The impact of COVID-19 vaccines on fertility-A systematic review and meta-analysis.

BACKGROUND: Despite literature's evidence about COVID-19 vaccines' safety, concerns have arisen regarding adverse events, including the possible impact on fertility, accentuated by misinformation and anti-vaccine campaigns. The present study aims to answer the question: Is there any impact of COVID-19 vaccines on the fertility of men and women of reproductive age? METHODS: PubMed, Scopus, Web of Science, Cochrane and Embase databases were searched for eligible studies until June 8th, 2022. The search was restricted to articles regarding humans, published in any languages, without additional restrictions. Studies' quality was assessed by the Newcastle-Ottawa and the Before and After Quality Assessment scales for cohort and pre-post studies, respectively. Random-effect meta-analyses were performed for parameters considered in ≥ 2 studies, calculating means, p-values and 95 % Confidence Intervals (CIs). RESULTS: Out of 1406 studies screened, 29 were included in the systematic review. These studies, conducted in Israel (34.5 %), USA (24.1 %), Russia (20.7 %) China (10.3 %), Italy (3.5 %), North America (3.5%) and Turkey (3.5 %) were of poor (34.5 %), moderate (58.6 %) and good (6.9 %) quality. Meta-analyses were performed for pre- and post-vaccination sperm progressive motility (44 %, 95 % CI 42 %-62 % vs 43 %, 95 % CI 31 %-59 % p = 0.07) and concentration (50.6 mln/ml, 95 % CI 35.1-72.8 vs 55.4 mln/ml, 95 % CI 37.4-82.2p = 0.12). Biochemical (0.51, 95 % CI 0.40-0.66 vs 0.60, 95 % CI 0.53-0.68p = 0.45) and clinical (0.45, 95 % CI 0.37-0.54 vs 0.47, 95 % CI 0.40-0.55 p = 0.31) pregnancy rate did not differ among vaccinated and not vaccinated groups. Subgroup meta-analyses based on the type of vaccine showed no significant difference: between vaccinated with mRNA vaccines and non-vaccinated regarding biochemical pregnancy rates; pre- and post-vaccination with Gam-COVID-Vac regarding testosterone, FSH and LH levels; pre- and post-vaccination with BNT162b2 vaccines regarding sperm volumes. CONCLUSION: Based on the studies published so far, there is no scientific proof of any association between COVID-19 vaccines and fertility impairment in men or women.

Interventions to address mental health issues in healthcare workers during infectious disease outbreaks: A systematic review.

Considering the importance of evidence on interventions to tackle mental health problems in healthcare workers (HCWs) during pandemics, we conducted a systematic review, aiming to identify and summarize the implemented interventions to deal with mental health issues of HCWs during infectious disease outbreaks and report their effectiveness. Web of Science, PubMed, Cochrane, Scopus, CINAHL and PsycInfo electronic databases were searched until October 2nd, 2020. Primary-data articles, describing any implemented interventions and their effectiveness were considered pertinent. Studies were screened according to the inclusion/exclusion criteria and subsequently data extraction was performed. Twenty-four articles, referring to SARS, Ebola, Influenza AH1N1 and COVID-19 were included. Interventions addressing mental health issues in HCWs during pandemics/epidemics were grouped into four categories: 1) informational support (training, guidelines, prevention programs), 2) instrumental support (personal protective equipment, protection protocols); 3) organizational support (manpower allocation, working hours, re-organization of facilities/structures, provision of rest areas); 4) emotional and psychological support (psychoeducation and training, mental health support team, peer-support and counselling, therapy, digital platforms and tele-support). These results might be helpful for researchers, stakeholders, and policymakers to develop evidence-based sustainable interventions and guidelines, aiming to prevent or reduce the immediate and long-term effect of pandemics on mental health status of HCWs.

The impact of oral contraceptive use on breast cancer risk: State of the art and future perspectives in the era of 4P medicine.

