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.

Impact of preoperative pelvic floor muscle function on the success of surgical treatment of pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: The objective of this study was to identify the potential characteristics of pelvic floor muscles (PFM) in the preoperative assessment that could be associated with post-surgical prolapse severity. We hypothesized that the same variables, if identified, could be addressed in preoperative rehabilitation to improve surgical results. METHODS: This was a single-center prospective observational study that included women who underwent surgical pelvic organ prolapse repair between 2020-2022. Genital prolapse was evaluated according to the Pelvic Organ Prolapse Quantification (POP-Q) system. All the participants underwent a PFM assessment, including a vaginal digital assessment and manometry (Peritron™ 9300 V) before surgery and at 1-, 3-, and 6-month follow-ups. Several PFM variables were recorded: vaginal resting pressure, vaginal pressure during maximal voluntary contraction (MVC), area under the curve during a 10-second MVC, ability to correctly contract the PFMs, and reflexive activation during cough and relaxation. The primary endpoint of the analysis was objective surgical success defined as POP-Q 0 or 1 at the 6-month follow-up. Additionally, a change in pelvic floor muscle function was recorded during postoperative visits. RESULTS: A total of 106 females were included in the study. Fifty-one were lost during the 6-month follow-up, which is a major limitation of the study. None of the examined parameters evaluating PFM were associated with surgical success. No statistically significant difference was found in MVC and PFM endurance before and after surgery. Post-surgery, a significant change was observed in the vaginal resting pressure and the ability to correct PFM activation and relaxation. CONCLUSIONS: Preoperative PFM function is not associated with surgical success 6 months after surgery.

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.

Comment on 'Importance of real-time measurement of sperm head morphology in intracytoplasmic sperm injection' by Fumiaki Itoi et al.

We present a commentary on the article published in the Zygote FirstView: 'Importance of real-time measurement of sperm head morphology in intracytoplasmic sperm injection' by Fumiaki Itoi and colleagues. We comment on the importance of providing the microscope setup details whenever sperm morphology visualization is discussed. The claim of ×6000-10,000 magnification is misleading as such levels of magnification are impossible to achieve.

The Opinions of Specialists in Obstetrics and Gynecology on the Indications for Pregnancy Termination in Poland-A Preliminary Cross-Sectional Study.

The physician's decision concerning pregnancy termination is influenced by a number of factors. The study aimed at obtaining the opinions of obstetricians and gynecologists with regard to the indications for pregnancy termination, the readiness to perform the procedure personally and the assessment of the determinants thereof. The survey study was conducted between 1 January 2020 and 31 December 2021 among physicians who performed diagnostic prenatal ultrasonography. A considerable majority of physicians participating in the study did not approve of termination without medical indications (62.5%). A marked majority of them considered the following cases as indications for pregnancy termination: severe fetal defects (90%), lethal defects (91.5%) and a disease threatening maternal life (91.5%). A small group of physicians declared that they were ready to perform a termination without medical indications (12.5%). However, they were ready to perform a pregnancy termination personally in cases of threat to maternal life (77.5%), severe fetal defects (75%), lethal fetal defects (75%) and a pregnancy being a result of rape (75%). No statistical significance was observed with regard to the influence of the respondents' sex, the fact of having children or the workplace on the issue of indications for pregnancy termination. It seems justified to develop case-centered counseling concerning abortion, based on specialists in perinatology, law and ethics, especially in countries with more restrictive abortion law or strongly religious societies.

Inflammation-Related Molecules at the Maternal-Fetal Interface during Pregnancy and in Pathologically Altered Endometrium.

The blastocyst expresses paternally derived alloantigens and induces inflammation during implantation. However, it is necessary for the onset of pregnancy. An abnormal response might result in a pathological course of pregnancy or pregnancy failure. On the other hand, a state of maternal immune tolerance is necessary to ensure the normal development of pregnancy by suppressing inflammatory processes. This article discusses recognized mechanisms and the significance of inflammatory processes for embryo implantation and pregnancy establishment. We would also like to present disorders involving excessive inflammatory response and their influence on events occurring during embryo implantation. The chain of correlation between the processes responsible for embryo implantation and the subsequent physiological course of pregnancy is complicated. Many of those interrelationships are still yet to be discovered. Undoubtedly, their recognition will give hope to infertile couples for the emergence of new treatments that will increase the chance of giving birth to a healthy child.

Sacral Neuromodulation in Pregnant Women-A Case Report and Literature Review.

Millions of women around the world suffer from an overactive bladder and urinary retention. A significant number of them are of reproductive age. For 25 years, SNM has been an effective therapy for treatment-resistant hyperactive bladder and idiopathic urinary retention. The paper presents a case of a 35-year-old pregnant woman with an overactive bladder resistant to pharmacological treatment, who responded positively to sacral neuromodulation. The patient decided against deactivating the neuromodulator and, after an uneventful course of pregnancy, she gave birth by a caesarean section to a healthy female infant. The use of SNM in pregnant patients remains a constant clinical challenge. The current literature was reviewed, but published studies do not provide a clear answer. Further studies with a long follow-up period are necessary to determine more accurately the effects of SNM therapy on the fetus and the course of pregnancy. Currently, it is recommended to deactivate SNM during pregnancy. However, it seems that an individual approach to the patient with information on the risks and benefits of continuing or discontinuing therapy should be the current procedure.