Publications by authors named "Felice Petraglia"

358 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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 Jan 23. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fertnstert.2020.12.022DOI Listing
January 2021

High grade cervical intraepithelial neoplasia positive biopsy: the importance of accurate pre-operative workup.

Minerva Ginecol 2020 Dec;72(6):413-419

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

Background: In cervical cancer screening programs, women with abnormal cytology and confirmation by biopsy are referred for colposcopy for histological evaluation.

Methods: We characterized the presence and the genotype of HPV by Linear Array HPV genotyping assay in cytological samples collected from about 400 women undergoing conization, with reported high CIN grade after biopsy.

Results: The most prevalent genotype was HPV 16, with an increasing presence depending on the severity of the CIN and with the highest incidence in the 26-35 age range. In the group of younger women (<25) we found the highest percentage of CIN3 (39.3%) and the lowest of CIN1 (17.9%). An increase of CIN1 with increasing age was observed. A different distribution of HPV presence was observed depending on CIN grade (P<0.001): CIN1 HPV negative samples were 46.3%, CIN2: 5.8% and CIN3: 1.4%. Interesting, in the analyzed cohort, we observed the presence of 30% of CIN1. Moreover, within CIN1, 85% of them were associated to negative HPV detection, this observation suggested that the detection of HPV presence may be useful to identify low CIN grade that should be reconsidered for surgical treatment.

Conclusions: These findings suggest implementing the protocol for the management of women with high risk precancer lesions, with a further HPV test before surgical treatment. The evaluation of HPV presence and genotype before conization might represent a useful tool in reducing or postpone the conization treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S0026-4784.20.04587-6DOI Listing
December 2020

Office hysteroscopy in pre- and post-menopausal women: a predictive model.

Gynecol Endocrinol 2021 Mar 26;37(3):206-210. Epub 2020 Dec 26.

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

Objectives: To assess the variables associated with success of office hysteroscopy (OH) in pre-menopausal and post-menopausal women and to develop a clinical model for predicting the outcome of OH.

Methods: This is a retrospective cohort study of consecutive patients ( = 3181) referred for an OH to a tertiary care university hospital between January 2018 and March 2020. Multivariate logistic regression analysis was used to investigate the variables for predicting the success of OH in all patients and in pre-menopausal and in post-menopausal patients separately. The logistic regression analysis of each variable was applied to develop a predictive model.

Results: The overall success rate of the procedure was 92.2%; 95.4% in pre-menopausal women and 87.6% in post-menopausal women. In the general population, independent predictors of procedure success were previous vaginally delivery and hysteroscopy, while previous cervical or uterine surgery were associated with incomplete OH. In the pre-menopausal group, the independent predictors of failure were treatment with GnRH, estroprogestins and infertility. In 89% of cases, our developed model was able to predict whether an OH would be successful in a particular patient. ROC analysis showed an area under the curve of 0.8746 (95% CI: 0.85354-0.89557).

Conclusions: The present study demonstrates the development of a simple and reliable clinical model for the identification of both pre-menopausal and menopausal patients with a high chance of OH success.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09513590.2020.1864316DOI Listing
March 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rbmo.2020.09.018DOI Listing
February 2021

New epigenetic mechanism involved in leiomyoma formation.

Fertil Steril 2021 Jan 4;115(1):94-95. Epub 2020 Dec 4.

Department of Experimental and Clinical Biomedical Sciences "Mario Serio," Obstetrics and Gynecology, University of Florence, Florence, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fertnstert.2020.09.143DOI Listing
January 2021

Insight on the Intracrinology of Menopause: Androgen Production within the Human Vagina.

Endocrinology 2021 Feb;162(2)

Andrology, Women's Endocrinology and Gender Incongruence Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio," University of Florence, Florence, Italy.

