The Role of One-Carbon Metabolism and Methyl Donors in Medically Assisted Reproduction: A Narrative Review of the Literature.

One-carbon (1-C) metabolic deficiency impairs homeostasis, driving disease development, including infertility. It is of importance to summarize the current evidence regarding the clinical utility of 1-C metabolism-related biomolecules and methyl donors, namely, folate, betaine, choline, vitamin B12, homocysteine (Hcy), and zinc, as potential biomarkers, dietary supplements, and culture media supplements in the context of medically assisted reproduction (MAR). A narrative review of the literature was conducted in the PubMed/Medline database. Diet, ageing, and the endocrine milieu of individuals affect both 1-C metabolism and fertility status. In vitro fertilization (IVF) techniques, and culture conditions in particular, have a direct impact on 1-C metabolic activity in gametes and embryos. Critical analysis indicated that zinc supplementation in cryopreservation media may be a promising approach to reducing oxidative damage, while female serum homocysteine levels may be employed as a possible biomarker for predicting IVF outcomes. Nonetheless, the level of evidence is low, and future studies are needed to verify these data. One-carbon metabolism-related processes, including redox defense and epigenetic regulation, may be compromised in IVF-derived embryos. The study of 1-C metabolism may lead the way towards improving MAR efficiency and safety and ensuring the lifelong health of MAR infants.

The Effect of Open and Closed Oocyte Vitrification Systems on Embryo Development: A Systematic Review and Network Meta-Analysis.

Background/Objectives: Open and closed vitrification systems are commonly employed in oocyte cryopreservation; however, there is limited evidence regarding a comparison of their separate impact on oocyte competence. This study uniquely brings to the literature, data on the effect of open versus closed vitrification systems on laboratory and clinical outcomes, and the effect of cooling and warming rates. Methods: A systematic search of the literature was performed using the databases PubMed/MEDLINE and the Cochrane Central Library, limited to articles published in English up to January 2023. A network meta-analysis was conducted comparing each vitrification system versus fresh oocytes. Results: Twenty-three studies were included. When compared to fresh oocytes, both vitrification devices resulted in lower fertilization rates per MII oocyte retrieved. When comparing the two systems in terms of survival rates, no statistically significant difference was observed. However, interestingly open systems resulted in lower cleavage and blastocyst formation rates per 2 pronuclear (2PN) oocyte compared to fresh controls, while at the same time no statistically significant difference was detected when comparing closed devices with fresh oocytes. Conclusions: In conclusion, closed vitrification systems appear to exert a less detrimental impact on the oocytes' competence, which is reflected in the blastocyst formation rates. Proof of superiority of one system versus the other may lead to standardization, helping to ultimately determine optimal practice in oocyte vitrification.

Embryo Transfer Procedural Parameters Do Not Predict IVF Cycle Outcome.

BACKGROUND: this study aims to assess the effect of embryo transfer (ET) performance parameters of a technical nature on IVF outcome. METHODS: A total of 1417 ETs from a single IVF center were included in this prospective observational study. The parameters investigated were as follows: the presence of cervical mucus post catheter withdrawal, the presence of blood, catheter reload, the employment of a tenaculum and stylet, catheter resistance as experienced by the physician and patient discomfort. RESULTS: When ET performance parameters were associated with clinical outcomes on a singular level, none of the ET parameters presented with any statistical significance. The evaluation of covariates indicated that the number and the quality of transferred embryos, as well as maternal age, exerted a statistically significant effect on clinical outcomes. In a multivariate analysis, only the presence of mucus along with significant catheter resistance presented with statistical significance; however, when adjusting for covariates, this combination showed no statistically significant effect on clinical outcomes. CONCLUSIONS: the results indicate that the time-consuming process of recording and analyzing ET performance parameters fails to offer any additional value in predicting the cycle's outcome, while factors like embryo quality and number, as well as maternal age, seem to be the sole robust predictive factors of an IVF cycle.

Effects of Hypericin on Cultured Primary Normal Human Dermal Fibroblasts Under Increased Oxidative Stress.

