Carlo Ticconi - Academia.edu (original) (raw)
Papers by Carlo Ticconi
Reproductive sciences, Apr 15, 2024
The current knowledge on adenomyosis as a risk factor for RPL is very scant. Overall 120 women we... more The current knowledge on adenomyosis as a risk factor for RPL is very scant. Overall 120 women were included in this retrospective observational study. They were divided in three groups each of which consisted of 40 subjects: Group 1: women with RPL who were diagnosed to have adenomyosis on transvaginal ultrasound (TVS); Group 2: patients with RPL without ultrasonographic findings of adenomyosis; Group 3: patients with ultrasound diagnosis of adenomyosis without RPL and at least one live birth pregnancy. The copresence of endometriosis was also investigated. Among women with RPL, patients with adenomyosis (Group 1) had higher number of pregnancy losses (p = 0.03) and lower age at first pregnancy loss (p = 0.03) than women without adenomyosis (Group 2). Moreover, they had more frequently primary RPL (p = 0.008). Adenomyosis of the inner myometrium was found more frequently (p = 0.04) in patients of Group 1 than in patients of Group 3 in which adenomyosis was mainly in the outer myometrium (p= 0.02). No differences were found in the severity of adenomyosis between these two groups of women. TVS findings for endometriosis were observed more frequently in women with adenomyosis without RPL (Group 3) than in the other two groups of patients. Adenomyosis can be a factor involved in RPL. Differences in adenomyosis localization are associated with different risks for RPL. Patients with RPL should be investigated for the presence of adenomyosis and also for the type and localization of the disease in the different myometrial layers.
International journal of molecular sciences, Feb 29, 2024
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Major depressive disorder (MDD) and osteoporosis are two common disorders with high morbidity and... more Major depressive disorder (MDD) and osteoporosis are two common disorders with high morbidity and mortality rates. Conflicting data have found associations between MDD and low bone mineral density (BMD) or osteoporosis, although causative factors are still unclear. A pilot study was designed with the aim to assess the relationship between MDD and BMD in postmenopausal women with MDD compared to healthy volunteers. We hypothesized that attachment style (AS) mediated this relationship.
PubMed, Oct 12, 2016
Introduction: Major depressive disorder (MDD) and osteoporosis are two common disorders with high... more Introduction: Major depressive disorder (MDD) and osteoporosis are two common disorders with high morbidity and mortality rates. Conflicting data have found associations between MDD and low bone mineral density (BMD) or osteoporosis, although causative factors are still unclear. A pilot study was designed with the aim to assess the relationship between MDD and BMD in postmenopausal women with MDD compared to healthy volunteers. We hypothesized that attachment style (AS) mediated this relationship. Methods: The sample was made of 101 postmenopausal women, 49 with MDD and 52 age-matched healthy volunteers. Structured clinical interview and Beck Depression Inventory (BDI) were performed to assesse MDD. AS was evaluated using the Relationship Questionnaire (RQ). BMD was measured by dual energy X-ray absorptiometry. Results: The univariate analysis showed that women with MDD had lower BMD values as compared to healthy volunteers. In the regression models MDD diagnosis and BDI score were not significant predictors of low BMD. The “preoccupied” pattern of insecure AS was a significant, independent predictor of decreased BMD in all skeletal sites: lumbar spine (p=0.008), femoral neck (p=0.011), total hip (p=0.002). Conclusions: This is the first study exploring the relationship between AS, MDD and BMD. Our results support the link between MDD and low BMD. We found that insecure AS was a risk factor for decreased BMD, regardless of depression. Insecure AS may play a role in the relationship between MDD and BMD or may constitute a risk factor itself. Therapeutic interventions focused on AS could improve psychiatric disorders and physical diseases related to low BMD.
