Association between endometrial senescent cells and immune cells in women with repeated implantation failure.

PURPOSE: The aim of this study was to compare women with recurrent implantation failure (RIF) and control group in terms of the associations between p16-positive senescent cells and certain types of immune cells in human endometrium during the mid-luteal phase METHODS: Immunohistochemical staining was performed in 116 endometrial biopsies taken from 57 women presenting RIF, and control group of 59 women who became pregnant after the first intracytoplasmic sperm injection. Endometrial tissue sections were stained immunohistochemically for p16 (Senescent cells), CD4 (T-helpers), CD8 (T-killers), CD14 (Monocytes), CD68 (Macrophages), CD56 (Natural killers), and CD79α (B-cells). The percentage of positively stained cells for each marker was calculated by HALO image analysis software. The quantity and the relationship between senescent cells and immune cells were assessed and compared between the two groups. RESULTS: The correlation coefficient was highest between senescent cells and CD4+ cells and was lowest between senescent cells and CD14+ cells in RIF women, similarly to the control group. However, most of the observed correlations among senescent and immune cells weaken notably or disappear in the RIF group. When comparing senescent cell-to-immune cell quantitative ratios, only p16+/CD4+ cell ratio was significantly higher in RIF women as compared with patients from the control group. CONCLUSION: Our study indicates that the quantity of senescent cells in human endometrium during the mid-luteal phase has the strongest association with the amount of T helpers. Moreover, the specificity of this association might have an important impact on the occurrence of RIF.

Interviewing children: the impact of the COVID-19 quarantine on children's perceived psychological distress and changes in routine.

BACKGROUND: The COVID-19 outbreak has resulted in governments implementing disease containment measures such as school closures, social distancing, and home quarantine. To date, only a few studies have drawn attention to the psychological impact of lockdown on Italian children's mental health. The present study aimed to investigate the psychological distress (anxiety and mood symptoms) and perceived changes in routine among Italian primary and middle school students during the COVID-19 quarantine. METHODS: This interview study was performed between the 18th of May and 7th of June 2020: it involved a sample of 82 children and adolescents living in Milan (Italy), attending primary and middle school (aged 6 to 14 years), and their parents. RESULTS: Almost 30 % of the subjects reported having struggled to adjust to home learning. 36 responders completely changed their dietary habits during the lockdown: they were not eating the same amount of food and were consuming more junk food. Sleep habits were also affected by the lockdown measures: 28 % of the sample had difficulties sleeping and wished to sleep in their parents' bed. Concerning psychological distress, 64 (78 %) children and adolescents had anxiety symptoms; 43.9 % of the students reported significant mood symptoms. CONCLUSIONS: Children are not indifferent to the dramatic impact of the COVID-19 epidemic: our data confirm their difficulties in adapting to the quarantine measures. The effects of stress exposure may not manifest later on during the children's development, and, for this reason, it would be interesting to follow up on these participants to improve our understanding of how long these outcomes may last.

Use of granulocyte colony-stimulating factor for the treatment of unexplained recurrent miscarriage: a randomised controlled trial.

BACKGROUND: Recurrent miscarriage (RM) is defined as the occurrence of three or more clinically detectable pregnancy losses in the first trimester. In most cases of RM, its aetiology remains unexplained. Granulocyte colony-stimulating factor (G-CSF), a cytokine, and its receptor are expressed in placental tissue. To investigate the effectiveness of G-CSF in preventing embryo demise, we administered G-CSF to women with RM. METHODS: A randomised controlled trial in women with RM treated with G-CSF or placebo was conducted in one private reproductive medicine clinic. Sixty-eight women with unexplained primary RM, all with at least four consecutive miscarriages and negative for all clinical investigations, were selected. Patients were randomized for s.c. treatment with G-CSF (n = 35) (1 microg/kg/day) starting on the sixth day after ovulation, or with placebo (n = 33). Patients were randomized using a computer-generated randomization number sequence. Pregnancy outcome (delivery of a healthy baby without major or minor malformations) was the primary outcome measure. RESULTS In the group treated with G-CSF, 29 out of 35 (82.8%) women delivered a healthy baby, whereas in the placebo group, this figure was only 16 out of 33 (48.5%) (P = 0.0061, odds ratio = 5.1; 95% confidence interval 1.5-18.4). Significantly higher beta-hCG levels were found in gestation weeks 5-9 in women treated with G-CSF versus placebo (P < 0.001). CONCLUSIONS: Our data show that G-CSF may be effective in the treatment of unexplained RM. However, further studies are needed to confirm the effectiveness of this treatment in women with unexplained RM, refractory to conventional treatment. The study was registered with a ICMJE recognized registry, the Clinical Trial.gov Protocol Registry System, with the number NCT00772122.

