Miracles of science: Birth after uterus transplantation.

AIM: The concept of regaining childbearing ability via uterus transplantation (UTx) motivates many infertile women to pursue giving birth to their own children. This article provides insight into maternal and neonatal outcomes of the procedure globally and facilitates quality of care in related medical fields. METHODS: The authors searched ISI Web of Science, MEDLINE, non-PubMed-indexed journals, and common search engines to identify peer-review publications and unpublished sources in scientific reference databases. RESULTS: The feasibility of the procedure has been proven with 46 healthy children in 88 procedures so far. Success relies upon dedicated teamwork involving transplantation surgery, obstetrics and reproductive medicine, neonatology, pediatrics, psychology, and bioethics. However, challenges exist owing to donor, recipient, and fetus. Fetal growth in genetically foreign uterine allograft with altered feto-maternal interface and vascular anatomy, immunosuppressive exposure, lack of graft innervation leading to "unable-to-feel" uterine contractions and conception via assisted reproductive technology create notable risks during pregnancy. Significant portion of women are complicated by at least one or more obstetric problems. Preeclampsia, gestational hypertension and diabetes mellitus, elevated kidney indices, and preterm delivery are common complications. CONCLUSIONS: UTx has short- and long-term satisfying outcome. Advancements in the post-transplant management would undoubtedly lead this experimental procedure into mainstream clinical practice in the near future. However, both women and children of UTx need special consideration due to prematurity-related neonatal problems and the long-term effects of transplant pregnancy. Notable health risks for the recipient and fetus should be discussed with potential candidates for UTx.

Serial measurement of soluble endoglin for risk assessment at the diagnosis of fetal growth restriction.

AIM: In this study, we aimed to investigate the soluble endoglin (sEng) levels in pregnant women with fetal growth restriction (FGR) and to examine the possible relation of the sEng levels with the time remaining to delivery and maternal and fetal complications. METHODS: A total of 42 pregnant women diagnosed with FGR were retrospectively reviewed. Using the maternal blood samples it is at the collected 24-37 gestational weeks, the sEng levels were measured. Fetal biometry measurements, umbilical artery, uterine artery, middle cerebral artery Doppler indices were documented. RESULTS: Of all patients, 17 (40%) were diagnosed with early-onset FGR, while 25 (60%) were diagnosed with late-onset FGR. Abnormal Doppler findings were present in 25 (60%) patients. Of 42 newborns, 18 (42%) were hospitalised in the neonatal unit. The mean sEng level calculated by taking the average of the first and second blood samples was 63.24 ± 49.83 ng/mL. There was no statistically significant difference in the mean sEng levels between those who gave birth within four, three, and two weeks after the diagnosis of FGR and those who did not. There was a positive significant correlation between the mean sEng levels and systolic blood pressure (r = 0.319, P = .04). CONCLUSIONS: We did not find a statistically significant relationship between the sEng level and the time remaining to the time of delivery in pregnant women with FGR. We found no statistically significant difference in sEng level between the groups in pregnant women with fetuses with FGR with or without maternal and fetal complications.

Effects of amnion derived mesenchymal stem cells on fibrosis in a 5/6 nephrectomy model in rats.

