Currently Available Treatment Modalities for Uterine Fibroids.

Uterine fibroids (leiomyomas and myomas) are the most common benign gynecological condition in patients presenting with abnormal uterine bleeding, pelvic masses causing pressure or pain, infertility and obstetric complications. Almost a third of women with fibroids need treatment due to symptoms. OBJECTIVES: In this review we present all currently available treatment modalities for uterine fibroids. METHODS: An extensive search for the available data regarding surgical, medical and other treatment options for uterine fibroids was conducted. REVIEW: Nowadays, treatment for fibroids is intended to control symptoms while preserving future fertility. The choice of treatment depends on the patient's age and fertility and the number, size and location of the fibroids. Current management strategies mainly involve surgical interventions (hysterectomy and myomectomy hysteroscopy, laparoscopy or laparotomy). Other surgical and non-surgical minimally invasive techniques include interventions performed under radiologic or ultrasound guidance (uterine artery embolization and occlusion, myolysis, magnetic resonance-guided focused ultrasound surgery, radiofrequency ablation of fibroids and endometrial ablation). Medical treatment options for fibroids are still restricted and available medications (progestogens, combined oral contraceptives andgonadotropin-releasing hormone agonists and antagonists) are generally used for short-term treatment of fibroid-induced bleeding. Recently, it was shown that SPRMs could be administered intermittently long-term with good results on bleeding and fibroid size reduction. Novel medical treatments are still under investigation but with promising results. CONCLUSIONS: Treatment of fibroids must be individualized based on the presence and severity of symptoms and the patient's desire for definitive treatment or fertility preservation.

Different doses of recombinant FSH and determining parameters of oxidative stress.

Background: This study aimed to examine if there is a connection between recombinant FSH dose and OS parameters in serum and the impact on IVF outcome. Methods: This study consisted of 101 participants that went through IVF procedures. Parameter that were tested are SOD, SH groups and MDA. Serum samples were drawn before stimulation and on the last day of ovarian stimulation. Results: Two groups were formed according to the dose of gonadotropins (rFSH). In both groups there were no significant differences in live-birth rate and miscarriage. In both groups mean serum MDA and SH-groups were significantly higher after ovarian stimulation, but mean serum SOD was significantly lower when compared to values before stimulation. There were less patients without OS before stimulation. Conclusions: Our results suggest that there is a difference in serum concentration in groups SOD, SH groups and MDA at the beginning and at the end ovarian stimulation. On the other hand, dose of rFSH is not related with change of parameters for oxidative stress, quality of oocytes, embryos, fertilization, pregnancies, and miscarriage rate. Patients without oxidative stress before the IVF procedure needed lower doses of gonadotropins during stimulation.

Predictive Role of Progesterone Levels for IVF Outcome in Different Phases of Controlled Ovarian Stimulation for Patients With and Without Endometriosis: Expert View.

The study aimed to review the role of basal, trigger, and aspiration day progesterone levels (PLs) as predictors of in vitro fertilization (IVF) success for patients with and without endometriosis. A non-systematic review was conducted by searching papers published in English during the period of 1990-2023 in MEDLINE and PubMed, Embase, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), and Web of Science. The most widely used IVF predictor success was the trigger day progesterone serum level. Many studies utilize the threshold level of 1.5-2.0 ng/ml. However, the predictive power of only progesterone level failed to show high sensitivity and specificity. Contrary, progesterone level on the trigger day combined with the number of mature retrieved oocytes had the highest predictive power. High baseline progesterone level was associated with poor IVF outcomes. Research on progesterone and IVF success in patients with endometriosis is limited but indicates that endometriosis patients seem to benefit from higher progesterone concentrations (≥ 37.1 ng/ml) in IVF cycles. Currently, there is limited data for a definitive insight into the mportance of progesterone in the estimation of IVF success. Nonetheless, this summarized evidence could serve as up-to-date guidance for the role of progesterone in the prediction of IVF outcomes, both in patients with and without endometriosis.

Reproductive and Obstetric Outcomes after Fertility-Sparing Treatments for Cervical Cancer: Current Approach and Future Directions.