Progesterone receptor expression in orbital cavernous hemangiomas.

Orbital cavernous hemangiomas (OCH) have thick and highly cellular vascular walls. Ultrastructural studies have demonstrated the smooth muscle nature of these cells. Vascular neoplasms can modify their morphological and clinical features under hormonal stimulation. The purpose of the present study was to investigate the presence of smooth muscle markers and sex steroid receptors in 12 cases of OCH. Orbital cases were compared with cutaneous hemangiomas and subcutaneous angioleiomyomas. Smooth muscle actin (SMA) and desmin were localized in spindle cells of the vascular walls of all 12 cases studied. OCH showed immunohistochemical positivity with progesterone receptor (PR) antibody both in smooth muscular and in endothelial cells. For comparison, sex steroid receptors were studied in 10 cases of cutaneous cavernous hemangioma and in 10 cases of subcutaneous angioleiomyoma. PR was found in smooth muscle and endothelial cells of 6 out of 10 cases of subcutaneous angioleiomyoma and in none of the cases of cutaneous cavernous hemangioma. No positivity was obtained with estrogen receptor (ER) antibody in any of the cases tested. The present data suggest that OCH share morphological and immunohistochemical features with subcutaneous angioleiomyomas. Furthermore, immunohistochemical positivity with PR antibody indicates that OCH have to be added to the list of mesenchymal lesions that express sex steroid receptors.

Serum CA 125 and first trimester abortion.

OBJECTIVE: The study was carried out to assess the clinical value of serum CA 125 in association with serum beta-human chorionic gonadotropin (hCG) for predicting pregnancy outcome. METHODS: One hundred spontaneous pregnancies, 52 non-threatened pregnancies and 48 with threatened abortions, observed in the Department of Obstetrics and Gynecology at the University 'La Sapienza', Rome, Italy, were evaluated during the first trimester using ultrasound examination, CA 125 and beta-hCG titrations. RESULTS: Threatened pregnancies had statistically significantly higher CA 125 serum values than non-threatened pregnancies, especially those with a negative outcome (P < 0.01). The CA 125 levels in the threatened pregnancies were positively correlated with the tropho-decidual hematoma volume (r=0.839, P < 0.0001). The CA 125-beta-hCG association showed a higher prognostic value (sensitivity 78.9%, specificity 96.5%) in assessing pregnancy outcome than CA 125 or 0-hCG alone (sensitivity 78.9% and 57.9%, respectively; specificity 75.8% and 86.2%, respectively). CONCLUSIONS: Our findings are in accordance with the hypothesis of a tropho-decidual origin of this marker, suggesting its possible usefulness in the prognostic evaluation of first trimester threatened abortion.

Breast cancer necrosis following fine needle aspiration biopsy.

Two cases of mammary carcinoma with nearly complete coagulative necrosis following fine needle aspiration biopsy (FNAB) are described. Although this occurrence rarely complicates a fine needle aspiration procedure, it seems to be a real possibility. Final diagnosis can be problematic and rests on the reassessment of the previous aspirate material, on the ghost architecture outlines of the infarct tumorous lesion and on any viable tissue left at the periphery of the lesion.

Systemic methotrexate treatment in early unruptured ectopic pregnancy.

Ectopic pregnancy is one of the most common and dangerous complications of the early pregnancy period. Until now diagnosis has been late because major symptoms occur after tubal rupture and so only demolitive surgery has been possible. At present, with the appearance of ultrasound in obstetrics an earlier diagnosis of this pathology can be made before tubal rupture so medical treatment has become possible. We treated a series of twelve patients with early ectopic pregnancy (9 tubal and 3 with no localized site of implantation) with intramuscular 0.5 mg/kg methotrexate and oral 0.1 mg/kg of folic acid (Citrovorum Factor) on alternate days, in the attempt to reduce hospitalization and obtain more effective and safer medical management. We observed a fall in serum beta-HCG levels after one cycle of treatment in 11 out of 12 patients and after two cycles of therapy in the remaining case. Minimal side-effects were observed in four cases. Three pregnancies occurred after treatment before the advised interval time and ended in blighted ovum. Methotrexate systemic therapy can be considered an elective treatment and a sufficiently safe management in early unruptured ectopic pregnancy when a good clinical selection of patients is performed.

