Human placental trophoblast progenitor cells (hTPCs) promote angiogenesis and neurogenesis after focal cerebral ischemia in rats.

INTRODUCTION: Reduction of blood flow below a threshold value in brain regions locally or globally is called cerebral ischemia and proper treatment requires either the restoration of normal blood flow and/or the administration of neuroprotective therapies. Human trophoblast progenitor cells (hTPCs) give rise to the placenta and are responsible for the invasion and vascular remodeling of the maternal vessels within the uterus. Here, we tested whether hTPCs promoted to differentiate along neural lineages may exhibit therapeutic properties in the setting of cerebral ischemia in vivo. MATERIALS AND METHODS: Cerebral ischemia was generated in rats via middle cerebral artery occlusion and, after 24 h, hTPCs were injected systemically via tail vein. Animals were sacrified at Day 3 or 11. RESULTS: TTC staining indicated that infarct volumes were smaller in hTPC treated animals. Visible myelin recovery was observed in the hTPC injected group with Luxol Fast Blue staining. On Day 11 after hTPC transplantation, DLX5 and VEGF expression, as well as 2 and 10 d after hTPC transplantation, NKX2.2 were significantly increased; while LHX6, Olig1, PDGFRα, VEGFR1 and VEGFR2 showed trends toward improved expression in brain tissue via immunoblot analysis. Neuron-like differentiated cells were positive for both NeuN and Cresyl Violet staining. CONCLUSION: Here, we demonstrate for the first time that hTPCs enhance the expression of angiogenic and neurogenic factors in rat brain after stroke. Transplantation of hTPCs could form the basis of novel therapeutic approaches for the treatment of stroke in the clinical setting.

High prevalence of vitamin D deficiency in Turkish women undergoing in vitro fertilization: A descriptive study.

The authors' aim in this study was to determine the vitamin D levels of Turkish women who were undergoing in vitro fertilization (IVF). The study design was a descriptive cohort study of a total of 208 infertile women at an IVF center in Turkey. Our findings showed that 4.3% of the women had a replete vitamin D level, 23.6% of the women had insufficient vitamin D levels, and 72.1% of women had deficient vitamin D levels. Our findings suggest that much more effective vitamin D support programs should be implemented for women who are seeking to become pregnant.

[Evaluation of Microscopic Examination, Culture and Polymerase Chain Reaction Tests in the Diagnosis of Trichomonas vaginalis Infection]. / Trichomonas vaginalis Enfeksiyonu Tanisinda Mikroskobik Inceleme, Kültür ve Polimeraz Zincir Reaksiyonu Testlerinin Degerlendirilmesi.

Sexually transmitted infections (STIs) are important as a public health problem all over the world. There are some difficulties in prevention and control programs of STIs due to clinical and laboratory diagnostic problems.The most common STIs are Chlamydia trachomatis infections, trichomoniasis and gonorrhea. The study aimed to investigate the direct microscopic examination, culture and polymerase chain reaction (PCR) tests in the diagnosis of Trichomonas vaginalis infection; to determine other microbiological agents that may cause vaginal discharge and to evaluate the various social variables in women with vaginal discharge admitted to the outpatient clinic of Obstetrics and Gynecology in Akdeniz University Hospital. Two hundred and fifteen patients were enrolled in the study. The socio-demographic features of the patients were recorded. Vaginal/endocervical swab specimens taken from patients were evaluated by microscopic examination. Swab specimens were inoculated into blood agar, MacConkey agar and chocolate agar for bacterial culture. Modified Trichosel broth with 5% horse blood (Becton Dickinson, USA) was used for Trichomonas spp. culture. The presence of C.trachomatis, Neisseria gonorrhoeae, and T.vaginalis in swab samples were investigated by multiplex PCR assay (BD Max CT/GC/TV, Becton Dickinson, USA). At least one pathogen was detected among 65 (30.3%) samples. T.vaginalis was detected by microscopic examination and PCR in four of 215 (1.9%) patients. Existence of yeast morphology was observed in 21 (9.8%) specimens by microscopic examination. Twenty four (11.2%) patients were diagnosed as bacterial vaginosis microscopically according to Nugent score system. Candida species grew in 32 (14.9%) and Streptococcus agalactiae grew in 2 (0.9%) of the specimens. C.trachomatis was detected in 2 (0.9%) samples and N.gonorrhoeae in 1 (0.5%) sample by PCR. In this study, 95.3% of the patients were married and 96.7% had only one sexual partner in the mean time. The rate of detection of pathogens were statistically higher in women who have had two or more pregnancies (p<0.05). In our study, T.vaginalis together with N.gonorrhoeae and C.trachomatis were investigated by PCR method in women with vaginal discharge. The use of multiplex PCR test allowed simultaneous investigation of multiple pathogens in the patient samples.

