Intracytoplasmic sperm injection versus conventional in vitro insemination in couples with non-male infertility factor in the 'real-world' setting: analysis of the HFEA registry.

BACKGROUND: In assisted reproductive technology (ART), the choice between intracytoplasmic sperm injection (ICSI) and conventional in vitro insemination (IVF) remains a pivotal decision for couples with female or unexplained infertility. The hypothesis that ICSI may not confer significant improvements in live birth rates in the absence of a male infertility factor was explored in this study. METHODS: This was a retrospective collection of data recorded by the Human Fertilisation and Embryology Authority (HFEA) in the UK from 2005 to 2018 and analysed through regression analysis models on both the entire dataset and a matched-pair subset. First fresh ART cycles were analysed according to the insemination technique in order to compare live birth as the main outcome. Cycles were included if complete information regarding infertility cause, female age, number of oocytes retrieved, allocation to ICSI or IVF, and treatment outcome in terms of live birth was available. Matching was performed at a 1:1 ratio between IVF and ICSI cycles according to the cause of infertility, female age, number of oocytes, and year of treatment. RESULTS: This study, based on 275,825 first cycles, revealed that, compared with IVF, ICSI was associated with higher fertilization rates and lower cycle cancellations rates. However, ICSI was associated with a lower chance of implantation and live birth than IVF in cycles with female-only infertility: in the entire dataset, the adjusted odds of having a live birth decreased by a factor of 0.95 (95% CI 0.91-0.99, p = 0.011), while in the matched-pair analyses it decreased by a factor of 0.91 (95% CI 0.86-0.96, p = 0.003) using ICSI compared to IVF. For unexplained infertility cycles, the adjusted odds ratios for live birth in ICSI compared to IVF cycles were 0.98 (95% CI 0.95-1.01) in the entire dataset and 0.97 (95% CI 0.93-1.01) in the matched-pair analysis. CONCLUSIONS: Compared with IVF, ICSI was associated with a reduction in live births when ART was indicated due to female-only factors. Additionally, no significant improvements were associated with the use of ICSI in cycles with unexplained infertility. Our findings impose a critical reevaluation regarding the use of ICSI over IVF for cases with female-only factors and unexplained infertility.

Pregnancy rate in IVF patients with unexpected poor response to ovarian stimulation.

OBJECTIVE: To evaluate whether an unexpected poor response (cases with ≤3 oocytes) leads to a reduction in the pregnancy rate in IVF cycles compared to a suboptimal response (controls with 4-9 oocytes) in women with adequate ovarian reserve. METHODS: A nested case-control study performed in a retrospective cohort of couples undergoing IVF at the Infertility Unit of the ASST Lariana. Cases and controls had adequate ovarian reserve and were matched 1:1 for female age and number of previous cycles. Cumulative clinical pregnancy rate per oocyte retrieval was the main outcome. RESULTS: Overall, 113 cases and 113 matched controls were included; the median number of available oocytes was 2 and 6, respectively. The cumulative pregnancy rate per cycle was significantly reduced in cases compared to controls with a crude odds ratio = 0.45 [95% Confidence Interval: 0.28-0.82]. A binomial logistic model indicated that an increase in one oocyte increases the odds for cumulative pregnancy rate per cycle by 1.27 in women with 9 oocytes or less. The cumulative pregnancy rates per cycle in cases and controls, according to female age were respectively: 29% versus 54% in patients aged <35 years (p = 0.036); 22% versus 43% in patients aged 36-39 years (p = 0.048) and 11% versus 13% in patients 40-45 years old (p = 0.72). Patients belonging to older age groups showed decreasing probability of cumulative clinical pregnancy rates both among cases and controls group (p < 0.05). CONCLUSIONS: The number of available oocytes significantly affects the probability of success in IVF cycles with unexpected impaired ovarian response.

