State of the art and emerging drug therapies for female infertility.

At present, infertility is a key-issue. When applicable, in vitro fertilization (IVF) has become the standard approach to treat this condition but a thorough investigation and, whenever possible, the individual diagnosis of the underlying causes of infertility are required. For many female causes, indeed, efficient medical therapies are available to achieve a fast solution of the problem. This review is based on the relevant literature indexed in PubMed and SCOPUS and is focused on the most recent clinical literature on the treatment of women (and couples) affected from infertility. The reduction in IVF treatment burden and risks are now considered pivotal to set 'patient-friendly' therapies and represent crucial issues for both patients and physicians. To this end, the researchers are now focusing their attention on old drugs with new indications and new compounds with more appropriate functions, to improve the compliance of the women and reduce the burden of infertility, a condition that is becoming an important issue in the modern world, also for the Public Health System.

A case of suspected illegal abortion: how clinicians may assist the forensic pathologist.

Abortion may be performed in a safe or unsafe manner, the latter being a frequent and dangerous event. It can also be performed in countries where abortion is legally recognised but, for various reasons, may be undertaken in an illegal environment. We present a case of a possible illegal abortion. A woman presented to the hospital with a dead fetus, saying that she was the victim of a car accident. Forensic and gynaecological examination of the woman were carried out, along with an autopsy of the fetus. It was discovered that the woman had performed a clandestine abortion. The differential diagnosis between illegal abortion and miscarriage represents a complicated issue and requires both clinical and forensic support. The gynaecologist may be of assistance to the forensic pathologist in confirming whether an illegal abortion has been performed.

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.

Failure to recognize preoperatively high-risk endometrial carcinoma is associated with a poor outcome.

OBJECTIVE: To evaluate the misdiagnosis between endometrial biopsy and definitive surgical pathology and to assess whether the failure in recognizing preoperatively high-risk endometrial carcinoma (EC) can impact oncological outcomes. STUDY DESIGN: A retrospective study was conducted to evaluate patients with EC diagnosed by preoperative endometrial biopsy who subsequently underwent surgical staging between 2006 and 2013 at our institution. In patients with a surgical diagnosis of high-risk EC, histotype and grade change between the endometrial biopsy and surgical specimen (discordance diagnosis) were evaluated and correlated to survival outcomes. Cox's regression model for multivariable analysis was used to evaluate the effect of several variables (age, stage, discordance in diagnosis, co-morbidities, frozen section, extensive surgical staging and adjuvant chemotherapy) on the survival rate. RESULTS: Data from 447 patients were reviewed. Among 109 women with surgical diagnosis of high-risk EC, 35 (32.1%) were preoperatively misdiagnosed. Of these 35 women, 24 (68.6%) cases were upgraded to grade 3, and 11 (3.4%) were upgraded to serous or clear cell type in the definitive specimen. The 5-year overall survival (OS; 70.2 vs. 86.8%; p=0.029), disease-specific survival (DSS; 72.5 vs. 88.2%; p=0.039) and recurrence free survival (RFS; 62.6 vs. 82.5%; p=0.024) were significantly lower in the high-risk EC patients who were preoperatively undiagnosed in the endometrial biopsy compared with patients with an appropriate preoperative histological diagnosis. Controlling for age, stage, co-morbidities, frozen section, extensive surgical staging and adjuvant chemotherapy, multivariable analysis revealed that discordance in diagnosis was associated with poorer survival outcomes. CONCLUSION: Failure to recognize preoperatively high-risk ECs is associated with worse outcomes.

Polycystic ovary syndrome: chemical pharmacotherapy.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disease among women of childbearing age. The clinical features are heterogeneous and vary in intensity. Hirsutism, menstrual disorders and infertility are the most frequent conditions observed; however, long-term complications (dyslipidemia, hypertension, cardiovascular disease, type 2 diabetes mellitus, endometrial cancer) are also often described. Each disorder may be managed by tailored strategies, employing sequential or combined pharmacological and/or non-pharmacological treatment. AREAS COVERED: The authors review the drugs used for PCOS management and discuss new approaches. A systematic MEDLINE search regarding the randomized controlled trials, retrospective and observational studies about medical treatments of PCOS, the Cochrane library for reviews and also search for registered trials on ClinicalTrials.gov is performed. EXPERT OPINION: A uniform treatment for PCOS patients does not exist. Clinicians should perform an accurate evaluation of patients' characteristics, identifying the phenotypic target and, subsequently, the best-tailored treatment to manage one or more clinical issues. Lifestyle intervention should always be the first recommended approach unless other issues indicate that drug or hormonal interventions are superior.

