Exploring the effect of cryopreservation in assisted reproductive technology and potential epigenetic risk.

Since the birth of the first baby by in vitro fertilization in 1978, more than 9 million children have been born worldwide using medically assisted reproductive treatments. Fertilization naturally takes place in the maternal oviduct where unique physiological conditions enable the early healthy development of the embryo. During this dynamic period of early development major waves of epigenetic reprogramming, crucial for the normal fate of the embryo, take place. Increasingly, over the past 20 years concerns relating to the increased incidence of epigenetic anomalies in general, and genomic-imprinting disorders in particular, have been raised following assisted reproduction technology (ART) treatments. Epigenetic reprogramming is particularly susceptible to environmental conditions during the periconceptional period and non-physiological conditions such as ovarian stimulation, in vitro fertilization and embryo culture, as well as cryopreservation procedure, might have the potential to independently or collectively contribute to epigenetic dysregulation. Therefore, this narrative review offers a critical reappraisal of the evidence relating to the association between embryo cryopreservation and potential epigenetic regulation and the consequences on gene expression together with long-term consequences for offspring health and wellbeing. Current literature suggests that epigenetic and transcriptomic profiles are sensitive to the stress induced by vitrification, in terms of osmotic shock, temperature and pH changes, and toxicity of cryoprotectants, it is therefore, critical to have a more comprehensive understanding and recognition of potential unanticipated iatrogenic-induced perturbations of epigenetic modifications that may or may not be a consequence of vitrification.

The Polymorphism Asn680Ser on the FSH Receptor and Abnormal Ovarian Response in Patients with Normal Values of AMH and AFC.

After the controlled ovarian stimulation (COS), the number of cumulus oocyte complexes collected is lower than predicted. The aim of this study is to understand if there is a possible reason for that deficient ovarian response. It was hypothesized that this is associated with the SNP (single-nucleotide polymorphism) of the FSH receptor (FSHr), specifically c.2039A > G, resulting in Asn680Ser. Two groups of patients were enrolled for this purpose: the normal (n = 36) and abnormal responses (n = 31). To predict the number of retrievable oocytes, according to the anti-Mullerian hormone (AMH) and the antral follicle count (AFC), the following formula was applied in a log scale: the number of oocytes retrieved = 2.584 − 0.015 × (age) − 0.035 × (FSH) + 0.038 × (AMH) + 0.026 × (AFC). Then, when the number of oocytes collected was less than 50% of the calculated value, it was proposed that the patients result in an abnormal response. DNA sample blood was collected from the women, and then the genetic assessment for the Asn680Ser of the FSHr was evaluated in both groups. The differences between the two categories were statistically analyzed with an independent samples t test, a Mann−Whitney U test and a Chi-squared test. In a patient with an abnormal response, a significant prevalence of the amino acid serine at position 680 of the FSHr compared to the counterpart group (p < 0.05) was detected. In conclusion, according to the results, the genetic evaluation of the FSHr could represent an accurate and predictive feature for patients undergoing assisted reproductive technology treatment.

Turner Syndrome Mosaicism 45,X/46,XY with Genital Ambiguity and Duchenne Muscular Dystrophy: Translational Approach of a Rare Italian Case.

Turner syndrome (gonadal dysgenesis with short stature and sterility) is characterized by chromosomal karyotype 45,X in 50% of cases or by mosaicism (45,X/46,XX and 45,X/46,XY) in 30-40% or X structural defects (deletions, long arm isochromosome, ring chromosome). When mosaic Turner syndrome (TS) occurs with a Y chromosome, there may be ambiguous genitalia. Duchenne muscular dystrophy (DMD) is an inherited neuromuscular disease with an X-Linked recessive pattern of inheritance that predominantly affects males, while females are usually asymptomatic. DMD has also been observed in groups of females affected by TS, not homozygous for the mutation. Here, we report a case of an Indian neonate born with ambiguous genitalia diagnosed prenatally by ultrasound who had a karyotype of 45,X/46,XY and who also had Duchenne muscular dystrophy caused by a de novo mutation in the DMD gene. Physical examination was normal without the typical dysmorphic features of TS with the exception of the genitourinary system showing ambiguous genitalia. Gender was assigned as female. At the age of three years, she had increasing difficulty walking, running, jumping and climbing stairs, proximal upper and lower extremity muscle weakness and a positive Gowers' sign. In addition, the serum creatine kinase (CK) value was over 30X the upper limit of normal. This study shows that DMD can occur in females with TS having 45,X/46,XY mosaicism and that this coexistence should be considered in women affected by TS who start to develop potential typical symptoms such as motor or developmental delay.