Facts, views & vision in ObGyn, Jun 30, 2022
Background: High discrepancy between current classifications was observed in the definition of ut... more Background: High discrepancy between current classifications was observed in the definition of uterine septa, especially for indentation lengths >5 <10mm. Objectives: To assess the discrepancy between current classifications in the diagnoses of septate uterus and to correlate them with reproductive outcomes; to detect 3D transvaginal ultrasound (TVS) additional measurements, which can better correlate small indentation lengths >5 <10mm to reproductive failures. Material and methods: Observational study enrolling 664 women of reproductive age with 3D ultrasound diagnosis of an indentation length ≥3mm. For each patient a detailed reproductive history was taken before performing 3D transvaginal examination. Patients with previous uterine surgery or metroplasty were excluded. Main Outcome Measure(s): Indentation lengths >5 <10mm showed high discrepancy in the diagnosis of uterine septum between different classifications. For these small indentations additional 3D measurements (indentation angle, septal width and septal length/ fundal myometrial thickness (L/M) ratio) were correlated to infertility and recurrent miscarriage. Results: Among the cohort, 215 patients showed an indentation length >5 <10mm; 136 tried to conceive: 69 (51%) were infertile, 38 (28%) had recurrent miscarriages (≥2) and 5 (4%) had at least one delivery. Recurrent miscarriage significantly correlated to an indentation angle >134°; whereas infertility to an indentation width <32mm and a L/M ratio >75%. Conclusions: Wide discrepancies between different classifications are more evident in indentation lengths >5 <10mm. Additional measurements on 3D coronal section may help to evaluate the risk of infertility or recurrent miscarriage. What is new? Additional 3D TVS measurements, beyond septal lengths, in particular for small fundal indentation, may help in predicting the risk of developing adverse reproductive outcomes.
Objectives: To investigate the efficacy of hCG in the management of recurrent early pregnancy los... more Objectives: To investigate the efficacy of hCG in the management of recurrent early pregnancy loss. Design: A prospective, randomized, controlled trial. Setting: Miscarriage Clinic, Women's Hospital, Liverpool, United Kingdom. Subjects: Eighty-one women attending the miscarriage clinic with idiopathic recurrent pregnancy loss were randomized to receive hCG supplementation or placebo in early pregnancy. Main Outcome Measure: The success rate or live birth rate. Results: In women with regular menstrual cycles it was found that hCG had no beneficial effect, the pregnancy success rate being 86% in both groups. However, women with oligomenorrhea had a pregnancy success rate of 40% in the placebo group but a statistically significant improvement to 86% if hCG was given. Conclusions: Human chorionic gonadotropin can be recommended for idiopathic recurrent pregnancy loss in women with oligomenorrhea.
Genetic Testing and Molecular Biomarkers, Jun 1, 2017
The aim of this study was to evaluate the expression of OLR1 and its alternative splicing isoform... more The aim of this study was to evaluate the expression of OLR1 and its alternative splicing isoform Loxin in unexplained recurrent miscarriage (uRM). Sixty-three women of reproductive age were recruited and were divided into four groups: 18 pregnant and 23 non-pregnant women with uRM, and 12 pregnant and 10 non-pregnant women with physiological pregnancies. Complementary DNA derived from peripheral blood mononuclear cells (PBMCs) was analyzed by quantitative real-time PCR to evaluate the expression of OLR1 and Loxin. Oxidized low-density lipoproteins (ox-LDLs) were assayed on serum by a commercially available kit. Pregnant uRM women presented a higher, though not significant, OLR1/Loxin ratio and a higher ox-LDLs serum level (p ≤ 0.05) compared with pregnant control women. OLR1 and Loxin levels were significantly decreased in non-pregnant uRM women compared with the control (OLR1: 0.00018 vs. 0.00043, p ≤ 0.005; Loxin: 0.00018 vs. 0.00060, p ≤ 0.005, respectively). Loxin expression decreased by about two-thirds (p ≤ 0.005) in pregnant women compared with non-pregnant control women. A higher expression of OLR1 in pregnant women compared with non-pregnant women with uRM (p ≤ 0.05) was observed, but no variation in Loxin expression was observed. The results of this study show an association of peripheral OLR1 and Loxin expression levels in uRM women, and they suggest the possible existence of an uncontrolled oxidative stress in these women in the first trimester of pregnancy.
