Do small for gestational age fetuses have placental pathologies?

PURPOSE: Although small for gestational age (SGA) does not cause adverse perinatal outcomes, the placental pathology for fetal growth restricted (FGR) and SGA fetuses is still unknown. The aim of this study is to evaluate the differences between placentas of early onset FGR, late onset FGR, SGA, and appropriate for gestational age (AGA) pregnancies in the manner of microvasculature and expression of anti-angiogenic PEDF factor and CD68. METHODS: The study included four groups (early onset FGR, late onset FGR, SGA and AGA). Placental samples were obtained just after labor in all of the groups. Degenerative criteria were investigated with Hematoxylin-eosin staining. Immunohistochemical evaluation with H score and m RNA levels of Cluster of differentiation 68 (CD68) and pigment epithelium derived factor (PEDF) were performed for each group. RESULTS: The highest levels of degeneration were detected in the early onset FGR group. In means of degeneration SGA placentas were found to be worse than the AGA placentas. The intensity of PEDF and CD68 were significant in early FGR, the late FGR and SGA groups compared to the AGA group (p < 0.001). The mRNA level results of the PEDF and CD68 were also parallel to the immunostaining results. CONCLUSION: Although SGA fetuses are considered constitutionally small, the SGA placentas also demonstrated signs of degeneration similar to the FGR placentas. These degenerative signs were not seen among the AGA placentas.

A new technology for the treatment of premature ovarian insufficiency: Cell sheet.

Premature ovarian insufficiency (POI) is defined as the development of hypergonadotropic hypogonadism before the age of 40 with definitive treatment being absent. In the current study, we aim to compare the efficacy of the cell sheet method with an intravenous (IV) application of adipose-derived mesenchymal stem cells (AdMSCs) to the POI with an animal model. In the current prospective study, 6-to-8-week-old Sprague Dawley rats were generated four groups: (i) a control group in which only PBS was administered; (ii) an only-POI group generated by cyclophosphamide; (iii) a POI group treated by way of IV AdMSCs; and (iv) a POI group treated by way of the cell sheet method. Twenty-eight days after an oophorectomy was performed, intracardiac blood was taken. Follicle count, immunohistochemical examination for GDF9, BMP15, and TUNEL were conducted, gene expressions of GDF9 and BMP15 were examined, and E2 was measured in the serum samples. With hematoxylin-eosin, in the third group, multi oocytes follicles were the most remarkable finding. In the fourth group, most of the follicles presented normal morphology. GDF9 involvement was similar between the first and fourth groups. BMP-15 immunoreactivity, in contrast to fourth group, was weak in all stages in the second and third groups. The current attempt represents a pioneer study in the literature in which a cell sheet method is used for the first time in a POI model. These results suggest that the cell sheet method may be a feasible and efficient method for the stem cell treatment of models with POI and could be a new treatment approach in POI.

A review of ex vivo placental perfusion models: an underutilized but promising method to study maternal-fetal interactions.

Studying the placenta can provide information about the mechanistic pathways of pregnancy disease. However, analyzing placental tissues and manipulating placental function in real-time during pregnancy is not feasible. The ex vivo placental perfusion model allows observing important aspects of the physiology and pathology of the placenta, while maintaining its viability and functional integrity, and without causing harm to mother or fetus. In this review, we describe and compare setups for this technically complex model and summarize outcomes from various published studies. We hope that our review will encourage wider use of ex vivo placental perfusion, which in turn would generate more knowledge to improve pregnancy outcomes.

Does Exposure of Smart Phones during Pregnancy Affect the Offspring's Ovarian Reserve? A Rat Model Study.

OBJECTIVE: We investigated the effect of prenatal exposure to smart phone radiation and the protective effect of omega-3 on ovarian reserve of offspring. Methods: 24 pregnant Wistar albino rats were divided into four groups. Group-I received neither radiofrequency (RF) radiation nor omega-3, group-II received RF, group-III received RF radiation and 300 mg omega-3 and group-IV received RF radiation and 600 mg Omega-3 till birth. At 42 days, bilateral oophorectomy was performed on all female offspring for follicle count and immunohistochemical staining (GDF9, FOXO1 and TUNEL). Results: Group-II had significantly lower mean number of primordial (p = 0.006), secondary follicles(p = 0.003) and a higher atresia score. Group-III variables were comparable with group-I variables. Group-IV had statistically higher median number of atretic follicles than group-I (p = 0.023). Conclusions: Ovarian reserve of offspring diminished with RF exposure during pregnancy. Omega-3 supplementation during pregnancy may reduce the potential premature ovarian failure.