Cervical cancer is one of the leading causes of cancer-related death in women of reproductive age. The established fertility-sparing approaches for the management of early-stage cervical cancer for women who plan pregnancy are associated with a decline in fecundity and an increased risk of pregnancy complications. This article aims to offer an overview of fertility-sparing approaches and the management of potential subfertility and pregnancy complications after these treatments. An extensive search for the available data about infertility and cervical cancer, fertility-sparing techniques in patients with cervical cancer, fertility treatment, obstetrical complications, and pregnancy outcomes in cervical cancer patients was completed. Fertility-preserving procedures such as loop electrosurgical excision procedure (LEEP), cold-knife conization, and trachelectomy in women diagnosed with cervical cancer can be considered as safe and effective treatments that preserve reproductive potential. Current fertility-preserving procedures, based on the balance of the oncological characteristics of patients as well as their desire for reproduction, allow one to obtain acceptable reproductive and obstetric outcomes in women treated for cervical cancer. Nevertheless, careful monitoring of pregnancies obtained after fertility-preserving procedures is recommended, since this cohort of patients should be considered at higher risk compared with a healthy population.

Severe Hemoperitoneum due to Ovarian Bleeding after Transvaginal Oocyte Retrieval with Surgical Management: A Retrospective Analysis and Comprehensive Review of the Literature.

Background and Objectives: Severe hemoperitoneum of ovarian bleeding origin is a rare but potentially life-threatening complication of transvaginal oocyte retrieval (TVOR) procedure. The study aimed to present a case series of surgically managed patients from our clinic with hemoperitoneum caused by ovarian bleeding after TVOR, as well as to perform a comprehensive literature review in order to summarize and analyze all published cases with this condition and their management. Materials and Methods: The data of 2939 patients, who underwent TVOR procedures for IVF/ICSI (in vitro fertilization, intracytoplasmic sperm injection) in our clinic between 2010 and 2021 were reviewed. Moreover, a systemic literature search was performed. Main outcome measures from the pooled analysis were incidence and risk factors, type of surgery, intraoperative finding and intervention leading to hemostasis. Results: In our Clinic 4 (0.136%), cases of hemoperitoneum due to ovarian bleeding were surgically managed. Moreover, 39 cases from 18 studies reported in the literature were identified. No risk factors besides lean women with PCOS were identified. In the pooled analysis, the bleeding symptoms appeared in 58.1% of patients within eight hours after TVOR and cumulatively in 81.4% cases during the 24 h after TVOR. The average time from TVOR to surgery was 27.19 ± 53.25 h. Hemostasis was mostly established using electrocoagulation, although few cases of ovariectomy were also reported. Embryo transfer at 60% of cases was postponed and embryos cryopreserved. Conclusions: Severe hemoperitoneum due to ovarian bleeding after TVOR is a rare event that should be treated by techniques of minimally invasive surgery whenever possible. Protocols should be developed to enable optimal management strategies for infertility patients. Embryos obtained should be cryopreserved.

Predictive Value of Basal Serum Progesterone for Successful IVF in Endometriosis Patients: The Need for a Personalized Approach.

The data regarding the role of progesterone (P4) in reproductive events of endometriosis patients are limited. This prospective study aimed to examine the predictive value of basal P4 serum levels for successful in vitro fertilization (IVF) in patients with primary infertility and endometriosis. The study included 73 patients divided according to endometriosis treatment (surgery vs. control-no treatment). The general data, basal hormonal status, and pregnancy rates were determined for every patient. Clinical pregnancy was achieved in 40.3% of patients, and more often in patients treated for endometriosis before IVF. The regression analysis showed that higher basal P4 serum levels were associated with achieving pregnancy through IVF. When regression was adjusted for the patient and IVF characteristics, higher basal P4 serum levels were associated with pregnancy achievement in both groups of women, along with the basal serum levels of FSH, LH, and AMH; EFI score; and stimulation protocol. The ROC analysis showed that the basal P4 serum level for successful IVF should be ≥0.7ng/mL. The basal P4 serum level cut-off for IVF success in endometriosis patients was determined for the first time. Constructed models for IVF success prediction emphasize the importance of determining the basal P4 serum levels for the personalized treatment of endometriosis-related infertility.

Prevalence, Risk Factors, and Pathophysiology of Nonalcoholic Fatty Liver Disease (NAFLD) in Women with Polycystic Ovary Syndrome (PCOS).