Chronic kidney disease (CKD) is characterized by disruption of the glomerulus, tubule and vascular structures by renal fibrosis. Mesenchymal stem cells (MSC) ameliorate CKD. We investigated the effects of human amnion derived MSC (hAMSC) on fibrosis using expression of transforming growth factor beta (TGF-ß), collagen type I (COL-1) and bone morphogenetic protein (BMP-7). We also investigated levels of urinary creatinine and nitrogen in CKD. We used a 5/6 nephrectomy (5/6 Nx) induced CKD model. We used 36 rats in six groups of six animals: sham group, 5/6 Nx group, 15 days after 5/6 Nx (5/6 Nx + 15) group, 30 days after 5/6 Nx (5/6 Nx + 30) group, transfer of hAMSC 15 days after 5/6 Nx (5/6 Nx + hAMSC + 15) group and transfer of hAMSC 30 days after 5/6 Nx (5/6 Nx + hAMSC + 30) group. We isolated 106 hAMSC from the amnion and transplanted them via the rat tail vein into the 5/6 Nx + hAMSC + 15 and 5/6 Nx + hAMSC + 30 groups. We measured the expression of BMP-7, COL-1 and TGF-ß using western blot and immunohistochemistry, and their gene expressions were analyzed by quantitative real time PCR. TGF-ß and COL-1 protein, and gene expressions were increased in the 5/6 Nx +30 group compared to the 5/6 Nx + hAMSC + 30 group. Conversely, both protein and gene expression of BMP-7 was increased in 5/6 Nx + hAMSC + 30 group compared to the 5/6 Nx groups. Increased TGF-ß together with decreased BMP-7 expression may cause fibrosis by epithelial-mesenchymal transition due to chronic renal injury. Increased COL-1 levels cause accumulation of extracellular matrix in CKD. Levels of urea, creatinine and nitrogen were increased significantly in 5/6 Nx + 15 and 5/6 Nx + 30 groups compared to the hAMSC groups. We found that hAMSC ameliorate CKD.

Ventriculoperitoneal shunt treatment in a pregnant renal transplant recipient with idiopathic intracranial hypertension: Case report and review of the literature.

Idiopathic intracranial hypertension (IIH) is a relatively uncommon disorder characterised by raised intracranial pressure without an established pathogenesis. Diagnosis of IIH requires the demonstration of symptoms and signs referable only to elevated intracranial pressure; cerebrospinal fluid (CSF) opening pressure >25cm H2O measured in the lateral decubitus position; normal CSF composition; and no evidence for an underlying structural cause demonstrated by using MRI or contrast-enhanced CT scan for typical patients and MRI and MR venography for atypical patients such as man, children and those with low body mass index. We present a 38-year old primigravid renal transplant patient at 7 weeks of gestation who presented with 2 weeks of intense, throbbing, holocranial headache, nausea, vomiting, photophobia, diplopia and progressive visual loss. When medical treatment fails and/or not appropriate to use due to the reported of teratogenic risks in pregnant women, surgical interventions gain importance. In this particular patient, venticuloperitoneal shunt was chosen as the CSF diversion technique. In this case report indications, contraindications in addition to outcomes regarding headache, vision loss and the resolution of papilloedema of the present surgery options for IIH are discussed.

Uterus transplantation: From animal models through the first heart beating pregnancy to the first human live birth.

Absolute uterine factor infertility affects 3-5% of the general population, and unfortunately this condition is untreatable. There are some available options, including surrogacy or adoption, but neither of these suits each and every woman who desires to have her own genetic child. With recent advances in surgery and transplant immunology, uterus transplantation may be a source of hope for these women with uterine infertility. In the last decade, a number of animal species including rats, mice, rabbits, pigs, sheep, and primates have been used as experimental models, and pregnancies were achieved in some of these. Human data consist of 11 subjects yielding positive pregnancy results with no live births in the second trial from Turkey and, more fortunately, live births from the latest trial from Sweden. In the light of all these studies, uterus transplantation has been proven to be a viable option for women with uterine factor infertility.

Associated anomalies with neural tube defects in fetal autopsies.

Neural tube defects (NTD), the consequences of aberrant neural tube closure during embryogenesis, have been mostly investigated in terms of their high prevalence, rate of mortalities and serious morbidities. A proper prenatal outcome counseling of couples coming across a fetal anomaly necessitates the detection and categorization of the primer abnormality, all the co-existing malformations. The aim of this work is to study the incidence and relevance of associated malformations in order to offer a complete pathology report with a true diagnosis. In this study, among 542 fetal autopsy 62 (%11.4) cases with NTD was recorded by the Akdeniz University Pathology Department between January 2006 and June 2012. Twenty (32.4%) NTD cases were associated with anomaly. Twelve cases of associated groups consisted of a congenital syndrome/association, spondylothoracic dysplasia, amniotic band syndrome, Meckel-Gruber syndrome, schisis association. The frequency of associated NTD was 32%, this result was higher than previous reports. NTDs have a significant genetic component to their etiology that interacts with environmental risk factors, which might pose Turkey to be a country with high prevalence of NTD. We want to emphasize that intensive screening, documentation of co-existent abnormalities of NTD, should be conducted in order to exhibit certain diagnosis, to perform proper prenatal genetic counseling of parents for on-going/future pregnancies.

