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of Science, MEDLINE, non-PubMed-indexed journals, and common search engines to identify peer-review publications and unpublished sources in scientific reference databases.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.

Intraoperative and Postoperative Outcomes of Pfannenstiel and Midline Skin Incisions in Placenta Accreta Spectrum Disorders: Single-Center Experience.

Background: We compared Pfannenstiel and midline skin incisions for cesarean hysterectomy in women with confirmed Placenta Accreta Spectrum Disorders. Aims: A retrospective cohort study was conducted to evaluate the outcomes of Pfannenstiel and midline skin incisions in women undergoing cesarean section hysterectomy for suspected placenta accreta at Akdeniz University Hospital between January 2010 and February 2022. Histopathological confirmation was obtained for all cases. Demographic, perioperative, and postoperative data, along with neonatal outcomes, were extracted from the hospital's electronic database. Possible complaints related to the incision site or other issues (e.g., vaginal dryness or sexual life) were identified through telephone interviews. Subjects were stratified into Pfannenstiel and midline incision cohorts, with subsequent data comparison. Results: Data from 67 women with a histopathologically confirmed PAS diagnosis were analyzed. Of these, 49 (73.1%) underwent Pfannenstiel incision, and 18 (26.9%) had a midline skin incision. Incisions were based on the surgeon's experience. Pfannenstiel incision was more common in antepartum hemorrhage, preoperative hemorrhage, and emergency surgery (p = 0.02, p = 0.014, p = 0.002, respectively). Hypogastric artery ligation occurred in 30 cases (61.2%) in the Pfannenstiel group but none in the midline group. Cosmetic dissatisfaction and sexual problems were more prevalent in the midline group (p < 0.05, all). Preoperative and postoperative blood parameters, transfused blood products, and neonatal outcomes were similar between the two groups. Conclusions: Relaparotomy, bladder injury, blood loss, and need for blood transfusion were more prevalent in the Pfannenstiel group, while greater dissatisfaction with the incision was observed in the midline incision group. Midline incision seems to be more favorable in patients with Placenta Accreta Spectrum (PAS). Patients may be informed regarding the worse cosmetic outcomes and possible sexual problems related to vaginal dryness when midline laparotomy is planned. But before opting for a Pfannenstiel incision, patients should receive comprehensive information regarding the potential risks of relaparotomy and bladder injury.

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.

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.

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.

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.

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.

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.

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.

The association between inherited thrombophilias and pregnancy-related hypertension recurrence.

PURPOSE: The aim of this study was to determine the association between inherited thrombophilias and pregnancy-related hypertension recurrence. METHODS: In this case-control study, blood samples were obtained from patients who had at least two pregnancies complicated with pregnancy-related hypertension (n = 41) and healthy, normotensive pregnancies delivered without any complication (n = 38). Following the DNA extraction, samples were tested for factor V Leiden, prothrombin G20210A and homozygous methylene tetrahydrofolate reductase (MTHFR) C677T mutations using reverse hybridization method. RESULTS: Common inherited thrombophilias were present in 26.8% of women with recurrent pregnancy-related hypertension group and 23.7% of control subjects (odds ratio 1.1; 95% confidence interval, 0.6-1.9). No significant difference was observed between two groups in terms of factor V Leiden, prothrombin G20210A and MTHFR C677T mutations. CONCLUSION: Our data suggest that factor V Leiden, prothrombin G20210A and MTHFR C677T mutations are not associated with pregnancy-related hypertension recurrence.

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.

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.

Conjoined twins in a trichorionic quadruplet pregnancy after ovulation induction with clomiphene citrate.

OBJECTIVE: We report a case of conjoined twins in a trichorionic quadruplet pregnancy after ovulation induction with clomiphene citrate for anovulation. METHODS: The diagnosis of a trichorionic quadruplet pregnancy was made in routine ultrasound at 11 weeks' gestation. RESULTS: Conjoined twinning was thoracopagus and presented with increased nuchal translucency. Selective termination of the conjoined twins was performed with potassium chloride injection. The patient delivered 2 healthy infants after an uneventful follow-up. CONCLUSION: Monozygotic twinning has increased with widespread usage of ovulation induction agents and assisted reproductive techniques. Early detection of conjoined twinning and chorionicity is essential for an optimal obstetric management and outcome.

CMV seroconversion in pregnants and the incidence of congenital CMV infection.