Gynecology & Obstetrics Case report, 2020
Journal of Clinical Medicine, Sep 1, 2020
The aim of this prospective cohort study was to determine whether women with recurrent pregnancy ... more The aim of this prospective cohort study was to determine whether women with recurrent pregnancy loss (RPL) have an increased risk of pregnancy complications compared to normal pregnant women. A total of 1092 singleton pregnancies were followed, 431 in women with RPL and 661 in normal healthy women. The prevalence of the following complications was observed: threatened miscarriage, miscarriage, cervical insufficiency, chromosomal/genetic abnormalities, fetal anomalies, oligohydramnios, polyhydramnios, fetal growth restriction, intrauterine fetal death, gestational diabetes mellitus (GDM), preeclampsia, placenta previa, abruptio placentae, pregnancy-related liver disorders, and preterm premature rupture of the membranes. The odds ratio and 95% CI for each pregnancy complication considered were determined by comparing women with RPL and normal healthy women. Women with RPL had an overall rate of pregnancy complications higher than normal women (OR = 4.37; 95% CI: 3.353-5.714; p < 0.0001). Their risk was increased for nearly all the conditions considered. They also had an increased risk of multiple concomitant pregnancy complications (OR = 4.64; 95% CI: 3.10-6.94, p < 0.0001). Considering only women with RPL, women with ≥3 losses had a higher risk of pregnancy complications than women with two losses (OR = 1.269; 95% CI: 1.112-2.386, p < 0.02). No differences were found in the overall risk of pregnancy complications according to the type, explained or unexplained, of RPL. Women with secondary RPL had an increased risk of GDM than women with primary RPL. Pregnancy in women with RPL should be considered at high risk.
American Journal of Reproductive Immunology, Dec 1, 2002
... by a variety of normal cell types and tissues, including macrophages, monocytes, endocrine gl... more ... by a variety of normal cell types and tissues, including macrophages, monocytes, endocrine glands ... is a cytokine involved in reproductive events such as ovulation and establishment of pregnancy. ... they were significantly higher in women at term with labor (spontaneous vaginal ...
Journal of Perinatal Medicine, May 30, 2023
Objectives To investigate whether high mobility group box 1 (HMGB1) is involved in unexplained re... more Objectives To investigate whether high mobility group box 1 (HMGB1) is involved in unexplained recurrent pregnancy loss (uRPL). Methods Plasma levels of HMGB1 were measured by ELISA in non-pregnant women with (n=44) and without (n=53 controls) uRPL. Their platelets and plasma-derived microvesicles (MVs) were also assayed for HMGB1. Endometrial biopsies were taken in selected uRPL (n=5) and control women (n=5) and the tissue expression of HMGB1 was determined by western blot and immunohistochemistry (IHC). Results plasma levels of HMGB1 were significantly higher in women with uRPL than in control women. HMGB1 content in platelets and MVs obtained from women with uRPL was significantly higher than that obtained from control women. HMGB1 expression in endometrium was higher in tissues obtained from women with uRPL than in tissues obtained from control women. IHC analysis revealed that HMGB1 is expressed in endometrium with different patterns between uRPL and control women. Conclusions HMGB1 could be involved in uRPL.
Human Reproduction, May 9, 2023
STUDY QUESTION Could epidermal growth factor-like domain 7 (EGFL7) be a factor involved in the pr... more STUDY QUESTION Could epidermal growth factor-like domain 7 (EGFL7) be a factor involved in the preparation of the endometrium for implantation and could its dysregulation be implicated in poor reproductive outcomes? SUMMARY ANSWER EGFL7 is highly expressed in the endothelium and glandular epithelium throughout the menstrual cycle; it is upregulated by stromal cells in secretory phase and appears strongly reduced in endometrial biopsies and isolated stromal cells of women with unexplained recurrent pregnancy loss (uRPL) and recurrent implantation failure (RIF). WHAT IS KNOWN ALREADY The secreted factor EGFL7, originally identified as a gene primarily expressed in endothelial cells, is also expressed by the mouse blastocyst and by mouse and human trophoblast cells. It regulates trophoblast migration and invasion by activating NOTCH1 signaling. NOTCH1 has been demonstrated to play a fundamental role in endometrial receptivity and its dysregulation may be involved in selected pregnancy complications characterized by altered endometrial receptivity, such as uRPL. STUDY DESIGN, SIZE, DURATION This is an exploratory study for which 84 endometrial biopsies were collected from normally fertile women, as well as from women with uRPL and RIF. PARTICIPANTS/MATERIALS, SETTING, METHODS Samples were collected from