Search

Study question Could factors inherent to individual centers, related to local clinical or laboratory variables, play a role in the increased incidence of monozygotic twins in IVF? Summary answer The rate of MZT did not significantly vary among IVF centers What is known already The risk of monozygotic twins (MZT) is increased in couples undergoing in vitro fertilization (IVF). Several systematic reviews have investigated the possible determinants linked to IVF, but results obtained have been inconclusive. Associations have been identified with the prolonged culture at blastocyst stage and young female age. Conventional IVF compared to ICSI, and assisted hatching emerged as possible additional risk factors, but evidence is controversial. Meta-analyses, however, cannot provide robust evidence because of the difficulty in performing multivariate analyses. Moreover, available investigations were retrospective and involved relatively small sample sizes hampering the quality of the collected data. Study design, size, duration This is a multicenter retrospective cohort study using the Italian ART National Registry database and involving the Centers reporting data from individual IVF cycles from 2015 to 2019. Eighteen IVF centers were included with a total of 87,076 IVF cycles reported during the study period. The primary aim of the study was to investigate whether the incidence of MZT differed among centers. Participants/materials, setting, methods Only single embryo transfer cycles were considered. Women who had sex-discordant twin deliveries were excluded. MZT rate was calculated as the number of multiple pregnancies out of the total number of clinical pregnancies. A binomial distribution model was used to determine the 95% CI of the frequency of MZT. The rates among centers were deemed heterogeneous if the 95% CI in at least one center did not include the mean MZT rate. Main results and the role of chance Ten centers reported data from 2015 to 2019, eight from 2017 to 2019. An analysis of the main characteristics of the centers revealed considerable variability. The total number of clinical pregnancies fulfilling our inclusion criteria were 10,440. Of these, 7 were found to be twin pregnancies with discordant gender and were excluded, leaving 10,433 for data analyses. The number of cases included per center varied between 11 and 2,823. Overall, 162 pregnancies were found to be multiple: 48 ended in a miscarriage, 28 spontaneously reduced to singletons and 86 women delivered two or more newborns. The vast majority were twins (n = 160), one was triplet, and one was quadruplet. Considering the denominator of 10,433 pregnancies, the rate of MZT was thus 1.5% (95%CI: 1.3 - 1.8%). The MZT rate among centers varied between 0% (95%CI: 0.0 - 25.9%) and 3.2% (95%CI: 1.3 - 8.1%). All the 95%CIs of the rates of MZT include the 1.5% common rate, thus rejecting the hypothesis that this incidence significantly differed among centers. Spearman correlations between the rate of MZT and variables associated with individual center policies could not identify any significant association. Even when restricting the analyses only to the largest centers, no association emerged. Limitations, reasons for caution Our study was limited by its retrospective nature. Furthermore, some centers provided less than 100 cases for data analysis and were therefore poorly informative. External confirmation from larger registries is therefore required. Wider implications of the findings This study provides evidences that the rate of MZT did not differ among IVF centers. Furthermore, no clinical and laboratory variables inherent to individual centers were identified in the determinism of IVF-associated MZT. Further studies are needed to identify the causes of increased risk of MZT in IVF practice. Trial registration number not applicable

Saponins represent a promising class of vaccine adjuvant. Together with the TLR4-ligand MPL, QS-21 is part of the Adjuvant System AS01, a key component of the malaria and zoster candidate vaccines that display demonstrated clinical efficacy. However, the mechanism of action of QS-21 in this liposomal formulation is poorly understood. Upon intra-muscular immunisation, we observed that QS-21 rapidly accumulated in CD169(+) resident macrophages of the draining lymph node where it elicited a local innate immune response. Depletion of these cells abrogated QS-21-mediated innate cell recruitment to the lymph node, dendritic cell (DC) phenotypic maturation as well as the adjuvant effect on T-cell and antibody responses to co-administered antigens. DCs rather than lymph node-resident macrophages were directly involved in T-cell priming by QS-21, as revealed by the decrease in antigen-specific T-cell response in Batf3(-/-) mice. Further analysis showed that the adjuvant effect of QS-21 depended on the integration of Caspase-1 and MyD88 pathways, at least in part through the local release of HMGB1. Taken together, this work unravels the key role of lymph node sentinel macrophage in controlling the adjuvant effect of a molecule proven to improve vaccine response in humans., SCOPUS: ar.j, info:eu-repo/semantics/published

Between January 1996 and December 2001, at the Department of Gynecology, Perinatology and Human Reproduction of the University of Florence, 49 ectopic pregnancies were submitted to medical treatment. The treatment schedule consisted of the administration of 100 mg of intravenous methotrexate (MTX). The patients included in this study fulfilled the following requisites: gestational period8 weeks; diameter of the ectopic gestational sac4 cm; serum level of human chorionic beta-gonadotropin (beta-hCG)5000 IU/ml; absence of clinical and ultrasound signs of tube rupture with initial hemoperitoneum; hematochemical tests compatible with chemotherapic treatment. All patients were followed with a dosage of serum beta-hCG repeated every 2-3 days after chemotherapy and with an ultrasound every 3-4 days. In case of documented success of treatment the patient was hospitalized for no more than 3 days after administration of the drug. In 1 case therapy took place in a day-hospital regimen. Medical treatment was effective in 35 patients out of 49 (71.4%) and led to negative beta-hCG in a median time of 11 days, with a range between 2 and 48 days. In the 14 non-responsive cases (28.6%), after a mean time of 6 days we proceeded to a traditional surgical approach or laparoscopy. In none of the cases did we find significant pharmacological toxicity, while in 9 patients (18.3%), severe painful symptoms appeared immediately after treatment, but resolved within 24 hours. Our results are interesting and in agreement with other experiences found in the literature. In our opinion, the advisability of a second administration in case of slow response, the comparison with an analogous intramuscular treatment, a more precise definition of the eligibility criteria, long-term follow-up of the patients, especially in case of subsequent pregnancies should all be further considered.

Background Questions remain as to whether surgical excision of ovarian endometriomas might cause damage to ovarian function. To test the hypothesis that ovarian surgery for endometrioma compromises ovarian function and accelerates ovarian failure. Methods In a tertiary university Clinic, longitudinal prospective cohort study. Patients who underwent laparoscopy for endometriosis between March 1993 and November 2007 were assessed for inclusion in the study. A prospective follow-up at 3, 6 and 12 months then yearly was conducted. Evolution of menstrual pattern, symptoms and reproductive outcomes were investigated. Results From over the 14-year period, 302 patients were included in the study. The mean age (±SD) of patients was 32.6 ± 5.6 years; the median duration of follow-up was 8.5 years (range 2-17 years). Menopause was documented in 43 women (14.3%) at a mean age of 45.3 ± 4.3 years (range 32-52 years). Women previously submitted to bilateral cystectomy were younger at menopause than those with monolateral endometrioma (42.1 ± 5.1 years versus 47.1 ± 3.5 years, P = 0.003). Premature ovarian failure (POF) was observed in 7 of 43 (16.3%) menopausal patients; the majority (4, 57.1%) after bilateral cystectomy. The relationship between the preoperative ovarian endometriomas total diameter and menopausal age was significant in case of surgery for bilateral endometriomas (R(2) = 0.754, P = 0.002). Conclusions Patients who had been operated on for bilateral endometriomas have an increased risk of POF. Ovarian parenchyma loss at the time of surgery seems related to cyst diameter. In the case of unilateral ovarian endometrioma, the contralateral intact ovary might adequately compensate.