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.
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.
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.
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.
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.
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.
Several studies, although with conflicting results, have sought to determine the concentration of soluble CTLA4 antigens in peripheral blood plasma and peritoneal fluid in patients with ...endometriosis-related infertility. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) through a search of the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library, Health Technology Assessment Database and Web of Science, and Clinical Trials research register. We included observational or prospective human and animal studies with any features related to endometriosis and/or infertility studies involving CTLA4-related pathogenesis published in English. The results of studies in which the size and characteristics of the observed groups were not stated were excluded. From the initial pool of 73 publications identified and screened, we finally included 5 articles to summarize the most recent knowledge about CTLA4-linked autoimmunity in the pathogenesis of endometriosis and related infertility. Evidence from clinical studies shows that CTLA4-based autoimmunity is involved in the maintenance of chronic inflammation in the peritoneal environment, with pre-clinical evidence of anti-CTLA antibodies as a potential novel target therapy for endometriosis. However, CTLA4 gene analyses do not support findings of CTLA4-linked autoimmunity as a primary determinant of the pathogenesis of endometriosis. These findings underlie the role of complex interactions within the family of immune checkpoint molecules involved. Further studies are needed to investigate the clinical relevance of anti-CTLA target therapy, taking into account the potential adverse events and repercussions of novel immunologic therapy modalities. However, with the general scarcity of studies investigating this topic, the clinical importance of CTLA4 autoimmunity still remains unclear.
SAŽETAK
Bolesti srca i krvožilnog sustava najučestaliji su uzrok smrtnosti u Europi. Prema najnovijim podatcima, čak 10% više smrtnosti od kardiovaskularnih bolesti zastupljeno je kod žena u odnosu ...na muškarce, što znači da u Europi zbog kardiovaskularnih razloga godišnje umire 300.000 žena više nego muškaraca. U većini istraživanja menopauza je istaknuta kao primarni čimbenik koji doprinosi povećanju kardiovaskularnog rizika u žena, usprkos metodološkim ograničenjima u obliku razdvajanja kronološkog starenja i menopauze. Proaterogene promjene u lipidogramu tijekom menopauzalne tranzicije smatraju se najsnažnijom poveznicom između nastupa menopauze i porasta kardiovaskularnog rizika. Kohortne studije nisu našle uzročnu povezanost nastupa menopauze s promjenama krvnog tlaka te homeostazom glukoze i inzulina, odnosno s rizikom razvoja šećerne bolesti. Uloga estrogena u očuvanju kardiovaskularnog zdravlja, uza sve gore opisane izravne učinke na srce i krvne žile, uključuje mehanizme kojima se regulira profil lipida, inzulinska osjetljivost te monocitno-makrofagni sustav, a čiji ispadi funkcije doprinose multifaktorijalnom procesu ateroskleroze koji u znatnoj mjeri modulira kardiovaskularni rizik. Sinteza brojnih istraživanja o molekularnim mehanizmima ističe da je estrogenska protekcija krvožilja i srca posljedica neposrednog učinka estrogena na vazodilataciju, angiogenezu, unaprjeđenje mitohondrijalne funkcije i sniženje razine oksidativnog stresa te supresiju fibroze. Promatrajući sve znanstvene spoznaje o utjecajima hormonskog nadomjesnog liječenja na profil kardiovaskularnog rizika, bitno je znati da je razvoj HNL-a bitno proširio mogućnost optimizacije i individualizacije terapije, a time su dodatno reducirani potencijalni rizici. Uz transdermalni put primjene, terapijske režime s niskim i ultraniskim dozama hormona te primjenu prirodnoga mikroniziranog progesterona i didrogesterona, kardiovaskularno zdravlje žena u menopauzi može biti značajno unaprijeđeno.
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).
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.
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.
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.
Purpose
To summarize available evidence comparing the transdermal and the oral administration routes of hormone replacement therapy (HRT) in postmenopausal women.
Methods
We performed a systematic ...review of the literature on multiple databases between January 1990 and December 2021. We included randomized controlled trials and observational studies comparing the transdermal and oral administration routes of estrogens for HRT in postmenopausal women regarding at least one of the outcomes of interest: cardiovascular risk, venous thromboembolism (VTE), lipid metabolism, carbohydrate metabolism, bone mineral density (BMD), and risk of pre-malignant and malignant endometrial lesions, or breast cancer.
Results
The systematic literature search identified a total of 1369 manuscripts, of which 51 were included. Most studies were observational and of good quality, whereas the majority of randomized controlled trials presented a high or medium risk of bias. Oral and transdermal administration routes are similar regarding BMD, glucose metabolism, and lipid profile improvements, as well as do not appear different regarding breast cancer, endometrial disease, and cardiovascular risk. Identified literature provides clear evidence only for the VTE risk, which is higher with the oral administration route.
Conclusions
Available evidence comparing the transdermal and oral administration routes for HRT is limited and of low quality, recommending further investigations. VTE risk can be considered the clearest and strongest clinical difference between the two administration routes, supporting the transdermal HRT as safer than the oral administration route.
