Melatonin decreases excessive polyspermy for single oocyte in pigs through the MT2 receptor.

Melatonin supplementation during in vitro maturation (IVM) improves porcine oocyte maturation and embryonic development by exerting antioxidative effects. Nevertheless, the mechanism by which melatonin prevents polyspermy after in vitro fertilization (IVF) remains unclear. Here, we examined the effects of melatonin on cytoplasmic maturation and the incidence of polyspermic penetration in porcine oocytes. No statistically significant difference was observed in the rate of first polar body formation between the groups (Control, Melatonin, Melatonin + Luzindole, and Melatonin + 4-P-PDOT). Interestingly, melatonin supplementation significantly improved the cytoplasmic maturation of porcine oocytes by enhancing the normal distribution of organelles (Golgi apparatus, endoplasmic reticulum and mitochondria) and upregulating organelle-related gene expressions (P < 0.05). However, these promotional effects were counteracted by melatonin antagonists, suggesting that melatonin enhances cytoplasmic maturation through its receptors in porcine oocytes. Melatonin supplementation also significantly improved the rate of diploid and blastocyst formation after IVF by promoting the normal distribution of cortical granules (P < 0.05). In conclusion, melatonin supplementation during in vitro maturation of porcine oocyte improves fertilization efficiency and embryonic developmental competence by enhancing cytoplasmic maturation.

Relationship status among lesbian and heterosexual couples 8-10 years after undergoing assisted reproductive treatment in Sweden.

Background: Infertility along with fertility treatments has been reported to have a devastating effect on the well-being of the individuals involved as well as their relationship. So far, the studies exploring the impact on the relationship have mainly focused on heterosexual couples facing infertility and undergoing treatment. There is, therefore, a lack of data on the potential role of sexual orientation, gamete origin, as well as treatment success on the risk of separation after fertility treatment. The purpose of this study was, thus, to explore whether sexual orientation, donation treatment, and fertility success affected the relationship well-being and to explore various separation-related aspects. Methods: We have performed a prospective cohort study of heterosexual and homosexual couples undergoing fertility treatment with autologous and donated gametes in Sweden and followed them for up to 10 years after receiving fertility treatment. In the current follow-up study, 660 individuals have been included. Results: Almost 39% of lesbian couples participating reported having separated as opposed to 11-17% of heterosexual couples undergoing treatment with own or donated gametes. Neither background factors nor treatment success protected against separation. By using the relationship satisfaction ENRICH tool, we were able to demonstrate that dissatisfaction of one of the lesbian spouses or heterosexual spouses undergoing oocyte donation increased significantly the risk of separation 8-10 years after treatment commencement. Conclusion: The findings can be used by fertility clinics to provide relationship tools to the treated couples in order to help them nurture their relationship and decrease the risk of separation in the long run.

Planned Immediate Chemotherapy and Cryopreservation of Oocytes or Embryos for Fertility Preservation in Women with Malignancies.

Purpose: Oocyte and embryo cryopreservation before gonadotoxic treatment are established methods to increase the likelihood of live births. Although several sociodemographic factors were found to be associated with undergoing fertility preservation (FP) treatment, clinical characteristics such as planned immediate chemotherapy were not fully investigated. We aimed to investigate whether the planned immediate chemotherapy is related to the decision to undergo oocyte/embryo cryopreservation for FP with adjustment for other clinical characteristics. Methods: This institutional cohort study included 491 premenopausal women aged 19 years or older who visited the FP clinic at a tertiary medical center between 2006 and 2019. The primary outcome was whether the participants underwent oocyte/embryo cryopreservation. We evaluated the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) of undergoing oocyte/embryo cryopreservation according to whether immediate chemotherapy was planned using univariable and multivariable logistic regression. Results: Women scheduled for immediate chemotherapy were much less likely to undergo oocyte/embryo cryopreservation than women not scheduled for immediate chemotherapy (OR = 0.46, 95% CI 0.27-0.76) in univariable logistic regression analysis. After adjustment for covariates such as marital status, type of malignancies, and calendar year period, women scheduled for immediate chemotherapy were still less likely to undergo oocyte/embryo cryopreservation than women not scheduled for immediate chemotherapy (OR = 0.31, 95% CI: 0.17-0.56). The association was not different according to the type of malignancies (p for interaction = 0.13). Regarding breast cancer, the OR for undergoing oocyte/embryo cryopreservation in women scheduled for immediate chemotherapy was robust compared with those not planned for immediate chemotherapy (OR = 0.25, 95% CI: 0.12-0.53). Conclusion: The present study demonstrated that planned immediate chemotherapy was negatively associated with undergoing oocyte/embryo cryopreservation. This information can be helpful for FP counseling.

