Spontaneous fertility after expectant or surgical management of rectovaginal endometriosis in women with or without ovarian endometrioma: a retrospective analysis.

OBJECTIVE: To investigate spontaneous pregnancy rate (SPRs) of women with rectovaginal endometriosis (RV) with/without ovarian endometrioma (OMA) and treated with the use of expectant or surgical management. DESIGN: Retrospective study. SETTING: University hospital. PATIENT(S): The study included patients with RV with or without OMA who tried to conceive spontaneously for 1 year either without undergoing surgery (group E; n = 284) or after surgery (group S; n = 221). The study population was further divided into four subgroups: women with RV without OMA who directly tried to conceive (group eRV; n = 121) or tried to conceive after surgery (group sRV; n = 96), and women with RV with OMA who directly tried to conceive (group eOMA; n = 163) or tried to conceive after surgery (group sOMA; n = 125). INTERVENTIONS(S): Expectant or surgical management. MAIN OUTCOME MEASURE(S): Crude and cumulative SPRs. RESULT(S): At 1 year, crude and cumulative SPRs were lower in group E (17.3% and 23.8%, respectively) than in group S (35.7% and 39.5%). Similarly, crude and cumulative SPRs were lower in group eRV (24.8% and 30.6%) than in group sRV (42.7% and 45.7%, respectively) and in group eOMA (11.7% and 18.0%) than group sOMA (30.4% and 34.5%). At 1 year, crude and cumulative SPRs were higher in group eRV (24.8% and 30.6%) than in group eOMA (11.7% and 18.0%), and in group sRV (42.7% and 45.7%) than in group sOMA (30.4% and 34.5%). CONCLUSION(S): Crude and cumulative SPRs are lower in women treated with the use of expectant rather than surgical management. The presence of OMAs decreases SPRs independently from the treatment modality adopted.

Efficacy and acceptability of long-term norethindrone acetate for the treatment of rectovaginal endometriosis.

OBJECTIVE: To study the efficacy of long-term treatment with norethindrone acetate (NETA) in patients with rectovaginal endometriosis. STUDY DESIGN: This retrospective cohort study included 103 women with pain symptoms caused by rectovaginal endometriosis. Patients received NETA alone (2.5mg/day up to 5mg/day) for 5 years. Primary outcome was the degree of satisfaction with treatment after 5 years of progestin therapy. Secondary outcomes were the assessment of any variation in pain symptoms and the volumetric assessment of the disease by magnetic resonance imaging (MRI). RESULTS: Sixty-one women completed the 5-year follow-up (61/103, 59.2%) with 16 women withdrawing because of adverse effects (38.1%). Overall, 68.8% (42/61) of the women who completed the study were satisfied or very satisfied of this long term NETA treatment. This represents a 40.8% (42/103) of the patients enrolled. Intensity of chronic pelvic pain and deep dyspareunia significantly decreased during treatment (p<0.001 versus baseline at 1 and 5year). Dyschezia improved after 1-year respect to baseline (p=0.008) but remained stable between first and second year (p=0.409). At the end of 5 years treatment, a radiological partial response was observed in 33 patients (55.9%, n 33/59); a stable disease in 19 patients (32.2%, n 19/59). Seven women (7/59, 11.9%) displayed a volumetric increase of rectovaginal endometriosis under NETA treatment. CONCLUSION: Five-year therapy with NETA is safe and well tolerated by women with rectovaginal endometriosis. Due to its low cost and good pharmacological profile, it represents a good candidate for long-term treatment in this setting.

Impact of large ovarian endometriomas on the response to superovulation for in vitro fertilization: A retrospective study.

