Biological therapies in the prevention of maternal mortality.

Although the maternal mortality rate has decreased and significant improvements have been made in maternal care, maternal death remains one of the substantial problems of our society. The leading causes of maternal death are postpartum hemorrhage, the most important cause of death in developing countries, and preeclampsia and venous thromboembolism, which are more prevalent in developed countries. To treat these conditions, a variety of therapeutic approaches, including pharmacologic agents and surgical techniques, have been adopted. However, a certain number of pregnant women do not respond to any of these options. That is the main reason for developing new therapeutic approaches. Biological medications are isolated from natural sources or produced by biotechnology methods. Heparin is already successfully used in the therapy of deep venous thrombosis and pulmonary embolism. Blood derivatives, used in an autologous or allogenic manner, have proven to be efficacious in achieving hemostasis in postpartum hemorrhage. Mesenchymal stem cells, alpha-1-microglobulin, and antithrombin exhibit promising results in the treatment of preeclampsia in experimental models. However, it is essential to evaluate these novel approaches' efficacy and safety profile throughout clinical trials before they can become a standard part of patient care.

Endometrium receptivity in premature ovarian insufficiency - how to improve fertility rate and predict diseases?

More empathized approach is required and is obligatory to women with premature ovarian insufficiency (POI) interested for pregnancy. In order to improve fertility rate in POI patients our suggestions would be: (1) To decrease FSH value to 10-15 IU/L by increasing estrogen. Oocyte donation can be suggested after a minimum of six month interval from FSH between 10-15 IU/L and when no dominant follicles are found. (2) To perform oral glucose tolerance test (OGTT). Insulin sensitizing agents has to be included, when indicated, 3-6 month before pregnancy. (3) TSH has to be 1-2.5 mM/L during 3-6 months before pregnancy. (4) Tests for thrombophyllia (Leiden V, FII, MTHFR, PAI) have to be obligatory. They are less expensive than those repeated in vitro fertilizations. Therapy has to be included according to the indications. (5) In order to regulate disturbed immune response in POI patients with endometriosis oral contraceptive therapy is needed for atleast six months prior to the pregnancy. (5) Encourage the patients and advice them about healthy life style and eating habits. (6) Add other drugs, when they are indicated. Complex interplay between endocrine, immunological, haematological, and psychological factors are very often underdetected in POI patients. It is very important to find out the real time for oocyte donation after correcting all the disturbances, improving endometrium receptivity and reaching women's acceptable psychological status. Untreated disturbances induce cardiovascular diseases, diabetes mellitus, thyroid diseases, coagulopathioes etc.

Clients' Perception of Outcome of Team-Based Prenatal and Reproductive Genetic Counseling in Serbian Service Using the Perceived Personal Control (PPC) Questionnaire.

This is the first study in Serbia and the region of South-East Europe dedicated to clients' perception of outcome and efficiency of prenatal and reproductive genetic counseling. The primary aim of this study was to assess overall value and success of genetic counseling in prenatal and reproductive care with regard to perceived personal control of clients, reflecting also in a part patient comprehension, knowledge retention, and empowerment in decision-making. The standardized Perceived Personal Control questionnaire (PPC) was used for the assessment of 239 female participants. First, we performed a complete validation of the psychometric characteristics of the Serbian-language version of the PPC questionnaire. The validation of the questionnaire permits other researchers from Serbian-speaking regions of South-East Europe to use this standard instrument to assess the effectiveness of prenatal genetic counseling in their communities and analyze advantages and disadvantages of their counseling models. We also measured social and demographic characteristics of participants. Further, we analyzed effects of our team-based prenatal and reproductive genetic counseling model through (a) calculation of PPC scores at three different stages (before initial, after initial, and before second counseling session), and (b) by assessing participants' responses by indication for referral (advanced maternal age, abnormal biochemical screening, family history of hereditary disorders, maternal exposure to drugs, exposure to radiation, exposure to infective agents, infertility or recurrent abortions, and miscellaneous). The results indicate that participants' knowledge after initial counseling increased significantly and after that remained stable and sustainable. A satisfactory level of confidence among participants had been achieved, in that many felt an increased sense of control over their situation and emotional response to it. Indirectly, these results indicate the success of a team-based prenatal genetic counseling model, which has not been assessed in the literature to date.