women in both the proliferative and secretory phases of the menstrual cycle and stratified into three sub-groups according to the patient clinical history: 20 fertile women (8 in proliferative and 12 in secretory phase), 41 women with uRPL (6 in proliferative and 35 in secretory phase), and 27 women with RIF (8 in proliferative and 19 in secretory phase). Immunohistochemistry, real-time PCR, and western blot analyses were performed to study the expression of EGFL7 and NOTCH1, as well as the NOTCH target genes. MAIN RESULTS AND THE ROLE OF CHANCE Analysis of spatial and temporal distribution of EGFL7 in endometrial biopsies from fertile women revealed higher levels of EGFL7 in samples from the secretory phase compared to proliferative phase. The expected expression of EGFL7 in endothelial cells was shown as well as the novel, not previously reported, expression in endometrial glands and stromal cells. EGFL7 was significantly reduced in the endometrium of women with uRPL and RIF in the secretory phases and this was associated with a downregulation of the NOTCH1 signaling pathway. Human recombinant EGFL7 was able to activate the NOTCH1 signaling pathway in endometrial stromal cells (EndSCs) obtained from fertile women but not in cells from uRPL or RIF patients. EndSCs from fertile women and decidualized in vitro for three days showed an upregulation of EGFL7 expression, whereas cells obtained from women with uRPL and RIF and decidualized in vitro did not. LIMITATIONS, REASONS FOR CAUTION This study was conducted with a relatively small number of patient samples. Although results are highly reproducible and consistent, additional observations from multicentric cohorts would strengthen the relevance of the data. Moreover, this is an in vitro study, which might only partially represent the in vivo conditions. WIDER IMPLICATIONS OF THE FINDINGS Our results demonstrate for the first time that EGFL7 is new player involved in decidualization and provide new insights into the pathophysiology of selected implantation defects and early pregnancy complications. Our studies have revealed that alterations in EGFL7 expression and the consequent dysregulation of NOTCH signaling are potential underlying causes of RIF and uRPL. Our results might have therapeutic relevance, as the EGFL7/NOTCH pathway may represent a potential target for medical intervention. STUDY FUNDING/COMPETING INTEREST(S) This study has been supported by the Grant for Fertility Innovation 2017 (Merck KGaA). There are no competing interests to disclose. TRIAL REGISTRATION NUMBER Not applicable.
Scientific Reports, 2020
RPL is a very debated condition, in which many issues concerning definition, etiological factors ... more RPL is a very debated condition, in which many issues concerning definition, etiological factors to investigate or therapies to apply are still controversial. ML could help clinicians to reach an objectiveness in RPL classification and access to care. Our aim was to stratify RPL patients in different risk classes by applying an ML algorithm, through a diagnostic work-up to validate it for the appropriate prognosis and potential therapeutic approach. 734 patients were enrolled and divided into 4 risk classes, according to the numbers of miscarriages. ML method, called Support Vector Machine (SVM), was used to analyze data. Using the whole set of 43 features and the set of the most informative 18 features we obtained comparable results: respectively 81.86 ± 0.35% and 81.71 ± 0.37% Unbalanced Accuracy. Applying the same method, introducing the only features recommended by ESHRE, a correct classification was obtained only in 58.52 ± 0.58%. ML approach could provide a Support Decision Sy...
Annali di ostetricia, ginecologia, medicina perinatale
Journal of Medical Virology, 2004
To investigate whether vertical transmission of the human herpesvirus 8 (HHV‐8) may occur during ... more To investigate whether vertical transmission of the human herpesvirus 8 (HHV‐8) may occur during pregnancy or at delivery, we enrolled 295 women recruited attending the Division of Obstetrics and Gynecology of a University Teaching of Rome Tor Vergata, S. Eugenio Hospital. The study population was divided in two groups: 245 pregnant women who underwent amniocentesis for genetic screening at 16–18 weeks gestation (group 1) and 50 women at the childbirth (group 2). Maternal blood was obtained from all women. Amniotic fluid (group 1) and cord blood (group 2) were obtained at midtrimester and at delivery, respectively. The presence of anti‐HHV‐8 antibodies in serum samples was investigated by an immunfluorescence assay. All amniotic fluids, maternal blood, and cord blood samples from HHV‐8 seropositive women were tested for the presence of HHV‐8 DNA sequences by the polymerase chain reaction. Thirty women, 27 of the group 1 and three of the group 2, were found to have anti‐HHV‐8 antibod...
