Giovanna Sighinolfi
@aou.mo.it
Scopus Publications
- Impaired glucose tolerance in women with BRCA1 versus BRCA2 pathogenic or likely pathogenic variants: Results from a prospective cohort study
Giovanni Grandi, Claudia Piombino, Giovanna Sighinolfi, Elena Barbieri, Marta Venturelli, Chiara Melotti, Rebecca Lippi Bruni, Valentina Grisendi, Riccardo Cuoghi Costantini, Mina Grippa, Emma Zattarin, Elena Tenedini, Elisabetta Razzaboni, Giulia Brigante, Roberto D’Amico, Benedetta Nanni, Renata Menozzi, Laura Cortesi, Massimo Dominici, Antonio La Marca, Angela Toss
Familial Cancer, 2026
Background Estrogens exert a beneficial effect on metabolism. Women carrying BRCA likely pathogenic/pathogenic variants (LP/PV) are at increased risk of premature menopause and may therefore be at higher risk of developing metabolic disorders later in life. In this single-center prospective cohort study, we investigated whether the specific BRCA mutation ( BRCA 1 vs. BRCA 2) has a differential impact on metabolism in women. Methods Eligible participants were BRCA LP/PV carriers who were premenopausal or underwent menopause –either natural or iatrogenic– within the 5 years prior to enrollment. Blood samples for lipid and glucose panels were obtained every 6 months, for a total of four time points. Body composition variables were evaluated at baseline and at the final follow-up using bioimpedance analysis. Glucose tolerance was assessed using the homeostatic model assessment for insulin resistance (HOMA-IR). Associations between lipid and glucose profile and patient characteristics were evaluated using univariable and multivariable linear regression models. Results Fifty-seven BRCA1 and 58 BRCA2 LP/PV carriers were included in the final analysis. At baseline, BRCA1 LP/PV carriers had a higher body mass index (BMI) (27.3 vs. 24.6 kg/m 2 , p = 0.01) and higher fat mass (27.3 vs. 21.9 kg, p = 0.013) than BRCA2 LP/PV carriers. Insulin levels and HOMA-IR were consistently higher in BRCA1 than in BRCA2 LP/PV carriers at all time points, and this difference was not attributable to age, BMI, menopausal status, risk-reducing salpingo-oophorectomy, previous chemotherapy or use of cholesterol-lowering agents. The lipid profile was similar between the groups, although BRCA1 LP/PV carriers showed a tendency toward a less favorable profile (higher LDL and lower HDL). Conclusions These prospective results suggest that BRCA1 LP/PV carriers might have impaired glucose tolerance and a greater tendency toward insulin resistance compared with BRCA2 LP/PV carriers: this first report needs further independent confirmations from other cohorts. - Reduced reproductive potential in young healthy women with hereditary breast and/or ovarian cancer syndrome
Giovanna Sighinolfi, Giovanni Grandi, Elena Barbieri, Marta Venturelli, Claudia Piombino, Chiara Melotti, Rebecca Lippi Bruni, Riccardo Costantini Cuoghi, Roberto D’Amico, Matteo Lambertini, Fedro A. Peccatori, Elena Tenedini, Massimo Dominici, Laura Cortesi, Antonio La Marca, Angela Toss
Communications Medicine, 2025
Young, healthy women carrying a pathogenic or likely pathogenic variant (P/LPV) in genes configuring the hereditary breast and/or ovarian cancer (HBOC) syndrome face several non-oncological issues. Among these, the implications on fertility are not yet entirely understood. Aiming to explore the ovarian reserve in young, healthy women with HBOC syndrome, we conducted a monocentric, prospective, observational cohort trial between January 2020 and September 2023. Eighty-seven healthy women aged less than 42 years with a P/LPV in HBOC predisposition genes were enrolled: 32 BRCA1 P/LPV carriers, 47 BRCA2 P/LPV carriers, and 8 carriers of P/LPV in other genes (TP53, RAD50, CHECK2, RAD51D, PALB2, ATM). AMH levels and antral follicular count (AFC) were evaluated as fertility biomarkers. No significant differences in demographic characteristics or mean levels of AMH or in AFC are observed between BRCA1 and BRCA2 P/LPV carriers. The distribution of AMH values is significantly lower compared to the general population (p = 0.019). The significant decrease in AMH levels is mostly ascribable to BRCA1 P/LPV carriers (p = 0.03). Both in the overall population and in BRCA1/2 P/LPV carriers, AFC decreases faster compared to those reported in the nomogram. A consistent trend for reduced reproductive