In this study, we investigated steroidogenic gene mRNA expression in human vaginas and verified the ability of human vagina smooth muscle cells (hvSMCs) to synthesize androgens from upstream precursor dehydroepiandrosterone (DHEA). As a readout for androgen receptor (AR) activation, we evaluated the mRNA expression of various androgen-dependent markers. hvSMCs were isolated from vagina tissues of women undergoing surgery for benign gynecological diseases. In these cells, we evaluated mRNA expression of several steroidogenic enzymes and sex steroid receptors using real time reverse transcription-polymerase chain reaction. Androgen production was quantified with liquid chromatography tandem-mass spectrometry (LC-MS/MS). In vaginal tissues, AR mRNA was significantly less expressed than estrogen receptor α, whereas in hvSMCs, its mRNA expression was higher than progestin and both estrogen receptors. In hvSMCs and in vaginal tissue, when compared to ovaries, the mRNA expression of proandrogenic steroidogenic enzymes (HSD3β1/β2, HSD17β3/β5), along with 5α-reductase isoforms and sulfotransferase, resulted as being more abundant. In addition, enzymes involved in androgen inactivation were less expressed than in the ovaries. The LC-MS/MS analysis revealed that, in hvSMCs, short-term DHEA supplementation increased Δ4-androstenedione levels in spent medium, while increasing testosterone and DHT secretion after longer incubation. Finally, androgenic signaling activation was evaluated through AR-dependent marker mRNA expression, after DHEA and T stimulation. This study confirmed that the human vagina is an androgen-target organ with the ability to synthesize androgens, thus providing support for the use of androgens for local symptoms of genitourinary syndrome in menopause.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/endocr/bqaa219DOI 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0040-1716687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932680PMC
May 2020

Sphingosine 1-phosphate receptors are dysregulated in endometriosis: possible implication in transforming growth factor β-induced fibrosis.

Fertil Steril 2021 Feb 6;115(2):501-511. Epub 2020 Sep 6.

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

Objective: To study the molecular mechanisms involved in the appearance of the fibrotic trait in endometriosis by investigating whether the signaling pathway of the bioactive sphingolipid sphingosine 1-phosphate (S1P) was altered in endometriotic lesions.

Design: Case-control laboratory study.

Setting: University research institute and university hospital.

Patient(s): A total of 75 women, with and without endometriosis, were included in the study.

Interventions(s): Endometrial samples were obtained from women affected (n = 15 endometrioma [OMA]; n = 30 deep infiltrating endometriosis [DIE]) and not (n = 30) by endometriosis by means of laparoscopic surgery, followed by clinical and imaging investigation and checking for the expression of fibrosis markers and genes implicated in S1P metabolism and signaling by means of real-time polymerase chain reaction.

Main Outcome Measure(s): The role of the S1P signaling axis in endometriosis-associated fibrosis was studied in vitro, where RNA interference approaches were used to investigate if S1P synthesis by sphingosine kinases (SKs) and specific S1P receptors (S1PRs) are implicated in the profibrotic effect of the cytokine transforming growth factor (TGF) β1.

Result(s): mRNA expression analysis of S1PR demonstrated a deep dysregulation of S1P signaling in endometriosis, characterized by increased expression of fibrosis markers: S1P was transcriptionally more expressed in OMA, and S1P and S1P mRNA levels were significantly augmented in both OMA and DIE. SK1 and its activating protein calcium- and integrin-binding protein 1 (CIB1) were significantly up-regulated in OMA and DIE. A crucial role for the SK/S1PR axis in the profibrotic effect elicited by TGFβ1 was highlighted in vitro.

Conclusion(s): The S1P signaling axis may represent a useful biomarker or innovative pharmacologic target for endometriosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fertnstert.2020.08.012DOI Listing
February 2021

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rbmo.2020.06.008DOI Listing
October 2020

Anti-inflammatory effects of androgens in the human vagina.

J Mol Endocrinol 2020 10;65(3):109-124

Andrology, Women's Endocrinology and Gender Incongruence Unit, Department of Experimental Clinical and Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy.