Reproductive sciences, Apr 15, 2024
The current knowledge on adenomyosis as a risk factor for RPL is very scant. Overall 120 women we... more The current knowledge on adenomyosis as a risk factor for RPL is very scant. Overall 120 women were included in this retrospective observational study. They were divided in three groups each of which consisted of 40 subjects: Group 1: women with RPL who were diagnosed to have adenomyosis on transvaginal ultrasound (TVS); Group 2: patients with RPL without ultrasonographic findings of adenomyosis; Group 3: patients with ultrasound diagnosis of adenomyosis without RPL and at least one live birth pregnancy. The copresence of endometriosis was also investigated. Among women with RPL, patients with adenomyosis (Group 1) had higher number of pregnancy losses (p = 0.03) and lower age at first pregnancy loss (p = 0.03) than women without adenomyosis (Group 2). Moreover, they had more frequently primary RPL (p = 0.008). Adenomyosis of the inner myometrium was found more frequently (p = 0.04) in patients of Group 1 than in patients of Group 3 in which adenomyosis was mainly in the outer myometrium (p= 0.02). No differences were found in the severity of adenomyosis between these two groups of women. TVS findings for endometriosis were observed more frequently in women with adenomyosis without RPL (Group 3) than in the other two groups of patients. Adenomyosis can be a factor involved in RPL. Differences in adenomyosis localization are associated with different risks for RPL. Patients with RPL should be investigated for the presence of adenomyosis and also for the type and localization of the disease in the different myometrial layers.
International journal of molecular sciences, Feb 29, 2024
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Major depressive disorder (MDD) and osteoporosis are two common disorders with high morbidity and... more Major depressive disorder (MDD) and osteoporosis are two common disorders with high morbidity and mortality rates. Conflicting data have found associations between MDD and low bone mineral density (BMD) or osteoporosis, although causative factors are still unclear. A pilot study was designed with the aim to assess the relationship between MDD and BMD in postmenopausal women with MDD compared to healthy volunteers. We hypothesized that attachment style (AS) mediated this relationship.
PubMed, Oct 12, 2016
Introduction: Major depressive disorder (MDD) and osteoporosis are two common disorders with high... more Introduction: Major depressive disorder (MDD) and osteoporosis are two common disorders with high morbidity and mortality rates. Conflicting data have found associations between MDD and low bone mineral density (BMD) or osteoporosis, although causative factors are still unclear. A pilot study was designed with the aim to assess the relationship between MDD and BMD in postmenopausal women with MDD compared to healthy volunteers. We hypothesized that attachment style (AS) mediated this relationship. Methods: The sample was made of 101 postmenopausal women, 49 with MDD and 52 age-matched healthy volunteers. Structured clinical interview and Beck Depression Inventory (BDI) were performed to assesse MDD. AS was evaluated using the Relationship Questionnaire (RQ). BMD was measured by dual energy X-ray absorptiometry. Results: The univariate analysis showed that women with MDD had lower BMD values as compared to healthy volunteers. In the regression models MDD diagnosis and BDI score were not significant predictors of low BMD. The “preoccupied” pattern of insecure AS was a significant, independent predictor of decreased BMD in all skeletal sites: lumbar spine (p=0.008), femoral neck (p=0.011), total hip (p=0.002). Conclusions: This is the first study exploring the relationship between AS, MDD and BMD. Our results support the link between MDD and low BMD. We found that insecure AS was a risk factor for decreased BMD, regardless of depression. Insecure AS may play a role in the relationship between MDD and BMD or may constitute a risk factor itself. Therapeutic interventions focused on AS could improve psychiatric disorders and physical diseases related to low BMD.