Hepatitis B virus in oocytes and embryos: pregnancy outcomes and children's health.

Objective: To investigate whether the presence of hepatitis B virus (HBV) in oocytes and embryos affects pregnancy outcomes for in vitro fertilization and embryo transfer (ET) as well as is related to the vertical transmission of HBV to children. Design: Retrospective cohort study. Setting: A university-affiliated fertility center. Patients: This study included 167 couples with at least 1 hepatitis B surface antigen-seropositive partner. These couples underwent in vitro fertilization-ET, and the discarded oocytes and embryos had been tested for HBV. Couples with HBV-positive oocytes or embryos were categorized as the positive group, whereas those couples with HBV-negative oocytes and embryos served as the negative group. Interventions: None. Main Outcome Measures: Pregnancy outcomes and the rate of children's HBV infection. Results: The pregnancy outcomes of fresh and frozen ETs were not associated with the presence of HBV in the oocytes and embryos. Of the 106 infants born, 1 child whose mother tested positive for hepatitis B surface antigen but had negative oocytes and embryos was infected with HBV. Additionally, 26.09% of children who had been administered passive immunization and active vaccinations did not reach protective levels of anti-HBV antibodies (hepatitis B surface antibodies) and became nonresponders. The negative rate of children's hepatitis B surface antibody was associated with the presence of HBV in oocytes and embryos (odds ratio, 3.01; 95% confidence interval, 1.04-9.25). Conclusions: The presence of HBV in oocytes and embryos did not affect pregnancy outcomes or result in the vertical transmission of HBV to the offspring of HBV carriers. Follow-up is needed for HBV-vaccinated children with an HBV-infected parent. Booster vaccinations are necessary for continued protection.

Expert Opinion on Refined and Extended Key Performance Indicators for Individualized Ovarian Stimulation for ART.

OBJECTIVE: To assess the adequate ovarian follicular development and oocyte recovery between ovarian potential (antral follicle count [AFC]) before the start of ovarian stimulation (OS) and oocyte quantity and quality at oocyte retrieval. A holistic overview of the current key performance indicators (KPIs) was applied to identify the complementary strengths and identify where the current repertoire can be expanded. DESIGN: Expert opinion. SUBJECTS: Not applicable. INTERVENTION: None. MAIN OUTCOME MEASURES: To formulate a proposal for a refined and expanded repertoire of KPIs for individualized OS for Assisted Reproductive Technology. RESULTS: The performance and outcomes of OS on ovarian follicular development can be evaluated through the application of defined KPIs. Current KPIs for OS are the ovarian sensitivity index (OSI), the follicular output rate (FORT), the oocyte retrieval rate (ORR), and the follicle to oocyte index (FOI). Notably, there are no specific KPIs dedicated to the assessment of follicular development (i.e., recruitment, selection, growth and dominance). In light of this, we recommend expanding the current KPIs for OS to include "Early FORT" (accounting for the number of follicles measuring ≥10-11 mm on Day 5/6 of OS relative to AFC) and "Modified FORT" (the ratio between the number of follicles measuring ≥12 mm at the time of oocyte maturation triggering and AFC); the extension of ORR to include two discrete categories at oocyte retrieval: follicles ≥12 mm and follicles ≥16 mm, to ensure all responsive follicles are accounted for; and FOI to be measured at oocyte maturation triggering and oocyte retrieval ("Advanced FOI"). CONCLUSIONS: Once validated and adopted in clinical practice, we envisage that the proposed expanded KPIs measuring the effect of OS on follicular development (recruitment, selection, growth and dominance) will increase the understanding of the relationship between ovarian reserve measured by AFC and oocyte quantity and quality at oocyte retrieval. This understanding will enable physicians to better evaluate the direct effect of different gonadotropins and doses on ovarian response, leading to a more personalized approach to OS in the context of ART treatment.

The effect of male factors on embryo morphokinetics: a retrospective analysis of 2726 blastocysts.