Chronic inflammation is involved in the genitourinary syndrome of menopause (GSM) and beneficial effects of androgens in the vagina have been described. We investigated the potential involvement of human vagina smooth muscle cells (hvSMCs) in the inflammatory response and the immunomodulatory effect of androgen receptor (AR) agonist dihydrotestosterone (DHT). HvSMCs isolated from menopausal women were evaluated for sex steroids receptors and toll-like receptors mRNA expression, and left untreated or treated in vitro with lipopolysaccharide (LPS) or IFNγ, in the presence or absence of DHT. We evaluated mRNA expression (by RT-PCR) and secretion in cell culture supernatants (by a bead-based immunoassay) of pro-inflammatory markers. Nuclear translocation of NF-κB (by immunofluorescence) and cell surface HLA-DR expression (by flow cytometry) were also evaluated. Similar experiments were repeated in rat vSMCs (rvSMCs). In hvSMCs and rvSMCs, AR was highly expressed. DHT pre-treatment inhibited LPS-induced mRNA expression of several pro-inflammatory mediators (i.e. COX2, IL-6, IL-12A and IFNγ), effect significantly blunted by AR antagonist bicalutamide. DHT significantly counteracted the secretion of IL-1RA, IL-2, IL-5, IL-15, FGF, VEGF and TNFα. LPS-induced NF-κB nuclear translocation was significantly inhibited by DHT, an effect counteracted by bicalutamide. DHT pre-treatment significantly decreased IFNγ-induced expression of HLA-DR, mRNA expression of iNOS, COX2 and MCP1, and secretion of IL-1, IL-2, IL-5, IL-6, MCP1 and GCSF. Similar effects were observed in rvSMCs. The activation of AR suppresses the inflammatory response in hvSMCs, reducing their potential to be involved in the initiation and maintaining of inflammation, thus representing a therapeutic strategy in conditions, such as the GSM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/JME-20-0147DOI Listing
October 2020

Epigenetics of Estrogen and Progesterone Receptors in Endometriosis.

Reprod Sci 2020 11 22;27(11):1967-1974. Epub 2020 Jul 22.

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

Endometriosis is an estrogen-dependent inflammatory gynecological disease. Increased estrogen activity and progesterone resistance are the main hormonal substrate of this disease and are associated with inflammatory response and debilitating symptoms, including pain and infertility. Estrogens and progesterone act via their specific nuclear receptors. The regulation of receptor expression by epigenetics maybe a critical factor for endometriosis. The present review aims to discuss the epigenetic mechanisms related to the expression of estrogen receptors (ERs) and progesterone receptors (PRs) in patients with endometriosis, including two classic epigenetic mechanisms: DNA methylation and histone modification, and, other non-classic mechanisms: miRNAs and lncRNA. Several in vitro and in vivo studies support the key role of epigenetics in the regulation of the expression of ERs and PRs, which may provide new molecules and targets for the diagnosis and treatment of endometriosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s43032-020-00226-2DOI Listing
November 2020

Intravenous immunoglobulin for the secondary prevention of stillbirth in obstetric antiphospholipid syndrome: A case series and systematic review of literature.

Autoimmun Rev 2020 Sep 16;19(9):102620. Epub 2020 Jul 16.

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

Objective: To evaluate the efficacy and safety of intravenous immunoglobulin (IVIg) in secondary prevention of pregnancy complications for patients with obstetric antiphospholipid syndrome (APS) and history of stillbirth.

Methods: We described three cases of obstetric APS patients with history of stillbirth treated with IVIg in four pregnancies. In addition, we conducted a systematic literature review on the use of IVIg in obstetric APS with history of stillbirth.

Results: Three patients with obstetric APS and history of stillbirth were treated with prophylactic IVIg, in addition to standard treatment (hydroxychloroquine, low-dose aspirin, low molecular weight heparin, and prednisone), in four pregnancies (three singleton and one twin). All pregnancies resulted in live healthy newborns. Long-term follow-up re-evaluations (24-53 months) did not shown any sign or symptom of active systemic disease, and the children were healthy. The systematic literature review retrieved only three cases of use of IVIg in obstetric APS patients with history of stillbirth. All three cases resulted in live healthy newborns. Only in one case, mild thrombocytopenia occurred during treatment, although this event was unlikely to be related to IVIg.

Conclusion: Our experience suggests that IVIg as secondary prevention of APS-related stillbirth is associated with good pregnancy and long-term outcomes, with no relevant safety concerns. However, the literature evidence on this topic is limited to few isolated cases, and further studies are needed to clarify which obstetric APS patients may benefit the most from IVIg.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.autrev.2020.102620DOI Listing
September 2020

Comorbidities, risk factors and maternal/perinatal outcomes in oocyte donation pregnancies.

