Effectiveness of Myo-Inositol on Oocyte and Embryo Quality in Assisted Reproduction: Systematic Review and Meta-Analysis of Randomized Clinical Trials.

INTRODUCTION: We sought to conduct a systematic review and meta-analysis of randomized clinical trials (RCTs) to evaluate the impact of myo-inositol on oocyte and embryo quality in women undergoing assisted reproduction. METHODS: The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist (registration number: CRD42023433328). Studies were identified by searching PubMed, Cochrane Library, Google Scholar, Scopus, Embase, and ClinicalTrials databases. RESULTS: Eight RCTs were included for qualitative analysis reporting on 820 participants. Four meta-analyses were performed. Numbers of retrieved oocytes in comparison of intervention and control group were higher in inositol group (mean difference [MD] = 0.41, 95% CI: 0.05-0.77, p = 0.02). Meta-analysis of two studies comparing numbers of oocytes among poor ovarian responder patients showed no significant difference between intervention and control group (MD = 0.50, 95% CI: 0.57-1.58, p = 0.36). Miscarriage rate has no statistically significant difference between the treatment and control groups (risk ratios [RRs] = 0.81, 95% CI: 0.20-3.32, p = 0.77). Inositol played no role in improving clinical pregnancy rates; there was no significant difference between the intervention group and the control group (RR = 1.41, 95% CI: 0.88-2.25, p = 0.15). CONCLUSION: Thus, we did not find any benefits of using myo-inositol on oocyte and embryo quality in women undergoing reproductive technologies. Further studies are needed to assess efficacy, safety, and high compliance by female patients.

Preimplantation genetic testing for aneuploidy in patients of different age: a systematic review and meta-analysis.

This study aimed to summarize the current knowledge on the benefits of in vitro fertilization/intracytoplasmic sperm injection with preimplantation genetic testing for aneuploidy (PGT-A) and to discuss the role of PGT-A in patients of different ages undergoing assisted reproduction. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 checklist. Registration number: CRD42022354697. Studies were identified by searching the PubMed, Cochrane Library, Google Scholar, Scopus, Embase, and ClinicalTrials databases. Seven meta-analyses were performed with additional stratification of age and prognosis of the women studied. Clinical pregnancy rate per embryo transfer in patients aged >35 years was higher in the PGT-A group (P=0.0002) than in controls. Live birth rate (LBR) per embryo transfer in women 35 years old or younger (P=0.002) was higher in the PGT-A group. The LBR per patient in women aged >35 years was higher in the PGT-A group (P=0.004). The effects of PGT-A on LBR in patients with poor prognosis showed a statistically significant increase (P=0.003). There was no significant difference in the rate between the two groups. PGT-A is effective and can be recommended for patients aged >35 years undergoing assisted reproduction to improve their reproductive outcomes. Moreover, our study showed the possible benefits of PGT-A in patients with a poor prognosis. Overall, our findings suggest that PGT-A is a valuable tool for improving the reproductive outcomes of assisted reproductive procedures in older women and those with a history of pregnancy complications.

Metformin and progestins in women with atypical hyperplasia or endometrial cancer: systematic review and meta-analysis.

PURPOSE: To assess metformin's effectiveness in adding it to progestin-based hormone therapy for treating atypical endometrial hyperplasia (AEH) and early endometrial cancer (EEC). METHODS: We conducted a systematic review and meta-analysis following PRISMA guidelines (registration number CRD42023399094). We searched databases for studies up to March 2023, including randomized and non-randomized clinical trials in English. RESULTS: Out of 280 studies, 9 studies (1104 patients) were eligible. A total of 408 patients were allocated to receive metformin, and 696 patients entered the control group. Primary analysis focused on evaluating the CR showed a significant difference in patients with AEH treated with metformin (RR = 1.10, 95% CI 1.02-1.20, p = 0.02). Relapse rate (RR = 0.62, 95% CI 0.33-1.17, p = 0.14) was also evaluated. Secondary analysis indicated higher pregnancy rates (RR = 1.28, 95% CI 1.04-1.57, p = 0.02) with no significant difference in live birth rates (RR = 0.56, 95% CI 0.29-1.10, p = 0.09). CONCLUSION: Combined therapy is effective. Metformin shows superiority to the standard regimen in achieving better CR rate in patients with AEH and benefits pregnancy rates but not recurrence or live birth rates. Therefore, the ideal fertility-sparing treatment for EC has not yet been determined and further clinical trials are needed.

Laser vaporization compared with other surgical techniques in women with ovarian endometrioma: a systematic review and meta-analysis.