PURPOSE: Male infertility may influence fertilization rates, embryo morphology, and implantation rates in in vitro fertilization (IVF) cycles. Oocyte competence plays a major role in embryo development, but there is a limited understanding of the connection between sperm quality, embryo development, and morphokinetic parameters using donor oocytes. The study evaluated if sperm quality may influence the morphokinetic parameters in IVF cycles. METHODS: A retrospective multicentric observational cohort study included 747 ICSI cycles using donor oocytes with fresh or frozen sperm. Embryos were cultured in time-lapse incubators until the blastocyst stage. The population was divided into three groups according to sperm concentration, as control group (> 16 mill/mL), severe oligospermia (0-5 mill/mL), and moderate oligospermia group (5-16 mill/mL). RESULTS: Morphokinetic analysis showed no difference in the time from the 2-cell to 6-cell stage of embryo development. A significant difference was observed on day 3 of embryo development, specifically at the 7-cell stage (t7), severe oligospermia 53.37 ± 9.81, moderate oligospermia 56.95 ± 9.78, and control 55.1 ± 8.85 h post-insemination (hpi) (p = 0.024), and 8-cell stage (t8), severe oligospermia 55.41 ± 10.83, moderate oligospermia 61.86 ± 12.38 hpi (p < 0.001), and control 58.61 ± 11.33. Accordingly, the synchrony of the four cleavages going from 4 to 8 cells (s3) was found statistically different among the groups in the severe oligospermia 8.05 ± 9.99, moderate oligospermia 11.66 ± 11.04 hpi, and control 8.55 ± 8.58 (p = 0.009). Morphokinetic time ranges were obtained for t6, t7, t8, and s3 in order to identify the good-quality blastocysts. CONCLUSIONS: Poor sperm quality is associated with alterations in morphokinetic parameters on day 3 in IVF cycles with donor oocytes, underlining the important role of spermatozoa during embryo development.

Bisphenol AP inhibits mouse oocyte maturation in vitro by disrupting cytoskeleton architecture and cell cycle processes.

Bisphenol A (BPA) is among the extensively researched environmental endocrine-disrupting chemicals (EDCs), and its utilization is restricted owing to the detrimental impacts it has on human health. Bisphenol AP (BPAP) is one of the alternatives to BPA, but the influence of BPAP on human health has not been elucidated. The objective of the current research was to determine the influence of BPAP exposure on the in vitro maturation of mouse oocytes and to explore its potential reproductive toxicity. BPAP exposure was found to inhibit polar body extrusion during mouse oocyte maturation, resulting in an arrest at the metaphase I stage of meiosis. Exposure to BPAP led to sustained activation of BubR1, preventing the degradation of both Securin and Cyclin B1. Mechanistically, BPAP exposure disrupts spindle assembly and chromosome alignment. Levels of acetylated α-tubulin were significantly elevated in BPAP-treated oocytes, reflecting decreased spindle stability. Exposure to BPAP also induced DNA damage and impaired DNA damage repair. In addition, BPAP exposure altered histone modification levels. In summary, this investigation suggests that exposure to BPAP can influence cytoskeletal assembly, interfere with cell cycle progression, induce DNA damage, alter histone modifications, and ultimately impede oocyte meiotic maturation. This investigation enhances understanding of the impact of bisphenol analogs on female gametes, underscoring that BPAP cannot be considered a reliable replacement for BPA.

The dose-dependent dual effects of alpha-ketoglutarate (AKG) on cumulus oocyte complexes during in vitro maturation.

In this study, we reported for the first time the dose-dependent dual effects of Alpha-Ketoglutarate (AKG) on cumulus oocyte complexes (COCs) during in vitro maturation (IVM). AKG at appropriate concentration (30 µM) has beneficial effects on IVM. This includes improved cumulus expansion, oocyte quality, and embryo development. These effects are mediated through multiple underlying mechanisms. AKG reduced the excessive accumulation of reactive oxygen species (ROS) in cumulus cells, reduced the consumption of GSH and NADPH. Cumulus GSH and NADPH were transported to oocytes via gap junctions, thereby reducing the oxidative stress, apoptosis and maintaining the redox balance in oocytes. In addition, AKG improved the mitochondrial function by regulating the mitochondrial complex 1 related gene expression in oocytes to maintain mitochondrial membrane potential and ATP production. On the other hand, oocyte generated GDF9 could also be transported to cumulus cells to promote cumulus expansion. Conversely, a high concentration of AKG (750 µM) exerted adverse effects on IVM and suppressed the cumulus expansion as well as reduced the oocyte quality. The suppression of the cumulus expansion caused by high concentration of AKG could be rescued with GDF9 supplementation in COCs, indicating the critical role of GDF9 in IVM. The results provide valuable information on the variable effects of AKG at different concentrations on reproductive physiology.