INTRODUCTION: Wound healing is a dynamic process that begins with inflammation, proliferation, and cell migration of a variety of fibroblast cells. As a result, identifying possible compounds that may improve fibroblast cell wound healing capacity is crucial. Hypericin is a natural quinine that has been reported to possess a wide range of pharmacological profiles, including antioxidant and anti-inflammatory, activities. Herein we examined for the first time the effect of hypericin on normal human dermal fibroblasts (NHDFs) under oxidative stress. METHODS: NHDF were exposed to different concentrations of hypericin (0-20 µg/mL) for 24 h. For the oxidative stress evaluation, H2O2 was used as a stressor factor. Cell viability and proliferation levels were evaluated. Immunohistochemistry and flow cytometry were performed to assess cell apoptosis levels and with confocal microscopy we identified the mitochondrial superoxide production under oxidative stress and after the treatment with hypericin. Scratch assay was performed under oxidative stress to evaluate the efficacy of hypericin in wound closure. To gain an insight into the molecular mechanisms of hypericin bioactivity, we analyzed the relative expression levels of genes involved in oxidative response and in wound healing process. RESULTS: We found that the exposure of NHDF to hypericin under oxidative stress resulted in an increase in cell viability and ATP levels. We found a decrease in apoptosis and mitochondrial superoxide levels after treatment with hypericin. Moreover, treatment with hypericin reduced wound area and promoted wound closure. The levels of selected genes showed that hypericin upregulated the levels of antioxidants genes. Moreover, treatment with hypericin in wound under oxidative stress downregulated the levels of proinflammatory cytokines, and metalloproteinases; and upregulated transcription factors and extracellular matrix genes. CONCLUSION: These findings indicated that hypericin possesses significant in vitro antioxidant activity on NHDF and provide new insights into its potential beneficial role in the management of diabetic ulcers.

Trophectoderm non-coding RNAs reflect the higher metabolic and more invasive properties of young maternal age blastocysts.

Increasing female age is accompanied by a corresponding fall in her fertility. This decline is influenced by a variety of factors over an individual's life course including background genetics, local environment and diet. Studying both coding and non-coding RNAs of the embryo could aid our understanding of the causes and/or effects of the physiological processes accompanying the decline including the differential expression of sub-cellular biomarkers indicative of various diseases. The current study is a post-hoc analysis of the expression of trophectoderm RNA data derived from a previous high throughput study. Its main aim is to determine the characteristics and potential functionalities that characterize long non-coding RNAs. As reported previously, a maternal age-related component is potentially implicated in implantation success. Trophectoderm samples representing the full range of maternal reproductive ages were considered in relation to embryonic implantation potential, trophectoderm transcriptome dynamics and reproductive maternal age. The long non-coding RNA (lncRNA) biomarkers identified here are consistent with the activities of embryo-endometrial crosstalk, developmental competency and implantation and share common characteristics with markers of neoplasia/cancer invasion. Corresponding genes for expressed lncRNAs were more active in the blastocysts of younger women are associated with metabolic pathways including cholesterol biosynthesis and steroidogenesis.

Development of a predictive model for luteal phase oocyte retrieval in poor responders undergoing natural cycle IVF.

The aim of this study is the development of a prediction model indicating successful application of Oocyte Retrieval performed during the Luteal Phase (LuPOR) in poor responders, as defined by the retrieval of at least one MII oocyte. Recruitment included 1688 poor responders diagnosed as per Bologna Criteria, undergoing natural cycle ICSI between 2012 and 2020. Oocyte collections were performed during the follicular phase and during the luteal phase similarly. Antral Follicle Count (AFC), Estradiol (E2) levels evaluated on both trigger days prior to Follicular Phase Oocyte Retrieval (FoPOR) and LuPOR, and the number of small follicles 8-12 mm that were not aspirated during FoPOR were identified as predictive factors indicative of an efficient LuPOR practice with an Area Under the Curve (AUC) of 0.86, 0.86, 0.89 as well as 0.82 respectively. The combination of the above-mentioned characteristics into a prediction model provided an AUC of 0.88, specificity and a sensitivity of 0.73 and 0.94 respectively and an accuracy of 0.89. The model provided a positive predictive value (PPV) of 93.5% and a negative predictive value (NPV) of 46.8%. The clinical conclusion of the present study aims to be of added value to the clinician, by providing a prediction model defining the POR population benefiting from LuPOR. The high PPV of this model may renders this tool helpful for the practitioner that considers LuPOR.