OBJECTIVE: To assess the response to superovulation for in vitro fertilization (IVF) in patients with unilateral endometriomas with diameter ≥5cm and in the contralateral healthy ovary. STUDY DESIGN: This retrospective analysis of a prospectively collected database included patients who underwent superovulation for IVF/ICSI cycles and had unoperated single unilateral endometrioma with diameter ≥5cm and healthy contralateral ovary. The primary outcome of the study was to compare the number of oocyte retrieved in the ovary with the endometrioma and the contralateral healthy ovary. RESULTS: The total number of follicles was lower in ovaries with endometriomas (2.6±1.3) than in healthy ovaries (4.8±2.0; p<0.001). The number of codominant follicles and the total number of oocytes retrieved were lower in ovaries with endometriomas (1.5±0.9 and 2.0±1.2) than in the contralateral ovaries (3.7±1.5 and 4.2±1.7; p<0.001, respectively). The number of oocytes retrieved suitable for fertilization was lower in ovaries with endometriomas (1.5±1.1) than in the healthy ovaries (3.3±1.5; p<0.001). The total number of oocytes retrieved and the number of oocytes retrieved suitable for fertilization were lower in ovaries with endometriomas respectively in 21 (80.8%) and in 20 (76.9%) cases. The decreased responsiveness to ovarian superovulation was confirmed considering women with ultrasonographic diagnosis of deep infiltrating endometriosis. 30.8% of patients had positive HCG; the pregnancy rate was 23.1%. CONCLUSION: The presence of large endometriomas (≥5cm) at time of IVF significantly decreases the number of oocyte retrieved compared with the contralateral healthy ovaries.

The role of fulvestrant in endometrial cancer.

INTRODUCTION: Endometrial cancer is the most common malignancy of the female genital tract in industrialized countries. The traditional treatment of endometrial cancer is based on a surgical approach. In recent years, systemic endocrine therapy has demonstrated good efficacy in recurrent or metastatic setting, delaying progression, ameliorating quality of life and palliating symptoms. Areas covered: Phase I and II studies on selective estrogen receptor down-regulators used for the treatment of endometrial cancer treatment have been reviewed. The pharmacokinetic and pharmacodynamic features of selective receptor down-regulators have been also investigated. Expert opinion: Selective estrogen receptor down-regulators may exhibit clinical efficacy in the treatment of gynecological malignancies due to their pure estrogen receptor antagonist properties. However, up to now data are still limited and some unsolved questions remain. Fulvestrant has poor oral bioavailability and low pharmacodynamic characteristics. Further trials are required to examine new selective estrogen receptor down-regulator agents with better pharmacodynamic and pharmacokinetic profiles.

Pharmacokinetics, pharmacodynamics and clinical efficacy of ospemifene for the treatment of dyspareunia and genitourinary syndrome of menopause.

INTRODUCTION: Ospemifene is a selective estrogen receptor modulator recently approved by the FDA for the treatment postmenopausal women experiencing moderate-to-severe dyspareunia and by the EMA for the treatment of moderate-to-severe symptomatic genitourinary syndrome of menopause (GSM) in women who are not suitable candidates for local vaginal estrogen therapy. AREAS COVERED: This review offers an explanation of the pharmacodynamics and of the pharmacokinetics of ospemifene, and gives readers a complete overview of Phase II and III studies on the clinical efficacy, tolerability and safety of this agent in the setting of GSM. EXPERT OPINION: Ospemifene is efficacious for improving vaginal dryness or dyspareunia as the patient-identified most bothersome symptom, and Phase III clinical trials (4648 patients) have shown good efficacy in terms of improvement of objective and subjective signs and measures of GSM in postmenopausal women. Future studies with a long-term follow-up are required to better elucidate its safety profile. In particular, on the basis of preclinical and early clinical findings of antagonistic to neutral effect on breast tissue, more research is needed to assess the treatment with ospemifene in breast cancer survivors.

Three-month treatment with ulipristal acetate prior to laparoscopic myomectomy of large uterine myomas: a retrospective study.

OBJECTIVE: To assess the usefulness of 3-month treatment with ulipristal acetate (UPA) before laparoscopic myomectomy of large uterine myomas. STUDY DESIGN: This retrospective analysis of a prospectively collected database included women of reproductive age requiring laparoscopic myomectomy with the following characteristics: FIGO type 3, 4 or 5 myomas; largest diameter of the main myoma ≥10cm; number of myomas ≤3; largest diameters of the other myomas ≤5cm (second myoma) and ≤3cm (third myoma). Patients either underwent direct surgery (group S) or were treated before surgery with UPA for 3 months (group UPA). RESULTS: The mean (±SD) intraoperative blood loss was lower in group UPA (507.1±214.9ml) than in group S (684.2±316.8; p=0.012). The total operative time was lower in group UPA (137.6±26.8min) than in group S (159.7±26.8min; p<0.001); there was no significant difference in the suturing time between the two study groups (p=0.076). Hemoglobin drop was lower in group UPA (1.1±0.5g/dl) than in group S (1.3±0.7g/dl; p=0.034). Six patients in group S and no patient in group UPA required postoperative blood transfusions (p=0.031). Complications were not different between the two groups (p=0.726). Moreover, preoperative treatment with UPA caused a significant increase in hemoglobin levels (11.9±1.6g/dl) compared with baseline (9.1±1.1g/dl; p<0.001). CONCLUSION: A 3-month treatment with UPA before laparoscopy for large uterine myomas decreases intraoperative blood loss, hemoglobin drop, postoperative blood transfusion and length of surgery.