potential in young, healthy women with HBOC syndrome is observed, particularly in BRCA1 P/LPV carriers. These findings need to be confirmed by larger studies including also women carrying P/LPV in other HBOC syndrome-related genes. Some young, healthy women have an increased chance of developing breast and/or ovarian cancer because they have inherited mutated genes from their parents. This is known as hereditary breast and/or ovarian cancer (HBOC) syndrome. We investigated whether these women also had issues with fertility. We measured two indicators of ovarian reserve. The ovarian reserve is the number of healthy eggs that a woman has in her ovaries. We found a trend for reduced reproductive potential in young, healthy women with HBOC syndrome. If these findings are confirmed by larger studies, fertility counseling could be helpful for this specific population of women. Sighinolfi et al. evaluate the ovarian reserve in young healthy women with hereditary breast and/or ovarian cancer (HBOC) syndrome. A consistent trend for reduced reproductive potential in young, healthy women with HBOC syndrome is observed, particularly in BRCA1 pathogenic/likely-pathogenic variant carriers. - Prenatal ultrasound signs of Aarskog-Scott syndrome in a twin pregnancy: A case report
Emma Bertucci, Simone Giulini, Giovanna Sighinolfi, Martina Benuzzi, Licia Lugli
International Journal of Gynecology and Obstetrics, 2024
SynopsisWe describe the case of Aarskog‐Scott syndrome in a twin pregnancy with the prenatal finding of shortened fetal long bones. - New insights into the role of LH in early ovarian follicular growth: a possible tool to optimize follicular recruitment
Antonio La Marca, Maria Longo, Giovanna Sighinolfi, Valentina Grisendi, Maria Giovanna Imbrogno, Simone Giulini
Reproductive Biomedicine Online, 2023
Evidence shows that LH participates in enhancing transition from the early stage to the antral stage of folliculogenesis. It has been demonstrated that functional LH receptors are expressed, albeit at a very low level and even in smaller follicles, during the phase that was traditionally considered to be gonadotrophin independent, suggesting a role for LH in accelerating the rate of progression of non-growing and primary follicles to the preantral/antral stage. Hypogonadotropic hypogonadism, together with other clinical conditions of pituitary suppression, has been associated with reduced functional ovarian reserve. The reduction in LH serum concentration is associated with a low concentration of anti-Müllerian hormone. This is the case in hypothalamic amenorrhoea, pregnancy, long-term GnRH-analogue therapy and hormonal contraception. The effect seems to be reversible, such that after pregnancy and after discontinuation of drugs, the functional ovarian reserve returns to the baseline level. Evidence suggests that women with similar primordial follicle reserves could present with different numbers of antral follicles, and that gonadotrophins may play a fundamental role in permitting a normal rate of progression of follicles through non-cyclic folliculogenesis. The precise role of gonadotrophins in early folliculogenesis, as well as their use to modify the functional ovarian reserve, must be investigated. - Chronic endometritis in recurrent implantation failure: Use of prednisone and IVF outcome
Simone Giulini, Valentina Grisendi, Giovanna Sighinolfi, Pierluigi Di Vinci, Daniela Tagliasacchi, Laura Botticelli, Antonio La Marca, Fabio Facchinetti
Journal of Reproductive Immunology, 2022 - The challenging screen detection of ovarian cancer in BRCA mutation carriers adhering to a 6-month follow-up program: results from a 6-years surveillance
Giovanni Grandi, Federica Fiocchi, Laura Cortesi, Angela Toss, Fausto Boselli, Margaret Sammarini, Giovanna Sighinolfi, Fabio Facchinetti
Menopause, 2022