Plasma kisspeptin levels in pregnancies with diabetes and hypertensive disease as a potential marker of placental dysfunction and adverse perinatal outcome.

BACKGROUND: The aim of this study was to prospectively evaluate plasma kisspeptin levels in 129 singleton pregnancies with diabetes [pregestational insulin-dependent diabetes mellitus (type 1) and gestational diabetes (GD)] and hypertensive disease [chronic hypertension (CH), gestational hypertension, and preeclampsia (PE)] as a potential marker of placental dysfunction and adverse perinatal outcome. STUDY DESIGN: Kisspeptin levels were evaluated in the first, second, and third trimesters in patients with type 1 diabetes (16 patients), H (22), and healthy control (25) and in the second and third trimesters in patients with GD (20), gestational hypertension (18), and PE (28). Maternal kisspeptin levels were correlated with pregnancy outcome, parameters of fetoplacental circulation, ultrasound-detected abnormalities of placental morphology, and placental weight at delivery. RESULTS: In pregnancies with type 1 diabetes and H, mean kisspeptin levels were significantly lower compared with the control group (p<0.001 in the first and second trimesters and p<0.05 in the third trimester). Decreased plasma kisspeptin levels in the second and third trimesters were found in patients with GD (p<0.001 in the second and third trimesters) and PE (p<0.001 in the second trimester and p<0.05 in the third trimester). In patients with PE and placental dysfunction, low kisspeptin levels in the third trimester were associated with adverse perinatal outcome. CONCLUSIONS: Our study demonstrates reduced kisspeptin levels in pregnancies with diabetes, H, PE, and placental dysfunction. In patients with PE and placental dysfunction, decreased kisspeptin levels were associated with adverse perinatal outcome. Larger studies are needed to investigate the role of kisspeptin as a potential marker of placental dysfunction and adverse perinatal outcome.

The Role of Cell and Gene Therapies in the Treatment of Infertility in Patients with Thyroid Autoimmunity.

There is a rising incidence of infertility worldwide, and many couples experience difficulties conceiving nowadays. Thyroid autoimmunity (TAI) is recognized as one of the major female infertility causes related to a diminished ovarian reserve and potentially impaired oocyte maturation and embryo development, causing adverse pregnancy outcomes. Growing evidence has highlighted its impact on spontaneously achieved pregnancy and pregnancy achieved by in vitro fertilization. Despite the influence of thyroid hormones on the male reproductive system, there is insufficient data on the association between TAI and male infertility. In past years, significant progress has been achieved in cell and gene therapies as emerging treatment options for infertility. Cell therapies utilize living cells to restore healthy tissue microenvironment and homeostasis and usually involve platelet-rich plasma and various stem cells. Using stem cells as therapeutic agents has many advantages, including simple sampling, abundant sources, poor immunogenicity, and elimination of ethical concerns. Mesenchymal Stem Cells (MSCs) represent a heterogeneous fraction of self-renewal, multipotent non-hematopoietic stem cells that display profound immunomodulatory and immunosuppressive features and promising therapeutic effects. Infertility has a genetic component in about half of all cases, although most of its genetic causes are still unknown. Hence, it is essential to identify genes involved in meiosis, DNA repair, ovarian development, steroidogenesis, and folliculogenesis, as well as those involved in spermatogenesis in order to develop potential gene therapies for infertility. Despite advances in therapy approaches such as biological agents, autoimmune disorders remain impossible to cure. Recent research demonstrates the remarkable therapeutic effectiveness of MSCs in a wide array of autoimmune diseases. TAI is one of many autoimmune disorders that can benefit from the use of MSCs, which can be derived from bone marrow and adipose tissue. Cell and gene therapies hold great potential for treating autoimmune conditions, although further research is still needed.

Influence of Autologous In Vitro Activation of Ovaries by Stem Cells and Growth Factors on Endocrine and Reproductive Function of Patients with Ovarian Insufficiency-A Clinical Trial Study.