Understanding the intricate impacts and mechanism of actions of adaptogens on reproductive function.

Adaptogens, comprising plants and mushrooms, modulate the immune system, energy balance, and various physiological processes, including reproduction. Despite their potential benefits, the impact of adaptogens on reproductive function remains understudied. This review examines the effects of common adaptogens on male and female reproductive functions, highlighting their regulation of neuro-endocrine-immune interactions crucial for reproduction. While existing literature reveals varying impacts on reproductive function, most adaptogens exhibit beneficial effects, modulating neuroimmunology and promoting gonadal steroidogenesis, spermatogenesis, and folliculogenesis through direct mechanisms or suppression of oxidative stress and inflammation. Further experimental research is necessary to elucidate the mechanisms of action of adaptogens, which would significantly advance the management of reproductive disorders and other diseases. Validating these findings in clinical trials is also essential.

Epigenetic Modifications Are Involved in Transgenerational Inheritance of Cadmium Reproductive Toxicity in Mouse Oocytes.

Maternal cadmium exposure during pregnancy has been demonstrated to have detrimental effects on offspring development. However, the impact of maternal cadmium exposure on offspring oocytes remains largely unknown, and the underlying mechanisms are not fully understood. In this study, we found that maternal cadmium exposure during pregnancy resulted in selective alteration in epigenetic modifications of mouse oocytes in offspring, including a decrease in H3K4me2 and H4K12ac, as well as an increase in DNA methylation of H19. Although ROS levels and mitochondrial activity remain at normal levels, the DNA damage marker γH2AX was significantly increased and the DNA repair marker DNA-PKcs was remarkably decreased in offspring oocytes from maternal cadmium exposure. These alterations are responsible for the decrease in the quality of mouse oocytes in offspring induced by maternal cadmium exposure. As a result, the meiotic maturation of oocytes and subsequent early embryonic development are influenced by maternal cadmium exposure. RNA-seq results showed that maternal cadmium exposure elicits modifications in the expression of genes associated with metabolism, signal transduction, and endocrine regulation in offspring ovaries, which also contribute to the disorders of oocyte maturation and failures in early embryonic development. Our research provides direct evidence of transgenerational epigenetic inheritance of cadmium reproductive toxicity in mouse germ cells.

A Compound Heterozygous Pathogenic Variant in ZP2 Gene Causes Female Infertility.

The oocyte maturation defect 6 is an autosomal recessive hereditary disease caused by a homozygous variant in ZP2 gene. It is characterized by female primary infertility due to an abnormally thin zona pellucida (ZP) and defective sperm binding. Here we identified a compound heterozygous variant (c.1924C > T and c.1695-2A > G) in ZP2 gene in a Chinese Han family. Quantitative real-time PCR showed that the variant c.1924C > T significantly decreased the expression of truncated ZP2 message RNA by the nonsense-mediated decay pathway. Minigene assays showed the c.1695-2A > G variant led to an extra-61-nt preservation of intron 15 at the junction between exons 15 and 16 during transcription. Both variants (c.1924C > T and c.1695-2A > G) resulted in truncated ZP2 proteins (p.R642X and p.C566Hfs*2) that lost the transmembrane domain, which prevented the secretion of the mutant ZP2 proteins and produced a structurally abnormal ZP, thus resulting in female infertility. This study further elucidated the pathogenic mechanism of these two variants and provided new support for the genetic diagnosis of female infertility.

An exploratory study of perceptions and utilization of genetic information in the intended parent experience of oocyte donor selection.