Veliparib for the treatment of ovarian cancer.

INTRODUCTION: Ovarian cancer represents the sixth most commonly diagnosed cancer among women, with an incidence of 6.1 cases per 100.000 women and a cumulative lifetime risk of 0.5%. Treatment is based on debulking surgery and platinum-based chemotherapy, with the potential combination with taxane. However, the recently available data on the genetic basis and aetiology of ovarian cancer has led to the development of new anticancer drugs. Poly(ADP-ribose) polymerase (PARP) inhibitors are one of the most promising new classes of targeted agents currently under investigation for the treatment of ovarian cancer. Veliparib is a small molecule that inhibits both PARP-1 and PARP-2 and was originally shown to be efficacious in BRCA-associated tumors. AREAS COVERED: This manuscript reviews the Phase I and II studies investigating the use of veliparib in ovarian cancer. This article also provides and discusses the pharmacokinetics and pharmacodynamics of veliparib. EXPERT OPINION: It is still being discussed whether PARP inhibitors should be used in a front-line or relapsed setting, alone or in combination with cytotoxic chemotherapy or as maintenance treatment. In terms of veliparib, further investigations are needed to explore its full potential in ovarian cancer. It is hoped that the ongoing phase 3 trials will help to further elucidate it potential as a treatment option.

Bevacizumab for the treatment of cervical cancer.

INTRODUCTION: Cervical cancer is still a major cause of morbidity and mortality in women. Early stages and locally advanced cervical cancer are currently treated respectively with surgery and chemoradiation with good prognosis. Persistent, recurrent and metastatic cervical cancers have a poor prognosis. Angiogenesis has been identified as a crucial factor for cervical cancer growth. Recently, research has increasingly focused on the development of targeted therapies, such as anti-angiogenic drugs. Amongst such drugs, bevacizumab, a recombinant humanized monoclonal antibody has been the subject of extensive investigation, including its use in cervical cancer. This was recently approved for the treatment of patients with metastatic, recurrent, or persistent cervical cancer. AREAS COVERED: The aim of this review is to discuss the role of bevacizumab in both locally advanced and metastatic or recurrent cervical cancer and to analyze the studies that have led to the approval of bevacizumab in cervical cancer. EXPERT OPINION: The use of bevacizumab in combination with other chemotherapies in cervical cancer has been proven safe and effective, with a significant improvement in overall survival of patients with advanced cervical cancer. Combination therapy using bevacizumab has been demonstrated to increase toxicity rates but it does not impair patient's quality of life.

Ulipristal Acetate Before High Complexity Hysteroscopic Myomectomy: A Retrospective Comparative Study.

STUDY OBJECTIVE: To evaluate the efficacy of preoperative treatment with ulipristal acetate (UPA) in patients undergoing high complexity hysteroscopic myomectomy. DESIGN: Retrospective analysis of a prospectively collected database (Canadian Task Force classification II-2). SETTING: University teaching hospital. PATIENTS: Patients of reproductive age requiring hysteroscopic myomectomy with STEPW (size, topography, extension, penetration, and wall) score 5 or 6. INTERVENTIONS: Patients included in the study either underwent direct surgery (group S) or received a 3-month preoperative treatment with UPA (group UPA). Based on a power calculation, 25 patients were required in each study group. MEASUREMENTS AND MAIN RESULTS: Myoma characteristics were similar in the 2 study groups. The 3-month UPA treatment caused a 21.9% (±10.3%) mean (±SD) percentage decrease in myoma volume. The number of complete resections (primary outcome of the study) was higher in group UPA (92.0%) than in group S (68.0%; p = .034). The operative time was lower in group UPA than in group S (p = .048), whereas there was no significant difference in fluid balance between the 2 study groups (p = .256). The incidence of complications was similar in the 2 groups (p = .609). Patient satisfaction at 3 months from surgery was higher in group UPA than in group S (p = .041). CONCLUSION: A 3-month preoperative treatment with UPA increases the possibility of complete resection in high complexity hysteroscopic myomectomy. It decreases the operative time and improves patient satisfaction at 3 months from surgery.