BACKGROUND: Premature ovarian failure (POF) can be found in 1% of women at the age of 35-40, mostly due to unknown causes. PI3K-Akt signaling is associated with both ovarian function and growth of primordial follicles. In this study, we examined the effects of autologous in vitro ovarian activation with stem cells and autologous growth factors on reproductive and endocrine function in patients with ovarian impairment. MATERIALS AND METHODS: The longitudinal prospective observational study included 50 patients (between 30 and 50 years) with a diagnosis of POF and infertility. This multicenter study was performed at Jevremova Special Hospital in Belgrade, Saint James Hospital (Malta), and Remedica Skoplje Hospital, between 2015 and 2018. All patients went through numerous laboratory testings, including hormonal status. The autologous bone marrow mesenchymal stem cells (BMSCs) and growth factors were used in combination for activation of ovarian tissue before its re-transplantation. The software package SPSS 20.0 was used for statistical analysis of the results. RESULTS: Differences in follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (PG) hormone concentrations before and after 3, 6, and 12 months post-transplantation were tested in correlation with the volume of transplanted ovarian tissue. A significant correlation (P=0.029) was found between the change in E2 level after 3 months and the volume of re-transplanted tissues. Also after re-transplantation, 64% of the patients had follicles resulting in aspiration of oocytes in 25% of positive women with follicles. CONCLUSION: The SEGOVA method could potentially solve many human reproductive problems in the future due to the large number of patients diagnosed with POF, as well asthe possibility of delaying menopause, thus improving the quality of life and general health (Registration number: NCT04009473).

Full-term interstitial retroperitoneal pregnancy with delivery of a healthy infant.

Implantation in the interstitial part of the oviduct is frequently associated with severe fetal and maternal morbidity. We present a patient with primary interstitial and secondary retroperitoneal ectopic pregnancy. The suspicion of an ectopic pregnancy was raised after an ultrasound examination during the 18th week of pregnancy. An almost complete lack of symptoms led us to discard the possibility of an ectopic pregnancy. This normal-course pregnancy advanced to term. Due to anhydramnios and fetal malpresentation, a laparotomy was performed at 39 weeks of pregnancy and a healthy infant was delivered via cesarean section.

Downregulation of autophagy gene expression in endometria from women with polycystic ovary syndrome.

Autophagy, a process of controlled cellular self-digestion, could be involved in cyclic remodeling of the human endometrium. We investigated endometrial mRNA expression of 23 autophagy-related (ATG) genes and transcription factors in healthy controls (n = 12) and anovulatory polycystic ovary syndrome (PCOS) patients (n = 24), as well as in their subgroup (n = 12) before and after metformin treatment. The mRNA levels of transcription factor forkhead box protein O1 (FOXO1) and several molecules involved in autophagosome formation (ATG13, RB1-inducible coiled-coil 1), autophagosome nucleation (ATG14, beclin 1, SH3-domain GRB2-like endophilin B1), autophagosome elongation (ATG3, ATG5, γ-aminobutyric acid receptor-associated protein - GABARAP), and delivery of ubiquitinated proteins to autophagosomes (sequestosome 1), were significantly reduced in anovulatory PCOS compared to healthy endometrium. Free androgen index, but not free estrogen index, insulin levels, or body mass index, negatively correlated with the endometrial expression of ATG3, ATG14, and GABARAP in PCOS patients. Treatment of PCOS patients with metformin (2 g/day for 3 months) significantly increased the endometrial mRNA levels of FOXO1, ATG3, and UV radiation resistance-associated gene. These data suggest that increased androgen availability in PCOS is associated with metformin-sensitive transcriptional downregulation of endometrial autophagy.

Hyperbaric oxygenation as a possible therapy of choice for infertility treatment.

Endometrial sonographic and color doppler features can be used to predict the occurrence of pregnancy in natural or stimulated cycles. Implantation will usually only take place if the endometrium has reach a certain stage of vascularisation and development. The aim of this study was to evaluate endometrial development -- endometrial thickness and reflectivity , subendometrial, endometrial and uterine perfusion, after hyperbaric oxygenation, using transvaginal color doppler. During a three years period 32 women with unexplained infertility were entered into a randomised study. The patients were treated in multiplaced HAUX chamber at pressure of 2.3 ATA during 70 minutes, 7 days consecutively beginning with day 5th of menstrual cycle. The evaluation of effects of hyperbaric oxygen therapy was carried out by transvaginal color doppler sonography which was continuously used starting from 8th day of menstrual cycle until the ovulation in the cycles when the therapy was applied , one month before and one month after the therapy. Folliculometry in the cycles when hyperbaric oxygen therapy at 2.3 ATA was applied, indicated an excellent response of endometrium. Thickness of endometrium at the time of ovulation was 11.0 +/- 2.6 mm. Desirable quality of endometrium was significantly better in the cycle when HBO therapy had been applied (p< 0.001). The doppler flowmetry of the uterine arteries indicated that the uterine blood vessel resistance was slightly higher than expected. Mapping of subendometrial blood vessels in the cycles covered by hyperbaric oxygen therapy showed the intensive capillary network of endometrium with low resistance Ri< 0.45. The oxygen used under higher pressure -- oxygen as a drug , may have an extraordinary significance for better outcome of pregnancy implantation by improving endometrial receptivity. If endometrial receptivity is conditioned by adequate vascularisation and oxygenation, then hyperbaric oxygen therapy is the treatment of choice.