PURPOSE: Utilization of oocyte donation has become an increasingly common practice in assisted reproductive technology (ART). Since the introduction of larger carrier screening (CS) panels and extended family medical histories (EFMH), studies have not examined how this information factors into the oocyte donor selection process. This exploratory, qualitative study provides further insight into what role, if any, donors' available genetic information (e.g., larger CS panels and EFMH) plays in selecting an oocyte donor. METHODS: An online screening survey was distributed to individuals who have undergone or are currently in the process of selecting an oocyte donor through the RESOLVE network and Mayo Clinic's Reproductive Endocrinology and Infertility clinic. From 13 survey respondents, six oocyte recipients subsequently participated in semi-structured telephone interviews and discussed their experiences as oocyte recipients including their perceptions of donors' available genetic information and process in choosing an oocyte donor. RESULTS: Genetic information was seen as valuable and reassuring for participants, particularly EFMH, but did not play a significant role in the selection process for these participants. Supplemental emergent themes provide context on the psychosocial complexities of the oocyte recipient experience and possible explanations for why genetic information is not a decisional priority. Participants indicated genetic information was not extensively discussed or fully explained by providers. CONCLUSIONS: Results demonstrate how genetic counselors can be more involved in the pre-selection process to discuss the utility and limitations of genetic information, as well as address psychosocial issues common to the oocyte recipient experience.

Control of sperm penetration using stereumamide A derived from Trichaptum fuscoviolaceum in the in vitro fertilization of pig oocytes.

Fungal metabolites are known to have potent and diverse properties such as antiviral, antidiabetic, antitumour, antioxidant, free radical scavenging, and antibacterial effects which can be utilized to treat diseases. In this study, we investigated the functional activity of stereumamide A (StA) derived from a culture broth of Trichaptum fuscoviolaceum during the in vitro fertilization (IVF) of pig oocytes, to determine its effects on sperm penetration. Oocytes matured in vitro were fertilized in the absence or presence of varying concentrations of StA (0-50 µg/ml StA). When StA was directly added into the IVF medium, significantly lower fertilization rates were seen with the 20 or 50 µg/ml StA (2.0-17.5%) treatments compared with those of 10 µg/ml StA or the controls (60.9-62.3%), whereas StA had no influence on the survival of oocytes and spermatozoa throughout the IVF process. For evaluating the control of sperm entry, mature oocytes were pre-incubated in a medium containing 20 µg/ml StA for 1 h, and then IVF was subsequently performed. The incidence of polyspermy was significantly reduced when oocytes were pre-incubated with StA (15.0% vs. 50.4-57.5% in controls). In conclusion, sperm penetration was inhibited in the medium in the presence of StA during IVF, while StA did not affect sperm motility and fertility competence. Fertilization was controlled when mature oocytes were incubated with StA prior to IVF, suggesting the possible use of the fungal metabolite in assisted reproductive technology for humans and animals.

The NAD+ precursor nicotinamide riboside protects against postovulatory aging in vitro.

PURPOSE: Postovulatory aging (POA) of oocytes is clinically significant as it mirrors the degeneration observed in maternally aged oocytes, leading to substantial impairments in oocyte quality and the success rates of artificial reproductive technology (ART). The molecular alterations associated with POA, such as the degeneration of the first polar body, an increase in perivitelline space, reactive oxygen species (ROS) accumulation, energy depletion, and chromosomal and DNA damage, underscore the urgency of finding interventions to mitigate these effects. This study aims to identify whether nicotinamide riboside (NR) can prevent POA during the process of in vitro culture and raise the success rates of ART. METHOD: Taking advantage of an in vitro postovulatory oocyte aging model, we examined the morphological integrity and NAD+ levels of ovulated mouse MII oocytes after 24 h of culturing. Following in vitro fertilization, we assessed the embryonic developmental potential of oocytes affected by POA. Using immunofluorescence and confocal microscopy, we measured the levels of ROS, mitochondrial function, and γH2AX. We also evaluated spindle assembly and chromosome alignment. Additionally, we detected the distribution of cortical granules to assess the metabolic and quality changes in POA oocytes with the supplementation of NR. To further our analysis, quantitative real-time PCR was conducted to measure the mRNA expression levels of antioxidant enzymes Sod1 and Gpx1 in the oocytes. RESULTS: With 200 µM NR supplementation during in vitro culture for 24 h, the oocytes from POA demonstrated reduced signs of aging-related decline in oocyte quality, including reduced ROS accumulation, improved mitochondrial function, and corrected mis-localization of cortical granules. This improvement in oocyte quality is likely due to the inhibition of oxidative stress via the NAD+/SIRT1 signaling pathway, which also helped to restore normal spindle assembly and chromosome alignment, as well as reduce the elevated levels of γH2AX, thereby potentially enhancing the embryonic development potential. CONCLUSION: Current research provides evidence that NR is an efficient and safe natural component that prevents the process of POA and is thus a potential ideal antiaging drug for raising the success rates of ART in clinical practice.