In this study, it was aimed to determine the ratio of CMV seroconversion in pregnant women, the prevalence of maternal CMV infection and also the incidence of congenital CMV infection in their newborns in the Antalya region of Turkey. During a one-year period, CMV-specific IgG and IgM were determined in all (n: 1027) pregnant women admitted at 8 to 20 weeks of gestation, an according to the presence or absence of anti CMV-IgM and CMV-IgG, pregnant women were classified as seropositive, seronegative and having maternal CMV infection. Differentiation of primary and recurrent CMV infection in women with both CMV-IgM (+) and CMV-IgG (+) antibody was determined by the avidity index (AI) of anti-CMV IgG. Ultrasonographic examination was done and amniocentesis was performed at 21 to 23 weeks of gestation in pregnants with primary infection. CMV DNA was investigated in the amniotic fluid by quantitative polymerase chain reaction (qPCR). Pregnants with recurrent infection were followed only by ultrasonography for the presence of fetal abnormalities. Neonates born to mothers with CMV infection were examined for the findings of congenital CMV infection and screened for anti- CMV-IgM, CMV DNA and CMV antigenemia in the first two weeks of life. The rate of seropositivity was found as 98.5% and the rate of seronegativity as 1.5% in pregnant women. The prevalence of maternal CMV infection was found as 1.2% and among these pregnant women, the incidence of primary and recurrent maternal CMV infection was 0.3% (3 women) and 0.8% (12 women), respectively. Congenital CMV infection was detected in one of the newborns born to mothers with primary infection while no infection was detected in any of the newborns of mothers with recurrent CMV infection, so the incidence of congenital CMV infection was found as 0.1% and the rate of intrauterine infection following the primary maternal infection was 33%. In conclusion, seroprevalence rate of CMV in pregnants is high and most (66%) infections are recurrent maternal CMV infection in our region. Thus, it does not seem to be cost-effective to screen all pregnant women for CMV infection, as in the other countries with high seropositivity rate.

Psychological effects of amniocentesis on women and their spouses: importance of the testing period and genetic counseling.

OBJECTIVE: To evaluate both women's and their spouses' reasons for undergoing amniocentesis, their concerns relating to the procedure as well as their psychological reactions and coping mechanisms during the testing period. METHODS: Eighty-five women undergoing amniocentesis and their spouses took part in the study. The couples completed a questionnaire that provided demographic data and insights into their experiences of amniocentesis. RESULTS: Age was the main reason for undergoing amniocentesis. When they first learned that they were going to undergo amniocentesis, women were more concerned about the potential danger to their fetus than their spouses. Most of participants believed that their pregnancy would continue after amniocentesis. However, they also stated that they were prepared for an abortion. Uncertainty and tension were two significant emotions experienced by couples while waiting for the test results. For the majority of women (80%) and men (42.3%) the strongest support was provided by their spouses during this period. In summary, we can conclude that the test did have a major psychological impact on both women and their spouses, but did not have a negative impact on their coping mechanisms. CONCLUSION: The psychological impact of amniocentesis on women and their spouses does not constitute a major obstacle to their ability to cope. However, a certain number of couples reported feelings of uncertainty, tension and anxiety about fetal injury. We strongly suggest that counseling should be given to high-risk families and that prenatal/antenatal care units must be established.

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.

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.

The mid-trimester genetic sonogram.

The genetic sonogram is a composite algorithm combining multiple individual markers to increase Down syndrome risk prediction. Transformation of sonographic information into a standard mathematical format represented an early challenge that has now been surmounted. Using increasingly sophisticated mathematical techniques, individual patient risk can be estimated. High diagnostic accuracy comparable to standard mid-trimester serum algorithms has been reported. Most recently, a few studies have reported the ability to combine serum and biochemical markers to achieve diagnostic accuracy comparable to first-trimester screen. Even fewer studies have reported combinations of ultrasound and maternal urine markers. While it is clear that consistently high sensitivity and specificity for Down syndrome can be achieved, almost all the studies are based on high-risk groups. Studies in low-risk populations have suffered from lack of standardization. The relevance of genetic sonogram in a low-risk population thus remains to be proven. The most significant challenge, however, remains the development of uniform and reproducible sonographic and measurement standards. This is likely to be the most important factor in optimizing the accuracy of the mid-trimester genetic sonogram.