Identification of candidate SNPs associated with embryo mortality and fertility traits in lactating Holstein cows.

Introduction: Targeted single nucleotide polymorphisms (SNPs) have been used in genomic prediction methodologies to enhance the accuracy of associated genetic transmitting abilities in Holstein cows. The objective of this study was to identify and validate SNPs associated with fertility traits impacting early embryo mortality. Methods: The mRNA sequencing data from day 16 normal (n = 9) and embryo mortality (n = 6) conceptuses from lactating multiparous Holstein cows were used to detect SNPs. The selection of specific genes with SNPs as preliminary candidates was based on associations with reproductive and fertility traits. Validation of candidate SNPs and genotype-to-phenotype analyses were conducted in a separate cohort of lactating primiparous Holstein cows (n = 500). After genotyping, candidate SNPs were filtered using a quality control pipeline via PLINK software. Continuous numeric and binary models from reproductive traits were evaluated using the mixed procedure for a generalized linear model-one way ANOVA or logistic regression, respectively. Results: Sixty-nine candidate SNPs were initially identified, but only 23 passed quality control procedures. Ultimately, the study incorporated 466 observations for statistical analysis after excluding animals with missing genotypes or phenotypes. Significant (p <0.05) associations with fertility traits were identified in seven of the 23 SNPs: DSC2 (cows with the A allele were older at first calving); SREBF1 and UBD (cows with the T or G alleles took longer to conceive); DECR1 and FASN (cows with the C allele were less likely to become pregnant at first artificial insemination); SREBF1 and BOLA-DMB (cows with the T allele were less likely to be pregnant at 150 days in milk). It was also determined that two candidate SNPs within the DSC2 gene were tag SNPs. Only DSC2 SNPs had an important allele substitution effect in cows with the G allele, which had a decreased age at first calving by 10 days. Discussion: Candidate SNPs found in this study could be used to develop genetic selection tools to improve fertility traits in dairy production systems.

Histology Atlas of the Developing Mouse Respiratory System From Prenatal Day 9.0 Through Postnatal Day 30.

Respiratory diseases are one of the leading causes of death and disability around the world. Mice are commonly used as models of human respiratory disease. Phenotypic analysis of mice with spontaneous, congenital, inherited, or treatment-related respiratory tract abnormalities requires investigators to discriminate normal anatomic features of the respiratory system from those that have been altered by disease. Many publications describe individual aspects of normal respiratory tract development, primarily focusing on morphogenesis of the trachea and lung. However, a single reference providing detailed low- and high-magnification, high-resolution images of routine hematoxylin and eosin (H&E)-stained sections depicting all major structures of the entire developing murine respiratory system does not exist. The purpose of this atlas is to correct this deficiency by establishing one concise reference of high-resolution color photomicrographs from whole-slide scans of H&E-stained tissue sections. The atlas has detailed descriptions and well-annotated images of the developing mouse upper and lower respiratory tracts emphasizing embryonic days (E) 9.0 to 18.5 and major early postnatal events. The selected images illustrate the main structures and events at key developmental stages and thus should help investigators both confirm the chronological age of mouse embryos and distinguish normal morphology as well as structural (cellular and organ) abnormalities.

Knowledge, attitude, and practice of embryo transfer among women who underwent in vitro fertilization-embryo transfer.

