Michele Morelli

Prophylactic salpingectomy in premenopausal low-risk women for ovarian cancer: Primum non nocere

OBJECTIVE The objective of this study is to compare ovarian function and surgical outcomes between patients affected by benign uterine pathologies submitted to total laparoscopic hysterectomy (TLH) plus salpingectomy and women in which standard TLH with adnexal preservation was performed. METHODS We retrospectively compared data of 79 patients who underwent TLH plus bilateral salpingectomy (group A), with those of 79 women treated by standard TLH without adnexectomy (sTLH) (group B). Ovarian reserve modification, expressed as the difference between 3 months post-operative and pre-operative values of Anti-Müllerian Hormone (AMH), Follicle Stimulating Hormone (FSH), Antral Follicle Count (AFC), mean ovarian diameters and Peak Systolic Velocity (PSV), was recorded for each patient. For each surgical procedure, operative time, variation of hemoglobin level (ΔHb), postoperative hospital stay, postoperative return to normal activity, and complication rate were recorded as secondary outcomes. RESULTS According to our post-hoc analysis, this equivalence study resulted to have a statistical power of 96.8%. Significant difference was not observed between groups with respect to ΔAMH (p=0.35), ΔFSH (p=0.15), ΔAFC (p=0.09), Δ mean ovarian diameters (p=0.57) and ΔPSV (p=0.61). In addition, secondary outcomes such as operative time (p=0.79), ΔHb (p=0.41), postoperative hospital stay (p=0.16), postoperative return to normal activity (p=0.11) and complication rate also did not show any significant difference. CONCLUSIONS The addition of bilateral salpingectomy to TLH for prevention of ovarian cancer in women who do not carry a BRCA1/2 mutations do not show negative effects on the ovarian function. In addition, no perioperative complications are related to the salpingectomy step in TLH.

Long-term Effectiveness of Presacral Neurectomy for the Treatment of Severe Dysmenorrhea Due to Endometriosis

STUDY OBJECTIVE To assess the long-term effectiveness of presacral neurectomy (PSN) in women with severe dysmenorrhea due to endometriosis treated with conservative laparoscopic surgical intervention. DESIGN Randomized, controlled trial (Canadian Task Force classification I). SETTING University-affiliated department of obstetrics and gynecology. PATIENTS One hundred forty-one sexually active women of reproductive age. INTERVENTION Conservative laparoscopic surgery without (group A) or with (group B) PSN. MEASUREMENTS AND MAIN RESULTS At entry and 24-months after surgical procedures, cure rates; frequency and severity of dysmenorrhea, dyspareunia, and chronic pelvic pain; and quality of life were evaluated. At follow-up visit, the cure rate was significantly (P<0.05) higher in group B (83.3%) than in group A (53.3%). The frequency and severity of dysmenorrhea, dyspareunia, and chronic pelvic pain were significantly (P<0.05) lower in both groups compared with baseline values, and only severity was significantly (P<0.05) lower in group B. A significant (P<0.05) improvement in quality of life was observed after surgery in both groups and was significantly (P<0.05) increased in group B compared with group A. CONCLUSION PSN improves long-term cure rates and quality of life in women treated with conservative laparoscopic surgery for severe dysmenorrhea due to endometriosis.

Wide excision of soft tissues adjacent to the ovary and fallopian tube does not impair the ovarian reserve in women undergoing prophylactic bilateral salpingectomy: results from a randomized, controlled trial.

OBJECTIVE To study the effects of the wide excision of soft tissues adjacent to the ovary and fallopian tube on ovarian function and surgical outcomes in women undergoing laparoscopic bilateral prophylactic salpingectomy. DESIGN Randomized, controlled trial. SETTING Teaching hospital. PATIENT(S) One hundred eighty-six women undergoing laparoscopic surgery for uterine myoma (n = 143) or tubal surgical sterilization (n = 43). INTERVENTION(S) Patients were randomly divided into two groups. In group A (n = 91), standard salpingectomy was performed. In group B (n = 95), the mesosalpinx was removed within the tubes. Prior to and 3 months after surgery, antimüllerian hormone (AMH), FSH, three-dimensional antral follicle count (AFC), vascular index (VI), flow index (FI), vascular-flow index (VFI), and OvAge were recorded for each patient. MAIN OUTCOME MEASURE(S) Ovarian reserve modification (Δ) before and after surgery was assessed as the primary outcome. Operative time, variation of the hemoglobin level (ΔHb), postoperative hospital stay, postoperative return to normal activity, and complication rate were assessed as secondary outcomes. RESULT(S) No significant difference was observed between groups for ΔAMH, ΔFSH, ΔAFC, ΔVI, ΔFI, ΔVFI, and ΔOvAge. Moreover, the groups were similar for operative time, ΔHb, postoperative hospital stay, postoperative return to normal activity, and complication rate. CONCLUSION(S) Even when the surgical excision includes the removal of the mesosalpinx, salpingectomy does not damage the ovarian reserve. Moreover, wide salpingectomy with excision of the mesosalpinx did not alter blood loss, hospitalization stay, or return to normal activities. CLINICAL TRIAL REGISTRATION NUMBER NCT02086370.

