyotype analysis was carried out in high-risk patients, with subsequent follow-up on pregnancy outcomes.ResultsNIPT results of 3163 pregnant women suggested 20 cases of high-risk fetal chromosome aneuploidy, of which 2185 cases were a single pregnancy. Of the 13 cases of high-risk chromosome aneuploidy in single pregnancies, seven were true positive, and six were false positive according to fetal or newborn chromosomal karyotype diagnosis. Twin pregnancies accounted for 978 cases in which NIPT indicated seven cases of high-risk chromosome aneuploidy; six of these cases were true positive, and one case was false positive according to fetal or newborn chromosomal karyotype diagnosis. The specificity, positive predictive value, and false-positive rate of trisomy 21 syndrome in IVF single embryo NIPT were 99.86%, 62.5%, and 0.14%, respectively. The specificity, positive predictive value, and false-positive rate of trisomy 18 syndrome were 99.95%, 66.67%, and 0.05%, respectively. The specificity of trisomy 13 syndrome was 99.91%, and the false-positive rate was 0.09%. The specificity of trisomy 21 syndrome in IVF twin NIPT was 99.89%, the positive predictive value was 83.33%, and the false-positive rate was 0.11%. The specificity and positive predictive value of fetal trisomy 18 syndrome were 100.00%, and the false-positive rate of it were 0.00%. Sensitivity and false-negative rates were 100% in all cases.ConclusionNIPT is an ideal prenatal test for IVF-pregnant women due to its high sensitivity and specificity in screening for fetal aneuploidy.

Cognitive behavioural therapy improves pregnancy outcomes of in vitro fertilization-embryo transfer treatment: a systematic review and meta-analysis.

ObjectiveThe study aim was to examine the effects of cognitive behavioural therapy (CBT) on the pregnancy outcomes of women receiving in vitro fertilization-embryo transfer (IVF-ET) treatment.MethodsA literature review was performed using the databases MEDLINE, the Cochrane Database, Embase, Chinese National Knowledge Infrastructure (CNKI) and WANFANG. Eligible studies were selected according to inclusion and exclusion criteria. Relevant data were extracted and the quality of studies assessed. Odds ratios with 95% confidence intervals were pooled to statistically analyse the difference between intervention and control groups.ResultsTen studies were selected for the systematic review and meta-analysis. The findings showed that CBT and cognitive-related therapy significantly improved the pregnancy rate of women undergoing IVF-ET treatment. Subgroup analysis showed that patients who received CBT, rather than complex psychological interventions, and those who received interventions delivered by professional psychologists, were more likely to become pregnant during IVF-ET treatment.ConclusionCBT and cognitive-related interventions had significant effects on the pregnancy outcomes of women receiving IVF-ET treatment. CBT treatment (rather than complex psychological interventions) provided by professional psychologists is strongly recommended.

Characterization of microRNAs in spent culture medium associated with human embryo quality and development.

BackgroundGiven implantation failure limits the improvement of in vitro fertilization (IVF) success rates, there is an urgency to identify potential biomarkers for embryo quality and predict the outcomes of IVF-embryo transfer (IVF-ET).MethodsUsing RNA-sequencing, we identified the expression profiles of 16 spent culture medium (SCM) collected from embryos at the cleavage on day 3 (D3 cleavage) and blastocyst stages on day 5 (D5 blastocyst) during IVF cycles. Differentially expressed miRNAs (DEmiRNAs) were then identified, and microRNA (miRNA)-messenger RNA (mRNA) interaction networks were constructed. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) confirmation and validation in the Gene Expression Omnibus (GEO) database were performed.ResultsCompared with the pregnant group, 29 DEmiRNAs were detected in the non-pregnant group at D3 cleavage, and 26 were detected in the non-pregnant group at D5 blastocyst. Among them, a total of six known miRNAs, including hsa-miR-199a-3p>hsa-miR-199b-3p, hsa-miR-199a-5p, hsa-miR-379-5p, hsa-miR-432-5p, hsa-miR-99a-5p, and hsa-miR-483-5p, were identified. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that these target genes of DEmiRNAs were associated with various biological processes (BPs). The results of validation in qRT-PCR and the GEO database suggested the reliability of our RNA-sequencing results.ConclusionsIn conclusion, we identified three miRNAs, including hsa-miR-199a-5p, hsa-miR-483-5p, and hsa-miR-432-5p, which may serve as biomarkers for embryo quality during IVF cycles.