Dehydroepiandrosterone supplementation attenuates ovarian ageing in a galactose-induced primary ovarian insufficiency rat model.

PURPOSE: Almost every female classic galactosemia patient develops primary ovarian insufficiency (POI). The unique pathophysiology of classic galactosemia, with a severely reduced follicle pool at an early age, requires a new therapeutic approach. This study evaluated the effect of dehydroepiandrosterone (DHEA) on ovarian tissue in a galactose-induced POI rat model. METHODS: Pregnant rats were fed with either a normal or a 35% galactose-containing diet from day 3 of conception continuing through weaning of the litters. Galactose-exposed female offspring were further divided into 5 groups on PND21. The first group received no application. Treatment groups were fed orally by gavage once daily with sesame oil (group 2), or DHEA at doses of 0.1 mg/kg (group 3), 1 mg/kg (group 4) or 10 mg/kg (group 5) until PND70. Fertility rates of mothers with galactosemia, body weights (BWs), and ovarian weights of the litters from PND21 to PND70 were recorded. Ovarian follicle count, immunohistochemistry for proliferation and apoptosis marker expressions and TUNEL for cell death assessment were performed in offspring ovaries. RESULTS: Decreased fertility, ovarian/body weights were observed under galactosemic conditions, together with decreased follicle number and increased atresia. Improved postnatal development, primordial follicle recruitment and follicular growth were observed after DHEA treatment. After DHEA treatment, the expression of Ki67 protein was found to be increased; elevated expression of cleaved-caspase-3 under galactosemia was found to be reduced. CONCLUSIONS: Our data suggests that DHEA treatment may be a potentially useful clinical therapy to improve ovarian ageing in women with POI-induced by galactosemia.

Does obesity have detrimental effects on IVF treatment outcomes?

BACKGROUND: The aim of this study was to investigate the influence of body mass index (BMI) on the in vitro fertilization (IVF) treatment outcomes in a cohort of women undergoing their first IVF, using an intracytoplasmic sperm injection (ICSI). METHODS: This retrospective cohort study included 298 cycles from women younger than 38 years old undergoing IVF-ICSI at a university infertility clinic. The treatment cycles were divided into three groups according to the BMI of the women involved: normal weight (18.5 ≤ BMI < 25 kg/m(2), 164 cycles), overweight (25 ≤ BMI < 30 kg/m(2), 70 cycles), and obese (BMI ≥ 30 kg/m(2), 64 cycles). The underweight women (BMI < 18.5 kg/m(2)) were not included in the analysis due to small sample size (n = 22). The patient characteristics and IVF-ICSI treatment outcomes were compared between the BMI groups. RESULTS: The total gonadotropin dose (p <0.001) and duration of stimulation (p = 0.008) were significantly higher in the obese group when compared to the normal BMI group. There were no significant differences across the BMI categories for the other IVF-ICSI cycle outcomes measured, including the number of retrieved oocytes, mature oocytes, embryos suitable for transfer, proportion of oocytes fertilized, and cycle cancellation rates (p >0.05 for each). Additionally, clinical pregnancy, spontaneous abortion, and the ongoing pregnancy rates per transfer were found to be comparable between the normal weight, overweight, and obese women (p >0.05 for each). CONCLUSION: Obese women might require a significantly higher dose of gonadotropins and longer stimulation durations, without greatly affecting the pregnancy outcomes.

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.

Assessment of women who applied for the uterine transplant project as potential candidates for uterus transplantation.