Comparison of pre-procedural anxiety and depression scores for patients undergoing chorion villus sampling and amniocentesis: An alternative perspective on prenatal invasive techniques.

OBJECTIVE: To compare the pre-procedural anxiety and depression levels of patients undergoing chorion villus sampling (CVS) and amniocentesis (AC). METHODS: Patients referred to our department for fetal karyotype analysis with a positive first or second trimester screening test for aneuploidy between January 2013 to June 2015 were included. CVS and AC procedures were performed in patients with gestation periods of between 11-14 and 16-20 weeks, respectively. Anxiety was evaluated using the Spielberger State-Trait Anxiety Inventory (STAI), and depression was assessed using the Beck Depression Inventory II (BDI-II). RESULTS: A total of 1,400 patients were included. Compared to first trimester controls, patients undergoing CVS had significantly higher STAI-state and BDI-II results. Likewise, patients undergoing AC had higher STAI-state and BDI-II scores than controls in the second trimester. In terms of STAI-trait results, no difference was found between the groups. Our results also showed that, compared to AC group, patients undergoing CVS had similar STAI-state, STAI-trait and but higher BDI-II scores. CONCLUSION: We conclude that evaluating the stress and depression levels of these patients should be one of the routine procedures in pregnancy follow-up.

Perinatal Diagnostic Approach to Fetal Skeletal Dysplasias: Six Years Experience of a Tertiary Center.

Skeletal dysplasias (SDs) constitute a group of heterogeneous disorders affecting growth morphology of the chondro-osseous tissues. Prenatal diagnosis of SD is a considerable clinical challenge due to phenotypic variability. We performed a retrospective analysis of the fetal autopsies series conducted between January 2006 and December 2012 at our center. SD was detected in 54 (10%) out of 542 fetal autopsy cases which included; 11.1% thanatophoric dysplasia (n = 6), 7.4% achondroplasia (n = 4), 3.7% osteogenesis imperfect (n = 2), 1.9% Jarcho-Levin Syndrome (n = 1), 1.9% arthrogryposis (n = 1), 1.9% Dyggve-Melchior-Clausen syndrome (n = 1), 72.1% of dysostosis cases (n = 39). All SD cases were diagnosed by ultrasonography. In 20 of the cases, amniocentesis was performed, 4 cases underwent molecular genetic analyses. Antenatal identification of dysplasia is important in the management of pregnancy and in genetic counseling. Our data analysis showed that SD is usually detected clinically after the 20th gestational week. Genetic analyses for SD may provide early diagnosis and management.

Chromosome abnormalities identified in 457 spontaneous abortions and their histopathological findings.

OBJECTIVE: About 15% of clinically recognized pregnancies result in spontaneous abortion in the first trimester and the vast majority of these are the result of chromosome abnormalities. Studies of chromosomal constitutions of first trimester spontaneous abortions have revealed that at least 50% of the abortions have an abnormal karyotype. In this study we aimed to report the single centre experience of anomalies detected in spontaneous abortions. MATERIAL AND METHOD: We present rare numerical and structural cytogenetic abnormalities detected in spontaneous abortion materials and the histopathological findings of rest material of abortion specimens in our study population. RESULTS: Among 457 cases, 382 were successfully karyotyped while cell culture of 75 cases failed. Cytogenetic abnormalities were detected in 127 of 382 cases (33.24%). Autosomal trisomies were the predominant chromosomal abnormalities with a frequency of 48.8%. Structural chromosomal abnormalities were infrequent in conception materials. The mean age of the mothers was highest in trisomy group, the difference being significantly important (ANOVA p < 0.001). The most frequent chromosomal abnormalities were Turner syndrome, triploidy and trisomy of chromosome 16 followed by trisomy of chromosomes 22 and 21 and tetraploidy. Double trisomies and structural chromosomal abnormalities were rare. Trisomies were more frequent in advanced maternal age. CONCLUSION: Detection of chromosomal abnormalities in spontaneous abortion materials is very important to clarify the causes of loss of pregnancy. Detection of structural chromosomal abnormalities in the cases and their carrier parents can provide proper genetic counseling to these families. These families can be directed towards pre-implantation genetic diagnosis to prevent further pregnancies with complications.