Postoperative administration of dienogest plus estradiol valerate versus levonorgestrel‐releasing intrauterine device for prevention of pain relapse and disease recurrence in endometriosis patients

In recent years, both dienogest, a fourth‐generation progestin, and levonorgestrel‐releasing intrauterine device have been found to be effective in terms of endometriosis‐related pelvic pain improvement. No data, however, are available about their efficacy in terms of postoperative recurrence prevention in women recently submitted to surgery for endometriosis at every stage. Our objective was to compare two postoperative medical approaches for pain control and reduction of recurrences in patients undergoing surgery for endometriosis.

Effect of different doses of progestin on uterine leiomyomas in postmenopausal women

OBJECTIVE(S) To evaluate the effects of two doses of medroxyprogesterone acetate (MPA) on uterine leiomyoma sizes and on uterine bleeding pattern in postmenopausal women treated with oral hormone replacement therapy (HRT). STUDY DESIGN Thirty natural postmenopausal women affected by uterine leiomyomas were enrolled and treated with oral micronized estradiol (E(2)) at dose of 2 mg per day, and randomized to receive in association MPA at dose of 2.5 mg daily (group A) or of 5 mg daily (group B). At the beginning of the study and after 1 year of treatment, uterine leiomyomata dimensions were measured using transvaginal ultrasonography (TV-USG). The subjects were instructed to note on a daily dairy the number and severity of abnormal uterine bleeding (AUB) episodes. RESULTS After 1 year of therapy, a significant changes in mean uterine leiomyomas size was observed in the group treated with higher dose of MPA. No significant differences in uterine bleeding were detected between the two groups. CONCLUSION(S) In postmenopausal women with uterine leiomyomas, it is necessary to use the minimal efficacious dose of progestin during HRT because of a higher risk to increase the tumors dimensions.

Mesial side ovarian incision for laparoscopic dermoid cystectomy: a safe and ovarian tissue-preserving technique

OBJECTIVE To evaluate safety and efficacy, in terms of spillage risk and ovarian tissue preservation, of mesial incision for laparoscopic dermoid cystectomy. DESIGN Randomized controlled trial. SETTING University. PATIENT(S) Sixty-seven women with dermoid cysts. INTERVENTION(S) Laparoscopic dermoid cystectomy performed by mesial incision (33 patients, study group) or antimesial incision (34 patients, control group). MAIN OUTCOME MEASURE(S) Spillage of intracystic content rate, operative times, chemical peritonitis rate, and intraoperative blood loss (ΔHb) as primary outcomes. Postoperative ovarian reserve (ΔFSH levels, basal antral follicle number, mean ovarian diameter, and peak systolic velocity at 3 and 12 months after surgery) as secondary outcome. RESULT(S) Spillage of intracystic content rate and operative time were significantly lower in the study than in the control group. None developed chemical peritonitis. ΔHb was higher in the study group but not significantly. During the follow-up, median FSH values were significantly lower in the study group, with no differences in the E(2) levels. Moreover, median basal antral follicle number, median ovarian diameter, and median peak systolic velocity were significantly higher in the study group. CONCLUSION(S) Ovarian mesial-side incision appears to be a safe as well as tissue-sparing technique. CLINICAL TRIAL REGISTRATION NUMBER .

Short-Term Administration of Tibolone plus GnRH Analog before Laparoscopic Myomectomy

STUDY OBJECTIVE To evaluate whether tibolone modifies the effectiveness of gonadotropin-releasing hormone (GnRH) analog administered before laparoscopic myomectomy. DESIGN Prospective, randomized, open, placebo-controlled clinical trial (Canadian Task Force classification I). SETTING University-affiliated hospital. PATIENTS Sixty-six women with symptomatic leiomyomas. INTERVENTIONS Patients received 2 months of treatment with GnRH analog and iron plus tibolone (group A) or placebo (group B); group C received only iron. Laparoscopic myomectomy was performed after medical treatment. MEASUREMENTS AND MAIN RESULTS Uterine volume, number and volume of leiomyomas, echogenicity and volume of the largest leiomyomas, hematologic values, and myoma-related symptoms were evaluated at baseline, 1 week before, and 1 week after surgery. We observed significant (p <0.05) reductions in uterine and leiomyomata volume, myoma-related symptoms, and improvement in hematologic values before surgery in groups A and B, without significant difference between groups compared with baseline values and group C. Operating time and blood loss were significantly (p <0.05) lower in groups A and B, without significant difference compared with group C. After surgery, significant numbers of women in group C had worsening of hematologic values (p <0.05). CONCLUSION Adding tibolone to the GnRH analog regimen before laparoscopic myomectomy does not modify the effectiveness of GnRH analog administered alone.