Introduction: The infertile patient's knowledge, attitude, and practice (KAP) toward embryo transfer may affect treatment outcomes and the mental health of women who underwent in vitro fertilization-embryo transfer (IVF-ET). This study aimed to investigate the KAP of embryo transfer among women who underwent IVF-ET. Methods: This cross-sectional study was conducted on women who underwent IVF-ET at our Hospital between May 2023 and November 2023, using a self-designed questionnaire. Results: A total of 614 valid questionnaires were finally included. The mean KAP scores were 19.46 ± 5.06 (possible range: 0 28), 39.41 ± 5.20 (possible range: 12-60), and 48.02 ± 6.75 (possible range: 0-60), respectively. The structural equation model demonstrated that knowledge has a direct effect on attitude (ß = 0.27, p < 0.001) and attitude has a direct effect on practice (ß = 0.55, p < 0.001) and anxiety (ß = 0.59, p < 0.001). Moreover, multivariable linear regression analysis showed that anxiety score [coefficient = 0.09, 95% confidence interval (CI): 0.03-0.16, p = 0.003], BMI (coefficient = 0.09, 95%CI: 0.03-0.16, p = 0.003), education (coefficient = 5.65-6.17, 95%CI: 1.09-10.7, p < 0.05), monthly per capita income (coefficient = 1.20-1.96, 95% CI: 0.21-3.07, p = 0.05), reasons for IVF (coefficient = -1.33-1.19, 95% CI: -2.49-0.09, p < 0.05), and more than 5 years of infertility (coefficient = -1.12, 95% CI: -2.11-0.13, p = 0.026) were independently associated with sufficient knowledge. Knowledge (coefficient = 0.19, 95% CI: 0.12-0.26, p < 0.001), anxiety (coefficient = 0.39, 95% CI: 0.34-0.45, p < 0.001), monthly per capita household income >10,000 (coefficient = 1.52, 95% CI: 0.61-2.43, p < 0.001), and three or more cycles of embryo transfer (coefficient = -2.69, 95% CI: -3.94-1.43, p < 0.001) were independently associated with active attitude. Furthermore, attitude (coefficient = 0.21, 95% CI: 0.11-0.30, p < 0.001) and anxiety (coefficient = 0.57, 95% CI: 0.49-0.65, p < 0.001) were independently associated with proactive practice. Discussion: Women who underwent IVF-ET had inadequate knowledge and negative attitudes but proactive practice toward embryo transfer, which were affected by anxiety, income, and reasons for IVF. It is necessary to strengthen the continuous improvement of patient education to improve the management of embryo transfer.

The association between female age and pregnancy outcomes in patients receiving first elective single embryo transfer cycle: a retrospective cohort study.

This study aimed to explore the relationship between female age and pregnancy outcomes in patients undergoing their first elective single embryo transfer (eSET) of in vitro fertilization (IVF) cycles. The retrospective cohort study encompassed 7089 IVF/intracytoplasmic sperm injection (ICSI) patients of the Reproductive Medicine Center, Henan Provincial Peoples' Hospital of China, from September 1, 2016, to May 31, 2022. Patients all received the first eSET in their IVF/ICSI cycles. A generalized additive model (GAM) was employed to examine the the dose-response correlation between age and pregnancy outcomes, namely the clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR). Logistic regression model was employed to ascertain the correlation between the CPR/OPR and age. The study cohort has an average age of 30.74; 3843 patients got clinical pregnancy rate of 61.40% and ongoing pregnancy rate of 54.21%. The multiple pregnancy rate of is 1.24%. For patients aged 34 and above, the CPR decreased by 10% for every 1-year increase in age (adjusted OR 0.90, 95% CI 0.84-0.96, p < 0.0001). Similarly, the OPR decreased by 16% for every 1-year increase in age (adjusted OR 0.84, 95% CI 0.81-0.88, p < 0.0001). Patients aged 35-37 years had an acceptable OPR of 52.4% after eSET, with a low multiple pregnancy rate (1.1%). Pregnancy outcomes were significantly better in blastocyst cycles compared to cleavage embryo cycles, and this trend was more pronounced in older patients. There was a non-linear relationship between female age and pregnancy outcomes in patients undergoing their first eSET cycles. The clinical pregnancy rate and ongoing pregnancy rate decreased significantly with age, especially in women older than 34 years. For patients under 37 years old, single embryo transfer should be prioritized. For patients over 38 years old with available blastocysts, eSET is also recommended.

Drinking water quality impacts oocyte viability and embryo development.