Multi-omics approach to reveal follicular metabolic changes and their effects on oocyte competence in PCOS patients.

Background: Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder linked with endocrine and metabolic disturbances. The underlying mechanism of PCOS, especially its effect on oocyte competence, remains unclear. The study aimed to identify abnormal follicular metabolic changes using a multi-omics approach in follicular fluid from PCOS patients and to determine their effects on oocyte competence. Methods: A total of 36 women with PCOS and 35 women without PCOS who underwent in vitro fertilization and embryo transfer were included in the study. Cumulus cells and follicular fluid samples were collected. Follicular fluid samples underwent metabolomic analysis, while cumulus cell clusters from the same patients were assessed using transcriptomic analysis. Clinical information of patients and assisted reproductive technology (ART) results were recorded. Transcriptomics and metabolomics were integrated to identify disrupted pathways, and receiver operation characteristics (ROC) analysis was conducted to identify potential diagnostic biomarkers for PCOS. Pearson correlation analysis was conducted to assess the relationship between metabolites in follicular fluid and oocyte competence (fertilization and early embryo development potential). Results: Through multi-omics analysis, we identified aberrantly expressed pathways at both transcriptional and metabolic levels, such as the citrate cycle (TCA cycle), oxidative phosphorylation, the cAMP signaling pathway, the mTOR signaling pathway, and steroid hormone biosynthesis. Ten candidate metabolites were identified based on metabolic profiling data from these altered pathways. Phytic acid, succinic acid, 2'-deoxyinosine triphosphate, and 4-trimethylammoniobutanoic acid in the follicular fluid exhibited high specificity and sensitivity in distinguishing PCOS. Among these metabolites, L-arginine showed a negative correlation with the 2PN fertilization rate and cleavage rate, while estrone sulfate showed a negative correlation with the high-quality embryo rate in the in-vitro fertilization (IVF) cycle. Conclusions: We have conducted a preliminary study of a novel metabolic signature in women with PCOS using a multi-omics approach. The alterations in key metabolic pathways may enhance our understanding of the pathogenesis of PCOS.

Clinical management of transgender and non-binary patients in the fertility preservation service: Current evidence.

Background: Transgender and non-binary individuals face unique challenges when it comes to fertility preservation (FP). Objective: Despite the growing prevalence of gender dysphoria (GD) and gender transitioning, there is a lack of clear guidelines and consensus on the management of these patients in the FP setting. Clinicians and institutions providing FP services should ensure that they are aware of the needs and circumstances of this underrepresented group of patients and offer them accurate and evidence-based information when counseling and tailoring their FP treatment. Materials and methods: For this scoping review, three major search engines were used. Including Embase, Epistemonikos, Google Scholar, MEDLINE and PubMed. Sources of grey literature were also explored (ResearchGate and Web of Science). The combination of only two keywords [transgender] AND [fertility preservation] was used up to May 2023. Results: The available evidence on clinical management and FP outcomes in transgender patients is limited and mainly originates from case reports or small case series. The main limitation of current FP services for transgender and non-binary individuals is the lack of scientific evidence regarding their care. Discussion: Overall, FP in transgender patients requires individualized and realistic plans, and psychological counseling should be offered. This review aims to provide the latest evidence coming from original studies to facilitate proper counseling and fertility management for these individuals. Conclusions: Inclusive health systems that provide comprehensive reproductive health care to transgender individuals can help them make informed decisions about FP and improve their quality of life. Future research is needed to establish more robust evidence-based guidelines for the management of transgender and non-binary individuals in the FP setting.

On the role of artificial intelligence in analysing oocytes during in vitro fertilisation procedures.