OBJECTIVE: To compare outcomes after laparoscopic cystectomy versus laser vaporization in women of reproductive age with ovarian endometrioma. EVIDENCE REVIEW: Our systematic review and meta-analysis was registered in PROSPERO (CRD42021281781) and was done according to the PRISMA 2020 checklist. Studies (published until October 2021) were identified by searching PubMed, Cochrane Library, Google Scholar, and ClinicalTrials.gov databases (key words "cystectomy", "laser vaporization", and "endometrioma"). The search was conducted independently by two investigators (L.P. and S.I.). Inclusion criteria were: women of reproductive age undergoing surgery for symptomatic endometriomas larger than 30 mm. The exclusion criteria were: women who undergo conservative treatment. Outcomes were: risk ratio for recurrence, ovarian reserve and pregnancy rates. The studies included were randomized clinical trials (RCTs) and nonrandomized clinical trials (prospective controlled, prospective cohort, retrospective studies, and other types of studies) that included a minimum of 10 patients and written in English. Tools recommended by the Cochrane Society achieved risk-of-bias assessment. RESULTS: Totally, 874 studies were found, 9 studies were included in qualitative synthesis (822 patients). All the authors compared the efficacy and safety of cystectomy or laser vaporization in reproductive-aged women with ovarian endometrioma. The overall risk of bias for the randomized trials was 80% 'some concerns' and 20% 'low', and for the cohort studies, 50% 'some concerns' and 50% 'low'. The primary meta-analysis focused on recurrence rates (4 studies included) with no statistically significant differences found between these two interventions (RR = 0.53, 95% CI 0.24 to 1.21, P = 0.13). The next meta-analysis estimated antral follicle count (3 studies) which was significantly lower in cystectomy group (RR = - 2.56, 95% CI - 3.71 to - 1.42, P < 0.0001). Pregnancy rates were analyzed in 3 studies with no statistically significant difference (RR = 0.96, 95% CI 0.81 to 1.14, P = 0.64). CONCLUSIONS: There was no statistical difference in the recurrence rate and pregnancy rates, but the antral follicle count was higher in the laser vaporization group. However, we need more clinical trials to make stronger recommendations.

Skin Rejuvenation in Women using Menopausal Hormone Therapy: A Systematic Review and Meta-Analysis.

OBJECTIVES: To evaluate the effect of menopausal hormone therapy (MHT) on skin aging in menopausal women. METHODS: Studies were identified by searching PubMed, Cochrane Library, Google Scholar, and ClinicalTrials.gov databases using the key words "hormone replacement therapy" AND "skin" AND "menopausal." Studies that used and compared oral/transdermal MHT with placebo or another type of treatment in menopausal women aged 45-55 years were selected. RESULTS: From 1,526 studies identified, 15 studies comprising 1,589 patients were included in the final analysis. Our meta-analysis aimed to compare skin elasticity (standard [Std] mean difference = 0.28; 95% confidence interval [CI], 0.03-0.54; P = 0.03), skin thickness (Std. mean difference = 1.27; 95% CI, 0.88-1.66; P < 0.00001), collagen content (Std. mean difference = 2.01; 95% CI, 1.42-2.61; P < 0.00001), and skin dryness (Std. mean difference = 0.15; 95% CI, -0.05 to 0.35; P = 0.14). CONCLUSIONS: MHT increases elasticity and collagen content in the skin, thereby reducing the severity of wrinkles and increasing skin thickness. Nevertheless, more well-conducted clinical trials are required to answer all questions in an evidence-based manner.

Effectiveness of inositol, metformin and their combination in women with PCOS undergoing assisted reproduction: systematic review and meta-analysis.

OBJECTIVE: Our study aims to compare the effect of metformin, inositol and their combinations on the efficiency in improving outcomes of assisted reproductive technologies in women with PCOS. DATA SOURCES: PubMed, The Cochrane Library, ClinicalTrials.gov, Embase, MEDLINE. The search was performed on studies published before November 14, 2021, to identify articles evaluating the effectiveness of treatment metformin and inositol on ART outcomes. STUDY SELECTION: The systematic review was conducted according to the PRISMA 2020 checklist and registered in the PROSPERO 2021 CRD42021287887. Randomized controlled trials (RCTs) in English that compared metformin or inositol or metformin + inositol treatment with placebo or no treatment in women with PCOS undergoing assisted reproduction were included. In addition, RCTs with comparison combination and single metformin or inositol treatment were also included. DATA EXTRACTION AND SYNTHESIS: 35 RCTs were included for qualitative analysis reporting on 4668 participants. In group of Metformin treatment were included 1891 patients, in Myo-inositol group - 281, in inositol + metformin group were included 110 participants and in control group (placebo or absence of treatment) - 1865 women with PCOS. 5 meta-analyses were performed. CPR in comparison of metformin and placebo in 1312 patients were higher in metformin group (RR = 1.30, 95% CI: 1.12 to 1.50, p = 0.0004). OHSS was less in metformin (RR = 0.34, 95% CI: 0.17 to 0.69, p = 0.003). However, LBR were not statistically significant (RR = 1.12, 95% CI: 0.93 to 1.36, p = 0.24). In comparison of inositol and no treatment there was also no difference in CPR (RR = 1.37, 95% CI: 0.79 to 2.38, p = 0.26). As for metformin and inositol meta-analysis in 220 patients with PCOS, CPR were higher in inositol group (RR = 1.52, 95% CI: 1.05 to 2.18, p = 0.03). Combination treatment included only two RCTs and was illegible for meta-analysis. CONCLUSION: To our knowledge, it is the first meta-analysis that estimates inositol treatment compared to metformin. Based on our systematic review and meta-analysis, metformin seems to be a good option for improving ART outcomes in women with PCOS. However, it is not clear whether inositol usage is adequate. Nevertheless, we need more clinical trials of good quality to answer all questions thoroughly.

