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 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.

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.

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.

Navigating assisted reproduction treatment in the time of COVID-19: concerns and considerations.

The COVID-19 pandemic has fueled numerous debates in the field of assisted reproductive technology (ART) as the effect of SARS-CoV-2 on pregnancy and infancy is still considered uncharted territory. Various theses and recommendations on what optimal practice is have emerged, as evidenced by surveys, webinars, and recent publications. ART specialists are faced with dilemmas in light of the lack of concrete scientific evidence required to pave the way towards future safe practice. Meanwhile, infertile couples were similarly left in limbo unable to exercise their reproductive autonomy unlike fertile couples-where achieving a pregnancy via natural conception is a matter of decision. ART treatment being classified as non-essential has only recently re-started, facing new challenges while enabling pregnancy at a time of uncertainty. This article highlights matters of bioethical nature to be considered in the ART world at the time of COVID-19 while presenting an all-inclusive critique of the current status. When pursuing pregnancy through IVF treatment during the pandemic, distancing and caution have the lead role in an effort to defend the health of the intended parents and future children. To promote patient autonomy along with our ethical, moral, and legal duty towards our patients, emphasis should be given on ascertaining shared decision-making, and ensuring that an appropriate all-inclusive informed consent is signed prior to initiating any IVF treatment.

Assessing the practice of LuPOR for poor responders: a prospective study evaluating follicular fluid cfDNA levels during natural IVF cycles.

PURPOSE: The aim of this study is to provide data on the practice of Luteal Phase Oocyte Retrieval (LuPOR). The authors assess cell-free DNA levels in follicular fluid (ff cfDNA) from poor responders undergoing natural cycles, and comparing it to respective data originating from follicular phase oocyte retrievals. METHODS: Forty-seven women were eligible for this prospective study. Participants were classified as poor responders based on Bologna criteria while being detected with a second follicular wave. Follicular fluid was collected and prepared for cfDNA extraction. Levels of cfDNA were quantified via Q-PCR employing the ALU115 and ALU247 primers. These primers are associated with apoptotic and necrotic events. Levels of ff cfDNA resulting from follicular phase oocyte retrieval (FoPOR) and LuPOR-performed in a single menstrual cycle were associated with the number and maturation status of yielded oocytes and the number and fertilization status of resulting zygotes. Survival rate following thawing of cryopreserved zygotes, along with the resulting number of cleavage stage and blastocyst stage embryos are provided. RESULTS: Mean levels of ALU115 were significantly lower during FoPOR when compared to LuPOR (0.79 ± 0.72 vs 1.46 ± 1.59 ng/µl, p = 0.02). Regarding the FoPOR group, a significant positive correlation of serum estradiol and ALU115 concentration (p = 0.04) was revealed. A significant negative correlation between serum estradiol and cfDNA integrity was observed both during FoPOR (p = 0.03) and LuPOR (p = 0.03). A significant lower number of retrieved (1.09 ± 0.28 vs 1.29 ± 0.58, p = 0.02) and MII oocytes (0.77 ± 0.55 vs 1.08 ± 0.61, p = 0.02) was observed when comparing the FoPOR to LuPOR groups respectively. The integrity of cfDNA was observed to be higher in FoPOR originating embryos that arrested either prior to cleavage (0.28 ± 0.13 vs 0.17 ± 0.10, p = 0.006) or prior to blastocyst formation (0.28 ± 0.12 vs 0.13 ± 0.06, p = 0.04). In the case of LuPOR originating embryos, cfDNA integrity was observed to be higher in embryos that arrested only prior to the blastocyst stage (0.27 ± 0.20 vs 0.11 ± 0.07, p = 0.008). Similarly, cfDNA integrity was observed to be lower in top quality blastocysts originating from FoPOR (0.07 ± 0.04 vs 0.17 ± 0.05, p = 0.03) and in top quality cleavage stage embryos (0.09 ± 0.06 vs 0.31 ± 0.22, p = 0.01) and blastocysts (0.06 ± 0.02 vs 0.14 ± 0.06, p = 0.02) originating from LuPOR. CONCLUSIONS: Our results indicate that ff originating from LuPOR presents with higher levels of cfDNA. The higher cfDNA levels are attributed to mainly apoptotic events, as the ALU247 levels and DNA integrity did not differ statistically significantly between FoPOR and LuPOR. The absolute mean level of ALU247 corresponding to necrotic events was higher in LuPOR. Regarding embryological data, cfDNA integrity was correlated with both number and quality of cleavage stage embryos in both FoPOR and LuPOR, along with blastocyst stage embryos in LuPOR. Necrotic events were associated with poorer blastocyst formation rate and blastocyst quality in LuPOR. As the comparison between FoPOR and LuPOR results to similar IVF laboratory data, the practice of LuPOR may stand as a promising approach for poor responders, while it merits further investigation.

