Assisted Reproductive Outcomes Research Articles

Associations between maternal MTHFR polymorphisms and embryological outcomes in Korean patients with infertility undergoing IVF/ICSI cycles

Objective Methylenetetrahydrofolatereductase (MTHFR) is important for folate metabolism, which is involved in DNA synthesis and cell growth. However, the relationship between Maternal MTHFR polymorphisms and outcomes in assisted reproduction remains controversial. This is the first study to explore the effect of MTHFR polymorphisms on the embryological outcomes in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles in Korean patients with infertility. Materials and methods This retrospective cohort study included 173 women who underwent MTHFR genotyping between July, 2021 and June, 2022. The embryologic outcomes of 301 IVF/ICSI cycles were compared between groups according to MTHFR polymorphisms using ANOVA and Chi-square test. Results Oocyte maturation rates were 80.0%, 75.0%, and 71.4% for MTHFR 677CC, 677CT, and 677TT, respectively. Cleaved embryo formation and transplantable embryo rates were comparable across various maternal MTHFR 677 genotypes. Good-quality embryo (GQE) rate was higher for MTHFR 677CT than those for 677CC and 677TT (40.0% vs. 29.4%, p = 0.001 and 40.0% vs. 33.3%, p = 0.025, respectively). When analyzing the combined MTHFR genotypes, the oocyte maturation rate was significantly lower in 677TT than in 677CC 1298AA/677CC 1298AC and 677CC 1298CC/677CT 1298AA/677CT 1298AC (71.4% vs. 76.7%, p = 0.012 and 71.4% vs. 75.7%, p = 0.029, respectively). The MTHFR 677CC/1298CC, 677CT/1298AA, and 677CT/1298AC genotypes had the highest GQE rates. Conclusions MTHFR 677TT genotype, which had the lowest enzymatic activity, had the lowest oocyte maturation rate. The combined MTHFR 677CC/1298CC, 677CT/1298AA, and 677CT/1298AC genotypes with intermediate enzyme activities had higher GQE rates. However, no differences were observed in the transplantable embryo rate between MTHFR genotypes.

Investigating the Imperative Role of microRNAs Expression in Human Embryo Implantation: A Narrative Review Based on Recent Evidence.

Embryo implantation is a highly complex process that requires the precise regulation of numerous molecules to be orchestrated successfully. Micro RNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play a crucial role in the regulation of embryo implantation. This article aims to summarize the key findings of the literature regarding the role of miRNAs in human embryo implantation, emphasizing their involvement in critical stages such as decidualization, endometrial receptivity and trophoblast adhesion. This review includes primary research articles from the past decade. The studies utilize a range of experimental methodologies, including gene expression analysis and in vitro studies. MicroRNAs, like miR-320a, miR-149, and miR30d secreted by preimplantation embryos and blastocysts significantly influence endometrial receptivity by promoting essential cellular processes, such as cell migration and trophoblast cell attachment, while others-miR17-5p, miR-193-3p, miR-372, and miR-542-3p-secreted from the endometrium regulate the decidualization phase. During the apposition and adhesion phases, miRNAs play a complex role by promoting, for example, miR-23b-3p, and inhibiting-as do miR-29c and miR-519d-3p-important biological pathways of these stages. During invasion, miR-26a-5p and miR-125-5p modulate important genes. This review underscores the critical impact of miRNAs in the regulation of embryo implantation and early pregnancy. The ability of miRNAs to modulate gene expression at various stages of reproduction presents promising therapeutic avenues for improving assisted reproductive technologies outcomes and addressing infertility. Further research into miRNA-based diagnostic tools and therapeutic strategies is essential to enhance our understanding of their role in reproductive health and to exploit their potential for clinical applications.

The association of men's beverage intake with semen quality and assisted reproduction outcomes in patients undergoing fertility treatment.