Normal reproductive function and fertility is considered a "sixth vital sign" because disruptions to this sensitive physiological system can forewarn other health issues, including exposure to environmental toxicants. We found that female mice exhibited profound loss of embryos during pre-implantation and fetal development coincident with a change to the source of their drinking water. When female mice were provided with tap water from the building in which they were housed (Water 2), instead of tap water from a neighboring building which was their previous supply (Water 1), ovulated oocytes were degenerated or had impaired meiotic maturation, and failed to form embryos. The harmful effects of Water 2 exposure were not reversible even following a recovery period; however, carbon-filtration of Water 2 removed the toxic contaminant. Water composition analysis to identify the responsible toxicant(s) found that trace elements were present at expected levels and phthalates were undetectable. Per- and Poly-fluoroalkyl Substances (PFAS), a family of persistent organic pollutants were detected at ∼4 ng/L. To investigate further, female mice were given drinking water categorized by level of PFAS contamination (0.6 ng/L, 2.8 ng/L, or 4.4 ng/L) for 9 weeks. Compared to mice consuming purified MilliQ water, mice consuming PFAS-contaminated water had decreased oocyte quality, impaired embryogenesis and reduced cell numbers in blastocysts. PFAS concentration in the drinking water was negatively correlated with oocyte viability. Importantly, the levels of PFAS detected in the tap water are within current "safe level" guidelines, and further research is needed to determine whether PFAS are responsible for the observed reproductive toxicity. However, this research demonstrating that water deemed suitable for human consumption has detrimental effects on mammalian embryo development has important implications for public health and water quality policies.

Enhancing Intracytoplasmic Sperm Injection Outcomes With Zeta Sperm Selection: A Case Report.

Sperm morphology significantly influences the fertilization capacity of male germ cells. Morphological abnormalities are frequently associated with an overproduction of reactive oxygen species (ROS), leading to further sperm damage and subsequent infertility. This case study examines a couple facing infertility, with male factor infertility identified as the primary issue, characterized by teratozoospermia and a high DNA fragmentation index (DFI). The objective was to assess the efficacy of zeta potential (ZP) as a sperm sorting technique for intracytoplasmic sperm injection (ICSI) in patients showing high DNA fragmentation. A 34-year-old male with abnormal sperm parameters underwent ICSI using the ZP technique for sperm separation, while his 28-year-old female partner received ovarian stimulation. This intervention resulted in the development of two good-quality blastocysts, resulting in a successful embryo transfer (ET) and a positive pregnancy outcome. Previous attempts using conventional assisted reproductive technologies (ART), including in vitro fertilization (IVF), followed by ICSI and ET, as well as other sperm selection methods, were not successful. The ZP-based approach demonstrated significant benefits by selecting spermatozoa with optimal parameters, such as negative membrane potential, thereby enhancing the success rate. This case emphasizes the advantages of personalized treatment strategies in managing male infertility and highlights the potential of advanced sperm sorting techniques in improving fertility outcomes.

Recryopreservation impairs blastocyst implantation potential via activated endoplasmic reticulum stress pathway and induced apoptosis.

Recryopreservation (recryo) is occasionally applied in clinical, while the underlying mechanism of impaired clinical outcomes after recryo remains unclear. In this study, frozen embryo transfer (FET) cycles of single blastocyst transfer in an academic reproductive medicine center were enrolled. According to the number of times blastocysts experienced cryopreservation, they were divided into the cryopreservation (Cryo) group and the Recryo group. Donated human blastocysts were collected and detected for mechanism exploration. It was found that recryo procedure resulted in impaired blastocyst developmental potential, including decreased implantation rate, reduced biochemical pregnancy rate, declined clinical pregnancy rate, higher early miscarriage rate, and lower live birth rate. Moreover, recryo led to impaired trophectoderm (TE) function, exhibiting lower human chorionic gonadotropin levels 12 days after FET. In addition, single-cell RNA sequencing showed that the expression of genes involved in cell adhesion and embryo development were altered. More specifically, activated endoplasmic reticulum (ER) pathway and induced apoptosis were further verified by immunofluorescence and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay involving in the recryo procedure. In conclusion, recryo could interfere with the process of blastocyst implantation by impairing TE function, affecting blastocyst adhesion, activating ER stress pathway and inducing apoptosis. It provides caution to embryologists about the potential risk of recryopreservation.