Background: Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine disorders in women's reproductive period of life. The presence of nonalcoholic fatty liver disease NAFLD, one of the leading causes of chronic liver disease in the Western world, is increased in women with PCOS. This review aims to present current knowledge in epidemiology, pathophysiology, diagnostics, and treatment of NAFLD in PCOS with an emphasis on the molecular basis of development of NAFLD in PCOS women. Methods: Authors investigated the available data on PCOS and NAFLD by a MEDLINE and Pub Med search during the years 1990-2021 using a combination of keywords such as "PCOS", "NAFLD", "steatohepatitis", "insulin resistance", "hyperandrogenaemia", "inflammation", "adipose tissue", and "obesity". Peer-reviewed articles regarding NAFLD and PCOS were included in this manuscript. Additional articles were identified from the references of relevant papers. Results: PCOS and NAFLD are multifactorial diseases, The development of NAFLD in PCOS women is linked to insulin resistance, hyperandrogenemia, obesity, adipose tissue dysfunction, and inflammation. There is the possible role of the gut microbiome, mitochondrial dysfunction, and endocannabinoid system in the maintenance of NAFLD in PCOS women. Conclusions: There is a need for further investigation about the mechanism of the development of NAFLD in PCOS women. New data about the molecular basis of development of NAFLD in PCOS integrated with epidemiological and clinical information could influence the evolution of new diagnostic and therapeutic approaches of NAFLD in PCOS.

Reproductive outcomes of IVF after comprehensive endometriosis treatment: a prospective cohort study.

OBJECTIVES: To evaluate the impact of pharmacological and surgical endometriosis treatment on IVF reproductive outcomes in patients with primary infertility. MATERIAL AND METHODS: The study, conducted over a five year period, included 73 patients with endometriosis associated primary infertility subjected to 77 cycles. Group I included patients treated for endometriosis before the IVF (subgroups A: surgical and pharmacological treatment and B: only surgical treatment). Group II included patients immediately subjected to IVF. Assessed outcomes were pregnancy rate (PR) per started cycle, fertilization rate (FR), implantation rate (IR) and live birth rate (LBR). RESULTS: Group IA included 25 patients, Group IB 21 and Group II 27 patients. FR and IR showed no significant differences between groups. PR was significantly higher in the Group I than Group II (49% vs 25%, p = 0.030). PR per started cycle was the highest in the Group IA and the lowest in the Group II (p = 0.040). LBR was significantly higher in whole Group I (p = 0.043) and subgroup IA (p = 0.020) than Group II. Group IA and IB did not differ regarding examined outcomes. Regression analysis showed that endometriosis pretreatment method can impact both achieving pregnancy (p = 0.036) and having a live born child (p = 0.008) after IVF. The combined surgical and pharmacological endometriosis treatment, shorter infertility duration, lower EFI score, using long protocol with FSH+HMG gonadotropins increase the probability of successful IVF. CONCLUSIONS: A combined surgical and pharmacological endometriosis treatment had a positive impact on IVF reproductive outcomes, both on pregnancy and on live birth rates.

Gestational Diabetes Mellitus and Antenatal Corticosteroid Therapy-A Narrative Review of Fetal and Neonatal Outcomes.

BACKGROUND: There, we review the pathogenesis of gestational diabetes mellitus (GDM), its influence on fetal physiology, and neonatal outcomes, as well as the usage of antenatal corticosteroid therapy (ACST) in pregnancies complicated by GDM. METHODS: MEDLINE and PubMed search was performed for the years 1990-2022, using a combination of keywords on such topics. According to the aim of the investigation, appropriate articles were identified and included in this narrative review. RESULTS: GDM is a multifactorial disease related to unwanted pregnancy course and outcomes. Although GDM has an influence on the fetal cardiovascular and nervous system, especially in preterm neonates, the usage of ACST in pregnancy must be considered taking into account maternal and fetal characteristics. CONCLUSIONS: GDM has no influence on neonatal outcomes after ACST introduction. The ACST usage must be personalized and considered according to its gestational age-specific effects on the developing fetus.

Neurological outcomes of antenatal corticosteroid therapy.

