Clinical Efficacy, Pharmacokinetics, and Safety of the Available Medical Options in the Treatment of Endometriosis-Related Pelvic Pain: A Scoping Review.

BACKGROUND: In this scoping review, we sought to identify published studies evaluating the drugs currently used in the treatment of endometriosis-related pelvic pain, with reflection on their chemical properties, pharmacokinetics, safety profile, and clinical efficacy. METHODS: A literature search was conducted with the use of the PubMed and EMBASE electronic databases, focusing on identifying articles published in English between January 1990 and 2023. RESULTS: Based on the included studies, current therapy options for the treatment of endometriosis-related pain identified and reviewed in this article were: (1) non-steroidal anti-inflammatory drugs; (2) combined oral contraceptive (COCs); (3) progestins; (4) gonadotropin-releasing hormone agonists and antagonists; (5) aromatase inhibitors (AIs); (6) selective estrogen and progesterone receptor modulators; and (7) levonorgestrel-intrauterine device. CONCLUSIONS: Based on the published evidence, clinicians should consider NSAIDs, COCs, and progestins as the first-line medical therapies. Compared with second-line options, such as GnRH agonists/antagonists or AIs, the abovementioned first-line options are well tolerated, efficacious, and exhibit lower overall price. Future research priorities should be to identify novel target therapies and to evaluate the effects of available drugs through different routes of administration.

Feasibility and Surgical Outcomes of Hysteroscopic Myomectomy of FIGO Type 3 Myoma: A Systematic Review.

The latest classification from the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) has reclassified type 3 myomas, changing their classification from intramural to submucosal. While hysteroscopic myomectomy is considered the gold standard treatment for patients experiencing symptoms from submucosal myomas, there are currently no specific guidelines available for managing type 3 myomas, and the optimal surgical approach remains uncertain. Methods: The search for suitable articles published in English was carried out using the following databases (PROSPERO ID CRD42023418602): MEDLINE, EMBASE, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), Health Technology Assessment Database, Web of Science and search register. Only original studies reporting data on hysteroscopic myomectomy of type 3 myoma were considered eligible. The main outcomes investigated were the effectiveness and feasibility of hysteroscopic myomectomy and reproductive outcomes after surgical treatment. Results: Two hundred and sixty-one studies were screened and nineteen of these were read for eligibility. Three studies encompassing 56 patients in total were included. Among the overall population studied, three patients needed an additional procedure to completely remove the myoma and five cases of post-surgical synechiae were recorded. No complications were reported. Of 42 patients wishing for pregnancy, the cumulative live birth rates before and after the hysteroscopic myomectomy were 14.3% and 42.9%, respectively. Conclusions: Hysteroscopic myomectomy appears to be a safe and feasible approach. Nevertheless, data reported in the literature are extremely scarce and based on studies with few patients enrolled. New evidence is needed to assess the safety and effectiveness of hysteroscopic treatment for FIGO type 3 myomas.

Effects of different progesterone levels on reproductive outcomes in assisted reproductive technologies: from molecular basis to treatment strategies.

PURPOSE: The aim of this narrative review is to offer an overview about the role of progesterone levels on pregnancy outcome in patients undergoing assisted reproductive technologies (ARTs). METHODS: A detailed computerized search of the literature was performed in the main electronic databases (MEDLINE, EMBASE, Web of Science) to determine the importance of elevated progesterone levels at different stages of the cycle for pregnancy rates in the in vitro fertilization (IVF) cycle. Our review also provides information on the differences between elevated progesterone levels and their interpretation in normal and in poorly responding women. RESULTS: After careful evaluation, our search strategy yielded a total of 15 included articles, showing the possible factors that may have had an impact on the increased progesterone level before human chorionic gonadotropin (HCG) injection and the different thresholds above which the pregnancy rate was lower. Furthermore, increased progesterone on cycle day 2 or 3 could serve as a marker for increased progesterone in the late follicular phase, which is associated with a lower pregnancy rate. CONCLUSION: Despite the literature data that support the negative effect of elevated progesterone on fresh cycles, due to lack of randomized controlled trials, the value of measuring progesterone in daily practice is questionable. Available evidence supports the detrimental effect of elevated progesterone in different subgroups of women, although there is still the need for defining different thresholds and durations of high progesterone exposure. The need for various thresholds for different cohorts of women, the inter-assay variability is making this decision harder.

Efficacy Comparison between Kegel Exercises and Extracorporeal Magnetic Innervation in Treatment of Female Stress Urinary Incontinence: A Randomized Clinical Trial.