Although some studies have investigated the relationships between beverage intake and reproductive health these have generated conflicting results. To evaluate the associations between men's beverage intake and semen quality parameters and couple outcomes of medically assisted reproduction. The relationship between preconception beverage intake and semen quality was evaluated in 896 semen samples from 343 men. The relation between beverage intake and medically assisted reproduction outcomes (fertilization, implantation, clinical pregnancy, total/clinical pregnancy loss, and live birth) was evaluated in 296 men and their female partners who underwent 714 medically assisted reproduction cycles: 306 intrauterine insemination cycles and 408 in vitro fertilization. Intake of caffeinated, alcoholic, sugar-sweetened, and artificially sweetened beverages and sub-groups were considered as exposures. Caffeinated, alcoholic, sugar-sweetened, and artificially sweetened beverage intake was not associated with semen quality parameters or with fertilization, implantation, clinical pregnancy, or live birth in couples undergoing medically assisted reproduction. When specific types of beverages were explored, there was an inverse association between a greater intake of coffee/tea with caffeine and lower live birth probabilities in couples undergoing in vitro fertilization cycles. The adjusted probabilities (95% confidence interval) of live birth in the lowest and highest tertiles of intake were 0.49 (0.38, 0.61) and 0.33 (0.24, 0.43) for coffee with caffeine, and 0.49 (0.33, 0.51) and 0.31 (0.22, 0.41) for tea with caffeine. A similar trend was detected with liquor intake and live birth probabilities: 0.45 (0.37, 0.53) and 0.32 (0.25, 0.41). We also found an association between a greater beer intake and higher live birth probabilities. The adjusted probabilities (95% confidence interval) in the lowest and highest quartile of intake were 0.32 (0.23, 0.42) and 0.51 (0.39, 0.62). Male preconception intakes of coffee, tea, and liquor were inversely associated, whereas beer intake was positively associated with the probability of live birth during infertility treatment.

Astaxanthin improves assisted reproductive technology outcomes in poor ovarian responders through alleviating oxidative stress, inflammation, and apoptosis: a randomized clinical trial

BackgroundPoor ovarian response (POR) to controlled ovarian stimulation (COS) remains challenging, especially in advanced-age women with diminished ovarian reserve, resulting in low live birth rates. Many patients prefer to conceive with their eggs, underscoring the need for improved treatments. This study explores astaxanthin potential as a COS adjuvant to improve ovarian response and assisted reproductive technology (ART) outcomes, considering its impact on oxidative stress (OS), inflammation, and apoptosis, which are key factors in POR.MethodsIn this randomized, triple-blind, placebo-controlled trial, 60 infertile POR patients from POSEIDON Group 4 (the poorest prognosis category, age > 35 and poor ovarian reserve (anti-müllerian hormone < 1.2 ng/ml or antral follicle count < 5) undergoing intracytoplasmic sperm injection were enrolled. Patients were assigned to receive either 12 mg/day AST or placebo for eight weeks. All patients underwent a gonadotropin-releasing hormone antagonist regimen for COS. ART outcomes were compared between groups. Blood serum and follicular fluid (FF) were analyzed for OS markers (superoxide dismutase [SOD], total antioxidant capacity [TAC], and malondialdehyde [MDA]), and pro-inflammatory cytokines (interleukin-6 [IL-6], interleukin-8 [IL-8], and vascular endothelial growth factor [VEGF]) via enzyme-linked immunosorbent assay kits, and cell-free DNA [cfDNA] (apoptotic marker) via ALU quantitative polymerase chain reaction.ResultsAfter the intervention, the AST group exhibited a significant elevation in serum (P = 0.013) and TAC (P = 0.030), accompanied by a significant reduction in serum MDA (P = 0.005). No significant differences between AST and placebo groups were observed in OS markers in FF. AST group showed significant reductions in the serum IL-6 (P < 0.001), IL-8 (P = 0.001), and VEGF (P = 0.002) levels following AST therapy. In the AST group, FF levels of IL-6 (P = 0 < 001), IL-8 (P = 0.036), VEGF (P = 0.006), and cfDNA (P < 0.001) were significantly lower than in the placebo group. Between-group comparisons showed significant differences in the alterations of serum SOD (P = 0.027), IL-6 (P < 0.001), and IL-8 (P = 0.035) levels between AST and placebo groups. The AST group showed significant increases in the number of retrieved oocytes (P = 0.003), MII oocytes (P = 0.004), frozen embryos (P = 0.037), and high-quality embryos (P = 0.014) compared to the placebo group.ConclusionAST shows promise as a COS adjuvant therapy, potentially enhancing some ART outcomes in POR through alleviating OS, inflammation, and apoptosis.Trial registrationClinical trial registration number: IRCT20230223057510N1, URL: https://irct.behdasht.gov.ir/trial/68870, registration date: 2023 March 16.Graphical

Comparison of Recombinant Cumulase with Bovine Derived Hyaluronidase for Oocyte Denudation before ICSI in Sibling Oocytes