Reprod Biomed Online 2020 Aug 15;41(2):309-315. Epub 2020 May 15.

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

Research Question: To evaluate pre-existing comorbidities, obstetric risk factors and adverse obstetric and neonatal outcomes in pregnancies conceived by oocyte donation, compared with naturally conceived pregnancies or by conventional IVF/intracytoplasmic sperm injection (IVF/ICSI).

Design: This retrospective single-centre contemporary cohort study reviewed data from singleton deliveries at the University Hospital of Careggi, Florence, from 2009 to 2017. Maternal and perinatal outcomes were analysed.

Results: The study included 25,851 pregnancies and newborns: 276 (1.1%) children were conceived after oocyte donation, 925 (3.6%) after IVF/ICSI and 24,650 (95.4%) after natural conception. Women in the oocyte donation group were significantly older compared with IVF/ICSI and natural conception groups (P < 0.0001) and had a higher prevalence of chronic hypertension compared with the natural conception group (P = 0.0090). They were administered anticoagulant medications more frequently during pregnancy. The incidence of gestational hypertension was significantly higher than in natural conception (aOR 3.6) and IVF/ICSI pregnancies (aOR 2.7). The incidence of Caesarean section in oocyte donation pregnancies was higher than in natural conception and IVF/ICSI groups (aOR 3.4 and 2.3, respectively). An 11-fold increased risk of post-partum haemorrhage (PPH) was found in oocyte donation versus natural conception and an almost four-fold increased risk was found in oocyte donation versus IVF/ICSI; prematurity and low birthweight were more frequent after oocyte donation versus natural conception (aOR 2.4 and 1.8, respectively).

Conclusions: Patients undergoing oocyte donation represent a group with increased comorbidities and risk factors for adverse obstetric outcomes. Oocyte donation seems to be independently associated with gestational hypertension and PPH. Pregnancies after oocyte donation warrant clinical surveillance with proper screening and, possibly, preventive strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rbmo.2020.04.020DOI Listing
August 2020

Inflammation calls for more: Severe pelvic inflammatory disease with or without endometriosis. Outcomes on 311 laparoscopically treated women.

J Gynecol Obstet Hum Reprod 2021 Mar 17;50(3):101811. Epub 2020 May 17.

Department of Obstetrics & Gynecology, Gynecologic Oncology and Minimally Invasive Pelvic Surgery, IRCCS Sacro Cuore Don Calabria Hospital - Negrar (Verona), Italy, International School of Surgical Anatomy, Italy.

Objective: To study possible associations between endometriosis and pelvic inflammatory disease (PID).

Design: Retrospective cohort analysis over 14 consecutive years, based on medical records and insurance coding in a tertiary care endometriosis reference center.

Setting: Tertiary care reference center for endometriosis.

Patients: Retrospective analysis on all women submitted to laparoscopy in our Unit MAIN OUTCOME MEASURES: Intra-operative data about complications and fertility-impairing procedures, intra-, peri- and post-operative complications.

Interventions: Retrospective disease codes-triggered chart analysis.

Results: The study population was divided into two groups: Group 1 included women with PID and no endometriosis (n = 115); Group 2 included women with PID and endometriosis (n = 96). Endometriosis had a prevalence of 63 % in patients submitted to surgery for PID, significantly higher than the one reported in general population and than the one reported in a Tertiary Care Endometriosis Unit. A significantly higher number of salpingectiomes was needed in group 2 patients (208 versus 80, p < 0.0001).

Conclusions: This study seems to confirm an higher prevalence of pelvic inflammatory disease in endometriosis patients. Intra-operative findings of PID with associated endometriosis show more aggressive patterns.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jogoh.2020.101811DOI Listing
March 2021

Clinical Findings and Disease Severity in Hospitalized Pregnant Women With Coronavirus Disease 2019 (COVID-19).