Authors Reply: Regarding "Stress Management and in Vitro Fertilization (IVF): A Pilot Randomized Controlled Trial".

Komiya et al recently sent a letter to the editor1 raising issues of reliability and validity of our study "Stress Management and in Vitro Fertilization (IVF): A Pilot Randomized Controlled Trial".2 Their comments focused on the default of the registration, the absence of any mention of case dropout, the ambiguity in the details of IVF treatment and the lack of specific figures on the background of the participants. However, the principles of CONSORT 2010 cannot be applied to Pilot Randomized and Feasibility Trials, only to Randomized Trials (RTs) or Randomized Controlled Trials (RCTs). Similarly, the CONSORT Extension 2016 suggested some principles for Pilot and Feasibility Trials, but again it does not directly apply to internal pilot studies, non-randomized pilot and feasibility studies, or phase II studies.3,4 Many international journals do not require registration for Pilot and Feasibility Trials, but only for RTs or RCTs,5 granted that clinical trial registration is not an indicator of low risk of bias.6 Thanks to the useful comments by Komiya et al, our article2 now includes online "Supplementary Materials" in which we clarify all their points one by one. Specifically, the Material and Method section of Supplementary Materials includes details for the Registration, the Flow Chart and the IVF Treatment, and the Results section includes details for the Background of the Participants. Thus, we believe that the level of reliability and validity of the study can be now examined and ensured.

Reporting on the Value of Artificial Intelligence in Predicting the Optimal Embryo for Transfer: A Systematic Review including Data Synthesis.

Artificial intelligence (AI) has been gaining support in the field of in vitro fertilization (IVF). Despite the promising existing data, AI cannot yet claim gold-standard status, which serves as the rationale for this study. This systematic review and data synthesis aims to evaluate and report on the predictive capabilities of AI-based prediction models regarding IVF outcome. The study has been registered in PROSPERO (CRD42021242097). Following a systematic search of the literature in Pubmed/Medline, Embase, and Cochrane Central Library, 18 studies were identified as eligible for inclusion. Regarding live-birth, the Area Under the Curve (AUC) of the Summary Receiver Operating Characteristics (SROC) was 0.905, while the partial AUC (pAUC) was 0.755. The Observed: Expected ratio was 1.12 (95%CI: 0.26-2.37; 95%PI: 0.02-6.54). Regarding clinical pregnancy with fetal heartbeat, the AUC of the SROC was 0.722, while the pAUC was 0.774. The O:E ratio was 0.77 (95%CI: 0.54-1.05; 95%PI: 0.21-1.62). According to this data synthesis, the majority of the AI-based prediction models are successful in accurately predicting the IVF outcome regarding live birth, clinical pregnancy, clinical pregnancy with fetal heartbeat, and ploidy status. This review attempted to compare between AI and human prediction capabilities, and although studies do not allow for a meta-analysis, this systematic review indicates that the AI-based prediction models perform rather similarly to the embryologists' evaluations. While AI models appear marginally more effective, they still have some way to go before they can claim to significantly surpass the clinical embryologists' predictive competence.

The impact of preimplantation genetic testing for aneuploidies (PGT-A) on clinical outcomes in high risk patients.