A familial interstitial 4q35 deletion with no discernible clinical effects.

Small deletions on the long arm of distal chromosome 4 do not appear to result in gross congenital malformations, with the most frequently reported clinical findings including mild to moderate intellectual disability, learning disabilities and minor dysmorphic features. Here we report on a cytogenetically detectable familial interstitial chromosome 4 long arm deletion with no discernible phenotypic effects in a mother and her two daughters. The karyotypes of the mother and her two daughters were: 46,XX,del(4)(q35.1q35.2). Based on the results of FISH analyses using whole chromosome specific and subtelomeric probes, the karyotype was designated as: 46,XX,del(4)(q35.1q35.2). ish del(4)(q35-qter)(WCP4+, 36P21+, dJ963K6-). Array-CGH analysis showed an interstitial deletion encompassing 5.75 Mb in the 4q35.1-q35.2 genomic region (chr4:184,717,878-190,469,337; hg19). This is the first report on a cytogenetically detectable familial interstitial chromosome 4 long arm deletion in which there are no discernible phenotypic effects. Both our findings and a review of the literature suggest that more detailed molecular analyses are needed in cases with distal chromosome 4 long arm deletions especially those with breakpoints in the 4q35 region to establish a more precise genotype-phenotype correlation.

A retrospective analysis of pregnancy outcomes after kidney transplantation in a single center.

BACKGROUND: We reported pregnancy outcomes after kidney transplantation in a single transplant center. METHODS: We reviewed the perinatal outcomes of female kidney transplant patients of reproductive age (18-40 years) from 1987 to 2011. RESULTS: A total of 246 patients were reviewed. Of these, 43 women registered a pregnancy following kidney transplantation. The mean patient age was 31.3 ± 4.2 years (range 24-40). The mean transplant-conception interval was 35.9 ± 12.6 months (range 24-120); 9 patients had a cadaveric allograft. The human leukocyte antigen match was ≥3/6 for 34 patients. The rate of live births was 29/43 (67.4%), miscarriage 10/43 (23.2%), preterm delivery 7/29 (24.1%), preeclampsia 5/29 (17.2%), and intrauterine growth retardation 2/29 (6.9%). Overall, 3/29 patients (10.3%) received a blood transfusion during pregnancy due to persistent symptomatic anemia, despite iron replacement and erythropoietin therapy; 24 patients (82%) had a cesarean section delivery; 3 patients had kidney rejection during pregnancy, with 2 occurring during the 6th postpartum month. CONCLUSION: Pregnancy should be considered a high risk in renal transplant recipients, necessitating close follow-up.

Rare congenital pulmonary malformation with diagnostic challenging: congenital pulmonary lymphangiectasia, report of four autopsy cases and review of literature.

Congenital pulmonary lymphangiectasia (CPL) is a rare congenital disorder that typically presents with intractable respiratory failure in the first few days of life. There is an association non-immun hydrops and CPL. In this study we reviewed four CPL cases between January 2006 and January 2014 among 684 fetal-pediatric autopsies. All cases were in the second trimester. In light microscopy there were marked dilatated channels in the subpleural -peribronchial-subseptal region of the lungs. The channels were lined with flattened cells which were expressing CD 31 and D2-40, negative for CD34. Although pulmonary interstitial emphysema (PIE) was considered an important differential diagnosis, a giant cell reaction surrounding the interstitial cystic lesions, a histological hallmark of PIE. CPL is characterized by dilatation of the pulmonary lymphatic vessels and occurs as a congenital anomaly. Noonan classified it into three groups. Primary developmental defect of pulmonary lymphatics is group 3. Group 3 is called also as CPL; normal regression of the connective tissue elements fails to occur after the 16th week of fetal life, associated with an aggressive clinical course, poor prognosis. In fetal autopsy examination CPL should be recognized if there is a fetus with pleural effusion, non-immune hydrops. There is no clinical evidence for CPL.