Obstet Gynecol 2020 08;136(2):252-258

Department of Woman, Mother and Neonate, L. Sacco Hospital, ASST Fatebenefratelli Sacco, Milan, the Department of Clinical and Biological Sciences, University of Milan, Milan, the Department of Obstetrics and Gynecology, Papa Giovanni XXIII Hospital, Bergamo, the Department of Obstetrics and Gynecology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, the Department of Clinical Sciences and Community Health, University of Milan, Milan, the Department of Obstetrics and Gynecology, A. Manzoni Hospital, ASST Lecco, Lecco, the Department of Obstetrics and Gynecology, University of Pavia, IRCCS Foundation Policlinico San Matteo, Pavia, the Department of Obstetrics and Gynecology, Santa Chiara Hospital, Trento, the Department of Obstetrics and Gynecology, AUSL Piacenza, Piacenza, the Obstetrics and Gynecology Unit, Department of Woman's and Child's Health, University Hospital of Padua, Padua, the Department of Experimental and Clinical Biomedical Sciences "Mario Serio," Obstetrics and Gynecology, University of Florence, Florence, the Department of Maternal Fetal Medicine, Fondazione MBBM, San Gerardo Hospital, University of Milano Bicocca, Monza, the Obstetrics Unit, Mother Infant Department, University Hospital Policlinico of Modena, Modena, and the Obstetrics and Gynecology Unit, Azienda Ospedaliera Bolognini, Seriate, Italy.

Objective: To investigate the clinical evolution of coronavirus disease 2019 (COVID-19) in hospitalized pregnant women and potential factors associated with severe maternal outcomes.

Methods: We designed a prospective multicenter cohort study of pregnant women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who were admitted to 12 Italian maternity hospitals between February 23 and March 28, 2020. Clinical records, laboratory and radiologic examinations, and pregnancy outcomes were collected. A subgroup of patients with severe disease was identified based on intensive care unit (ICU) admission, delivery for respiratory compromise, or both.

Results: Seventy-seven patients were included, 14 of whom had severe disease (18%). Two thirds of the patients in the cohort were admitted during the third trimester, and 84% were symptomatic on admission. Eleven patients underwent urgent delivery for respiratory compromise (16%), and six were admitted to the ICU (8%). One woman received extracorporeal membrane oxygenation; no deaths occurred. Preterm delivery occurred in 12% of patients, and nine newborns were admitted to the neonatal intensive care unit. Patients in the severe subgroup had significantly higher pregestational body mass indexes (BMIs) and heart and respiratory rates and a greater frequency of fever or dyspnea on admission compared with women with a nonsevere disease evolution.

Conclusion: In our cohort, one in five women hospitalized with COVID-19 infection delivered urgently for respiratory compromise or were admitted to the ICU. None, however, died. Increased pregestational BMI and abnormal heart and respiratory rates on admission were associated with severe disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/AOG.0000000000003979DOI Listing
August 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/humupd/dmaa009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317284PMC
June 2020

Expression of Matrix Metalloproteinases and Their Inhibitors in Endometrium: High Levels in Endometriotic Lesions.

Int J Mol Sci 2020 Apr 18;21(8). Epub 2020 Apr 18.

Department of Molecular and Developmental Medicine, Siena University, 53100 Siena, Italy.

Endometriosis is a condition defined as presence of endometrium outside of the uterine cavity. These endometrial cells are able to attach and invade the peritoneum or ovary, thus forming respectively the deep infiltrating endometriosis (DIE) and the ovarian endometrioma (OMA), the ectopic lesions feature of this pathology. Endometriotic cells display high invasiveness and share some features of malignancy with cancer cells. Indeed, the tissue remodeling underlining lesion formation is achieved by matrix metalloproteinases (MMPs) and their inhibitors. Therefore, these molecules are believed to play a key role in development and pathogenesis of endometriosis. This study investigated the molecular profile of metalloproteinases and their inhibitors in healthy ( = 15) and eutopic endometrium ( = 19) in OMA ( = 10) and DIE ( = 9); moreover, we firstly validated the most reliable housekeeping genes allowing accurate gene expression analysis in these tissues. Gene expression, Western blot, and immunofluorescence analysis of MMP2, MMP3, and MMP10 and their tissue inhibitors TIMP1 and TIMP2 demonstrated that these enzymes are finely tuned in these tissues. In OMA lesions, all the investigated MMPs and their inhibitors were significantly increased, while DIE expressed high levels of MMP3. Finally, in vitro TNFα treatment induced a significant upregulation of , , and in both healthy and eutopic endometrial stromal cells. This study, shedding light on MMP and TIMP expression in endometriosis, confirms that these molecules are altered both in eutopic endometrium and endometriotic lesions. Although further studies are needed, these data may help in understanding the molecular mechanisms involved in the extracellular matrix remodeling, a crucial process for the endometrial physiology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21082840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215833PMC
April 2020

The impact of assisted reproductive technology on prenatally diagnosed fetal growth restriction in dichorionic twin pregnancies.