Objective: Approximately 25% of ovarian cancer (OC) cases are related to an inherited predisposition. Genetic mutations for the oncosuppressor genes BRCA1 and 2 have the best-known linkage to a higher incidence of OC and breast cancer, in approximately 70% to 80% of hereditary OC cases. To provide the first comprehensive clinical description of screen-detected (SD) OCs during a 6-years surveillance of a cohort of young BRCA carriers and carriers who refuse risk-reducing salpingo-oophorectomy. Methods: A prospective cohort study in a university hospital describing 191 women with BRCA1 and 2 mutations adhering continuously to our surveillance between 2015 and 2020, including a 6-monthly evaluation of cancer antigen 125 (CA 125) with concomitant transvaginal ultrasound (TVUS) performed by a dedicated specialist. Main outcomes were tumor's laterality, CA 125 at diagnosis, TVUS and computed tomography (CT) findings. Results: Risk-reducing salpingo-oophorectomy was performed in 58/191 (30.4%) of mutation carriers during the study period (one OC case identified). Nine SD-OCs and no interval OCs were found in the remaining 133 women. OCs (FIGO stage I or II: 88.9%) occur mainly in BRCA 1 (77.8%), being bilateral in 85.7% BRCA 1 and unilateral in 100% BRCA 2. No lesions involved only the tubes: left ovaries/tubes were more frequently involved. We have described three new possible scenarios regarding imaging: 1) Evident cases (33.3%, TVUS and CT obvious for OC, CA 125 sensitivity: 100%), 2) Possible cases (55.6%, TVUS and CT are in general accordance, documenting new TVUS signs: increased solid pattern of the ovary with peripheral cortical small cysts, hypoechoic circular mass near the ovary, intraparenchymal small hyperechoic foci), and 3) Hidden cases (11.1%, the smallest lesion but the highest stage (IIIA2), with CA 125 44.2 U/mL and concomitant endometrial hyperplasia). Conclusions: Different diagnostic tools must integrate to ensure early diagnosis of OC in BRCA mutation carriers adhering to a follow-up program. - Satisfaction with prophylactic risk-reducing salpingo-oophorectomy in BRCA mutation carriers is very high and little dependent on the participants' characteristics at surgery: a prospective study
Giovanni Grandi, Margaret Sammarini, Laura Cortesi, Angela Toss, Laura Botticelli, Federico Varliero, Giovanna Sighinolfi, Elena Barbieri, Fabio Facchinetti
Menopause, 2021
Objective: BRCA carriers are recommended to undergo prophylactic risk-reducing salpingo-oophorectomy (RRSO). Possible adverse health impacts of RRSO, particularly when done before natural menopause, can reduce the long-term satisfaction with this risk-reducing strategy. The aim of this study was to prospectively evaluate the level of satisfaction of women undergoing RRSO, also in relation to some specific characteristics at RRSO. Methods: A prospective cohort study was performed in the Modena Family Cancer Clinic of the University Hospital of Modena (Italy). All BRCA1/2 confirmed mutation carriers who decided to undergo RRSO were recruited between 2016 and 2019. Results: Fifty-five women (29 BRCA1 and 26 BRCA2) (mean age: 50.4 ± 7.7 years [range 35-79]) were included with a mean follow-up after RRSO of 660.9 days (1.8 years) (range 35-1,688 days) (median: 549 days). No intraepithelial (Serous Tubal Intraepithelial Carcinoma)/invasive cancers were found (0%) at RRSO. No vasomotor symptoms at 1 month after surgery were reported by 11/22 (50%) premenopausal women at RRSO. All women (100%) with new “RRSO-caused” vasomotor symptoms with no previous breast cancer initiated postmenopausal hormone therapy. At the final follow-up the satisfaction rate (0-100 visual analog scale points) of the participants was 96.4 ± 8.6 points (range 62-100). To the question “Would you undergo RRSO again if it was proposed today? (0-100 visual analog scale points)” the answer was 99.4 ± 3.2 points (range 79-100). These scores were in general very high and did not change in the different groups according to pre/postmenopausal status at RRSO, cancer survivors versus healthy women at RRSO, BRCA status, hormone therapy users/nonusers after RRSO, “RRSO-caused” symptoms versus not RRSO-caused (P > 0.05). Conclusions: Findings from this prospective study suggest that satisfaction with RRSO is very high and little dependent on the participants’ characteristics at surgery. Women at high risk for ovarian cancer are very satisfied with their choice of risk-reduction strategy. Video Summary: http://links.lww.com/MENO/A712. - New strategies of ovarian stimulation based on the concept of ovarian follicular waves: From conventional to random and double stimulation
Giovanna Sighinolfi, Sesh Kamal Sunkara, Antonio La Marca
Reproductive Biomedicine Online, 2018 - Female age, serum antimüllerian hormone level, and number of oocytes affect the rate and number of euploid blastocysts in in vitro fertilization/intracytoplasmic sperm injection cycles
