Impact of Maternal Age on Oocyte and Embryo Competence

The overall success of human reproduction, either spontaneously or after IVF, is highly dependent upon maternal age. The main reasons for age-related infertility include reduced ovarian reserve and decreased oocyte/embryo competence due to aging insults, especially concerning an increased incidence of aneuploidies and possibly decreased mitochondrial activity. Age-related chromosomal abnormalities mainly arise because of meiotic impairments during oogenesis, following flawed chromosome segregation patterns such as non-disjunction, premature separation of sister chromatids, or the recent reverse segregation. In this review, we briefly discuss the main mechanisms putatively impaired by aging in the oocytes and the deriving embryos. We also report the main strategies proposed to improve the management of advanced maternal age women in IVF: fertility preservation through oocyte cryopreservation to prevent aging; optimization of the ovarian stimulation and enhancement of embryo selection to limit its effects; and oocyte donation to circumvent its consequences

DuoStim – a reproducible strategy to obtain more oocytes and competent embryos in a short time-frame aimed at fertility preservation and IVF purposes. A systematic review

Recent evidence suggests that follicular development occurs in a wave-like model during the ovarian cycle, where up to three cohorts of follicles are recruited to complete folliculogenesis. This understanding overtakes the previous dogma stating that follicles grow only during the follicular phase of the menstrual cycle. Therefore, in in vitro fertilization (IVF), novel protocols regarding ovarian stimulation have been theorized based on the use of gonadotrophins to prompt the growth of antral follicles at any stage of the menstrual cycle. These unconventional protocols for ovarian stimulation aim at a more efficient management of poor-prognosis patients, otherwise exposed to conflicting outcomes after conventional approaches. DuoStim appears among these unconventional stimulation protocols as one of the most promising. It combines two consecutive stimulations in the follicular and luteal phases of the same ovarian cycle, aimed at increasing the number of oocytes retrieved and embryos produced in the short time-frame. This protocol has been suggested for the treatment of all conditions requiring a maximal and urgent exploitation of the ovarian reserve, such as oncological patients and poor responders at an advanced maternal age. At present, data from independent studies have outlined the consistency and reproducibility of this approach, which might also reduce the drop-out between consecutive failed IVF cycles in poor-prognosis patients. However, the protocol must be standardized, and more robust studies and cost-benefit analyses are needed to highlight the true clinical pros and cons deriving from DuoStim implementation in IVF

Severe male factor in in vitro fertilization: definition, prevalence, and treatment. An update

Infertility affects 10%-15% of couples worldwide. Of all infertility cases, 20%-70% are due to male factors. In the past, men with severe male factor (SMF) were considered sterile. Nevertheless, the development of intracytoplasmic sperm injection (ICSI) drastically modified this scenario. The advances in assisted reproductive technology (ART), specifically regarding surgical sperm retrieval procedures, allowed the efficacious treatment of these conditions. Yet, before undergoing ICSI, male factor infertility requires careful evaluation of clinical and lifestyle behavior together with medical treatment. Epidemiologically speaking, women whose male partner is azoospermic tend to be younger and with a better ovarian reserve. These couples, in fact, are proposed ART earlier in their life, and for this reason, their ovarian response after stimulation is generally good. Furthermore, in younger couples, azoospermia can be partially compensated by the efficient ovarian response, resulting in an acceptable fertility rate following in vitro fertilization (IVF) techniques. Conversely, when azoospermia is associated with a reduced ovarian reserve and/or advanced maternal age, the treatment becomes more challenging, with a consequent reduction in IVF outcomes. Nonetheless, azoospermia seems to impair neither the euploidy rate at the blastocyst stage nor the implantation of euploid blastocysts. Based on the current knowledge, the assessment of male infertility factors should involve: (1) evaluation - to diagnose and quantify seminologic alterations; (2) potentiality - to determine the real possibilities to improve sperm parameters and/or retrieve spermatozoa; (3) time - to consider the available "treatment window", based on maternal age and ovarian reserve. This review represents an update of the definition, prevalence, causes, and treatment of SMF in a modern ART clinic