Progesterone immunosuppressive levels and luteal steroid profiles in the cycles induced with clomiphene citrate.

Several studies have focused their attention on the possible interferences of the endocrine with the immunity system; these interrelations have been summoned to explain some aspects of the implantation. It has already been demonstrated that progesterone could play an immunosuppressive role, allowing the implantation of allotransplantation. However, the individual plasmatic levels of the substance needed to produce that effect still unknown. With the aim of determining the certain immunosuppressive progesterone levels in women with normal ovulatory function, and in order to determine if the other principal steroids might also have immunosuppressive effects, in 47 women affected by sine causa infertility, treated with 100 mg. die of Clomiphene Citrate (from day 3 to day 7) we evaluated the plasma levels of progesterone, 17-OH-Progesterone and 17 beta-Estradiol. The assays were made on the 7th, 11th and 14th post-ovulation days both in women who conceived (immunosuppressive effect present) and in women who did not achieve pregnancy (immunosuppressive effect absent). The results achieved showed a significant difference only in the progesterone values, while those of the other steroids were not significantly different, indicating thus that progesterone is the main element responsible for the immunosuppressive phenomenon and that the seriated evaluation in the luteal phase of this steroid could be used as a marker of achieved implantation.

Preterm labour and neonatal parameters.

OBJECTIVES: Our objective was to identify those neonatal factors associated with survival in preterm infants. MATERIAL AND METHODS: We examined a population of 457 preterm newborns delivered between 1 January-31 December 1990, with birthweight between < 1000 gr and > 2000 gr, in respect to umbilical pH values, plasmatic glucose values, 5-minute Apgar score and gestational age. Data were abstracted from the maternal intrapartum records and the neonatal records, with specific attention to neonatal parameters. RESULTS: A positive correlation between birthweight and 5-minute Apgar score, between birthweight, pH and glucose values was noted. No such relationship existed between pH values and 5-minute Apgar score. Within birthweight groups the distribution of neonatal mortality rate was 85.18% in ELBW (Extremely Low Birth Weight) and only 5.26% in LBW (Low Birth Weight). CONCLUSION: The importance of the echographic estimate of the fetal weight must be emphasized, since a birthweight of 1500 gr represents the cut-off for the neonatal morbidity and mortality, and also an accurate clinical evaluation of the risk of preterm labour or pathologies in order to improve the estimate of childbirth timing.

Transvaginal ultrasonographic diagnosis of adenomyosis in female patients suffering from uterine fibromatosis.

Adenomyosis is an underestimated pathology frequently responsible of unknown origin pelvic pain and uterine enlargement. It is hyperestrinic condition with poor specific symptomatology and preoperative diagnostic tools are very few. The most important of them, ultrasound, has improved its diagnostic capacity with the introduction of transvaginal way of examination. However, for the ultrasound resemblance, the common etiopathogenetic origin and the symptomatologic likeness between adenomyosis and uterine leiomyomatosis, a problem still open is the differential diagnosis between these two pathologies especially when both are present in the same subject. In our study where the preoperative ultrasound was followed by surgical finding, we try to give some ultrasonographical guidelines to discern among these two pathologic conditions.

[Clinical evaluation of DHEA-S plasma levels and possible therapeutic value of the hormone in the third trimester]. / Valutazione clinica dei livelli plasmatici di DHEA-S e del possibile ruolo terapeutico dell'ormone nel III trimestre di gravidanza.

Three groups of women were studied. The first included women without obstetric or systemic pathology; in these, plasma concentrations of progesterone, E, and DHEA-S were assayed at 30-40 weeks of pregnancy. The second group comprised women after physiological first delivery at term, and in these the plasma levels of the same hormones were assessed. In the third group, comprising women at 38 weeks of pregnancy with unripened cervix and DHEA-S plasma levels that were by 1-2 weeks below those of women with ripened cervix of the same gestational age, the effect of repeated perfusion with DHEA-S was examined.