Pentosan polysulfate in patients with bladder pain syndrome/interstitial cystitis with Hunner's lesions or glomerulations: systematic review and meta-analysis.

Background: Bladder pain syndrome/interstitial cystitis (BPS/IC) is a persistent pain perceived in the urinary bladder region, accompanied by at least one symptom, such as pain worsening with bladder filling and daytime or nighttime urinary frequency without any proven infection or obvious pathology. The aim of this study is to evaluate the efficacy and safety of pentosan polysulfate (PPS) in patients with BPS/IC. Methods: Systematic search was performed by PRISMA checklist. Electronic databases, including PubMed and Cochrane library, were checked until 2021 using keywords: 'pentosan polysulfate', 'pain syndrome', 'interstitial cystitis', and bibliography of relevant papers was checked. Inclusion criteria: Patients with confirmed diagnosis of BPS/IC and cystoscopy criteria - Hunner's lesions. Exclusion criteria included hypersensitivity, pregnancy, lactation, and oral therapy for BPS/IC in the period of 1 month before the study and abstracts or unpublished papers. Results: In total, 13 clinical trials were included in systematic review and 7 were included in meta-analysis. Studies evaluated the effectiveness and safety of oral PPS versus placebo or other treatment options. In the first meta-analysis, three studies compared oral PPS with placebo: [relative risk (RR) = 2.07, 95% confidence interval (CI): 1.37-3.13, p = 0.0006]. The second meta-analysis of two studies compared oral PPS with another treatment options (intravesical liposome and CyA): (RR = 0.44, 95% CI: 0.10-1.93, p = 0.28). The third meta-analysis of two studies included intravesical regimen of PPS compared with intravesical placebo: (RR = 1.09, 95% CI: 0.54-2.22, p = 0.80). The majority of studies do not report any particular serious side effects. Conclusion: PPS treatment has a statistically significant effect over placebo on the subjective improvement of patients with BPS/IC. There was no difference between PPS and other treatment options. Intravesical regimen of PPS had no significant impact on response rates. None of included studies reported severe side effects after intervention.

Comparison of effectiveness of hyaluronan gel, intrauterine device and their combination for prevention adhesions in patients after intrauterine surgery: Systematic review and meta-analysis.

OBJECTIVE: Our study aims to compare the effects of using hyaluronan gel, an intrauterine device, and their combination to prevent intrauterine adhesions. METHODS: The systematic review was conducted according to the PRISMA 2020 checklist and has been registered in the PROSPERO. INCLUSION AND EXCLUSION CRITERIA: randomized controlled trials (RCTs) in English, patients after intrauterine surgery were included. Patients with hypersensitivity and pelvic inflammatory disease were excluded. DATA SOURCES: PubMed, The Cochrane Library, ClinicalTrials.gov, Embase, and MEDLINE. The search was performed on studies published before February 1, 2021 to identify articles evaluating the effectiveness of hyaluronan gel, an intrauterine device, and their combination in the prevention of intrauterine adhesions. RESULTS: 8 RCTs were included for qualitative analysis reporting on 1226 participants. Five randomized trials compared recurrence rates between two groups: hyaluronan gel and control (RR = 0.53, 95% CI: 0.40 to 0.69, P < .00001). Hyaluronan gel had a significant role on reducing adhesion formation after surgical intervention. Meta-analysis of pregnancy rates compared hyaluronan gel usage and group with IUD or lack of treatment (RR = 1.58, 95% CI: 1.10 to 2.27, P = .01). Hyaluronan gel group had significantly higher pregnancy rates compared with another group in this meta-analysis. CONCLUSION: Based on our study, it has become more evident that hyaluronic acid is an effective and safe method after adhesiolysis to prevent recurrence and lead to pregnancy in comparison with other techniques. Nevertheless, further research is needed to achieve more answers regarding adhesions prevention.

