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.

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.

Acute hepatitis in a paediatric patient: immune-mediated drug-induced liver injury or albendazole-induced autoimmune hepatitis?

INTRODUCTION: Drug-induced liver injury (DILI) is one of the most common causes of liver damage. A large number of drugs, dietary supplements, and herbal medications can cause hepatotoxicity. In some situations, it is difficult to distinguish between DILI and autoimmune hepatitis, especially when the mechanism is immune-mediated. Albendazole is a drug that has been used for decades for the treatment of parasitic infections in humans. One of the side effects is liver enzyme elevation, but rarely requires the discontinuation of therapy. Previous experience has shown that hypersensitivity is the most common mechanism of albendazole hepatotoxicity. CASE REPORT: Here we presented a paediatric patient in whom albendazole induced severe liver injury. In laboratory analyses, in addition to markedly elevated transaminases and parameters of cholestasis, there was also a significant increase in IgG, so autoimmune hepatitis was considered. Even though the liver histology indicated toxic liver disease, prednisolone was started. Corticosteroid therapy resulted in the complete normalization of liver function, as well as IgG. With the cessation of corticosteroid therapy, transaminases, bilirubin and gamma-glutamyl transferase (GGT) remained within normal levels, but an increase in anti-smooth muscle antibodies (SMA) was noted in immunological analyses after one year of follow-up. CONCLUSIONS: Immune-mediated hepatotoxicity from albendazole is one possible mechanism of liver injury. The use of albendazole in the treatment of parasitic infections, especially in children, requires close monitoring. The question remains as to whether albendazole is a drug that can induce autoimmune hepatitis in the paediatric population.

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.

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.

Oxidative Stress Markers in GnRH Agonist and Antagonist Protocols in IVF.

BACKGROUND: Our aim was to study the effect of GnRH agonist and antagonist protocols of ovarian stimulation on oxidative stress parameters in serum and the influence of oxidative stress parameters change on the outcome of IVF cycles. METHODS: This prospective study included 82 patients who underwent IVF procedures. We determined SOD, MDA and SH groups in serum. Serum samples were obtained between the second and fourth day of the cycle and on the day of HCG administration during ovarian stimulation. RESULTS: Patients were divided into two groups depending on the protocol of stimulation. The mean total and mature oocytes number and number of fertilized oocytes were higher in GnRH agonist group. There was no significant difference in biochemical pregnancy, miscarriage and live-birth rate in both groups. Mean serum SOD was significantly lower, while mean serum MDA and SH groups were significantly higher after ovarian stimulation. Delivery rate was higher in patients without OS while miscarriage rate was higher in patients with OS. CONCLUSIONS: Our study confirmed that there is a difference in the concentration of oxidative stress parameters before and after ovarian stimulation. IVF outcome is better in patients without OS after ovarian stimulation. However, the protocol of ovarian stimulation is neither associated with a change in oxidative stress parameters nor with the outcome of ART procedures.

Neonatal outcome in pregnant patients with antiphospholipid syndrome.

AIMS: The study aim was to evaluate pregnancy outcomes in patients with antiphospholipid syndrome (APS) and to determine which clinical parameters present risk factors for adverse pregnancy outcomes in these patients. METHODS: The study included 55 patients with APS treated at the Clinic for Ob/Gyn, Clinical Center of Serbia, from 2006 to 2012. The control group consisted of 55 healthy pregnant women. Data regarding previous pregnancies and conception method were registered. Immunological and laboratory tests were performed. Pregnancy outcomes, including miscarriage, intrauterine fetal death, hypertensive disorders, diabetes mellitus, phlebothrombosis, fetal growth restriction, premature delivery, delivery method, perinatal asphyxia, respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis were followed. RESULTS: The premature delivery rate in APS patients was 31.8%, and pregnancy loss was 18.2%. Significantly more patients with APS had thrombocytopenia, pregnancy losses, intrauterine growth restriction, and perinatal asphyxia compared with the control group. More miscarriages, preterm delivery, lower birth weight, preeclampsia, and IgM anticardiolipin antibody levels significantly correlated with adverse pregnancy outcomes. Although rare, respiratory distress syndrome can also worsen neonatal health status. According to ROC analysis, previous miscarriages correctly explained 66.3% of adverse pregnancy outcome cases. We generated four equations of adverse pregnancy outcome risk factors. CONCLUSIONS: The most important prognostic factor for pregnancy outcome in APS patients is the number of previous miscarriages. Using appropriate current therapeutic protocol can enable live birth of a healthy newborn in most cases.

Madelung disease: a rare case associated with gynaecomastia and scrotal involvement.

Madelung disease is rare, and characterised by accumulation of fatty non-encapsulated tissue in the head, neck, shoulders, and upper extremities. The aetiology is not completely known, but the association with alcohol intake is clear. We present a neglected case that was associated with bilateral asymmetrical gynaecomastia. To the best of our knowledge, this is a pattern of involvement not previously reported. The treatment of choice is lipectomy for severe cases and liposuction for less extensive accumulations of fat.

[Medicamentous abortion with mifepristone and misoprostol in Serbia and Montenegro].

