Bernard-Soulier Syndrome from the Perspective of the Obstetrician: A Case Report with a Review of the Literature.

OBJECTIVE: Bernard-Soulier syndrome (BSS) is one of the rare inherited platelet disorders that is characterized by macrothrombocytopenia and adhesion abnormality due to the absence or malfunctioning of the membrane GPIb-IX-V complex. There is no high-quality evidence on obstetric management of BSS owing to its rarity. Here we report an uncomplicated delivery of an adolescent with BSS and review the literature on the topic of BSS and pregnancy. METHODS: PUBMED, EMBASE, COCHRANE, and Google Scholar databases were searched up to April 2022 without language and year restriction using the terms "Bernard Soulier" and "Pregnancy". The primary objectives were to evaluate maternal and fetal outcomes. The secondary objectives were to analyze pregnancy complications, gestational age at delivery, mode of delivery, administered prophylaxis, treatment approaches, duration of postpartum hospitalization, and the postpartum requirement of blood and blood product. RESULTS: The patient was a 19-year-old and 39-week pregnant woman who was diagnosed with BSS at the age of 10 by flow cytometry and genetic analysis. Single donor platelet transfusions and oral tranexamic acid were administered as prophylaxis at the peripartum period. She was delivered by cesarean section due to failure of labor. The postpartum period was uneventful for both mother and neonate. In the literature review, postpartum hemorrhage (PPH) was found in 52.9% (27/51) of deliveries. Late PPH occurred more frequently than early PPH (35.3 and 31.4%, respectively). 49% (25/51) of pregnancies had severe thrombocytopenia, and antepartum hemorrhage was observed in 11.8% (6/51) of those. The platelet count was in close relation to antenatal complications. 64.7% (33/51) of the patients were delivered via cesarean section. PPH and late PPH were found to be more common in those who delivered vaginally compared to those who delivered by caesarean section. It was observed that PPH was less common in women who were given prophylaxis in the peripartum period. CONCLUSION: BSS is an inherited macro-thrombocytopathy that may cause adverse maternal and neonatal outcomes. The optimal mode and timing of delivery remain unclear. A multidisciplinary approach with prophylaxis at the peripartum period should be applied.

Metabolomic analysis of endometrial cancer by high-resolution magic angle spinning NMR spectroscopy.

PURPOSE: To analyze endometrial metabolite profiles between patients with endometrial cancer and controls. METHODS: Seventeen (17) women with endometrium cancer and 18 controls were enrolled in this study. 1H HR-MAS (High Resolution-Magic Angle Spinning) NMR (Nuclear Magnetic Resonance) spectroscopy data obtained from endometrial tissue samples of patients with endometrial cancer and control group were analyzed with bioinformatics methods. RESULTS: Principal component analysis (PCA) and the partial least squares discriminant analysis (PLS-DA) score plots obtained with the multivariate statistical analysis of pre-processed spectral data shows a separation between the samples from patients with endometrial cancer and controls. Analysis results suggest that the levels of lactate, glucose, o-phosphoethanolamine, choline, glycerophosphocholine, phosphocholine, leucine, isoleucine, valine, glutamate, glutamine, n-acetyltyrosine, methionine, taurine, alanine, aspartate and phenylalanine are increased in patients with endometrial cancer compared to the controls. CONCLUSION: The metabolomics signature of patients with endometrial cancer is different from that of benign endometrial tissue.

Metabolomics analysis of placental tissue obtained from patients with fetal growth restriction.

AIM: The aim of this study was to determine whether there was a difference in placental metabolite profiles between patients with fetal growth restriction (FGR) and healthy controls. METHODS: The study included 10 patients with FGR diagnosis with 14 healthy controls with both matched maternal age and body mass index. 1 H HR-MAS NMR spectroscopy data obtained from placental tissue samples of patients with FGR and healthy control group were analyzed with bioinformatics methods. The obtained results of metabolite levels were further validated with the internal standard (IS) quantification method. RESULTS: Principal component analysis (PCA) and the partial least squares discriminant analysis (PLS-DA) score plots obtained with the multivariate statistical analysis of preprocessed spectral data shows a separation between the samples from patients with FGR and healthy controls. Bioinformatics analysis results suggest that the placental levels of lactate, glutamine, glycerophosphocholine, phosphocholine, taurine, and myoinositol are increased in patients with FGR compared to the healthy controls. CONCLUSIONS: Placental metabolic dysfunctions are a common occurrence in FGR.

