New clinical targets of d-chiro-inositol: rationale and potential applications

Introduction Inositols have a key role in ovarian physiology and the literature reports a wealth of studies about the major isomer, myo-inositol (MI). However, information aboutd-chiro-inositol (DCI) is still scarce, despite the ratio MI:DCI is tissue-specific and actively maintained by an insulin-dependent epimerase enzyme. Areas covered This expert opinion provides an overview of the physiological contribution of DCI in regulating steroidogenesis. DCI indeed mediates the intracellular signaling of insulin, which induces the biosynthesis of androgens. Studies on second messengers of insulin also revealed that DCI has a specific role in modulating the activity of aromatase enzyme. Specifically, recent findings demonstrated that DCI influences the enzyme gene expression, thus reducing the conversion of androgens into estrogens. Expert opinion Available evidence suggests that the effects of DCI administration may be similar to those of aromatase inhibitors, but without causing hypo-estrogenic states. Therefore, DCI treatments should be evaluated for either estrogen-dependent gynecological conditions or low testosterone states in male subjects

Diagnosis: Patient Evaluation (Flowchart)

The diagnosis of intrauterine adhesions (IUAs) and Asherman\u2019s syndrome has always been challenging. The development of diagnostic techniques and the raised awareness of the condition have led to a more reliable diagnosis and management of this intrauterine pathology. In this chapter, we summarize how to make the diagnosis of IUAs and Asherman\u2019s syndrome, starting from the clinical suspicion, the first-level techniques (ultrasound scan), and the second-level ones for confirmation (hysteroscopy, or when this is not available, hysterosalpingography, sonohysterography, and magnetic resonance imaging). In particular, we highlight the key diagnostic elements for each step of the diagnostic process to suggest a specific flowchart to follow

Endometriosis and gynaecological cancers: molecular insights behind a complex machinery

Endometriosis is described as the presence of both endometrial glandular and stromal cells outside the uterine cavity. A major characterization of this disease is ectopic implantation of endometrial cells with in- creased migration. It is one of the leading causes of morbidity among premenopausal women, with a preva- lence of 10–16% of women of reproductive age. Despite over century of intensive research, none of the current treatment options represents a real cure. Based on the current knowledge, endometriosis, particularly its atypi- cal version, is considered to be a transitional form from benign disease to tumour. However, the exact mecha- nisms of this conversion are still not fully established

Is color Doppler ultrasonography reliable in diagnosing adnexal torsion? A large cohort analysis

IntroductionColor Doppler ultrasonography (CDU) is widely used to diagnose adnexal torsion (AT). However, its validity remains questionable due to its low sensitivity. Our study aimed to evaluate the accuracy of CDU for the preoperative diagnosis of AT.Material and methodsThe electronic medical records of patients who were taken to the operating room with the diagnosis of suspected AT were reviewed. Patients having surgically/pathologically-proven AT were compared with patients who were found to have a different pathology at the time of surgery. CDU validity was assessed using a 2 x 2 table and compared with a diagnostic model that consists of the Doppler findings, patient's age, and previous surgical history.ResultsAT was diagnosed correctly in 74.6% of cases. Absent Doppler flow was seen in only 18.6% of cases. Although its specificity and positive predictive value were high, CDU had very low sensitivity and negative predictive value. The combined diagnostic model exceeded CDU alone in terms of diagnostic accuracy.ConclusionsThe use of CDU alone is not a reliable modality to exclude AT. Absent Doppler flow is a sign of ovarian necrosis. Clinical correlation between CDU findings and the patient's symptoms makes the diagnosis of AT more timely and accurate

Is color Doppler ultrasonography reliable in diagnosing adnexal torsion? A large cohort analysis

IntroductionColor Doppler ultrasonography (CDU) is widely used to diagnose adnexal torsion (AT). However, its validity remains questionable due to its low sensitivity. Our study aimed to evaluate the accuracy of CDU for the preoperative diagnosis of AT.Material and methodsThe electronic medical records of patients who were taken to the operating room with the diagnosis of suspected AT were reviewed. Patients having surgically/pathologically-proven AT were compared with patients who were found to have a different pathology at the time of surgery. CDU validity was assessed using a 2 x 2 table and compared with a diagnostic model that consists of the Doppler findings, patient's age, and previous surgical history.ResultsAT was diagnosed correctly in 74.6% of cases. Absent Doppler flow was seen in only 18.6% of cases. Although its specificity and positive predictive value were high, CDU had very low sensitivity and negative predictive value. The combined diagnostic model exceeded CDU alone in terms of diagnostic accuracy.ConclusionsThe use of CDU alone is not a reliable modality to exclude AT. Absent Doppler flow is a sign of ovarian necrosis. Clinical correlation between CDU findings and the patient's symptoms makes the diagnosis of AT more timely and accurate