AIM: To review the medical charts of women who applied for the uterine transplant project from June 2008 to June 2011 in our hospital retrospectively (18-40 years). METHODS: The data for 144 women were retrieved, and information was collected on the etiology of uterine factor infertility(UFI); ovarian reserve tests; and accompanying anatomic, infectious, genetic and endocrinological problems. RESULTS: There were 119 patients with primary amenorrhea and uterovaginal agenesis and 25 patients with a history of hysterectomy. The complete Müllerian agenesis patients formed the largest group of the UFI patients with better anti-Müllerian hormone levels and antral follicle count. Anatomical anomalies such as a solitary pelvic kidney may accompany Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) and impede surgery. The mean ages in MRKH, hysterectomy and complete androgen insensitivity syndrome (CAIS) cases were 24.7, 35.0 and 34.4 years, respectively. The karyotype analysis showed 46XX (MRKH) in 109 patients and 46XY (CAIS) in 10 of the primary amenorrhea patients. CONCLUSION: Hysterectomy may deteriorate ovarian blood flow and decrease ovarian reserve. Fertility preservation may be considered in young woman undergoing hysterectomy.

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.

Effect of injectable medroxyprogesterone acetate and etonogestrel implants on GABA-A and serotonin receptors in white and gray matter of the brain: experimental study in rats.

The aim of this study was to evaluate the time-dependent effect of progesterone-only contraceptives on the brain and to obtain an improved understanding of mood disorders experienced under this medication. A total of 66 Wistar albino rats were divided into three groups: etonogestrel (ENG) implant (group 1, n = 30); depot medroxyprogesterone acetate (MPA)-injectable (group 2, n = 30); and control (group 3, n = 6) groups. Groups 1 and 2 were each divided into five subgroups, which were examined every 10 d for up to 50 d after medication administration, to evaluate its time-dependent effect. There was no difference in terms of gamma-aminobutyric acid (GABA) and serotonin immunohistochemical staining in white and gray matter among the subgroups of group 1. In group 2, there was a significant decrease in serotonin receptor staining intensity in white and gray matter on day 50, when compared to the control group (p = 0.041). When the subgroups of group 2 were compared, there was a significant decrease in serotonin receptor staining intensity in white and gray matter on days 40 and 50 when compared to day 10. In conclusion, we showed that ENG and MPA have no effect on apoptosis and GABA-A receptors in the brain. We also showed that MPA has time-dependent effects on serotonin receptors, which may be a possible mechanism involved in mood disorders during long-term usage of injectable progesterone-only contraceptives.

Reproductive Outcomes of Dual Trigger versus hCG Alone in Women Undergoing In Vitro Fertilization with Fresh Embryo Transfer Cycles.

Aim: To investigate the effect of the triggering method on the results of fresh embryo transfer in patients who underwent gonadotropin-releasing hormone antagonist cycles. Methods: The study was conducted retrospectively at a university-based tertiary reproductive center. The sample consisted of a total of 295 patients, of whom 111 were in the human chorionic gonadotropin (hCG) trigger group and 184 were in the dual trigger group. The main outcome measure of this study was the live birth rate, and secondary outcomes were the implantation rate, clinical pregnancy rate, miscarriage rate, and good-quality embryo rate. Results: Patient demographics and baseline characteristics did not significantly differ between the dual and hCG trigger groups. The results also indicated statistically nonsignificant differences between the two groups in terms of the number of oocytes retrieved (p > 0.05), the number of mature oocytes (p > 0.05), and the fertilization rate (p > 0.05). The number of good-quality embryos (p=0.002) was higher in the dual trigger group compared with the hCG trigger group. However, the rates of clinical pregnancy and live births did not significantly differ between the groups (p > 0.05). Conclusions: Although the number of total and high-quality embryos obtained was higher in the dual trigger group, there were no significant differences between the two groups in terms of pregnancy outcomes. The fresh embryo transfer yielded similar rates of implantation and live births in both trigger groups.

Demographic distributions and clinical results of assisted reproduction techniques in Turkey in 2019: a descriptive survey.