The Effect of Progesterone Elevation on the Day of Trigger Administration: A Review of the Literature.

Since the advent of assisted reproductive technology, different variables have been shown to affect pregnancy outcomes. One of the most prevalent studied events is the premature rise in serum progesterone concentrations on the day of trigger administration during cycles of ovarian stimulation. This phenomenon, classically known as premature luteinization, has been observed significantly for decades and has been linked to adverse pregnancy outcomes and lower live birth rates. Ultimately, a quest to find a precise serum progesterone concentration cut-off value that can be effectively used to predict pregnancy outcomes prior to trigger administration is still underway. The purpose of the current research was to study the available literature on the relationship between serum progesterone on the day of trigger administration in controlled ovarian stimulation cycles used for IVF in an attempt to identify a cut-off serum progesterone concentration that can be used to effectively predict future pregnancy outcomes in fresh transfers. This study is a review of the literature and is based on information and data gathered from 36 published articles. The majority of the literature shows that a serum progesterone concentration cut-off of 1.5 ng/ml (4.77 nmol/L) can be used prior to trigger administration to effectively predict pregnancy outcomes. Premature progesterone elevation on the day or prior to the trigger administration is associated with adverse pregnancy outcomes in IVF cycles. Other factors such as follicle number, serum concentration of other hormones, and ovarian response to ovarian stimulation should also be considered to predict the success of IVF protocols.

Evaluation of the Effect of Embryo Transfer Methods on Pregnancy Outcomes: A Retrospective Study and Future Perspectives.

Background: Trans-abdominal ultrasound (TAUS) and transvaginal ultrasound (TVUS) are used for embryo transfer. However, few studies were conducted to compare the methods and assess their effect on pregnancy outcomes. Methods: A retrospective cohort study was conducted at Mahdieh Hospital in Tehran, analyzing 506 ICSI cycles with fresh embryo transfer. The study period was from April 2019 to March 2022. Following the evaluation of patients' profile, they were divided into two groups of TAUS (n=250) and TVUS (n=256). The pregnancy outcomes included positive test of ß-HCG, history of miscarriage, ectopic pregnancy (EP), clinical pregnancy, and the duration of the embryo transfer were compared between two groups. Mann-Whitney U test, Pearson Chi-Square test, Fisher's exact test, and logistic regression were used for data analysis. Results: The rate of chemical and clinical pregnancy in the TAUS group was higher compared to the TVUS group, which was statistically significant (p<0.05). The rate of live term birth and live preterm birth was higher in the TAUS group compared to the TVUS group, though the difference was insignificant. Moreover, EP and abortion rates were higher in TVUS group compared to the TAUS group, but the differences were not statistically significant. The odds ratio of achieving pregnancy was higher with TAUS compared to TVUS, but this was only statistically significant for the age variable. Conclusion: The use of TAUS method appears to be associated with improved pregnancy outcome, including higher rates of chemical and clinical pregnancy, compared to TVUS. Yet, further research is needed to confirm these findings and elucidate underlying mechanisms.

Preovulation body mass index and pregnancy after first frozen embryo transfer in patients with polycystic ovary syndrome and insulin resistance.

OBJECTIVE: To examine the association between preovulation body mass index and pregnancy outcomes after frozen embryo transfer in patients with polycystic ovary syndrome with insulin resistance. DESIGN: This was a single-center, retrospective cohort study. SUBJECTS: Women with infertility, diagnosed with polycystic ovary syndrome and insulin resistance, and treated at the Reproductive Medicine Center, Second People's Hospital of Nanning, China, between January 2020 and August 2023, were included. EXPOSURE: Patients were divided into four groups according to their body mass index (BMI): slim (<18.5 kg/m2), normal (18.5≤ BMI <24 kg/m2), overweight (24≤ BMI <28 kg/m2), or obese (≥28 kg/m2). MAIN OUTCOME MEASURES: The main pregnancy outcomes included rates of embryo implantation, biochemical pregnancy, clinical pregnancy, and ongoing pregnancy. RESULTS: In total, 282 eligible patients were included. A linear association was observed between the BMI and clinical pregnancy outcomes of the first frozen embryo transfer (P for nonlinearity>0.05). After accounting for all potential variables, each 1 kg/m2 increase in BMI was linked to a 2% decrease in the embryo implantation rate (P<0.05), 11% decrease in the frequency of biochemical pregnancy (P<0.05), and 9% decrease in the both clinical (P<0.05) and ongoing pregnancy rates. CONCLUSION: In patients with polycystic ovary syndrome and insulin resistance, a higher BMI was associated with lower rates of embryo implantation, biochemical pregnancy, clinical pregnancy, and ongoing pregnancy.