Whole-genome analysis uncovers recurrent IKZF1 inactivation and aberrant cell adhesion in blastic plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematological malignancy with a poorly understood pathobiology and no effective therapeutic options. Despite a few recurrent genetic defects (eg, single nucleotide changes, indels, large chromosomal aberrations) have been identified in BPDCN, none are disease-specific, and more importantly, none explain its genesis or clinical behavior. In this study, we performed the first high resolution whole-genome analysis of BPDCN with a special focus on structural genomic alterations by using whole-genome sequencing and RNA sequencing. Our study, the first to characterize the landscape of genomic rearrangements and copy number alterations of BPDCN at nucleotide-level resolution, revealed that IKZF1, a gene encoding a transcription factor required for the differentiation of plasmacytoid dendritic cell precursors, is focally inactivated through recurrent structural alterations in this neoplasm. In concordance with the genomic data, transcriptome analysis revealed that conserved IKZF1 target genes display a loss-of-IKZF1 expression pattern. Furthermore, up-regulation of cellular processes responsible for cell-cell and cell-ECM interactions, which is a hallmark of IKZF1 deficiency, was prominent in BPDCN. Our findings suggest that IKZF1 inactivation plays a central role in the pathobiology of the disease, and consequently, therapeutic approaches directed at reestablishing the function of this gene might be beneficial for patients.

Shooting STAR: reinterpreting the data from the 'Single Embryo TrAnsfeR of Euploid Embryo' randomized clinical trial.

Preimplantation genetic testing for aneuploidy (PGT-A) still remains controversial in clinical practice. Recently, the randomized controlled trial, 'Single Embryo TrAnsfeR of Euploid Embryo' (STAR) by Munné and coworkers showed a similar live birth rate per intention to treat in the two study groups (PGT-A and controls). A wrong diagnosis and/or biopsy-related damage to the embryo might underlie these results. To assess the impact of these factors on the efficiency of PGT-A, the live birth rate of 'euploid' embryos transferred in the PGT-A group was compared with its ideal value, namely the live birth rate of embryos with the potential to implant and to give rise to a baby in the control group. This estimate has been derived using the results of the genetic testing reported in the STAR trial. According to this model, the STAR trial has demonstrated that transferring only blastocysts classified as 'euploid' after PGT-A leads to a reduction from 82.2% to 50.0% of the live birth rate for competent embryos, thus supporting the idea that PGT-A is associated with some embryo wastage.

Oocyte Retrieval during Laparoscopic Vaginoplasty to Reduce Invasiveness in the Treatment of Mayer-Rokitansky-Küster-Hauser Syndrome.

STUDY OBJECTIVE: To evaluate the treatment of patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome with a combination of oocyte retrieval and surgical vaginoplasty in a single laparoscopic procedure. DESIGN: A case series. SETTING: The study was conducted at 2 tertiary referral facilities for MRKH syndrome in Milan, Italy, between July 2017 and September 2018. PATIENTS: Eleven patients presented with MRKH and required surgical vaginoplasty while expressing a desire for future fertility. INTERVENTIONS: Two experienced surgeons and an expert in assisted reproductive technology performed concomitant vaginoplasty according to the modified technique of Davydov and laparoscopic oocyte retrieval for gamete cryopreservation. MEASUREMENTS AND MAIN RESULTS: Before the procedure, patients underwent extensive counseling and gave written consent. At the start of surgery, 10.4 ± 4.4 (mean ± standard deviation [SD]) oocytes were retrieved laparoscopically, and 8.8 ± 3.1 (SD) mean mature oocytes were cryopreserved. After oocyte retrieval, the steps of the modified Davydov technique were followed. The total operative time was 116 ± 16 minutes (mean ± SD), and no intraoperative/postoperative complications were observed. CONCLUSION: This is the first report of combined oocyte retrieval and vaginoplasty for patients with MRKH syndrome. The approach was found to be feasible in patients with a desire for future fertility. It is our belief that physicians treating patients with MRKH should refer patients to centers with expertise in both vaginoplasty and assisted reproductive technology.

Assessment of pre-implantation genetic testing for embryo aneuploidies: A SWOT analysis.

The recently re-named pre-implantation genetic testing for determining embryo aneuploidies (PGT-A) is presently very popular although its acceptance by the scientific community is controversial. This approach still encounters drawbacks. This paper uses a SWOT (strengths, weaknesses, opportunities and threats) analysis to discuss salient points to be considered when examining the pre-implantation genetic testing (PGT-A) strategy to gather information from a range of perspectives. One of the strengths associated with the procedure is represented by an increase in implantation rate although data from the highest level of evidence do not support an increase in cumulative pregnancy rates. The current difficulty in the management of mosaicisms represents a weakness of PGT-A. The application of the strategy represents an opportunity to favor the single embryo transfer while other advantages, such as reduction of time to pregnancy and emotional distress are controversial. Potential important threats, at present still undefined, are represented by the biopsy-related damage to the blastocyst and the impact on neonatal and long-term outcomes.