First successful pregnancy outcome after intrauterine insemination in a woman with primary infertility and essential thrombocythemia treated with interferon-alpha and aspirin.

INTRODUCTION: The management of pregnancy in young women with essential thrombocythemia is complex and may present a difficult problem. An adverse pregnancy outcome due to thrombosis or bleeding is a common complication. in addition, little is known about fertility in these women prior to the disease. CASE OUTLINE: We present the first case of a young woman with primary infertility and essential thrombocythemia who had uneventfully delivered a healthy boy in the fortieth week of pregnancy. Her platelet count was normalized during treatment with interferon-alfa. The patient failed to become pregnant in the natural way and after three attempts of programmed intercourse. She conceived only following intrauterine insemination. During pregnancy, the patient was carefully controlled by a hematologist and gynecologist. CONCLUSION: Natural course and prognosis of essential thrombocythemia is not adversely affected by pregnancy. In these women, the pregnancy should be planned only after normalization of platelet count. The interferon-alpha should be administered before the pregnancy to regulate and maintain the platelet count within the normal range. Intrauterine insemination with minimal hormonal stimulation due to the risk of thrombosis could be recommended as the safest treatment option of infertility in women with essential thrombocythemia.

The role of hysteroscopy in diagnosis and treatment of postmenopausal bleeding.

BACKGROUND/AIM: Abnormal uterine bleeding is the most common problem which brings woman to the gynecologist during the postmenopausal period. The aim of this study was to define the significance of hysteroscopy as a diagnostic procedure for the evaluation of patients with postmenopausal bleeding, as well as to define it as a surgical procedure by which the cause of bleeding can be treated in most cases in the same sitting. METHODS: The study involved 148 female patients referred to the Clinic for Gynecology and Obstetrics in Nis for postmenopausal bleeding in the period of 12 months. Hysteroscopy with endometrial biopsy were performed in all the patients. Biopsy materials were directed to histological examination, and the hysteroscopic and histological findings were compared afterwards. Polyps and submucous miomas were hysteroscopically removed in the same sitting and also directed to histological examination. RESULTS: The success rate of the method was 95.1%, while complications occurred in 1.37% of the cases. The hysteroscopic findings were normal in almost 30% of the cases, and the most common pathological finding was endometrial polyp. The sensitivity of hysteroscopy in the detection of intrauterine pathology was 100%, the specificity 81%, the positive predictive value 92% and the negative predictive value 100%. In 69.7% of the patients the cause of bleeding was hysteroscopically removed. Hysteroscopy was performed in 58.1% of the patients in the same sitting, and in 11.6% of the patients after obtaining histological findings. CONCLUSION: Hysteroscopy is a safe, highly sensitive diagnostic procedure, thus being an ideal method for evaluation of patients with postmenopausal bleeding. The application of hysteroscopy with endometrial biopsy leads to accurate diagnosis. An adequate diagnosis is crucial for the selection of relevant treatment of postmenopausal bleeding and avoidance of unnecessary major surgical procedures. Except for being a diagnostic method hysteroscopy, is also an outpatient minimally invasive surgical procedure for treating the cause of bleeding in the majority of cases in the same sitting.

[Term pregnancy after minimally invasive surgical treatment of Herlyn-Werner-Wunderlich syndrome].