Background and Objectives: To estimate the effectiveness of Kegel exercises versus extracorporeal magnetic innervation (EMI) in the treatment of stress urinary incontinence (SUI). Materials and Methods: A parallel group, randomized clinical trial was conducted in the Department of Obstetrics and Gynecology, Clinical Hospital Centre Zagreb, Croatia. After assessing the inclusion/exclusion criteria, each eligible participant was randomized to one of the two observed groups by flipping a coin: the first group underwent treatment with Kegel exercises for 8 weeks, while the second group underwent EMI during the same time interval. The primary outcome was the effectiveness of treatment as measured by the ICIQ-UI-SF overall score, eight weeks after the commencement of treatment. Results: During the study period, 117 consecutive patients with SUI symptoms were assessed for eligibility. A total of 94 women constituted the study population, randomized into two groups: Group Kegel (N = 48) and Group EMI (N = 46). After 8 weeks of follow-up, intravaginal pressure values in the EMI group were 30.45 cmH2O vs. the Kegel group, whose values were 23.50 cmH2O (p = 0.001). After 3 months of follow-up, the difference was still observed between the groups (p = 0.001). After the end of treatment and 3 months of follow-up, the values of the ICIQ-UI SF and ICIQ-LUTSqol questionnaires in the EMI group were lower than in the Kegel group (p < 0.001). Treatment satisfaction was overall better in the EMI group than in the Kegel group (p < 0.001). Conclusions: Patients treated with EMI had a lower number of incontinence episodes, a better quality of life, and higher overall satisfaction with treatment than patients who performed Kegel exercises.

Overactive Bladder or Anxiety: Which Came First?

OBJECTIVE: Although available diagnostic criteria are intelligible, combination of OAB and anxiety in the same patient presents a perfect example of medical causality dilemma, commonly stated as the question: "which came first: the chicken or the egg?". The aim of this review article is to address available insights in bidirectional association between OAB and anxiety. METHODS: In this review article, we included different types of studies whose results are presented as relative risk (RR) or odds ratio (OR) with a 95% accuracy. A literature search was conducted with the use of the PubMed and EMBASE electronic databases focusing on identifying articles published in English between 1990 and 2020. RESULTS: The electronic searches, after duplicate records removal, provided a total of 126 citations. Of these, 107 were excluded after title/abstract screening (not relevant to the review). We examined the full text of 19 publications remaining to summarize possible mechanisms between OAB and anxiety. According to examined literature, our result synthesis provides insight in epidemiology, pathophysiology, diagnostic and therapeutic approach of both conditions. CONCLUSION: Temporal relationship between OAB and anxiety is not very well documented because available longitudinal cohort studies are limited. The limitation of the published literature is that most were population-based symptom studies demonstrating high risk of bias. Although data from analysed studies suggest that anxiety and OAB and anxiety might be casually related, studies provided on clinical population are warranted. In addition to the traditional urologic factors, we recommend that psychosocial factors such as anxiety should be assessed routinely in patients with OAB.

Validation of the Croatian Version of the 8-Item Overactive Bladder Questionnaire (OAB-V8).

OBJECTIVES: The present study was conducted with the aim to translate, adapt, and validate the 8-item Overactive Bladder Questionnaire (OAB-V8) in Croatia. METHODS: This study included a total of 58 female patients with OAB and 66 healthy women. The translation to Croatian followed standardized procedure. All eligible participants completed OAB-V8 at inclusion and 2 weeks after to assess test-retest reliability. Cronbach α coefficient was calculated to assess internal consistency. RESULTS: Our study demonstrated high internal consistency for all items at both visits (Cronbach α between 0.799 and 0.847), with stable internal consistency reliability across items during the 2-week period. However, the exception is the item "waking up at night to urinate," which significantly changed during the 2-week period. Intraclass correlation for OAB-V8 items ranged from 0.810 to 1.0, with Spearman correlations greater than 0.9 for all items (P < 0.01). There were strong significant correlations between frequency of urination during daytime and uncomfortable and sudden urge to urinate, and between nocturia and waking up at night. Discriminative validity showed statistically significant score differences between patients and the control group. CONCLUSIONS: The Croatian version of the OAB-V8 was successfully translated, adapted, and validated so the questionnaire is now ready for use as a reliable tool for initial screening and assessing patients with OAB in everyday Croatian clinical practice.

The pharmacoeconomic impact of follitropin alpha biosimilars in IVF therapy in Europe: a report of the literature.