Breast cancer is the most commonly occurring cancer in women, the second most frequent cancer overall, and it causes the greatest number of cancer-related deaths among women. The significant increased concern of breast cancer worldwide may be attributed to the prolonged life expectancy and the adoption of the western lifestyle with its related risks factors. A woman's risk for breast cancer is linked to her reproductive history and with her lifetime hormonal exposure. Among the known risk factors for breast cancer, several studies investigated the possible role of the assumption of hormonal "pills" in both breast cancer incidence and development. Nevertheless, data about the association between the assumption of oral contraceptives and breast cancer incidence are still controversial and not conclusive. Given the public health importance of breast cancer and the popularity of hormonal "pills" as contraceptive, the impact of oral contraceptive use on breast cancer risk assumes relevance from both a clinical and a social point of view. Therefore, in this review we wanted to illustrate this issue by addressing the following major themes: a) the role of sex steroid hormones in female breast development and carcinogenesis; b) the clinical impact of hormonal oral contraception according to the state of the art literature; c) the actual scientific debate and future perspectives.

Implementing carrier screening for cystic fibrosis outside the clinic: ethical analysis in the light of the personalist view.

BACKGROUND: Cystic Fibrosis (CF) is an autosomal recessive genetic disease. Two models for screening CF are normally used: newborn screening and population-based CF carrier screening. In turn, there are three main models of population-based CF carrier screening: prenatal carrier screening, preconception carrier screening, and carrier screening outside clinical settings. AIM: To evaluate, in the light of the personalist view, the use of carrier screenings for CF outside the clinic, i.e. in non-clinical settings, such as school and workplaces. METHODS: Analysis has been carried out according to the "Personalist approach" (also called "Triangular model"), an ethical method for performing ethical analysis within HTA process. It includes factual, anthropological and ethical data in a ''triangular'' normative reflection process. FINDINGS: Implementing carrier screening for cystic fibrosis outside the clinical settings allows acquisition of knowledge for informing reproductive choices, that can be considered as valuable; benefit-risk ratio seems to be not much favorable; autonomous and responsible decisions can be taken only under certain conditions; economic advantage is difficult to determine; therefore, from a personalist view, implementing carrier screenings outside the clinic seems not to be ethically justified. CONCLUSIONS: In accordance with the personalist perspective, public health programs providing carrier screenings outside the clinic should not be implemented.

Sustainability of Endovenous Iron Deficiency Anaemia Treatment: Hospital-Based Health Technology Assessment in IBD Patients.

Iron deficiency anaemia (IDA) is the main extraintestinal manifestation affecting patients with inflammatory bowel disease (IBD). The Health Technology Assessment approach was applied to evaluate the sustainability of intravenous (IV) iron formulations in the Italian hospital setting, with particular focus on ferric carboxymaltose. Data on the epidemiology of IBD and associated IDA, in addition to the efficacy and safety of IV iron formulations currently used in Italy, were retrieved from scientific literature. A hospital-based cost-analysis of the outpatient delivery of IV iron treatments was performed. Organizational and ethical implications were discussed. IDA prevalence in IBD patients varies markedly from 9 to 73%. IV iron preparations were proven to have good efficacy and safety profiles, and ferric carboxymaltose provided a fast correction of haemoglobin and serum ferritin levels in iron-deficient patients. Despite a higher price, ferric carboxymaltose would confer a beneficial effect to the hospital, in terms of reduced cost related to individual patient management and additionally to the patient by reducing the number of infusions and admissions to healthcare facilities. Ethically, the evaluation is appropriate due to its efficacy and compliance. This assessment supports the introduction of ferric carboxymaltose in the Italian outpatient setting.

An innovative chemical strategy for PCR-free genetic detection of pathogens by an integrated electrochemical biosensor.

An innovative chemical strategy integrated in a miniaturized electrochemical device was developed for sensitive detection of a pathogen genome (HBV virus) without any amplification step. The results show a limit of detection comparable to the standard qRT-PCR method (20 copies per reaction), paving the way to future development of genetic PoC devices addressing automatized and low-cost molecular diagnostics.

[Genetic test for cancer and intra-family communication: freedom vs. responsibility]. / Test genetici in oncologia e comunicazione intrafamiliare: autonomia vs responsabilità.