Intravaginal misoprostol alone versus intravaginal misoprostol and extraamniotic Foley catheter for second trimester pregnancy termination: an observational study.

BACKGROUND: No systematic empirical research exists addressing the question of optimal pregnancy termination method in second trimester pregnancies. OBJECTIVES: The purpose of this study was to determine the efficacy and safety of intravaginal misoprostol and extraamniotic Foley catheter combination for second trimester pregnancy termination. METHODS: A single center observational study was conducted in a total of 91 pregnancies. Women who met the termination of pregnancy criteria due to feto-maternal indications between 13 to 26 gestational weeks were included into the study. Study participants received intravaginal misoprostol in combination with Foley catheter (n = 46) or intravaginal misoprostol alone (n = 45). RESULTS: The efficacy of intravaginal misoprostol and Foley catheter insertion combination was comparable to that of intravaginal misoprostol alone in terms of time to abortion/birth [median (95% Confidential Interval [95% CI]): 14.33 (11.33-17.25) hours and 12.08 (9.50-15.33) hours, respectively Hazard Ratio: 0.73, 95% CI: 0.47 to 1.12, p = 0.14 (log-rank)]. The only serious maternal event was uterine rupture observed in one woman in Foley combination group. CONCLUSION: The combination of intravaginal misoprostol and extraamniotic Foley catheter for second trimester pregnancy termination does not provide additional efficacy.

The expression of cell cycle related proteins PCNA, Ki67, p27 and p57 in normal and preeclamptic human placentas.

Placenta is a transitional area making many physiological activities between mother and fetus and therefore, it is a critical organ influencing the outcome of pregnancy. Fetal growth is directly related to placental development. Accurate placental development depends on coordinated action of trophoblasts' proliferation, differentiation and invasion. Information on cell cycle related proteins that control these events is limited and how they are affected in preeclampsia is not fully understood yet. Therefore, in this study, in order to understand the role of cell cycle regulators in preeclamptic placentas we aimed to determine the spatio-temporal immunolocalizations of cell cycle regulators in preeclamptic and normal human term placentas. Term placentas were obtained from women diagnosed with preeclampsia and from normal pregnancies with informed consent following cesarean deliveries. Placental samples were stained via immunohistochemistry with PCNA, Ki67, p27, p57, vimentin and cytokeratin 7 antibodies and were examined by light microscopy. PCNA and Ki67 staining intensities significantly increased in villous parts, significantly decreased in basal plates of PE group and did not change in chorionic plates. Staining intensities of cell cycle inhibitors p27 and p57 significantly increased in all parts of preeclamptic placentas compared to control. Placental abnormalities of preeclamptic placentas might be associated with proliferation and cell cycle arrest mechanisms' alterations occurred in preeclampsia.

Immunohistochemical distribution of cell cycle proteins p27, p57, cyclin D3, PCNA and Ki67 in normal and diabetic human placentas.

