Endometriosis-associated infertility: surgery or IVF?

Endometriosis is a chronic disease frequently associated with female infertility. The choice of treatment in case of endometriosis is one of the most discussed topics in Reproductive Medicine. The approach to the patient with endometriosis and infertility should be tailored based on different parameters. The localization of the disease, the severity of symptoms and the age of the patient are just some of them. Management options include surgery, in-vitro fertilization (IVF), or a combination of both. Data, mostly uncontrolled, would favor surgery at any stage of endometriosis, increasing the chances of natural conception compared to expectant management. Laparoscopic excision of the ovarian endometrioma should be the treatment of choice when there is associated pain. Surgery should be performed following appropriate techniques to reduce the possible damage to the ovarian reserve. Pregnancy rates around 50% have been consistently reported after surgery, which compare favorably with those obtained with IVF. IVF, on the other hand, may be preferred in case of associated male or tubal factor, in case of a reduced ovarian reserve, or if previous surgery has failed, particularly if there is no associated pain, and when the ultrasonographic features of the ovarian cyst are reassuring. Sometimes IVF may be preceded by surgery, when a difficult access to follicles at pick-up, due to the size and location of the ovarian cyst, or to severe adhesions, is anticipated. Due to the lack of solid evidence in the scenario of endometriosis-associated infertility, robust data from randomized clinical trials (RCTs) are strongly needed.

Non-invasive treatment of vulvovaginal atrophy in menopause with CO2 laser.

Genitourinary syndrome of menopause (GSM) may affect up to 90% of menopausal women, including vulvovaginal atrophy (VVA), burning, pain, bleeding, irritation, dyspareunia, anorgasmia, and urinary symptoms. Vaginal symptoms from lack of estrogens can have a significant impact on the sexual health and quality of life (QoL) in as many as 50% of postmenopausal women. Several therapeutic alternatives, both hormonal and non- hormonal, have been proposed. Microablative CO2 laser is one of the three non-surgical energy-based therapies, with Erbium:YAG laser and temperature-controlled radiofrequency (RF). Microablative CO2 laser induces morphological changes in vaginal tissues and results of several clinical trials suggest that this type of laser improves symptoms of GSM. Moreover, this treatment seems to be safe. Given the increasingly widespread use of laser CO2 as a non-hormonal alternative treatment for GSM, the authors reviewed the current published literature evaluating this therapy, to compare efficacy and safety of different protocols.

Efficacy of Antibiotic Prophylaxis for Hysteroscopy: A Meta-Analysis of Randomized Trials.

OBJECTIVE: To assess the efficacy and side effects of antibiotic prophylaxis compared with placebo or no treatment in women undergoing hysteroscopy. DATA SOURCES: A structured search was carried out in PubMed-Medline, Embase, and Cochrane Controlled Trials Register databases through December 31, 2018. METHODS OF STUDY SELECTION: The search included a combination of the following terms: "hysteroscopy," "endoscopic surgery," "antibiotic prophylaxis." The following outcomes were selected: postoperative fever, infection rate, pelvic inflammatory disease (PID) and abscess occurrence, postoperative antibiotic requirement, and side effects occurrence (lower abdominal pain, vomiting, diarrhea, anaphylactic reaction). A random-effects model was used at meta-analysis. Study quality and bias risk were assessed with the Cochrane tool. TABULATION, INTEGRATION, AND RESULTS: Five randomized controlled trials comparing efficacy of antibiotic prophylaxis with placebo or no treatment were included in the meta-analysis. Overall, pooled incidence of events was very low in both groups (fever, 3.79% vs 1.8%; overall infection, .52% vs .58%; postoperative antibiotic therapy, 1.18% vs 1.32%; and lower abdominal pain, 12.46% vs 9.31%). Moreover, the incidence of serious infections requiring further actions (PID or abscess) appeared to be extremely low (.2% in pretreated women and none in control groups). No one trial individually or the pooled analysis showed a statistically significant benefit of antibiotics prophylaxis over placebo for the outcome considered. CONCLUSION: The use of antibiotics appears not to be beneficial to prevent infection after hysteroscopy; however, the lack of high-quality studies makes it difficult to draw firm conclusions. Considering the very low infection rate highlighted after hysteroscopic procedures, a difference will probably never be proven in a randomized trial. A larger population and program data to confirm these results are therefore warranted.

Role of intraperitoneal chemotherapy in ovarian cancer in the platinum-taxane-based era: A meta-analysis.

PURPOSE: Intravenous (IV) chemotherapy has been compared with intraperitoneal (IP) chemotherapy in randomized clinical trials in advanced ovarian cancer (OC). The aim of this meta-analysis was to evaluate efficacy and toxicity of IV and IP and identify differences in outcomes. METHODS: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement was applied. Random-effects models were used. Primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and the proportion of patients with grade ≥2 acute toxicity. RESULTS: Four randomized clinical trials representing 2461 patients were identified. The hazard ratio (HR) of PFS was 0.88 (95% CI 0.80-0.98; p = 0.01, I2 = 24%) in favor of IP chemotherapy. IP chemotherapy was also associated with significant OS improvement compared with IV chemotherapy, with HR of 0.79 (95% CI 0.67-0.92; p = 0.003, I2 = 0%). Globally, grade ≥2 toxicities were reduced with IV chemotherapy. CONCLUSION: This meta-analysis shows the superiority of IP chemotherapy over IV infusion in terms of clinical outcomes but toxicity rates. Its precise role in the management of advanced OC remains to be determined.

