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RUOLO DI VITAMINE E MICRONUTRIENTI NELLA DIAGNOSI E CURA DELL¿INFERTILITÀ DI COPPIA
Introduction
Maternal nutritional status is considered by many Authors to be closely related to the reproductive success. The human reproductive process, from a probabilistic point of view, is ineffective and, in spite of the scientific research progressively adding elements to the understanding of reproductive failure, the mechanisms underlying the failure to conceive, the embryonic arrest and the occurrence of neonatal malformations remain largely unknown. In this area, nutrition and micronutrient status represent an important research target for two main aspects: 1) nutrition as a cause of reproductive failures 2) nutritional status as a key variable influencing the chance of success in assisted reproduction procedures.
Aim
This PhD project has been focused on the study of specific analytes in infertile couples, with particular reference to the probability of success in terms of pregnancy given particular conditions of deficiency / insufficiency.
Methods and results
The project was conducted at the “Infertility Unit” of the Fondazione IRCCS Ca 'Granda Ospedale Maggiore Policlinico of Milan in collaboration with the Department of Clinical Sciences and Community at the University of Milan, in order to assess the baseline status of specific micronutrients and place it in relation to the chances of getting pregnant using assisted reproductive technologies. Evaluated analytes (vitamin D, folate, homocysteine, vitamin B12, vitamin E, vitamin E, iron and ferritin) were selected based on their involvement in the reproductive process. Subjects were recruited from couples treated for infertility; in the study of serum levels in infertile compared to subfertile women, recruitment was performed among pregnant women during the first trimester prenatal screening (U.O. Obstetrics and Gynecology). Several outcomes were evaluated using case series disjointed or partially overlapping. In particular, the PhD work was divided into 5 main studies, the characteristics of which are summarized in the following scheme:
Study: 1
Analyte: Vitamin D
Main Outcome: Pregnancy Rate in in vitro fertilization cycles
Design: Prospective cross-sectional
Subjects: 480 women in infertile couples
Main results: Women with 25 (OH) D ≥ 20 ng / ml are more likely to have a pregnancy compared to those with 25 (OH) D insufficiency.
Adjusted OR = 2.15 (95% CI: 1.23-3.77) (p = 0 .007).
Study: 2
Analyte: Vitamin D
Main Outcome: Concordance of serum levels between partners
Design: Prospective cross-sectional
Subjects: 103 infertile couples
Main results: 71% of infertile couples showed concordance between a condition of sufficiency or insufficiency between partners. This frequency is higher than expected in case of random assortment between partners(p = 0.007).
Study: 3
Analyte: Vitamin D
Main outcome: Serum levels in fertile versus subfertile women
Design: Prospective case-control
Subjects: 73 cases and 73 controls
Main results: Vitamin D status does not affect the natural fertility. OR for subfertility (time to pregnancy> 12 months) in women with low vitamin D = 0.85 (95% CI: 0.44-1.62)
Study: 4
Analytes: Folate, Homocystein, Vitamin B12, Vitamin A, Vitamin E, Iron, Ferritin
Main outcome: Rate of insufficiency
Design: Prospective cross-sectional
Subjects: 269 women in infertile couples
Main results: Only a minority of women attending an Infertility Unit show pre-gestational values of intraerythrocytic folate (12%) and vitamin B12 (44%)
Study: 5
Analytes: Folate, Homocystein, Vitamin B12
Main outcome: Pregnancy Rate in in-vitro fertilization cycles
Design: Prospective cross-sectional
Subjects: 209 women in infertile couples
Main results: Women with serum and intraerythrocytic folate in the third tertile of concentration are more likely to obtain a clinical pregnancy in in-vitro fertilization cycles. OR = 2.8 (1.5-5.3) and 2.1 (1.1-4.0), respectively.
Conclusion
Infertile couples, and women in particular, have a high incidence of vitamin D, folate and vitamin B12 insufficiency. This condition, with specific regards to vitamin D and folate, while represents a risk factor for complications of a possible pregnancy, is strongly associated with a lower success rate of in-vitro fertilization. Further studies are needed to identify possible causal relationships between insufficiency of specific analytes and reproductive failure. The demonstration of a benefit in terms of pregnancies per in-vitro fertilization cycle through the use of supplementation of micronutrients would be a result of huge interest because it would represent the rationale for an effective, economic and easy intervention, to be implemented in an area where progress is slow and mostly dependent on expensive technologies
Closed versus open vitrification systems for human oocytes and embryos : a mini-review
Vitrification is an established and successful technique for preserving human oocytes and embryos. It can be achieved either by direct (open systems) or indirect (closed systems) contact with liquid nitrogen and there is not a consensus on the optimum vitrification protocol. Scientific societies agree that there are no particular concerns regarding vitrification other than direct contact with a non sterile product. Moreover, European directives pose the need for aseptic procedures as a critical point. Therefore, several strategies have been developed in order to avoid the risk of contamination, including closed devices and liquid nitrogen sterilization. There have been concerns with closed vitrification devices that a reduction in cooling rate compared to open vitrification systems due to thermal insulation of samples would cause ice crystal formation resulting in impaired results. It has been proposed that a correct exposure to cryoprotective agents before closed vitrification and a high warming rate can adequately compensate the reduction in cooling rates. This reduction in cooling rate can also be prevented with direct plunging of samples in sterile liquid nitrogen followed by hermetical cryostorage (semi-closed system). Studies comparing different protocols suggest that aseptic vitrification is an effective strategy both for embryos and oocytes