The placenta is a regulator organ for many metabolic activities between mother and fetus. Therefore, fetal growth is directly related to the placental development. Placental development is a series of events that depend on the coordinated action of trophoblasts' proliferation, differentiation and invasion. Studies on cell cycle related proteins which control these events are fairly limited. How placental tissue proliferation is affected by diabetes is not exactly known yet. Therefore in this study, the immunohistochemical localizations of cell cycle related proteins like PCNA, Ki67, cyclin D3, p27 and p57 in the differentiation, proliferation and apoptosis mechanisms of normal and diabetic placentas were investigated. Information on cell cycle related proteins that control these events is limited and how they are affected in diabetes mellitus is not fully understood yet. Therefore, in this study, to understand the role of cell cycle regulators in diabetic placentas we aimed to determine the spatio-temporal immunolocalizations of cell cycle regulators in diabetic and normal human term placentas. Term placentas were obtained from diabetic women and from normal pregnancies with informed consent following caesarean deliveries. Placental samples were stained via immunohistochemistry with PCNA, Ki67, cyclin D3, p27 and p57 antibodies and were examined by light microscopy. When compared to control placentas, PCNA, Ki67 and cyclin D3 staining intensities significantly increased in villous parts of diabetes group. Moreover, Ki67 and cyclin D3 stainings also significantly increased in basal plates and chorionic plate respectively. In chorionic plates, p27 and p57 staining intensities significantly decreased in diabetic group. p57 staining also significantly decreased in villous parts of diabetic placentas. Placental abnormalities seen in diabetic placentas could be associated with proliferation and cell cycle arrest mechanisms' alterations occurred in diabetes mellitus.

Clinical pregnancy after uterus transplantation.

OBJECTIVE: To present the first clinical pregnancy after uterus transplantation. DESIGN: Case study. SETTING: Tertiary center. PATIENT(S): A 23-year-old Mayer-Rokitansky-Kuster-Hauser syndrome patient with previous vaginal reconstruction and uterus transplantation. INTERVENTION(S): Eighteen months after the transplant, the endometrium was prepared for transfer of the thawed embryos. MAIN OUTCOME MEASURE(S): Implantation of embryo in an allografted human uterus. RESULT(S): The first ET cycle with one day 3 thawed embryo resulted in a biochemical pregnancy. The second ET cycle resulted in a clinical pregnancy confirmed with transvaginal ultrasound visualization of an intrauterine gestational sac with decidualization. CONCLUSION(S): We have presented the first clinical pregnancy in a patient with absolute uterine infertility after uterus allotransplantation. Although the real success is the delivery of a healthy near-term baby, this clinical pregnancy is a great step forward and a proof of concept that the implantation phase works.

Prenatal diagnosis of mobile flap-like tissue on the ventricular septal defect in a newborn with trisomy 18.

Trisomy 18 is the second most common autosomal trisomy in liveborn infants. Various congenital malformations, mental retardation, and high rate of infant mortality in the first year of life are characteristic features of trisomy 18. Congenital heart disease occurs in over 90% of these patients and the most common cardiac lesions are ventricular septal defect, patent ductus arteriosus and atrial septal defect. This is a case report of a baby born with trisomy 18 (postnatal diagnosis) in whom there was an unusual echocardiographic appearance of a mobile structure ("flap-like") around the area of a VSD-which was imaged prenatally.

Prenatal diagnosis of ß-thalassemia and other hemoglobinopathies in southwestern Turkey.

Our aim was to evaluate the prenatal diagnosis of ß-thalassemia (ß-thal) and other hemoglobinopathies in a region with high frequency. After detection by premarital or antenatal screening, 312 patients underwent 420 prenatal diagnostic procedures for 407 fetuses in a 10-year period. Fetal samples were collected by chorionic villi sampling (CVS) in the first trimester and amniocentesis and cordocentesis in the second trimester. Mutation analyses of ß-globin and cytogenetic analyses were performed and the most common mutations detected were: IVS-I-110 (G>A), IVS-II-1 (G>A), IVS-I-6 (T>C) and IVS-II-745 (C>G). Hb S [ß6(A3)Glu→Val, GAG>GTG)] was the most common hemoglobin (Hb) variant with a frequency of 6.3%. Among 407 fetuses, 105 (25.8%) were diagnosed as affected, while 201 (49.4%) were carriers and 101 (24.8%) were normal. Cytogenetic analyses revealed nine fetuses (2.3%) with numerical chromosomal abnormalities as regular or mosaicism. Prenatal diagnosis of common hemoglobinopathies is safe and effective. Performing cytogenetic analysis in excess fetal material is an acceptable option.