Is cervical swab an efficient method for developing a new noninvasive prenatal diagnostic test for numerical and structural chromosome anomalies?

Background/aim: Prenatal diagnosis is vital to obtain healthy generation for risky pregnancies. There have been several approaches, some of which are routinely applied in clinics to evaluate the possible prenatal deficiencies and/or diseases. In the present study, we aimed to isolate the fetal cells from endocervical samples and try to identify possible anomalies which were proved by Amniocentesis (AS) and chorionic villus sampling (CVS) methods. Materials and methods: Endoservical specimens were collected from 100 pregnant women. Cells were separated in parallel by fluorescence-activated cell sorting (FACS) and magnetic-activated cell sorting (MACS) using human leukocyte antigen (HLA) G233 and placental alkaline phosphatase (PLAP) antibodies. CMA (comprehensive meta-analysis) were carried out and male fetuses were confirmed with Sex determining region Y (SRY) amplification. Results: The percent of HLA G233 and placental and placental alkaline phosphatase (PLAP) positive cells were 4.55% and 84.59%, respectively. The percent of cells positive for both markers was 14.75%. CMA analyses were not informative. (SRY) was amplified in 67% of the samples. Conclusion: However, the success rate of the both cell sorting and scanning of DNA anomalies by aCGH and/or RT-PCR was limited, preventing the applicability of this proposal in the clinics. Still, the success of the proposed method depends on the development of the novel fetal cell-specific antibodies and the improvements in the sorting systems.

A cross-sectional study in non-anaemic pregnant women in Turkey to assess necessity of iron supplementation.

BACKGROUND: Iron deficiency is the most common cause of anaemia in pregnancy. Guidelines recommend different threshold values for iron supplementation. AIMS: To determine trimester-specific reference ranges for haematological values (haemoglobin, hematocrit and ferritin) in healthy pregnant women who have not used any iron supplementation during pregnancy to guide future iron treatment. METHODS: A prospective cross-sectional study was carried out on 168 pregnant women aged 18-45 years, with singleton pregnancies in the first trimester, Hb ≥ 11 g/dL and ferritin ≥ 12 µg/L, and not using iron supplementation. Multiple pregnancies, pregnancies with obstetric complications and smokers were excluded from the study. Mean haemoglobin (Hb) and ferritin values, trimester-specific reference ranges and percentile values of Hb and ferritin were determined for each trimester. The normality of the variables was tested using the Kolmogorov-Smirnov test. RESULTS: Mean Hb decreased significantly between trimesters from 12.6 to 11.9 and then 11.5 g/dL. In addition, Hb, hematocrit and ferritin decreased significantly from the first to the second trimester (P < 0.001 for all) but stayed comparable between the second and third trimesters (P = 0.246, P = 0.575, P = 0.408, respectively). The lower reference value for Hb was calculated as 10.67, 10.08 and 9.18 g/dL for 10-14, 20-24 and 30-34 gestational weeks respectively. CONCLUSION: This pioneer study allows us to understand that iron supplementation may not be needed as any decrease is due to physiological haemodilution. These results may prevent unnecessary iron prescription during pregnancy.

Prevalences of subclinical and overt hypothyroidism with universal screening in early pregnancy.

PURPOSE: To reveal the prevalence of subclinical and overt hypothyroidism among Turkish population during pregnancy. Also to investigate the prevalence of hypothyroidism using ATA 2017 criteria. METHODS: This is a cross-sectional study. Patients were consisted of 1416 consecutive pregnant women who were universally screened for thyroid disease in their first trimester between 2013 and 2015. Thyroid-stimulating hormone (TSH) and free T4 (FT4) levels were analyzed during the first antenatal visit (before 12 weeks of gestation). We compared different cutoffs for TSH. We further determined the 2.5th and 97.5th percentiles for TSH and FT4. RESULTS: Initially, the cutoff of 2.5 IU/ml was selected. Accordingly, 305 women (22.3%) had subclinical hypothyroidism and 22 (1.6%) was diagnosed with overt hypothyroidism. When the cutoff was increased to 4 IU/ml, only 40 (2.9%) women were diagnosed with hypothyroidism. Prevalences of overt hypothyroidism and subclinical hypothyroidism were 0.6% and 2.3%, respectively. CONCLUSION: Universal screening of pregnant women with TSH, using the 2.5 mIU/L cutoff; one in four women was found to be a candidate for thyroid hormone replacement in our cohort. When the cutoff was determined to be 4 mIU/L, prevalence of hypothyroidism decreased approximately 10 times.