[The pharmacological options for an immediate intervention in threatened premature labor]. / Opzioni farmacologiche per un intervento immediato nella minaccia di parto pretermine.

The following preparations, with different mechanism of action, have been comparatively tested for induction of immediate tocolysis in case of threatened preterm labour: Hyoscine butylbromide, ritodrine, ketoprofen and the association of ritodrine with ketoprofen. Hyoscine butylbromide was found to be very easy to handle, but its myolytic effect is modest. Ritodrine and ketoprofen have shown a high and quantitatively similar tocolytic power. But even better results have been achieved with the association of ritodrine with ketoprofen which has shown a total myolytic effect. The authors suggest some hypotheses concerning the mechanism of action of these drugs, and some precautions for their correct clinical use.

[Diagnostic possibility in neonatal bacterial infections]. / Possibilità diagnostiche nelle infezioni batteriche neonatali.

Bacterial infections in neonates may be acquired in utero, as is the case in congenital syphilis, or after delivery, such as late onset B streptococcal meningitis. Although some infections remain localized and may even be self-limiting, the majority of neonatal bacterial infections require speedy diagnosis and immediate and appropriate treatment. Severe invasive bacterial infections are rare but catastrophic; they are more common in intensive care wards. Neonatal, maternal, and environmental factors favoring bacterial infections are discussed together with their main clinical features. Useful diagnostic parameters are examination of the placenta, leukocyte counting, erythrocyte sedimentation rate, and C-reactive protein. If a bacterial infection is suspected in a baby that is sick or in poor general condition (low birth weight, therapies, environmental conditions) a "septic therapeutic approach" must be adopted which includes examination and culture of blood, cerebrospinal fluid, and urine, as well as of any other suitable material according to clinical and laboratory findings. Pathogens most frequently involved in neonatal infections (streptococci, staphylococci, Listeria, gram-negative enteral bacteria) can be presumptively identified by comparatively simple laboratory tests. The valid interpretation of the results of these tests is dependent upon the degree to which the laboratory personnel is familiar with techniques of identification and assessment of sensitivity, as well as on the close cooperation between clinical department and laboratory from the start and all along the course of the disease.

[An increase in the median plasma values of progesterone in luteal deficiencies treated with clomifene citrate in the early follicular phase]. / Incremento dei valori plasmatici medi di progesterone nei difetti luteali trattati con citrato di clomifene in fase follicolare precoce.

A clinical study performed during 265 cycles in 63 normo-ovulating and normo-menstruating patients, of whom 27 with a luteal phase defect (LPD), assessed by morphological, hormonal, echographic and clinic criteria. These were given Clomiphene Citrate, 100 mg per day from the second to sixth day of the cycle, for a total of 108 cycles. The other 36 patients, without any luteal abnormality, were utilized as a control group during 156 cycles. At the end of the study there were no significant differences in hormonal, echographic and morphological parameters between the two groups.

CA-125 and ovarian hyperstimulation.

The ovarian hyperstimulation syndrome (OHSS) has become more and more frequent in relation to the spread of the method of superovulation by means of pharmacologic induction and consequently the necessity of measures suitable for preventing and controlling it has been more and more improved. Among them the discovery of indicators which could reveal as early and sensitive as possible the onset and, when it is possible, also the degree of severity of this syndrome, holds an important position. Till now only the serum estradiol concentration performed this task, among the other things, in an incomplete and not-well defined manner, but its inadequacy has stimulated once again the search for new substances which would allow attention to be drawn to the development, entity and evolution of this syndrome in compliance with necessary requisites with greater timeliness, and tenacity. Therefore the behaviour of the serum CA-125 levels has been evaluated for the first time in 31 cycles of 31 patients, which were stimulated by gonadotropins (FSH, FSH/LH, HCG), of which 21 underwent ovarian hyperstimulation of various degree (10 of I, 8 of II and 3 of III grade), while the other 10 had no complications. The blood levels of this marker rose above the limit considered physiological (35 UI/ml) during the luteal phase in all the stimulated cycles and, in hyperstimulated ones always exceeded 70 UI/ml; in addition the serum CA-125 levels correlated very well with ovarian dimensions, degree of severity of the syndrome and estrogenic concentrations during only luteal phase, in the hyperstimulated cycles and continued to remain high or even increased in case of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)