Pathways to motherhood: A single-center retrospective study on fertility preservation and reproductive outcomes in patients with breast cancer.

BACKGROUND: Breast cancer treatments often have negative effects on fertility, which pose challenges among patients who want to be parents in the future. This study aimed to examine the efficacy of oocyte cryopreservation, embryo cryopreservation, and ovarian tissue cryopreservation in patients with breast cancer. METHODS: This retrospective review evaluated 42 patients with breast cancer who underwent fertility preservation at our center from January 2012 to December 2022. This review encompassed the demographic characteristics of the patients, cancer stages, treatment details, and types of fertility preservation procedures and their outcomes. RESULTS: The average age at disease diagnosis was 33.4 years. Approximately 90.4% of patients presented with early-stage cancer (≤2). Of 42 patients, 26 underwent oocyte cryopreservation; 17, embryo cryopreservation; and 2, ovarian tissue cryopreservation. Further, three patients received mixed treatment. The overall live birth rate was 63.2%. There are more live births in embryo cryopreservation group. The successful pregnancy group was significantly younger and had a remarkably higher quantity of preserved oocytes/embryos than the nonsuccessful pregnancy group. The oocyte and embryo utilization rates in cryopreservation were 7.69% and 52.94%, respectively. These findings underscored the importance of prompt, informed discussions about fertility preservation options. CONCLUSION: Fertility preservation in patients with breast cancer have promising reproductive outcomes, with embryo cryopreservation being particularly effective. Prompt counseling and individualized fertility preservation strategies are important for improving the likelihood of posttreatment pregnancy. Nevertheless, future research on the long-term psychological and emotional effects of different fertility preservation methods must be performed.

Individual variation in the emergence of anterior-to-posterior neural fates from human pluripotent stem cells.

Variability between human pluripotent stem cell (hPSC) lines remains a challenge and opportunity in biomedicine. In this study, hPSC lines from multiple donors were differentiated toward neuroectoderm and mesendoderm lineages. We revealed dynamic transcriptomic patterns that delineate the emergence of these lineages, which were conserved across lines, along with individual line-specific transcriptional signatures that were invariant throughout differentiation. These transcriptomic signatures predicted an antagonism between SOX21-driven forebrain fates and retinoic acid-induced hindbrain fates. Replicate lines and paired adult tissue demonstrated the stability of these line-specific transcriptomic traits. We show that this transcriptomic variation in lineage bias had both genetic and epigenetic origins, aligned with the anterior-to-posterior structure of early mammalian development, and was present across a large collection of hPSC lines. These findings contribute to developing systematic analyses of PSCs to define the origin and consequences of variation in the early events orchestrating individual human development.

Oligoasthenospermia Correlates with Increased Preeclampsia Incidence in Subfertile Couples Undergoing In Vitro Fertilization and Embryo Transfer (IVF-ET): A Secondary Analysis of a Randomized Clinical Trial.