Sonographic findings in postmenopausal women with a prior endometrial ablation: interpretation and management of women with endometrial thickening and bleeding.

OBJECTIVE: To understand the meaning of endometrial thickening and bleeding in postmenopausal women who had previously undergone endometrial ablation (EA). DESIGN: Retrospective observational study. Canadian Task Force III. SETTING: Obstetrics and Gynecology Unit, Magna Graecia University, Catanzaro, Italy. PATIENTS: Sixty-three postmenopausal women who had previously undergone EA. INTERVENTIONS: A retrospective evaluation of clinical charts of postmenopausal women who had a follow-up visit after EA between January 2000 and August 2014. MEASUREMENTS AND MAIN RESULTS: The rates of endometrial thickening (with or without bleeding), endometrial atrophy, and cancer were determined. Postmenopausal bleeding was reported in 9 patients (14.3%). Endometrial thickening was observed in 51 patients (80.9%; mean ± SD endometrial thickness, 7.7 ± 3.0 mm). A significantly (p < .05) greater number of patients with an endometrial thickness of 5 to 10 mm was observed compared with those with an endometrial thickness of <5 mm or >10 mm. A significant (p = .001) difference in increase in endometrial thickness was observed between patients with and without bleeding. Overall, hysteroscopy plus endometrial biopsy was scheduled in 24 patients. In all bleeding women, a histological diagnosis of endometrial atrophy was demonstrated. Concerning bleeding-free women, in 14 patients with endometrial thickening of >10 mm, mucosal atrophy was detected. The only bleeding-free patient in whom an endometrial echogenic fluid collection was detected had a histological diagnosis of endometrioid endometrial cancer. Thus, patients who underwent hysteroscopy had a 95.8% rate of mucosal atrophy and a 4.2% rate of endometrial cancer. The overall cancer rate in our global population (menopause with previous EA) was 1.6%. CONCLUSION: Postmenopausal bleeding and sonographic detection of endometrial thickening in patients with previous EA are not necessarily related to a malignant disease. Nonetheless, ultrasound visualization of endometrial thickening plus an echogenic endometrial fluid collection in these patients always warrants an invasive diagnostic procedure regardless of whether or not bleeding is reported.

An unusual extremely distant noncommunicating uterine horn with myoma and adenomyosis treated with laparoscopic hemihysterectomy.

A 41-year-old woman referred to us with dysmenorrhea and severe pelvic pain although she was previously submitted to right laparotomic adnexectomy for ovarian endometrioma and to a subsequent operative laparoscopy for pelvic adhesions. After ultrasound examination, the patient underwent diagnostic hysteroscopy and operative laparoscopy which confirmed the clinic suspect of an unicornuate uterus. However, it was very unusual to see an extremely distanced right horn, without communication with uterus, without adnexa, and with a small myoma belonging to it. Moreover, omentum and bowel were attached to fundus of right horn and thick adhesions fixed it to rectum and right pelvic wall. Therefore, identification of anatomical structures was difficult, as it was extremely arduous to isolate the ureter, which was involved inside the adhesions surrounding the right uterine horn. Nevertheless, laparoscopic right hemihysterectomy was successfully performed and right horn was sent to our pathologist who recognized hypotrophic endometrium and adenomyosis.

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.

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

AIM: 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. MATERIAL AND METHODS: Ninety-two patients undergoing surgery for endometriosis and subsequent treatment by estradiol valerate + dienogest (EP) (group A) or levonorgestrel-releasing uterine device (LNG-IUD) (Group B) between January 2009 and June 2010 were retrospectively analyzed. The primary endpoints were pain relapse and disease recurrence rate at 12 and 24 months. The secondary endpoint was patient satisfaction with the therapy at 24 months. RESULTS: Forty-eight patients in Group A and 44 in Group B were examined. At 12 and 24 months a statistically greater reduction both in Ca125 levels and VAS score was seen in women treated with EP compared to LNG-IUD. The recurrence rate at 12 and 24 months follow-up was slightly lower, but not at a significant level, in Group A than in Group B. Finally, satisfaction with treatment at 24 months was significantly higher in Group B. CONCLUSION: EP administration is significantly more effective than LNG-IUD in reducing pelvic pain and more effective in reducing recurrence rate but not at a significant level. LNG-IUD, however, has significantly higher patient satisfaction.