Background: The COMT gene polymorphism is associated with neurological and psychiatric disorders and pain perception. The present study investigates the existence of anxiety and pain perception in ...relation to the COMT (catechol-O-methyltransferase) gene polymorphism in labouring women (during “natural” childbirth) with or without inhaled analgesia. Methods: A total of 181 women who chose vaginal birth were enrolled in this study. To present the difference in pain perception, the parturients were divided into one group (n = 90) that chose labour analgesia with inhaled nitrous oxide (50% nitrous oxide and 50% oxygen) and one group (n = 91) without analgesia. The blood samples were taken during the pregnancy as a part of routine pregnancy controls in the hospital. The COMT gene polymorphism was detected with the PCR technique. The pain perception of parturients was self-evaluated two times according to the VAS (Visual Analogue Scale), and anxiety as a personality trait was determined with the STAI-T (State Trait Anxiety Inventory). Pain perception as well as anxiety were compared according to COMT genotypes. Results: In the 181 pregnant women, there were 40 women (22%) of wild homozygotes (GG) of COMT, 95 women (53%) of mutant heterozygotes (GA), and 46 women (25%) of mutant homozygotes (AA). A negative association of pain perception with the GA (mutant heterozygote) polymorphism of the COMT gene versus the wild-type (GG polymorphism) was observed. The GA polymorphism of the COMT gene was associated with 0.46 units lower pain perception compared to the wild type (GG). The anxiety trait score in group AA was lower than in groups GA and GG. The difference reached statistical significance only when comparing AA versus GA (p > 0.042). Analgesic efficacy of nitrous oxide was noticed in 22% of labouring women who reported moderate pain (VAS score 4–7). Conclusions: The COMT gene polymorphism was associated with pain perception and anxiety among parturients. The COMT gene polymorphism GA was associated with negative pain perception among labouring women. Nitrous oxide showed statistical significance in anxiolytic efficacy during labour in women with mild anxiety as a personality trait. Anxiolytic efficacy of nitrous oxide has shown better efficacy in parturients with the COMT gene polymorphism AA.
Several scoring systems exist for the management of acute appendicitis (AA) during pregnancy. However, the systems are based on the nonpregnant adult population. The aim of this study was to create a ...highly accurate scoring system that can be applied to pregnant women and to compare it to the most commonly used scores in general population and pregnant women. The creation and subsequent implementation of a highly accurate score system could shorten the diagnostic period and minimize the use of (ionizing) diagnostic imaging allowing the selection of the best treatment approach in pregnant patients with acute appendicitis. A single-center, retrospective cohort observational study was conducted at the University Hospital Centre Zagreb, Zagreb, Croatia. Data were extracted from medical records of pregnant patients with suspected AA from January 2010 to December 2020. A total of 59 pregnant patients diagnosed with AA during pregnancy were identified, 41 were treated surgically, and 18 had non-surgical management. The main objective of our study was the detection of predictive factors of AA during pregnancy. Anorexia, pain migration to the right lower quadrant, rebound pain, axillary temperature over 37.3 °C, CRP/platelet ratio > 0.0422, neutrophil/lymphocyte ratio > 7.182, and ultrasonic signs of AA were scored. Scoring in Appendicitis TriMOdal Score (ATMOS) consists of positive clinical parameter, each bringing 1 point and other parameters mentioned above that bring 2 points each. The score ranges from 0 to 10. Our model of ATMOS yields a high area under the receiver-operating characteristic curve of 0.963. The positive likelihood ratio is 9.97 (95% CI 2.64–38.00), and the negative likelihood ratio is 0.1 (95% CI 0.03–0.31), meaning that 94% of cases with ATMOS > 4 have AA, while less than 13% with an ATMOS ≤ 4 have the diagnosis of AA. The potential of ATMOS differentiating AA during pregnancy was demonstrated. Future prospective, randomized trials are needed to evaluate its accuracy and whether it should be used instead of Alvarado or Tzanakis scores in clinical decision-making.
Trial registration number
ClinicalTrials.gov-NCT05202483. Date of registration: January 21, 2022.
Free radicals and oxidant molecules are part of our organism in a stable balance. However, when addressing female infertility, questions about their role in oocyte quality arise. This review outlines ...the major alterations of redox homeostasis in the follicular fluid through pathophysiological conditions in female reproduction and its potential effect on IVF outcome. A review of the literature was accurately performed. Manuscripts investigating follicular fluid biomarkers, especially related to oxidant molecules, were screened and used in this review. Studies assessing the follicular reactive species were found and screened. Moreover, studies assessing the IVF outcomes related to biomarkers were considered. The results are provided in an analytical pathway. The study of biomarkers confirms the shift to enhanced oxidizing modification of macromolecules and antioxidative consumption in the follicular fluid of women undergoing IVF treatment. A lack of congruency in methods appears to be marked in the design of scientific studies. However, it is not clear whether redox disbalance has a disruptive effect on the oocyte competence or whether it plays a role in the oocyte maturation process. Red-ox balance plays a questionable role in IVF outcomes. Possible further insights may consider the antioxidant role of adjuvants during controlled ovarian stimulation cycles.
