Publications by authors named "Silvia Vannuccini"

37 Publications

Different Gestational Diabetes Phenotypes: Which Insulin Regimen Fits Better?

Front Endocrinol (Lausanne) 2021 9;12:630903. Epub 2021 Mar 9.

Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Careggi University Hospital, Florence, Italy.

Objective: Maternal characteristics and OGTT values of pregnancies complicated by gestational diabetes mellitus (GDM) were evaluated according to treatment strategies. The goal was to identify different maternal phenotypes in order to predict the appropriate treatment strategy.

Methods: We conducted a retrospective study among 1,974 pregnant women followed up for GDM in a tertiary referral hospital for high-risk pregnancies (Careggi University Hospital, Florence, Italy) from 2013 to 2018. We compared nutritional therapy (NT) alone (n = 962) NT and insulin analogues (n = 1,012) group. Then, we focused on different insulin analogues groups: long acting (D), rapid acting (R), both D and R. We compared maternal characteristics of the three groups, detecting which factors may predict the use of rapid or long-acting insulin analogue alone combined therapy.

Results: Among women included in the analysis, 51.3% of them needed insulin therapy for glycemic control: 61.8% D, 28.3% combined D and R, and 9.9% R alone. Age >35 years, pre-pregnancy BMI >30, family history of diabetes, previous GDM, altered fasting plasma glucose (FPG), hypothyroidism, and assisted reproductive technologies (ART) were identified as maternal variables significantly associated with the need of insulin therapy. Altered 1-h and 2-h glucose plasma glucose level at OGTT, age >35 years, and previous GDM were found as independent predicting factors for the use of combined therapy with rapid and long acting analogues for glycemic control. On the contrary, pre-pregnancy BMI <25 and normal fasting plasma glucose values at OGTT were found to be significantly associated to the use of rapid insulin analogue only.

Conclusion: A number of maternal and metabolic variables may be identified at the diagnosis of GDM, in order to identify different GDM phenotypes requiring a personalized treatment for glycemic control.
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http://dx.doi.org/10.3389/fendo.2021.630903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985539PMC
March 2021

Comorbidities and Quality of Life in Women Undergoing First Surgery for Endometriosis: Differences Between Chinese and Italian Population.

Reprod Sci 2021 Mar 9. Epub 2021 Mar 9.

Obstetrics and Gynecology, Department of Experimental and Clinical Biomedical Sciences, Careggi University Hospital, University of Florence, Largo Brambilla, 3, 50134, Florence, Italy.

An observational cross-sectional study was conducted in a group (n = 371) of fertile age women with endometriosis, by administering a structured questionnaire, in order to evaluate the incidence of gynecological and systemic comorbidities and the impact on quality of life (QoL) in two different groups of Italian and Chinese patients affected by endometriosis. Chinese (n = 175) and Italian (n = 196) women were compared regarding systemic (inflammatory, autoimmune, and mental) and gynecological comorbidities, pain symptoms, and QoL, by using the Short Form 12 (SF-12). Italian patients resulted younger at the diagnosis and suffered more frequently from severe pain than Chinese ones. Deep infiltrating endometriosis (DIE) and mixed phenotypes were more frequent in Italian patients, whereas ovarian (OMA) and superficial endometriosis (SUP) were more common in the Chinese. The Italian group showed more systemic comorbidities, and those disorder were already present before the diagnosis of endometriosis. Furthermore, the Italian group showed lower SF-12 physical and mental scores, suggesting a worse health-related QoL in Italian endometriotic patients. A number of differences has been observed between Italian and Chinese women with endometriosis in terms of comorbidities and QoL, which may be related to the ethnicity, the different health system organization and the social and cultural background.
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http://dx.doi.org/10.1007/s43032-021-00487-5DOI Listing
March 2021

Fetal nondiabetic-macrosomia: risk factors for pregnancy adverse outcome and comparison of two growth curves in the prediction of cesarean section.

J Matern Fetal Neonatal Med 2021 Feb 24:1-8. Epub 2021 Feb 24.

Department of Biochemical, Experimental and Clinical Sciences "MarioSerio", University of Florence, Florence, Italy.

Background: Randomized trials reported no difference whether induction or expectant management is performed in non-diabetic women with large for gestational age babies but no tool has been validated for the prediction of high risk cases.

Aim: Assessing the performance of different growth curves in the prediction of complications.

Methods: Data from 1066 consecutive non-diabetic women who delivered babies ≥4000 g were collected. Logistic regression analysis was used to analyze the impact of the maternal variables on: instrumental delivery, shoulder dystocia (SD), perineal tears, cesarean section (CS), and postpartum hemorrhage. Intergrowth21 curves and customized Gardosi's curves were compared in terms of prediction of adverse outcomes.

Findings: Induction of labor was performed in 23.1% cases. The rate of CS was 17%. Hemorrhage, fetal distress, and SD occurred in 2%, 1.3%, and 2.7% of cases, respectively. Induction was significantly associated with instrumental delivery ( < .001), CS ( = .001), third and fourth degree perineal tears ( = .031), and post-partum hemorrhage ( = .02). The cutoff of 90th percentile according to Intergrowth21 did not show significant performance in predicting CS, while the same cutoff according to the Gardosi curves showed an OR 1.92 (CI 1.30-2.84) ( = .0009).

Discussion: Gardosi curves showed a better performance in predicting the risk of CS versus Intergrowth curves. Induction is significantly associated with adverse outcome in non-diabetic women with LGA babies.
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http://dx.doi.org/10.1080/14767058.2021.1888918DOI Listing
February 2021

Is primary dysmenorrhea a precursor of future endometriosis development?

Gynecol Endocrinol 2021 Apr 11;37(4):287-293. Epub 2021 Feb 11.

Department of Biomedical, Experimental and Clinical Sciences, Division of Obstetrics and Gynecology, University of Florence, Florence, Italy.

Primary dysmenorrhea (PD) is the most common gynecologic disorder during adolescence and it is characterized by crampy lower abdominal pain that occurs during menstruation. Secondary dysmenorrhea, in contrast, has the same clinical features but occurs in women with a disease that could account for their symptoms (endometriosis, adenomyosis, uterine fibroids, pelvic inflammatory disease). Endometriosis is the most common cause of secondary dysmenorrhea and it should be considered in patients with persistent and clinically significant dysmenorrhea despite treatment. It is often diagnosed after a long delay, increasing the likelihood of pain chronicity and fertility problems at a later age. Women who suffer from dysmenorrhea in adolescence have higher risk of endometriosis in future. The open question is if endometriosis was already present at the onset of dysmenorrhea but undiagnosed or if PD favors subsequent development of endometriosis-associated pain. Since PD is associated with higher risk for developing chronic pain state and shares some of the same pain pathways of endometriosis (prostaglandins overproduction, inflammation, peripheral sensitization, central sensitization and abnormal stress responses), a correlation between PD and endometriosis is suggested. To know whether it is a risk factor for the development of endometriosis-associated pain may provide an opportunity for early intervention and prevention. The present review aims to investigate the clinical and pathogenetic features of PD and endometriosis in order to identify a possible association between the two conditions.
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http://dx.doi.org/10.1080/09513590.2021.1878134DOI Listing
April 2021

Sphingosine 1-phosphate signaling in uterine fibroids: implication in activin A pro-fibrotic effect.