The Definition of the Upper Limit of Adolescent Age in Terms of Adverse Pregnancy Outcomes.

Introduction This study aims to reveal the maternal and neonatal adverse outcomes, associated with adolescent pregnancies in our country, to investigate whether the 20 to 21-year-age group, which is very close to the adolescent age, is similar to the adolescent age group in terms of adverse outcomes, and so to contribute to the definition of the upper limit in adolescent age for pregnancy. Methods Four hundred and twenty-four pregnant women under the 20-year-age, 450 pregnant women at 20 to 21-year-age, and 450 pregnant women between 22 and 25-year-age were included in this retrospective study. Maternal demographic features, clinical characteristics, obstetric complications, maternal outcomes, neonatal complications, and neonatal outcomes were collected from the medical records of the participants. Results There were statistically significant differences between under 20-year-age and 22 to 25-year-age, regarding gestational age at birth, maternal duration of hospitalization after delivery, mode of delivery, preterm delivery rate, very low birth weight, and low birth weight, first minute Apgar score, the presence of transient tachypnea of the newborn. Conclusion The upper age limit for the adolescent age, which is considered risky in terms of maternal and neonatal adverse outcomes, was found to be compatible with the upper age limit, which is 19 years, defined by World Health Organization.

The effect of seminal plasma cadmium and lead levels on semen parameters in male subjects of infertile couples: a prospective cohort study.

The aim of this prospective study was to investigate whether there is a relationship between seminal plasma cadmium (Cd) and lead (Pb) levels and semen parameters in male partners of infertile couples. Two hundred fifty one (251) men recruited with no history of occupational exposure to toxic metals. After semen analysis, seminal Cd and Pb levels were measured using atomic absorption spectrometry. Cadmium levels in men with hypospermia was significantly higher than men with normal semen volume (p = .049). In contrast, there was no statistically significant difference in median seminal Pb levels between men with hypospermia and men with normal semen volume (p = .13). There was no statistically significant association between seminal plasma Cd and Pb levels sperm concentration, motility, morphology and total progressively motile sperm count. These findings suggest that environmental Cd exposure may contribute to low semen volume in male partners of infertile couples.IMPACT STATEMENTWhat is already known on this subject? Toxic metals may adversely affect both male and female reproductive system.What the results of this study add? Seminal plasma cadmium levels in men with hypospermia were statistically significantly higher than men with normal semen volume.What the implications are of these findings for clinical practice and/or further research? Patients should be informed about possible adverse effects of toxic metals.

The role of prokineticins in recurrent implantation failure.

The aim of the present study was to investigate the expression patterns of prokineticins (PROK) and prokineticin receptors (PROKR) in the endometrium of women with recurrent implantation failure (RIF). Fifteen (15) women with RIF and 15 fertile controls were enrolled in this study. Endometrial samples were taken from study participants with an endometrial biopsy cannula during the implantation window. Real time polymerase chain reaction and immunohistochemistry were used to determine PROK/PROKR mRNA expression and protein localization, respectively. PROK1 mRNA levels were 6.09 times higher compared to endometrial samples obtained from women with RIF than in samples obtained from fertile controls, whereas PROKR1 mRNA levels were 2.46 times lower in endometrial samples obtained from women with RIF than in samples from fertile controls. In addition, decreased PROKR1 was supported by immunohistochemistry analysis at protein level. There was no statistically significant difference between women with RIF and fertile controls regarding PROK2 and PROKR2 levels. Altered expression of the PROK1/PROKR1 system could be one of the numerous abnormalities in the endometrium of women with RIF.

Stress in couples undergoing assisted reproductive technology.

