Carolina Scala

Desogestrel‐only contraceptive pill versus sequential contraceptive vaginal ring in the treatment of rectovaginal endometriosis infiltrating the rectum: a prospective open‐label comparative study

To compare the efficacy of two hormonal therapies in treating symptoms caused by bowel endometriosis.

Dienogest in the treatment of endometriosis

Introduction: Dienogest (DNG) is an oral progestin, derivative of 19-nortestosterone, that has recently been introduced for the treatment of endometriosis. Areas covered: This review examines the clinical efficacy, safety and tolerability of DNG in the treatment of endometriosis. The material included in the current manuscript was searched and obtained via Medline, Pubmed and EMBASE, from inception until February 2014. The term ‘dienogest’ was associated with the following search terms: ‘endometriosis’, ‘pharmacokinetics’, ‘safety’ and ‘efficacy’. Expert opinion: Several trials demonstrated the clinical efficacy, safety and tolerability of DNG. However the use of DNG is associated with some limitations. So far, no study investigated the potential of contraceptive effect of this treatment and therefore, it should be recommended with other methods of contraception (e.g., barrier methods). A further limitation of the use of DNG as daily therapy in the long term is that the cost of the therapy is higher than other progestins available on the market and combined oral contraceptives. Therefore, future studies should be designed to compare the efficacy and safety of DNG with other progestins.

Risk Factors for Coarctation of the Aorta on Prenatal Ultrasound: A Systematic Review and Meta-Analysis

Background: Prenatal diagnosis of coarctation of the aorta (CoA) is still challenging and affected by high rates of false-positive diagnoses. The aim of this study was to ascertain the strength of association and to quantify the diagnostic accuracy of different ultrasound signs in predicting CoA prenatally. Methods: Medline, Embase, CINAHL, and Cochrane databases were searched. Random-effects and hierarchical summary receiver operating characteristic model meta-analyses were used to analyze the data. Results: Seven hundred ninety-four articles were identified, and 12 (922 fetuses at risk for CoA) articles were included. Mean mitral valve diameter z score was lower ( P <0.001) and the mean tricuspid valve diameter z score was higher in fetuses with CoA than in those without CoA ( P =0.01). Mean aortic valve diameter z score was lower in fetuses with CoA than in healthy fetuses ( P ≤0.001), but the ascending aorta diameter, expressed as z score or millimeters, was similar between groups ( P =0.07 and 0.47, respectively). Mean aortic isthmus diameter z scores measured either in sagittal ( P =0.02) or in 3-vessel trachea view ( P <0.001) were lower in fetuses with CoA. Conversely, the mean pulmonary artery diameter z score, the right/left ventricular and pulmonary artery/ascending aorta diameter ratios were higher ( P <0.001, P =0.02, and P =0.02, respectively) in fetuses with CoA in comparison with controls, although aortic isthmus/arterial duct diameter ratio was lower in fetuses with CoA than in those without CoA ( P <0.001). The presence of coarctation shelf and aortic arch hypoplasia were more common in fetuses with CoA than in controls (odds ratio, 26.0; 95% confidence interval, 4.42–153; P <0.001 and odds ratio, 38.2; 95% confidence interval, 3.01–486; P =0.005), whereas persistent left superior vena cava ( P =0.85), ventricular septal defect ( P =0.12), and bicuspid aortic valve ( P =0.14) did not carry an increased risk for this anomaly. Multiparametric diagnostic models integrating different ultrasound signs for the detection of CoA were associated with an increased detection rate. Conclusions: The detection rate of CoA may improve when a multiple-criteria prediction model is adopted. Further large multicenter studies sharing the same imaging protocols are needed to develop objective models for risk assessment in these fetuses. # Clinical Perspective {#article-title-31}Background: Prenatal diagnosis of coarctation of the aorta (CoA) is still challenging and affected by high rates of false-positive diagnoses. The aim of this study was to ascertain the strength of association and to quantify the diagnostic accuracy of different ultrasound signs in predicting CoA prenatally. Methods: Medline, Embase, CINAHL, and Cochrane databases were searched. Random-effects and hierarchical summary receiver operating characteristic model meta-analyses were used to analyze the data. Results: Seven hundred ninety-four articles were identified, and 12 (922 fetuses at risk for CoA) articles were included. Mean mitral valve diameter z score was lower (P<0.001) and the mean tricuspid valve diameter z score was higher in fetuses with CoA than in those without CoA (P=0.01). Mean aortic valve diameter z score was lower in fetuses with CoA than in healthy fetuses (P⩽0.001), but the ascending aorta diameter, expressed as z score or millimeters, was similar between groups (P=0.07 and 0.47, respectively). Mean aortic isthmus diameter z scores measured either in sagittal (P=0.02) or in 3-vessel trachea view (P<0.001) were lower in fetuses with CoA. Conversely, the mean pulmonary artery diameter z score, the right/left ventricular and pulmonary artery/ascending aorta diameter ratios were higher (P<0.001, P=0.02, and P=0.02, respectively) in fetuses with CoA in comparison with controls, although aortic isthmus/arterial duct diameter ratio was lower in fetuses with CoA than in those without CoA (P<0.001). The presence of coarctation shelf and aortic arch hypoplasia were more common in fetuses with CoA than in controls (odds ratio, 26.0; 95% confidence interval, 4.42–153; P<0.001 and odds ratio, 38.2; 95% confidence interval, 3.01–486; P=0.005), whereas persistent left superior vena cava (P=0.85), ventricular septal defect (P=0.12), and bicuspid aortic valve (P=0.14) did not carry an increased risk for this anomaly. Multiparametric diagnostic models integrating different ultrasound signs for the detection of CoA were associated with an increased detection rate. Conclusions: The detection rate of CoA may improve when a multiple-criteria prediction model is adopted. Further large multicenter studies sharing the same imaging protocols are needed to develop objective models for risk assessment in these fetuses.