What is the true place of a double stimulation and double oocyte retrieval in the same cycle for patients diagnosed with poor ovarian reserve? A systematic review including a meta-analytical approach.

PURPOSE: This systematic review including a meta-analytical approach aims to investigate the safety and efficacy of employing a double ovarian stimulation (DuoStim) and a subsequent double oocyte retrieval in the same menstrual cycle, in poor ovarian reserve (POR) patients. METHODS: A systematic search of literature was performed in the databases of PubMed/MEDLINE, Embase, and Cochrane Central Library up until March 2019. Both prospective and retrospective cohort studies considered suitable for inclusion reported on women with POR undergoing a DuoStim in the follicular (FPS) and luteal phase (LPS) of the same menstrual cycle. Following the systematic review of the literature, a meta-analytical approach was attempted. RESULTS: This study indicates that DuoStim is correlated with a higher number of retrieved oocytes, mature MII oocytes, and good-quality embryos in comparison to conventional stimulation. Additionally, LPS seems to be correlated with an equal or an even higher overall performance in comparison to FPS. CONCLUSION: DuoStim favors an enhanced clinical outcome in regard to the total number of yielded oocytes, mature oocytes, and available embryos, along with the quality of obtained embryos. Sourced data indicate that LPS is not correlated with a higher aneuploidy rate. This option may present as promising for the time-sensitive nature of POR patients' management, by enabling a higher oocyte yield during a single menstrual cycle.

Could the Age Difference of a Single Calendar Year between Patients Undergoing IVF at 34, 35 or at 36 Years Old Affect the IVF Outcome? A Retrospective Data Analysis.

Background and Objectives: Clinicians are called to overcome age-related challenges in decision making during In Vitro Fertilization (IVF) treatment. The aim of this study was to investigate the possible impact of a single calendar year difference among patients aged 34, 35 and 36 on IVF outcomes. Materials and Methods: Medical records between 2008 and 2019 were analyzed retrospectively. The study group consisted of women diagnosed with tubal factor infertility. Sample size was divided in three categories at 34, 35 and 36 years of age. Embryo transfer including two blastocysts was performed for every patient. Comparisons were performed regarding hormonal profile, response to stimulation, quality of transferred embryos, positive hCG test and clinical pregnancy rate. Results: A total of 706 women were eligible to participate. Two-hundred and forty-eight women were 34, 226 were 35 while the remaining 232 were 36 years old. Regarding the hormonal profile, the number of accumulated oocytes and the quality of embryos transferred, no statistically significant difference was documented between the three age groups. Women aged 34 and 35 years old indicated a significantly increased positive hCG rate in comparison to women aged 36 years old (p-value = 0.009, p-value = 0.023, respectively). Women aged 34 and 35 years old presented with a higher clinical pregnancy rate in comparison to those aged 36 years old (p-value = 0.04, p-value = 0.05, respectively). Conclusion: A calendar year difference between patients undergoing IVF treatment at 34 or 35 years of age does not appear to exert any influence regarding outcome. When treatment involves patients above the age of 35, then a single calendar year may exert considerable impact on IVF outcome. This observation indicates that age 35 may serve as a valid cut-off point regarding IVF outcome.

Assessing Clinical Embryology Research: A Global Bibliometric Analysis.

Background and Objectives: The evaluative strength of available bibliometric tools in the field of clinical embryology has never been examined in the literature. The aim is to bring insight regarding the identity of clinical embryology research, introducing concerns when solely relying on the methodology of bibliometric analysis. Methods: An all-inclusive analysis of the most bibliometrically highlighted scientific contributions regarding the cornerstones of clinical embryology was performed employing the Scopus, Web of Science (WoS) and PubMed databases, between 1978-2018. An analysis of the number of publications, respective citations and h-index, g-index, along with m-quotient is presented. The top 30 contributing authors for each distinctive area of research are listed. An attempt at visualizing the yearly published articles, clusters, and collaborations of authors, along with the geographic origin of publications, is also presented. Results: Combining all searches and keywords yielded 54,522 results. In the Scopus database, employing the keyword "In Vitro Fertilization" yielded 41,292 results. The publications of the top five authors in each research field were analytically presented and compared to the total number of publications for each respective field. The research field of Preimplantation Genetic Diagnosis/Screening/Testing was allocated the highest percentage of publications produced by the top five authors. Regarding journal bibliometrics, based on the year 2017 metrics, there are only 29 journals according to WoS that refer to "Reproductive Biology", ranking it 187th among 235 disciplines. The USA produced the highest number of publications (12,537). Conclusion: Results indicate an explosion of interest published in the literature regarding the field of clinical embryology. Further analysis on collaborations and the trends involved should be of added value as productivity between countries varies significantly. This may guide researchers, in vitro fertilization professionals, and prospective authors during literature search, while proving useful regarding manuscript design and concurring on keywords and abstract content.