Storage time does not modify the gene expression profile of cryopreserved human metaphase II oocytes.

STUDY QUESTION: Does storage time have any impact on the transcriptome of slowly frozen cryopreserved human metaphase II (MII) oocytes? SUMMARY ANSWER: The length of cryostorage has no effect on the gene expression profile of human MII oocytes. WHAT IS KNOWN ALREADY: Oocyte cryopreservation is a widely used technique in IVF for storage of surplus oocytes, as well as for fertility preservation (i.e. women undergoing gonadotoxic therapies) and oocyte donation programs. Although cryopreservation has negative impacts on oocyte physiology and it is associated with decrease of transcripts, no experimental data about the effect of storage time on the oocyte molecular profile are available to date. STUDY DESIGN, SIZE, DURATION: This study included 27 women, ≤38 years aged, without any ovarian pathology, undergoing IVF treatment. Surplus MII oocytes were donated after written informed consent. A total of 31 non-cryopreserved oocytes and 68 surviving slow-frozen/rapid-thawed oocytes (32 oocytes cryostored for 3 years and 36 cryostored for 6 years) were analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Pools of ≈10 oocytes for each group were prepared. Total RNA was extracted from each pool, amplified, labeled and hybridized on oligonucleotide microarrays. Analyses were performed by R software using the limma package. MAIN RESULTS AND THE ROLE OF CHANCE: Comparison of gene expression profiles between surviving thawed oocytes after 3 and 6 years of storage in liquid nitrogen found no differently expressed genes. The expression profiles of cryopreserved MII oocytes significantly differed from those of non-cryopreserved oocytes in 107 probe sets corresponding to 73 down-regulated and 29 up-regulated unique transcripts. Gene Ontology analysis by DAVID bioinformatics resource disclosed that cryopreservation deregulates genes involved in oocyte function and early embryo development, such as chromosome organization, RNA splicing and processing, cell cycle, cellular response to DNA damage and to stress, DNA repair, calcium ion binding, malate dehydrogenase activity and mitochondrial activity. Among the probes significantly up-regulated in cryopreserved oocytes, two corresponded to ovary-specific expressed large intergenic noncoding (linc)RNAs. LIMITATIONS, REASONS FOR CAUTION: Data validation in a larger cohort of samples would be beneficial, although we applied stringent criteria for gene selection (fold-change >3 or <1/3 and FDR < 0.1). Further research should be undertaken to verify experimentally that the length of cryostorage has no effect on gene expression profile of vitrified/warmed MII oocytes, as well as to include in analyses 'older' frozen oocytes. WIDER IMPLICATIONS OF THE FINDINGS: Confirmation that the length of storage does not alter the gene expression profile of frozen oocytes is noteworthy for the safety issue of long-term oocyte banking, i.e. fertility preservation, gamete donation. STUDY FUNDING/COMPETING INTEREST: This study was supported by a grant of the Italian Ministry of Health (CCM 2012) and by Ferring Pharmaceutical company. The authors have no conflicts of interest to declare.

Three-month treatment with triptorelin, letrozole and ulipristal acetate before hysteroscopic resection of uterine myomas: prospective comparative pilot study.