Stress, anxiety, and depression in infertile couples are not associated with a first IVF or ICSI treatment outcome

BackgroundPsychological distress may exert a negative influence on reproductive function of couples at reproductive age. Couples seeking assisted reproductive technology (ART) treatment may have a higher prevalence of psychological distress than fertile couples. However, whether psychological distress is associated with the outcome of ART treatment remains unknown. We aimed to investigate the association of pre-treatment psychological distress and clinical pregnancy rate among infertility couples undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment.MethodsThis nested case-control study was conducted based on women who underwent their first fresh IVF or ICSI cycle in the Jiangsu Birth Cohort Study (JBC) between November 2015 and January 2019. A total of 150 women who did not obtain clinical pregnancy after first IVF or ICSI fresh embryo transfer were identified as cases, and a total of 300 age matched women who obtained clinical pregnancy were identified as controls. Conditional logistic regression analyses were used to investigate the association between psychological distress and the outcome of first IVF or ICSI treatment, adjusting for multiple potential confounders.ResultsNo statistically significant association was observed between score of maternal symptoms of psychological distress and clinical pregnancy. Adjusted ORs of logistic regression were 1.00 (95% CI 0.97-1.03) for anxiety, 0.98 (95% CI 0.95-1.02) for depression, and 0.98 (95% CI 0.95-1.01) for perceived stress, respectively. When treat depression and anxiety as categorical variables, 62 (13.8%) were classified as clinical depression, 11 (2.4%) were classified as clinical anxiety, among 450 women in the present study. Psychological distress symptoms were also not associated with clinical pregnancy rate. Adjusted ORs of logistic regression were 0.27 (95% CI 0.03-2.33) for anxiety, 0.88 (95% CI 0.46-1.68) for depression, respectively.ConclusionsOur findings firstly indicated that psychological distress experienced prior to IVF/ICSI treatment was not associated with clinical pregnancy.

Early detection of pregnancy after IVF and embryo transfer with hyperglycosylated HCG versus Elecsys HCG+β assay

Research questionIs measurement of hyperglycosylated HCG (hHCG) superior to beta-HCG (HCG+β) for early pregnancy detection after IVF and embryo transfer? DesignBlood samples were collected on day 4 (+1), 7 (+1) and 11 (+2) after embryo transfer from women aged 18–45 years undergoing first or second fresh or frozen IVF embryo transfer cycles. Biochemical pregnancy was assessed on-site by HCG determination on day 11; clinical pregnancy was assessed by ultrasound on day 21 (+4/–3). Serum hHCG (immunochemiluminometric assay) and HCG+β (Elecsys® HCG+β assay) concentrations were measured. Performance of hHCG and HCG+β for predicting pregnancy was evaluated and cut-offs selected. ResultsIn total, 155 women were enrolled and underwent IVF and embryo transfer. Area under the curve (AUC) (95% CI) on day 4 was not significantly different for hHCG (AUC 0.88; 95% CI 0.83 to 0.94) and HCG+β (AUC 0.90; 95% CI 0.84 to 0.95), as was predictive performance on day 7 and 11, with higher AUC estimates compared with day 4. Applying cut-offs derived according to Youden's index on day 4 (hHCG, 100 pg/ml; HCG+β, 1.30 mIU/ml), both biomarkers demonstrated high negative predictive values for ruling out pregnancy (hHCG, 83.8%; HCG+β, 82.8%) and high positive predictive values for ruling in pregnancy (hHCG, 89.0%; HCG+β, 84.9%) on day 21. Diagnostic performance improved from day 4 to day 11. ConclusionsPredictive performance for early pregnancy post-IVF embryo transfer of day-5 blastocysts was not significantly different for hHCG and HCG+β; hHCG superiority over HCG+β was not shown.

ERAP, KIR, and HLA-C Profile in Recurrent Implantation Failure.

