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.

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.

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.

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.

Toxic Metal and Trace Element Concentrations in Blood and Outcome of In Vitro Fertilization in Women.

The aim of this study was to investigate the association of trace element and toxic metal concentrations in blood and the outcome of in vitro fertilization (IVF). The study included 104 consecutive patients that underwent assisted reproductive technology (ART) procedures. The following parameters were determined: cadmium (Cd), mercury (Hg), arsenic (As), and lead (Pb); and copper (Cu), zinc (Zn), selenium (Se), and magnesium (Mg). Serum samples were obtained before commencing stimulation. Patients with smoking habit had significantly higher Pb concentrations (P = 0.022), as well as higher concentrations of As and Hg but not significantly. All subjects were divided into groups of pregnant and nonpregnant patients. Pregnant patients had lower mean values of Mg (P = 0.009), As (P < 0.05), and Pb (P = 0.034), compared to nonpregnant, and a significant correlation between pregnancy outcome and concentrations of Mg, Cd, and Pb was found. Women who had had delivered had lower Mg (P = 0.009) and Cd (P = 0.014) concentrations. There was a significant correlation of the negative outcome of IVF procedure with higher concentrations of Pb (P = 0.046) and Cd (P = 0.012). In conclusion, our results suggest that there is a difference in Mg, Pb, and Cd concentrations between pregnant and nonpregnant women. There was no association between toxic metals and number and quality of oocytes and embryos, while there was with fertilization rate. Concerning trace elements, we did not find the correlation of trace elements with oocyte number and quality, nor with a number of fertilized oocytes, except for Cu. Patients who were pregnant had lower concentrations of Mg.

Pregnancy-induced hypertension is associated with down-regulation of Kir6.1 in human myometrium.

It is generally accepted that activity of K+ channels maintain resting membrane potential and uterine quiescence during pregnancy, which is, at least in part, mediated by down-regulation of ATP-sensitive K+ (KATP) channels. Pregnancy-induced hypertension (PIH) is associated with pre-term and late pre-term labour. Here, we have used real time RT-PCR to compare mRNA levels of KATP channel subunits in PIH parturient and control parturient. We have found that Kir6.1, a pore forming, myometrial KATP channel subunit is down-regulated in PIH patients. This could perfectly explain increased rate of pre-term labour in patients suffering from PIH.

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.

[Assessment of the natural course and treatment of premalignant uterine cervical lesions in pregnancy].

INTRODUCTION: Premalignant changes of the uterine cervix occur with similar frequency during pregnancy and in non-pregnant women. Due to the fact that any surgery on the cervix can jeopardize pregnancy, it is important to define the protocol of procedures for the treatment of these changes during pregnancy. OBJECTIVE: The aim of the study was to investigate the natural course of premalignant cervical changes during pregnancy and the impact of their treatment on the pregnancy course. METHODS: Study involved all patients with colposcopically, cytologically and hystopathologically diagnosed premalignant cervical changes during pregnancy from 2002 to 2008. Patients were divided into two groups according to the applied treatment during pregnancy: surgery or monitoring by regular colposcopic and cytological examinations. The two groups were compared concerning treatment outcome, persistence or regression of changes and pregnancy duration. RESULTS: Study involved 58 patients. Spontaneous remission of lesions occurred after pregnancy in 63.79% of cases. High-grade squamous intraepithelial lesion (H-SIL) demonstrated a higher rate of persistency in comparison with low-grade squamous intraepithelial lesion (L-SIL) (X2=25.115; p<0.05). Only one finding of L-SIL progressed into H-SIL in the monitored group. Patients who underwent conization during pregnancy had a significantly more frequent preterm deliveries (X2=14.369; p<0.05). CONCLUSION: The obtained high rate of spontaneous regression of cervical changes after pregnancy as well as the lower incidence of preterm births in patients who were not treated by conization during pregnancy, confirm that patients with premalignant cervical changes should be, if invasion is excluded, under follow-up throughout pregnancy by regular colposcopic and cytological examinations. Therapeutic conization, due to numerous complications, should be performed only when there is a suspected presence of a more severe form of the disease (micro invasive and invasive carcinoma).

KATP channels are up-regulated with increasing age in human myometrium.

It is well established that ageing is associated with decrease in myometrial efficiency and higher incidence of labour complications. In myometrium, the presence of ATP-sensitive K+ (KATP) channels has been detected and they could be a factor in regulating uterine quiescence in pregnancy and contractions during labour. Here, we have examined a possibility of ageing-mediated regulation of KATP channels in the human myometrium. Myometrial samples were taken from non-pregnant women undergoing hysterectomy (n=34) and from women undergoing caesarean section in late pregnancy (n=36). Real time RT-PCR revealed that mRNAs of all known KATP channel subunits were present in the human myometrium. In non-pregnant myometrium, ageing up-regulated SUR2B/Kir6.1, subunits forming KATP channels in this tissue, without affecting the expression of other channel subunits. In the late pregnant myometrium, the level of subunits that do not form functional KATP channels was not affected by age within 20-41 age range. However, uterine SUR2B and Kir6.1 were up-regulated in parturient over 35 years. An ageing-induced increase in those channel subunits was confirmed by Western blotting. Thus, this study suggests that KATP channels are up-regulated with increasing age in human myometrium. This may help explain, at least partially, increased rate of birth complications in women aged over 35 years.