PURPOSE: To investigate whether preimplantation genetic testing for aneuploidy (PGT-A) improves the clinical outcome in patients with advanced maternal age (AMA), recurrent miscarriages (RM), and recurrent implantation failure (RIF). METHODS: Retrospective cohort study from a single IVF center and a single genetics laboratory. One hundred seventy-six patients undergoing PGT-A were assigned to three groups: an AMA group, an RM group, and a RIF group. Two hundred seventy-nine patients that did not undergo PGT-A were used as controls and subgrouped similarly to the PGT-A cohort. For the PGT-A groups, trophectoderm biopsy was performed and array comparative genomic hybridization was used for PGT-A. Clinical outcomes were compared with the control groups. RESULTS: In the RM group, we observed a significant decrease of early pregnancy loss rates in the PGT-A group (18.1% vs 75%) and a significant increase in live birth rate per transfer (50% vs 12.5%) and live birth rate per patient (36% vs 12.5%). In the RIF group, a statistically significant increase in the implantation rate per transfer (69.5% vs 33.3%) as well as the live birth rate per embryo transfer (47.8% vs 19%) was observed. In the AMA group, a statistically significant reduction in biochemical pregnancy loss was observed (3.7% vs 31.5%); however, live birth rates per embryo transfer and per patient were not significantly higher than the control group. CONCLUSION: Our results agree with recently published studies, which suggest caution in the universal application of PGT-A in women with infertility. Instead, a more personalized approach by choosing the right candidates for PGT-A intervention should be followed.

The Role of Interleukins in Recurrent Implantation Failure: A Comprehensive Review of the Literature.

Recurrent implantation failure (RIF) is a multifactorial condition affecting 10-15% of in vitro fertilization (IVF) couples. Data suggest that functional dysregulation of the endometrial immune system constitutes one of the main pathophysiological mechanisms leading to RIF. The aim of this article is to provide a thorough presentation and evaluation of the role of interleukins (ILs) in the pathogenesis of RIF. A comprehensive literature screening was performed summarizing current evidence. During implantation, several classes of ILs are secreted by epithelial and stromal endometrial cells, including IL-6, IL-10, IL-12, IL-15, IL-18, and the leukemia inhibitory factor. These ILs create a perplexing network that orchestrates both proliferation and maturation of uterine natural killer cells, controls the function of regulatory T and B cells inhibiting the secretion of antifetal antibodies, and supports trophoblast invasion and decidua formation. The existing data indicate associations between ILs and RIF. The extensive analysis performed herein concludes that the dysregulation of the ILs network indeed jeopardizes implantation leading to RIF. This review further proposes a mapping of future research on how to move forward from mere associations to robust molecular data that will allow an accurate profiling of ILs in turn enabling evidence-based consultancy and decision making when addressing RIF patients.

The Role of Uterine Natural Killer Cells on Recurrent Miscarriage and Recurrent Implantation Failure: From Pathophysiology to Treatment.

Uterine natural killer (uNK) cells constitute a unique uterine leucocyte subpopulation facilitating implantation and maintaining pregnancy. Herein, we critically analyze current evidence regarding the role of uNK cells in the events entailed in recurrent implantation failure (RIF) and recurrent miscarriages (RM). Data suggest an association between RIF and RM with abnormally elevated uNK cells' numbers, as well as with a defective biological activity leading to cytotoxicity. However, other studies do not concur on these associations. Robust data suggesting a definitive causative relationship between uNK cells and RIF and RM is missing. Considering the possibility of uNK cells involvement on RIF and RM pathophysiology, possible treatments including glucocorticoids, intralipids, and intravenous immunoglobulin administration have been proposed towards addressing uNK related RIF and RM. When considering clinical routine practice, this study indicated that solid evidence is required to report on efficiency and safety of these treatments as there are recommendations that clearly advise against their employment. In conclusion, defining a causative relationship between uNK and RIF-RM pathologies certainly merits investigation. Future studies should serve as a prerequisite prior to proposing the use of uNK as a biomarker or prior to targeting uNK cells for therapeutic purposes addressing RIF and RM.

Introducing intrauterine antibiotic infusion as a novel approach in effectively treating chronic endometritis and restoring reproductive dynamics: a randomized pilot study.