Assisted Reproductive Technology (ART) with Intra-cytoplasmic Sperm Injection (ICSI) commonly utilizes Bovine-Derived Hyaluronidase for oocyte denudation. The emergence of Recombinant Cumulase as an alternative merit an examination of its impact upon ICSI outcomes. We compared the effects of Recombinant Cumulase and Bovine-Derived Hyaluronidase on oocyte denudation during ICSI, investigating impact upon fertilization rates, blastulation rates, and euploidy rates, aiming to improve clinical practice and optimize ART for patient outcomes. This was a retrospective observational study involving 59 patients undergoing ICSI conducted at First IVF Fertility Centre, Abu Dhabi, United Arab Emirates. Oocytes from each patient were divided one group which employed Recombinant Cumulase, and the other group utilised Bovine-Derived hyaluronidase. Parameters such as age, number of oocytes retrieved, denudation outcomes, and euploidy rates were assessed to determine enzyme impact. Comparative analysis revealed no substantial difference in fertilisation rates or embryo development (blastocyst rate) between recombinant Cumulase and bovine-derived Hyaluronidase. However, the recombinant Cumulase group exhibited significantly higher (p&lt;0.05) rates of normal euploid embryos (Recombinant Cumulase-48.5%; Bovine Derived Hyaluronidase- 38.0%), indicating a potential advantage. However, the results are from small cohort and need to be validated with large sample size. Selecting enzymes for ART procedures is challenging. Although no significant differences were observed in fertilisation rates, the Recombinant Cumulase group treated oocytes exhibited yielding higher normal euploid embryo rates. Not many studies have looked at the Euploidy rates with use of different enzymes for oocyte denudation. Further investigations are essential to refine best practices and advance patient outcomes in assisted reproduction.

Which is the current knowledge on man-made endocrine- disrupting chemicals in follicular fluid? An overview of effects on ovarian function and reproductive health.

The increase in female reproductive disorders, such as polycystic ovary syndrome, endometriosis, and diminished ovarian reserve that lead to subfertility and infertility, has encouraged researchers to search and discover their underlying causes and risk factors. One of the crucial factors that may influence the increasing number of reproductive issues is environmental pollution, particularly exposure to man-made endocrine-disrupting chemicals (EDCs). EDCs can interfere with the ovarian microenvironment, impacting not only granulosa cell function but also other surrounding ovarian cells and follicular fluid (FF), which all play essential roles for oocyte development, maturation, and overall reproductive function. FF surrounds developing oocytes within an ovarian follicle and represents a dynamic milieu. EDCs are usually found in biological fluids, and FF is therefore of interest in this respect. This narrative review examines the current knowledge on specific classes of EDCs, including industrial chemicals, pesticides, and plasticizers, and their known effects on hormonal signaling pathways, gene expression, mitochondrial function, oxidative stress induction, and inflammation in FF. We describe the impact of EDCs on the development of reproductive disorders, oocyte quality, menstrual cycle regulation, and their effect on assisted reproductive technique outcomes. The potential transgenerational effects of EDCs on offspring through animal and first-human studies has been considered also. While significant progress has been made, the current understanding of EDCs' effects on ovarian function, particularly in humans, remains limited, underscoring the need for further research to clarify actions and effects of EDCs in the ovary.

Peripheral fatty acids and outcome of assisted reproduction

IntroductionThe present study investigates the relationship between the fatty acid levels in whole blood, in women undergoing IVF and four successive ART outcomes. Material and methodsA cross-sectional study was performed on data from a prospective cohort study conducted between 2014 and 2016. ResultsParticipants were 238 women undergoing in vitro fertilization (IVF) and participating in a study on the role of lifestyle habits and diet on ART outcomes. Blood PUFAs were measured by gas chromatography. Overall, higher blood levels of monounsaturated fatty acids, oleic acid, higher n6/n3 ratio and arachidonic/docosahexaenoic acid ratio were associated with more favorable ART outcomes. On the contrary, higher concentrations of long-chain PUFAs tended to be negatively associated with the considered outcomes. ConclusionsFurther prospective studies are needed to determine the ranges of fatty acid concentrations that are optimal for women with sub-fertility.

Microfluidics-A novel technique for high-quality sperm selection for greater ART outcomes.

Microfluidics represent a quality sperm selection technique. Human couples fail to conceive and this is so in a significant population of animals worldwide. Defects in male counterpart lead to failure of conception so are outcomes of assisted reproduction affected by quality of sperm. Microfluidics, deals with minute volumes (μL) of liquids run in small-scale microchannel networks in the form of laminar flow streamlines. Microfluidic sperm selection designs have been developed in chip formats, mimicking invivo situations. Here sperms are selected and analyzed based on motility and sperm behavioral properties. Compared to conventional sperm selection methods, this selection method enables to produce high-quality motile sperm cells possessing non-damaged or least damaged DNA, achieve greater success of insemination in bovines, and achieve enhanced pregnancy rates and live births in assisted reproduction-in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Besides, the concentration of sperm available to oocyte can be controlled by regulating the flow rate in microfluidic chips. The challenges in this technology are commercialization of chips, development of fully functional species-specific microfluidic tools, limited number of studies available in literature, and need of thorough understanding in reproductive physiology of domestic animals. In conclusion, incorporation of microfluidic system in assisted reproduction for sperm selection may promise a great success in IVF and ICSI outcomes. Future prospectives are to make this technology more superior and need to modify chip designs which is cost effective and species specific and ready for commercialization. Comprehensive studies in animal species are needed to be carried out for wider application of microfluidic sperm selection in invitro procedures.