PURPOSE: To determine the associations between pre-treatment self-reported stress level, salivary cortisol levels, and clinical pregnancy outcome in couples undergoing assisted reproductive technology treatment (ART). STUDY DESIGN: Seventy-five couples (150 patients) undergoing ART treatment were enrolled in this study. Psychological variables were assessed using the Perceived Stress Scale, Beck Anxiety Inventory, State-Trait Anxiety Inventory, and Beck Depression Inventory. Salivary cortisol levels were obtained from each couple prior to commencing gonadotropin treatment at several times (upon waking and at 15, 30, and 60 min after waking). RESULTS: There was no statistically significant association between the self-reported stress levels and the ART treatment outcome in couples. Women with a successful outcome after ART treatment had higher median salivary cortisol levels than women who had an unsuccessful result [24.7 (19.9-63.1) vs. 20.7 (10.4-30.4), respectively]. There was no statistically significant difference in the median salivary cortisol levels of men in relation to ART treatment outcome. Salivary cortisol levels of the couples were not correlated. CONCLUSIONS: Women who had higher median salivary cortisol levels in the pre-treatment period had a higher clinical pregnancy rate. This result suggests that moderately increased activity of the hypothalamic-pituitary-adrenal axis during ART treatment might be associated with successful conception.

RETROSPECTIVE ANALYSIS OF BORDERLINE OVARIAN TUMORS: OUTCOMES AT A SINGLE CENTER.

We wanted to discuss our experiences in the approach to borderline ovarian tumors, which constitute a group different from epithelial ovarian tumors with respect to their biological structure in line with retrospective information gathered from our cases. A total of 25 patients operated on for the indication of adnexal masses diagnosed as borderline ovarian tumors based on frozen section results were included in our study. Patient age, tumor diameter, tumor markers and surgeries performed were discussed in the light of the literature. Statistical analyses were performed using the SPSS software. The patient mean age was 43.84±11.34 years. The mass was localized in the right (n=13), left (n=11) or both (n=1) adnexal regions. The mean tumor diameter was 12.9±5.84 cm. Histopathologic examination established the diagnosis of serous borderline (n=14 patients) and mucinous borderline (n=11) ovarian tumors. Although the results of our study are consistent with current literature data, a greater number of current studies should be performed on borderline ovarian tumors, which are defined as a class of tumors different from epithelial ovarian tumors.

Metabolomics analysis of follicular fluid in women with ovarian endometriosis undergoing in vitro fertilization.

The purpose of this study was to investigate whether a change in the follicular fluid metabolomics profile due to endometrioma is identifiable. Twelve women with ovarian endometriosis (aged<40 years, with a body mass index [BMI] of <30 kg/m2) and 12 age- and BMI-matched controls (women with infertility purely due to a male factor) underwent ovarian stimulation for intracytoplasmic sperm injection (ICSI). Follicular fluid samples were collected from both of groups at the time of oocyte retrieval for ICSI. Next, nuclear magnetic resonance (NMR) spectroscopy was performed for the collected follicular fluids. The metabolic compositions of the follicular fluids were then compared using univariate and multivariate statistical analyses of NMR data. Univariate and multivariate statistical analyses of NMR data showed that the metabolomic profiles of the follicular fluids obtained from the women with ovarian endometriosis were distinctly different from those obtained from the control group. In comparison with the controls, the follicular fluids of the women with ovarian endometriosis had statistically significant elevated levels of lactate, ß-glucose, pyruvate, and valine. We conclude that the levels of lactate, ß-glucose, pyruvate, and valine in the follicular fluid of the women with endometrioma were higher than those of the controls. Abbreviations: ASRM: American Society for Reproductive Medicine; BMI: body mass index; CPMG: Carr-Purcell-Meiboom-Gill; E2: estradiol; ESHRE: European Society of Human Reproduction and Embryology; ERETIC: electronic to access in vivo concentration; FF: follicular fluid; FSH: follicle-stimulating hormone; hCG: human chorionic gonadotropin; HEPES: 2-hydroxyethyl-1-piperazineethanesulfonic acid; ICSI: intracytoplasmic sperm injection; IVF: in vitro fertilization; NMR: nuclear magnetic resonance spectroscopy; PCA: principal component analysis; PCOS: polycystic ovary syndrome; PLS-DA: partial least squares discriminant analysis; ppm: parts per million; PULCON: pulse length-based concentration determination; TSP: 3-(trimethylsilyl)-1-propanesulfonic acid sodium salt; VIP: variable importance in projection.