INTRODUCTION: Uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis represents a complex congenital anomaly, also known in the literature as Herlyn-Werner-Wunderlich (HWW) syndrome. CASE OUTLINE: A 16-year-old patient presented with secondary amenorrhoea and abdominal pain. Her history revealed anorexia nervosa; she had menarche at the age of 14; her menstrual cycles were regular, with progressive dysmenorrhoea. Nine months after the explorative laparotomy performed at the regional healthcare center there was no a definitive diagnosis. Pelvic examination showed a paravaginal pelvic mass located on the right side. Magnetic resonance imaging of the abdomen and pelvis confirmed the diagnosis of HWW syndrome. Transvaginal excision and marsupialisation of the vaginal septum were performed. Regular menstrual cycles were resumed after four years following the treatment of anorexia nervosa. Twelve years after the operation, the patient conceived spontaneously; pregnancy developed in the left non-obstructed uterus. She underwent Cesarean section at the 37th gestational week and gave birth to a healthy female infant. CONCLUSION: HWW syndrome is an uncommon cause of abdominal pain and progressive menstrual discomfort shortly after menarche. It is therefore essential to maintain a high index of suspicion of the existence of this syndrome in such cases, since prompt and adequate treatment prevents the development of complications and allows for preservation of the reproductive potential of both hemi-uteri.

The effects of adjuvant insulin therapy among pregnant women with IGT who failed to achieve the desired glycemia levels by diet and moderate physical activity.

OBJECTIVE: Evaluation of adjuvant insulin therapy effects on glycemic control, perinatal outcome and postpuerperal glucose tolerance in impaired glucose tolerance (IGT) pregnant women who failed to achieve desired glycemic control by dietary regime. METHODS: A total of 280 participants were classified in two groups: Group A patients continued with dietary regime and Group B patients were treated with adjuvant insulin therapy. Glycemic control was assessed by laboratory and ultrasonograph means. Pregnancy outcomes were evaluated by prevalence of pregnancy induced hypertension (PIH), high birth weight, neonatal hypoglycemia and caesarean section rates. Postpuerperal glucose tolerance was assessed by oral glucose tolerance test (oGTT). RESULTS: All laboratory and ultrasound indicators of glycemic control had significantly lower values in Group B. Group A women were more likely to develop the EPH (Edema, Proteinuria, Hypertension) syndrome, 20% versus 7.86% (p = 0.003). High birth weight occurred more frequently in Group A, but the difference was not significant (p = 0.197). Higher rate of caesarean delivery was in Group A than in Group B, 16.43% versus 26.43% (p = 0.041). The difference in neonatal hypoglycemia was not significant (p = 0.478). Pathological oGTT results were observed in 73 Group A patients and in 15 Group B patients. CONCLUSION: Lower caesarean section rates and the EPH syndrome incidence are the benefits of adjuvant insulin therapy in IGT patients.

Developing retroperitoneal anaplastic carcinoma with choriocarcinoma focus after ovarian non-gestastional choriocarcinoma: a case report.

INTRODUCTION: Choriocarcinoma is a malignant form of gestational trophoblastic neoplasm (GTN). It is a rare event but also a curable malignancy. In the majority of instancies it developes after any gestational event. In some cases it developes as non-gestational extrauterine malignancy. Prognosis of choriocarcinoma is poor when invasion and metastases appear early and spread fast. This form of choriocarcinoma can lead to incurable and letal outcome. CASE REPORT: We presented a 20-year-old patient with abdominal and retroperitoneal malignancy--anaplastic carcinoma combined with choriocarcinoma metastases in. Tumor developed three months after left adnexectomy which had been done because of adnexal tumor. Choriocarcinoma was immunohistochemicaly confirmed in adnexal masses. Two courses of chemotherapy, metotrexate + folic acid (MTX+FA) regimen, were administrated. The initial serum beta human chorionic gonadotropin level stayed unknown as well as the last one after the treatment. The patient came from the other country and was hospitalized because of pelvic and abdominal pain and palpable abdominal masses in hypogastrium with progressive anemia. The human chorionic gonadotropin level was 38 mIU/L. Tumor biopsy was done and choriocarcinoma metastases were immunohistochemicaly confirmed with predominant anaplastic carcinoma. Five day course of MTX + cyclophosphamide regimen was administrated and the patient was prepared for operative treatment. Relaparotomy was perforemed and tumor completely exceeded. Tumor mass mostly developed retroperitonely and partialy in abdominal cavity infiltrating intestinal wall with rupture of sigmoid colon. Anaplastic carcinoma, with large fields of necrosis and bleeding, was confirmed after histological examination. Immunohistochemical examination excluded choriocarcinoma in tumor mass. After 20 blood units transfusion, one course of chemotherapy and tumor excision, the patient left hospital on the 9th postoperative day. The patient rejected chemotherapy which was recommended according to the protocol and died one month after the operation. CONCLUSION: Non-gestational metastatic choriocarcinoma complicated with another type of malignancy with early spread of the disease and low responsiriness to chemotherapy has poor prognosis and leads to lethal outcome.