Epirubicin: a new entry in the list of fetal cardiotoxic drugs? Intrauterine death of one fetus in a twin pregnancy. Case report and review of literature.

BACKGROUND: Current knowledge indicate that epirubicin administration in late pregnancy is almost devoid of any fetal cardiotoxicity. We report a twin pregnancy complicated by breast cancer in which epirubicin administration was causatively linked to the death of one twin who was small for gestational age (SGA) and in a condition of oligohydramnios and determined the onset of a transient cardiotoxicity of the surviving fetus/newborn. CASE PRESENTATION: A 38-year-old caucasic woman with a dichorionic twin pregnancy was referred to our center at 20 and 1/7 weeks for a suspected breast cancer, later confirmed by the histopathology report. At 31 and 3/7 weeks, after the second chemotherapy cycle, ultrasound examination evidenced the demise of one twin while cardiac examination revealed a monophasic diastolic ventricular filling, i.e. a diastolic dysfunction of the surviving fetus who was delivered the following day due to the occurrence of grade II placental abruption. The role of epirubicin cardiotoxicity in the death of the first twin was supported by post-mortem cardiac and placental examination and by the absence of structural or genomic abnormalities that may indicate an alternative etiology of fetal demise. The occurrence of epirubicin cardiotoxicity in the surviving newborn was confirmed by the report of high levels of troponin and transient left ventricular septal hypokinesia. CONCLUSION: Based on our findings we suggest that epirubicin administration in pregnancy should be preceded by the screening of some fetal conditions like SGA and oligohydramnios that may increase its cardiotoxicity and that, during treatment, the diastolic function of the fetal right ventricle should be specifically monitored by a pediatric cardiologist; also, epirubicin and desamethasone for lung maturation should not be closely administered since placental effects of glucocorticoids may increase epirubicin toxicity.

Breast cancer during pregnancy: a retrospective study on obstetrical problems and survival.

OBJECTIVES: Breast cancer is one of the most common cancers occurring in pregnancy. Data on survival of these patients and their obstetrical complications are still limited. STUDY DESIGN: We conducted a case-control, retrospective study to evaluate the overall survival (OS) of 22 patients with breast cancer in pregnancy (BCP) and 45 non-pregnant women with breast cancer (BC) matched for age, stage and hormonal status. RESULTS: Survival of BCP and BC patients using Kaplan-Meier analysis was similar (86.4% in cases and 80% in controls p=0.392) and BCP patients had survival consistent with the stage of the disease, providing that the treatment had been in agreement with the recommended protocols. The overall incidence of premature delivery was 54.6% and complications were observed in three newborns out of 23 (13%). CONCLUSIONS: Preterm labor induction without any obstetrical indication following woman's request to continue chemotherapy outside pregnancy can be reduced by explaining the risks of early delivery and the lack of effects of many chemotherapeutic regimens on the fetus.

Current role and safety profile of aromatase inhibitors in early breast cancer.

The current adjuvant therapy for breast cancer is in a continous progress; standard therapeutic strategies include the use of chemotherapy, molecular targeted drugs and hormonal agents, according to well-established prognostic and predictive factors. Among the hormonal drugs, for a long period tamoxifen has been the gold standard of adjuvant therapy in postmenopausal women with hormone receptor-positive (HR+) early breast cancer. In the last years an expanding use of aromatase inhibitors occurred in this subset of patients, because the third-generation class of these agents (anastrozole, letrozole and exemestane) showed to be more effective and safe than tamoxifen and are now recommended as the preferred hormonal approach to postmenopausal hormone-sensitive patients, according to national and international guidelines. Treatment choices with these agents include the use of an aromatase inhibitor as an upfront strategy for 5 years, as a sequential approach after 2-3 years of tamoxifen, or as an extended use after the classical 5 years of tamoxifen. The improved efficacy of aromatase inhibitors over tamoxifen has been largely demonstrated in terms of better disease-free survival, reductions in the occurrence of early distant metastasis as well as improvement of overall survival. Moreover, according to the optimal duration of therapy, presently it is not known whether aromatase inhibitor therapy, as tamoxifen, should be limited to 5 years. In terms of safety profile, the side effects of aromatase inhibitors, as compared with selective estrogen receptor modulators, are different, reflecting the specific mechanism of action of these drugs. There is strong evidence that aromatase inhibitors are well tolerated, with a lower incidence of gynecological symptoms (vaginal bleeding, discharge and endometrial neoplasia), venous thromboembolic events and hot flushes than tamoxifen. On the other hand, the use of aromatase inhibitors has been associated with loss of bone density, arthralgia, myalgia, and a negative effect on lipid metabolism and cardiovascular risk. More extensive and mature studies are necessary to well establish the safety of aromatase inhibitors when given to patients with breast cancer for a long time.