Facts, views & vision in ObGyn, Jun 30, 2022
Background: High discrepancy between current classifications was observed in the definition of ut... more Background: High discrepancy between current classifications was observed in the definition of uterine septa, especially for indentation lengths >5 <10mm. Objectives: To assess the discrepancy between current classifications in the diagnoses of septate uterus and to correlate them with reproductive outcomes; to detect 3D transvaginal ultrasound (TVS) additional measurements, which can better correlate small indentation lengths >5 <10mm to reproductive failures. Material and methods: Observational study enrolling 664 women of reproductive age with 3D ultrasound diagnosis of an indentation length ≥3mm. For each patient a detailed reproductive history was taken before performing 3D transvaginal examination. Patients with previous uterine surgery or metroplasty were excluded. Main Outcome Measure(s): Indentation lengths >5 <10mm showed high discrepancy in the diagnosis of uterine septum between different classifications. For these small indentations additional 3D measurements (indentation angle, septal width and septal length/ fundal myometrial thickness (L/M) ratio) were correlated to infertility and recurrent miscarriage. Results: Among the cohort, 215 patients showed an indentation length >5 <10mm; 136 tried to conceive: 69 (51%) were infertile, 38 (28%) had recurrent miscarriages (≥2) and 5 (4%) had at least one delivery. Recurrent miscarriage significantly correlated to an indentation angle >134°; whereas infertility to an indentation width <32mm and a L/M ratio >75%. Conclusions: Wide discrepancies between different classifications are more evident in indentation lengths >5 <10mm. Additional measurements on 3D coronal section may help to evaluate the risk of infertility or recurrent miscarriage. What is new? Additional 3D TVS measurements, beyond septal lengths, in particular for small fundal indentation, may help in predicting the risk of developing adverse reproductive outcomes.
Objectives: To investigate the efficacy of hCG in the management of recurrent early pregnancy los... more Objectives: To investigate the efficacy of hCG in the management of recurrent early pregnancy loss. Design: A prospective, randomized, controlled trial. Setting: Miscarriage Clinic, Women's Hospital, Liverpool, United Kingdom. Subjects: Eighty-one women attending the miscarriage clinic with idiopathic recurrent pregnancy loss were randomized to receive hCG supplementation or placebo in early pregnancy. Main Outcome Measure: The success rate or live birth rate. Results: In women with regular menstrual cycles it was found that hCG had no beneficial effect, the pregnancy success rate being 86% in both groups. However, women with oligomenorrhea had a pregnancy success rate of 40% in the placebo group but a statistically significant improvement to 86% if hCG was given. Conclusions: Human chorionic gonadotropin can be recommended for idiopathic recurrent pregnancy loss in women with oligomenorrhea.
Genetic Testing and Molecular Biomarkers, Jun 1, 2017
The aim of this study was to evaluate the expression of OLR1 and its alternative splicing isoform... more The aim of this study was to evaluate the expression of OLR1 and its alternative splicing isoform Loxin in unexplained recurrent miscarriage (uRM). Sixty-three women of reproductive age were recruited and were divided into four groups: 18 pregnant and 23 non-pregnant women with uRM, and 12 pregnant and 10 non-pregnant women with physiological pregnancies. Complementary DNA derived from peripheral blood mononuclear cells (PBMCs) was analyzed by quantitative real-time PCR to evaluate the expression of OLR1 and Loxin. Oxidized low-density lipoproteins (ox-LDLs) were assayed on serum by a commercially available kit. Pregnant uRM women presented a higher, though not significant, OLR1/Loxin ratio and a higher ox-LDLs serum level (p ≤ 0.05) compared with pregnant control women. OLR1 and Loxin levels were significantly decreased in non-pregnant uRM women compared with the control (OLR1: 0.00018 vs. 0.00043, p ≤ 0.005; Loxin: 0.00018 vs. 0.00060, p ≤ 0.005, respectively). Loxin expression decreased by about two-thirds (p ≤ 0.005) in pregnant women compared with non-pregnant control women. A higher expression of OLR1 in pregnant women compared with non-pregnant women with uRM (p ≤ 0.05) was observed, but no variation in Loxin expression was observed. The results of this study show an association of peripheral OLR1 and Loxin expression levels in uRM women, and they suggest the possible existence of an uncontrolled oxidative stress in these women in the first trimester of pregnancy.