OBJECTIVE: To compare the usefulness of preoperative treatment with triptorelin, letrozole or ulipristal acetate or no treatment before hysteroscopic removal of uterine submucosal myomas. STUDY DESIGN: Single center prospective non-randomized comparative pilot study. The study included consecutive premenopausal patients undergoing hysteroscopic resection of myomas graded as type 0, type 1 or type 2 according to the FIGO classification with diameter between 20 and 35 mm. Exclusion criteria were: associated polyps, associated non-hysteroscopic surgical procedures, >2 myomas requiring hysteroscopic resection. This study enrolled patients who underwent either direct surgery (group S; n=23) or 3-month preoperative treatment with triptorelin (3.75 mg every 28 days; group T; n=20), letrozole (2.5 mg/day; group L; n=11) or ulipristal acetate (5 mg/day; group U; n=7). Patients underwent hysteroscopic resection of the myomas. RESULTS: All medical treatments caused a significant decrease in the volume of myomas (group T, p<.001; group L, p<.001; group U, p=.006); however, the percentage decrease in myoma volume was lower in group U than in group T (p=.001) and in group L (p=.010). The hysteroscopy time was higher in group S than in group T (p<.001) and in group L (p=.001); there was no significant difference in the hysteroscopy time between group S and group U (p=.206). Fluid absorption was lower in group T than in group S (p=.002) and in group L than in group S (p=.048); fluid absorption was similar in group S and group U (p=.110). Intra- and postoperative complications, postoperative pain, and patient satisfaction were similar in the four study groups. Surgeon's evaluation of operative difficulty was better in group T than in group S (p<.005). CONCLUSIONS: Preoperative treatment with triptorelin and letrozole decreases the hysteroscopy time and the volume of fluid absorbed during hysteroscopic resection of uterine submucosal myomas.

Oxaliplatin for the treatment of ovarian cancer.

INTRODUCTION: Oxaliplatin is an important drug in treatment of several solid tumors. Ovarian cancer (OC) is sensitive to chemotherapy and the overall response rate with primary therapy is about 75%. Unfortunately, 60 - 70% of patients experience recurrence requiring additional treatments and finally die of progressive disease within 5 years of the initial diagnosis. Currently, a platinum-based combination therapy is recommended in platinum-sensitive disease while a non-platinum single-agent therapy is preferred in platinum-resistant disease that is characterized by a low response rate. AREAS COVERED: In this article, the authors review the Phase II and Phase III studies of oxaliplatin as an OC therapy. Furthermore, the authors discuss the pharmacokinetic and pharmacodynamic features of oxaliplatin. EXPERT OPINION: Platinum emerged as the mainstay of OC treatment in frontline therapy, and platinum compounds remain a critical component of chemotherapy also in relapsed disease. Unfortunately, increasing exposure to carboplatin/cisplatin raises the risk of resistance or hypersensitivity to platinum. Several studies have demonstrated the safety and effectiveness of oxaliplatin, both alone and in combination regimens, in relapsed OC, demonstrating a good tolerability profile. Moreover, the therapeutic spectrum of oxaliplatin might be extended to OC patients who experienced hypersensitivity to carboplatin because of its favorable toxicity profile and at least equal efficacy.

Endometriosis: the effects of dienogest.

INTRODUCTION: Ectopic endometrial tissue is found in 2% to 6% of women of reproductive age, in up to 60% of those with dysmenorrhoea, and in up to 30% of women with subfertility, with a peak incidence at around 40 years of age. However, symptoms may not correlate with laparoscopic findings. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of dienogest for the treatment of endometriosis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2014 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: Five studies were included. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: dienogest versus placebo or no treatment; dienogest versus gonadorelin analogues; dienogest versus combined oral contraceptives; dienogest versus other progestogens.

Intraoperative Transrectal Ultrasonography for Hysteroscopic Metroplasty: Feasibility and Safety.

The primary objective of this prospective comparative nonrandomized study was to assess the feasibility and safety of intraoperative transrectal ultrasonography (TRUS) during hysteroscopic metroplasty (HM). The secondary objective of the study was to assess whether TRUS facilitates complete removal of the uterine septum. Septate uterus was diagnosed by 3-dimensional transvaginal ultrasonography (3D-TVS) and confirmed by magnetic resonance imaging. In the control group (HM group; n = 18), patients underwent HM according to the traditional standard of operative hysteroscopy. In the study group (HM+TRUS group; n = 27), HM and TRUS were performed simultaneously; the hysteroscopic procedure was continued until a normal uterine fundus was observed. At 6 to 8 weeks after HM, 3D-TVS was performed to identify the numbers of complete resections (residual septum absent or <5 mm), suboptimal resections (residual septum 5-10 mm), and incomplete resections (residual septum > 10 mm). The 2 study groups did not differ significantly in terms of demographic and clinical characteristics, or in the volume of fluid infused and absorbed. There were no severe intraoperative or postoperative complication in either group; 2 patients in the HM+TRUS group and 1 patient in the HM group experienced urinary tract infection (p = .807). At 6 to 8 weeks after HM, the number of suboptimal resections and incomplete resections was higher in the HM group than in the HM+TRUS group (p = .031). Residual septum >10 mm (incomplete resection) was seen in 1 patient in the HM group but in no patients in the HM+TRUS group. Intraoperative TRUS can be performed safely during HM, and may increase the likelihood of complete resection of the uterine septum; however, this finding should be confirmed by larger studies.