Fertil Steril 2021 Jun 23;115(6):1576-1585. Epub 2021 Jan 23.

Department of Experimental and Clinical Biomedical Sciences "M. Serio," University of Florence, Florence, Italy.

Objective: To explore the link between sphingosine 1-phosphate (S1P) signaling and leiomyoma and the possible S1P cross-talk with the fibrotic effect of activin A.

Design: Case-control laboratory study.

Setting: University institute and university hospital.

Patient(s): Patients with uterine fibroids (n = 26).

Interventions(s): Tissue specimens of leiomyoma and normal myometrium were obtained from patients undergoing myomectomy or total hysterectomy.

Main Outcome Measure(s): Expression of mRNA levels of the enzyme involved in S1P metabolism, S1P receptors, and S1P transporter Spns2 was evaluated in matched leiomyoma/myometrium specimens and cell populations. The effects of inhibition of S1P metabolism and signaling was evaluated on activin A-induced fibrotic action in leiomyoma cell lines.

Result(s): The expression of the enzymes responsible for S1P formation, sphingosine kinase (SK) 1 and 2, and S1P, S1P, and S1P receptors was significantly augmented in leiomyomas compared with adjacent myometrium. In leiomyoma cells, but not in myometrial cells, activin A increased mRNA expression levels of SK1, SK2, and S1P. The profibrotic action of activin A was abolished when SK1/2 were inhibited or S1P were blocked. Finally, S1P augmented by itself mRNA levels of fibrotic markers (fibronectin, collagen 1A1) and activin A in leiomyomas but not in myometrial cells.

Conclusion(s): This study shows that S1P signaling is dysregulated in uterine fibroids and involved in activin A-induced fibrosis, opening new perspectives for uterine fibroid treatment.
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http://dx.doi.org/10.1016/j.fertnstert.2020.12.022DOI Listing
June 2021

Long-term hormonal treatment reduces repetitive surgery for endometriosis recurrence.

Reprod Biomed Online 2021 Feb 22;42(2):451-456. Epub 2020 Sep 22.

Department of Clinical Experimental and Biomedical Sciences, University of Florence Florence, Italy. Electronic address:

Research Question: How effective is medical hormonal treatment in preventing endometriosis recurrence and in improving women's clinical symptoms and quality of life?

Design: This observational cross-sectional study evaluated the effects of hormonal medical treatment (progestins, gonadotrophin-releasing hormone analogues or continuous oral contraceptives) on endometriosis recurrence, current clinical symptoms and quality of life in three groups of patients: Group A (n = 34), no hormonal treatment either before or after the first endometriosis surgery; Group B (n = 76), on hormonal treatment after the first endometriosis surgery; and Group C (n = 75), on hormonal treatment both before and after the first endometriosis surgery.

Results: Group C patients were characterized by a lower rate of endometriosis reoperation (P = 0.011) and a lower rate of dysmenorrhoea (P = 0.006). Women who experienced repetitive endometriosis surgery showed worse physical (P = 0.004) and mental (P = 0.012) status than those who received a single surgery, independent of the treatment.

Conclusion: Hormonal treatments represent a valid cornerstone of endometriosis management and may be useful as an alternative to surgery, but also before surgery, to plan better, and after surgery in order to reduce the risk of recurrence. Medical counselling is very helpful in choosing the correct and individualized endometriosis treatment. In fact, the gold standard for modern endometriosis management is the individualized approach and surgery should be considered, depending on the clinical situation and a patient's symptoms.
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http://dx.doi.org/10.1016/j.rbmo.2020.09.018DOI Listing
February 2021

Adenomyosis: Mechanisms and Pathogenesis.

Semin Reprod Med 2020 May 8;38(2-03):129-143. Epub 2020 Oct 8.

Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, California.

Adenomyosis is a common disorder of the uterus, and is associated with an enlarged uterus, heavy menstrual bleeding (HMB), pelvic pain, and infertility. It is characterized by endometrial epithelial cells and stromal fibroblasts abnormally found in the myometrium where they elicit hyperplasia and hypertrophy of surrounding smooth muscle cells. While both the mechanistic processes and the pathogenesis of adenomyosis are uncertain, several theories have been put forward addressing how this disease develops. These include intrinsic or induced (1) microtrauma of the endometrial-myometrial interface; (2) enhanced invasion of endometrium into myometrium; (3) metaplasia of stem cells in myometrium; (4) infiltration of endometrial cells in retrograde menstrual effluent into the uterine wall from the serosal side; (5) induction of adenomyotic lesions by aberrant local steroid and pituitary hormones; and (6) abnormal uterine development in response to genetic and epigenetic modifications. Dysmenorrhea, HMB, and infertility are likely results of inflammation, neurogenesis, angiogenesis, and contractile abnormalities in the endometrial and myometrial components. Elucidating mechanisms underlying the pathogenesis of adenomyosis raise possibilities to develop targeted therapies to ameliorate symptoms beyond the current agents that are largely ineffective. Herein, we address these possible etiologies and data that support underlying mechanisms.
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http://dx.doi.org/10.1055/s-0040-1716687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932680PMC
May 2020

Emergency surgery for appendectomy and incidental diagnosis of superficial peritoneal endometriosis in fertile age women.

Reprod Biomed Online 2020 Oct 20;41(4):729-733. Epub 2020 Jun 20.

Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Obstetrics and Gynecology, Careggi University Hospital Florence, Italy. Electronic address:

Research Question: This study aimed to evaluate the presence of superficial peritoneal endometriosis (SUP) in women referred to emergency surgery for right iliac fossa (RIF) pain and undergoing an appendectomy, considering which factors may be useful to suspect and identify endometriosis.

Design: An observational case-control study was conducted on a group (n = 149) of fertile age women. After surgery, Group A was selected upon the diagnosis of endometriosis (n = 34); Group B (n = 115) represented the controls. Demographics, comorbidities and clinical findings were registered and analysed.

Results: Appendicitis of various grades of severity was diagnosed in all patients, but SUP was also identified in 23%, of which 14.7% also presented with endometriosis of the appendix. Women in Group A reported chronic pelvic pain, dysmenorrhoea, dyspareunia and oral contraceptive use more frequently. At multivariate analysis, factors associated with endometriosis were: age <40 years, autoimmune disorders, multiple allergies, abdominal chronic pain, associated gynaecological pain symptoms, Alvarado score ≤6, and inconclusive ultrasound findings.