OvAge: a new methodology to quantify ovarian reserve combining clinical, biochemical and 3D-ultrasonographic parameters

BackgroundIn the last decade, both endocrine and ultrasound data have been tested to verify their usefulness for assessing ovarian reserve, but the ideal marker does not yet exist. The purpose of this study was to find, if any, a statistical advanced model able to identify a simple, easy to understand and intuitive modality for defining ovarian age by combining clinical, biochemical and 3D-ultrasonographic data.MethodsThis is a population-based observational study. From January 2012 to March 2014, we enrolled 652 healthy fertile women, 29 patients with clinical suspect of premature ovarian insufficiency (POI) and 29 patients with Polycystic Ovary syndrome (PCOS) at the Unit of Obstetrics & Gynecology of Magna Graecia University of Catanzaro (Italy). In all women we measured Anti Müllerian Hormone (AMH), Follicle Stimulating Hormone (FSH), Estradiol (E2), 3D Antral Follicle Count (AFC), ovarian volume, Vascular Index (VI) and Flow Index (FI) between days 1 and 4 of menstrual cycle. We applied the Generalized Linear Models (GzLM) for producing an equation combining these data to provide a ready to use information about women ovarian reserve, here called OvAge. To introduce this new variable, expression of ovarian reserve, we assumed that in healthy fertile women ovarian age is identical to chronological age. ResultsGzLM applied on the healthy fertile controls dataset produced the following equation OvAge = 48.05 - 3.14*AHM + 0.07*FSH - 0.77*AFC - 0.11*FI + 0.25*VI + 0.1*AMH*AFC + 0.02*FSH*AFC. This model showed a high statistical significance for each marker included in the equation. We applied the final equation on POI and PCOS datasets to test its ability of discovering significant deviation from normality and we obtained a mean of predicted ovarian age significantly different from the mean of chronological age in both groups.ConclusionsOvAge is one of the first reliable attempt to create a new method able to identify a simple, easy to understand and intuitive modality for defining ovarian reserve by combining clinical, biochemical and 3D-ultrasonographic data. Although design data prove a statistical high accuracy of the model, we are going to plan a clinical validation of model reliability in predicting reproductive prognosis and distance to menopause.

Effect of tibolone on breast symptoms resulting from postmenopausal hormone replacement therapy

OBJECTIVE To evaluate the incidence of breast symptoms in a population treated with various hormone replacement therapy (HRT) regimens and to detect the variations in breast symptomatology after HRT changing to tibolone administration. METHODS This prospective placebo-controlled clinical trial was conducted on healthy women on HRT reporting breast symptoms. A questionnaire was given to each woman to detect breast symptomatology. Breast tenderness and mastalgia were evaluated using a visual analogue scale (VAS). According to the choice of the each woman with breast symptoms, the HRT was changed to tibolone (2.5 mg/day per os) or to calcium carbonate (1 tab/day, placebo group). The duration of treatment was of 12 months. After 6 and 12 months breast symptomatology was re-evaluated. RESULTS Among the 600 screened women, 64 (10.7%) were suffering from breast symptomatology. After 6 and 12 months of treatment with tibolone or placebo, mean VAS score for breast tenderness and for mastalgia resulted significantly (P<0.05) decreased, without differences between groups, in comparison with basal value. Only one woman had no improvement from the breast symptoms with tibolone administration. CONCLUSIONS Shifting from classical HRT to tibolone is followed by a significant reduction of breast symptomatology in postmenopausal women with breast complaints similar to that obtained with treatment withdrawal.

Improvement in chronic pelvic pain after gonadotropin releasing hormone analogue (GnRH-a) administration in premenopausal women suffering from adenomyosis or endometriosis: a retrospective study

Abstract The aim of this study was to evaluate the improvement in catamenial chronic pelvic pain (CPP) after Gonadotropin Releasing Hormone analogue (GnRH-a) administration in women affected by adenomyosis or endometriosis. We retrospectively analysed clinical data of 63 premenopausal women with clinical suspect of adenomyosis (15 women, Group A) or endometriosis (48 women, Group B), which received GnRH-a in order to reduce CPP intensity during the time on surgery waiting list. Main outcome measures were variation of CPP intensity, numbers of days requiring analgesics and lost work productivity before and three months after GnRH-a administration. Compared to baseline, a significant decrease in CPP intensity (p < 0.05) was observed in both groups, even if this reduction was significantly higher in Group A than in Group B (p < 0.001). In both groups, moreover, a significant reduction in number of days requiring analgesics (p < 0.05) and lost work productivity (p < 0.05) was detected. In conclusion, GnRH-a administration in women with clinical suspect of adenomyosis induces a greater reduction in CPP when compared to women with endometriosis, thus representing a potential ex adiuvantibus criteria, helping TV-US in the clinical diagnosis of adenomyosis.