Fetal Cell Microchimerism; Normal and Immunocompromised Gestations in Mice.

Objective: To compare fetal cell microchimerism in normal and immunocompromised gestations. Materials and methods: The study consists of two groups of mature female mice. In the control group and the immunocompromised study group, 5 mg of saline and cyclosporine were injected intraperitoneally, respectively. In the second step, all female mice were mated with "Actine-Luc (+) green fluorescent protein (GFP)" transgenic male mice. Immunohistochemical studies (ALPL-antiluciferase, cytokeratin-antiluciferase, and CD 105-antiluciferase) were carried out on maternal liver, skin, and lung tissues at 6-7th and 14-15th gestational days, and postpartum 3-4th, 12th, and 18-24 months. Results: GFP (+) cells were detected in maternal liver and skin but not in lung tissue. Liver was the most affected tissue. GFP was found to be more intense in the immunocompromised group. Conclusion: Fetal microchimerism was demonstrated in maternal liver and skin and found to be more intensive in the immunocompromised group.

Does ischemia reperfusion affect fecundability in a rat model?

BACKGROUND: Adnexal torsion constitutes 2.7% of all gynecological emergencies. Because normal follicular growth has been demonstrated after examination of surgical specimens retrieved from oophorectomies, organ-sparing strategy has gained more popularity irrespective of the appearance of the ovary. However, the functionality of the remaining follicles has not been known. The aim of the study was to evaluate the effect of ischemia-reperfusion on fecundability in a rat model with adnexal torsion. METHODS: A total of 30 female adult Wistar albino rats were assessed. In the first laparotomy, right ovaries were twisted for 8 (Group I, n = 10) or 24 (Group II, n = 10) hours. Second laparotomy was performed to untwist the torsion side and oophorectomy to the other side. In the control group (Group III, n = 10), left ovaries were removed and right ovaries were kept without any intervention. After 30 days from the last operation, female rats were mated for 10 days and euthanized 4 days later. Fecundability was calculated using beta-human chorionic gonadotropin (hCG) levels for detection of pregnancy rates. RESULTS: The mean beta-hCG values in control, 8-hour, and 24-hour groups between pregnant rats were 19.8 ± 26.02, 11.7 ± 0.17, and 22.97 ± 11.87 mIU/mL, respectively. Whereas two out of 10 rats (20%) conceived in the 8-hour group, three out of 10 rats (30%) got pregnant in the 24-hour group. In total, whereas five out of the 20 rats got pregnant in the experimental groups, in the control group, seven out of 10 subjects conceived (25% vs 70 %, p = 0.018). CONCLUSION: Although there was a statistical difference between experimental and control groups, statistical significance was not reached among 8-hour and 24-hour torsion subgroups. In this context, patients with torsion but treated with detorsion should be further investigated for their fecundability potency and be informed accordingly.

Examination of cervical swabs of patients with endometriosis using Fourier transform infrared spectroscopy.

PURPOSE: There is no established non-invasive method to diagnose patients with endometriosis. As a nondestructive type of radiation, infrared light might be used for discrimination by causing vibration of the covalent bonds of the molecules when absorbed by the tissues. The aim of the study was to test whether cervical swab can be used to diagnose women with endometriosis using Fourier transform infrared spectroscopy (FTIR). METHODS: In this prospective case-control study, women between 18-45 years old and undergoing laparoscopy due to various reasons were recruited (n = 20). According to the findings during laparoscopy, patients were stratified as stage I-II or stage III-IV endometriosis groups. Women lacking any visible lesions of endometriosis were recruited as controls. A cervical swab was taken from all patients just before the surgical procedure and pulled into a tube containing saline solution. FTIR spectra were obtained and the fingerprint region (1750-850 cm-1) was used for analyses. RESULTS: Finally, three samples in stage I-II, five samples in stage III-IV and five samples in the control group were analyzed. Hierarchical cluster analysis and principal component analysis were performed as the chemometric method. A total of ten observable peaks were detected in the absorbance spectra of samples. The peaks at 1450 and 1405 cm-1 originating from lipids and proteins significantly increased in the stage III-IV endometriosis group when compared with controls. In addition, nucleic acid/carbohydrate ratio was significantly lower in the stage I-II group indicating that the alteration of the carbohydrate level might be important. CONCLUSIONS: Examination of cervical swab with FTIR spectroscopy might be a proper candidate for a non-invasive diagnostic approach of endometriosis.

