Norethindrone acetate versus extended-cycle oral contraceptive (Seasonique®) in the treatment of endometriosis symptoms: A prospective open-label comparative study.

INTRODUCTION: This patient preference prospective study was designed to compare patients' satisfaction in women with endometriosis treated either by an extended-cycle oral contraception (OC) or by norethindrone acetate (NETA). METHODS: This patient preference prospective study included women of reproductive age with endometriosis. Patients were submitted to one of the following 12 months' treatments: Group A, continuous oral treatment with NETA (2.5 mg/day) and Group B, a 91-day extended-cycle OC (LNG/EE 150/30 mcg for 84 days and EE 10 mcg for 7 days). Patient satisfaction was the primary endpoint. RESULTS: There was no statistically significant difference in the rate of satisfied patients at 12-month follow up between the two study groups, 82.2% and 68.4% in Group A and Group B respectively (p = 0.143). At 6 and 12-months, there was a significant amelioration in the intensity of all pain in both groups. The median number of days of unscheduled bleeding during the first cycle was significantly higher in Group B compared to Group A. CONCLUSION: Both NETA and extended-cycle OC are effective in treating pain symptoms related to endometriosis. Extended-cycle OC may cause more unscheduled bleeding, but the rate of satisfaction for those who completed the treatment was similar in the two groups.

Interpersonal sensitivity and persistent attenuated psychotic symptoms in adolescence.

Interpersonal sensitivity defines feelings of inner-fragility in the presence of others due to the expectation of criticism or rejection. Interpersonal sensitivity was found to be related to attenuated positive psychotic symptom during the prodromal phase of psychosis. The aims of this study were to examine if high level of interpersonal sensitivity at baseline are associated with the persistence of attenuated positive psychotic symptoms and general psychopathology at 18-month follow-up. A sample of 85 help-seeking individuals (mean age = 16.6, SD = 5.05) referred an Italian early detection project, completed the interpersonal sensitivity measure and the structured interview for prodromal symptoms (SIPS) at baseline and were assessed at 18-month follow-up using the SIPS. Results showed that individuals with high level of interpersonal sensitivity at baseline reported high level of attenuated positive psychotic symptoms (i.e., unusual thought content) and general symptoms (i.e., depression, irritability and low tolerance to daily stress) at follow-up. This study suggests that being "hypersensitive" to interpersonal interactions is a psychological feature associated with attenuated positive psychotic symptoms and general symptoms, such as depression and irritability, at 18-month follow-up. Assessing and treating inner-self fragilities may be an important step of early detection program to avoid the persistence of subtle but very distressing long-terms symptoms.

Influence of adenomyosis on pregnancy and perinatal outcomes in women with endometriosis.

OBJECTIVES: Several studies have investigated the correlation between endometriosis and adverse pregnancy and perinatal outcomes. However, the role of adenomyosis as a risk factor for adverse perinatal outcome in women with endometriosis has yet to be established. The aim of this study was to explore if fetal and maternal outcomes, in particular the incidence of a small-for-gestational-age (SGA) infant, are different in pregnant women with endometriosis only from in those with the concomitant presence of diffuse or focal adenomyosis. METHODS: This was a retrospective analysis of data collected prospectively during a 3-year period. We included 206 pregnant women with endometriosis: 148 (71.8%) with endometriosis only, 38 (18.4%) with focal adenomyosis and 20 (9.7%) with diffuse adenomyosis. Adenomyosis was diagnosed using ultrasonography and was classified as focal or diffuse. The study included patients who conceived spontaneously or by an assisted reproductive technique. Demographics, ultrasound variables and outcome were compared between women with endometriosis only and those with diffuse and those with focal adenomyosis. Logistic regression analysis was performed to assess the association of variables with SGA at birth in women with diffuse and those with focal adenomyosis. RESULTS: The three groups were similar in demographic characteristics (age, body mass index, mode of conception). Patients with diffuse adenomyosis compared with those with endometriosis only had significantly lower pregnancy-associated plasma protein A (0.61 vs 0.88 multiple of the median, P < 0.001), higher mean uterine artery pulsatility index in the first (2.23 vs 1.67, P < 0.001) and second (1.30 vs 0.94, P < 0.001) trimesters of pregnancy, and higher incidence of SGA (40% vs 10.8%, P < 0.001). No statistically significant differences were found in patients with focal adenomyosis compared with those with endometriosis only. Logistic regression analysis demonstrated that diffuse adenomyosis (odds ratio = 3.744; 95% CI, 1.158-12.099; P = 0.027) was the only independent risk factor for SGA. CONCLUSIONS: The presence of diffuse adenomyosis in pregnant women with endometriosis is strongly associated with delivery of a SGA infant. Women with diffuse adenomyosis should be treated as being at high risk of placental dysfunction, and these pregnancies might therefore need closer monitoring. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Magnetic resonance enema vs rectal water-contrast transvaginal sonography in diagnosis of rectosigmoid endometriosis.