Conclusions: The incidental finding of SUP in fertile age women presenting with an acute RIF pain and undergoing emergency surgery is a relevant observation. Clinical history and symptoms should guide surgeons in performing a correct diagnosis and in referring the patient to the gynaecology specialist.
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http://dx.doi.org/10.1016/j.rbmo.2020.06.008DOI Listing
October 2020

Progesterone receptor ligands for the treatment of endometriosis: the mechanisms behind therapeutic success and failure.

Hum Reprod Update 2020 06;26(4):565-585

Division of Obstetrics and Gynecology, Department of Biomedical, Experimental and Clinical Sciences, Careggi University Hospital University of Florence, Florence, Italy.

Background: Despite intense research, it remains intriguing why hormonal therapies in general and progestins in particular sometimes fail in endometriosis.

Objective And Rationale: We review here the action mechanisms of progesterone receptor ligands in endometriosis, identify critical differences between the effects of progestins on normal endometrium and endometriosis and envisage pathways to escape drug resistance and improve the therapeutic response of endometriotic lesions to such treatments.

Search Methods: We performed a systematic Pubmed search covering articles published since 1958 about the use of progestins, estro-progestins and selective progesterone receptor modulators, to treat endometriosis and its related symptoms. Two reviewers screened the titles and abstracts to select articles for full-text assessment.

Outcomes: Progesterone receptor signalling leads to down-regulation of estrogen receptors and restrains local estradiol production through interference with aromatase and 17 beta-hydroxysteroid dehydrogenase type 1. Progestins inhibit cell proliferation, inflammation, neovascularisation and neurogenesis in endometriosis. However, progesterone receptor expression is reduced and disrupted in endometriotic lesions, with predominance of the less active isoform (PRA) over the full-length, active isoform (PRB), due to epigenetic abnormalities affecting the PGR gene transcription. Oxidative stress is another mechanism involved in progesterone resistance in endometriosis. Among the molecular targets of progesterone in the normal endometrium that resist progestin action in endometriotic cells are the nuclear transcription factor FOXO1, matrix metalloproteinases, the transmembrane gap junction protein connexin 43 and paracrine regulators of estradiol metabolism. Compared to other phenotypes, deep endometriosis appears to be more resistant to size regression upon medical treatments. Individual genetic characteristics can affect the bioavailability and pharmacodynamics of hormonal drugs used to treat endometriosis and, hence, explain part of the variability in the therapeutic response.

Wider Implications: Medical treatment of endometriosis needs urgent innovation, which should start by deeper understanding of the disease core features and diverse phenotypes and idiosyncrasies, while moving from pure hormonal treatments to drug combinations or novel molecules capable of restoring the various homeostatic mechanisms disrupted by endometriotic lesions.
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http://dx.doi.org/10.1093/humupd/dmaa009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317284PMC
June 2020

Ultrasound findings in infertile women with endometriosis: evidence of concomitant uterine disorders.

Gynecol Endocrinol 2020 Sep 5;36(9):808-812. Epub 2020 Mar 5.

Department of Clinical and Experimental Biomedical Sciences, University of Florence, Florence, Italy.

Endometriosis is a gynecological disease characterized by pain and infertility. The diagnosis is very often made during the infertility work-up, together with other reproductive diseases and uterine disorders. A retrospective cohort study was conducted on infertile women with clinical or ultrasound suspect of endometriosis, undergoing an ultrasound (US) evaluation by a team of expert sonographers ( = 419), with the aim to evaluate the prevalence of concomitant uterine disorders. The US coexistence of endometriosis with uterine fibroids and/or adenomyosis was investigated according to three age intervals (<35years; 35 ≥ years <45; ≥45 years) and to endometriosis phenotypes: ovarian endometriosis (OMA), deep infiltrating endometriosis (DIE), or both. The US diagnosis of fibroids was made in 3.1% of cases, adenomyosis was found in 21.2%, and the co-existence of both uterine disorders with endometriosis was reported in 14.6% of patients. When analyzed according to age, patients aged >35 years were more likely to be affected by uterine fibroids ( = .003), adenomyosis ( = .030) and both adenomyosis and fibroids ( < .0001). No statistically significant association was found between endometriosis phenotypes and myometrial pathologies. Uterine disorders coexistence should be considered in the assessment of women with endometriosis, in order to better define a treatment strategy for infertility, especially in women older than 35 years.
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http://dx.doi.org/10.1080/09513590.2020.1736027DOI Listing
September 2020

Diagnosing adenomyosis: an integrated clinical and imaging approach.

Hum Reprod Update 2020 04;26(3):392-411

Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134, Florence, Italy.

Background: Adenomyosis is a benign uterine disorder where endometrial glands and stroma are pathologically demonstrated within the uterine myometrium. The pathogenesis involves sex steroid hormone abnormalities, inflammation, fibrosis and neuroangiogenesis, even though the proposed mechanisms are not fully understood. For many years, adenomyosis has been considered a histopathological diagnosis made after hysterectomy, classically performed in perimenopausal women with abnormal uterine bleeding (AUB) or pelvic pain. Until recently, adenomyosis was a clinically neglected condition. Nowadays, adenomyosis may also be diagnosed by non-invasive techniques, because of imaging advancements. Thus, a new epidemiological scenario has developed with an increasing number of women of reproductive age with ultrasound (US) or magnetic resonance imaging (MRI) diagnosis of adenomyosis. This condition is associated with a wide variety of symptoms (pelvic pain, AUB and/or infertility), but it is also recognised that some women are asymptomatic. Furthermore, adenomyosis often coexists with other gynecological comorbidities, such as endometriosis and uterine fibroids, and the diagnostic criteria are still not universally agreed. Therefore, the diagnostic process for adenomyosis is challenging.

Objective And Rationale: We present a comprehensive review on the diagnostic criteria of adenomyosis, including clinical signs and symptoms, ultrasound and MRI features and histopathological aspects of adenomyotic lesions. We also briefly summarise the relevant theories on adenomyosis pathogenesis, in order to provide the pathophysiological background to understand the different phenotypes and clinical presentation. The review highlights the controversies of multiple existing criteria, summarising all of the available evidences on adenomyosis diagnosis. The review aims also to underline the future perspective for diagnosis, stressing the importance of an integrated clinical and imaging approach, in order to identify this gynecological disease, so often underdiagnosed.

Search Methods: PubMed and Google Scholar were searched for all original and review articles related to diagnosis of adenomyosis published in English until October 2018.

Outcomes: The challenge in diagnosing adenomyosis starts with the controversies in the available pathogenic theories. The difficulties in understanding the way the disease arises and progresses have an impact also on the specific diagnostic criteria to use for a correct identification. Currently, the diagnosis of adenomyosis may be performed by non-invasive methods and the clinical signs and symptoms, despite their heterogeneity and poor specificity, may guide the clinician for a suspicion of the disease. Imaging techniques, including 2D and 3D US as well as MRI, allow the proper identification of the different phenotypes of adenomyosis (diffuse and/or focal). From a histological point of view, if the diagnosis of diffuse adenomyosis is straightforward, in more limited disease, the diagnosis has poor inter-observer reproducibility, leading to extreme variations in the prevalence of disease. Therefore, an integrated non-invasive diagnostic approach, considering risk factors profile, clinical symptoms, clinical examination and imaging, is proposed to adequately identify and characterise adenomyosis.