Radiomics analysis in gastrointestinal imaging: a narrative review

Background and Objective: To present an overview of radiomics radiological applications in major gastrointestinal oncological non-oncologic diseases, such as colorectal cancer, pancreatic cancer, gastro- oesophageal cancer, gastrointestinal stromal tumor (GIST), hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and non-oncologic diseases, such as liver fibrosis, nonalcoholic steatohepatitis, and inflammatory bowel disease. Methods: A search of PubMed databases was performed for the terms “radiomic”, “radiomics”, “liver”, “small bowel”, “colon”, “GI tract”, and “gastrointestinal imaging” for English articles published between January 2013 and July 2022. A narrative review was undertaken to summarize literature pertaining to application of radiomics in major oncological and non-oncological gastrointestinal diseases. The strengths and limitation of radiomics, as well as advantages and major limitations and providing considerations for future development of radiomics were discussed. Key Content and Findings: Radiomics consists in extracting and analyzing a vast amount of quantitative features from medical datasets, Radiomics refers to the extraction and analysis of large amounts of quantitative features from medical images. The extraction of these data, integrated with clinical data, allows the construction of descriptive and predictive models that can build disease-specific radiomic signatures. Texture analysis has emerged as one of the most important biomarkers able to assess tumor heterogeneity and can provide microscopic image information that cannot be identified with the naked eye by radiologists. Conclusions: Radiomics and texture analysis are currently under active investigation in several institutions worldwide, this approach is being tested in a multitude of anatomical areas and diseases, with the final aim to exploit personalized medicine in diagnosis, treatment planning, and prediction of outcomes. Despite promising initial results, the implementation of radiomics is still hampered by some limitations related to the lack of standardization and validation of image acquisition protocols, feature segmentation, data extraction, processing, and analysi

Circulating irisin levels in functional hypothalamic amenorrhea: a new bone damage index? A pilot study.

Purpose: Patients with functional hypothalamic amenorrhea (FHA) could commonly have bone damage, often preceded by metabolic alterations due to a relative energy deficit state. To date, there are no markers capable of predicting osteopenia before it is manifested on DXA. Irisin is a myokine that promotes the differentiation of osteoblastic cells and appears to be inversely correlated with the incidence of bone fragility and fractures in postmenopausal women. The aim of this study was to measure irisin levels in FHA patients and to correlate it with bone density parameters. Methods: Thirty-two patients with FHA and 19 matched controls underwent the same clinical and laboratory evaluation. Results: Irisin and body mass index (BMI) were significantly lower in the case group than in healthy controls (2.03 ± 0.12 vs. 2.42 ± 0.09 p < 0.05 and 19.43 ± 2.26 vs. 22.72 ± 0.67 p < 0.05, respectively). Additionally, total body mass density (BMD g/cm2) was significantly lower in the case group than in the healthy controls (1.09 ± 0.08 vs. 1.14 ± 0.05, p < 0.05), without signs of osteopenia. Conclusions: The FHA group showed lower irisin levels associated with significantly reduced BMD parameters that did not reach the severity of osteopenia. Therefore, we could speculate that irisin could predict DXA results in assessing modifications of body composition parameters. Future research is warranted to study these parameters in a larger population to confirm our results, so that irisin could be used as a predictor and screening method for bone deprivation. Furthermore, irisin is strictly related to energy metabolism and could be an indirect marker of nutritional status in FHA patients, identifying earlier states of energy deficit. Keywords: Amenorrhea; Body composition; Bone diseases; Energy metabolism; Osteoporosis

The Impact of Unbalanced Maternal Nutritional Intakes on Oocyte Mitochondrial Activity: Implications for Reproductive Function

Accumulating evidence on the effect of nutrition on reproduction is emerging from both animal and human studies. A healthy dietary pattern and nutrient supplementation, especially during the peri-conceptional period, might be helpful to achieve a live birth, although the mechanisms implicated are not fully understood. The endocrine system and the ooplasmic organelles apparatus, in particular the mitochondria, are clearly key elements during oogenesis and subsequent embryo development, and their proper functioning is associated with nutrition, even beyond maternal aging. Several studies in animal models have reported various adverse effects on mitochondria caused by unbalanced dietary intakes such as high fat diet, high fat high sugar diet, and low protein diet. The alterations produced might include mitochondrial intracellular distribution, content, structure, biogenesis, and functioning. This review summarizes the key role of mitochondria in female reproduction and the effects of different dietary macronutrient compositions on oocyte mitochondrial activity with their possible short-, medium-, and long-term effects

Double stimulation in the same ovarian cycle (DuoStim) is an intriguing strategy to improve oocyte yield and the number of competent embryos in a short timeframe

: Proper ovarian stimulation regimens are crucial for any patient undergoing in-vitro fertilization (IVF). However, maximizing the oocyte yield in advanced maternal age patients with poor or suboptimal response is still a challenge. In fact, no standard treatment has been outlined yet to manage these women. Across the last years, an improved efficiency of the IVF units via blastocyst culture, vitrification and reliable embryo selection approaches paved the way to the investigation of novel unconventional stimulation protocols, like double stimulation in a single ovarian cycle (DuoStim). DuoStim, by conjugating follicular phase stimulation (FPS) and luteal phase stimulation (LPS) in the same ovarian cycle, allows to maximize the number of oocytes obtained in a short timeframe, a precious outcome when we aim at shortening time to pregnancy. In this regard, LPS seems to contribute to conventional stimulation with more oocytes with a comparable competence as FPS, retrieved per ovarian cycle. Although any stimulation protocol which exploits anovulatory waves of follicular growth needs a thorough investigation, no evidence has been produced to question the safety of DuoStim, which to date represents the most intriguing strategy to treat poor prognosis in IVF