Aberrant right subclavian artery in fetuses with Down syndrome: a systematic review and meta‐analysis

The primary objective was to estimate the prevalence of aberrant right subclavian artery (ARSA) in fetuses with Down syndrome. Secondary objectives were to assess the prevalence of ARSA in euploid fetuses, the feasibility of ultrasound evaluation of the right subclavian artery (RSA) in the first and second trimesters of pregnancy, the performance of ARSA in screening for trisomy 21 and its association with other abnormalities.

Preoperative treatment with letrozole in patients undergoing laparoscopic myomectomy of large uterine myomas: a prospective non-randomized study

OBJECTIVE To assess the efficacy of preoperative treatment with aromatase inhibitors (AIs) in premenopausal women undergoing laparoscopic myomectomy of large uterine myomas. STUDY DESIGN Prospective non-randomized assessor-blind comparative trial. RESULTS This study included 80 patients undergoing laparoscopic myomectomy of large uterine myomas (≥8cm). Forty patients were treated with a combination of oral letrozole (2.5mg/day) and norethindrone acetate (2.5mg/day) continuously in the three months prior to surgery (group A) and 40 patients received no treatment before surgery (group B). The total operative time (mean±SD, range) was significantly lower in group A (121.5±19.9min; 89-181min) than in group B (134.4±16.8min; 111-185min; p<0.001). The time required to close the hysterotomies (mean±SD, range) was lower in group A (27.1±5.1min; 16-39min) than in group B (37.1±9.6min; 17-57min; p<0.001). The intraoperative blood loss (mean±SD, range) was lower in group A (271.0±125.6ml; 95-625ml) than in group B (460.4±205.7ml; 180-1115ml; p<0.001). No major complication occurred in any case. The cleavage plane was better defined in group B compared with group A (p<0.001). The quality of the myometrial scar, defined by ultrasound evaluation, was similar in the two study groups both at one-week (p=0.356) and at 3-month follow-up (p=0.201). CONCLUSIONS The total operative time, the time required to close the hysterotomies and the intraoperative blood loss significantly decrease after preoperative treatment with letrozole. Future randomized studies should compare the efficacy of preoperative administration of AIs and GnRHa prior to laparoscopic myomectomy.