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Does maternal age affect assisted reproduction technology success rates after euploid embryo transfer? A systematic review and meta-analysis
Importance: Maternal age-related embryo aneuploidy is considered the most significant limiting factor for a favorable outcome after assisted reproduction technology (ART) procedures. Thus, preimplantation genetic testing for aneuploidies has been proposed as a strategy to genetically evaluate embryos before transfer to the uterus. However, whether embryo ploidy justifies all the aspects of age-related fertility decline remains controversial. Objective: To investigate the effect of different maternal ages on ART success rates after transfer of euploid embryos. Data Sources: ScienceDirect, PubMed, Scopus, Embase, the Cochrane library, Clinicaltrials.gov, EU Clinical Trials Register, and World Health Organization International Clinical Trials Registry were searched from inception until November 2021 using combinations of relevant keywords. Study Selection and Synthesis: Observational and randomized controlled studies were included if they investigated the impact of maternal age on ART outcomes after the transfer of euploid embryos and reported frequencies of women achieving ongoing pregnancy or live birth. Main Outcomes: The ongoing pregnancy rate or live birth rate (OPR/LBR) after euploid embryo transfer comparing women <35 vs. women ≥35 years old was the primary outcome. Secondary outcomes included implantation rate and miscarriage rate. Subgroup and sensitivity analyses were also planned to explore the sources of inconsistency among studies. The quality of studies was assessed using a modified version of the Newcastle-Ottawa Scale, and body of evidence was evaluated using the Grading of Recommendations Assessment Development and Evaluation working group methodology. Results: A total of 7 studies were included (n = 11,335 ART embryo transfers of euploid embryos). A higher OPR/LBR (odds ratio, 1.29; 95% confidence interval [CI], 1.07–1.54; I2 = 40%) in women aged <35 years than in women ≥35 with a risk difference equal to 0.06 (95% CI, 0.02–0.09) was found. In line, implantation rate was higher in the youngest group (odds ratio, 1.22; 95% CI, 1.12–1.32; I2 = 0%). A statistically significant higher OPR/LBR was also found comparing women aged <35 to women 35–37, 38–40, or 41–42. A gradient relationship between age and OPR/LBR could be observed in proportion meta-analysis, especially if restricted to studies with low risk of bias. Conclusion and Relevance: Increasing maternal age is associated with a decline in ART success rates independent of embryo ploidy. This message contributes to an appropriate patient's counseling before starting preimplantation genetic testing for aneuploidies procedures. PROSPERO Registration Number: CRD42021289760. © 2023 American Society for Reproductive Medicin
Does Maternal Age Affect Assisted Reproduction Technology Success Rates After Euploid Embryo Transfer? A Systematic Review and Meta-analysis
Despite recent advancements in assisted reproductive technology (ART), the rate of live birth in advanced-age women remains suboptimal. Although many factors likely contribute, age-related embryo aneuploidy is considered the most significant determinant of cycle outcomes and has the lowest rate among women in their middle to late 20s but rises steadily from age 31 through 43 years. Preimplantation genetic testing for aneuploidies is routinely conducted to genetically evaluate embryos before transfer; however, the benefits are uncertain, and it has become a contested procedure in the field of reproductive medicine. Research on factors other than embryo chromosome segregation errors that may affect reproductive outcomes is needed.This systematic review and meta-analysis aimed to investigate whether increasing maternal age may limit ART success independent of ploidy status. Studies that evaluated the impact of maternal age on ART outcomes after the transfer of euploid embryos and included assessment of ongoing pregnancy rate (OPR) or live birth rate (LBR) were included. Ongoing pregnancy was defined as pregnancy beyond 12 weeks' gestation. The primary study outcome was comparison of OPR or LBR in women younger than 35 years compared with those 35 years or older. Additional analyses included evaluation of implantation rate and miscarriage rate (MR), as well as comparison between different age groups (ie, <35 vs 35-37, 38-40, 41-42, >42 years; <38 vs >= 38 years). The body of evidence was assessed by 2 investigators using the GRADE methodology. Meta-analysis of binary outcomes was performed with a random-effects model, and study outcomes were expressed using odds ratio (OR) with 95% confidence intervals (CIs).A total of 7 studies were included in this meta-analysis including 2 multicenter randomized controlled trials and 5 retrospective trials comprising a total of 11,335 embryo transfer cycles. Aneuploidy rate in biopsied blastocysts was reported in 4 studies and ranged between 28.9% and 54.2%. Meta-analysis revealed a significantly higher OPR/LBR (OR, 1.29; 95% CI, 1.07-1.54; P = 0.006; RD, 0.06; 95% CI, 0.02-0.09) among women younger than 35 years compared with those 35 years or older. In addition, the implantation rate was significantly higher in the youngest group (OR, 1.22; 95% CI, 1.12-1.32; P < 0.00001; RD, 0.04; 95% CI, 0.02-0.06), and there was a trend toward a lower MR (OR, 0.084; 95% CI, 0.71-1.00; P = 0.05; RD, -0.02; 95% CI, -0.03 to 0.00).The results of this study suggest that the increase in maternal age is associated with a lower OPR/LBR even after the transfer of euploid blastocysts. Notably, this gradient relationship between age and OPR/LBR remained when sensitivity analysis was conducted restricting analysis to only studies with low risk of bias
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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