Nutrition as Personalized Medicine against SARS-CoV-2 Infections: Clinical and Oncological Options with a Specific Female Groups Overview.

Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is acknowledged that vulnerable people can suffer from mortal complications of COVID-19. Therefore, strengthening the immune system particularly in the most fragile people could help to protect them from infection. First, general nutritional status and food consumption patterns of everyone affect the effectiveness of each immune system. The effects of nutrition could impact the level of intestinal and genital microbiota, the adaptive immune system, and the innate immune system. Indeed, immune system cells and mediators, which are crucial to inflammatory reaction, are in the structures of fats, carbohydrates, and proteins and are activated through vitamins (vit) and minerals. Therefore, the association of malnutrition and infection could damage the immune response, reducing the immune cells and amplifying inflammatory mediators. Both amount and type of dietary fat impact on cytokine biology, that consequently assumes a crucial role in inflammatory disease. This review explores the power of nutrition in the immune response against COVID-19 infection, since a specific diet could modify the cytokine storm during the infection phase. This can be of vital importance in the most vulnerable subjects such as pregnant women or cancer patients to whom we have deemed it necessary to dedicate personalized indications.

Efficacy of Systematic Early-Second-Trimester Ultrasound Screening for Facial Anomalies: A Comparison between Prenatal Ultrasound and Postmortem Findings.

Second-trimester 2D ultrasound (US) assessment of the fetal anatomy, as proposed by worldwide guidelines, allows detecting the majority of fetal malformation. However, the detection rates of fetal facial anomalies seem to still be low, mostly in cases of isolated facial malformation. The purpose of this research was to assess and analyze the concordance between the antenatal imaging findings from second-trimester US screening and the results of fetal postmortem autopsy. Between January 2010 and January 2020, there were 43 cases where fetuses with prenatal ultrasound diagnosis of a face abnormality, associated or not with a genetic syndrome or chromosomal disorder, following intrauterine death (IUD) or termination of pregnancy (TOP) after the 13 weeks of pregnancy, underwent autopsy in the Pathological Anatomy section of Bari Polyclinic specializing in feto-placental autopsies. The diagnosis of the fetal facial defects at ultrasound was compared with the findings at autopsy in all cases. A very high level of agreement between prenatal ultrasound and autopsy findings was found for facial abnormalities associated with genetic syndromes or numerical abnormality of chromosomes. A lower level of concordance was instead found in isolated facial defects or those associated with other organ anomalies, but not associated with genetic syndrome or numerical chromosome anomaly. A detailed examination of aborted fetuses led to successful quality control of early-second-trimester ultrasound detection of facial anomalies; however, it was less accurate for the isolated ones. It is, thus, reasonable to propose a systematic early-second-trimester prenatal ultrasound screening for facial anatomy by operators specialized in fetal medicine field, using 2D, 3D, and 4D techniques (two-, three-, and four-dimensional ultrasound).

A Multi-Institutional Informed Consent Proposal as a Prevention Tool for Combined Oral Contraceptive Intake and Thrombotic Risk.

Combined oral contraceptives (COC), are among the most widely used contraceptive methods in the world today. Despite the different changes in terms of estrogen/progestogen combinations and dosages, the thromboembolic risk for a woman who takes combined oral contraceptives persists to date. METHODS: The review of relevant literature and international guidelines on prescription of combined oral contraceptives made it possible to create a proposal for informed consent to be used for prescribing. RESULTS: The several sections of our consent proposal were designed according to a rationale in order to cover all the aspects presented by worldwide guidelines: how to take, adverse effects, advertisements, extra-contraceptive benefits and effects, a checklist for condition at risk of thromboembolism, the signature of the woman. CONCLUSIONS: An informed consent to standardize combined oral contraceptives prescription can improve women's eligibility, mitigate thromboembolic risk, and assure legal protection to healthcare providers. In this systematic review in particular, we refer to the Italian medical-legal scenario, to which our group of researchers belongs. However, the model proposed was designed in the respect of main healthcare organization guidelines, and it could be easily used by any center in the world.