Wider Implications: The development of the diagnostic tools allows the physicians to make an accurate diagnosis of adenomyosis by means of non-invasive techniques, representing a major breakthrough, in the light of the clinical consequences of this disease. Furthermore, this technological improvement will open a new epidemiological scenario, identifying different groups of women, with a dissimilar clinical and/or imaging phenotypes of adenomyosis, and this should be object of future research.
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http://dx.doi.org/10.1093/humupd/dmz049DOI Listing
April 2020

Dysmenorrhea and Heavy Menstrual Bleeding in Elite Female Athletes: Quality of Life and Perceived Stress.

Reprod Sci 2020 03 6;27(3):888-894. Epub 2020 Jan 6.

Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134, Florence, Italy.

In female athletes, the incidence of menstrual disorders is variable, and their impact on perceived stress and quality of life (QoL) is poorly known.The aim of the present study was to investigate the menstrual cycle characteristics and disorders in athletes performing different sports, also evaluating perceived stress and QoL according to their menstrual cycle features. A cross-sectional survey was conducted in nulliparous elite athletes of reproductive age, and the study population included 112 cases. Three questionnaires were administered on (1) gynecological health, (2) perceived stress scale (PSS), and (3) short form QoL (SF-12). A group of women not practising regular sport activities (n = 103) was used as control. Data obtained in elite athletes were also analyzed according to the static and dynamic component percentage of practised sports in 3 sub-groups. Athletes had a significantly higher incidence of irregular periods and heavy menstrual bleeding (HMB) (p < 0.01) and a lower incidence of dysmenorrhea (p < 0.01) than controls. Furthermore, athletes had a better physical QoL (53.9 ± 5.9 vs 51.2 ± 6.0) (p < 0.05) but higher PPS level (17.3 ± 4.8 vs 13.8 ± 4.8) and a worse mental QoL (44.9 ± 9.9 vs 47.6 ± 9.0) (p < 0.05) than controls. HMB was associated with lower mental scores (39.7 ± .8.9 vs 45.6 ± 9.9) and higher PSS scores (19.8 ± .3.2 vs 17.0 ± .4.9) than those observed in athletes with normal bleeding. No difference was found in different sports regarding gynecological health, PSS level, and QoL. An increased incidence of HMB should be considered in elite athletes with increased PSS and impaired QoL.
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http://dx.doi.org/10.1007/s43032-019-00092-7DOI Listing
March 2020

Is Stress a Cause or a Consequence of Endometriosis?

Reprod Sci 2020 01 6;27(1):39-45. Epub 2020 Jan 6.

Department of Experimental, Clinical and Biomedical Sciences, Obstetrics and Gynecology, University of Florence, Careggi University Hospital, Largo Brambilla 3, 50134, Florence, Italy.

Clinical studies clearly indicate that endometriosis is a condition associated with high levels of chronic stress. The stress intensity correlates with pain severity and disease extension. However, it is unknown whether chronic stress represents a primary cause of endometriosis and, therefore, if avoiding or treating chronic stress may reduce the risk of developing endometriosis. Repeated, uncontrolled stress either before or after experimental endometriosis induction promotes disease mechanisms and accelerates lesion growth in rodents. Furthermore, patients with endometriosis have a heightened risk of other inflammatory and immune-related diseases, many of which have also been associated with stress. Here, we review the latest evidences regarding the relationship between chronic stress and endometriosis and discuss the potential bidirectional aspect of such association. Further research may clarify if endometriosis is a cause and/or a consequence of stress and whether stress-reducing therapies are effective to mitigate symptoms and slow down the development of endometriotic lesions.
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http://dx.doi.org/10.1007/s43032-019-00053-0DOI Listing
January 2020

Surgical treatment of endometriosis: prognostic factors for better quality of life.

Gynecol Endocrinol 2019 Nov 3;35(11):1010-1014. Epub 2019 Jun 3.

Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Careggi University Hospital , Florence , Italy.

The present study investigated the effect of surgical treatment of endometriosis on physical and mental health. We undertook a prospective survey including 153 premenopausal women with histological diagnosis of endometriosis. The Short Form 12 (SF-12) questionnaire comprising physical and mental component scales was used. Two groups of patients were distinguished: Group A ( = 42) with SF-12 scores above the median in both physical and mental scales; Group B ( = 111) with SF-12 scores below the median in either physical or mental scale. Group A was diagnosed and operated for endometriosis for the first time at an older age (30 vs. 26 years), had undergone more frequently a single surgical intervention (64% vs. 46%), was less affected by symptom or lesion recurrence and had reported less intense current pain symptoms than Group B. Having the first endometriosis surgery at a later age was an independent predictor of better health status (adjusted odds ratio 1.146 per year, 95% confidence interval 1.058-1.242) after accounting for the potential confounding effects of reoperation, pelvic pain and time elapsed since the first surgery. In conclusion, patients with endometriosis who had a single surgery at an older age have good symptom control and better quality of life (QoL).
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http://dx.doi.org/10.1080/09513590.2019.1616688DOI Listing
November 2019

Recent advances in understanding and managing adenomyosis.

F1000Res 2019 13;8. Epub 2019 Mar 13.

Obstetrics and Gynecology, Department of Maternity and Child Health, University Hospital Florence, Careggi University Hospital, Florence, Largo Brambilla 3, 50134, Italy.

Adenomyosis is a benign uterine disorder in which endometrial glands and stroma are pathologically demonstrated in the uterine myometrium and it is considered a specific entity in the PALM-COEIN FIGO (polyp; adenomyosis; leiomyoma; malignancy and hyperplasia; coagulopathy; ovulatory dysfunction; endometrial; iatrogenic; and not yet classified - International Federation of Gynecology and Obstetrics) classification of causes of abnormal uterine bleeding (AUB). Although it has always been considered the classic condition of multiparous women over 40 years old who have pain and heavy menstrual bleeding, diagnosed at hysterectomy, the epidemiological scenario has completely changed. Adenomyosis is increasingly identified in young women with pain, AUB, infertility, or no symptoms by using imaging techniques such as transvaginal ultrasound and magnetic resonance. However, there is no agreement on the definition and classification of adenomyotic lesions from both the histopathology and the imaging point of view, and the diagnosis remains difficult and unclear. A uniform and shared reporting system needs to be implemented in order to improve our understanding on imaging features, their relationship with pathogenic theories, and their importance in terms of clinical symptoms and response to treatment. In fact, adenomyosis pathogenesis remains elusive and not a single theory can explain all of the different phenotypes of the disease. Furthermore, adenomyosis often coexists with other gynecological conditions, such as endometriosis and uterine fibroids, increasing the heterogeneity of available data. Treatment requires a lifelong management plan as the disease has a negative impact on quality of life in terms of menstrual symptoms, fertility, and pregnancy outcome and has a high risk of miscarriage and obstetric complications.
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http://dx.doi.org/10.12688/f1000research.17242.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419978PMC
June 2020

Influence of assisted reproductive technologies on maternal and neonatal outcomes in early preterm deliveries.