Novel drug delivery methods for improving efficacy of endometriosis treatments

Pharmacotherapy has a key role in the management of endometriosis. However, a significant proportion of patients gains only intermittent or limited benefits. In this regard, alternative and novel drug delivery methods are of paramount importance to improve efficacy and compliance of available treatments and develop alternative medical approaches

Evaluation of menstrual irregularities after COVID-19 vaccination: Results of the MECOVAC survey

We investigated menstrual irregularities after the first and second doses of the COVID-19 vaccine. Women answered a customised online questionnaire (ClinicalTrial.gov ID: NCT05083065) aimed to assess the vaccine type, the phase of the menstrual cycle during which the vaccine was administered, the occurrence of menstrual irregularities after the first and second doses, and how long this effect lasted. We excluded women with gynaecological and non-gynaecological diseases, undergoing hormonal and non-hormonal treatments, in perimenopause or menopause, as well as those who had irregular menstrual cycles in the last 12 months before vaccine administration. According to our data analysis, approximately 50-60% of reproductive-age women who received the first dose of the COVID-19 vaccine reported menstrual cycle irregularities, regardless of the type of administered vaccine. The occurrence of menstrual irregularities seems to be slightly higher (60-70%) after the second dose. Menstrual irregularities after both the first and second doses of the vaccine were found to self-resolve in approximately half the cases within two months. Based on these results, we suggest to consider these elements during the counselling of women who receive the COVID-19 vaccine, letting them know about the potential occurrence of temporary and self-limiting menstrual cycle irregularities in the subsequent month(s)

Clitoral reconstructive surgery after female genital mutilation: A systematic review

To summarize available evidence on clitoral reconstruction after Female genital mutilations/cut (FGM/C)

Linzagolix: a new GnRH-antagonist under investigation for the treatment of endometriosis and uterine myomas

Introduction Uterine myomas and endometriosis are benign hormone-dependent diseases affecting women of reproductive age. Substantial efforts have been made to develop innovative medical options for treating these gynecologic diseases. Elagolix and relugolix have been approved in some countries for treating endometriosis and myomas, respectively; however, linzagolix (OBE 2109, KLH 2109) is a new oral gonadotropin-releasing hormone (GnRH) antagonist in phase II-III trials. Treatment options for women with contraindications for hormonal therapies or who refuse particular options, are the driving force behind the development of new drugs in this area. Area covered This drug evaluation highlights definitive and preliminary results from previous and ongoing studies of linzagolix for the treatment of endometriosis and myomas. Expert opinion Linzagolix showed a dose-dependent and rapidly reversible action on the pituitary-gonadal axis. In a recent phase II trial (EDELWEISS), linzagolix significantly reduced pain related to endometriosis and improved quality of life at single daily doses of 75-200 mg. The preliminary results of international, double-blind phase III trials (PRIMROSE 1 and 2) reported its efficacy in treating heavy menstrual bleeding related to myomas with a good safety profile. Further studies will determine the necessity of add-back therapy during long-term use of linzagolix

Comparison of three biopsy forceps for hysteroscopic endometrial biopsy in postmenopausal patients (HYGREB-1): A multicenter, single-blind randomized clinical trial

Objective To compare three types of biopsy forceps for hysteroscopic endometrial biopsy in postmenopausal women.Methods Postmenopausal women undergoing operative hysteroscopy with endometrial biopsy for abnormal uterine bleeding or endometrial thickness (>= 5 mm) were included. Operative hysteroscopy with endometrial biopsy was performed by hysteroscopic forceps. Women were randomized (1:1:1 ratio) in three groups and allocated to undergo endometrial biopsy by hysteroscopy using spoon, alligator, or snake forceps.Results Seventy-five women were included in the study, 25 in each group. The duration of the biopsy was comparable between the three groups (P = 0.334) with a median of 180 seconds (range 20-480 seconds). No differences were observed about the number of attempts (P = 0.602), the use of another instrument (P = 0.276), and the biopsy appropriateness (P = 0.592). The spoon forceps group reported higher levels of pain compared to the alligator and snake forceps groups (P < 0.001). The spoon forceps received significantly lower scores by the operator compared to the alligator and snake forceps (P < 0.001). The alligator and snake forceps reported wider biopsy than the spoon forceps (P < 0.001).Conclusion Snake and alligator hysteroscopic forceps may be considered the first choice to perform an endometrial biopsy in postmenopausal women.ClinicalTrials.gov: NCT03427957