Fertility specialists' views, behavior, and attitudes towards the use of endometrial scratching in Italy.

BACKGROUND: Endometrial scratching (ES) or injury is intentional damage to the endometrium performed to improve reproductive outcomes for infertile women desiring pregnancy. Moreover, recent systematic reviews with meta-analyses and randomized controlled trials demonstrated that ES is not effective, data on the safety are limited, and it should not be recommended in clinical practice. The aim of the current study was to assess the view and behavior towards ES among fertility specialists throughout infertility centers in Italy, and the relationship between these views and the attitudes towards the use of ES as an add-on in their commercial setting. METHODS: Online survey among infertility centers, affiliated to Italian Society of Human Reproduction (SIRU), was performed using a detailed questionnaire including 45 questions with the possibility to give "closed" multi-choice answers for 41 items and "open" answers for 4 items. Online data from the websites of the infertility centers resulting in affiliation with the specialists were also recorded and analyzed. The quality of information about ES given on infertility centers websites was assessed using a scoring matrix including 10 specific questions (scored from 0 to 2 points), and the possible scores ranged from 0 to 13 points ('excellent' if the score was 9 points or more, 'moderate' if the score was between 5 and 8, and 'poor' if it was 4 points or less). RESULTS: The response rate was of 60.6% (43 questionnaires / 71 infertility SIRU-affiliated centers). All included questionnaires were completed in their entirety. Most physicians (~ 70%) reported to offer ES to less than 10% of their patients. The procedure is mainly performed in the secretory phase (69.2%) using pipelle (61.5%), and usually in medical ambulatory (56.4%) before IVF cycles to improve implantation (71.8%) without drugs administration (e.g., pain drugs, antibiotics, anti-hemorrhagics, or others) before (76.8%) or after (64.1%) the procedure. Only a little proportion of infertility centers included in the analysis proposes formally the ES as an add-on procedure (9.3%), even if, when proposed, the full description of the indications, efficacy, safety, and costs is never addressed. However, the overall information quality of the websites was generally "poor" ranging from 3 to 8 and having a low total score (4.7 ± 1.6; mean ± standard deviation). CONCLUSIONS: In Italy, ES is a procedure still performed among fertility specialists for improving the implantation rate in IVF patients. Moreover, they have a poor attitude in proposing ES as an add-on in the commercial setting.

Uptake of Trastuzumab Biosimilars for the Treatment of HER2-Positive Breast Cancer: A Real-World Experience from a Cancer Center.

BACKGROUND: The introduction of trastuzumab biosimilars in clinical practice plays an important role in promoting the sustainability of healthcare systems. By contrast, the switching process can be challenging to the clinics. This survey describes the switching process at a National Cancer Institute over a period of 2 years. METHODS: Data regarding all trastuzumab-based regimens for breast cancer (BC) from 1 January 2019 and 31 December 2020 were extracted from both adverse drug reactions (ADRs) reporting systems and electronic systems involved in inventory management, prescribing, dispensing, and administration. Both patients under monotherapy and combination treatment regimens were included. There were no exclusion criteria. RESULTS AND CONCLUSIONS: Overall 354 patients received at least one trastuzumab-based regimen for a total of 493 lines of treatment and 5769 administrations. Biosimilar were used in 34.3% of trastuzumab-based treatments. No differences between biosimilars and reference drug have been observed in terms of ADRs. The effective cost-saving of the first 2 years is greater than EUR 800,000 and it is estimated to increase over time.

Reliability of diagnostic fluid hysteroscopy in the assessment of cervical invasion by endometrial carcinoma: a comparative study with transvaginal sonography and MRI.