Array-based CGH of primary cutaneous CD8+ aggressive EPIDERMO-tropic cytotoxic T-cell lymphoma.

Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (pcAECyTCL) is a rare provisionally categorized cutaneous lymphoma characterized by an aggressive course. Its pathogenesis and molecular mechanisms are still unknown, and only two individual cases have so far been molecularly characterized. The aim of this study was to define the pattern of numerical chromosomal alterations in tumor samples taken from 20 patients with pcAECyTCL at the time of diagnosis by means of array-comparative genomic hybridization (a-CGH). a-CGH detected numerous genomic aberrations in all the patients and, putting these together as a whole, they affected all the chromosomes. However, no specific profile of recurrent copy number alterations (CNAs) was found. Most of the gains involved regions previously described in other aggressive cutaneous lymphomas such as 7q, 8q24.3, and 17q, whereas the most significant CNA was the loss of 9p21.3 (CDKN2A-CDKN2B), which has already been found in a variety of malignant tumors and is associated with aggressive cutaneous T-cell lymphomas. In brief, CGH analysis revealed a large number of CNAs with only few recurring regions that probably do not represent driving events. The genomic instability found in this aggressive variant of cutaneous lymphoma may therefore be a secondary event but, at the time of the diagnosis of pcAECyTCL, the genomic integrity of tumor cells is already compromised.

Extracellular MicroRNA Signature of Human Helper T Cell Subsets in Health and Autoimmunity.

Upon T cell receptor stimulation, CD4+ T helper (Th) lymphocytes release extracellular vesicles (EVs) containing microRNAs. However, no data are available on whether human CD4+ T cell subsets release EVs containing different pattern of microRNAs. The present work aimed at filling this gap by assessing the microRNA content in EVs released upon in vitro T cell receptor stimulation of Th1, Th17, and T regulatory (Treg) cells. Our results indicate that EVs released by Treg cells are significantly different compared with those released by the other subsets. In particular, miR-146a-5p, miR-150-5p, and miR-21-5p are enriched, whereas miR-106a-5p, miR-155-5p, and miR-19a-3p are depleted in Treg-derived EVs. The in vitro identified EV-associated microRNA signature was increased in serum of autoimmune patients with psoriasis and returned to healthy levels upon effective treatment with etanercept, a biological drug targeting the TNF pathway and suppressing inflammation. Moreover, Gene Set Enrichment Analysis showed an over-representation of genes relevant for T cell activation, such as CD40L, IRAK1, IRAK2, STAT1, and c-Myb in the list of validated targets of Treg-derived EV miRNAs. At functional level, Treg-derived (but not Th1/Th17-derived) EVs inhibited CD4+ T cell proliferation and suppressed two relevant targets of miR-146a-5p: STAT1 and IRAK2. In conclusion, our work identified the miRNAs specifically released by different human CD4+ T cell subsets and started to unveil the potential use of their quantity in human serum to mark the pathological elicitation of these cells in vivo and their biological effect in cell to cell communication during the adaptive immune response.

Vitamin D and Endometrium: A Systematic Review of a Neglected Area of Research.

Growing evidence supports a role of vitamin D (VD) in reproductive health. Vitamin D receptor (VDR) is expressed in the ovary, endometrium, and myometrium. The biological actions of VD in fertility and reproductive tissues have been investigated but mainly using animal models. Conversely, the molecular data addressing the mechanisms underlying VD action in the physiologic endometrium and in endometrial pathologies are still scant. Levels of VDR expression according to the menstrual cycle are yet to be definitively clarified, possibly being lower in the proliferative compared to the secretory phase and in mid-secretory compared to early secretory phase. Endometrial tissue also expresses the enzymes involved in the metabolism of VD. The potential anti-proliferative and anti-inflammatory effects of VD for the treatment of endometriosis have been investigated in recent years. Treatment of ectopic endometrial cells with 1,25(OH)2D3 could significantly reduce cytokine-mediated inflammatory responses. An alteration of VD metabolism in terms of increased 24-hydroxylase mRNA and protein expression has been demonstrated in endometrial cancer, albeit not consistently. The effect of the active form of the vitamin as an anti-proliferative, pro-apoptotic, anti-inflammatory, and differentiation-inducing agent has been demonstrated in various endometrial cancer cell lines.