The Impact of Magnetic Activated Cell Sorting (MACS) on Assisted Reproduction Outcomes

Objectives The study’s objectives were to evaluate the benefits of adding the magnetically activated cell sorting (MACS) technique to the traditional density gradient sperm wash method for advanced sperm selection in intracytoplasmic sperm injection (ICSI) cycles by comparing fertilisation rates, embryo quality, blastocyst formation, and pregnancy rates. Material and Methods A retrospective observational study was conducted at ARMC Aegis Hospital Perinthalmanna, Kerala. The study group was 116 patients taken during ICSI cycles done from October 2021 to September 2023, with 58 patients in the study (MACS after density gradient centrifugation) and 58 in control (density gradient centrifugation alone). Cases and controls were determined by the willingness of the patient to do MACS in sperm selection after discussion with their clinician. Patients with a severe male factor with sperm morphology &lt;4% were included in the study, with the female partner having regular cycles, normal AFC, and AMH &gt; 1 ng/ml. Patients with seminal infection, known genetic errors, female partners with endometriosis, PCOS, infections, malformations and previous poor responders were excluded. Spermatozoa are incubated with microbeads for 15 min at room temperature (100 μl/10 million) in MACS, after which they are placed into a separation column that contains magnetised iron spheres in it that is magnetised. While the unlabelled cells flow through the MACS column, the micro-bead labelled cells are trapped there subsequently, ICSI was performed using the processed sperm sample. The 2PN (Pro-nuclei) embryos, blastocysts, embryo quality, clinical pregnancies, and live births were noted and statistically analysed. Results The study and control groups were demographically similar; both cases (MACS group) and control group Density Gradient Centrifugation (DGC) group were under a 95% confidence interval. Results of the MACS group were compared with the DGC group. 2 PN status, number of embryos, Grade I embryos, day 5 blastocyst formation, live birth rates, and the number of positive pregnancies were examined in both groups. Analysis showed an increase in the 2 PN status, number of embryos, Grade I embryos, and day 5 blastocyst formation in the MACS group compared to the conventional DGC method. However, embryo grades (Grade I embryos) in the MACS group were high compared to the DGC group (P-value &lt; 0.01). Conclusion For couples with severe male factors and defective sperm morphology, the study finds that MACS may be recommended as an additional option to standard sperm processing.

The effect of music interventions on anxiety, pain, and pregnancy rates in women undergoing fertility treatment before oocyte collection and embryo transfer: Systematic review and meta-analysis of randomized controlled trials

IntrodutionThe present review aimed to evaluate the available evidence in the literature on the effect of music interventions on improving outcomes related to anxiety, pain, and pregnancy rates of women undergoing fertility treatment, prior to oocyte collection and embryo transfer. MethodWe searched the following databases from database inception to 2 May 2024, PUBMED, Embase, Web of Science, and the Turkish Academic Network and Information Center (ULAKBIM). Randomized controlled trials (RCT) in Turkish and English languages were included in the screening. Articles were scanned using MeSH-based keywords. The data were analyzed using the Review Manager computer program (Version 5.4.1). ResultsA total of 8 RCTs, including 1634 female patients, were included in our review. Music interventions significantly reduced anxiety scores prior to oocyte collection or fertilization compared to the control group (Standardised Mean Difference (SMD):0.26, 95 % CI:0.39 to 0.13, Z = 3.91, p < 0.0001). Moreover, after the music treatment, there was a significant improvement in the pain score during the procedure (SMD:0.96, 95 % CI:1.72 to -0.20, Z = 2.49, p = 0.01). Although more women in the music interventions group experienced an increase in the clinical pregnancy rate compared to the control group, there was no evidence of an effect on pregnancy rate (SMD:0.14, 95 % CI:2.63 to 2.34, Z = 0.11, p = 0.91). ConclusionMusic interventions appears to improve anxiety and pain scores in female patients receiving fertility treatment when administered during oocyte collection and fertilization. They may increase the clinical pregnancy rate but this not statistically significant. More research with larger sample sizes is needed to investigate the impact of music interventions on assisted reproductive technology clinical outcomes.

Analysis of assisted reproductive outcomes in patients with atypical endometrial hyperplasia and early-stage endometrial cancer after fertility-sparing treatment.