Gynecology & Obstetrics Case report, 2020
Journal of Clinical Medicine, Sep 1, 2020
The aim of this prospective cohort study was to determine whether women with recurrent pregnancy ... more The aim of this prospective cohort study was to determine whether women with recurrent pregnancy loss (RPL) have an increased risk of pregnancy complications compared to normal pregnant women. A total of 1092 singleton pregnancies were followed, 431 in women with RPL and 661 in normal healthy women. The prevalence of the following complications was observed: threatened miscarriage, miscarriage, cervical insufficiency, chromosomal/genetic abnormalities, fetal anomalies, oligohydramnios, polyhydramnios, fetal growth restriction, intrauterine fetal death, gestational diabetes mellitus (GDM), preeclampsia, placenta previa, abruptio placentae, pregnancy-related liver disorders, and preterm premature rupture of the membranes. The odds ratio and 95% CI for each pregnancy complication considered were determined by comparing women with RPL and normal healthy women. Women with RPL had an overall rate of pregnancy complications higher than normal women (OR = 4.37; 95% CI: 3.353-5.714; p < 0.0001). Their risk was increased for nearly all the conditions considered. They also had an increased risk of multiple concomitant pregnancy complications (OR = 4.64; 95% CI: 3.10-6.94, p < 0.0001). Considering only women with RPL, women with ≥3 losses had a higher risk of pregnancy complications than women with two losses (OR = 1.269; 95% CI: 1.112-2.386, p < 0.02). No differences were found in the overall risk of pregnancy complications according to the type, explained or unexplained, of RPL. Women with secondary RPL had an increased risk of GDM than women with primary RPL. Pregnancy in women with RPL should be considered at high risk.
American Journal of Reproductive Immunology, Dec 1, 2002
... by a variety of normal cell types and tissues, including macrophages, monocytes, endocrine gl... more ... by a variety of normal cell types and tissues, including macrophages, monocytes, endocrine glands ... is a cytokine involved in reproductive events such as ovulation and establishment of pregnancy. ... they were significantly higher in women at term with labor (spontaneous vaginal ...
Journal of Perinatal Medicine, May 30, 2023
Objectives To investigate whether high mobility group box 1 (HMGB1) is involved in unexplained re... more Objectives To investigate whether high mobility group box 1 (HMGB1) is involved in unexplained recurrent pregnancy loss (uRPL). Methods Plasma levels of HMGB1 were measured by ELISA in non-pregnant women with (n=44) and without (n=53 controls) uRPL. Their platelets and plasma-derived microvesicles (MVs) were also assayed for HMGB1. Endometrial biopsies were taken in selected uRPL (n=5) and control women (n=5) and the tissue expression of HMGB1 was determined by western blot and immunohistochemistry (IHC). Results plasma levels of HMGB1 were significantly higher in women with uRPL than in control women. HMGB1 content in platelets and MVs obtained from women with uRPL was significantly higher than that obtained from control women. HMGB1 expression in endometrium was higher in tissues obtained from women with uRPL than in tissues obtained from control women. IHC analysis revealed that HMGB1 is expressed in endometrium with different patterns between uRPL and control women. Conclusions HMGB1 could be involved in uRPL.
Human Reproduction, May 9, 2023
STUDY QUESTION Could epidermal growth factor-like domain 7 (EGFL7) be a factor involved in the pr... more STUDY QUESTION Could epidermal growth factor-like domain 7 (EGFL7) be a factor involved in the preparation of the endometrium for implantation and could its dysregulation be implicated in poor reproductive outcomes? SUMMARY ANSWER EGFL7 is highly expressed in the endothelium and glandular epithelium throughout the menstrual cycle; it is upregulated by stromal cells in secretory phase and appears strongly reduced in endometrial biopsies and isolated stromal cells of women with unexplained recurrent pregnancy loss (uRPL) and recurrent implantation failure (RIF). WHAT IS KNOWN ALREADY The secreted factor EGFL7, originally identified as a gene primarily expressed in endothelial cells, is also expressed by the mouse blastocyst and by mouse and human trophoblast cells. It regulates trophoblast migration and invasion by activating NOTCH1 signaling. NOTCH1 has been demonstrated to play a fundamental role in endometrial receptivity and its dysregulation may be involved in selected pregnancy complications characterized by altered endometrial receptivity, such as uRPL. STUDY DESIGN, SIZE, DURATION This is an exploratory study for which 84 endometrial biopsies were collected from normally fertile women, as well as from women with uRPL and RIF. PARTICIPANTS/MATERIALS, SETTING, METHODS Samples were collected from