Effectiveness and safety of bulking agents versus surgical methods in women with stress urinary incontinence: a systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: The objective was to evaluate the efficacy and safety of bulking agents compared with surgical methods for female stress urinary incontinence. METHODS: Inclusion and exclusion criteria: women with stress urinary incontinence. Bulking agents versus any surgical treatment as a comparison. Patients with other types of incontinence and treatment were excluded. Electronic databases (PubMed, MEDLINE, and the Cochrane Library) were searched from 2000 until 2021 to identify articles evaluating the effectiveness and safety of urethral bulking agents versus surgical methods. Risk-of-bias assessment tools recommended by the Cochrane Society were used to evaluate the risk of bias in the studies included. RESULTS: Six studies were included in the quantitative synthesis for a total of 710 patients. Our systematic review and meta-analysis showed that bulking agents are less effective than surgical procedures according to subjective improvement after treatment (RR = 0.70, 95% CI: 0.53 to 0.92, p = 0.01). There was no statistically significant difference between these two methods with regard to complications after the intervention (RR = 1.30, 95% CI: 0.30 to 5.66, p = 0.73). CONCLUSION: The main limitation of this systematic review and meta-analysis was the absence of a common objective outcome measure to evaluate effectiveness. However, it shows that bulking agents are less effective than surgical procedures in subjective improvement. Safety analysis showed no significant difference between these methods. Hence, we believe that the first and final surgery is considered to be the best.

Efficacy of photodynamic therapy in women with HSIL, LSIL and early stage squamous cervical cancer: a systematic review and meta-analysis.

BACKGROUND: We sought to conduct a systematic review and meta-analysis of randomized and non-randomized clinical trials to assess the efficacy of photodynamic therapy (PDT) in cervical epithelial neoplasia (CIN) and early-stage cervical cancer. Additionally, according to the results, we tried to consider which stage of CIN is more sensitive to PDT. METHODS: A systematic search was conducted using electronic databases including PubMed, ClinicalTrials.gov, the Cochrane Library, and Google Scholar. INCLUSION CRITERIA: all patients had confirmed low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), or an early-stage cervical cancer - the cancer is less than 3 mm deep into the cervix -IA; type of photosensitizer and any type of wavelength. EXCLUSION CRITERIA: women who were previously treated with PDT; Risk of bias assessment was carried out for each study included in the systematic review using the Cochrane Handbook for Systematic Reviews of Interventions: RoB-2 was used to assess the risk of bias in randomized studies, while ROBINS-I - in non-randomized ones. RESULTS: We identified 2213 publications, but only 6 met the inclusion criteria and were included in the synthesis. PDT is most effective when patients have CIN 2 or photosensitizer is administered intravenously. CONCLUSION: Based on our systematic review and meta-analysis, it could be concluded that photodynamic therapy may be a practical approach in CIN (LSIL) regression compared with placebo. Nevertheless, we need more evidence and long-term follow-up to answer all questions thoroughly.

Collagen type 3A1 and 1A1 polymorphisms in women with pelvic organ prolapse and urinary incontinence assessed with Sanger sequencing method.

INTRODUCTION: This case-control trial investigates the prevalence of COL3A1 and COL1A1 gene polymorphisms in female patients suffering pelvic organ prolapse (POP) and stress urinary incontinence (SUI) in comparison with controls. MATERIAL AND METHODS: Inclusion criteria were having one or more risk factors for SUI and POP. Exclusion criteria were hereditary connective tissue diseases as well as surgeries for POP/SUI for the control group. The rs1800255 polymorphism in COL3A1 gene was considered as a local substitution of guanine (G) for adenine (A). The rs1800012 polymorphism in COL1A1 gene was considered as a local substitution of guanine (G) for thymine (T). Genotyping was performed by Sanger sequencing method, followed by estimation of sensitivity and specificity for POP and SUI. RESULTS: Fifty-two patients with POP and SUI (mean age 64.4 years) and 21 women were included in the control group (mean age 63.2 years). Homozygous genotype (AA) in COL3A1 was found in 10% of patients suffering from POP or SUI. No women in the control group had this genotype. The single nucleotide polymorphism (SNP) had high specificity (1.0) for POP/SUI, but low sensitivity (0.1). Heterozygous genotype (AG) in COL3A1 had a sensitivity equal to 0.47 and specificity of 0.62. Homozygous genotype (TT) in COL1A1 was found in only 2% of patients with POP/SUI, but was not found in controls. Heterozygous genotype (TG) in COL1A1 has sensitivity equal to 0.25 and specificity of 0.74. CONCLUSIONS: POP/SUI patients have specific SNPs in COL1A1 and COL3A1 sequenced by Sanger method.