The Genetics of Non-Syndromic Primary Ovarian Insufficiency: A Systematic Review

Several causes for primary ovarian insufficiency (POI) have been described, including iatrogenic and environmental factor, viral infections, chronic disease as well as genetic alterations. The aim of this review was to collect all the genetic mutations associated with non-syndromic POI. All studies, including gene screening, genome-wide study and assessing genetic mutations associated with POI, were included and analyzed in this systematic review. Syndromic POI and chromosomal abnormalities were not evaluated. Single gene perturbations, including genes on the X chromosome (such as BMP15, PGRMC1 and FMR1) and genes on autosomal chromosomes (such as GDF9, FIGLA, NOBOX, ESR1, FSHR and NANOS3) have a positive correlation with non-syndromic POI. Future strategies include linkage analysis of families with multiple affected members, array comparative genomic hybridization (CGH) for analysis of copy number variations, next generation sequencing technology and genome-wide data analysis. This review showed variability of the genetic factors associated with POI. These findings may help future genetic screening studies on large cohort of women

Development of a Nomogram Predicting the Risk of Persistence/Recurrence of Cervical Dysplasia

Background: Cervical dysplasia persistence/recurrence has a great impact on women's health and quality of life. In this study, we investigated whether a prognostic nomogram may improve risk assessment after primary conization. Methods: This is a retrospective multi-institutional study based on charts of consecutive patients undergoing conization between 1 January 2010 and 31 December 2014. A nomogram assessing the importance of different variables was built. A cohort of patients treated between 1 January 2015 and 30 June 2016 was used to validate the nomogram. Results: A total of 2966 patients undergoing primary conization were analyzed. The median (range) patient age was 40 (18-89) years. At 5-year of follow-up, 6% of patients (175/2966) had developed a persistent/recurrent cervical dysplasia. Median (range) recurrence-free survival was 18 (5-52) months. Diagnosis of CIN3, presence of HR-HPV types, positive endocervical margins, HPV persistence, and the omission of HPV vaccination after conization increased significantly and independently of the risk of developing cervical dysplasia persistence/recurrence. A nomogram weighting the impact of all variables was built with a C-Index of 0.809. A dataset of 549 patients was used to validate the nomogram, with a C-index of 0.809. Conclusions: The present nomogram represents a useful tool for counseling women about their risk of persistence/recurrence after primary conization. HPV vaccination after conization is associated with a reduced risk of CIN2+

Vitamin D Deficiency in a Cohort of Neapolitan Pregnant Women: Do We Really Live in the City of the Sun?

Background: Insufficient serum 25-hydroxyvitamin D [25(OH)D] levels are a global public health issue, and pregnant women are a significant at-risk group. We aimed to assess maternal serum 25(OH)D concentrations in a cohort of Neapolitan pregnant women and the association with dietary habits, to define which patients are at increased risk of hypovitaminosis and how we can identify them. Methods: This was a prospective observational study. We included 103 pregnant women attending a routine third trimester obstetric examination. Information on obstetrical history and socio-demographic characteristics were obtained through interviews and medical records. Vitamin D intake was assessed using a food frequency questionnaire. Serum 25(OH)D concentration was measured by DiaSorin Liaison and the cut-off value for deficiency was set at 20 ng/mL. Results: Among the 103 pregnant women recruited, 71 (68.9%) were Vitamin D deficient (mean value 12.6 +/- 0.5 ng/mL). No statistically significant differences were found between the women involved in the study for: maternal age, pre-pregnancy body mass index (BMI), gestational weight gain, and gestational age at investigation. Women with hypovitaminosis reported a significantly lower intake of milk/yoghurt, cheeses/dairy products and fish. Maternal hypovitaminosis D significantly correlated with low birth weight. Conclusions: Our study confirms that Vitamin D deficiency is a common finding also in sunny areas. Patients with low level of Vitamin D reported a lower intake of food rich of this micronutrient. An accurate anamnesis can be an easy way to identify pregnant women at risk of hypovitaminosis D for whom screening and supplementation can be suitable

The impact of obesity on haemodynamic profiles of pregnant women beyond 34 weeks' gestation