To explore the assisted reproductive outcomes of patients with atypical endometrial hyperplasia (AEH) and early-stage endometrial cancer (EEC) who achieved complete remission after conservative treatment and to provide reference for clinical selection of appropriate conservative treatment. This retrospective cohort study included seven patients with EEC and 62 patients with AEH who underwent invitro fertilization or intracytoplasmic sperm injection at the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University between August 2015 and October 2023. The authors divided the participants into two groups based on the type of fertility-sparing treatment received: the oral medication group and the levonorgestrel-releasing intrauterine system (LNG-IUS) group. The primary outcome was the cumulative clinical pregnancy rate. Secondary outcomes included clinical pregnancy rate per transfer cycle, embryo utilization rate, and high-quality embryo rate. The LNG-IUS group had a significantly higher rate of usable embryos compared with the oral medication group (80.8% vs 91.1%, P = 0.005) and also had a thinner endometrial thickness on the day of embryo transfer. The cumulative clinical pregnancy rate was higher in the LNG-IUS group compared with the medication group (46.7% vs 78.9%, P = 0.037), and the difference was statistically significant. For patients with AEH and EEC with fertility needs, the conservative treatment method of LNG-IUS can achieve better assisted reproductive outcomes.

Angiotensin II type-1 receptor autoantibody positively correlates with the rate of metaphase I oocytes in infertility with ovulatory disorder

The renin-angiotensin system (RAS) plays an important role in reproductive function. Our previous study identified that angiotensin II type-1 receptor autoantibody (AT1-AA), an autoantibody that activates RAS, was closely associated with infertility. However, its distribution in different types of infertility remained unclear. This study was designed to explore the distribution of AT1-AA in infertile patients and the connections between AT1-AA and oocyte development and pregnancy outcome. A total of 184 infertile women participated, with samples collected from peripheral venous blood. ELISA was used to detect AT1-AA levels in their sera. It was observed that the proportion of ovulation-disorder factors in AT1-AA-positive group was significantly higher than that in negative group (P=0.001). In 59 infertile women with ovulatory disorders, compared with negative group, AT1-AA-positive group had lower rate of retrieval (P=0.032) and metaphase II (MII) oocytes (P=0.011) but higher proportion of metaphase I (MI) oocytes (P=0.019). A negative correlation was found between the levels of AT1-AA and rate of retrieval and MII oocytes (P=0.027; P=0.043), whereas a positive correlation was observed with the proportion of MI oocytes (P=0.002). Moreover, a specific predictive value for proportion of reaching MII and MI oocytes was exhibited by AT1-AA (P < 0.01; P < 0.05). But no significant difference in embryonic parameters or pregnancy outcomes between two groups was observed (P > 0.05). This study revealed that serum AT1-AA levels were significantly increased in infertile women with ovulatory disorders and positively correlated with proportion of MI oocytes, but not associated with outcomes of assisted reproduction.

Extreme ambient heat and outcomes of assisted reproduction in the continental United States, 1996 to 2018

Extreme ambient heat and outcomes of assisted reproduction in the continental United States, 1996 to 2018

Impact of daily breakfast intake on the outcomes of assisted reproductive technology procedures

ObjectiveTo assess the relationship between meal consumption frequency and assisted reproductive technology (ART) outcomes among female patients with infertility. Research Methods & ProceduresThis cohort study was conducted from February 2022 to January 2024 at Tokyo Medical University Hospital. Overall, 101 female patients with infertility issues and without a history of stroke, heart disease, cancer, or type 1 or type 2 diabetes were enrolled in this study. The factors extracted from the questionnaire included demographic information, meal consumption frequency before ART and at 20 years of age, smoking status, and alcohol consumption status. Data on other factors, including age, body mass index, anti-Müllerian hormone level, and parity history, were collected from medical records. The assessed clinical outcomes included number of transplanted embryos, clinical pregnancies, ongoing pregnancies, live births, and miscarriages. ResultsAfter adjusting for potential confounding factors, including age, smoking status, alcohol consumption status, body mass index, anti-Müllerian hormone level, and parity history, a multivariate analysis of ART outcomes was performed. Patients were categorized into groups based on the frequency of weekly consumption of breakfast, lunch, and dinner. Patients who consumed breakfast 6–7 times a week were significantly more likely to have higher rates of live birth and lower rates of miscarriage in pregnancies conceived through ART. ConclusionsConsumption of breakfast 6–7 times a week before ART was associated with increased success rates following ART. This highlights the potential importance of regular breakfast consumption for optimizing ART outcomes.