Fetal free thyroxine concentrations in pregnant women with autoimmune thyroid disease.

CONTEXT: Fetuses from mothers with autoimmune thyroid disease (AITD) may be affected by antithyroid antibodies, antithyroid drugs, and iodine. OBJECTIVE: The study correlated fetal free T(4) (fT4) with fetal ultrasound parameters and maternal thyroid function, thyroid antibodies, and medication dose from mothers with AITD. DESIGN AND SETTING: The study was designed as a prospective cohort study and conducted in an academic referral center. PATIENTS: Eighty-three of 85 women with AITD completed the study; 38 were treated for hyperthyroidism and 25 for hypothyroidism, and 20 were euthyroid. MAIN OUTCOME MEASURES: Outcomes were as follows: 1) fetal-fT4, TSH, ultrasound parameters (morphology, biometrics, heart rate); and 2) maternal-fT4, TSH, antithyroid drug dose, and antithyroid antibodies, thyroid peroxidase and TSH receptor (TRAK). Parameters were determined at the same time, between the 22nd and 33rd wk gestation. RESULTS: A total of 48.3% of fetuses from hyperthyroid mothers, 60% of fetuses from hypothyroid mothers, and 10% of fetuses from euthyroid mothers had elevated fT4 levels (P = 0.006). In hypothyroid mothers, the presence of both thyroid antibodies was related to fetal hyperthyroidism, whereas absence was related to fetal euthyroidism (P = 0.019). Hyperthyroid mothers (TRAK-positive, thyroid peroxidase-negative) with hyperthyroid fetuses had significantly higher mean TRAK than hyperthyroid mothers with euthyroid fetuses (13.7 vs. 3.7 IU/liter; P = 0.02). Fetal fT4 correlated weakly negatively with maternal TSH within the normal range, but not with ultrasound parameters or with antithyroid drug dose. CONCLUSION: High fetal fT4 levels were unexpectedly frequent in women with AITD, including maternal autoimmune hypo- and hyperthyroidism. Further studies are needed, as well as noninvasive methods to assess fetal thyroid function.

[Fetal multicystic kidney disease--outcome and follow up].

INTRODUCTION: Congenital fetal anomalies are the great problem and one of the main causes of increased perinatal mortality and morbidity. The aim of this study is to determine the outcome of prenataly detected multicystic dysplastic kidney and to point to the necessity of postnatal diagnostic procedures. MATERIAL AND METHODS: The retrospective-prospective study encompasses 38 cases of the prenatally diagnosed unilateral fetal multicystic dysplastic kidney. The associated anomalies were revealed either by autopsy findings when the pregnancy was terminated, or when the pregnancy continued, by clinical and operative findings the newborns. RESULTS: The autopsy finding revealed bilateral multicystic displastic kidney or unilateral mylticystic displastic kidney and the agenesis of the contralateral kidney. The postnatal evaluation of the newborns with unilateral multicistic disease revealed that 84.3% of them had some concomitant anomaly of the urinary tract, most of them had an anomaly of the contralateral kidney (31.4%). The surgery was performed in 73.6% of children, in 17% of children the kidney function deteriorated after the surgery. CONCLUSION: The findings of bilateral multicystic kidney disease and unilateral multicystic kidney disease and amnion are the indication to terminate the pregnancy. The finding of an isolated unilateral multicystic dysplastic kidney require thorough examination, both prenatally and postnatally. We propose obligatory serial prenatal ultrasound examinations, followed by postnatal ultrasound, isotope scan, and urinary cystourethography.

[Association of fetal unilateral multicystic kidney disease with other urinary tract anomalies]. / Udruzenost unilateralne multicisticne displazije bubrega fetusa sa drugim anomalijama urinarnog sistema.