Introduction: To study the impact of biosimilars in assisted reproductive treatments, we performed a review of the literature. Biosimilars are a bioequivalent chemical drug referred to the original. Their production is strongly requested in order to reduce drug cost and reduce health economic impact on national health system. In assisted reproductive treatments different gonadotropin biosimilars are being produced.Areas covered: For this reason, we performed a review of the literature on follitropin alfa Gonal-F biosimilar, Ovaleap and Bemfola, to assess their cost efficacy in national health system. Cost effective (CE) analysis and incremental cost-effectiveness ratio (ICER) were used as parameters for biosimilar impact evaluation in the national health system economy. In particular, they had only slight impact on cost reduction of recombinant follitropin alfa products in Europe.Expert opinion: considering cost-effective analysis, Gonal-F remains the first choice for national health systems. However, well-designed powered methods are strongly needed to assess biosimilars cost-effectiveness.

Retrospective analysis of the use of two recombinant follitropin alfa injections in patients undergoing in vitro fertilization treatment with the gonadotropin-releasing hormone antagonist protocol.

AIM: To evaluate the clinical efficacy of biosimilar (Ovaleap) compared with the referenced follitropin alfa (Gonal-f), within the context of antagonistic multiple doses protocol of controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) techniques. METHODS: A retrospective, monocentric study included 229 infertile women aged 22 to 43 years who underwent their first cycle of COH for the purpose of the IVF or ICSI during the period of 2017. Eligible patients underwent ovarian stimulation with either Ovaleap (n = 152) or Gonal-f (n = 77) starting at Cycle Day 2 and were receiving gonadotropin-releasing hormone (GnRH) antagonist in either fixed or flexible antagonist protocol manner. RESULTS: Ovaleap-treatment resulted in fewer number of oocytes retrieved in regard to Gonal-f-treatment, with the median of seven oocytes retrieved in the Ovaleap group versus nine in the Gonal-f group (U = 5369.5, P = 0.3079). Clinical pregnancy rate was 24.3% in the overall study sample and 31.9% in women with embryo transfer, in the Ovaleap group. Similarly, in the Gonal-f group these rates were 25.0% and 34.5%, respectively. Only four patients experienced ovarian hyperstimulation syndrome, with one case in Ovaleap-treatment group and three cases in Gonal-f-treatment group. CONCLUSION: While the clinical efficacy profile favored using Gonal-f formulation of follitropin alfa, this analysis showed that there is no significant difference in the number of oocytes retrieved between Ovaleap and Gonal-f follitropin alfa formulations, used within GnRH antagonist protocols of COH.

Questionnaire on the Midwives' Knowledge About Oral Emergency Contraception.

The aim of the study was to assess the level of knowledge of midwives working in different clinical settings about oral emergency contraception. The study included 225 midwives; during the period from December 2015 to February 2016, they completed a 16-item web-based survey using the SurveyMonkey software available on the Croatian Midwives Chamber site. In total 277 participants started to fill out the survey and 225 participants responded to all 16 questions. Demographic, educational and professional characteristics of the participants in this survey are provided. Distri-bution of participant responses to questions regarding basic reproductive endocrinology, unplanned pregnancies and emergency contraception clearly revealed important gaps in the group knowledge. There was evident gap in the knowledge about emergency contraception in the study group of Croa-tian midwives. Having in mind the study group grounds in gynecology and obstetrics, and their public health relevance, targeted educational activities both during midwife formal education and on-job are required to improve the group knowledge about emergency contraception. National guidelines on oral emergency contraception are an at hand learning tool and the most appropriate local source of information on emergency contraception. Various initiatives should be considered for this document to become an integral part of formal midwife education and regular part of their on-job trainings.

Patient-reported outcome of solifenacin treatment among women experiencing urinary urgency and urgency incontinence.

OBJECTIVE: To evaluate treatment success and tolerability of solifenacin among women with urinary urgency (UU) and urgency urinary incontinence (UUI). METHODS: In a prospective, observational, multicenter pilot study in Slovenia and Croatia, 100 women with UU and UUI were enrolled between January 2011 and July 2011. Patients received 5mg of solifenacin once daily for 12 weeks and completed a 3-day bladder diary, urgency questionnaire, Urogenital Distress Inventory (UDI), and Incontinence Impact Questionnaire (IIQ). RESULTS: Overall, 91 women completed 12 weeks of treatment. Severity, frequency, and bother of UU significantly had decreased at weeks 4 and 12 (P<0.001). Improvement in UU led to an improvement in mean IIQ score: a reduction in UU frequency had the greatest impact (P=0.006). The mean treatment success rate was 74.2% (by visual analog score) and was closely related to the mean change in irritative UDI score (r=0.39; P<0.001). Treatment success was greatest for patient perception of intensity of urgency scale (PPIUS; P=0.003), UU bother (P=0.017), and micturition frequency (P<0.026). Dry mouth occurred in 35.2% of women at 4 weeks, and 27.7% at week 12. CONCLUSION: Solifenacin treatment was effective and well-tolerated among women with UU and UUI. All overactive bladder symptoms had improved by week 12.