Drug safety evaluation of ulipristal acetate in the treatment of uterine fibroids.

INTRODUCTION: Ulipristal acetate (UPA) is a selective progesterone-receptor modulator (SPRM). SPRMs are a new class of progesterone-receptor ligands that exert tissue selective agonist, antagonist or mixed agonist-antagonist activity in target cells. UPA inhibits the proliferation, induces apoptosis of leiomyoma cells in vitro and demonstrates potent progesterone antagonist activity in vitro and in vivo. AREAS COVERED: This manuscript aims to review the available data on safety of UPA in the treatment of uterine fibroids. Data and articles included in this manuscript were obtained via PubMed, Medline and Embase up to November 2014. EXPERT OPINION: UPA is efficacious in the treatment of uterine fibroids before surgery; it decreases leiomyoma volume and uterine bleeding; furthermore, it improves quality of life. Short-term administration of UPA has been shown to be safe at short follow-up (months) and it is associated with minimal adverse side effects; further studies with longer follow-up are required to define the safety profile of UPA on endometrial histology.

Impaired increase of plasma abscisic Acid in response to oral glucose load in type 2 diabetes and in gestational diabetes.

The plant hormone abscisic acid (ABA) is present and active in humans, regulating glucose homeostasis. In normal glucose tolerant (NGT) human subjects, plasma ABA (ABAp) increases 5-fold after an oral glucose load. The aim of this study was to assess the effect of an oral glucose load on ABAp in type 2 diabetes (T2D) subjects. We chose two sub-groups of patients who underwent an oral glucose load for diagnostic purposes: i) 9 treatment-naive T2D subjects, and ii) 9 pregnant women with gestational diabetes (GDM), who underwent the glucose load before and 8-12 weeks after childbirth. Each group was compared with matched NGT controls. The increase of ABAp in response to glucose was found to be abrogated in T2D patients compared to NGT controls. A similar result was observed in the women with GDM compared to pregnant NGT controls; 8-12 weeks after childbirth, however, fasting ABAp and ABAp response to glucose were restored to normal in the GDM subjects, along with glucose tolerance. We also retrospectively compared fasting ABAp before and after bilio-pancreatic diversion (BPD) in obese, but not diabetic subjects, and in obese T2D patients, in which BPD resulted in the resolution of diabetes. Compared to pre-BPD values, basal ABAp significantly increased 1 month after BPD in T2D as well as in NGT subjects, in parallel with a reduction of fasting plasma glucose. These results indicate an impaired hyperglycemia-induced ABAp increase in T2D and in GDM and suggest a beneficial effect of elevated ABAp on glycemic control.

Second surgery for recurrent unilateral endometriomas and impact on ovarian reserve: a case-control study.

OBJECTIVE: To investigate the impact on ovarian reserve of second laparoscopic surgery for recurrent unilateral endometriomas. DESIGN: Case-control study. SETTING: University teaching hospital. PATIENT(S): This study included patients who underwent stripping of endometriomas (diameter ≥4 cm) and were followed-up at our institution. Case subjects had second surgery for recurrent unilateral endometriomas (n = 18); control subjects had no recurrence and no second surgery (n = 18). INTERVENTION(S): This case-control study was based on a retrospective analysis of a prospectively collected database including patients who underwent surgery for endometriomas at our institution. MAIN OUTCOME MEASURE(S): The primary outcome of the study was to assess the changes in antimüllerian hormone (AMH) levels in each study group and between the two study groups. The secondary outcomes of the study were to assess the changes in basal FSH, antral follicle count (AFC), and ovarian volume in each study group and between the two study groups. RESULT(S): In both study groups, primary surgery decreased AMH, increased basal FSH, and decreased the AFC of the operated ovary. Before second surgery, case subjects had AMH, basal FSH, and AFC similar to control subjects. After second surgery, case subjects had lower AMH, higher basal FSH, and lower AFC of the affected ovary than before surgery; the volume of the operated ovary was lower than that of the contralateral ovary. CONCLUSION(S): The laparoscopic stripping of recurrent ovarian endometriomas is associated with a high risk of ovarian reserve damage and ovarian failure. CLINICAL TRIAL REGISTRATION NUMBER: NCT02047838.