The chronic nature of Chronic Endometritis (CE) along with the challenging management and infertility entailed, call for cutting-edge therapeutic approaches. This study introduces the novel treatment of intrauterine antibiotic infusion (IAI) combined with oral antibiotic administration (OAA), and it assesses respective performance against the gold standard treatment of OAA. Data sourced herein reports on treatment efficiency and fertility restoration for both patients aiming to conceive naturally or via In Vitro fertilization. Eighty CE patients, 40 presenting with recurrent implantation failure, and 40 with recurrent pregnancy loss, were enrolled in the IVF and the natural conception arm respectively. Treatment was subjected to randomization. Effectively treated patients proceeded with either a single IVF cycle or were invited to conceive naturally over a 6-month period. Combination of IAI and OAA provided a statistically significant enhanced effectiveness treatment rate (RR 1.40; 95%CI 1.07-1.82; p = 0.01). No statistically significant difference was observed regarding the side-effects rate (RR 1.33; 95%CI 0.80-2.22; p = 0.52). No statistically significant difference was observed for either arm regarding live-birth rate. Following an intention-to-treat analysis, employment of IAI corresponds to improved clinical pregnancy rate-albeit not reaching statistical significance. In conclusion, complimentary implementation of IAI could provide a statistically significant enhanced clinical treatment outcome.

Molecular Drivers of Developmental Arrest in the Human Preimplantation Embryo: A Systematic Review and Critical Analysis Leading to Mapping Future Research.

Developmental arrest of the preimplantation embryo is a multifactorial condition, characterized by lack of cellular division for at least 24 hours, hindering the in vitro fertilization cycle outcome. This systematic review aims to present the molecular drivers of developmental arrest, focusing on embryonic and parental factors. A systematic search in PubMed/Medline, Embase and Cochrane-Central-Database was performed in January 2021. A total of 76 studies were included. The identified embryonic factors associated with arrest included gene variations, mitochondrial DNA copy number, methylation patterns, chromosomal abnormalities, metabolic profile and morphological features. Parental factors included, gene variation, protein expression levels and infertility etiology. A valuable conclusion emerging through critical analysis indicated that genetic origins of developmental arrest analyzed from the perspective of parental infertility etiology and the embryo itself, share common ground. This is a unique and long-overdue contribution to literature that for the first time presents an all-inclusive methodological report on the molecular drivers leading to preimplantation embryos' arrested development. The variety and heterogeneity of developmental arrest drivers, along with their inevitable intertwining relationships does not allow for prioritization on the factors playing a more definitive role in arrested development. This systematic review provides the basis for further research in the field.

Stress management and In Vitro Fertilization (IVF): A pilot randomized controlled trial.

The objective of the study was to evaluate the psychological effect of an intervention of 8 stress-management sessions in women undergoing in vitro fertilization (IVF). Moreover, the overall IVF success was assessed against the fluctuation of the participants' stress levels. A total of 144 women participated in the study with 74 of them in the intervention group and 70 women in the control group. Demographics and medical history of all participants were recorded. The intervention group only underwent 8 weekly stress management sessions. During the 1st and 8th week of the study, both groups completed the Depression, Anxiety, Stress Scale 21 (DASS-21), the Perceived Stress Scale 14 (PSS-14) and the Fertility Problem Inventory (FPI). Following the intervention, the outcome of the IVF cycles, as defined by clinical pregnancy rates, were recorded. Our results indicated that total stress in the intervention group declined significantly (p<0.001) in respect to all the parameters of the PSS-14, DASS-21 and FPI scales, with the exception of the need for parenthood dimension that did not change significantly in the intervention group (p=0.002), while significantly increased in the control group (p<0.001). The difference of stress levels between the two groups for each scale as well as in total was also significant. There were no significant differences in the demographic data, lifestyle and medical history of the participants and their spouses between the two groups. The IVF success rate was found to be related to the levels of perceived stress on the PSS-14 scale (p=0.029) but not to any of the dimensions of DASS-21(p=0.197) and FPI (p=0.611) scales. Definitive factors affecting the IVF success were the participants' age (p=0.046), which was negatively correlated to IVF success, and the spouses' medical history of cryptorchidism (undescended testicles) (p=0.05). The high significance of these variables probably limited the effect of the intervention for stress relief on IVF success. This pilot study revealed encouraging results regarding the positive effect of interventions for stress management in women undergoing fertility treatment, however the possible contribution of such interventions to overall IVF success rates requires further investigation.