Intrapartum ultrasound and mother acceptance: A study with informed consent and questionnaire.

Introduction: Intrapartum ultrasound (IU) is used in the delivery ward; even if IU monitors the labouring women, it could be perceived as a discomfort and even as an" obstetric violence", because it is a young technique, not often well "accepted". A group of clinicians aimed at obtain an informed consent from patients, prior to perform a translabial ultrasound (TU). The aim of this study was to evaluate the acceptance of both translabial and transabdominal IU. Methods: In this study, performed at the University Hospital of Bari (Unit of Obstetrics and Gynecology), were enrolled 103 patients in the first or second stage of labor in singleton cephalic presentation. A statistical frequency and an association analysis were performed. As a significant result, we consider the peace of mind/satisfaction and the" obstetric violence". IU was performed both transabdominal and translabial to determine the presentation, head positions, angle of progression and head perineum distance. During the first and second stage of labor, the ASIUG questionnaires (Apulia study intrapartum ultrasonography group) were administered. Results: 74 (71, 84%) patients underwent IU and 29 had a vaginal examination (28, 15%). Significant less "violence" has been experienced with a IU (73 out 74/98, 65%) and only one person (1 /1, 35%) recorded that. On the contrary, 10 patients (10/29) perceived that "violence" (34, 48%) while 19 (65, 52%) did not respond on a similar way, after a vaginal examination (VE). More patients felt satisfaction (71 out 74/95, 95%) with the use of IU and only 3 (3/4, 05%) felt unease. A different picture was evident in the vaginal examination group. Only 17 patients (17 out 29/58, 62%) felt comfort while 12 (41, 38%) felt unease. Conclusions: In our study, IU use is well accepted by most of patients, because it could reassure women about their fetal condition. Moreover, they can see the fetus on the screen, while the obstetrician is performing the US and this is important for a visual feedback, in comparison with the classical VE.

Diffusion of laparoscopic appendectomies in Italy: a national audit.

A national audit focused on laparoscopic appendectomy was promoted by the Italian Association of Hospital Surgeons (ACOI). Four-hundred and sixty surgical practices received an e-mail questionnaire. Data concerning epidemiology, timetable, surgeon's age, selection of patients, laparotomic conversion, behaviour in the case of a normal appendix, and technical aspects were investigated. The response rate was 51.7%. The median number of appendectomies performed is 50-100 each year in a surgery ward. Laparoscopic operations are very common (93%), but mostly performed in less than 50% of the observed cases. There is no significant difference between the number of operations during the day vs. at night, and they are performed by a limited (<30%) group of surgeons, equally composed of physicians aged above and below 40. The majority of surgeons adopt an "all comers" policy regarding laparoscopic appendectomy, including selected older patients (>70 years old). There are no standard indications for conversion, while the behaviour in the presence of a normal appendix is generally removal. Even if laparoscopic appendectomy is not yet considered a gold standard, it is widely diffused in Italy, and the audit's data show different behaviours between subgroups.

Asynclitism and Its Ultrasonographic Rediscovery in Labor Room to Date: A Systematic Review.

Asynclitism, the most feared malposition of the fetal head during labor, still represents to date an unresolved field of interest, remaining one of the most common causes of prolonged or obstructed labor, dystocia, assisted delivery, and cesarean section. Traditionally asynclitism is diagnosed by vaginal examination, which is, however, burdened by a high grade of bias. On the contrary, the recent scientific evidence highly suggests the use of intrapartum ultrasonography, which would be more accurate and reliable when compared to the vaginal examination for malposition assessment. The early detection and characterization of asynclitism by intrapartum ultrasound would become a valid tool for intrapartum evaluation. In this way, it will be possible for physicians to opt for the safest way of delivery according to an accurate definition of the fetal head position and station, avoiding unnecessary operative procedures and medication while improving fetal and maternal outcomes. This review re-evaluated the literature of the last 30 years on asynclitism, focusing on the progressive imposition of ultrasound as an intrapartum diagnostic tool. All the evidence emerging from the literature is presented and evaluated from our point of view, describing the most employed technique and considering the future implication of the progressive worldwide consolidation of asynclitism and ultrasound.

Lactobacillus crispatus M247 oral administration: Is it really an effective strategy in the management of papillomavirus-infected women?

