Uterine fibroids: current research on novel drug targets and innovative therapeutic strategies.

INTRODUCTION: Uterine fibroids, the most common nonmalignant tumors affecting the female genital tract, are a significant medical challenge. This article focuses on the most recent studies that attempted to identify novel non-hormonal therapeutic targets and strategies in UF therapy. AREAS COVERED: This review covers the analysis of the pharmacological and biological mechanisms of the action of natural substances and the role of the microbiome in reference to UFs. This study aimed to determine the potential role of these compounds in UF prevention and therapy. EXPERT OPINION: While there are numerous approaches for treating UFs, available drug therapies for disease control have not been optimized yet. This review highlights the biological potential of vitamin D, EGCG and other natural compounds, as well as the microbiome, as promising alternatives in UF management and prevention. Although these substances have been quite well analyzed in this area, we still recommend conducting further studies, particularly randomized ones, in the field of therapy with these compounds or probiotics. Alternatively, as the quality of data continues to improve, we propose the consideration of their integration into clinical practice, in alignment with the patient's preferences and consent.

Follicular Fluid Proteomic Analysis to Identify Predictive Markers of Normal Embryonic Development.

Ageing populations, mass "baby-free" policies and children born to mothers at the age at which they are biologically expected to become grandmothers are growing problems in most developed societies. Therefore, any opportunity to improve the quality of infertility treatments seems important for the survival of societies. The possibility of indirectly studying the quality of developing oocytes by examining their follicular fluids (hFFs) offers new opportunities for progress in our understanding the processes of final oocyte maturation and, consequently, for predicting the quality of the resulting embryos and personalising their culture. Using mass spectrometry, we studied follicular fluids collected individually during in vitro fertilisation and compared their composition with the quality of the resulting embryos. We analysed 110 follicular fluids from 50 oocyte donors, from which we obtained 44 high-quality, 39 medium-quality, and 27 low-quality embryos. We identified 2182 proteins by Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH-MS) using a TripleTOF 5600+ hybrid mass spectrometer, of which 484 were suitable for quantification. We were able to identify several proteins whose concentrations varied between the follicular fluids of different oocytes from the same patient and between patients. Among them, the most important appear to be immunoglobulin heavy constant alpha 1 (IgA1hc) and dickkopf-related protein 3. The first one is found at higher concentrations in hFFs from which oocytes develop into poor-quality embryos, the other one exhibits the opposite pattern. None of these have, so far, had any specific links to fertility disorders. In light of these findings, these proteins should be considered a primary target for research aimed at developing a diagnostic tool for oocyte quality control and pre-fertilisation screening. This is particularly important in cases where the fertilisation of each egg is not an option for ethical or other reasons, or in countries where it is prohibited by law.

The effect of ulipristal acetate on tumor necrosis factor α, insulin-like growth factor 1, and plasminogen activator inhibitor-1 serum levels in patients with symptomatic uterine fibroids.

Introduction: Uterine fibroids (UFs) are benign tumors of the female reproductive system originating from the smooth muscle of the uterus. Currently, progesterone is known to play a key role in the differentiation of the myometrial tissue to form UFs and their abnormal growth. The mechanism of action of progesterone in UF tumorigenesis involves its effect on increasing the concentrations and dysregulation of selected growth factors. Material and methods: A retrospective cohort study was performed to evaluate and compare tumor necrosis factor α (TNF-α), insulin-like growth factor 1 (IGF-1), plasminogen activator inhibitor-1 (PAI-1) serum concentrations in patients with UFs without prior hormonal treatment, patients with UFs treated with a 3-month standard ulipristal acetate (UPA - a type of selective progesterone receptor modulator) scheme (5 mg/day) and in control patients without UFs. A total of 120 patients were divided into 3 groups (controls, UFs with UPA treatment, UFs without UPA treatment). Results: There were no significant differences in TNF-α serum concentrations between patients with UFs who underwent UPA treatment and patients who did not. Serum concentrations of IGF-1 and PAI-1 did not show significant intergroup differences. Conclusions: No significant differences were found between TNF-α concentrations in the serum of patients with UFs treated with UPA, and patients without UPA treatment. In addition, our data analysis did not show significant differences in the concentrations of IGF-1 and PAI-1 between patients with UFs and the control group. Further studies on the dependence of specific symptoms on selected growth factors are mandatory.

Can pelvic floor muscle function before surgery determine the outcome of surgical treatment of stress urinary incontinence in women?

AIM: The study aimed to determine whether pelvic floor muscle (PFM) function before surgery may correlate with the success of surgical interventions for treating stress urinary incontinence (SUI). Our hypothesis was that addressing identified variables in preoperative rehabilitation could potentially improve surgical outcomes. METHODS: This prospective observational study was conducted at a single center and enrolled women qualified to mid-urethral tape insertion for SUI between 2020 and 2022. Digital palpation and manometry (Peritron™ 9300 V) were used to evaluate PFM function. The following parameters were acquired: vaginal resting pressure, vaginal pressure during maximal voluntary contraction (MVC), the area under the curve during a 10-second MVC, moreover the ability to perform correct PFM contraction, reflexive PFM contraction during cough and relaxation were assessed. All measurements were performed before the surgical treatment and during follow-up assessments at 1, 3, and 6 months postoperatively. The primary endpoint of the study was defined as objective cure, characterized by a negative cough stress test (CST), along with a subjective assessment based on the Urogenital Distress Inventory-6 (UDI-6) and Incontinence Impact Questionnaire-7 (IIQ-7). RESULTS: The study involved 57 eligible female participants, all of whom completed the 6-month follow-up. Objective cure was observed in 75.44% of cases, while subjective cure was reported in 33%. There was no association between PFM parameters and surgical outcomes. CONCLUSION: The success of surgical treatment of SUI 6 months postsurgery is not related to preoperative pelvic floor muscle function.

Quality of Life and Sexual Satisfaction in the Early Period of Motherhood-A Cross-Sectional Preliminary Study.

The aim of the study was to assess the impact of breastfeeding-related fatigue and family support on the sexuality and quality of life of mothers during early motherhood. A cross-sectional preliminary study was conducted between 1 October 2021 and 15 May 2022 in 65 women being in early postpartum period. We used the authors' questionnaire developed for the purposes of the study; the Sexual Satisfaction Scale for Women-SSS-W; the Mell-Krat scale for women; and the General Health Questionnaire-GHQ28. A significant negative correlation was found between the age of the patients and the reduction in somatic symptoms (GHQ28 questionnaire) (r = -0.315, p = 0.011). Women working professionally achieved significantly higher results in the SSS-W contentment category (r = 0.313, p = 0.014). Frequent sexual activity reduced disorders in social functioning (the GHQ28 questionnaire) (r = -0.107, p = 0.283). Women who breastfed up to 5 times a day (p = 0.033) reached significantly higher SSS-W scores in terms of communication. The partner's help significantly contributed to higher sexual satisfaction in the aspect of compatibility (p = 0.004) and the overall level of satisfaction determined with the SSS-W questionnaire (p = 0.016). The presented study suggests that older mothers who are employed and supported by a partner have a higher level of contentment, sexual satisfaction and quality of life.