The effect of endocrine-disrupting chemicals in follicular fluid: The insights from oocyte to fertilization

Endocrine-disrupting chemicals (EDCs) exhibited the detriment in female reproductive health. Our objective was to investigate the individual and mixture effects of EDCs present in follicular fluid, the environment in which oocytes grow and develop, on early reproductive outcomes. We recruited 188 women seeking reproduction examination from the Study of Exposure and Reproductive Health (SEARCH) cohort between December 2020 and November 2021. We assessed the concentrations of 7 categories of 64 EDCs in follicular fluid, and measured early reproductive outcomes, including retrieved oocytes, mature oocytes, normal fertilized oocytes, and high-quality embryos. In this study Monomethyl phthalate (MMP) (2.17 ng/ml) were the compounds found in the highest median concentrations in follicular fluid. After adjusting for multiple testing, multivariate regression showed that multiple EDCs were significantly negatively associated with early assisted reproduction outcomes. For example, MMP showed a significant negative correlation with the number of high quality embryos (β: −0.1, 95 % CI: −0.15, −0.04). Specifically, eight types of EDCs were significantly negatively associated with four early assisted reproductive outcomes (β range: −0.2 ∼ -0.03). In the mixed exposure model, we found that mixtures of EDC were significantly negatively correlated with all four outcomes. In the quantile g-computation (QGCOMP) model, for each interquartile range increase in the concentration of EDC mixtures, the number of oocytes retrieved, mature oocytes, normally fertilized oocytes, and high-quality embryos decreased by 0.46, 0.52, 0.77, and 1.2, respectively. Moreover, we identified that phthalates (PAEs) predominantly contributed to the negative effects. Future research should validate our findings.

Sperm chromatin dispersion assay reliability and assisted reproductive technology outcomes: Systematic review and meta-analysis.

Elevated sperm DNA fragmentation has potential implications for semen quality and fertility. The commonly used sperm chromatin dispersion test offers an indirect estimation but has limitations in terms of bias and variability. This study aimed to assess the reliability of the sperm chromatin dispersion assay for predicting assisted reproductive technology outcomes. This systematic review included studies published until December 2023 that adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed/MEDLINE, Scopus, and Google Scholar databases were searched. Various assisted reproductive technology outcomes in patients with high (≥30%) versus low (<30%) sperm DNA fragmentation were compared using a sperm chromatin dispersion assay and including a sub-analysis of intracytoplasmic sperm injection versus in vitro fertilization. A comprehensive meta-analysis software facilitated quantitative analysis with statistical comparisons between cases and controls. Interstudy heterogeneity was assessed, and sensitivity and publication bias tests were performed. Of the 199 abstracts assessed, 64 full-text articles were screened, and 44 articles were qualitatively synthesized. Fourteen articles representing 5346 participants were quantitatively analyzed. Using the sperm chromatin dispersion assay, elevated sperm DNA fragmentation was associated with lower fertilization and embryo cleavage rates. Notably, high sperm DNA fragmentation levels did not affect the clinical pregnancy, implantation, miscarriage, or live birth outcomes. Sub-analysis revealed lower fertilization, embryo cleavage, clinical pregnancy, live birth rates, and higher miscarriage rates in the intracytoplasmic sperm injection subgroup only. The sperm chromatin dispersion assay did not show significant differences in pregnancy or live birth rates between the high- and low-sperm DNA fragmentation groups. Noteworthy, high sperm DNA fragmentation was associated with worse assisted reproductive technology outcomes in the intracytoplasmic sperm injection group. Given the current quality of the evidence, affected by the experimental design and the absence of correction for female factors of infertility, clinicians should be wary of the assay's limited predictive power for pregnancy and live birth outcomes.

Aging promotes accumulation of senescent and multiciliated cells in human endometrial epithelium.