Personalized Nutrition in the Management of Female Infertility: New Insights on Chronic Low-Grade Inflammation

Increasing evidence on the significance of nutrition in reproduction is emerging from both animal and human studies, suggesting a mutual association between nutrition and female fertility. Different “fertile” dietary patterns have been studied; however, in humans, conflicting results or weak correlations are often reported, probably because of the individual variations in genome, proteome, metabolome, and microbiome and the extent of exposure to different environmental conditions. In this scenario, “precision nutrition”, namely personalized dietary patterns based on deep phenotyping and on metabolomics, microbiome, and nutrigenetics of each case, might be more efficient for infertile patients than applying a generic nutritional approach. In this review, we report on new insights into the nutritional management of infertile patients, discussing the main nutrigenetic, nutrigenomic, and microbiomic aspects that should be investigated to achieve effective personalized nutritional interventions. Specifically, we will focus on the management of low-grade chronic inflammation, which is associated with several infertility-related diseases

Maternal body mass index associates with blastocyst euploidy and live birth rates: the tip of an iceberg?

Research question: Does maternal preconceptional body mass index (BMI) associate with mean blastocyst euploidy rate (m-ER) per patient and live birth rate (LBR) after vitrified-warmed euploid single embryo transfer (SET)? Design: Observational study conducted between April 2013 and March 2020 at a private IVF clinic, involving 1811 Caucasian women undergoing trophectoderm biopsy and comprehensive chromosome testing. The outcomes of 1125 first vitrified-warmed euploid SET were also analysed. Patients were clustered as normal weight (BMI 18.5-25; n = 1392 performing 859 SET), underweight (BMI <18.5; n = 160 performing 112 SET) and overweight (BMI >25; n = 259 performing 154 SET). m-ER per patient was the primary outcome. The secondary outcomes were all clinical outcomes per euploid SET. All data were adjusted for confounders through regression analyses. Results: The m-ER per patient decreases as maternal BMI increases from 17 up to 22-23 before reaching a plateau. A linear regression adjusted for maternal age confirmed this moderate association (unstandardized coefficient B: -0.6%, 95% confidence interval [CI]: -1.1 to -0.1%, P = 0.02). All clinical outcomes were similar between normal weight and underweight women. Overweight women, instead, showed higher miscarriage rate per clinical pregnancy (n = 20/75, 26.7% versus n = 67/461, 14.5%; odds ratio [OR] adjusted for blastocyst quality and day of full blastulation: 2.0, 95% CI: 1.1-3.6, P = 0.01) and lower LBR per SET (n = 55/154, 35.7% versus n = 388/859, 45.2%; OR adjusted for blastocyst quality and day of full blastulation: 0.67, 95% CI: 0.46-0.96, P = 0.03). Conclusion: These data indicate a need for future research on more sensitive metrics to assess body fat mass and distribution, as well as on the mechanisms leading to lipotoxicity, thereby impairing embryo competence and/or endometrial receptivity. Overweight women should be informed of their higher risk for miscarriage and, whenever possible, encouraged to lose weight, especially before transfer

Automated Identification of Coronary Arteries in Assisting Inexperienced Readers: Comparison between Two Commercial Vendors

Background: to assess the performance and speed of two commercially available advanced cardiac software packages in the automated identification of coronary vessels as an aiding tool for inexperienced readers. Methods: Hundred and sixty patients undergoing coronary CT angiography (CCTA) were prospectively enrolled from February until September 2021 and randomized in two groups, each one composed by 80 patients. Patients in group 1 were scanned on Revolution EVO CT Scanner (GE Healthcare), while patients in group 2 had the CCTA performed on Brilliance iCT (Philips Healthcare); each examination was evaluated on the respective vendor proprietary advanced cardiac software (software 1 and 2, respectively). Two inexperienced readers in cardiac imaging verified the software performance in the automated identification of the three major coronary vessels: (RCA, LCx, and LAD) and in the number of identified coronary segments. Time of analysis was also recorded. Results: software 1 correctly and automatically nominated 202/240 (84.2%) of the three main coronary vessels, while software 2 correctly identified 191/240 (79.6%) (p = 0.191). Software 1 achieved greater performances in recognizing the LCx (81.2% versus 67.5%; p = 0.048), while no differences have been reported in detecting the RCA (p = 0.679), and the LAD (p = 0.618). On a per-segment analysis, software 1 outperformed software 2, automatically detecting 942/1062 (88.7%) coronary segments, while software 2 detected 797/1078 (73.9%) (p p < 0.001). Conclusions: automated cardiac software packages are a reliable and time-saving tool for inexperienced reader. Software 1 outperforms software 2 and might therefore better assist inexperienced CCTA readers in automated identification of the three main vessels and coronaries segments, with a consistent time saving of the reading session