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

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.

Efficacy of the levonorgestrel intrauterine system (LNG-IUS) in the prevention of the atypical endometrial hyperplasia and endometrial cancer: retrospective data from selected obese menopausal symptomatic women.

The aim of this retrospective study was to evaluate the efficacy of levonorgestrel intrauterine system-releasing (LNG-IUS) insertion in preventing atypical endometrial hyperplasia (AH) and endometrial cancer (EC) in symptomatic postmenopausal overweight/obese women. A total of 34 overweight/obese postmenopausal women, presenting abnormal uterine bleeding (AUB) and endometrial hyperplasia (EH), and who were submitted to LNG-IUS insertion, were identified from registry data. Endometrial histology at LNG-IUS insertion showed simple EH in 20 cases (58.8%), complex EH in 14 cases (41.2%). At 36 months, 91% of patients showed no recurrence of AUB and a significant reduction in the mean endometrial thickness (from 8.2 ± 2.2 to 3.2 ± 1.5 mm, p < 0.05) was observed. Histologic regression of EH was observed in 27 (79.4%) and 33 (97.5%) cases at 12 and 36 months, respectively. None of the women in which EH persisted, reported cellular atypia or cancer progression at 12 and 36 months of follow-up. LNG-IUS represents an effective treatment option to manage postmenopausal obese women affected by AUB and EH. The device seems to be able to prevent the onset of AH and EC in women at high risk. Further prospective controlled studies in a well selected group of women are needed.

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: .

Laparoscopic surgery vs laparotomy for early stage endometrial cancer: long-term data of a randomized controlled trial.

OBJECTIVE: The purpose of the study was to compare the long-term safety and efficacy of laparoscopic surgery and laparotomy approaches to early stage endometrial cancer. STUDY DESIGN: This was a prospective long-term extension study of a randomized controlled study that included 84 patients with clinical stage I endometrial cancer (laparoscopic surgery group, 40 women; laparotomy group, 38 women). Safety and efficacy data were evaluated and analyzed by the intention-to-treat principle. RESULTS: After a follow-up period of 78 months (interquartile range, 7; range, 19-84 months) and 79 months (interquartile range, 6; range, 22-84 months) for laparoscopic surgery and laparotomy groups, respectively, no difference in the cumulative recurrence rates (8/40 [20.0%] and 7/38 [18.4%]; P = .860) and deaths (7/40 [17.5%] and 6/38 [15.8%] patients; P = .839) was detected between groups. No significant differences in overall (P = .535) and disease-free (P = .512) survival were observed. CONCLUSION: The laparoscopic surgery approach to early stage endometrial cancer is as safe and effective a procedure as the laparotomy approach.

Laparoscopic treatment for endometrial cancer: a meta-analysis of randomized controlled trials (RCTs).

OBJECTIVE: To define, if any, type I clinical evidence regarding the safety and efficacy of the laparoscopic approach to endometrial cancer. METHODS: Meta-analysis of randomized controlled trials (RCTs). RESULTS: Four RCTs were identified and included in the final analysis. No significant difference between laparoscopic and laparotomic approaches to endometrial cancer in overall [odds ratio (OR)=0.80, 95%CI 0.37 to 1.70, P=0.695], disease-free (OR=0.76, 95%CI 0.34 to 1.72, P=0.655), and cancer-related (OR=0.89, 95%CI 0.19 to 4.13, P=0.815) survival was observed. Significantly longer operative time (OR=53.48, 95%CI 37.28 to 69.68, P=0.0002), lower intraoperative blood loss (OR=-266.86, 95%CI -454.82 to -78.90, P=0.005) and postoperative complications (OR=0.40, 95%CI 0.23 to 0.70, P=0.007) were associated to laparoscopy. No effect of laparoscopy on pelvic (OR=0.62, 95%CI -1.47 to 2.71, P=0.560) and para-aortic (OR=1.49, 95%CI -2.49 to 5.60, P=0.477) nodes yield, and intraoperative complications (OR=1.60, 95%CI 0.49 to 5.22, P=0.390) was observed. CONCLUSIONS: Even if limited by few RCTs with short-term follow-up, our data suggest that laparoscopic approach should be considered an effective and safe procedure for patients with early stage endometrial cancer as well as laparotomic one. Notwithstanding the longer operative time, advantages of the laparoscopy over traditional laparotomy regard intraoperative blood loss and postoperative complications.