OBJECTIVE: To evaluate whether intergroup differences in the risk of maternal pregnancy complications following in vitro fertilization (IVF) vary with male factor. DESIGN: A post hoc exploratory secondary analysis of data from a multicenter, randomized, controlled, non-inferiority trial (NCT03118141). SETTING: Academic fertility centers. SUBJECTS: A total of 1131 subfertile women with complete recording of their male partner's semen parameters during the trial were enrolled. All participants underwent intracytoplasmic sperm injection (ICSI) followed by frozen embryo transfer (FET) as part of their assisted reproductive technology (ART) treatment protocol. INTERVENTIONS: Women were divided into an oligoasthenospermia group (n=405) and a normospermia group (n=726) according to the quality of male sperm. MAIN OUTCOME MEASURES: Pregnancy complications, principally including the incidence of preeclampsia. RESULTS: Notably, we found that the risk of maternal preeclampsia was significantly higher in the oligoasthenospermia group than in the normospermia group (P=0.035). After adjustments for confounding factors by multivariate logistic regression analysis, the incidence of preeclampsia in the oligoasthenospermia group was still significantly higher than that in the normospermia group (6.55% vs. 3.60%; OR=0.529; 95% CI=0.282-0.992; P-adj=0.047). However, there were no significant differences in terms of embryo quality, cumulative live birth rate, other pregnancy complications or neonatal outcomes between the two groups (P>0.05). CONCLUSION: Oligoasthenospermia was associated with a higher risk of maternal preeclampsia in subfertile couples undergoing IVF-ET treatment. In clinical practice, it is essential to thoroughly evaluate the sperm quality and quantity of male partners before IVF-ET. Further research is needed to establish the causal relationships between semen quality and adverse pregnancy complications, particularly preeclampsia, and to explore potential interventions.

Assisted oocyte activation significantly improves zygote formation, cleavage, and implantation rates in patients with a history of fertilization failures.

Background: Fertilization check performed at the 18th hour following classic in vitro fertilization procedure (IVF) or intracytoplasmic sperm injection (ICSI) is a critical stage in assisted reproduction. The success of the treatment is significantly reliant on the quantity of zygotes exhibiting two pronuclei. Consequently, low fertilization rates or complete fertilization failure are highly undesirable outcomes for both patients and reproductive specialists. Applying additional calcium ionophore for oocyte activation subsequent to ICSI may offer benefits and potentially enhance treatment outcomes, particularly for patients who have experienced low or absent fertilization rates (FR) in previous treatment cycles. The aim of the study is to evaluate the efficacy of Ca2+ ionophore application for oocyte activation. Methods: A retrospective analysis of 924 oocytes obtained from 120 patients who underwent ICSI cycles with a history of low or no fertilization as a result of previous unsuccessful treatment rounds. The next ART cycle followed with additional oocyte Ca2+ ionophore activation applied in 57 of the cases in order to optimize the treatment process (Group 1), and 63 patients were included and their outcomes followed as a control group (Group 2).We conducted a comparative analysis of results in both groups. The study's primary outcomes encompassed fertilization, cleavage embryo quality, blastocyst rate, and established clinical pregnancies. Results: At day 1 fertilization check we had 274/386 zygotes (71%FR) in group 1 and 132/410 in group 2 (32.2%FR), (P < 0.0001). Twenty-two (34.9%) cycles in group 2 resulted in total fertilization failure (TFF). At the cleavage stage top-quality embryos from group 1 were significantly higher (P = 0.0021) in comparison to group 2. Forty-eight embryo transfers (ET) were performed in group 1 resulting in 41.67% clinical pregnancies versus 33 ET and only 4 pregnancies (12.12%) for group 2 (P = 0.0044). Conclusions: The results confirm the appropriateness of assisted oocyte activation as an additional method in cases of previous fertilization failure cycles.

Exploring the Effects of Lignin Nanoparticles in Different Zebrafish Inflammatory Models.