BACKGROUND/AIM: Medicamentous abortion was first introduced in Serbia and Montenegro in September 2001. The aim of this study was to assess the efficiency, side effects, and acceptability of medicamentous abortion using mifeprostone orally (600 mg), and 48 hours later, misoprostol both orally and vaginally in different regiments in our population (400 mcg, 600 mcg, 800 mcg). METHODS: A total of 235 consecutive women with pregnancies up to 49 days of gestational age were assigned to 4 groups according to the different misoprostol regiment (group I 400 mcg, group II 600 mcg, group III 800 mcg orally, and group IV 800 mcg both orally and vaginally). The principal outcome measure was a successful abortion defined as a complete expulsion of intrauterine contents without a need for surgical intervention 14 days after the procedure. Other outcome measures were the following: drug related effects, and adverse effects related to the abortion process. RESULTS: In general, the success rate was 50%, 89.48%, 75% and 92.11% in the groups I, II, III, and IV, respectively, as judged by the complete expulsion of the intrauterine contents without surgical intervention (t1:4 = 7.005; t2:4 = 0.3872, t3:4 = 2.9784, p < 0.01). The incidence of adverse effects (vomiting, abdominal pain, bleeding, and fever) was low in general, but among our groups it occurred mostly with the higher doses of orally applied misoprostol (800 and 600 mcg). Only one case required urgent curettage for heavy vaginal bleeding, and two blood transfusions, as well. No cases of intact pregnancies were recorded in the study. CONCLUSION: Our study showed that a mifepristone dose of 600 mg orally, and misoprostol 400 mcg orally and 400 mcg vaginally were most effective. Thus, a combination of mifepristone and misoprostol for medicamentous abortion should take a higher proportion in the termination of early pregnancy in our population.

[Effects of tibolone on the risk factors for cardiovascular diseases in postmenopausal women].

BACKGROUND/AIM: Tibolone is a preparation that belongs to the group of steroidal substances. The effects of the use of the use of tibolone are the consequence of the activities of its metabolities, considering that their hormonal activity depends on the type of tissue in which they develop. The aim of this study was to evaluate the influence of the use of tibolone on risk factors for the development of cardiovascular diseases in postmenopausal women. METHODS: A prospective observational stady included 94 patients who had the concentration of 17beta estradiol < 50 pg/ml and who was in menopause more than a year. Out of the total number of patients, 63 accepted to receive tibolone 2.5 mg daily (tibolone group), while 31 of the patients refused to take tibolone (control group). We measured the concentration of lipids (cholesterol, LDL cholesterol, HDL cholesterol, triglicerides), antitrombin III, fibrinogen, and C-reactive protein, before and after the treatment within a 6-month period. Then, we compared the difference between the values of concentrations and tested the statistical significance of the difference. We also evaluated the changes of values in the concentrations of the examinated parametars inside a 6-month period in the control group. RESULTS: In 31 patients of the control group, from the control group there were no significant changes in the values of the defined parametars as compared to their initial values after six months. But there were changes of statistical significance (p < 0.001) in values of the concentrations of the exeminated parametars before and after the treatment in the tibolone group. In fact, we recorded decreases in the total cholesterol by 17.8%, HDL cholesterol by 27%, LDL cholesterol by 4% (without statistical significance p > 0.05) and triglicerids by 35%. There were no statistical differences in the concentrations of antitrombin III, fibrionogen, and C-reactive proteine in the tibolone group before and after the treatment CONCLUSION: The use of tibolone dose decrease the concentration of the total cholesterol, triglicerides, HDL cholesterol, without a significant decrease of LDL cholesterol. Also, the use of tibolone does not have any significant effect on the concentrations of antitrombin III, fibrinogen and C-reactive proteine. The number of serum parameters measured in this study was limited, thus that was the reason to discuss only about the metabolism of lipids in the patients from the tibolone group. The final condusion about the risk for cardiovascular diseases in the patients on tibolone, howerer, reqnires were extensive further clinical exeminations.

Comparison of two therapeutic protocols in patients with antiphospholipid antibodies and recurrent miscarriages.

AIM: To compare the effects of two therapeutic protocols for the patients with recurrent miscarriages associated with the presence of antiphospholipid (anticardiolipin) antibodies. METHODS: A prospective observational study included 20 patients with antiphospholipid antibodies in the first group who received low-molecular heparin and aspirin. The second group of 20 patients, in addition to this therapy, received immunotherapy (intravenous immunoglobulin). Aspirin was administered at the time of a positive pregnancy test, and low-molecular heparin not before the fetal heart activity registration by ultrasound. Intravenous immunoglobulin was given prior to the conception or at the beginning of the pregnancy. We compared these groups according to the pregnancy outcomes and the occurrence of complications during pregnancy, using standard statistical tests. RESULTS: The rate of positive gestational outcome in the patients treated with aspirin and low-molecular heparin was 85% (17/20), and in the second group it was 90% (18/20). There was no significant difference in pregnancy outcomes between these groups (p > 0.05), except for the occurence of preeclampsia and thrombocytopenia, which were recorded only in the aspirin and low-molecular heparin group, but with no statistical significance (p > 0.05) compared to the second group, which received immunoglobulin additionally. CONCLUSION: There was no significant difference (p > 0.05) in pregnancy outcomes between the two studied therapeutic protocols, but the therapy with aspirin and low-molecular heparin was cheaper and easier to apply than the therapy with immunoglobulins. The results of our study confirmed that the final pathogenic mechanisms in recurrent fetal miscarriages were inflammation and thrombosis of the uteroplacental blood vessels.