What changes occur in the endometrium during aging, and do they impact fertility? Both the transcriptome and cellular composition of endometrial samples from women of advanced maternal age (AMA) are significantly different from that of samples from young women, suggesting specific changes in epithelial cells that may affect endometrial receptivity. Aging is associated with the accumulation of senescent cells in aging tissues. Reproductive aging is mostly attributed to the decline in ovarian reserve and oocyte quality, whereas the endometrium is a unique complex tissue that is monthly renewed under hormonal regulation. Several clinical studies have reported lower implantation and pregnancy rates in oocyte recipients of AMA during IVF. Molecular studies have indicated the presence of specific mutations within the epithelial cells of AMA endometrium, along with altered gene expression of bulk endometrial tissue. Endometrial transcriptome profiling was performed for 44 women undergoing HRT during the assessment of endometrial receptivity before IVF. Patients younger than 28 years were considered as the young maternal age (YMA) group (age 23-27 years) and women older than 45 years were considered as the AMA group (age 47-50 years). Endometrial biopsies were obtained on Day 5 of progesterone treatment and RNA was extracted. All endometrial samples were evaluated as being receptive based on the expression of 68 common endometrial receptivity markers. Endometrial samples from another 24 women classified into four age groups (YMA, intermediate age group 1 (IMA1, age 29-35), intermediate age group 2 (IMA2, age 36-44), and AMA) were obtained in the mid-secretory stage of a natural cycle (NC) and used for validation studies across the reproductive lifespan. A total of 24 HRT samples (12 YMA and 12 AMA) were subject to RNA sequencing (RNA-seq) and differential gene expression analysis, 20 samples (10 YMA and 10 AMA) were used for qPCR validation, and 24 NC samples (6 YMA, 6 IMA1, 6 IMA2 and 6AMA) were used for RNA-seq validation of AMA genes across the woman's reproductive lifespan. Immunohistochemistry (IHC) was used to confirm some expression changes at the protein level. Computational deconvolution using six endometrial cell type-specific transcriptomic profiles was conducted to compare the cellular composition between the groups. Comparisons between YMA and AMA samples identified a lower proportion of receptive endometria in the AMA group (P = 0.007). Gene expression profiling identified 491 differentially expressed age-sensitive genes (P adj < 0.05) that revealed the effects of age on endometrial epithelial growth and receptivity, likely contributing to decreased reproductive performance. Our results indicate that changes in the expression of the cellular senescence marker p16INK4a and genes associated with metabolism, inflammation, and hormone response are involved in endometrial aging. Importantly, we demonstrate that the proportion of multi-ciliated cells, as discovered based on RNA-seq data deconvolution and tissue IHC results, is affected by endometrial aging, and propose a putative onset of age-related changes. Furthermore, we propose that aging has an impact on the transcriptomic profile of endometrial tissue in the context of endometrial receptivity. The raw sequencing data reported in this article are deposited at the Gene Expression Omnibus under accession code GSE236128. This retrospective study identified changes in the endometrium of patients undergoing hormonal replacement and validated these changes using samples obtained during a NC. However, future studies must clarify the importance of these findings on the clinical outcomes of assisted reproduction. The findings reported in this study have important implications for devising future strategies aimed at improving fertility management in women of advanced reproductive age. This research was funded by the Estonian Research Council (grant no. PRG1076), Horizon 2020 innovation grant (ERIN, grant no. EU952516), Enterprise Estonia (grant no. EU48695), MSCA-RISE-2020 project TRENDO (grant no. 101008193), EU 874867 project HUTER, the Horizon Europe NESTOR grant (grant no. 101120075) of the European Commission, the EVA specialty program (grant no. KP111513) of the Maastricht University Medical Center (MUMC+), MICIU/AEI/10.13039/501100011033 and FEDER, EU projects Endo-Map (grant no. PID2021-12728OB-100), ROSY (grant no. CNS2022-135999), and the National Science Fund of Bulgaria (grant no. KII-06 H31/2). The authors declare no competing interests.

Analysis of assisted reproductive outcomes for gynecologic cancer survivors: a retrospective study

ObjectiveTo examine the reproductive outcomes of assisted reproductive technology (ART) in gynecologic cancer patients and to assess maternal and neonatal complications.MethodsWomen diagnosed with gynecologic cancer who underwent their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment between 2013 and 2021 at Shanghai Ji Ai Genetics and IVF Institute were included in this study. Infertile women without any history of cancer were matched to the cancer group. The primary outcome was the cumulative live birth rate. Baseline and follow-up data were compared between groups using Student’s t-tests for normally distributed variables and with Chi-square test for categorical variables. A propensity score-based patient-matching approach was adopted to ensure comparability between individuals with and without specific cancer type.ResultsA total of 136 patients with a history of gynecologic cancer and 241 healthy infertile controls were included in this study. Endometrial cancer constituted 50.70% of the cases and cervical cancer constituted 34.60% of the cases. The cancer group exhibited significantly shorter duration of stimulation, lower levels of estradiol, lower number of retrieved oocytes, day-3 embryos, and blastocysts compared to the control group (P < 0.05). The cumulative live birth rate of the gynecologic cancer group was significantly lower than that of the control group (36.10% vs. 60.50%, P < 0.001). Maternal and neonatal complications did not significantly differ between the groups (P > 0.05). The endometrial cancer and cervical cancer groups showed significantly lower cumulative live birth rates than their matched controls (38.60% vs. 64.50%, P = 0.011 and 24.20% vs. 68.60%, P < 0.001, respectively).ConclusionsThese findings highlight the decreased occurrence of pregnancy and live birth in female gynecologic cancer patients undergoing ART, particularly in endometrial cancers and cervical cancers. These findings have important implications for counseling and managing gynecologic cancer patients undergoing ART.

The clinical effectiveness of the Mind/Body Program for Infertility on wellbeing and assisted reproduction outcomes: a randomized controlled trial in search for active ingredients.