Purpose: Lignin is the most abundant source of aromatic biopolymers and has gained interest in industrial and biomedical applications due to the reported biocompatibility and defense provided against bacterial and fungal pathogens, besides antioxidant and UV-blocking properties. Especially in the form of nanoparticles (NPs), lignin may display also antioxidant and anti-inflammatory activities. Methods: To evaluate these characteristics, sonochemically nano-formulated pristine lignin (LigNPs) and enzymatically-phenolated one (PheLigNPs) were used to expose zebrafish embryos, without chorion, at different concentrations. Furthermore, two different zebrafish inflammation models were generated, by injecting Pseudomonas aeruginosa lipopolysaccharide (LPS) and by provoking a wound injury in the embryo caudal fin. The inflammatory process was investigated in both models by qPCR, analyzing the level of genes as il8, il6, il1ß, tnfα, nfkbiaa, nfk2, and ccl34a.4, and by the evaluation of neutrophils recruitment, taking advantage of the Sudan Black staining, in the presence or not of LigNPs and PheLigNPs. Finally, the Wnt/ß-catenin pathway, related to tissue regeneration, was investigated at the molecular level in embryos wounded and exposed to NPs. Results: The data obtained demonstrated that the lignin-based NPs showed the capacity to induce a positive response during an inflammatory event, increasing the recruitment of cytokines to accelerate their chemotactic function. Moreover, the LigNPs and PheLigNPs have a role in the resolution of wounds, favoring the regeneration process. Conclusion: In this paper, we used zebrafish embryos within 5 days post fertilization (hpf). Despite being an early-stage exemplary, the zebrafish embryos have proven their potential as predicting models. Further long-term experiments in adults will be needed to explore completely the biomedical capabilities of lignin NPs. The results underlined the safety of both NPs tested paved the way for further evaluations to exploit the anti-inflammatory and pro-healing properties of the lignin nanoparticles examined.

Follicular Fluid Metabolomics: Tool for Predicting IVF Outcomes of Different Infertility Causes.

Infertility affects approximately 15% of couples at child-bearing ages and assisted reproductive technologies (ART), especially in vitro fertilization and embryo transfer (IVF-ET), provided infertile patients with an effective solution. The current paradox is that multiple embryo transfer that may leads to severe obstetric and perinatal complications seems to be the most valid measure to secure high success rate in the majority of clinic centers. Therefore, to avoid multiple transfer of embryos, it is urgent to explore biomarkers for IVF prognosis to select high-quality oocytes and embryos. Follicular fluid (FF), a typical biofluid constituted of the plasma effusion and granulosa-cell secretion, provides essential intracellular substances for oocytes maturation and its variation in composition reflects oocyte developmental competence and embryo viability. With the advances in metabolomics methodology, metabolomics, as an accurate and sensitive analyzing method, has been utilized to explore predictors in FF for ART success. Although FF metabolomics has provided a great possibility for screening markers with diagnostic and predictive value, its effectiveness is still doubted by some researchers. This may be resulted from the ignorance of the impact of sterility causes on the FF metabolomic profiles and thus its predictive ability might not be rightly illustrated. Therefore, in this review, we categorically demonstrate the study of FF metabolomics according to specific infertility causes, expecting to reveal the predicting value of metabolomics for IVF outcomes.

Does it affect the live birth rates to have a maximum endometrial thickness of 7, 8, or 9 mm in in-vitro fertilization-embryo transfer cycles?

Objective: To assess the effect of endometrial thickness (EMT) on live birth rates (LBR) in women with endometrial lining between 7.0-9.9 mm. Methods: This retrospective cohort study included women who underwent fresh and frozen embryo transfers between 2008 and 2018, grouped according to their maximum EMT; group 1: 7.0-7.9 mm, group 2: 8.0-8.9 mm, and group 3: 9.0-9.9 mm and underwent blastocyst transfer. Results: The study included 7091 in-vitro fertilization cycles: 1,385 in group 1, 3,000 in group 2, and 2,706 in group 3. The combined LBR was 22.2%. The mean age of women at oocyte retrieval day was 36.2±4.5 years. There was no difference in female age at oocyte retrieval or in the quality of embryos transferred between the three groups. Group 1 had more diagnoses of diminished ovarian reserve (25.5% vs. 19.5% and 19.1%; P=0.001) and less male factor infertility compared with groups 2 and 3, respectively (25.0% vs. 28.8% and 28.5%; P=0.02). LBR was higher with increasing endometrial thickness, groups 2 vs. group 1 (22.0% vs. 17.4%; P=0.0004), group 3 vs. group 1 (25.0% vs. 17.2%; P<0.001), and group 3 vs. group 2 (25.0% vs. 22.0%; P=0.008). After controlling for confounding factors, these three groups did not differ in LBR (group 1 vs. group 2, OR, 1.08; 95% CI, 0.83-1.4; P=0.54 and group 1 vs. group 3, OR, 1.16; 95% CI, 0.9-1.5; P=0.24). Conclusion: Live birth rates in women with endometrial thickness between 7.0-9.9 mm were not affected by different cut-offs when blastocyst transfer was performed.