PLoS One 2020 16;15(4):e0231028. Epub 2020 Apr 16.

Department of Health Sciences, University of Florence, Florence, Italy.

Objective: Whether the use of assisted reproductive technologies (ART) affects the outcome of twin pregnancies is still a matter of debate. Previous studies have evaluated the association between birth weight and ART, without a clear distinction between fetal growth restriction (FGR), a condition at higher risk of adverse outcome, and constitutionally small for gestational age (SGA) fetuses. The aim of this study was to determine whether dichorionic (DC) twin pregnancies obtained by ART have a greater risk of developing FGR, defined by accurate ultrasound criteria, than those spontaneously conceived (SC), and to compare the severity of ultrasound features in the growth restricted fetuses.

Methods: A retrospective study was conducted on DC twin pregnancies delivered between 2010 to 2018 at a tertiary hospital. Twin pregnancies conceived spontaneously were compared with those obtained via in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), after exclusion of cases with major fetal or uterine malformations. The primary outcome was the incidence of FGR. Secondary outcome was the rate of SGA neonates, defined by a birth weight less than the 10th percentile. The ultrasound characteristics of the growth restricted fetuses in the two groups were also compared. The groups were compared using univariate and multivariate analyses.

Results: Six hundred and seventy-eight DC twin pregnancies were identified. Of these, 367 (54.1%) conceived via IVF/ICSI and 311 (45.9%) conceived spontaneously. The incidence of FGR was not significantly different between the ART and the SC groups (7.9% vs 8.4% respectively, p = 0.76, adjusted OR 0.84, 95% CI 0.53-1.32). Growth restricted fetuses of the two groups showed similar occurrence of an estimated fetal weight less than the 3rd percentile, similar abnormalities in Doppler studies and similar gestational age at diagnosis. There was no difference in the incidence of delivery of an SGA neonate (p = 0.47) or in the rate of maternal complications and preterm delivery between the groups.

Conclusions: Twin pregnancies conceived by assisted reproductive technologies do not have a higher risk of ultrasound-diagnosed FGR than spontaneously conceived twin pregnancies, and fetuses diagnosed with growth restriction in the two groups show similar severity of the ultrasound findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231028PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162456PMC
July 2020

Quercetin and indole-3-carbinol inhibit extracellular matrix expression in human primary uterine leiomyoma cells.

Reprod Biomed Online 2020 Apr 23;40(4):593-602. Epub 2020 Jan 23.

Department of Experimental and Clinical Medicine, Faculty of Medicine, Università Politecnica delle Marche, 60020 via Tronto 10/a Ancona, Italy. Electronic address:

Research Question: What is the effect of quercetin and indole-3-carbinol (I3C) on extracellular matrix expression, cell migration and proliferation in human myometrial and uterine leiomyoma cells.

Design: Myometrial and leiomyoma cells were treated with quercetin or I3C at different concentrations (10 µg/ml; 50 µg/ml; 100 µg/ml; and 250 µg/ml) for 48 h to measure mRNA and protein expressions of extracellular matrix (collagen 1A1, fibronectin and versican), as well as cell migration and the proliferation rate.

Results: Quercetin decreased mRNA levels of collagen 1A1 in myometrial (P < 0.0001) and leiomyoma cells (P < 0.0001). Quercetin reduced mRNA and protein levels of fibronectin in myometrial cells (P < 0.05) and fibronectin protein in leiomyoma cells (P < 0.05). I3C reduced collagen 1A1 mRNA levels in myometrial (P < 0.05) and leiomyoma cells at higher dose (P < 0.05). The protein levels of fibronectin were also reduced in both myometrial and leiomyoma cells with highest dose of I3C (P < 0.05), although mRNA levels were not affected in leiomyoma cells. Neither quercetin nor I3C treatment altered versican mRNA levels in both cell types. A significant reduction of the migration of both myometrial and leiomyoma cells in response to quercetin was observed (P < 0.05) and I3C (P < 0.05 for myometrial and P < 0.01 for leiomyoma cells) treatment. Both quercetin and I3C significantly reduced myometrial cell proliferation (P < 0.05).