J Gynecol Obstet Hum Reprod 2019 Dec 18;48(10):845-848. Epub 2019 Mar 18.

Department of Health Sciences, Obstetrics and Gynecology Branch, University of Florence, Florence, Italy.

Introduction: Compared to spontaneous conception (SC), pregnancies conceived through assisted reproductive technologies (ART) carry worse pregnancy and neonatal outcomes. Evidences focused on preterm births are limited. Early preterm delivery is a critical situation for medical management and parental counselling. The aim of this study was to analyze if ART procedures influenced pregnancy and neonatal outcomes in singleton pregnancies with early preterm delivery.

Material And Methods: This was a retrospective case control study. The population consisted of all consecutive early preterm deliveries occurred at Careggi University Hospital in Florence (Italy) between 2010 and 2017. Cases were considered patients who conceived though ART, including intra cytoplasmic sperm injection (ICSI), in vitro fertilization and embryo transfer (IVF-ET), intra uterine insemination (IUI) and ovarian stimulation. Controls were patients who conceived in the natural way. Main outcomes of the study were: birth weight, umbilical artery pH, Apgar score at 1 and 5 min, gestational age at delivery and mode of delivery. Secondary outcomes were: spontaneous preterm labor initiation, gestational diabetes mellitus, intrauterine growth restriction (IUGR), cholestasis of pregnancy, intra uterine fetal demise (IUFD), placenta previa, fetal malformations, pregnancy induced hypertensive (PIH) disorders (gestational hypertension, preeclampsia and hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome) and postpartum hysterectomy. Shapiro-Wilk test was used to check the normality of the data; Mann-Whitney test was used to compare two continuous variables not-normally distributed. Multiple and binomial logistic regression analyses were used to adjust the results of the statistical analysis for potential confounding factors. The analysis for the main outcomes was performed for all deliveries and then repeated for spontaneous deliveries, separately.

Results: Seventy-one patients had ART and 640 SC. We found no differences in birthweight, umbilical artery pH, Apgar at 1 and 5 min and gestational age at delivery between ART and SC groups. C-section rate, placenta previa and PIH disorders were higher in the ART group. The higher prevalence of C-sections in the ART group was not statistically significant after adjusting for age and parity in the whole population but resulted significantly different when analyzing the subgroup of patients with spontaneous initiation of labor.

Conclusions: Fetal outcomes seem to be equal between ART and SC in early preterm neonates ; C-section rate and pregnancy complications such as placenta previa and PIH disorders seem to be higher in the ART group. These information should be part of the family counselling in these cases. We suggest that clinicians, after management of preterm delivery had been properly addressed, should not apply different management in ART compared to SC pregnancies.
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http://dx.doi.org/10.1016/j.jogoh.2019.03.008DOI Listing
December 2019

Peripartum and postpartum outcomes in uncomplicated term pregnancy following ART: a retrospective cohort study from two Italian obstetric units.

Hum Reprod Open 2018 24;2018(3):hoy012. Epub 2018 Jul 24.

Department of Health Sciences, University of Florence, Careggi University Hospital, Largo Brambilla, Florence, Italy.

Study Question: Do singleton uncomplicated term pregnancies conceived by assisted reproductive technology (ART) have adverse peripartum and postpartum outcomes?

Summary Answer: Term pregnancies following ART, even if uncomplicated until birth, have a higher risk of retained placenta and postpartum hemorrhage (PPH).

What Is Known Already: There is consistent evidence that pregnancies following ART have higher incidence of complications during pregnancy. However, few studies specifically investigated birth outcomes in ART term pregnancies.

Study Design Size Duration: A retrospective cohort study was conducted on 14 415 deliveries at two university tertiary care obstetric units. Clinical data were extracted by reviewing obstetric records of all deliveries from 1 January 2010 to 31 December 2014, in a standardized electronic database regarding the mother's health before and during pregnancy, complications during pregnancy and at birth, and neonatal outcome.

Participants/materials Setting Methods: Following an accurate evaluation of exclusion criteria (multiparity, maternal pre-pregnancy diseases, prior uterine surgery, fetal malformations, intrauterine deaths, elective cesarean section and pregnancy complications), the group of uncomplicated singleton term pregnancies from autologous ART conception by fertilization (IVF) or intracytoplasmic sperm injection (ICSI) ( = 188) was compared with a maternal age and body mass index (BMI) matched group of spontaneous pregnancies ( = 1168). Cases of intrauterine insemination (IUI) ( = 14) and ovulation induction with timed intercourse ( = 18) were not included. Labor, delivery and postpartum outcomes were evaluated. Odds ratios (OR) were adjusted with multivariable logistic regression to maternal age, BMI, nationality and gestational age at birth.

Main Results And The Role Of Chance: The age of women in the final analysis ranged from 25 to 45 years, while BMI ranged from 17 to 34 kg/m. Uncomplicated term pregnancies with ART conception had a higher risk of operative delivery (adjusted OR 1.40, 95% confidence interval (CI) 1.01-1.95), retained placenta (adjusted OR 2.63, 95% CI 1.31-5.26) and PPH (adjusted OR 2.86 95% CI 1.37-5.99). Conversely, ART conception did not increase the risk of induced labor (adjusted OR 1.18, 95% CI 0.85-1.65). However, patients that conceived by ART and underwent labor induction had a higher risk of failed induction compared with the control group (adjusted OR 2.53, 95% CI 1.23-5.21). Infants born after ART had a similar birthweight, Apgar score and arterial blood pH compared with spontaneously-conceived ones.

Limitations Reasons For Caution: The database lacked specific information about causes of infertility, smoking habit, family income and details on ART (fresh versus frozen cycle, IVF versus ICSI), limiting, in part, our analysis of the results. However, only autologous IVF/ICSI pregnancies were included in order to prevent bias related to conception by oocyte/embryo donation. conception ART cases were excluded because they were too few to allow comparison with IVF/ICSI. Nevertheless, the inclusion of only uncomplicated pregnancies provides a highly homogeneous and still representative population sample. Study sample is representative of a well-resourced obstetric facility in a high-income country, limiting to some extent the generalizability of study results.

Wider Implications Of The Findings: Pregnancies conceived by autologous ART that proceed uncomplicated until term may require counseling about the risk of placental retention with PPH.