A Case Series on Platelet-Rich Plasma Revolutionary Management of Poor Responder Patients.

Poor responders are described as those In Vitro Fertilization (IVF) patients who are failing to respond to controlled ovarian stimulation protocols. Extensive research has focused on crafting the optimal treatment. However, it appears that each approach fails to be established as effective or guaranteed towards successful management. Platelet-Rich Plasma (PRP) is a novel, highly promising approach that has been successfully applied for an array of medical issues. In this case series, we present 3 poor responder patients with the common denominator of: failed IVF attempts, poor oocyte yield, and poor embryo quality. The option of oocyte donation was rejected. All patients were treated with autologous PRP ovarian infusion following written consent. Within a 3-month interval, follicle-stimulating hormone decreased by 67.33%, while Anti-Müllerian hormone increased by 75.18%. These impressive results on the biochemical infertility markers alone are classified as a complete biological paradox, coupled by improved embryo quality. Results report a natural conception at 24 weeks, an uncomplicated healthy pregnancy at 17 weeks and a successful live birth. To our knowledge, this is the first time such an approach and results are reported, where PRP treatment on poor responders lead to overcoming their challenging reproductive barrier.

The Impact of Autoantibodies on IVF Treatment and Outcome: A Systematic Review.

The role of autoantibodies in in vitro fertilization (IVF) has been discussed for almost three decades. Nonetheless, studies are still scarce and widely controversial. The aim of this study is to provide a comprehensive systematic review on the possible complications associated to autoantibodies (AA) impeding the chances of a successful IVF cycle. An Embase, PubMed/Medline and Cochrane Central Database search was performed on 1 December 2018, from 2006 until that date. From the 598 articles yielded in the search only 44 relevant articles ultimately fulfilled the inclusion criteria and were qualitatively analyzed. Five subsets of results were identified, namely, thyroid related AA, anti-phospholipid antibodies, anti-nuclear antibodies, AA affecting the reproductive system and AA related to celiac disease. It may be implied that the majority of auto-antibodies exert a statistically significant effect on miscarriage rates, whereas the effects on clinical pregnancy and live birth rates differ according to the type of auto-antibodies. While significant research is performed in the field, the quality of evidence provided is still low. The conduction of well-designed prospective cohort studies is an absolute necessity in order to define the impact of the different types of autoantibodies on IVF outcome.

The Impact of the Economic Recession in Greece on Assisted Reproduction Demand: A Retrospective Longitudinal Study.

BACKGROUND AND OBJECTIVES: Since 2009, the decline of the Greek economy has been in the spotlight of the world's financial agenda. This study assesses the economic crisis' impact on assisted reproduction demand dynamics. MATERIALS AND METHODS: Patient records were recruited between 2005-2017. In 2013 the clinic proceeded with a cost reduction. The studied time-frames were defined accordingly: Period A: Prior to economic crisis, Period B: During the economic crisis-prior to cost reduction, and Period C: During the economic crisis-following cost reduction. Analysis focused on parameters reflecting on patient characteristics, decision to inquire on IVF treatment, embarking on it, and proceeding with multiple cycles. RESULTS: The mean annual number of first visit patients was significantly decreased during Period B (1467.00 ± 119.21) in comparison to period A (1644.40 ± 42.57) and C (1637.8 ± 77.23). Furthermore, Period C in comparison to B and A, refers to women of more advanced age (37.27 ± 5.62 vs 36.04 ± 5.76 vs 35.53 ± 5.28), reporting a longer infertility period (8.49 ± 6.25 vs 7.01 ± 5.66 vs 6.46 ± 5.20), being inclined to abandon IVF treatment sooner (2.78 ± 2.51 vs 2.60 ± 1.92 vs 4.91 ± 2.28). CONCLUSIONS: A decline regarding assisted reproduction techniques (ART) demand was noted as anticipated. Redefining the cost of infertility treatments may contribute towards overcoming the troubling phenomenon of postponing pregnancy due to financial concerns.