Antonio La Marca, Maria Giulia Minasi, Giovanna Sighinolfi, Pierfrancesco Greco, Cindy Argento, Valentina Grisendi, Francesco Fiorentino, Ermanno Greco
Fertility and Sterility, 2017 - How to personalize ovarian stimulation in clinical practice
Giovanna Sighinolfi, Valentina Grisendi, Antonio La Marca
Journal of the Turkish German Gynecology Association, 2017
Controlled ovarian stimulation (COS) in in vitro fertilization (IVF) cycles is the starting point from which couple’s prognosis depends. Individualization in follicle-stimulating hormone (FSH) starting dose and protocol used is based on ovarian response prediction, which depends on ovarian reserve. Anti-Müllerian hormone levels and the antral follicle count are considered the most accurate and reliable markers of ovarian reserve. A literature search was performed for studies that addressed the ability of ovarian reserve markers to predict poor and high ovarian response in assisted reproductive technology cycles. According to the predicted response to ovarian stimulation (poor- normal- or high- response), it is possible to counsel couples before treatment about the prognosis, and also to individualize ovarian stimulation protocols, choosing among GnRH-agonists or antagonists for endogenous FSH suppression, and the FSH starting dose in order to decrease the risk of cycle cancellation and ovarian hyperstimulation syndrome. In this review we discuss how to choose the best COS therapy, based on ovarian reserve markers, in order to enhance chances in IVF. - Live birth rates in the different combinations of the Bologna criteria poor ovarian responders: A validation study
Antonio La Marca, Valentina Grisendi, Simone Giulini, Giovanna Sighinolfi, Alessandra Tirelli, Cindy Argento, Claudia Re, Daniela Tagliasacchi, Tiziana Marsella, Sesh Kamal Sunkara
Journal of Assisted Reproduction and Genetics, 2015 - The menstrual cycle regularization following d-chiro-inositol treatment in PCOS women: A retrospective study
Antonio La Marca, Valentina Grisendi, Giulia Dondi, Giovanna Sighinolfi, Antonio Cianci
Gynecological Endocrinology, 2015 - The ovarian response to controlled stimulation in IVF cycles may be predictive of the age at menopause
A. La Marca, G. Dondi, G. Sighinolfi, S. Giulini, E. Papaleo, A. Cagnacci, M. J. Faddy
Human Reproduction, 2014 - Polymorphisms in gonadotropin and gonadotropin receptor genes as markers of ovarian reserve and response in in vitro fertilization
Antonio La Marca, Giovanna Sighinolfi, Cindy Argento, Valentina Grisendi, Livio Casarini, Annibale Volpe, Manuela Simoni
Fertility and Sterility, 2013 - Prediction of Age at Menopause from Assessment of Ovarian Reserve May Be Improved by Using Body Mass Index and Smoking Status
Antonio La Marca, Giovanna Sighinolfi, Enrico Papaleo, Angelo Cagnacci, Annibale Volpe, Malcolm J. Faddy
Plos One, 2013 - Possibilities and limits of ovarian reserve testing in ART
Antonio La Marca, Cindy Argento, Giovanna Sighinolfi, Valentina Grisendi, Marilena Carbone, Giovanni D'Ippolito, Alfredo Carducci Artenisio, Gaspare Stabile, Annibale Volpe
Current Pharmaceutical Biotechnology, 2012 - Anti-Müllerian hormone-based prediction model for a live birth in assisted reproduction
A. La Marca, S.M. Nelson, G. Sighinolfi, M. Manno, E. Baraldi, L. Roli, S. Xella, T. Marsella, D. Tagliasacchi, R. D’Amico, A. Volpe
Reproductive Biomedicine Online, 2011 - Age-specific nomogram for the decline in antral follicle count throughout the reproductive period
Antonio La Marca, Elena Spada, Giovanna Sighinolfi, Cindy Argento, Alessandra Tirelli, Simone Giulini, Silvano Milani, Annibale Volpe
Fertility and Sterility, 2011 - Normal serum concentrations of anti-Müllerian hormone in women with regular menstrual cycles
A. La Marca, G. Sighinolfi, S. Giulini, M. Traglia, C. Argento, C. Sala, C. Masciullo, A. Volpe, D. Toniolo
Reproductive Biomedicine Online, 2010 - Primary ovarian insufficiency: Autoimmune causes
Antonio La Marca, Annalisa Brozzetti, Giovanna Sighinolfi, Stefania Marzotti, Annibale Volpe, Alberto Falorni
Current Opinion in Obstetrics and Gynecology, 2010 - Anti-Müllerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART)
A. La Marca, G. Sighinolfi, D. Radi, C. Argento, E. Baraldi, A. C. Artenisio, G. Stabile, A. Volpe
Human Reproduction Update, 2009