Study Funding/competing Interests: The authors have no conflict of interest and funding to declare.
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http://dx.doi.org/10.1093/hropen/hoy012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276695PMC
July 2018

Human leukocyte antigen DQ2/DQ8 positivity in women with history of stillbirth.

Am J Reprod Immunol 2018 11 19;80(5):e13038. Epub 2018 Aug 19.

Division of Obstetrics and Gynecology, Department of Biomedical, Experimental and Clinical Sciences, Careggi University Hospital, University of Florence, Florence, Italy.

Problem: The aim of this study was to investigate the prevalence of human leukocyte antigens (HLA) DQ2 and DQ8 haplotypes, two common polymorphisms associate with celiac disease (CD), in women with previous stillbirth, but not affected by CD.

Method Of Study: Women with history of unexplained term stillbirth referred to our Center for High-Risk Pregnancies for a preconception counseling, and women with previous uncomplicated pregnancies, were enrolled as cases and controls. Celiac women were excluded from the study. Genetic tests for HLA DQ2/DQ8 were performed, and patients' data were compared.

Results: The population included 56 women with a previous term stillbirth and 379 women with history of uncomplicated pregnancies. The prevalence of HLA-DQ2 or DQ8 positivity was significantly higher in cases than in controls (50% vs 29.5%) (P = 0.0031). Women with HLA DQ8 genotype have a significantly higher risk of stillbirth (OR: 2.84 CI: 1.1840-6.817) and in case of DQ2 genotype the OR for stillbirth was even higher (OR: 4.46 CI: 2.408-8.270). In the stillbirth group, SGA neonates were significantly more frequent in those with HLA-DQ2/DQ8 haplotypes than in those resulted negative to genetic testing (85.7% vs 42 .8%, P = 0.004).

Conclusion: In women with history of term stillbirth, a significantly higher prevalence of HLA DQ2/DQ8 haplotypes has been found compared to women with previous uneventful pregnancies. In addition, HLA DQ2/DQ8 positivity was significantly associated with suboptimal fetal growth in intrauterine fetal death cases, as shown by an increased prevalence of SGA babies.
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http://dx.doi.org/10.1111/aji.13038DOI Listing
November 2018

Is pulsating cord blood sampling a suitable and reliable method for cord gas analysis at birth?

Acta Obstet Gynecol Scand 2018 12 9;97(12):1532. Epub 2018 Sep 9.

Department of Health Sciences, University of Florence, Obstetrics and Gynecology, Careggi University Hospital, Florence, Italy.

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http://dx.doi.org/10.1111/aogs.13434DOI Listing
December 2018

Role of medical therapy in the management of uterine adenomyosis.

Fertil Steril 2018 03;109(3):398-405

Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Obstetrics and Gynecology, Careggi University Hospital, Florence, Italy. Electronic address:

Adenomyosis is a benign uterine condition affecting women at various ages with different symptoms. The management of these patients is still controversial. Few clinical studies focusing on medical or surgical treatment for adenomyosis have been performed. No drug is currently labelled for adenomyosis and there are no specific guidelines to follow for the best management. Anyhow, medical treatments are effective in improving symptoms (pain, abnormal uterine bleeding and infertility). The rationale for using medical treatment is based on the pathogenetic mechanisms of adenomyosis: sex steroid hormones aberrations, impaired apoptosis, and increased inflammation. Several nonhormonal (i.e., nonsteroidal anti-inflammatory drugs) and hormonal treatments (i.e., progestins, oral contraceptives, gonadotropin-releasing hormone analogues) are currently used off-label to control pain symptoms and abnormal uterine bleeding in adenomyosis. Gonadotropin-releasing hormone analogues are indicated before fertility treatments to improve the chances of pregnancy in infertile women with adenomyosis. An antiproliferative and anti-inflammatory effect of progestins, such as dienogest, danazol and norethindrone acetate, suggests their use in medical management of adenomyosis mainly to control pain symptoms. On the other hand, the intrauterine device releasing levonorgestrel resulted is extremely effective in resolving abnormal uterine bleeding and reducing uterine volume in a long-term management plan. Based on new findings on pathogenetic mechanisms, new drugs are under development for the treatment of adenomyosis, such as selective progesterone receptor modulators, aromatase inhibitors, valproic acid, and anti-platelets therapy.
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http://dx.doi.org/10.1016/j.fertnstert.2018.01.013DOI Listing
March 2018

The influence of fetal sex on the antenatal diagnosis of small for gestational age.

J Matern Fetal Neonatal Med 2019 Jun 2;32(11):1832-1837. Epub 2018 Jan 2.

b Department of Maternal and Fetal Medicine, Women's Center, Fetal Medicine Unit , John Radcliffe Hospital, Oxford University Hospitals National Institute for Health Research Foundation Trust , Oxford , UK.

Objective: We evaluated the influence of fetal sex on the antenatal diagnosis and detection of small for gestational age (SGA).

Methods: The cohort consisted of unselected singleton pregnancies, undergoing routine biometry and cerebroplacental ratio (CPR) assessment at 36 weeks. Locally fitted equations for centiles and Z scores were used. "Ultrasound SGA" was defined as estimated fetal weight (EFW) < 10th centile, "SGA at birth" as birthweight (BW) < 10th centile adjusted for sex.

Results: Among 4112 pregnancies, there were 235 female "ultrasound SGA" fetuses and 177 male; (odds ratios (OR) 1.502 (1.223 - 1.845)); the detection rate of SGA at birth was 50.6% and 40.9%, respectively (OR 1.479 (0.980 - 2.228)). In "ultrasound SGA" girls the abdominal circumference growth velocity (ACGV) between 20 and 36 weeks was less frequently in the lowest decile (OR 0.490 (0.320 - 0.750)), with no differences in CPR.

Conclusions: Females are more commonly diagnosed as SGA; those diagnosed may be at less risk than males.
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http://dx.doi.org/10.1080/14767058.2017.1419180DOI Listing
June 2019

Mental health, pain symptoms and systemic comorbidities in women with endometriosis: a cross-sectional study.

J Psychosom Obstet Gynaecol 2018 12 13;39(4):315-320. Epub 2017 Oct 13.

d Obstetrics and Gynecology, Department of Biomedical, Experimental and Clinical Sciences "Mario Serio" , University of Florence, Careggi University Hospital, Largo Brambilla , Florence , Italy.

Introduction: Endometriosis is a gynecological disease with a severe impact on quality of life. The aim of this study is to assess mental health status in a group of women with endometriosis, investigating their clinical history, pain symptoms and systemic comorbidities.

Methods: An observational cross-sectional study was performed on a group of Italian Caucasian women with endometriosis (n = 134). All patients filled the 'Patient Health Questionnaire' (PHQ), a self-administered screening tool for mental health disorders. The characteristics of endometriosis, pain symptoms and their severity, the presence and types of comorbid systemic disorders were added into the same survey.