Conclusions: The in-vitro anti-fibrotic, anti-migratory and anti-proliferative effects of quercetin and I3C form the scientific basis for developing new therapeutic, preventive agents, or both, for uterine leiomyomas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rbmo.2020.01.006DOI Listing
April 2020

Robotic treatment for urinary tract endometriosis: preliminary results and surgical details in a high-volume single-Institutional cohort study.

Surg Endosc 2020 07 13;34(7):3236-3242. Epub 2020 Mar 13.

Department of Urology, University of Florence, Unit of Oncologic Minimally-Invasive Urology and Andrology, Careggi University Hospital, San Luca Nuovo, Florence, Italy.

Background: Aim of the study was to present the surgical techniques and the postoperative outcomes in women treated with robotic excision for deep endometriosis involving the urinary tract.

Materials And Methods: We retrospectively reviewed the prospectively recorded clinical data of women consecutively undergoing minimally invasive treatment for complex endometriosis involving urinary tract in our center between January 2012 and June 2018. All the patients received a preoperative multidisciplinary evaluation with the general surgeon, the gynecologist and the urologist due to the frequent concomitant involvement of bowel and genital system. Patients undergoing robotic surgery were treated with the Si or Xi da Vinci surgical system.

Results: A total of 74 consecutive patients were enrolled. Twenty-eight (37.8%) patients underwent conventional laparoscopy and 46 (62.2%) robotic surgery. Only patients treated with robotic approach were considered for the final analyses. Overall, 17 (36.9%) patients were treated with partial cystectomy, 13 (28.3%) with ureteral reimplantation, 10 (21.7%) patients were treated with ureteral lysis, 4 (8.7%) with removal of bladder endometrial node without opening the mucosa layer and 2 (4.3%) with ureteral end-to-end anastomosis. Concomitant involvement of bowel and genital system was registered in 14 (30.4%) and 32 (69.5%) patients, respectively. No conversions to laparotomy were recorded. Overall, 5 (10.9%) patients experienced postoperative complications, of which only one was a major complication (Clavien 3b). At a median follow-up of 31.3 (IQR 17.6-43.3) months, 4 (8.7%) patients experienced disease recurrence at the level of urinary tract.

Conclusions: Robotic excision of urological endometriosis represents a safe and effective treatment option, since a limited rate of surgical complications was recorded even in cases of multi-organ disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00464-020-07502-xDOI Listing
July 2020

HPV genotype distribution and age correlation in a selected Italian population undergoing conization.

Minerva Ginecol 2020 Feb;72(1):1-11

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

Background: Detection and genotyping of human papillomavirus (HPV) has gained increasing importance in cervical cancer prevention and treatment of cervical intraepithelial neoplasia (CIN). This study aims to determine the HPV type distribution in cervical specimens obtained from women diagnosed with CIN. We evaluated in a selected Italian population the distribution of HPV genotypes.

Methods: Cervical samples were collected from women undergoing laser CO2 conization for high grade at Colposcopic Laser Surgery Unit of the Careggi University Hospital and at the Colposcopy Service of Local Health Unit Toscana Centro in Florence, Italy, between September 2014 and February 2017. HPV genotyping was performed using the LINEAR ARRAY® HPV Genotyping Test.

Results: Three hundred and six patients were enrolled. HPV infection was detected on 244 samples (79.7%). A different rate of mono- and poly-infections was observed, with higher poly-infection rates in younger women. Moreover, depending on different age groups (clustered in 5-years interval from 22 to 69 years old) significant different distribution of HPV was fund as genotype, phylogenetic type and cancer-related risk.

Conclusions: Our results suggest that some physiological conditions (i.e. menopause), could influence selection and clearance of specific HPV genotypes. The results of this study represent the basis for supporting the HPV genotyping as clinical tool providing benefits in the management of women with high CIN grade.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S0026-4784.20.04506-2DOI Listing
February 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s43032-019-00053-0DOI Listing
January 2020