The correlation of biochemical and morphologic parameters in the assessment of sperm maturity.

OBJECTIVE: To examine the relationship between biochemical markers and morphologic sperm characteristics, including head, neck, and tail changes. METHODS: The study evaluated 154 patients who went to the Andrology Laboratory of the Clinic of Urology, Clinical Center of Serbia. Patients were divided into 4 groups: normozoospermic, oligozoospermic, severe oligozoospermic, and asthenozoospermic, according to the sperm concentration and motility. RESULTS: The differences in creatine kinase (CK) and CK-M levels between normozoospermic and the 2 groups of oligozoospermic patients were significantly different (P <.01). The CK and CK-M levels correlated negatively with sperm concentration and sperm motility, but correlated positively with the pathologic sperm form. Patients with CK values >0.093 have a total number of pathologic forms higher than 0.40 (87.5% sensitivity, 77.3% specificity, the area under the curve was 0.832, P <.001). Patients with CK values <0.09 U/L have normal spermatogenesis and pathologic disorder of the head <15%, neck <12%, and tail <10%. CONCLUSION: The relation between sperm morphology and biochemical markers included in the maturation process is established during the sperm genesis process. If the results of these markers are used together with the morphology of the spermatozoa in the interpretation of infertility, it would lead us to better insight of the fertility potential of the each patient.

Reliability and relationship of colposcopical, cytological and histopathological findings in the diagnostic process.

BACKGROUND/AIM: The question about the accuracy of cytology and colposcopy is more and more asked due to false positive and negative findings on the basis of which the decision on biopsy is made. The aim of this study was to examine reliability of biopsies based only on abnormal colposcopical findings, before receiving the results of Papanicolaou (PA) smear, by comparing findings of colposcopical, cytological and histopathological (HP) examinations as well as determining validity of these diagnostic methods. METHODS: The study involved all patients who had their regular colposcopical and cytological examinations in the outpatient department during a two-year period (2009-2010) in the Clinic for Gynecology and Obstetrics, Clinical Center of Serbia, Belgrade. The material for HP examination was obtained by colposcopically directed biopsy, due to abnormal colposcopical findings and without waiting for PA smear results. The data obtained by these methods were statistically analyzed and compared. Furthermore, validity of colposcopical and cytological examinations was assessed. Results. Out of 127 patients highly significantly more patients had more malignant cervical changes on colposcopical exam compared to HP (p = 0.000), and cytological exam (p = 0.000). Highly significantly more patients had more malignant cervical changes on PA smear than HP exam (p = 0.000), unless when findings were assessed in the widest sense of benign and malignant changes when there were no significant differences in these findings (p = 0.450). Sensitivity of colposcopy as a diagnostic method was 87.5%, specificity 24.14%, positive predictive value (+PV) was 34.65% and negative predictive value (-PV) 80.77%. Sensitivity of PA smear as a diagnostic method was 62.5%, specificity 87.36%, +PV was 69.44%, and -PV 83.52%. CONCLUSION: Regarding the results of our study it is best to make a decision on treatment according to findings of all the three methods. Cytological analysis is more reliable than colposcopical examination. Therefore, it is advisable that following abnormal colposcopical findings, PA smear should always be taken and only after receiving the results further diagnostics can be planned (biopsy and HP). A final decision on the therapy has to be made based on HP findings which are the only method that can give the ultimate reliable diagnosis of cervical changes.

Pregnancy in patient with Swyer syndrome.

OBJECTIVE: To report a case of successful pregnancy and delivery after IVF and ET in a patient with Swyer syndrome. DESIGN: Case report. SETTING: Unit of Assisted Reproduction, Gynecology and Obstetrics Institute, University of Belgrade. PATIENT(S): A 30-year-old patient with 46,XY gonadal dysgenesis. INTERVENTION(S): Chromosomal analysis, diagnostic laparoscopy, IVF using donor oocytes, ET, and cesarean delivery. MAIN OUTCOME MEASURE(S): Successful pregnancy and live birth. RESULT(S): Successful treatment, pregnancy, and delivery. CONCLUSION(S): A patient with 46,XY gonadal dysgenesis in a donor oocyte program, can maintain a normal pregnancy and delivery.

Age and body mass related changes of cardiovascular risk factors in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is considered a metabolic disorder closely related to obesity, insulin resistance (IR), hyperinsulinemia and unfavorable lipid profile, all increasing the risk for the occurrence of cardiovascular diseases. The aim of this study was to assess age and body mass index (BMI) related changes of cardiovascular risk factors in 90 women with PCOS. The cut-off age point was 30 years and for BMI 27.8 kg/m2. In all patients systolic and diastolic blood pressure (BP), metabolic parameters comprising values of glucose and insulin during oral glucose tolerance test (OGTT), and basal lipid values were determined. Significant increase in blood pressure (BP) indices, basal insulin values and insulin resistance (IR) assessed by HOMA model were observed with aging and the increase of BMI, while the parameters of glucose metabolism, total cholesterol and triglycerides were significantly elevated only with aging. However, the correlation between the indices of arterial blood pressure, and lipid and glucose metabolism parameters occurred only in patients over 30 years of age, pointing to the causative relation and the consequent deterioration of IR and lipid profile with aging, influencing cardiovascular function in women with PCOS.