women in both the proliferative and secretory phases of the menstrual cycle and stratified into three sub-groups according to the patient clinical history: 20 fertile women (8 in proliferative and 12 in secretory phase), 41 women with uRPL (6 in proliferative and 35 in secretory phase), and 27 women with RIF (8 in proliferative and 19 in secretory phase). Immunohistochemistry, real-time PCR, and western blot analyses were performed to study the expression of EGFL7 and NOTCH1, as well as the NOTCH target genes. MAIN RESULTS AND THE ROLE OF CHANCE Analysis of spatial and temporal distribution of EGFL7 in endometrial biopsies from fertile women revealed higher levels of EGFL7 in samples from the secretory phase compared to proliferative phase. The expected expression of EGFL7 in endothelial cells was shown as well as the novel, not previously reported, expression in endometrial glands and stromal cells. EGFL7 was significantly reduced in the endometrium of women with uRPL and RIF in the secretory phases and this was associated with a downregulation of the NOTCH1 signaling pathway. Human recombinant EGFL7 was able to activate the NOTCH1 signaling pathway in endometrial stromal cells (EndSCs) obtained from fertile women but not in cells from uRPL or RIF patients. EndSCs from fertile women and decidualized in vitro for three days showed an upregulation of EGFL7 expression, whereas cells obtained from women with uRPL and RIF and decidualized in vitro did not. LIMITATIONS, REASONS FOR CAUTION This study was conducted with a relatively small number of patient samples. Although results are highly reproducible and consistent, additional observations from multicentric cohorts would strengthen the relevance of the data. Moreover, this is an in vitro study, which might only partially represent the in vivo conditions. WIDER IMPLICATIONS OF THE FINDINGS Our results demonstrate for the first time that EGFL7 is new player involved in decidualization and provide new insights into the pathophysiology of selected implantation defects and early pregnancy complications. Our studies have revealed that alterations in EGFL7 expression and the consequent dysregulation of NOTCH signaling are potential underlying causes of RIF and uRPL. Our results might have therapeutic relevance, as the EGFL7/NOTCH pathway may represent a potential target for medical intervention. STUDY FUNDING/COMPETING INTEREST(S) This study has been supported by the Grant for Fertility Innovation 2017 (Merck KGaA). There are no competing interests to disclose. TRIAL REGISTRATION NUMBER Not applicable.
Scientific Reports, 2020
RPL is a very debated condition, in which many issues concerning definition, etiological factors ... more RPL is a very debated condition, in which many issues concerning definition, etiological factors to investigate or therapies to apply are still controversial. ML could help clinicians to reach an objectiveness in RPL classification and access to care. Our aim was to stratify RPL patients in different risk classes by applying an ML algorithm, through a diagnostic work-up to validate it for the appropriate prognosis and potential therapeutic approach. 734 patients were enrolled and divided into 4 risk classes, according to the numbers of miscarriages. ML method, called Support Vector Machine (SVM), was used to analyze data. Using the whole set of 43 features and the set of the most informative 18 features we obtained comparable results: respectively 81.86 ± 0.35% and 81.71 ± 0.37% Unbalanced Accuracy. Applying the same method, introducing the only features recommended by ESHRE, a correct classification was obtained only in 58.52 ± 0.58%. ML approach could provide a Support Decision Sy...
Annali di ostetricia, ginecologia, medicina perinatale
Journal of Medical Virology, 2004
To investigate whether vertical transmission of the human herpesvirus 8 (HHV‐8) may occur during ... more To investigate whether vertical transmission of the human herpesvirus 8 (HHV‐8) may occur during pregnancy or at delivery, we enrolled 295 women recruited attending the Division of Obstetrics and Gynecology of a University Teaching of Rome Tor Vergata, S. Eugenio Hospital. The study population was divided in two groups: 245 pregnant women who underwent amniocentesis for genetic screening at 16–18 weeks gestation (group 1) and 50 women at the childbirth (group 2). Maternal blood was obtained from all women. Amniotic fluid (group 1) and cord blood (group 2) were obtained at midtrimester and at delivery, respectively. The presence of anti‐HHV‐8 antibodies in serum samples was investigated by an immunfluorescence assay. All amniotic fluids, maternal blood, and cord blood samples from HHV‐8 seropositive women were tested for the presence of HHV‐8 DNA sequences by the polymerase chain reaction. Thirty women, 27 of the group 1 and three of the group 2, were found to have anti‐HHV‐8 antibod...