Investigating the Role of the microRNA-34/449 Family in Male Infertility: A Critical Analysis and Review of the Literature.

There is a great body of evidence suggesting that in both humans and animal models the microRNA-34/449 (miR-34/449) family plays a crucial role for normal testicular functionality as well as for successful spermatogenesis, regulating spermatozoa maturation and functionality. This review and critical analysis aims to summarize the potential mechanisms via which miR-34/449 dysregulation could lead to male infertility. Existing data indicate that miR-34/449 family members regulate ciliogenesis in the efferent ductules epithelium. Upon miR-34/449 dysregulation, ciliogenesis in the efferent ductules is significantly impaired, leading to sperm aggregation and agglutination as well as to defective reabsorption of the seminiferous tubular fluids. These events in turn cause obstruction of the efferent ductules and thus accumulation of the tubular fluids resulting to high hydrostatic pressure into the testis. High hydrostatic pressure progressively leads to testicular dysfunction as well as to spermatogenic failure and finally to male infertility, which could range from severe oligoasthenozoospermia to azoospermia. In addition, miR-34/449 family members act as significant regulators of spermatogenesis with an essential role in controlling expression patterns of several spermatogenesis-related proteins. It is demonstrated that these microRNAs are meiotic specific microRNAs as their expression is relatively higher at the initiation of meiotic divisions during spermatogenesis. Moreover, data indicate that these molecules are essential for proper formation as well as for proper function of spermatozoa per se. MicroRNA-34/449 family seems to exert significant anti-oxidant and anti-apoptotic properties and thus contribute to testicular homeostatic regulation. Considering the clinical significance of these microRNAs, data indicate that the altered expression of the miR-34/449 family members is strongly associated with several aspects of male infertility. Most importantly, miR-34/449 levels in spermatozoa, in testicular tissues as well as in seminal plasma seem to be directly associated with severity of male infertility, indicating that these microRNAs could serve as potential sensitive biomarkers for an accurate individualized differential diagnosis, as well as for the assessment of the severity of male factor infertility. In conclusion, dysregulation of miR-34/449 family detrimentally affects male reproductive potential, impairing both testicular functionality as well as spermatogenesis. Future studies are needed to verify these conclusions.

The effects of aging on molecular modulators of human embryo implantation.

Advancing age has a negative impact on female fertility. As implantation rates decline during the normal maternal life course, age-related, embryonic factors are altered and our inability to monitor these factors in an unbiased genome-wide manner in vivo has severely limited our understanding of early human embryo development and implantation. Our high-throughput methodology uses trophectoderm samples representing the full spectrum of maternal reproductive ages with embryo implantation potential examined in relation to trophectoderm transcriptome dynamics and reproductive maternal age. Potential embryo-endometrial interactions were tested using trophectoderm sampled from young women, with the receptive uterine environment representing the most 'fertile' environment for successful embryo implantation. Potential roles for extracellular exosomes, embryonic metabolism and regulation of apoptosis were revealed. These biomarkers are consistent with embryo-endometrial crosstalk/developmental competency, serving as a mediator for successful implantation. Our data opens the door to developing a diagnostic test for predicting implantation success in women undergoing fertility treatment.

Evaluating different strategies for poor ovarian response management: a retrospective cohort study and literature review.

This retrospective study compares four different strategies for managing poor ovarian response (POR), namely, conventional stimulation (300 IUs) IVF-fresh embryo transfer (CONVF), mild stimulation (150 IUs) IVF-fresh embryo transfer (MILDF), mild stimulation embryo banking (MILDB), and embryo banking in natural cycles (NATB). In total, 796 POR patients were considered eligible. Statistical analysis revealed a shorter duration of stimulation and a lower required amount of gonadotropins in MILDF compared with CONVF (9.34 ± 1.17 versus 10.37 ± 1.14; 1402 ± 176 versus 3110 ± 343, P < 0.001). Comparing MILDF and MILDB, a higher number of available oocytes and embryos was observed in MILDB (2.36 ± 1.15 versus 6.58 ± 1.11; 1.72 ± 1.02 versus 3.51 ± 0.61, P < 0.001). Moreover, the MILDB presented with a lower number of required oocyte retrievals and a higher number of oocytes per oocyte retrieval compared with NATB (3.90 ± 1.56 versus 7.15 ± 1.80; 1.95 ± 0.74 versus 0.89 ± 0.20, P < 0.001). Data indicate that MILDF is equally efficient and associated with a shorter duration of stimulation and a lower required amount of gonadotropins compared with CONVF. Embryo accumulation may be more efficient compared with a fresh embryo transfer. MILDB may be a more efficient approach compared with NATB. To conclude, embryo accumulation following mild stimulation appears to form the optimal strategy for POR management. More studies are needed to verify these conclusions.