OBJECTIVE: To compare the accuracy of magnetic resonance enema (MR-e) and rectal water-contrast transvaginal sonography (RWC-TVS) in the diagnosis of rectosigmoid endometriosis. METHODS: This prospective study included 286 patients of reproductive age with clinical suspicion of rectosigmoid endometriosis. Patients underwent MR-e and RWC-TVS before laparoscopic excision of endometriotic lesions. The findings of MR-e and RWC-TVS were compared with surgical and histological results. RESULTS: Of the 286 patients included in the study, 151 (52.8%) had rectosigmoid endometriosis. MR-e and RWC-TVS had similar accuracy in the diagnosis of rectosigmoid endometriosis (P = 0.063). In the diagnosis of rectosigmoid endometriosis with MR-e, the sensitivity was 95.4% (95% CI, 90.7-99.1%), specificity was 97.8% (95% CI, 93.6-99.5%), positive predictive value (PPV) was 98.0% (95% CI, 94.1-99.6%), negative predictive value (NPV) was 95.0% (95% CI, 89.9-97.9%), positive likelihood ratio (LR+) was 42.91 (95% CI, 14.01-131.46) and negative likelihood ratio (LR-) was 0.05 (95% CI, 0.02-0.10). For diagnosis with RWC-TVS, sensitivity was 92.7% (95% CI, 87.3-96.3%), specificity was 97.0% (95% CI, 92.6-99.2%), PPV was 97.2% (95% CI, 93.0-99.2%), NPV was 92.3% (95% CI, 86.6-96.1%), LR+ was 31.29 (95% CI, 11.90-82.25) and LR- was 0.08 (95% CI, 0.04-0.13). MR-e and RWC-TVS underestimated the size of the endometriotic nodules; for both imaging techniques the underestimation was greater for nodules with a diameter ≥ 30 mm. There was no significant difference in the mean intensity of pain experienced by the patients during the two examinations. CONCLUSIONS: RWC-TVS should be the first-line investigation in patients with clinical suspicion of rectosigmoid endometriosis and physicians should be trained in performing this examination. Considering that MR-e is more expensive than RWC-TVS, it should be used only when the findings of RWC-TVS are unclear. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Computed tomographic colonography vs rectal water- contrast transvaginal sonography in diagnosis of rectosigmoid endometriosis: a pilot study.

OBJECTIVES: To compare the performance of computed tomographic colonography (CTC) and rectal water-contrast transvaginal sonography (RWC-TVS) in the diagnosis of rectosigmoid endometriosis, and compare precision in estimating the length of the rectosigmoid nodules and the distance between the nodules and the anal verge. METHODS: This prospective study included 70 patients of reproductive age with clinical suspicion of rectosigmoid endometriosis. Patients underwent RWC-TVS and CTC before laparoscopic excision of endometriotic nodules. The findings of RWC-TVS and CTC were compared with surgical and histological results. RESULTS: Of the 70 patients included in the study, 40 (57.1%) had rectosigmoid endometriosis. CTC and RWC-TVS had similar accuracy in the diagnosis of rectosigmoid endometriosis (P = 0.508) and similar precision in estimating the length of the endometriotic nodules (P = 0.077). CTC was more precise than RWC-TVS in estimating the distance between the rectosigmoid nodule and the anal verge (P < 0.001). The intensity of pain experienced during CTC was higher than that perceived during RWC-TVS (P < 0.001); however, intestinal distension for CTC was well-tolerated in all patients without significant adverse effects. CONCLUSIONS: RWC-TVS and CTC have similar accuracy in the diagnosis of rectosigmoid endometriosis and similar precision in estimating the size of the nodules; however, CTC is more precise than RWC-TVS in estimating the distance between the nodules and the anal verge, yet patients tolerate RWC-TVS better than CTC. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Efficacy of safety catheter devices in the prevention of occupational needlestick injuries: applied research in the Liguria Region (Italy).