Primary cutaneous acral CD8 positive T-cell lymphoma with extra-cutaneous involvement: A long-standing case with an unexpected progression.

Primary cutaneous acral CD8+ T-cell lymphoma (acral CD8+ TCL) is a new provisional entity characterized by acral skin lesions and an indolent course. We describe an extraordinary case characterized by relapsed nodules with CD8+ cytotoxic infiltrates on the left ear. After 35 years, the skin lesions spread to other acral sites, and a mass with the same histological features as the other skin lesions appeared on the nose. Multiple courses of chemotherapy led to stable disease. Histological examinations carried out at different times showed the gradual transformation of the neoplastic cells, with an increased proliferation index. Genomic analysis revealed losses in the regions harboring the genes involved in cell cycle control. This is the first case of an acral CD8+ TCL with a very long history of indolent nodular lesions progressing to extra-cutaneous sites.

Application of failure mode and effect analysis in an assisted reproduction technology laboratory.

Assisted reproduction technology laboratories have a very high degree of complexity. Mismatches of gametes or embryos can occur, with catastrophic consequences for patients. To minimize the risk of error, a multi-institutional working group applied failure mode and effects analysis (FMEA) to each critical activity/step as a method of risk assessment. This analysis led to the identification of the potential failure modes, together with their causes and effects, using the risk priority number (RPN) scoring system. In total, 11 individual steps and 68 different potential failure modes were identified. The highest ranked failure modes, with an RPN score of 25, encompassed 17 failures and pertained to "patient mismatch" and "biological sample mismatch". The maximum reduction in risk, with RPN reduced from 25 to 5, was mostly related to the introduction of witnessing. The critical failure modes in sample processing were improved by 50% in the RPN by focusing on staff training. Three indicators of FMEA success, based on technical skill, competence and traceability, have been evaluated after FMEA implementation. Witnessing by a second human operator should be introduced in the laboratory to avoid sample mix-ups. These findings confirm that FMEA can effectively reduce errors in assisted reproduction technology laboratories.

Clinicopathological and molecular study of primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma.

BACKGROUND: Primary cutaneous CD4+ small-/medium-sized pleomorphic T-cell lymphoma (CD4+ PCSM-TCL) is a rare lymphoproliferative disorder with a favorable prognosis. Distinguishing it from other cutaneous lymphomas is often a challenge. METHODS: We retrospectively collected CD4+PCSM-TCL cases from two centers (MD Anderson Cancer Center, USA and University of Milan, Italy) and evaluated their clinicopathological features. Array-comparative genomic hybridization (aCGH) analysis was performed on 11 cases. RESULTS: A total of 62 patients were identified. Single lesions were the most common clinical presentations (79%). Five patients (8%) showed multiple MF-like plaques. All patients' disease had an indolent course. The infiltrate was nodular and diffuse, multinodular or superficial but in all cases, it was characterized by small/medium pleomorphic CD4+/CD279(PD1+) lymphocytes grouped in clusters and 'pseudorosettes' around B-cells. aCGH analysis showed no significant genomic abnormalities. Single lesions were mainly treated with surgical excision (91%) and/or radiotherapy (95%) with low rate of relapse (12%). For multiple lesions, topical steroids, nitrogen mustard and phototherapy were mainly used but the rate of relapse was high (69%). CONCLUSIONS: CD4+PCSM-TCL is characterized by heterogeneous clinical presentations. The arrangement of atypical cells in clusters or pseudorosettes is a useful criterion for diagnosis. The absence of significant genomic alterations is in agreement with its indolent behavior.

Sézary Syndrome in a 17-Year-Old Boy: Clinicopathologic Features and Genomic Profile.

We describe the case of a 17-year-old Hispanic boy who had had erythroderma and diffuse lymphadenopathy for approximately 6 months. A diagnosis of Sézary syndrome was made on the basis of the histologic features of the skin; the presence of the same T-cell clone on the skin, blood, and bone marrow; and the high CD4(+) lymphocyte count with an aberrant phenotype in peripheral blood; bone marrow involvement was also present. The patient was treated with systemic gemcitabine and achieved partial remission.