BACKGROUND/AIM: Multicystic dysplastic kidney represents a disorder in the fetus development presented prenatally of postnatally, this deserving special attention due to a risk of additional anomalies in children with this disorder. The aim of this study was to determine the incidence and type of common anomalies of the urinary system in the prenatal diagnosis of unilateral multicystic dysplastic kidney, and point out the necessity of postnatal diagnostic procedures in order to evaluate the state of the urinary system. METHODS: This retrospective-prospective study encompassed 38 cases of prenatally diagnosed unilateral fetal multicystic dysplastic kidney, presented to the Council for Fetal Anomalies from the Institute for Gynecology and Obstetrics of the Clinical Centre of Serbia and the University Children's Clinic within a three-year period. Associated anomalies were revealed by autopsy findings when pregnancy was terminated, ie resumed with clinical and operative findings of born children. RESULTS: In every case of terminated pregnancy and death after birth the autopsy revealed additional renal or exstrarenal anomaly which were not prenataly detected. Postnatal evaluation of survived children with unilateral multicistic disease revealed that 31.4% of them have an anomaly of the contralateral kidney, 26.3% anomaly of the ipsilateral side, 13.2% anomaly of the lower portions of the urinary system and the same percent an additional extrarenal anomaly. The surgery was performed in 73.6% of children, more than half of the interventions were related to extrarenal anomaly. In 17% of children the kidney function was deteriorated after surgery. CONCLUSION: Children suffering from unilateral multicystic dysplastic kidney have a greater chance of exhibiting an anomaly of the contralateral kidney and the urinary system in general. Therefore, they require thorough examination, both prenatally and postnatally. We propose obligatory serial professional prenatal ultrasound examinations, followed by postnatal ultrasound, isotope scan, and we especially emphasize the need for performing urinary cystouretherography, bearing in mind the high incidence of the vesicoureteral reflux of the contralateral kidney. In addition to nephrectomy, cytoscopy and colposcopy also need to be performed for the purpose of discovering possible hidden anomalies of the urogenital system.

Changes in Doppler blood flow velocity in middle cerebral artery in response to airborne sound in low- and high-risk human fetuses.

OBJECTIVE: To examine fetal auditory perception in low- and high-risk pregnancies in period from 27 to 31 weeks gestational age with the aim to establish diagnostic parameters in prenatal detection of the degree of hearing development in a fetus. METHODS: Method of prenatal hearing screening was applied on 80 women divided in two groups: Control group (C=22), consisted of pregnant women with low-risk pregnancies, and Experimental group (E=58), consisted of pregnant women with high-risk pregnancies (pregnancies with diagnosis of: preterm delivery, hypertension and/or intrauterine growth restriction (IUGR), diabetes). PHS was applied in period from 27 to 31 weeks gestational age. Brain circulation changes in fetal middle cerebral artery (MCA) caused by defined sound stimulus, as the indicator of fetal auditory reactions, were registered on Doppler ultrasound apparatus. After visualization of MCA, a sound stimulus was delivered. The stimulus consisted of one defined sound which is a digitally produced sound with the intensity of 90 dB, frequency range of 1500-4500 Hz, and duration of 0.2s (click) and it was presented only once. Measurements in observed artery were taken before (baseline) and after defined sound stimulation. RESULTS: Results showed that the absolute and relative difference in Pulsatility index (baseline and after sound stimulation) were greater for the high-risk group compared to the low-risk group (absolute difference: mean=0.36 vs mean=0.36) (relative difference: mean = ∼ 18% vs mean = ∼ 12%). When the low-risk group and the three high-risk group mean pairs were compared using multiple t-test, the diabetic group differed from the low-risk and two other high-risk groups; the low-risk and the two other high-risk groups did not differ from each other. Fetuses from pregnancies with diagnosis of diabetes demonstrated the most expressive reactibility and significantly higher absolute and relative changes of Pi values (absolute difference: mean=0.54, relative difference: mean=25.49%). CONCLUSION: The values of Pulsatility index (Pi) registered by PHS in low- and high-risk pregnancies may be used as differential and diagnostic parameters in fetal auditory perception examination. Fetuses from pregnancies with diagnosis of diabetes demonstrated significantly higher absolute and relative changes of Pi values compared to other groups of examined fetuses.