Objective: The aim of this study was to describe characteristics and outcomes of assisted reproductive technology (ART) cycles performed in 2019 in Turkey. Material and Methods: One-hundred and sixty-five ART centers in Turkey were invited to submit data. The survey was sent to center directors via e-mail with anonymous links by Qualtrics™. The survey involved questions about their patient characteristics, clinical practices, and outcomes. Results: Forty-one (24.8%) centers responded to e-mails, and data gathered from 25 centers was included in the analyses. In 25 centers, 18,127 fresh or frozen transfers were carried out during the study period, of which 7796 (43.0%) were fresh and the rest were either frozen (45.2%) or embryo transfers (ET) with preimplantation genetic testing (PGT) (11.8%). The live birth rate per ET was as 30.6%, 40.1%, and 50.7% in fresh, frozen and PGT cycles, respectively. A single embryo was transferred in 65.3% of all transfers and singleton live births comprised 86.1% of all deliveries. For cycles with intrauterine insemination, 1407 were started in 2019, and 195 clinical pregnancies, 150 live births with 19 multiple pregnancies occurred. A total of 1513 ART cycles were initiated for foreign patients. Russia (29.6%), Germany (7.4%), Iraq (4.6%), Uzbekistan (3.1%), and Syria (1.4%) were the top five countries with most patients coming to Turkey for ART. Conclusion: The survey results are in parallel with the reports of international institutions and organizations. With repeated editions, the data collected with annual surveys can be used to inform ART practices in the coming years.

Investigation of the relationship between reproductive disorders and chromosomal abnormalities in a large-scale, single-center 10-year retrospective study.

OBJECTIVE: Chromosomal changes are an important cause of reproductive disorders. This study investigated the chromosomal changes and prevalence of pathologies in individuals admitted to our Genetic Evaluation Center over a 10-year period due to a reproductive disorder. MATERIALS & METHODS: The chromosomal findings of 4345 individuals with reproductive disorders who applied to our Genetic Evaluation Center at Akdeniz University in Antalya, Turkey between 2011 and 2021 were retrospectively evaluated. RESULTS: In this study, an abnormal karyotype was found in a total of 138 individuals (87 males and 51 females). Although the incidence of this abnormal karyotype varied among the diseases in the reproductive disorder subgroups, it was most frequently seen in azoospermia (17.0%). Of the 138 abnormalities, 75 were numerical and 54 were structural. The remaining 9 abnormalities consisted of 6 sex reversals and 3 patients with both numerical and structural anomalies. Additionally, the X chromosome was the chromosome most frequently involved in these abnormalities, being observed in 40.6% of patients. CONCLUSION: This 10-year, single-center study involved one of the largest case series in the literature to investigate the subtypes of reproductive disorders and their chromosomal relationship. Although the importance of chromosome analysis has been deemphasized, it is still recommended for use by the guidelines and, as the results of this study demonstrate, is still a highly effective method in the investigation of reproductive disorders. Furthermore, chromosome analysis of individuals diagnosed with a reproductive disorder is also very important in the practice of the increasingly utilized preimplantation genetic diagnosis (PGD).

Human Trophoblast Progenitor Cells Express and Release Angiogenic Factors.

Trophoblast stem cells develop from polar trophectoderm and give rise to the cells that generate the placenta. Trophoblast cells are responsible for the uterine invasion and vascular remodeling during the implantation of the embryo. However this knowledge is not yet to be confirmed for trophoblast progenitor cells (TPCs). In this study, we aimed to demonstrate that human TPCs (hTPCs) express and release angiogenic factors for the first time. TPCs were isolated from the term placenta. Then immunophenotyping was performed by FACS method by analyzing caudal type homeobox 2 (CDX2) and eomesodermin (EOMES). Immunofluorescence staining of CDX2 and EOMES was performed on these cells. Lastly, angiogenesis-related proteins were detected by western blot and ELISA assays. The isolated cells were positive for trophoblast stem cell markers CDX2 and EOMES in 92.5% and 92.7% of cells, respectively showing the characteristics of TPCs. The investigation of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 1 (VEGFR1), and vascular endothelial growth factor receptor 2 (VEGFR2) at protein and mRNA level in comparison with human umbilical vein endothelial cells (HUVECs), revealed that human TPCs (hTPCs) have higher levels of VEGF and VEGFR1 transcripts. Additionally soluble forms of VEGF and VEGFR1 were detected in supernatants of hTPCs. With this information, TPCs seem to be promising for regenerative cell therapies by increasing angiogenesis.