Does the Mind/Body Program for Infertility (MBPI) perform better, due to certain distinctive elements, than a partly matched support group in improving the wellbeing and medically assisted reproduction (MAR) outcomes of women with elevated distress levels in a clinical setting? While robust enhancements occurred in the wellbeing overall, the cognitive behavioural and formalized stress management elements of the MBPI allowed a significantly stronger improvement in trait anxiety, but not in other mental health and MAR outcomes, compared with a support group. Mind-body psychological programmes adjacent to MAR have been found to improve women's mental states and possibly increase chances of pregnancy. However, not enough is known about the programme's effectiveness among patients with elevated distress levels in routine clinical settings, nor is it clear which of its particular ingredients are specifically effective. A pre-post design, single-centre, randomized controlled trial was performed between December 2019 and October 2022 (start and end of recruitment, respectively). The sample size (n = 168) was calculated to detect superiority of the MBPI in improving fertility-related quality of life. Randomization was computer-based, with random numbers concealing identities of patients until after allocation. The trial was conducted at a large university teaching hospital. A total of 168 patients were randomly assigned to the mind-body (MBPI) group (n = 84) and the fertility support (FS) control group (n = 84). Patients received a 10-week, 135-min/week group intervention, with the FS group following the same format as the MBPI group, but with a less restricted and systematic content, and without the presumed effective factors. The number of patients analysed was n = 74 (MBPI) and n = 68 (FS) for post-intervention psychological outcomes, and n = 54 (MBPI) and n = 56 (FS) for pregnancy outcomes at a 30-month follow-up. Significant improvements occurred in both groups in all psychological domains (adjusted P < 0.001), except for treatment-related quality of life. Linear mixed-model regression analysis did not reveal significantly greater pre-post improvements in the MBPI group than in the FS group in fertility-related quality of life (difference in differences (DD) = 4.11 [0.42, 7.80], d = 0.32, adjusted P = 0.124), treatment-related quality of life (DD = -3.08 [-7.72, 1.55], d = -0.20, adjusted P = 0.582), infertility-specific stress (DD = -2.54 [-4.68, 0.41], d = -0.36, adjusted P = 0.105), depression (DD = -1.16 [3.61, 1.29], d = -0.13, adjusted P = 0.708), and general stress (DD = -0.62 [-1.91, 0.68], d = -0.13, adjusted P = 0.708), but it did show a significantly larger improvement in trait anxiety (DD = -3.60 [-6.16, -1.04], d = -0.32, adjusted P = 0.042). Logistic regression showed no group effect on MAR pregnancies, spontaneous pregnancies, or live births. The follow-up only covered MAR-related medical outcomes and no psychological variables, and their rates were not equal in the two groups. Biological factors other than age, aetiology, and duration of infertility may have confounded the study results. Loss to follow-up was between 5% and 10%, which may have led to some bias. The psychologically and medically heterogeneous sample, the normal clinical setting and the low attrition rate all raise the external validity and generalizability of our study. The MBPI works not only in controlled conditions, but also in routine MAR practice, where it can be introduced as a cost-effective, low-intensity psychological intervention, within the framework of stepped care. More studies are needed to further identify its active ingredients. The authors received no financial support for the research, authorship, and/or publication of this article. The authors have no conflict of interest to disclose. ClinicalTrials.gov NCT04151485. 5 November 2019. 15 December 2019.

Effect of sequential cleavage and blastocyst embryo transfer compared to single cleavage stage embryo transfer on assisted reproductive technology outcome: An RCT.

Assisted reproductive technology (ART), offers hope for many infertile couples by increasing the chance of successful pregnancy. The success of in vitro fertilization depends on various factors, in which embryo transfer (ET) is one of the critical steps influencing in vitro fertilization success rates. Extended embryo culture and blastocyst-stage ET have been considered in ART due to their potential benefits including improved implantation rates. This study aimed to compare the outcomes of sequential ET vs single cleavage-stage ET in women undergoing a fresh ET cycle with a limited number of embryos. This randomized clinical trial was conducted on 140 women undergoing infertility treatments and candidates for fresh ET at the Research and Clinical Center for Infertility, Yazd, Iran from August 2023 to January 2024. Women with a number of embryos from 2-5 ( 2 and 5 available embryos) were randomly divided into 2 groups: One group underwent sequential ET (one cleavage-stage ET followed by one blastocyst ET) and the other group underwent single-step 2 cleavage-stage ET. The primary outcome was clinical pregnancy, and the secondary outcome included chemical pregnancy and early abortion rates. Our findings showed significantly higher rates of clinical (33.5% vs 13.6%, p = 0.003) and chemical (41.3% vs 18.2%, p = 0.004) pregnancies in the sequential ET group compared to the single-step cleavage ET group. The early abortion rate was higher in single-step cleavage ET (13% vs 44.4%, p = 0.053). Sequential fresh ET is a useful choice in women who have a limited number of embryos and can improve ART outcomes.