Fetal intraabdominal umbilical vein varix: antenatal diagnosis and management.

OBJECTIVE: Fetal intraabdominal vein varix (FIUVV) is a sonographic finding with unknown prevalence. We aimed to point out this particular abnormality and review possible associations and complications which may arise. METHOD: We performed an unrestricted literature search via PubMed and included all cases diagnosed with FIUVV. CASE PRESENTATION: A 24-year-old, gravida 1 para 0 woman was referred to our clinic with possible diagnosis of FIUVV. We confirmed the diagnosis and detailed sonogram was normal. Beyond the gestational age of 32 weeks, intruterine growth restriction became evident. Close fetal surveillance was performed. We did not detect any thrombus formation within the varix or signs of cardiac decompansation during these visits. Delivery was planned after completion of 37 weeks. A healthy baby weighing 2100 g was delivered and discharged without any complications. CONCLUSION: It is generally accepted that fetal anatomic survey is necessary after detection of FIUVV. Karyotyping could be performed for those cases associated with additional structural malformations. Close surveillance of fetal well being and growth is important. Possibility of thrombus formation within the varix should be kept in mind.

Prevalence of gestational diabetes mellitus evaluated by universal screening with a 75-g, 2-hour oral glucose tolerance test and IADPSG criteria.

OBJECTIVE: To determine the prevalence of gestational diabetes mellitus (GDM) and its association with maternal age among Turkish women diagnosed by International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria. METHODS: A cross-sectional study was conducted in 2013-2015 among non-diabetic pregnant women aged 18-49 years who were universally screened for GDM by IADPSG criteria. The percentage of women meeting each diagnostic threshold and the prevalence of GDM by age group were calculated. Linear trends were evaluated by logistic regression. RESULTS: Among 1434 women screened, 159 (11.1%, 95% confidence interval 9.5%-12.7%) were diagnosed with GDM; eleven of these women had been diagnosed according to a fasting glucose level in the first trimester. The prevalence of GDM was 6.6% (10/151), 7.3% (37/507), 8.8% (42/479), 16.7% (45/270), and 35.2% (25/71) among women aged younger than 25, 25-29, 30-34, 35-39, and 40 years or older, respectively. GDM prevalence increased with age (P<0.001). The numbers of women diagnosed with GDM in the second trimester who exceeded one, two, and three thresholds of the 2-hour oral glucose tolerance test were 66 (44.6%), 52 (35.1%), and 30 (20.3%), respectively. CONCLUSION: Prevalence of GDM was correlated with maternal age. Most women diagnosed in the second trimester exceeded the threshold at only one of the three timepoints.

Age related normogram for antral follicle count in general population and comparison with previous studies.

OBJECTIVE: To construct antral follicle count (AFC) nomogram of general population for every age and to compare our data with previous studies to assess whether available AFC nomograms present any geographical inconsistency. STUDY DESIGN: A prospective cross-sectional study was conducted to document AFC nomogram among women in 20-50 years with regular menstrual bleeding. Patients admitted with hirsutism, menstrual irregularity, diagnosis of current/history of endometrioma and hormonal drug use within the last 6 months were excluded. For the final analysis, a total of 381 eligible women were recruited in which all scanning was performed in the early follicular phase. The 25th, 50th and 75th percentiles were compared with previous nomogram. RESULTS: The mean decrease of AFC in each year was 0.41. Among the age groups, there were no statistical significance between 20-24, 25-29 and 30-34, whereas decline in AFC was obvious after 35 years and beyond. The figures comparing our data and previous studies depicted similar steady decline at 25th, 50th and 75th percentiles. CONCLUSION: The current age related nomogram presented a steady decline in AFC that became significant after 35 years in otherwise healthy women with regular menstrual bleeding. Those percentiles might be used as a reference guide to point out the current status of ovarian reserve for a given woman. Additionally, producing nomogram might enforce using percentiles instead of constant thresholds to define various medical conditions such as polycystic ovarian morphology or diminished ovarian reserve. However, longitudinal data with larger sample size are still needed for the validation of those percentiles.

Assessment of Cervicovaginal Cancer Antigen 125 Levels: A Preliminary Study for Endometrial Cancer Screening.