Healthcare workers who use or may be exposed to needles are at risk of needlestick injuries, which can lead to serious infections by bloodborne pathogens. These injuries can be avoided by eliminating the unnecessary use of needles and using safety devices. The present study was aimed at evaluating the impact of a safety-engineered device, with passive fully automatic needlestick protection, on the rate of needlestick injuries among healthcare workers. The setting of the study was a network of five public healthcare institutions situated in a Northern Italian Region. Data on the type of device, the number of employees and the number of catheter devices used per year were collected through regular meetings with healthcare workers over a period of five years. The most notable result of this study was the huge risk reduction associated with safety devices. Indeed, the risk of needlestick injuries due to conventional devices was found to be 25-fold higher than that observed for safety devices. However, it is noteworthy that a considerable part of this excess can be explained by the different background number of devices used. Moreover, descriptive analysis suggested that individuals with a poor/moderate training level had a lower risk than those with good/high training, though the difference was not statistically significant. In conclusion, there is convincing evidence of a causal connection between the introduction of safety devices and the reduction in needlestick injuries. This consideration should prompt the introduction of safety devices into daily clinical practice.

Group 3 innate lymphoid cells regulate neutrophil migration and function in human decidua.

Innate lymphoid cells (ILCs) have a central role in innate defenses against pathogens, lymphoid organogenesis, and tissue remodeling. They have been detected in human decidua, however, their role in this tissue remains unclear. Successful pregnancy requires an early inflammatory phase favoring implantation and tissue remodeling as well as a subsequent regulatory phase to prevent fetal rejection and supporting neoangiogenesis. Here, we show that, during the first trimester of pregnancy, neutrophils infiltrate decidua basalis and are more abundant in normal pregnancy than in spontaneous miscarriages. Decidual neutrophils localize in proximity of NCR+ILC3, which may influence neutrophil migration and survival given their production of CXCL8 and granulocyte macrophage colony-stimulating factor (GM-CSF). Moreover, NCR+ILC3-derived GM-CSF was found to induce the expression of heparin-binding EGF-like growth factor and IL1ra in neutrophils, two proteins/cytokines involved in tissue remodeling and maintenance of pregnancy. Our data suggest that the simultaneous presence of NCR+ILC3 and neutrophils in decidual tissues and their possible cross talk, may have a role in the early phases of pregnancy.

Programmed intermittent epidural bolus versus continuous epidural infusion for pain relief during termination of pregnancy: a prospective, double-blind, randomized trial.

BACKGROUND: Pain is a major concern during medical abortion but no evidence-based recommendations for optimal analgesia during medical termination of pregnancy are available. We compared two methods of epidural analgesia during second trimester termination of pregnancy, with the primary aim of assessing the incidence of motor block. METHODS: Women were randomly assigned to receive continuous epidural infusion (CEI Group; n=52) or programmed intermittent epidural bolus (PIEB Group; n=52). Assessment of motor block was performed every hour. Patients with a modified Bromage score <6 were considered to have motor block. RESULTS: Motor block occurred more frequently in the CEI Group compared with the PIEB Group (46.2% vs. 5.8%, P<0.001). Pain scores were low and comparable between groups. Patients in the CEI Group experienced nausea more frequently than those in the PIEB Group (34.6% vs. 13.5%, P=0.022). The degree of satisfaction was higher in the PIEB Group compared with the CEI Group. CONCLUSIONS: During second trimester termination of pregnancy in our patient groups, a programmed intermittent epidural bolus technique was associated with less motor block and greater patient satisfaction than continuous epidural infusion. Both techniques had similar analgesic efficacy.

Aberrant right subclavian artery in fetuses with Down syndrome: a systematic review and meta-analysis.