AIM OF THE STUDY: The aim of the study was to investigate whether antenatal corticosteroid therapy (ACST) could impact neurological condition, as assessed through muscular tone, of prematurely born infants. METHODS: All 82 patients at risk of preterm delivery treated and delivered over 12 months were divided into two equal groups regarding the use of ACST. The investigated parameters were pregnancy complications, biophysical profile, Apgar score, gestational age of delivery and all postpartum complications. Neurological development and muscular tone were evaluated at the 1st, 3rd, 6th and 12th months of life using Vojta's method, which classifies muscular tone as good, hypotonic or hypertonic. RESULTS: After therapy, infants from the treated and control groups differed in biophysical profile, Apgar score, length of intensive care, occurrence of respiratory distress syndrome and intraventricular haemorrhage. During the follow-up, significantly more infants from the ACST group had good muscular tone when compared with those from the control group. Regression analysis showed that ASCT can significantly impact an infant's muscular tone. Still, the week of delivery and the complications such as diabetes mellitus, intrauterine growth restriction and respiratory distress syndrome, could change the association of ACST and infants' muscular tone. CONCLUSION: ACST was associated with the positive neurological outcomes of prematurely born infants when assessed through their muscular tone.

Clinical and ultrasonographic parameters in assessment of labor induction success in nulliparous women.

Purpose: Evaluation of simplified Bishop score and ultrasound cervicometry in the assessment of labor induction success in nulliparous women.Methods: Prospective cohort study included 146 nulliparous women with singleton pregnancy and indications for labor induction. Prior to labor induction, cervicometry and Bishop score were determined. Upon delivery, patients were classified as those delivered vaginally and by cesarean section (CS) after unsuccessful labor induction.Results: Bishop score >5 was found in 47.95% of vaginally delivered women and 12.33% of patients delivered by CS (p < .01). Cervicometry had appropriate findings in 34.2% of vaginally delivered women and 75.3% of those delivered by CS (p < .01). Bishop score (>5 versus ≤5) had lower sensitivity (52.05%) and specificity (12.33%) than cervicometry (good versus unfavorable findings) (sensitivity 65.75%, specificity 75.34%) for prediction of labor induction success. If Bishop score was ≤5, cervicometry had 50.0% sensitivity and 78.13% specificity, while if Bishop score was >5, 82.86% sensitivity and 55.56% specificity. Obtained model for predicting labor induction outcome in nulliparous women based on their clinical and ultrasonographical characteristics identified the Bishop score as the most important predictor.Conclusions: Study confirmed the usefulness of simplified Bishop score and ultrasound cervicometry in the assessment of labor induction success in nulliparous women.

Predictors of IVF/ICSI success following treatment of endometriosis as the cause of primary infertility.

OBJECTIVES: Treatment of endometriosis prior to IVF/ICSI could be followed by the significant reduction of ovarian reserve. The aim is to identify potential markers of the IVF/ICSI outcome in patients with endometriosis associated infertility and to evaluate their clinical significance. MATERIAL AND METHODS: The prospective cohort study included 73 patients with primary infertility caused by endometriosis that were subjected to 77 IVF/ICSI cycles. Patients were classified into two groups. In the first group some type of treatment had previously been applied, and in the second group patients were immediately subjected to the IVF/ICSI procedures. RESULTS: When pregnancy was achieved, there were significantly more patients under 35 years of age, more patients with primary infertility duration up to 3 years, and more patients with endometriosis that was previously treated (77.4%) (p < 0.039). In the cases of the successful outcome Endometriosis Fertility Index > 7, lower basal FSH and FSH/LH ratio were found, as well as significantly higher basal E2, basal P4 and AMH. Significantly lower doses of gonadotropins were needed in cases of the successful outcome, and long protocol with agonists was more frequently used. Multivariate logistic regres-sion analysis showed that previous therapy of endometriosis, P4 ≥ 0.7 ng/mL, AMH ≥ 0.9 ng/mL, A class of embryos, and the use of long protocol with agonists were predictors of the successful IVF/ICSI outcome. CONCLUSIONS: Therapy for endometriosis, AMH and P4 levels appeared to be predictors for the successful IVF/ICSI outcome and the use of long protocol with agonists could be advised in these cycles.

[Poor Ovarian Response to Stimulation for In Vitro Fertilization].