AIM: We primarily aimed to compare the levels of serum and cervicovaginal cancer antigen 125 (CA 125) in women with and without endometrial carcinoma in order to reveal whether cervicovaginal CA 125 could be used as a non-invasive method. METHODS: A preliminary case-control study was designed. The study group consisted of patients who were operated for endometrial adenocarcinoma or endometrial intraepithelial neoplasia. The control group consisted of patients who underwent surgery for benign gynecological diseases. Serum and cervicovaginal secretions were immediately collected before surgery to compare levels of CA 125. RESULTS: The mean cervicovaginal CA 125 levels in patients with endometrial cancer and controls were 1,598.1 ± 1,691.1 versus 947.0 ± 1,282.7 U/ml, respectively (p = 0.016). Whereas area under receiver operating characteristic curve was 0.62 for serum CA 125, it was 0.68 for cervicovaginal CA 125. The optimal threshold of CA 125 in cervicovaginal secretion was calculated to be 575 U/ml, which detected endometrial precancer or cancer with sensitivity of 78% and specificity of 57%. The positive and negative predictive values for this threshold were 38.7 and 88.2%, respectively. CONCLUSION: In conclusion, detection of CA 125 in cervicovaginal secretion has a potential role for the non-invasive screening of endometrial precancers and cancers.

The impact of adnexal torsion on antral follicle count when compared with contralateral ovary.

STUDY OBJECTIVE: In women with adnexal torsion, there is an absence of data whether ovarian reserve is affected when treated by detorsion and conservative surgery. We aimed to evaluate ovarian reserve by counting the antral follicles and estimating the ovarian volume in the operated side compared with the contralateral ovary. DESIGN: A case-control study (Canadian Task Force classification II-2). SETTING: In vitro fertilization center, Hacettepe University Faculty of Medicine and Etlik Zubeyde Hanim Women's Health and Research Hospital, Ankara, Turkey. PATIENTS: Patients who underwent conservative surgery because of adnexal torsion between January 2008 and August 2012 were retrospectively investigated from patient files and computer-based data. Eighteen patients were eligible for the study protocol and further evaluated for their ovarian reserve with ultrasonography. INTERVENTIONS: Comparing ovarian reserve in the torsioned and contralateral sides with ultrasonography by physicians who were blind to the previously operated side. MEASUREMENT AND MAIN RESULTS: The mean age was 28.3 ± 5.8 years. The mean antral follicle count on the operated and contralateral ovaries were 12.3 ± 8.4 and 11.3 ± 7.4, respectively (p = .23). The respective figure for ovarian volume was 7.6 ± 4.2 and 9.1 ± 5.3 mL (p = .063). Among 3 patients seeking to become pregnant, 1 of them conceived spontaneously and one achieved pregnancy with clomiphene citrate use. CONCLUSION: The finding of the current study suggests that ovarian reserve reflected by the antral follicle count is not compromised in patients treated with detorsion of the twisted adnexa.

Lymphovascular space involvement is the sole independent predictor of lymph node metastasis in clinical early stage endometrial cancer.

PURPOSE: To determine clinicopathological risk factors associated with lymph node metastasis in endometrial cancer (EC). METHODS: Clinicopathological data of patients who underwent comprehensive surgical staging for clinical early stage EC between 2001 and 2010 at Hacettepe University Hospital was retrospectively reviewed. RESULTS: Two hundred and sixty-one patients were included. There were 26 patients (10.0%) with lymph node metastasis. Of these, 14 (5.4%) had pelvic lymph node metastasis, 8 (3.1%) had both pelvic and paraaortic lymph node metastasis, and 4 (1.5%) had isolated paraaortic metastasis. Univariate analysis revealed tumor size >2 cm, type II cancer, grade III histology, cervical stromal invasion, deep myometrial invasion, positive peritoneal cytology, adnexal involvement, serosal involvement, and presence of lymphovascular space involvement (LVSI) as significant clinicopathological factors associated with retroperitoneal lymph node metastasis. For paraaortic metastasis either isolated or with pelvic lymph node metastasis, significant factors were grade III disease, cervical stromal invasion, deep myometrial invasion, positive peritoneal cytology, adnexal involvement, serosal involvement, pelvic lymph node metastasis, and presence of LVSI. The only factor associated with isolated paraaortic lymph node metastasis was LVSI. Multivariate analysis revealed LVSI as the only independent factor for both retroperitoneal and paraaortic lymph node metastasis (odds ratio 14.9; 95% confidence interval 3.8-59.0; p < 0.001, and odds ratio 20.9; 95% confidence interval 1.9-69.9; p = 0.013, respectively). CONCLUSION: Lymphovascular space involvement is the sole predictor of lymph node metastasis in EC. Therefore, LVSI status should be requested from the pathologist during frozen examination whenever possible to consider when a decision to perform or omit lymphadenectomy is made.