OBJECTIVE: This study aimed at comparing the reliability of diagnostic fluid hysteroscopy, transvaginal sonography (TVS), and magnetic resonance imaging (MRI) to assess pre-operatively the presence of cervical involvement by endometrial carcinoma. METHODS: Cervical involvement was assessed by diagnostic fluid mini-hysteroscopy, TVS and MRI before surgery in 100 patients with histological diagnosis of endometrial carcinoma. Results were compared with pathological examination on surgical specimen. The sensitivity, the specificity, the positive and negative predictive values, the accuracy, the positive and negative likelihood ratios (LR) of the three techniques for recognizing the cervical involvement by the carcinoma were calculated. RESULTS: At histology cervical involvement was found in 15 cases. Compared to TVS and MRI, hysteroscopy showed the highest sensitivity (0.53, 0.67 and 0.93, respectively). The specificity of MRI was significantly higher than both hysteroscopy and TVS (0.95, 0.88 and 0.82, respectively). The diagnostic accuracy of hysteroscopy (0.89) and MRI (0.91) was similar and significantly higher than TVS (0.78). The LR for a positive result of MRI was 14.16, that was 2.08 and 4.68 times higher than that of hysteroscopy and TVS, respectively. CONCLUSIONS: In conclusion, this study demonstrates that in women with endometrial carcinoma the exclusion of cervical canal involvement at hysteroscopy is more reliable than at MRI and TVS while MRI is the most reliable technique for predicting cervical involvement. In the pre-surgical work-up of patients affected by endometrial carcinoma hysteroscopy and MRI are both useful for staging and planning the correct surgical strategy.

Reliability, feasibility, and safety of minihysteroscopy with a vaginoscopic approach: experience with 6,000 cases.

OBJECTIVE: To assess the reliability, feasibility, and safety of lens-based minihysteroscopy. DESIGN: Retrospective comparative study. SETTING: Academic research environment. PATIENT(S): Women with different indications for hysteroscopy. INTERVENTION(S): Six thousand seventeen outpatient diagnostic hysteroscopies with a minihysteroscope (2.7-mm outer diameter [OD] telescope with 3.5-mm OD single-flow diagnostic sheath) and 4,204 with traditional hysteroscope (4-mm OD telescope with 5-mm OD single-flow diagnostic sheath). All hysteroscopies were performed using a vaginoscopic approach and saline to distend the uterus. MAIN OUTCOME MEASURE(S): Rate of successful introduction of the hysteroscope, rate of satisfactory examinations, pain intensity experienced using an arbitrary pain scale (0 = no pain; 1 = low pain; 2 = moderate pain; 3 = severe pain), and number of side effects and complications. RESULT(S): In the minihysteroscopy, group rates of successful introduction and satisfactory examinations were significantly higher than in the traditional hysteroscope group (99.52% vs.72.53% and 98.53% vs. 92.33%, respectively), while pain and vagal reactions were significantly lower (0.10 +/- 0.34 vs.1.09 +/- 0.53 and 2.25% vs.17.12%, respectively). CONCLUSION(S): Hysteroscopy with lens-based minihysteroscopes was easier, less painful, more reliable, and safer than with 5-mm hysteroscopes. Minihysteroscopy with a vaginoscopic approach is a very well tolerated, effective, and safe outpatient procedure.

Effects of tibolone on plasma levels of nitric oxide in postmenopausal women.

OBJECTIVE: To determine the effects of tibolone on nitric oxide (NO) plasma levels in postmenopausal women. DESIGN: Randomized, double-blind, placebo-controlled, cross-over trial. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Eighteen healthy women who have been in postmenopause for 1-4 years. INTERVENTION(S): Women received either tibolone 2.5 mg/day (group A) or placebo (group B) for 1 month; then the treatment was inverted for the second month. MAIN OUTCOME MEASURE(S): Plasma concentration of NO stable oxidation products and blood pressure were evaluated at baseline, month 1, and month 2. RESULT(S): Baseline concentration of NO metabolites were similar in both groups. At month 1, mean concentration of NO metabolites increased significantly in group A alone. At the end of month 2, NO metabolite levels in group A returned to baseline, whereas in group B they increased significantly. CONCLUSION(S): Tibolone induced a sustained increase in plasma levels of NO in postmenopausal women, suggesting that tibolone may exert a direct cardiovascular protective effect in postmenopausal women.

Tolerability and cardiovascular complications of outpatient diagnostic minihysteroscopy compared with conventional hysteroscopy.