Comparison of markers of ovarian reserve between patients with complete müllerian agenesis and age-matched fertile and infertile controls.

OBJECTIVE: To investigate ovarian reserve in complete müllerian agenesis (CMA) patients and to compare the ovarian reserve of CMA patients with that of age-matched fertile and infertile controls. DESIGN: Prospective cohort study. SETTING: University gynecology outpatient clinic. PATIENT(S): Fifty-eight typical CMA (type A) patients, 8 atypical CMA (type B) patients, 39 fertile patients, and 38 infertile patients were compared for ovarian reserve. INTERVENTION(S): Ovarian reserve was evaluated via antimüllerian hormone (AMH) levels and antral follicle counts (AFCs). MAIN OUTCOME MEASURE(S): Investigation of ovarian reserve in CMA patients and a comparison of the ovarian reserve of the CMA patients with that of age-matched fertile and infertile controls. RESULT(S): Fifty-eight type A and eight type B CMA patients and 39 fertile and 38 infertile control patients were assessed for ovarian reserve. The mean (±SD) ages of the type A and type B CMA patients and the fertile and infertile groups were 25.8 ± 5.3, 33.3 ± 5.9, 32.6 ± 4.8, and 33.9 ± 3.3 years, respectively. After age standardization of the groups, AMH levels and AFCs were found to be lower in the atypical CMA group. The differences in AMH levels and AFC were found to be highly significant. CONCLUSION(S): The present study showed that atypical CMA patients had decreased ovarian reserve compared with age-matched fertile and infertile controls.

Immunolocalization of cell cycle proteins (p57, p27, cyclin D3, PCNA and Ki67) in intrauterine growth retardation (IUGR) and normal human term placentas.

Placental development involves a series of events that depend on the coordinated action of proliferation, differentiation and invasion of trophoblasts. Studies on cell cycle related proteins controlling these events are fairly limited. It is still not fully determined how placental tissue proliferation is affected by intrauterine growth retardation (IUGR). Information on cell cycle related proteins that control these events is limited and how they are affected in IUGR is not fully understood. The aim of this study was to understand the role of cell cycle regulators in IUGR placentas and to determine the spatio-temporal immunolocalization of these cell cycle regulators in human IUGR and normal term placentas. Placental samples were stained immunohistochemically with PCNA, Ki67, cyclin D3, p27 and p57 antibodies and were examined by light microscopy. In all regions of IUGR placentas, PCNA, Ki67 and cyclin D3 staining intensities were statistically significantly decreased compared to normal controls. p27 staining intensity of the IUGR group was statistically significantly increased in villous parts and chorionic plates in comparison with the normal term placentas. Moreover, p57 staining intensity was statistically significantly increased in all parts of the IUGR group compared to controls. The observed placental abnormalities in IUGR placentas may be associated with arrest mechanisms affecting cell proliferation and cell cycle alterations in IUGR.

Fetal circulatory variation in an acute incident causing bradycardia.

Umbilical artery\vein, middle cerebral artery, and ductus venosus Doppler velocimetry were performed at 33 weeks of gestation in the settings of an intrauterine growth restricted fetus during a heart rate deceleration. Interestingly, we recorded a sudden onset redistribution of fetal blood flow with fetal bradycardia. Spontaneous normalization of waveforms was observed once fetal heart rate returned to normal. Our case provides evidence to circulatory variation of a human fetus resulting from an acute incident causing bradycardia.

Fatal Disseminated Tuberculous Peritonitis following Spontaneous Abortion: A Case Report.

We describe a rare case of fatal disseminated tuberculous peritonitis in a young woman with rapid progressive clinical course following spontaneous abortion of 20-week gestation. Clinical and laboratory findings were initially unremarkable. She underwent diagnostic laparoscopy which revealed numerous tiny implants on the peritoneum and viscera. Histopathology showed chronic caseating granulomas, and the tissue culture grew Mycobacterium tuberculosis. At fifth day of the antituberculous treatment multiorgan failure occurred in terms of pulmonary, hepatic, and renal insufficiency. She developed refractory metabolic acidosis with coagulopathy and pancytopenia, and she died of acute respiratory distress syndrome and septic shock on her twelfth day of hospitalization.