BACKGROUND: Recent studies have shown the importance of the microbiota in women's health. Indeed, the persistence of Human Papilloma Virus (HPV)-related lesions in patients with dysbiosis can be the antechamber to cervical cancer. The aim of this study was to evaluate whether long term administration of oral Lactobacillus crispatus can restore eubiosis in women with HPV infections and hence achieve viral clearance. METHODS: In total, 160 women affected by HPV infections were enrolled at the Department of Gynecological Obstetrics of "San Paolo" Hospital, Italy between February 2021 and February 2022. The women were randomly assigned to two groups, one in treatment with oral Lactobacillus crispatus M247 (group 1, n = 80) versus the control group, that hence only in follow-up (Group 2, n = 80). RESULTS: After a median follow-up of 12 months (range 10-30 months), the likelihood of resolving HPV-related cytological anomalies was higher in patients in treatment with the long term oral probiotic (group 1) versus the group that perfom only follow-up (group 2) (60.5% vs. 41.3%, p = 0.05). Total HPV clearance was shown in 9.3% of patients undergoing only follow-up compared to 15.3% of patients in the group taking long term oral Lactobacillus crispatus M247 (p = 0.34). However, the percentage of HPV-negative patients, assessed with the HPV-DNA test, documented at the end of the study period was not significantly different from the control group. CONCLUSIONS: Despite the limitations of our analysis, we found a higher percentage of clearance of PAP-smear abnormalities in patients who took long term oral Lactobacillus crispatus M247 than in the control group. Larger studies are warranted, but we believe that future research should be aimed in this direction. Trial registration This study is retrospectively registered.

SARS-CoV-2 Vaccines and Adverse Effects in Gynecology and Obstetrics: The First Italian Retrospective Study.

The most common effects reported by the Italian Medicine Agency following administration of SARS-CoV-2 vaccine are myalgia, soreness to the arm of inoculation, fever, and asthenia. To date, there are no specific and official reports registered by the Italian Medicine Agency on possible alterations of the menstrual cycle, or of the female reproductive system, following the vaccine. Actually, clinical experience showed a spread of transient adverse drug reactions of the menstrual cycle, following the administration of all COVID-19 vaccine types, both mRNA and Adenovirus vectored ones. In this work, we conducted the first retrospective study on Italian patients vaccinated for SARS-CoV-2 in the period between April 2021 and April 2022, to report the onset of menstrual changes after the vaccine in order to understand: etiology, duration of possible adverse effects, and the extent of the phenomenon. We recruited 100 women aged 18-45, vaccinated for SARS-CoV-2, who were asked to complete a questionnaire consisting of 12 multiple choice questions about the effects of the vaccine on the reproductive system. Thirty-seven of them received three doses of the vaccine, while the remaining 63 received two doses. Symptoms such as delayed menstruation and abnormal uterine bleeding (metrorrhagia, menometrorrhagia, and menorrhagia) were generally reported within the first three weeks of vaccination, especially after the second dose, with a percentage of 23% and 77%, respectively. These preliminary data suggest that this problem may be broader and deserving of further investigation in the future.

Uterine Fibroids and Diet.

Uterine myomas or fibroids are the most common benign female tumors of the reproductive organs, associated with significant morbidity and quality of life impairment. Several epidemiological risk factors for their occurrence have been identified so far, including nutrition and dietary habits. In this investigation, authors reviewed, as a narrative review, the data about diet and uterine myoma development in order to homogenize the current data. A PubMed search was conducted for the years 1990-2020, using a combination of keywords of interest for the selected topic. The authors searched the databases, selecting the randomized clinical studies, the observational studies, and the basic (experimental), clinical, and epidemiological researches. Once they collected the articles, they analyzed them according to the number of citations of each article, starting from the most cited to the least cited articles. Subsequently, authors collected the data of each article and inserted them in the various research paragraphs, summarizing the data collected. In this way, they crossed the available data regarding the association between nutrition habits and dietary components and myoma onset and growth. Many nutrients and dietary habits are associated with myoma development risk. These factors include low intakes of fruit, vegetables, and vitamin D, as well as pollutants in food. Despite the available data on the influence of some foods on the development of fibroids, further research is mandatory to understand all the nutrition risk factors which contribute to myoma growth and how exactly these risk factors influence myoma pathogenesis.