OBJECTIVES: The primary objective was to estimate the prevalence of aberrant right subclavian artery (ARSA) in fetuses with Down syndrome. Secondary objectives were to assess the prevalence of ARSA in euploid fetuses, the feasibility of ultrasound evaluation of the right subclavian artery (RSA) in the first and second trimesters of pregnancy, the performance of ARSA in screening for trisomy 21 and its association with other abnormalities. METHODS: Web-based databases (PubMed, EMBASE and MEDLINE) were searched up to July 2014. The STROBE, PRISMA and QUIPS instruments were used to assess all included studies and for reporting of methodology, results and conclusions. Original studies that reported prenatal ultrasound evaluation of ARSA, assessment of its prevalence in Down-syndrome and euploid fetuses, feasibility of ultrasound evaluation of the RSA in the first and second trimesters of pregnancy and correlation of ARSA with other abnormalities were included, excluding duplications and case reports. Collected data were summarized to estimate prevalence and feasibility. A meta-analysis was performed pooling the study-specific positive and negative likelihood ratios (LR+ and LR-), detection rates and false-positive rates for trisomy 21. RESULTS: Prevalence of ARSA in Down-syndrome fetuses was 23.6% (95% CI, 19.4-27.9%), whereas in euploid fetuses it was 1.02% (95% CI, 0.86-1.10%). Ultrasound evaluation of the RSA course and origin in the first and second trimesters of pregnancy was feasible in 85% and 98% of cases (first and second trimester, respectively) and it was directly related to sonographic experience and fetal crown-rump length and inversely related to maternal body mass index. In more than 20% of fetuses with ARSA there was an association with other abnormalities but ARSA seemed to be an independent marker of trisomy 21. The meta-analysis showed that ARSA is a significant risk factor for Down syndrome (pooled LR+ = 26.93, 95% CI, 19.36-37.47, P for effect < 0.001, P for Q = 0.3, I(2) = 17.3%), whereas normal RSA is a significant protective marker (pooled LR- = 0.71, 95% CI, 0.51-0.99, P for effect = 0.043, P for Q = 0.9, I(2) = 0%). CONCLUSIONS: ARSA appears to be a clinically useful prenatal ultrasound marker of Down syndrome. Additional testing when ARSA is diagnosed should involve evaluation of all risk factors by applying a mathematical model. There is insufficient evidence to recommend fetal karyotyping in cases with isolated ARSA. If the background risk is higher or additional markers are present, full fetal karyotyping is advisable, including analysis for 22q11 microdeletion.

Identification of diverse innate lymphoid cells in human decidua.

Innate lymphoid cells (ILCs) are developmentally related cells that play an important role in innate defenses and tissue remodeling. So far, only natural killer (NK) cells have been identified and functionally characterized in human decidua where they contribute to induction of immune suppression, neo-angiogenesis, and tissue building/remodeling. The presence of other ILC subsets in human decidua has not been yet characterized. Here we identify in human decidua, during early pregnancy, two subsets of decidual group 3 ILC (ILC3), including lymphoid tissue inducer (LTi)-like cells and natural cytotoxicity receptors (NCRs)(+)ILC3 and interferon-(IFN)γ-producing ILC1, different from NK cells. Decidual LTi-like cells produced interleukin -17 (IL-17) and tumor necrosis factor (TNF), while NCR(+)ILC3 released IL-22 and IL-8. Importantly, NCR(+)ILC3 and LTi-like cells established functional interactions with stromal cells. Decidual LTi-like cells differentiated into NCR(+)ILC3, whereas they marginally contributed to NK cell generation. Our data suggest that decidual ILC3 may play a role in innate defenses and in vessel and tissue building, thus contributing to maintenance of pregnancy.

Endometriotic ovarian cysts do not negatively affect the rate of spontaneous ovulation.