Genetic tests affect not only single patients but also their genetic relatives. In some cases, they in fact allow to acquire information not only about a single patient, but also about those who are genetically linked (genetic relatives). By appealing to the principle of autonomy, the patient can refuse to be informed of the test result, or to inform their relatives on the risk of a pathology. How might the relatives' right to know be reconciled with the will of a patient who refuses to know or to inform? Among the large number of moral dilemmas that this field can raise, the article aims to reply to the above mentioned question and to analyse in depth some aspects of intra-family communication within the field of genetic tests for cancer.

[On the moral dutifulness of using vaccinations]. / Sulla "doverosità morale" dell'uso di vaccine.

People had contradictory opinions on using vaccinations over time: an initial opposition, later large favour and then doubts and perplexities. In recent times, some movements, blogs and associations stigmatize the use of vaccinations and they are increasingly asking to remove mandatory vaccinations in countries where they are active. The impact of the antivaccination campaigns should not be underestimated, considering that, for example, in Italy, due to these campaigns, adhesions to vaccinations are decreasing by 1% per year, and in reference to rubella and measles, adhesions decreased by 25% in some regions of the country. Overcoming the choice between mandatory and recommended vaccinations, the paper deals with the topic of using preventive immunization starting from the concept of "moral dutifulness".

The legislation on living organ donation in Western Europe: legal and ethical analysis and impact on clinical practice.

In Europe there are various directives on living organ donation (LOD) that are applied differently in member countries. The objectives of this study were as follows: (1) to identify the most relevant normative differences among the countries of Western Europe, and (2) to evaluate the evolution of LOD data in these countries. We performed comparative analysis of national legislations to identify the most significant common and different regulatory elements that were evaluated subsequently from an ethical-legal point of view. For data analysis on LOD, we used the EULOD database of donations in Europe. Relevant legislative differences emerged among European countries. Through legal and ethical analysis, it has possible to delineate two legal guidelines: on the one hand, based primarily on informed consent applying the principle of individual autonomy, and on the other hand, informed consent associated with legal and medical criteria. From 1992 to 2009, countries with standards based primarily on individual informed consent showed an increase in LOD from 5.5% to 25.3%, which was greater than those in countries that had additional legal requirements, namely, from 1.6% to 16.0.%. The distinct transpositions of the European Directives among singles countries related to LOD are based essentially only on the request for informed consent or for additional medical and legal requirements. The former practices which increases LOD, can facilitate "organ tourism."

Ethical evaluation of risks related to living donor transplantation programs.

The shortage of available cadaveric organs for transplantation and the growing demand has incresed live donation. To increase the number of transplantations from living donors, programs have been implemented to coordinate donations in direct or indirect form (cross-over, paired, and domino chain). Living donors with complex medical conditions are accepted by several transplantation programs. In this way, the number of transplants from living has exceeded that from cadaver donors in several European countries. No mortality has been reported in the case of lung, pancreas, or intestinal Living donations, but the perioperative complications range from 15% to 30% for pancreas and lung donors. In living kidney donors, the perioperative mortality is 3 per 10,000. Their frequency of end-stage renal disease does not exceed the United States rate for the general population. However, long-term follow-up studies of living donors for kidney transplantations have several limitations. The frequency of complications in live donor liver transplantation is 40%, of these, 48% are possibly life-threatening according to the Clavien classification. Residual disability, liver failure, or death has occurred in 1% of cases. The changes in live donor acceptance criteria raise ethical issues, in particular, the physician's role in evaluating and accepting the risks taken by the living donor. Some workers argue to set aside medical paternalism on behalf of the principle of donor autonomy. In this way the medical rule "primum non nocere" is overcome. Transplantation centers should reason beyond the shortage of organs and think in terms of the care for both donor and recipient.

Transmission of male infertility and intracytoplasmic sperm injection (mini-review).