The mother’s uterine immune system is dominated by uterine natural killer (NK) cells during the first trimester of pregnancy. These cells express killer cell immunoglobulin-like receptors (KIRs) of inhibitory or activating function. Invading extravillous trophoblast cells express HLA-C molecules, and both maternal and paternal HLA-C allotypes are presented to KIRs. Endoplasmic reticulum aminopeptidase 1 (ERAP1) and 2 (ERAP2) shape the HLA class I immunopeptidome. The ERAPs remove N-terminal residues from antigenic precursor peptides and generate optimal-length peptides to fit into the HLA class I groove. The inability to form the correct HLA class I complexes with the appropriate peptides may result in a lack of immune response by NK cells. The aim of this study was to investigate the role of ERAP1 and ERAP2 polymorphisms in the context of KIR and HLA-C genes in recurrent implantation failure (RIF). In addition, for the first time, we showed the results of ERAP1 and ERAP2 secretion into the peripheral blood of patients and fertile women. We tested a total of 881 women. Four hundred ninety-six females were patients who, together with their partners, participated in in vitro fertilization (IVF). A group of 385 fertile women constituted the control group. Women positive for KIR genes in the Tel AA region and HLA-C2C2 were more prevalent in the RIF group than in fertile women (p/pcorr. = 0.004/0.012, OR = 2.321). Of the ERAP polymorphisms studied, two of them (rs26653 and rs26618) appear to affect RIF susceptibility in HLA-C2-positive patients. Moreover, fertile women who gave birth in the past secreted significantly more ERAP1 than IVF women and control pregnant women (p < 0.0001 and p = 0.0005, respectively). In the case of ERAP2, the opposite result was observed; i.e., fertile women secreted far less ERAP2 than IVF patients (p = 0.0098). Patients who became pregnant after in vitro fertilization embryo transfer (IVF-ET) released far less ERAP2 than patients who miscarried (p = 0.0032). Receiver operating characteristic (ROC) analyses indicate a value of about 2.9 ng/ml of ERAP2 as a point of differentiation between patients who miscarried and those who gave birth to a healthy child. Our study indicates that both ERAP1 and ERAP2 may be involved in processes related to reproduction.

Development and Validation of Prediction Model for High Ovarian Response in In Vitro Fertilization-Embryo Transfer: A Longitudinal Study.

Objective To develop and validate a prediction model for high ovarian response in in vitro fertilization-embryo transfer (IVF-ET) cycles. Methods Totally, 480 eligible outpatients with infertility who underwent IVF-ET were selected and randomly divided into the training set for developing the prediction model and the testing set for validating the model. Univariate and multivariate logistic regressions were carried out to explore the predictive factors of high ovarian response, and then, the prediction model was constructed. Nomogram was plotted for visualizing the model. Area under the receiver-operating characteristic (ROC) curve, Hosmer-Lemeshow test and calibration curve were used to evaluate the performance of the prediction model. Results Antral follicle count (AFC), anti-Müllerian hormone (AMH) at menstrual cycle day 3 (MC3), and progesterone (P) level on human chorionic gonadotropin (HCG) day were identified as the independent predictors of high ovarian response. The value of area under the curve (AUC) for our multivariate model reached 0.958 (95% CI: 0.936-0.981) with the sensitivity of 0.916 (95% CI: 0.863-0.953) and the specificity of 0.911 (95% CI: 0.858-0.949), suggesting the good discrimination of the prediction model. The Hosmer-Lemeshow test and the calibration curve both suggested model's good calibration. Conclusion The developed prediction model had good discrimination and accuracy via internal validation, which could help clinicians efficiently identify patients with high ovarian response, thereby improving the pregnancy rates and clinical outcomes in IVF-ET cycles. However, the conclusion needs to be confirmed by more related studies.

Analysis of the levels of hope and influencing factors in infertile women with first-time and repeated IVF-ET cycles