STUDY QUESTION: Do endometriotic ovarian cysts influence the rate of spontaneous ovulation? SUMMARY ANSWER: Endometriotic cysts, no matter what their volume, do not influence the rate of spontaneous ovulation in the affected ovary. WHAT IS KNOWN ALREADY: Endometriotic ovarian cysts may negatively affect spontaneous ovulation in the affected ovary. STUDY DESIGN, SIZE, DURATION: This was a prospective observational study performed between September 2009 and June 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study included women of reproductive age with regular menstrual cycles and unilateral ovarian endometriomas (diameter ≥20 mm) desiring to conceive. Exclusion criteria were: hormonal therapies in the 3 months prior to study entry and previous adnexal surgery. Patients underwent serial transvaginal ultrasound to assess the side of ovulation (for up to six cycles). MAIN RESULTS AND THE ROLE OF CHANCE: Ovulation was monitored in 1199 cycles in 244 women (age, mean ± SD, 34.3 ± 4.9 years). 55.3% of the patients had left endometriomas and 44.7% had right endometriomas (P = 0.024). The mean (±SD) diameter of the endometriomas was 5.3 cm (±1.7 cm). Ultrasonographically documented ovulation occurred in 596 cycles in the healthy ovary (49.7%; 95% CI, 46.8-52.6%) and in 603 cycles in the affected ovary (50.3%; 95% CI, 47.1-53.2%; P = 0.919). This observation was confirmed in patients with diameter of the cyst ≥4 cm (n = 166) and in those with diameter of the cyst ≥6 cm (n = 45). One hundred and five patients spontaneously conceived (43.0%; 95% CI, 36.7-49.5%). LIMITATIONS, REASON FOR CAUTION: The high pregnancy rate reported in this study was observed in a selected population of women with endometriomas and cannot be extrapolated to all patients with endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: Since ovarian endometriomas do not impair spontaneous ovulation, the impact on fertility of surgical excision of ovarian endometriomas should be further investigated.

Mitochondrial DNA in Day 3 embryo culture medium is a novel, non-invasive biomarker of blastocyst potential and implantation outcome.

In assisted reproduction technology, embryo competence is routinely evaluated on morphological criteria. Over the last decade, efforts in improving non-invasive embryo assessment have looked into the secretome of embryos. Human embryos release genomic DNA (gDNA) and mitochondrial DNA (mtDNA) into the culture medium, and the mtDNA/gDNA ratio is significantly correlated with embryo fragmentation. Here, we investigate whether mtDNA/gDNA ratio in embryo spent medium is correlated with blastulation potential and implantation. The mtDNA/gDNA ratio was assessed in 699 Day 3 culture media by quantitative polymerase chain reaction (qPCR) to investigate its correlation with embryo morphology, blastocyst development and implantation. A logistic regression model evaluated whether mtDNA/gDNA ratio in the secretome may improve the prediction of blastulation. We found that embryos that successfully developed into blastocysts exhibited a significantly higher mtDNA/gDNA ratio in the culture medium compared with those that arrest (P = 0.0251), and mtDNA/gDNA, combined with morphological grading, has the potential to predict blastulation better than morphology alone (P = 0.02). Moreover, mtDNA/gDNA ratio was higher in the media from good-quality embryos that reached the full blastocyst stage on Day 5 compared with those that developed more slowly (P < 0.0001). With respect to blastocyst morphology, higher trophectoderm quality was associated with a higher mtDNA/gDNA ratio in the culture medium. Finally, a high mtDNA/gDNA ratio in spent medium was associated with successful implantation outcome (P = 0.0452) of good-quality embryos. In summary, the mtDNA/gDNA ratio in the Day 3 embryo secretome, in combination with morphological grading, may be a novel, non-invasive, early biomarker to improve identification of viable embryos with high developmental potential.

Mitochondrial DNA content in embryo culture medium is significantly associated with human embryo fragmentation.