Imidafenacin for the treatment of overactive bladder

Introduction: Imidafenacin (KRP-197/ONO-8025) is the latest antimuscarinic (AM) developed for the treatment of overactive bladder syndrome (OAB) and, at the moment, it is marketed only in Japan. This compound has been developed to improve the tolerability of AM therapy by binding specifically the M3 receptor subtype, thus limiting undesirable adverse events (AEs). Areas covered: This systematic review offers a brief explanation of the mechanism of action and of the pharmacokinetics of imidafenacin and helps readers to understand the clinical efficacy, tolerability, and safety of the compound in the setting of OAB therapy. Expert opinion: Imidafenacin is an AM drug with excellent efficacy, tolerability, and safety. It is indicated for patients with nocturia, nocturnal polyuria, and benign prostatic hyperplasia. This compound, due to its pharmacokinetic properties, gives the opportunity to be easily adjusted in its dosages. Further studies should assess the pharmacokinetics, clinical efficacy, safety, and tolerability of imidafenacin in Caucasian and African populations because this AM agent, at the moment, has been evaluated just in Asian populations. More studies should evaluate and compare efficacy, safety, and tolerability of imidafenacin also with other largely utilized AMs, such as oxybutynin, tolterodine, and fesoterodine, or with the other M3 selective compound, darifenacin.

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.

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.

Current understanding on pharmacokinetics, clinical efficacy and safety of progestins for treating pain associated to endometriosis

ABSTRACT Introduction: Endometriosis is a chronic estrogen and progestogen responsive inflammatory disease associated with pain symptoms and infertility. The medical therapy of endometriosis aims to induce decidualization within the hormonally dependent ectopic endometrium, and it is often administered to ameliorate women’ pain symptoms or to prevent post-surgical disease recurrence. A variety of progestins have been used in monotherapy for the medical management of women with endometriosis. Areas covered: This review aims to offer the reader a complete overview of pharmacokinetic (PK) and clinical efficacy of progestins for the treatment of endometriosis. Expert opinion: Each progestin has a distinct PK parameters and pharmacodynamics affinity not only for progesterone receptor, but also for other steroid receptors, such as estrogen, androgen, and glucocorticoid. Moreover, progestins can also be delivered in different formulations. All these characteristics influence their final biological effect. Randomized, controlled, non-blinded studies support the use of oral progestin-only treatment for pelvic pain associated with endometriosis. Currently, the only two progestins approved by Food and Drug Administration (FDA) for the treatment of endometriosis are norethindrone acetate (NETA) and depot medroxyprogesterone acetate (DMPA).

Folate receptor alpha antagonists in preclinical and early stage clinical development for the treatment of epithelial ovarian cancer

ABSTRACT Introduction: The prognosis of patients affected by ovarian cancer has not substantially changed in the last decades and improving survival still remains a challenge. In the promising era of ‘personalized therapy’ several new biologic therapies are currently being investigated: in this setting, targeting the folate receptor (FR) has been considered a new potential strategy for biologic therapy. Areas covered: The aim of the current review is to summarize, giving a critical overview,promising folate receptor alpha antagonists under preclinical or early clinical development for ovarian cancer. Expert opinion: Two categories of therapeutics are included in this class: FRα targeted mAbs and FRα-binding-ADC (Antibody drug conjugates); both share the interesting possibility of selecting patients via a biomarker which is already available. In the first class, farletuzumab has reached the most advanced stage in clinical evaluation and results of a Phase II randomized trial are awaited to assess its efficacy in a specific patients’ setting. MOv18 IgE represents a novel strategy to target FRα expressing cells, which has shown encouraging results in preclinical studies: further evaluation is needed in the clinical setting. IMGN 853 is an innovative FRα-binding ADC under development, with only preliminary results of a Phase I trial available.