PGT-A: who and when? Α systematic review and network meta-analysis of RCTs.

PURPOSE: Wide controversy is still ongoing regarding efficiency of preimplantation genetic testing for aneuploidy (PGT-A). This systematic review and meta-analysis, aims to identify the patient age group that benefits from PGT-A and the best day to biopsy. METHODS: A systematic search of the literature was performed on MEDLINE/PubMed, Embase and Cochrane Central Library up to May 2020. Eleven randomized controlled trials employing PGT-A with comprehensive chromosomal screening (CCS) on Day-3 or Day-5 were eligible. RESULTS: PGT-A did not improve live-birth rates (LBR) per patient in the general population (RR:1.11; 95%CI:0.87-1.42; n=1513; I2=75%). However, PGT-A lowered miscarriage rate in the general population (RR:0.45; 95%CI:0.25-0.80; n=912; I2=49%). Interestingly, the cumulative LBR per patient was improved by PGT-A (RR:1.36; 95%CI:1.13-1.64; n=580; I2=12%). When performing an age-subgroup analysis PGT-A improved LBR in women over the age of 35 (RR:1.29; 95%CI:1.05-1.60; n=692; I2=0%), whereas it appeared to be ineffective in younger women (RR:0.92; 95%CI:0.62-1.39; n=666; I2=75%). Regarding optimal timing, only day-5 biopsy practice presented with improved LBR per ET (RR: 1.37; 95% CI: 1.03-1.82; I2=72%). CONCLUSION: PGT-A did not improve clinical outcomes for the general population, however PGT-A improved live-birth rates strictly when performed on blastocyst stage embryos of women over the 35-year-old mark.

Abnormal fertilization in ICSI and its association with abnormal semen parameters: a retrospective observational study on 1855 cases.

Intracytoplasmic sperm injection (ICSI) efficiently addresses male factor infertility. However, the occurrence of abnormal fertilization, mainly characterized by abnormal pronuclei (PN) patterns, merits investigation. To investigate abnormal fertilization patterns following ICSI and identify their respective associations with abnormal parameters in semen analysis (SA), a retrospective observational study including 1855 cycles was performed. Male infertility diagnosis relied on the 2010 WHO criteria. The population was divided into groups based on their SA results. The presence of 2PNs and extrusion of the second polar body (PB) indicated normal fertilization. A Kruskal-Wallis test along with a Wilcoxon post hoc evaluation and Bonferroni correction was employed for comparison among the groups. For the pregnancy rate, logistic regression was employed. No correlation was established between the SA abnormalities and the 1PN or 3PN formation rates. The highest and lowest 0PN rates were reported for the oligoasthenoteratozoospermic and normal groups, respectively. The lowest cleavage formation rates were identified in the oligoasthenozoospermic and oligoasthenoteratozoospermic groups. The aforementioned groups along with the oligoteratozoospermic group similarly presented the lowest blastocyst formation rates. For the clinical pregnancy rate, no statistically significant difference was observed. In conclusion, the incidence of two or more abnormal SA parameters - with the common denominator being oligozoospermia - may jeopardize normal fertilization, cleavage, and blastocyst rates. Once the developmental milestone of achieving blastocyst stage status was achieved, only oligoasthenozoospermia and oligoasthenoteratozoospermia were associated with lower rates. Interestingly, following adjustment for the number of blastocysts, no statistically significant differences were observed.