STUDY OBJECTIVE: To assess acceptability and cardiovascular complications of hysteroscopy performed with minihysteroscopes compared with those performed with conventional hysteroscopes. DESIGN: Prospective, randomized clinical trial (Canadian Task Force classification I). SETTING: Academic research center. PATIENTS: One hundred women with abnormal uterine bleeding. INTERVENTIONS: Hysteroscopy with a 3.5-mm minihysteroscope or conventional 5-mm endoscope with no anesthesia. MEASUREMENTS AND MAIN RESULTS: Duration of examinations, pain, and occurrence of vasovagal reactions were recorded. Pain was assessed by visual analog scale ranging from zero to 20 before (pain expectancy) and at the end of the procedure. Occurrence of vasovagal reactions was assessed by monitoring blood pressure and pulse rate at 1-minute intervals during the procedure. A heart rate of less than 60/minute or a reduction greater than 20% compared with baseline was considered a vasovagal reaction; similarly, a reduction in blood pressure exceeding baseline value by 20% was considered a result of vagal stimulation. Mean duration was shorter for minihysteroscopy than for conventional hysteroscopy. The mean (SD) level of pain experienced during minihysteroscopy also was significantly lower (0.76 +/- 0.65 vs 1.46 +/- 0.86, 95% CI-1.0-0.4, p <0.0001). The number of instrumentally recorded (1 vs 11 cases) and clinical vasovagal reactions (0 vs 6 cases) was also significantly lower in the minihysteroscopy group than in the conventional hysteroscopy group (p <0.002 and <0.02, respectively). CONCLUSION: New-generation minihysteroscopes make hysteroscopy easier and less painful, and carry a lower risk of vasovagal reactions than hysteroscopy performed with conventional instruments. In our experience, minihysteroscopy with vaginoscopic approach and saline distention is well tolerated, effective, and a true outpatient procedure.

Blood to the cornual area of the uterus is mainly supplied from the ovarian artery in the follicular phase and from the uterine artery in the luteal phase.

BACKGROUND: The blood supply to the uterus is provided by the uterine and ovarian arteries, which form anastomoses. Yet the flow direction through this anastomoses and the primary source of blood supply to the tubes and uterine cornua remains unknown. To clarify this issue, we studied the spatial propagation of temperature changes following cooling of the upper vaginal area. METHODS: A thermocatheter with eight measurement points at 5-mm intervals was inserted into the uterus of nine women in the follicular phase and 11 in the luteal phase. The distal tip was positioned in the cornual area and temperatures were registered every 2 s. The vagina was then cooled for 7 min with 25 degrees C saline. RESULTS: The pattern of uterine cooling based on local counter-current transfer differed between the follicular and luteal phase. Cooling of the cornual area was significantly lower in the luteal phase compared with the follicular phase, indicating a shift in the prevailing source of arterial supply in that area following ovulation. CONCLUSIONS: The divide between the territories irrigated by the uterine and ovarian arteries moves between the follicular and luteal phase. This constitutes the first description of a functionally determined shift in the territorial divide of two vascular systems, and has numerous practical implications.

Twice-weekly transdermal estradiol and vaginal progesterone as continuous combined hormone replacement therapy in postmenopausal women: a 1-year prospective study.

OBJECTIVE: The purpose of this study was to evaluate the acceptability and endometrial safety of a twice-weekly administration of transdermal estradiol (0.05 mg) systems and vaginal progesterone gel (Crinone [Serono, Rome, Italy] 4%, 45 mg/d) as a continuous combined nonoral hormone replacement therapy regimen. STUDY DESIGN: Thirty-five postmenopausal women took part in this 1-year prospective observational trial. The bleeding pattern, blood pressure, weight, endometrial thickness, and endometrial histologic characteristics of the women were monitored. Mean values were compared before and after treatment by paired Student t tests. RESULTS: Twenty-six (74.3%) women completed the study and were totally amenorrheic. A total of 350 cycles yielded valuable data. Of these, 287 (82%) cycles were amenorrheic. At month 3, blood pressure and weight decreased significantly. At final assessment, endometrial thickness was significantly greater than baseline (4.6 +/- 0.9 vs 3.6 +/- 0.9 mm; P <.0005), and histologic examination revealed endometrial atrophy in 24 (92.3%) cases and signs of decidualization in 2 cases. CONCLUSION: Transdermal estradiol and a twice-weekly administration of the vaginal progesterone gel Crinone constitutes a new, viable hormone replacement therapy regimen. It represents a practical option for a no-bleed treatment, ensuring both high endometrial protection and the inherent safety linked to administrating physiologic hormones nonorally.