PurposeTo explore the hope levels and influencing factors in infertile women undergoing first-time and repeated in vitro fertilization-embryo transfer (IVF-ET) cycles.MethodsThis study was a cross-sectional and convenient sampling study conducted among patients undergoing IVF-ET from January to June 2019. Patients were divided into first-time and repeated groups by the number of IVF-ET cycles, and then a questionnaire survey was administered. The questionnaire included demographic information, Herth hope index (HHI) scale, Locke-Wallace short marital-adjustment test scale and social support rating scale. Multiple linear regression was used to analyse the influencing factors associated with hope levels.ResultsA total of 298 IVF-ET patients were recruited for the study, including 150 (50.3%) in the first-time cycle group and 148 (49.7%) in the repeated cycle group. The HHI score of the repeated cycle group was significantly lower than that of the first-time cycle group (34.4 ± 3.5 vs. 37.5 ± 3.7, P < 0.001). Multiple linear regression analysis indicated that repeated IVF-ET and age were independently negatively correlated with HHI, with standardized coefficient β values of − 0.895 and − 0.223, respectively (both P < 0.001). High education level (P = 0.002), high monthly income (P = 0.020), high degree of short marital-adjustment test (P < 0.001) and social support rating (P < 0.001) were independently positively correlated with HHI.ConclusionInfertile women undergoing repeated IVF-ET have low hope levels. Maintaining a good marriage adjustment and establishing a good social support and relationship network could effectively improve their hope levels.

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.

Comparison of live birth rates after IVF–embryo transfer with and without preimplantation genetic testing for aneuploidies

Research questionDoes the use of preimplantation genetic testing for aneuploidies (PGT-A) result in higher live birth rates when compared with both fresh and frozen embryo transfers (FET) not utilizing PGT-A? DesignRetrospective cohort study at a single tertiary centre using inverse probability of treatment weighting (IPTW) to adjust for differences in baseline characteristics between groups. ResultsA total of 107 FET using PGT-A from 74 patients, along with 321 fresh and 286 FET not using PGT-A from 381 patients met the inclusion criteria for this study. In the IPTW-adjusted analysis of transfer-level data, PGT-A transfers resulted in a significantly higher live birth rate when compared with both non-PGT-A fresh (49.5% versus 38.6%, P = 0.036) and FET (50.6% versus 35.8%, P = 0.016). When data were analysed per retrieval level, the live birth rate was similar and acceptably high with or without PGT-A (63.7% versus 52.3%, P = 0.09). ConclusionWhen comparing PGT-A to non-PGT-A fresh and FET, PGT-A embryo transfers have a significantly higher live birth rate. However, this difference did not persist at a per-retrieval level. Further investigation is needed to understand in what scenarios PGT-A has clinical significance and whether differences in the number of available embryos for transfer negates the benefit of PGT-A.

In vitro fertilization-embryo transfer in patients with unexplained recurrent pregnancy loss.

Background:Empiric therapy for patients with unexplained recurrent pregnancy loss (URPL) is not precise. Some patients will ask for assisted reproductive technology due to secondary infertility or advanced maternal age. The clinical outcomes of URPL patients who have undergone in vitro fertilization-embryo transfer (IVF-ET) require elucidation. The IVF outcome and influencing factors of URPL patients need further study.Methods:A retrospective cohort study was designed, and 312 infertile patients with URPL who had been treated during January 2012 to December 2015 in the Reproduction Center of Peking University Third Hospital were included. By comparing clinical outcomes between these patients and those with tubal factor infertility (TFI), the factors affecting the clinical outcomes of URPL patients were analyzed.Results:The clinical pregnancy rate (35.18% vs. 34.52% in fresh ET cycles, P = 0.877; 34.48% vs. 40.27% in frozen-thawed ET cycles, P = 0.283) and live birth rate (LBR) in fresh ET cycles (27.67% vs. 26.59%, P = 0.785) were not significantly different between URPL group and TFI group. URPL group had lower LBR in frozen-thawed ET cycles than that of TFI group (23.56% vs. 33.56%, P = 0.047), but the cumulative LBRs (34.69% vs. 38.26%, P = 0.368) were not significantly different between the two groups. The increased endometrial thickness (EMT) on the human chorionic gonadotropin day (odds ratio [OR]: 0.848, 95% confidence interval [CI]: 0.748–0.962, P = 0.010) and the increased number of eggs retrieved (OR: 0.928, 95% CI: 0.887–0.970, P = 0.001) were protective factors for clinical pregnancy in stimulated cycles. The increased number of eggs retrieved (OR: 0.875, 95% CI: 0.846–0.906, P < 0.001), the increased two-pronucleus rate (OR: 0.151, 95% CI: 0.052–0.437, P < 0.001), and increased EMT (OR: 0.876, 95% CI: 0.770–0.997, P = 0.045) in ET day were protective factors for the cumulative live birth outcome.Conclusion:After matching ages, no significant differences in clinical outcomes were found between the patients with URPL and the patients with TFI. A thicker endometrium and more retrieved oocytes increase the probability of pregnancy in fresh transfer cycles, but a better normal fertilization potential will increase the possibility of a live birth.