Association of Fibroblast Growth Factor-1 Promoter Polymorphism and its Serum Concentrations with Repeated Implantation Failure after In vitro Fertilisation: A Cross-sectional Study.

Background: Fibroblast growth factors (FGFs) play a key role in embryo implantation and support endometrial trophoblastic interaction. Aim: The aim of the study was to evaluate the association between FGF-1 (rs34011) gene variety and its serum concentration with repeated implantation failure (RIF). Setting and Design: The design of the study was a cross-sectional study. Materials and Methods: Four hundred infertile women with a history of RIF and 400 healthy women undergoing the first in vitro fertilisation-embryo transfer attempt with successful delivery (controls) were enrolled in the study. Genomic DNA was extracted from peripheral blood leucocytes and genotyped by Tetra-Primer Amplification Refractory Mutation System-Polymerase Chain Reaction. Serum FGF-1 concentration was evaluated with enzyme-linked immunosorbent assay. Statistical Analysis Used: The ANOVA test was used to analyse the difference between the means of the groups. Results: In RIF group, the genotype frequencies of the GG, GA and AA were 59%, 33.5% and 7.5%, respectively, whereas in controls were 72.5%, 24% and 3.5%, respectively. The G and A allele frequencies in the RIF group were 75.75% and 24.25%, while in controls were 84.5% and 15.5%, respectively (P < 0.0001). We have also shown that serum FGF-1 concentration in RIF and control groups was 17 ± 3.55 and 23.62 ± 4.91 pg/mL, respectively (P = 0.008). We have also shown that AA genotype is significantly associated with decreased serum FGF-1 concentration in RIF (AA, GA and GG serum levels were 9.55 ± 2.65, 14 ± 3.35 and 22.55 ± 7.26 pg/mL, and in controls were 12.22 ± 2.27, 18.44 ± 5.98 and 26.66 ± 8.29 pg/mL, respectively). Conclusion: The current study suggests that a significant association between FGF-1 (rs34011) promoter polymorphism and its serum concentration with RIF. The study also suggests that AA genotype is linked to lower FGF-1 serum levels and may play a risk factor for RIF.

The pregnancy rescue case versus typical abortion.

Hendricks' pregnancy rescue case (PRC) tries to show that abortion is typically morally wrong. I argue here that there are at least two morally relevant differences between the abortion in PRC and the typical abortion so that the latter isn't morally wrong even if the former is morally wrong. I develop five modifications to PRC to show that these two differences are morally important. First, in PRC we don't know whether the person gives informed consent to the abortion, nor does the medical professional who will perform the abortion, and so the abortion can't be performed because the patient gives informed consent to it. Second, not preventing the death of the fetus in PRC brings about the death of an additional fetus gestating in a separate pregnant person, whereas most abortions don't entail the termination of another's pregnancy.

Transcriptional insights from the human embryo identify laminin-511 as a suitable matrix for human trophoblast stem cell culture.

The establishment of culture conditions to propagate self-renewing human trophoblast stem cells in long-term culture provides a paradigm for in vitro modelling of trophoblast. The extracellular matrix (ECM) is a critical determinant of cell identity and behaviour. Therefore, models aiming to reproduce cells in vitro should recapitulate the native cell-ECM microenvironment. Here, we mine human embryo transcriptional datasets to identify ECM components and cognate receptors expressed in the trophectoderm. Following, we identify laminin-511-E8 protein fragment as a physiologically relevant ECM capable of maintaining hTSCs in the stem cell state and retaining differentiation ability.