The fact that genetic aetiology is responsible for approximately one third of all kinds of male sterility has led to concerns regarding the application of artificial reproductive technologies in the cases of azoospermia and severe oligozoospermia. Congenital sterility could be caused by gene mutation, quantitative or structural abnormality of sexual chromosomes or autosomes. The possibility of inherited transmission of male sterility within the context of applying artificial reproductive technologies is analysed in the article. Klinefelter's syndrome, mutation of cystic fibrosis transmembrane conductance regulator (CFTR) gene, which causes cystic fibrosis, and mutation of azoospermia factor zone (AZF) of Y-chromosome are among the most frequent genetic causes of severe oligozoospermia and azoospermia. The probability of a mutation of the CFTR gene being transmitted to the next generation is 50%. The probability of inherit transmission of Klinefelter's syndrome of mosaic karyotype could reach 70%. The probability of transmission of AZF mutation to children of male sex, generated with ICSI, is 100%. The percent of men with AZF mutation among users of ICSI centers, ranges from 3.2% to 14%. It means that at least 3.2 % of all boys conceived with ICSI will be sterile because of mutation in the AZF zone of Y-chromosome. It should be noted that genetic analysis and counselling do not always occur before the beginning of artificial fertilization cycles. Parents-to-be do not always have an opportunity to learn about the genetic risks of their unborn child and make any subsequent and responsible decisions. Among the decisions is a choice of not resorting to ART, but to live with the infertility and explore other opportunities for parenthood. Responsibility for high risk of conceiving a child with genetic anomalies rests not only with the parents, but also with all of society, including those responsible for research, technology, and legislation, in the health care profession.

Ethical implications of predictive DNA testing for hereditary breast cancer.

Predictive medicine offers the possibility of detecting many common diseases that have a genetic basis, such as cancer; however, a genetic alteration might only indicate susceptibility to, not certainty of, disease. Whereas means for identifying a greater susceptibility to disease have been developed, effective interventions have progressed much more slowly. Awareness of one's susceptibility to disease without an actual possibility of intervention can lead to an unacceptable use of such information, or have a dramatic psychological impact on the person involved. Are the risks connected with the knowledge of susceptibility to genetic disease proportional to the benefits that such knowledge may provide? Does the knowledge of one's genetic condition constitute a service to the individual and society, or is this predominantly harmful for the person involved? The problem is vast, and involves medical, psychological, social, political and ethical dilemmas. These dilemmas, common to all predictive medicine, are most evident in predictive DNA testing for hereditary breast cancer. In our analysis, we will first examine the ethical values involved in genetic testing, highlighting the special ethical issues raised by predictive DNA testing for hereditary breast cancer. Next we will deal with genetic counseling, which, in our opinion, is the 'ethos' for ethically justifying predictive DNA testing.

A case of forearm amputation after ovarian stimulation for in vitro fertilization-embryo transfer.

OBJECTIVE: To report a case of forearm amputation after ovarian stimulation for IVF-ET. DESIGN: Case report. SETTING: A university hospital. PATIENT(S): A 41-year-old woman, who had coagulation disorder as a result of an ovarian hyperstimulation syndrome (OHSS) for IVF-ET. INTERVENTION(S): Retrospective evaluation of angiographic studies and surgical treatment. MAIN OUTCOME MEASURE(S): Medical follow-up after forearm amputation due to OHSS. RESULT(S): The patient underwent many cycles of IVF-ET with administration of purified FSH (75 IU 10 times per day, for 12 days) and chorionic gonadotropin (5,000 IU). The patient had a coagulation disorder as a result of OHSS, with thrombosis of the axillary vein, recurring after thromboarterectomy and leading to the paradoxical result of the amputation of an arm. CONCLUSION(S): An ethical evaluation of this case is mandatory, since the desire for pregnancy, the role of medical science, health, and human life itself are all factors involved.

Catalysis and inhibition of ligand substitution in palladium(II) square-planar complexes: effects of DNA.