Autoimmunity and Cytokine Imbalance in Inherited Epidermolysis Bullosa.

In order to evaluate the serum anti-skin autoantibodies and cytokine concentrations in patients with different epidermolysis bullosa (EB) types and severity, 42 EB patients and 38 controls were enrolled. Serum anti-skin antibodies were significantly higher in the patients than in the controls (p = 0.008, p < 0.001, p < 0.001, p < 0.001 and p < 0.001 for desmoglein 1 (DSG1) desmoglein 3 (DSG3), bullous pemphigoid 180 (BP180), BP230 and type VII collagen (COL7), respectively). The same trend was observed for interleukin (IL)-1ß, IL-2, IL-6, IL-10, tumor necrosis factor-ß, and interferon-γ (p < 0.001, p < 0.001, p < 0.001, p = 0.008, p < 0.001 and p = 0.002, respectively). Increases in anti-skin antibodies and cytokine concentrations were higher in patients with recessive dystrophic EB than in those with different types of EB, in generalized cases than in localized ones, and in patients with higher Birmingham Epidermolysis Bullosa Severity (BEBS) scores than in those with a lower score. The BEBS score was directly correlated with BP180, BP230, COL7 (p = 0.015, p = 0.008 and p < 0.001, respectively) and IL-6 (p = 0.03), whereas IL-6 appeared significantly associated with DSG1, DSG3, BP180, BP230 and COL7 (p = 0.015, p = 0.023, p = 0.023, p = 0.015 and p = 0.005, respectively). This study showed that autoimmunity and inflammatory responses are frequently activated in EB, mainly in severe forms, suggesting the use of immunosuppressive drugs or biologicals that are active against pro-inflammatory cytokines to reduce clinical signs and symptoms of disease.

Iron availability is increased in individual human ovarian follicles in close proximity to an endometrioma compared with distal ones.

STUDY QUESTION: Does the iron content of an endometrioma represent a potential source of toxicity for the adjacent follicles? SUMMARY ANSWER: The presence of an endometrioma increases iron and H/L ferritin levels, and transferrin receptor (TfR1) mRNA in individual follicles proximal to the endometrioma and is accompanied by reduced oocyte retrieval. WHAT IS KNOWN ALREADY: Levels of free iron in endometriotic ovarian cysts are much higher than those in normal serum or in non-endometriotic ovarian cysts. The presence of an endometrioma exerts a detrimental effect on the surrounding healthy ovarian tissue as reflected by a reduced number of developing follicles and oocytes retrieved in IVF cycles. STUDY DESIGN, SIZE, DURATION: This is a research study with prospective collection and evaluation of individual follicles (follicular fluid and luteinized granulosa cells) from the affected and the healthy ovaries of 13 women with unilateral endometrioma. PARTICIPANTS/MATERIALS, SETTING, METHODS: Individual follicular samples (145) were obtained from 13 women with endometriosis-related infertility undergoing IVF-ICSI procedures from May 2012 to March 2013. All women had unilateral endometrioma not previously treated with surgery; the contralateral ovary was free of endometriomas and previous surgery. The average ± SEM age was 35.36 ± 2.5 years with anti-Mullerian hormone levels of 2.03 ± 0.55 ng/ml. Follicles were classified as: (i) proximal follicles, in physical contact with the endometrioma; (ii) distal follicles, present in the affected ovary but not in close contact with the endometrioma and (iii) contralateral follicles, in the contralateral healthy ovary. Iron content was measured by the FerroZine method. H/L ferritin subunits were evaluated by specific enzyme-linked immunosorbant assays. Expression of H ferritin and TfR1 was examined by semi-quantitative RT-PCR. Oocyte retrieval rates and Day 3 embryo quality were analyzed. MAIN RESULTS AND THE ROLE OF CHANCE: Total iron levels were higher in endometrioma-proximal follicles compared with endometrioma-distal ones (P = 0.009) and to follicles in the healthy ovary (P = 0.02). L ferritin was higher in proximal versus distal follicles (P = 0.044) or follicles from the healthy ovary (P = 0.027). H ferritin was higher in the proximal and distal follicles compared with follicles in the healthy ovary (P = 0.042 and P = 0.0067, respectively). H ferritin transcript levels in granulosa cells were higher in proximal follicles versus follicles from healthy ovary (P = 0.02). TfR1 transcript levels were higher in proximal versus distal follicles (P = 0.03) and versus follicles from the healthy ovary (P = 0.04). The oocyte retrieval rate was lower in proximal and distal follicles than in follicles from the healthy ovary (P = 0.001 and P = 0.04, respectively). LIMITATIONS, REASONS FOR CAUTION: This is a study on a relatively small sample size and confirmation in a larger group of patients may be required. The method used to purify luteinized granulosa cells offers the best combination of purity, viability and total number of cells recovered. However, a minor contamination by CD45(+) cells (<5%) cannot be excluded. WIDER IMPLICATIONS OF THE FINDINGS: This study represents a further in-depth analysis of the toxic influence of the endometrioma content on the surrounding follicles. We demonstrate the presence of iron-related compounds that are potentially toxic to developing ovarian follicles adjacent to the endometrioma during IVF. Our findings provide novel information that suggests that when surgical removal of the endometrioma is not the option, follicle aspiration at sites distant from the endometrioma might increase the probability of retrieving oocytes. STUDY FUNDING/COMPETING INTEREST(S): This project was supported by Fondazione Giorgio Pardi, Milan, Italy. The authors have no competing financial interests in relation to the content of this research paper. TRIAL REGISTRATION NUMBER: NA.