STUDY QUESTION: Is the amount of cell-free DNA released by human embryos into culture medium correlated with embryo morphological features? SUMMARY ANSWER: The mitochondrial DNA (mtDNA) content of culture medium is significantly associated with the fragmentation rate on Days 2 and 3 of embryo development, whether the oocyte came from women ≤ 35 or >35 years old. WHAT IS KNOWN ALREADY: Cellular fragmentation is often utilized as one of the morphological parameters for embryo quality assessment. The amount of cellular fragments is considered to be an important morphological parameter for embryo implantation potential. It has been hypothesized that fragments are apoptotic bodies or anuclear cytoplasmatic pieces of blastomeres, although no definitive conclusion has been drawn about their pathogenesis. STUDY DESIGN, SIZE, DURATION: Human fertilized oocytes were individually cultured from Day 1 to Days 2 and 3. A total of 800 samples (166 spent media from Day 2 and 634 from Day 3) were enrolled into the present study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Double-stranded DNA (dsDNA) was quantified in 800 spent embryo culture media by Pico Green dye fluorescence assay. After DNA purification, genomic DNA (gDNA) and mtDNA were profiled by specific quantitative PCR. Statistical analyses defined correlations among DNA contents, embryo morphology and maternal age. MAIN RESULTS AND THE ROLE OF CHANCE: Different independent tests confirmed the presence of DNA into embryo culture medium and, for the first time, we demonstrate that both gDNA and mtDNA are detectable in the secretome. The amount of DNA is larger in embryos with bad quality cleavage compared with high-grade embryos, suggesting that the DNA profile of culture medium is an objective marker for embryo quality assessment. In particular, DNA profiles are significantly associated with fragmentation feature (total dsDNA: P = 0.0010; mtDNA; P = 0.0247) and advanced maternal age. LIMITATIONS, REASONS FOR CAUTION: It is necessary to establish whether DNA profiling of spent embryo culture medium is a robust onsite test that can improve the prediction of blastulation, implantation and/or pregnancy rate. WIDER IMPLICATIONS OF THE FINDINGS: The approach we are proposing may provide a novel, non-invasive, objective tool for embryo quality grading. The correlation between a high mtDNA concentration and the fragmentation rate of embryos is suggestive that fragments are mainly anuclear cytoplasmatic debris arising during cleavage. Therefore, blastomere shaping as an early event during in vitro development may play a homeostatic role and be related to embryo competence. STUDY FUNDING/COMPETING INTEREST: This project was funded by Merck Serono (Grant for Fertility Innovation 2011). The sponsor had no role in study design, data collection, data analysis, data interpretation and writing of the paper. Authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01397136.

Pemetrexed disodium in ovarian cancer treatment.

INTRODUCTION: Current therapies for recurrent ovarian cancer (OC) yield relatively modest improvements in survival. Many drugs are available but recently a renewed interest is addressed on antimetabolite drugs. Pemetrexed (PEM) is a multitargeted antifolate cytotoxic agent mainly used in lung cancer. AREAS COVERED: This review summarizes the available evidence on the use of PEM in the treatment of OC. This article consists of material obtained via Medline, PubMed and EMBASE literature searches, up to November 2011. Currently available published data on mechanism of action, pharmacokinetics, safety and efficacy of PEM in the treatment of recurrent OC are described. EXPERT OPINION: Eight trials evaluated the use of PEM in OC patients. Studies using PEM in combination with carboplatin in platinum-sensitive OC suggested that the response rate is similar to other combination therapies. However, based on the absence of randomized trials comparing this doublet with currently used combination treatments, it is difficult to draw conclusions on the efficacy of PEM regimens in these patients. In platinum-resistant OC patients, two studies suggested that PEM alone might have equivalent activity to other single-agent treatment. Further pharmacogenomic and clinical data are warranted to better define the role of PEM in the treatment of recurrent OC.

Relation between maternal thrombophilia and stillbirth according to causes/associated conditions of death.

OBJECTIVE: To investigate maternal thrombophilia in cases of Stillbirth (SB), also an uncertain topic because most case series were not characterised for cause/associated conditions of death. STUDY DESIGN: In a consecutive, prospective, multicentre design, maternal DNA was obtained in 171 cases of antenatal SB and 326 controls (uneventful pregnancy at term, 1:2 ratio). Diagnostic work-up of SB included obstetric history, neonatologist inspection, placenta histology, autopsy, microbiology/chromosome evaluations. Results audited in each centre were classified by two of us by using CoDAC. Cases were subdivided into explained SB where a cause of death was identified and although no defined cause was detected in the remnants, 64 cases found conditions associated with placenta-vascular disorders (including preeclampsia, growth restriction and placenta abruption - PVD). In the remnant 79 cases, no cause of death or associated condition was found. Antithrombin activity, Factor V Leiden, G20210A Prothrombin mutation (FII mutation) and acquired thrombophilia were analysed. RESULTS: Overall, the presence of a thrombophilic defect was significantly more prevalent in mothers with SBs compared to controls. In particular, SB mothers showed an increased risk of carrying Factor II mutation (OR=3.2, 95% CI: 1.3-8.3, p=0.01), namely in unexplained cases. Such mutation was significantly associated also with previous SB (OR=8.9, 95%CI 1.2-70.5). At multiple logistic regression, Factor II mutation was the only significantly associated variable with SB (adj OR=3.8, 95% CI: 1.3-13.5). CONCLUSION: These data suggest that Factor II mutation is the only condition specifically associated with unexplained SB and could represents a risk of recurrence. PVD-associated condition is unrelated to thrombophilia.