The kinetics of substitution, by thiourea, of ethylenediamine (en) or N,N'-dimethylethylenediamine (Me(2)en) coordinated to palladium(II) in the complexes [Pd(4,4'-R(2)bpy)(en)](PF(6))(2) (bpy = 2,2'-bipyridine; R = H or Me), [Pd(en)(2)](PF(6))(2) and [Pd(Me(2)en)(2)](PF(6))(2) have been studied at 25 degrees C, pH 7 and various ionic strength values, in the presence of calf thymus DNA. The rate of the reaction in water depends on ionic strength, pH, and nucleophile concentration; at fixed pH and ionic strength the k(obsd) values are correlated to the square of the thiourea concentration. This rate law is not altered by the presence of DNA, but the rate of reaction is influenced, depending on the nature of ancillary ligand, L-L, bound to palladium. DNA inhibits the substitution process when L-L is bpy or 4,4'-Me(2)bpy and catalyzes the same reaction when L-L is en or Me(2)en. These opposite kinetic effects can be related to the noncovalent interactions of the various complexes with the DNA double helix. Inhibition of the reactivity of the complexes [Pd(4,4'-R(2)bpy)(en)](2+) is due to protection of the reaction center from nucleophile attack by DNA. Acceleration of the reaction when L-L is en or Me(2)en is related to the dependence of the rate of reaction on pH. If, due to the higher activity of water under the electric field of phosphate groups, hydronium ion concentration on DNA surface is higher than in the bulk solution, the enzyme-like dependence of the rate of reaction on [DNA] is due to progressive accumulation of the complexes around the double helix. Regardless of the complexes' nature, the rate constant values obtained in DNA at pH 7 correspond to values determined in water at pH 5. This pH value on the DNA surface, lower by about two units with respect to the bulk solution, is in good agreement with theoretical predictions. Acceleration of ethylenediamine substitution has been observed for all of the complexes studied in the presence of sodium polyvinylsulfonate.

Influence of DNA on the rate of ligand substitution in platinum(II) terpyridine complexes.

The kinetics of substitution of pyridine or 2-methylpyridine, by iodide or thiourea, in the complexes [Pt(4'-R'terpy)(2-Rpy)](BF4)2 (R' = o-tolyl or H; R = H or CH3) has been studied, at 25 degrees C, pH 7, and various ionic strength values, in the presence of and without calf thymus DNA. The reactions occur in one observable step, and plots of kobsd against nucleophile concentration give straight lines with zero intercepts. DNA inhibits all the reactions studied without altering the rate law; the second-order rate constants k2 decrease systematically on increasing DNA concentration and are larger at higher ionic strength values. Partitioning of the ionic reactants in solution on electrostatic grounds can account for this kinetic effect in the reaction with iodide. Iodide is kept off the double helix proximity while the dicationic complexes concentrate on it. The inhibiting effect observed for the uncharged reagent thiourea can be related to the specific binding mode of the complexes to DNA. The complexes studied are effective intercalators to double helix, and this type of interaction, which prevents attack of thiourea at platinum, decreases their actual concentration in solution. The inhibiting effect is larger for [Pt(terpy)(py)]2+ that is a better intercalator. Likewise, the decrease in the rate of substitution of 2-Rpy, at a given [DNA] on decreasing ionic strength, is due to the influence of ionic strength on the complex-DNA interactions.

Calcium antagonists and hormone release. V. Effects of a calcium-antagonist (verapamil) on pituitary hormone release in hypersecretory states.

Twenty-five patients with various syndromes of pituitary hyperfunction, of tumoral and nontumoral origin, were infused with verapamil (VE), a Ca2+-channel blocker (5 mg/h X 3 h) to assess the calcium dependence of the augmented hormone secretion. In 5 hypogonadal women with elevated gonadotropin secretion, VE produced a marked inhibition of LH (54.6%) and FSH (49.4%) release, comparable to that observed in normal subjects who were infused with VE. In 5 patients with latent or mild hypothyroidism, TSH levels decreased during the VE infusion, and the magnitude of the decrease was directly correlated with the basal levels (r = 0.986, p less than 0.01). In patients harboring a pituitary tumor, differential effects of VE infusion were observed: it induced an inhibition (28.5%) of ACTH secretion in patients with Cushing's disease; in acromegalic patients, no alterations in HGH levels were noted; on the contrary, in prolactinoma patients, a clear PRL increment (47.2%) was present. These experiments confirm that the need for extracellular Ca2+ varies from hormone to hormone and that VE infusion can modify the secretion of pituitary hormone in a hypersecretory state, as well as those hormones which are unaffected by VE infusion in basal condition.