The strategy of group embryo culture based on pronuclear pattern on blastocyst development: a two center analysis.

PURPOSE: To compare two embryo grouping strategies. METHODS: Retrospective time-course analysis in two different centres. Two culture protocols were used at the zygote stage: "Random Group" in which zygotes were randomly grouped and "Definite Group" in which zygotes were grouped based on pronuclear pattern. Embryo culture was extended to blastocyst stage. Primary and secondary outcomes were respectively the blastulation rate and the cumulative clinical pregnancy and implantation rates. RESULT(S): A similar blastulation rate [42 and 41% day (5 + 6) blastocysts] was obtained in the two groups. Conversely, after adjusting for baseline and cycle variables, cumulative pregnancy [adjusted Odds Ratio = 2.10 (95%CI: 1.08-4.07)] and implantation [adjusted Odds Ratio = 1.78 (95%CI: 1.06-2.97)] rates were significantly higher in the "Random Group" compared to the "Definite Group". CONCLUSION(S): Two strategies of group culture gave similar results in terms of blastulation rate but the random grouping of zygotes improves pregnancy and implantation rates in IVF-cycles.

Basal progesterone level as the main determinant of progesterone elevation on the day of hCG triggering in controlled ovarian stimulation cycles.

PURPOSE: Modest increases of serum progesterone at human chorionic gonadotrophin (hCG) administration in controlled ovarian hyperstimulation (COH) cycles have been shown to have a negative impact on pregnancy outcomes. The aim of this study was to identify early predictors of progesterone elevation at hCG. DESIGN: Pregnancy outcome of 303 consecutive patients undergoing COH and fresh day-3 embryo transfer was analysed. Considering the non-linear relationship between progesterone at hCG triggering and pregnancy outcomes, partial area under the curve (pAUC) analysis was used to implement marker identification potential of receiver operating characteristic (ROC) curve analysis. Multivariate logistic analysis was then performed to identify predictors of progesterone rise. RESULTS: Pregnancy outcomes could be predicted by pAUC analysis (pAUC = 0.58, 95 % CI 0.51-0.66, p = 0.02) and a significant detrimental cut-off could be calculated (progesterone at hCG > 1.35 ng/ml). Total dose of rFSH administered, E2 level at hCG but mostly basal progesterone level (OR = 12.21, 95 % CI 1.82-81.70) were predictors of progesterone rise above the cut-off. CONCLUSION: Basal progesterone is shown to be the main prognostic factor for progesterone elevation. This observation should be taken into consideration in the clinical management of IVF/ICSI cycles to improve pregnancy outcomes.

Technological grandparents: how communication technologies can improve the well-being of the elderly?