A Novel Nomogram for Individualized Gonadotropin Starting Dose in GnRH Antagonist Protocol.

Controlled ovarian stimulation (COS) is one of the most vital parts of in vitro fertilization-embryo transfer (IVF-ET). At present, no matter what kinds of COS protocols are used, clinicians have to face the challenge of selection of gonadotropin starting dose. Although several nomograms have been developed to calculate the appropriate gonadotropin starting dose in gonadotropin releasing hormone (GnRH) agonist protocol, no nomogram was suitable for GnRH antagonist protocol. This study aimed to develop a predictive nomogram for individualized gonadotropin starting dose in GnRH antagonist protocol. Single-center prospective cohort study was conducted, with 198 women aged 20-45 years underwent IVF/intracytoplasmic sperm injection (ICSI)-ET cycles. Blood samples were collected on the second day of the menstrual cycle. All women received ovarian stimulation using GnRH antagonist protocol. Univariate and multivariate analysis were performed to identify predictive factors of ovarian sensitivity (OS). A nomogram for gonadotropin starting dose was developed based on the multivariate regression model. Validation was performed using concordance statistics and bootstrap resampling. A multivariate regression model based on serum anti-Müllerian hormone (AMH) level, antral follicle count (AFC), and body mass index (BMI) was developed and accounted for 59% of the variability of OS. An easy-to-use predictive nomogram for gonadotropin starting dose was established with excellent accuracy. The concordance index (C-index) of the nomogram was 0.833 (95% CI, 0.829-0.837). Internal validation using bootstrap resampling further showed the good performance of the nomogram. In conclusion, gonadotropin starting dose in antagonist protocol can be predicted precisely by a novel nomogram.

THE EFFECT OF LAPAROSCOPIC SURGERY UNDER GENERAL ANESTHESIA ON PREGNANCY OUTCOMES IN PATIENTS WITH HETEROTOPIC PREGNANCY FOLLOWING IVF-ET

To evaluate the effects of laparoscopic surgery under general anesthesia on pregnancy outcomes of patients with heterotopic pregnancy (HP) following in vitro fertilization-embryo transfer (IVF-ET). This retrospective study reviewed 24 patients with HP following IVF-ET between January 2018 and August 2020. The patients had been divided into two groups according to whether fetal heart activities were detected by ultrasound preoperatively in intrauterine pregnancy (IUP) at diagnosis. General characteristics, clinical characteristics, pregnancy outcomes were compared between the group with heart activity in IUP (18cases) and the group without heart activity in IUP (6 cases). The general and clinical characteristics were comparable except previous ectopic pregnancy history and fetal status in IUP after surgery between two groups. The rate of previous ectopic pregnancy in group with heart activity in IUP was 33.3% versus 0 in group without heart activity in IUP (p=0.04). Postoperative transvaginal ultrasound (TVS) scans had confirmed that four cases were not able to continue intrauterine pregnancies: 1 patient (16.7%) with heart activity in IUP versus 3 patients (50.0%) without heart activity in IUP, the difference was statistically significant (P=0.02). Among the 20 patients who were able to continue intrauterine pregnancy after surgery, the live birth rate, miscarriage rate, premature birth rate, term birth rate, cesarean section rate, male rate, low birth weight infant rate of the group with heart activity in IUP were 88.2%, 11.8%, 17.6%, 70.6%, 93.3%, 53.3%, 20.0%, which were 66.7%, 33.3%, 0, 66.7%, 100%, 100%, 0 in the group without heart activity in IUP respectively, there were no significant differences between the two groups (P>0.05). Among the neonates, one premature neonate was diagnosed with Pilot type sequence sign at birth, and the rest neonates had no birth defects. Laparoscopic surgery under general anesthesia in early pregnancy was safe for HP patients. Early diagnosis and timely surgical treatment may lead to favorable pregnancy outcomes, especially for the patients with heart activity in IUP.