Current opinion on bevacizumab on endometrial cancer treatment.

INTRODUCTION: Advanced or recurrent endometrial cancer is still a challenge for clinicians as it has a poor prognosis despite treatment efforts. Thus, there is an urgent need for new agents with activity in this subset of patients. The increased knowledge of the molecular aspects of endometrial carcinogenesis has led to the development of molecular targeted therapies and in particular anti-angiogenic drugs. One of the most promising of these agents is bevacizumab , a recombinant humanized immunoglobulin monoclonal antibody to VEGF. AREAS COVERED: The objective of this paper is to discuss the role of angiogenesis in endometrial cancer and analyze the rational of bevacizumab use, alone or in combination with other therapies, in endometrial cancer patients. We reviewed the most important preclinical and clinical studies published on this topic up to March 2014. EXPERT OPINION: Bevacizumab in combination with others targeted therapies, chemotherapy or radiotherapy demonstrated promising anti-tumor activity. Despite the good oncological outcomes of these recent clinical experiences, caution must be used in light of significant toxicity reported in this subset of heavily pre-treated patients. The identification of biomarkers able to predict either the efficacy or toxicity of anti-angiogenic drugs is a compelling need.

Progestin-only contraception compared with extended combined oral contraceptive in women with migraine without aura: a retrospective pilot study.

OBJECTIVE: To evaluate the effect of a desogestrel progestogen-only pill (POP) compared to continuous combined oral contraception (COC) on migraine patterns in women with migraine without aura. STUDY DESIGN: A retrospective analysis of prospective headache charts from migrainous women who used the POP or COC in our clinic between July 2009 and July 2013. The quality and quantity of migraine attacks and use of medications were evaluated at three and six months. Health related quality of life was evaluated after 6 months' treatment. RESULTS: Fifty-three patients were evaluable for the analysis (22 in the COC group and 31 in the POP group). Six months' POP treatment led to a statistical reduction in migraine days; headache days; pain intensity; number of days with severe pain and days with pain medication. The only statistical difference between the two groups was a reduction in the number of days with pain medication in the POP group compared to the COC group (p=0.044). After 6 months' treatment a quality of life improvement was seen only in the POP group, but no statistical differences were found when comparing the two groups. CONCLUSIONS: Our preliminary data confirm that POP therapy improves migraine patterns and quality of life after 6 months' treatment in women with migraine without aura and it decreases the analgesic consumption with respect to an extended COC therapy. As POP represents a healthier opportunity, in terms of vascular risk, than combined contraception, its role in migrainous women deserves to be further investigated.

Dienogest in women with persistent endometriosis-related pelvic pain during norethisterone acetate treatment.

OBJECTIVE: To evaluate patient satisfaction at 6-months dienogest (DNG) treatment in women with symptomatic rectovaginal endometriosis who had pain persistence and were unsatisfied after 6-months of norethisterone acetate (NETA) therapy. STUDY DESIGN: This 24-weeks pilot open-label prospective study enrolled 25 women. The main outcome was the degree of patient satisfaction measured by using a Likert scale. Secondary outcomes were to evaluate differences in endometriosis-related pain, quality of life, sexual function changes and volumetric nodules changes during DNG compared to NETA treatment. RESULTS: Patient satisfaction improved at 3- and 6-months (p<0.001, respectively) treatment with DNG compared with baseline treatment with NETA. Six months DNG treatment decreased the intensity of all the endometriosis-associated pain (chronic pelvic pain, dyspareunia, dyschezia) compared to baseline (p<0.001 for all comparisons). Quality of life and quality of sexual life evaluated with the EHP-30 and FSFI, respectively, increased after 6 months treatment. The volume of the endometriotic nodules did not significantly change during treatment. CONCLUSIONS: This study confirms the efficacy of DNG in treating symptomatic women with rectovaginal endometriosis even in a particular endometriotic subpopulation of NETA "resistant" patients. Further randomized clinical trials comparing these two progestins both in first than second line are warranted.