The ageing of the population is one of the most significant social transformations that the twenty first century is showcasing and a challenge that impacts society at large. The elderly, inasmuch as everybody else, are confronted with continuous transformations that are induced by technology, although they seldom benefit from the opportunities that technology entails. The digital divide amongst various segments of the population is often age-related and due to different reasons, including biological, psychological, social and financial ones. There is an ongoing reflection pertaining to the factors that hinders the full adoption of ICTs by the elderly and a question regarding what can be done to overcome their poor involvement in technology. This article, based on the results of a recent research, which has been conducted in Italy, aims at highlighting the importance of engaging the elderly in the use of technology as a key to building bridges between generations.

Elective Single Cleavage-Stage Embryo Transfer in IVF Patients with Suboptimal Ovarian Response is Not Detrimental to Cumulative Pregnancy and Reduces Multiple Pregnancy Rates.

Purpose: To evaluate whether elective single embryo transfer in patients with suboptimal response to ovarian stimulation is detrimental to pregnancy rates compared to double embryo transfer. Methods: A case-control retrospective study was performed in a cohort of couples undergoing IVF at the Infertility Unit of the ASST Lariana with ≤ 9 oocytes and at least 2 viable embryos. A total of 424 women were analyzed in the "double embryo transfer" group (n = 212) and elective "single embryo transfer" group (n = 212); they were matched 1:1 for female age, ovarian reserve and number of previous cycles. Cumulative clinical pregnancy rate per oocyte retrieval was the main outcome. Results: The cumulative pregnancy rate per cycle, including the fresh embryo and subsequent frozen embryo transfers, was 26% and 26%, respectively. Considering the main confounding factors, a binomial logistic model indicated that the cumulative clinical pregnancy rate was not significantly affected when a single embryo transfer was performed in women recovering up to nine oocytes. Conclusion: Live birth rate was similar between the two groups, while twin pregnancies were significantly reduced in women receiving single embryo transfer suggesting that elective single embryo transfer in patients with a limited number of embryos is not detrimental to pregnancy rates.

Chromosomal, gestational, and neonatal outcomes of embryos classified as a mosaic by preimplantation genetic testing for aneuploidy.

OBJECTIVE: To understand the clinical risks associated with the transfer of embryos classified as a mosaic using preimplantation genetic testing for aneuploidy. DESIGN: Analysis of data collected between 2017 and 2023. SETTING: Multicenter. PATIENTS: Patients of infertility treatment. INTERVENTION: Comparison of pregnancies resulting from embryos classified as euploid or mosaic using the 20%-80% interval in chromosomal intermediate copy numbers to define a mosaic result. MAIN OUTCOME MEASURES: Rates of spontaneous abortion, birth weight, length of gestation, incidence of birth defects, and chromosomal status during gestation. RESULTS: Implanted euploid embryos had a significantly lower risk of spontaneous abortion compared with mosaic embryos (8.9% [n = 8,672; 95% confidence interval {CI95} 8.3, 9.5] vs. 22.2% [n = 914; CI95 19.6, 25.0]). Embryos with mosaicism affecting whole chromosomes (not segmental) had the highest risk of spontaneous abortion (27.6% [n = 395; CI95 23.2, 32.3]). Infants born from euploid, mosaic, and whole chromosome mosaic embryos had average birth weights and lengths of gestation that were not statistically different (3,118 g and 267 days [n = 488; CI95 3,067, 3,169, and 266, 268], 3052 g and 265 days [n = 488; CI95 2,993, 3,112, and 264,267], 3,159 g and 268 days [n = 194; CI95 3,070, 3,249, and 266,270], respectively). Out of 488 infants from mosaic embryo transfers (ETs), one had overt gross abnormalities as defined by the Centers for Disease Control and Prevention. Most prenatal tests performed on pregnancies from mosaic ETs had normal results, and only three pregnancies produced prenatal test results reflecting the mosaicism detected at the embryonic stage (3 out of 250, 1.2%; CI95 0.25, 3.5). CONCLUSION: Although embryos classified as mosaic experience higher rates of miscarriage than euploid embryos (with a particularly high frequency shortly after implantation), infants born of mosaic ETs are similar to infants of euploid ETs. Prenatal testing indicates that mosaicism resolves during most pregnancies, although this process is not perfectly efficient. In a small percentage of cases, the mosaicism persists through gestation. These findings can serve as risk-benefit considerations for mosaic ETs in the fertility clinic.