Evaluation of the Second Follicular Wave Phenomenon in Natural Cycle Assisted Reproduction: A Key Option for Poor Responders through Luteal Phase Oocyte Retrieval.

Background: Emergence of Luteal Phase Oocyte Retrieval (LuPOR) may revolutionize the practice regarding the time-sensitive nature of poor responders ascertaining a higher number of oocytes, in a shorter amount of time. This may be especially important in view of employing the approach of natural cycles for Poor Responders. We suggest the acronym LuPOR describing the clinical practice of luteal phase oocyte retrieval. The aim of the study is to offer insight regarding the identity of LuPOR, and highlight how this practice may improve management of the special subgroup of poor responders. Materials and Methods: The present retrospective observational clinical study includes the collection and statistical analysis of data from 136 poor responders who underwent follicular oocyte retrieval (FoPOR) and subsequent LuPOR in natural cycles, during their In Vitro Fertilization (IVF) treatment, from the time period of 2015 to 2018. All 136 participants were diagnosed with poor ovarian reserve (POR) according to Bologna criteria. The 272 cycles were categorized as follows: 136 natural cycles with only FoPORs (Control Group) and 136 natural cycles including both FoPORs and LuPORs. Results: Our primary results indicate no statistically significant differences with regards to the mean number of oocytes, the maturation status, and fertilization rate between FoPOR and LuPOR in natural cycles. Secondarily, we demonstrate a statistically significant higher yield of oocytes (2.50 ± 0.78 vs. 1.25 ± 0.53), better oocyte maturity status (1.93 ± 0.69 vs. 0.95 ± 0.59) and higher fertilization rate (1.31 ± 0.87 vs. 0.61 ± 0.60) in natural cycles including both FoPOR and LuPOR, when compared to cycles including only FoPOR. Conclusion: Our study may contribute towards the establishment of an efficient poor responders' management through the natural cycle approach, paving a novel clinical practice and ascertaining the opportunity to employ oocytes and embryos originating from a luteal phase follicular wave.

Efficient treatment of chronic endometritis through a novel approach of intrauterine antibiotic infusion: a case series.

BACKGROUND: Early diagnosis and efficient management of Chronic Endometritis (CE) in patients seeking fertility treatment are two components every practitioner wishes to address. With respect to endometrial restoration, antibiotic treatment appears to perform well. However, regarding the improvement of In Vitro Fertilization (IVF) success rates, literature evidence is inconclusive, and consensus on optimal treatment has yet to be reached. This manuscript uniquely brings to literature the first report on effective employment of intrauterine antibiotic infusion to treat CE and contribute to addressing the infertility related to it. CASE PRESENTATION: In this case series, we present 3 patients reporting numerous previous failed IVF attempts accompanied with diagnosed CE which failed to be properly treated in the past. Following initial assessment in our clinic and verification of CE findings, an oral antibiotic regime was administered based on the infectious agent detected. Re-evaluation concluded slightly improved microbiological environment in the endometrium but persisting inflammation. Antibiotic intrauterine infusion was proposed to the patients as an alternative practice. All our patients achieved a pregnancy shortly following intrauterine treatment with one patient reporting a live birth of twin babies and two patients currently reporting an ongoing pregnancy. CONCLUSIONS: The implications of this case series contribute to medical knowledge and extend to both effective treatment of CE and subsequent management of related infertility. The current line of treatment of CE through oral antibiotic regimes highlights the need for exploring new options and calls for larger studies on the clinical implication of their use. This novel approach enabled natural conception for patients presenting with established Recurrent Implantation Failure (RIF) having undergone numerous futile IVF attempts. The clinical impact from the practitioner's perspective is considerable allowing for an alternative line of treatment that merits further investigation.

Association between male Infertility and seminal plasma levels of growth hormone and insulin-like growth factor-1.

Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) have been proposed to play a pivotal role in male infertility due to their anabolic effects. The aim of this study was to investigate possible associations between seminal plasma levels of GH and IGF-1 and sperm parameters. Fifty men participated in this study. Semen analysis was performed, while cell-free seminal plasma was collected following sperm centrifugation. Seminal plasma concentrations of IGF-1 and GH were determined by enzyme-linked immunosorbent assay (ELISA). Due to the presence of asthenozoospermia in all participants who presented with abnormal sperm parameters, the participants were further subdivided into normal (group A), asthenozoospermic (group B) and asthenozoospermic plus at least one additional abnormal parameter (group C). A marginally nonsignificant statistical difference (p = 0.063) was revealed between the GH levels corresponding to the asthenozoospermic and the normal group with the latter presenting with higher GH levels. A statistically significant positive correlation (p < 0.05) was noted between levels of GH and IGF-1 in group C. The above relationship has also been observed in men with low sperm concentration, vitality, volume and abnormal morphology. These novel findings require further investigation in order for the biological significance of those associations to be clarified.