Results: According to PHQ algorithms, 59% of patients were affected by at least one psychiatric disorder, with a significant correlation with pain symptoms (p = 0.0026). Patients with severe pain showed a higher incidence of multiple psychiatric disorders (p = 0.026) and somatoform disorder than those with mild pain (p = 0.0009). There was no correlation between the presence of psychiatric disorders and age, BMI, parity, infertility, need for surgery, number of intervention, localization of endometriotic lesions and systemic comorbidities.

Discussion: Women with endometriosis showed a high frequency of PHQ results positive for psychiatric disorders, with a significant association with pain severity.
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http://dx.doi.org/10.1080/0167482X.2017.1386171DOI Listing
December 2018

A reference range of fetal abdominal circumference growth velocity between 20 and 36 weeks' gestation.

Prenat Diagn 2017 Nov 6;37(11):1084-1092. Epub 2017 Oct 6.

Fetal Medicine Unit, Department of Maternal and Fetal Medicine, Women's Center, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Objective: To create a single equation and reference range for abdominal circumference growth velocity (ACGV) between 20 and 36 weeks in singleton pregnancies.

Method: Observational study of pregnant women having routine scans for abdominal circumference (AC) at 20 and 36 weeks' gestation. Exclusion criteria were multiple pregnancy, abnormal karyotype, major fetal abnormalities, and absent data on first-trimester dating. Scan image quality and AC measurement reliability were assessed according to INTERGROWTH-21st criteria. Regression models for the AC mean and standard deviation were fitted separately at 20 and 36 weeks, and z scores were calculated. Abdominal circumference growth velocity was defined as the z score difference between 20 and 36 weeks divided by the interval in days and multiplied by 100.

Results: The study population included 3334 fetuses. The equation for ACGV is (((AC  - 53.090 - 1.081*GA )/(0.057638*GA  + 0.622741)) - ((AC  + 68.349 - 1.571*GA )/(0.06265*GA  - 2.55361)))*100/(GA  - GA ), where AC is expressed in millimeters and GA is gestational age in days. The 3rd, 5th, 10th, 50th, 90th, 95th, and 97th centiles are -1.8997, -1.6785, -1.3091, -0.0069, 1.3255, 1.7279, 1.9973, respectively.

Conclusion: We have defined ACGV between 20 and 36 weeks, and we have established its reference range. Further studies are needed to evaluate the clinical significance of growth patterns in the tail ends of this distribution.
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http://dx.doi.org/10.1002/pd.5145DOI Listing
November 2017

Fetal middle cerebral artery Doppler in late-term pregnancy: a predicting factor for failed induction of labor.

J Matern Fetal Neonatal Med 2018 Oct 25;31(20):2756-2762. Epub 2017 Jul 25.

c Department of Biomedical, Experimental and Clinical Sciences "Mario Serio" , Careggi University Hospital, University of Florence , Florence , Italy.

Purpose: To study the role of fetal middle cerebral artery (MCA) Doppler evaluated prior to induction of labor in late-term pregnancies, in order to build an ultrasound-based predictive model for failed induction.

Materials And Methods: A prospective cohort study on 250 nulliparous women carrying singleton late-term pregnancies was conducted. Prior to induction, each patient underwent to an ultrasound evaluation for fetal MCA Doppler. Additional ultrasound parameters such as cervical length (CL), membranes thickness, amniotic fluid index, placental location, and estimated fetal weight (EFW) were collected. According to the type of response, women were divided into three groups: (A) responders within 24 h; (B) responders after 24 h, and (C) no responders.

Results: Women who failed to enter active labor showed significantly higher fetal MCA pulsatility index (PI), longer CL and higher EFW. The estimated probability of logistic regression model combining the three variables achieved a sensitivity of 94.2% and a specificity of 86.36% (AUC, 0.926; 95% CI, 0.884 - 0.956, p < .0001) using as decision probability value the cut off >0.1838.

Conclusions: In late-term pregnancies, an ultrasound-based model including cervical length, MCA PI, and EFW achieved a good accuracy in predicting those women who are likely to fail induction of labor.
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http://dx.doi.org/10.1080/14767058.2017.1355900DOI Listing
October 2018

Pathogenesis of adenomyosis: an update on molecular mechanisms.

Reprod Biomed Online 2017 Nov 27;35(5):592-601. Epub 2017 Jun 27.

Department of Biomedical, Experimental and Clinical Sciences "Mario Serio," University of Florence, Careggi University Hospital, Largo Brambilla, 50134, Florence, Italy. Electronic address:

Adenomyosis is a uterine disorder becoming more commonly diagnosed in women of reproductive age because of diagnostic imaging advancements. The new epidemiological scenario and the clinical evidence of pelvic pain, abnormal uterine bleeding and infertility are changing the classic perspective of adenomyosis as a premenopausal disease. In the last decade, the evaluation of multiple molecular mediators has improved our knowledge of pathogenic mechanisms of adenomyosis, supporting that this is an independent disease from endometriosis. Although they share common genetic mutations and epigenetic changes in sex steroid hormone receptors and similar inflammatory mediators, an increasing number of recent studies have shown pathogenic pathways specific for adenomyosis. A PubMed search up to October 2016 summarizes the key mediators of pain, abnormal uterine bleeding and infertility in adenomyosis, including sex steroid hormone receptors, inflammatory molecules, extracellular matrix enzymes, growth factors and neuroangiogenic factors.
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http://dx.doi.org/10.1016/j.rbmo.2017.06.016DOI Listing
November 2017

Deep Infiltrating Endometriosis and Endometrial Adenocarcinoma Express High Levels of Myostatin and Its Receptors Messenger RNAs.

Reprod Sci 2017 12 27;24(12):1577-1582. Epub 2017 Mar 27.

1 Department of Molecular and Developmental Medicine, Obstetrics and Gynecology, University of Siena, Siena, Italy.

Myostatin is a growth factor member of the transforming growth factor β superfamily, which is known to play major roles in cell proliferation and differentiation. The present study investigated the messenger RNA (mRNA) expression of myostatin and myostatin receptors (activin receptor-like kinase 4 [ALK4], transforming growth factor (TGF)-β type I receptor kinase [ALK5] and activin receptor type IIB [ActRIIB]) in endometrium of healthy women during menstrual cycle as well as in benign (endometriosis, polyps) and malignant (endometrial adenocarcinoma) conditions. Endometrial specimens were collected by hysteroscopy, whereas endometriotic lesions were collected by laparoscopy, and adenocarcinomas were sampled after hysterectomy. Total RNA was extracted from tissue homogenates, and gene expression was assessed by quantitative real-time polymerase chain reaction. Myostatin and myostatin receptors mRNAs were expressed by healthy endometrium throughout the menstrual cycle, with no differences between the proliferative and secretory phase. The highest myostatin mRNA expression was found in patients with deep infiltrating endometriosis (DIE) and in endometrial carcinoma; expression was also found in ovarian endometrioma (OMA ) and endometrial polyps. Myostatin receptors mRNA expression was higher in DIE and adenocarcinomas compared to control endometrium. The expression of ALK5 and ActRIIB in OMA was higher than in controls, whereas polyps had an increased expression of ALK5 mRNA. In conclusion, the present data showed for the first time the expression of myostatin in healthy endometrium and a higher expression in endometriosis and endometrial cancer, suggesting myostatin involvement in human endometrial physiology and related pathologies.
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http://dx.doi.org/10.1177/1933719117698579DOI Listing
December 2017

Is fetal analgesia necessary during prenatal surgery?