Nowadays, the most adopted technique to address infertility problems is in vitro fertilisation (IVF). However, its success rate is limited, and the associated procedures, known as assisted reproduction technology (ART), suffer from a lack of objectivity at the laboratory level and in clinical practice. This paper deals with applications of Artificial Intelligence (AI) techniques to IVF procedures. Artificial intelligence is considered a promising tool for ascertaining the quality of embryos, a critical step in IVF. Since the oocyte quality influences the final embryo quality, we present a systematic review of the literature on AI-based techniques used to assess oocyte quality; we analyse its results and discuss several promising research directions. In particular, we highlight how AI-based techniques can support the IVF process and examine their current applications as presented in the literature. Then, we discuss the challenges research must face in fully deploying AI-based solutions in current medical practice. Among them, the availability of high-quality data sets as well as standardised imaging protocols and data formats, the use of physics-informed simulation and machine learning techniques, the study of informative, descriptive yet observable features, and, above all, studies of the quality of oocytes and embryos, specifically about their live birth potential. An improved understanding of determinants for oocyte quality can improve success rates while reducing costs, risks for long-term embryo cultures, and bioethical concerns.

Gene expression levels in cumulus cells are correlated with developmental competence of bovine oocytes.

The generation of mammalian embryos by in vitro culture is hampered by the failure of many of the embryos to develop to the blastocyst stage. This problem occurs even when cumulus-oocyte complexes (COCs) with good morphology are visually selected and used for culture. Because cumulus cells are important for oocyte maturation and subsequent embryo development, here we compared gene expression patterns in cumulus cells of COCs that developed in vitro to the blastocyst stage with those of COCs that failed to develop. Cumulus cells were aspirated from bovine COCs selected for in vitro culture. Oocyte developmental competence was evaluated by screening for cleavage and development to the blastocyst stage. The collected cumulus cells were used to quantify mRNA levels of FSH receptor (FSHR), insulin-like growth factor-1 receptor (IGF-1R), anti-Müllerian hormone (AMH), AMH receptor II (AMHRII), epidermal growth factor receptor (EGFR), estrogen receptor ß (ERß), B cell lymphoma/leukemia-2 associated X (Bax), and cysteine-aspartic acid protease-3 (Caspase-3). We found that the expression levels of FSHR, IGF-1R, AMH, and EGFR were higher in cumulus cells from COCs that developed to blastocysts as compared with those that failed to develop, whereas expression levels of Bax and Caspase-3 were lower in cumulus cells of COCs that matured to the blastocyst stage. Positive correlations were found between FSHR and IGF-1R expression (r = 0.59) and between ERß and EGFR expression (r = 0.43) in cumulus cells from COCs that developed to the blastocyst stage. Our findings indicate that gene expression levels in cumulus cells are correlated with the developmental competence of bovine oocytes. Measurement of gene expression in cumulus cells therefore offers a non-invasive means of predicting oocyte developmental competence.

Regulation of outer kinetochore assembly during meiosis I and II by CENP-A and KNL-2/M18BP1 in C. elegans oocytes.

During cell division, chromosomes build kinetochores that attach to spindle microtubules. Kinetochores usually form at the centromeres, which contain CENP-A nucleosomes. The outer kinetochore, which is the core attachment site for microtubules, is composed of the KMN network (Knl1c, Mis12c, and Ndc80c complexes) and is recruited downstream of CENP-A and its partner CENP-C. In C. elegans oocytes, kinetochores have been suggested to form independently of CENP-A nucleosomes. Yet kinetochore formation requires CENP-C, which acts in parallel to the nucleoporin MEL-28ELYS. Here, we used a combination of RNAi and Degron-based depletion of CENP-A (or downstream CENP-C) to demonstrate that both proteins are in fact responsible for a portion of outer kinetochore assembly during meiosis I and are essential for accurate chromosome segregation. The remaining part requires the coordinated action of KNL-2 (ortholog of human M18BP1) and of the nucleoporin MEL-28ELYS. Accordingly, co-depletion of CENP-A (or CENP-C) and KNL-2M18BP1 (or MEL-28ELYS) prevented outer kinetochore assembly in oocytes during meiosis I. We further found that KNL-2M18BP1 and MEL-28ELYS are interdependent for kinetochore localization. Using engineered mutants, we demonstrated that KNL-2M18BP1 recruits MEL-28ELYS at meiotic kinetochores through a specific N-terminal domain, independently of its canonical CENP-A loading factor activity. Finally, we found that meiosis II outer kinetochore assembly was solely dependent on the canonical CENP-A/CENP-C pathway. Thus, like in most cells, outer kinetochore assembly in C. elegans oocytes depends on centromeric chromatin. However, during meiosis I, an additional KNL-2M18BP1 and MEL-28ELYS pathway acts in a non-redundant manner and in parallel to canonical centromeric chromatin.