Objective: We aimed to compare the haemodynamic profiles of obese and non-obese pregnant women, alongside describing the haemodynamic changes that occur in hypertensive disorders of pregnancies with an Appropriate for Gestational Age Fetus (HDP-AGA) beyond 34 weeks' gestation.Study design: In this prospective case-control study, maternal haemodynamic assessment was carried out by a trained operator using an UltraSonic Cardiac Output Monitor during a routine clinical assessment after 34 weeks of gestation. Indexed and non-indexed parameters were evaluated.Main outcome measures: Maternal hemodynamic parameters.Results: Obese and non-obese women did not differ for non-indexed parameters (Cardiac Output, Stroke Volume, Systemic Vascular Resistance). Using indexed parameters, corrected for Body Surface Area, obese women presented significantly lower Cardiac Index z-score (-0.23 +/- 0.5 vs 0.26 +/- 1.2; p = 0.004), Stroke Volume Index z-score (-0.27 +/- 0.8 vs 0.31 +/- 1.0; p < 0.0001) and significantly higher Systemic Vascular Resistance Index (0.16 +/- 0.8 vs -0.36 +/- 0.7; p < 0.0001). In obese women, HDP-AGA (n = 19) had significantly higher Systemic Vascular Resistance Index z-score (1.26 +/- 1.7 vs 0.16 +/- 0.8; P = 0.009) and significantly lower Stroke Volume Index (-0.68 +/- 0.8 vs -0.27 +/- 0.8; 0.049).Conclusion: Using indexed parameters, differences in haemodynamic profiles between obese and non obese women can be highlighted. Obese women seem to present a cardiac maladapation to the pregnancy (reduced cardiac index and stroke volume and increased vascular resistance) that could explain the increased risk of complications in this subgroup

Impact of COVID-19 on Breastfeeding among SARS-CoV-2 Infected Pregnant Women: A Single Centre Survey Study

Background: Although current guidelines recommend that mothers with suspected or confirmed SARS-CoV-2 infection should be encouraged to initiate and continue breastfeeding, up-to-date literature shows conflicting data regarding breastfeeding experiences in infected women. This survey aimed to report on the psychological impact of SARS-CoV-2 infection on breastfeeding practice and medical counselling in a single tertiary center in Southern Italy. Methods: One-hundred breastfeeding women with SARS-CoV-2 infection at delivery were given an anonymous questionnaire regarding breastfeeding and women’s perception of the impact of COVID-19 on breastfeeding. Results: 75% of women reported they had difficulty breastfeeding; among them, 66 (66%) declared that separation from their babies after delivery affected their ability to breastfeed. Incidence of reported difficulties in breastfeeding was higher in women who underwent caesarean section compared to women with vaginal delivery (56/65, 86.2% vs. 19/35, 54.3%, χ2 = 12.322, p < 0.001) and in women with a hospital stay of more than 5 days (48/57, 84.2% vs. 23/37, 62.2%, χ2 = 5.902, p = 0.015). Furthermore, the incidence of difficulties in breastfeeding was higher in women who subsequently decided to use exclusively infant formula compared to women who mixed maternal milk with infant formula and women who breastfed exclusively with maternal milk (48/49, 98% vs. 20/25, 80% vs. 7/26, 26.9%, χ2 = 46.160, p < 0.001). Conclusions: Our survey highlights the importance of healthcare support and information on hygiene practices to decrease the perceived stress related to breastfeeding for infected mothers under restrictions, especially in women undergoing cesarean section and with a long hospital stay

Myeloid Sarcoma of the Breast as Blast Phase of JAK2-Mutated (Val617Phe Exon 14p) Essential Thrombocythemia: A Case Report and a Systematic Literature Review

Introduction: Myeloid sarcoma (MS) is a mass-forming proliferation of myeloid blasts. Frequently, it arises as blast phase of pre-existing myeloproliferative, myelodysplastic disorders or consequent to bone marrow transplant. Its molecular characterization has become an increasingly important requirement for the diagnostic definition of this solid leukemia. Case presentation: Our case report concerns an MS arising in the breast of a woman with a previous diagnosis of JAK2-mutated essential thrombocythemia (Val617Phe exon 14p) mimicking, on histology, a lobular carcinoma of the breast. The immunohistochemical study of the neoplasm provided the key that solved the diagnostic doubt and the immunohistochemical evaluation of NPM protein expression, which turn out to be negative, provided a clear indication on the molecular status and prognosis of the disease. A year later, the neoplasm relapsed in the pelvic area. Discussion: This diagnostic challenge led us to review the literature of the past 10 years concerning MS of the breast. To the best of our knowledge, this was the first case of MS of the breast occurring in a patient with a history of essential thrombocythemia and recurred in the pelvic region