J Matern Fetal Neonatal Med 2018 May 16;31(9):1241-1245. Epub 2017 Apr 16.

b Department of Molecular and Developmental Medicine, Division of Obstetrics and Gynecology , University of Siena , Siena , Italy.

Fetal pain and fetal anesthesia are still matter of debate: some authors hypothesize that several intrauterine endocrine neuroinhibitors (ENIn) anesthetize the fetus, keeping it in a constant state of sleep, and making pharmacological fetal anesthesia useless for fetal surgery, while others argue fetal pain is possible and shoud be prevented with fetal anesthesy.

Aim: To retrieve evidences about fetal pain, fetal arousability and about the level of sedation induced by the ENIn, in order to assess the necessity of direct fetal anesthesia during prenatal fetal surgery.

Methods: We performed a careful literature review (1990-2016) on fetal arousability, and on the possibility that ENIn at the average fetal blood levels induce actual anesthesia. We retrieved the papers that fulfilled the research criteria, with particular attention to the second half of pregnancy, the period when most fetal surgery is performed.

Results: Fetuses are awake about 10% of the total time in the last gestational weeks, and they can be aroused by external stimuli. ENIn have not an anesthetic effect at normal fetal values, but only when they areartificialy injected at high doses; their blood levels in the last trimester of average pregnancies are not dissimilar either in the fetus or in the mother.

Conclusions: During the second half of the pregnancy, external stimuli can awake the fetuses, although they spend most of the time in sleeping state; the presence of ENIn is absolutely not enough to guarantee an effective anesthesia during surgery. Thus, direct fetal analgesia/anesthesia is mandatory, though further studies on its possible drawbacks are necessary.
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http://dx.doi.org/10.1080/14767058.2017.1311860DOI Listing
May 2018

Twin pregnancies after assisted reproductive technologies: the role of maternal age on pregnancy outcome.

Eur J Obstet Gynecol Reprod Biol 2016 Nov 21;206:198-203. Epub 2016 Sep 21.

Obstetrics and Gynecology, Department of Health Sciences, University of Florence, Florence, Italy.

Objectives: Our aim was to investigate whether advanced maternal age (≥40years) still impairs the outcome of twin pregnancies after assisted reproductive techniques (ART).

Study Design: The retrospective observational study evaluated 430 nulliparous dichorionic diamniotic twin pregnancies conceived with ART. The population was divided into women <40 years old (Group A, n=265) and ≥40 years old (Group B, n=165).

Results: Gestational diabetes mellitus and gestational hypertension/preeclampsia were significantly more frequent in nulliparous twin pregnancies after ART ≥40years compared to <40years (p=0.021 and p<0.001, respectively). In univariate analysis of twin pregnancies after ART, there was only a trend of higher incidence of total preterm birth (PB) rate within mother aged ≥40 years old (p=0.104). However, Group A showed higher rate of spontaneous preterm birth (SPB) <37 weeks, whereas Group B showed significantly higher rate of iatrogenic PB <37 weeks of gestation (p=0.023 and p=0.001, respectively). For delivery <32 weeks of gestation, the rate of SPB in Group A was significantly higher (p=0.002). A higher incidence of PB was observed in Group B after heterologous treatment (p<0.001). Despite this, the absolute prevalence of PB in the entire population is higher in Group A, both after autologous (22.5%) and heterologous (25%) ART treatment, than in Group B (10.1% vs 21.4%).

Conclusions: Our data indicate that nulliparous twin pregnancies conceived with ART in mothers ≥40 years old did not show significantly higher incidence of PB, even if an increased rate of iatrogenic PB <37 weeks is showed.
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http://dx.doi.org/10.1016/j.ejogrb.2016.09.019DOI Listing
November 2016

Endocrinology of human parturition.

Ann Endocrinol (Paris) 2016 Jun 5;77(2):105-13. Epub 2016 May 5.

Obstetrics and Gynecology, Department of Molecular and Developmental Medicine, University of Siena, "S. Maria alle Scotte", viale Bracci, 53100 Siena, Italy. Electronic address:

The mechanisms involved in human pregnancy maintenance and parturition are highly complex and involve mother, fetus and placenta. The "final common pathway" to delivery is composed by inflammatory and endocrine interactive paths that tip the balance in favor of coordinated uterine contractility and cervical dilation. These mechanisms involve a shift from progesterone to estrogen dominance, CRH action, increased sensitivity to oxytocin, gap junction formation, and increased prostaglandins activity. Complementary changes in the cervix involve a decrease in progesterone dominance and the actions of prostaglandins and relaxin, via connective tissue alterations, leading to cervical softening and dilation. Neuronal, hormonal, inflammatory and immune pathways participate in initiation of labor and the utero-placental unit plays a major role in the synthesis and release of parturition mediators.
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http://dx.doi.org/10.1016/j.ando.2016.04.025DOI Listing
June 2016

CD93 and dystroglycan cooperation in human endothelial cell adhesion and migration adhesion and migration.

Oncotarget 2016 Mar;7(9):10090-103

Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy.

CD93 is a transmembrane glycoprotein predominantly expressed in endothelial cells. Although CD93 displays proangiogenic activity, its molecular function in angiogenesis still needs to be clarified. To get molecular insight into the biological role of CD93 in the endothelium, we performed proteomic analyses to examine changes in the protein profile of endothelial cells after CD93 silencing. Among differentially expressed proteins, we identified dystroglycan, a laminin-binding protein involved in angiogenesis, whose expression is increased in vascular endothelial cells within malignant tumors. Using immunofluorescence, FRET, and proximity ligation analyses, we observed a close interaction between CD93 and β-dystroglycan. Moreover, silencing experiments showed that CD93 and dystroglycan promoted endothelial cell migration and organization into capillary-like structures. CD93 proved to be phosphorylated on tyrosine 628 and 644 following cell adhesion on laminin through dystroglycan. This phosphorylation was shown to be necessary for a proper endothelial migratory phenotype. Moreover, we showed that during cell spreading phosphorylated CD93 recruited the signaling protein Cbl, which in turn was phosphorylated on tyrosine 774. Altogether, our results identify a new signaling pathway which is activated by the cooperation between CD93 and dystroglycan and involved in the control of endothelial cell function.
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http://dx.doi.org/10.18632/oncotarget.7136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891106PMC
March 2016