Are computational applications the "crystal ball" in the IVF laboratory? The evolution from mathematics to artificial intelligence.

Mathematics rules the world of science. Innovative technologies based on mathematics have paved the way for implementation of novel strategies in assisted reproduction. Ascertaining efficient embryo selection in order to secure optimal pregnancy rates remains the focus of the in vitro fertilization scientific community and the strongest driver behind innovative approaches. This scoping review aims to describe and analyze complex models based on mathematics for embryo selection, devices, and software most widely employed in the IVF laboratory and algorithms in the service of the cutting-edge technology of artificial intelligence. Despite their promising nature, the practicing embryologist is the one ultimately responsible for the success of the IVF laboratory and thus the one to approve embracing pioneering technologies in routine practice. Applied mathematics and computational biology have already provided significant insight into the selection of the most competent preimplantation embryo. This review describes the leap of evolution from basic mathematics to bioinformatics and investigates the possibility that computational applications may be the means to foretell a promising future for the IVF clinical practice.

Postponing Pregnancy Through Oocyte Cryopreservation for Social Reasons: Considerations Regarding Clinical Practice and the Socio-Psychological and Bioethical Issues Involved.

Oocyte freezing for 'social reasons' refers to women of reproductive age who are aiming to prolong, protect and secure their fertility. The term emerged to describe application of the highly promising technique, namely vitrification on oocytes retrieved through controlled ovarian stimulation (COS) from women intending to preserve their fertility for social reasons. These women opt to cryopreserve their oocytes at a point in their life when they need to postpone childbearing on the grounds of so called 'social' reasons. These reasons may include a highly driven career, absence of an adequate partner, financial instability, or personal reasons that make them feel unprepared for motherhood. This is a sensitive and multifaceted issue that entails medical, bioethical and socio-psychological components. The latest trend and the apparent increase noted on oocyte freezing for 'social reasons' has prompted our team of fertility specialists, embryologists, obstetricians, gynecologists and psychologists to proceed with a thorough, critical and all-inclusive comprehensive analysis. The wide range of findings of this analysis involve concerns of embryology and epigenetics that shape decisions made in the IVF laboratory, issues regarding obstetric and perinatal concerns on the pregnancy concluding from these oocytes and the respective delivery management and neonatal data, to the social and bioethical impact of this trend's application. This literature review refers to matters rising from the moment the 'idea' of this option is 'birthed' in a woman's thoughts, to proceeding and executing it clinically, up until the point of the pediatric follow up of the children born. We aim to shed light to the controversial issue of oocyte freezing, while objectively exhibit all aspects regarding this complex matter, as well as to respectfully approach how could the prospect of our future expectations be shaped from the impact of its application.

Prognostic value of T786C and G894T eNOS polymorphisms in sickle cell disease.

Endothelial Nitric Oxide Synthase (eNOS) is crucial for vascular homeostasis. Polymorphisms T786C and G894T affect eNOS regulation and have been related to various diseases. Sickle Cell Disease (SCD), a clinically diverse chronic hemolytic anemia, implies impaired nitric oxide bioavailability. Our aim was to determine eNOS genotype for T786C and G894T polymorphisms in Greek patients with SCD and to elucidate its consequences and effects if any on clinical phenotype. Seventy nine steady state cases, mostly compound heterozygous for Sickle Cell anemia/beta thalassemia and 48 controls were measured. Peripheral blood DNA was extracted and genotyped with PCR-RFLPs and Sanger sequencing. Total RNA was extracted from 18 patients and 9 controls and eNOS mRNA levels were determined by real-time PCR. Genotypes, allele distribution and eNOS mRNA levels did not differ between patients and controls, or among patients with different beta globin gene mutations. The 786CC genotype was more common in S/S and ß0/S patients with retinopathy. Moreover, 894TT S/S and ß0/S patients tended to have a higher hematocrit than 894GG and GT ones. However, the T786C eNOS genotype does not seem to affect peripheral blood cell-derived eNOS mRNA levels, at least in steady state conditions. This work is the first one describing the effects of eNOS polymorphisms on different forms of SCD, the first enrolling SCD patients of Caucasian origin and the first determining eNOS mRNA levels in peripheral blood from steady-state SCD patients.