The term "poor respond (POR) patients" is used for the group of women who respond badly to usual doses of gonadotropins in in vitro fertilization (IVF) treatments; the consequence is low pregnancy rate. A consensus was reached on the minimal criteria needed to define POR. At least two of the following three features must be present: 1. advanced maternal age (40 years or more) 2. previous POR (3 or less oocytes with a conventional stimulation protocol) 3. abnormal ovarian reserve (AMH 0.5-1.1 ng/ml or AFC 5-7).The aim is to find better therapeutic options for these patients. Increased levels of day 3 follicle stimulating hormone (FSH) and estradiol (E2), as well as decreased levels of anti-Müllerian hormone (AMH) and antral follicle count (AFC), can be used to assess ovarian reserve, as indirect predictive tests. A larger number of well designed, large scale, randomized, controlled trials are needed to assess the efficacy of different management strategies for poor responders: flare up gonadotropin releasing hormone (GnRH) agonist protocols, modified long GnRH agonist mini-dose protocols, luteal initiation GnRH agonist stop protocol, pretreatment with estradiol--GnRH antagonist in luteal phase, natural cycle aspiration or natural cycle aspiration GnRH antagonist controlled, adjuvant therapy with growth hormone or dehydroepiandrosterone (DHEA). The results of up to now used protocols are unsatisfactory and stimulation of the ovulation in poor responders remains a challenge, especially when bearing in mind that in the majority of cases the patients will be menopausal in relatively short period of time.

Utilization of ultrasound as a diagnostic tool in the preoperative assessment of patients with adnexal masses.

PURPOSE: To evaluate the reliability of ultrasound scan (US) findings in the preoperative assessment of the nature of adnexal masses in females. METHODS: After detailed history, a preoperative US examination was performed in all women. Tumor diameter, localization, the presence of solid, cystic and multilocular components, excrescences, metastasis and free fluid were assessed. Doppler scan was done and pulsatility (PI) and resistance indices (RI) were determined. These data were compared with postoperatively obtained histopathological findings and statistically analyzed. RESULTS: The study included 609 women out of which 20.7% had malignant, 73.7% benign, and 5.6% border-line tumors. Patients with malignant tumors were oldest (p<0.001). There were significantly more positive US parameters in malignant than in benign tumors (p<0.001). Also, there were significant differences (p<0.001) between malignant, benign and borderline tumors regarding all examined US and Doppler parameters except tumor multilocularity. RI had sensitivity 75%, specificity 61.2%, positive predictive value (PPV) 42.70% and negative predictive value (NPV) 96.16%. PI had sensitivity 50%, specificity 35.3%, PPV 8.37% and NPV 25.93%. Sensitivity of US characteristics was 94.34%, specificity 30.62%, PPV 22.27% and NPV 96.25%. CONCLUSIONS: US pattern characteristics and Doppler parameters were found to be moderately reliable in discriminating malignant, benign and borderline adnexal tumors. Tumor of solid or mixed consistency, presence of ascites and excrescences were the best predictors of malignancy.

Bilateral ampulary pregnancy after clomifen citrate and intrauterine insemination--a unique case report.

We report a case with bilateral tubal ampullary pregnancy after Clomifen Citrate medication. The first conception in the right tube was after intrauterine insemination or intercourse performed before insemination, while the second one was achieved 10 d after insemination, during the intercourse, in the left tube. This life-threatening and routinely unexpected finding must always have in mind all doctors dealing with patients in emergency care, especially those receiving fertility enhancing drugs. According to the literature data available, this is the first and unique such case in the literature.

Introduction of new Tumor Marker Age Score in clinical practice: Validity evaluation for differentiation benign from malignant adnexal masses.

OBJECTIVE: The aim of the study was to examine several tumor markers and their correlation with pathohistological findings in patients with adnexal masses. METHODS: Study involved 139 patients, 84 of them with benign, 47 with malignant and 8 with borderline adnexal tumor. Levels of CA 125, CA 19-9, CEA and CA 15-3 were obtained preoperatively and assessed regarding the specific pathohistological diagnose and the patient's age. Obtaining these results led us to divide the patient's CA 125 levels with age and by doing that we have attained a new Tumor Marker Age score (TMA score). RESULTS: Patients with malignant adnexal tumors had significantly higher levels of CEA (p<0.05), CA 125, CA 19-9 and CA 15-3 tumor markers (p<0.01), in comparison with patients with benign tumors. TMA score highly statistically correlate with the tumor type (benignant/malignant). CONCLUSIONS: With the increase of tumor marker levels and the patient's age the malignant nature of adnexal tumors is more often. Results of our study highlight the importance of the use of combined tumor markers (at least CA-125 and CA 19-9) in women with adnexal masses. Those levels along with the patient's age and new TMA score could preoperatively predict malignant nature of the tumor.