Vitamin D, reproductive disorders and assisted reproduction: evidences and perspectives

Vitamin D is an important nutrient involved in many fundamental health outcomes. However, its influence on female reproductive function remains ambiguous. Cholecalciferol seems to have a role in the reproductive processes and in the patients affected by polycystic ovary syndrome, endometriosis, uterine myomas and premature ovarian failure. Moreover, it may play an import- ant role in the assisted reproductive techniques, given that it is capable of influencing oocyte quality, but also an adequate preparation of the endometrium for embryonic implantation. Although promising, available evidence is based on a limited number of in vitro, in vivo and clin- ical studies. We provide an overview of the association between vitamin D and female infertility reporting the most recent data published in the literature. Nevertheless, properly randomised clinical trials are mandatory to achieve more conclusive results about the promising role of vita- min D in the management of female assisted reproduction

Use of Artificial Intelligence in Obstetrics: not quite ready for prime time

Artificial Intelligence (AI) is finding several applications in healthcare settings. The aim of our review is to report evidence about AI application in obstetrics. Through a narrative review of the literature, we described AI use in different obstetric areas: prenatal diagnosis, fetal heart monitoring, prediction and management of pregnancy-related complications (preeclampsia, preterm birth, gestational diabetes mellitus and placenta accreta spectrum), and labor. AI seems to be a promising tool to help clinicians in daily clinical activity. The main advantages that emerged from this review are related to the reduction of inter- and intra-operator variability, time reduction of procedures and improvement of overall diagnostic performance. However, nowadays, the diffusion of these systems in routine clinical practice raises several issues. Reported evidence are still very limited and further studies are needed to confirm clinical applicability of AI. Moreover, a better training of clinicians that are designed to use these systems should be ensured and evidence-based guidelines regarding this topic should be produced, in order to enhance the strengths of artificial systems and minimize their limits

Associations between Maternal Dietary Patterns, Biomarkers and Delivery Outcomes in Healthy Singleton Pregnancies: Multicenter Italian GIFt Study

Background: Maternal nutrition represents a critical risk factor for adverse health outcomes in both mother and offspring. We aimed to investigate associations between maternal nutritional habits, biomarker status, and pregnancy outcome among Italian healthy normal-weight pregnancies. Methods: Multicenter prospective cohort study recruiting Italian healthy normal-weight women with singleton spontaneous pregnancies at 20 ± 2 weeks (T1) in Milan and Naples. All patients underwent nutritional evaluations by our collecting a 7-day weighed dietary record at 25 ± 1 weeks (T2) and a Food Frequency Questionnaire at 29 ± 2 weeks (T3). Maternal venous blood samples were collected at T3 to assess nutritional, inflammatory and oxidative biomarker concentrations (RBCs folate, vitamin D, hepcidin, total antioxidant capacity). Pregnancy outcomes were collected at delivery (T4). General linear models adjusted for confounding factors were estimated to investigate associations between maternal dietary pattern adherence, nutrient intakes, biomarker concentrations and delivery outcomes. Results: 219 healthy normal-weight pregnant women were enrolled. Vitamin D and RBCs folate concentrations, as well as micronutrient intakes, were consistently below the recommended range. In a multi-adjusted model, maternal adherence to the most prevalent ‘high meat, animal fats, grains’ dietary pattern was positively associated with hepcidin concentrations and negatively associated with gestational age at delivery in pregnancies carrying female fetuses. Hepcidin plasma levels were further negatively associated to placental weight, whereas vitamin D concentrations were positively associated to neonatal weight. Conclusions: A high adherence to an unbalanced ‘high meat, animal fats, grains’ pattern was detected among Italian normal-weight low-risk pregnancies, further associated with maternal pro-inflammatory status and gestational age at delivery. This evidence underlines the need for a dedicated nutritional counseling even among low-risk pregnancies