Treatment of unruptured cornual pregnancies by local injections of methotrexate or potassium chloride under transvaginal ultrasonographic guidance.

OBJECTIVE: To demonstrate the outcome of intralesional management and show the safety of local treatment of cornual pregnancy. METHODS: Eight patients were treated with local methotrexate or potassium chloride injection. All patients underwent transvaginal ultrasound examination and were diagnosed by the criteria defined by Timor-Tritsch. In the case of fetal heart beat observation, potassium chloride was injected; and in the case of no heart beat detection, methotrexate was used. A follicle aspiration needle was inserted directly into the gestational sac under transvaginal guidance. RESULTS: Although it has been considered to be a risk factor, none of the patients in our study had previous ectopic pregnancy, history of infertility / in vitro fertilization, or cornual pregnancy. One of the patients had a medical history of abortion. In four cases, methotrexate was injected, and three patients received potassium chloride as a local treatment. None of the patients had any complication in the peri- or postoperative period. CONCLUSION: Using a local approach, the treatment agent can reach the area of the cornual pregnancy in high concentrations. Based on this case series, a local approach seems to be an effective and fertility-sparing method for treating unruptured cornual pregnancies.

The impact of thyroid-stimulating hormone levels in euthyroid women on intrauterine insemination outcome.

BACKGROUND: The aim of this study was to examine the effect of thyroid-stimulating hormone (TSH) levels on intrauterine insemination (IUI) outcomes among euthyroid women. METHODS: A retrospective cohort study was conducted. A total of 302 women who started their first IUI cycle in our fertility center were included in this study. The patients were categorized into two groups based on their preconception TSH values: 0.38-2.49 mIU/Land 2.50-4.99 mIU/L. The clinical pregnancy rate was the main outcome parameter. As secondary parameters, we evaluated the differences in spontaneous abortion rate, live-birth delivery rate, and perinatal outcomes according to the preconception TSH threshold (< 2.5 and < 5.00 mIU/L). RESULTS: There was no significant difference between the two groups with respect to clinical pregnancy, miscarriage, and live-birth rates with an odds ratio of 1.67 (95% CI: 0.79-3.53), 1.08 (95% CI: 0.09-13.1), and 1.79 (95% CI: 0.77-4.2), respectively. In addition, there were no significant differences in perinatal outcomes (gestation at delivery, birth weight, and neonatal intensive care unit-administration rate) between the two groups. CONCLUSIONS: Our findings indicate that among euthyroid patients, preconception TSH values in the high-normal range (between 2.5 and 4.9 mIU/L) do not have a negative effect on IUI outcomes. TRIAL REGISTRATION: This study is retrospectively registered by Ethical Review Board at Inonu University in 19th December 2017; Ethics approval no is 2017-27-20.

Blood Cadmium Concentrations in Women with Ectopic Pregnancy.

The purpose of this study is to investigate the relationship between the blood level of cadmium and the occurrence of ectopic pregnancy. Forty-one (41) case patients with ectopic pregnancy and 41 uncomplicated intrauterine pregnant patients as controls were recruited. The concentrations of cadmium (Cd) were measured from blood samples using atomic absorption spectrometry. The cases and controls were similar in age, body mass index, and smoking habits. The median blood level of Cd was 0.32 µg/l (interquartile range [IQR] 0.00-0.71) in the women with ectopic pregnancies and 0.34 µg/l (IQR 0.09-0.59) in the controls. There was no significant association between blood cadmium levels and ectopic pregnancy.

Metabolic and carbohydrate characteristics of different phenotypes of polycystic ovary syndrome.

OBJECTIVE: To compare the prevalence of various metabolic and cardiovascular risk factors and insulin resistance between polycystic ovary syndrome (PCOS) patients with or without hyperandrogenism. MATERIAL AND METHODS: This is a retrospective cross-sectional study involving women with PCOS as diagnosed according to the Androgen Excess (AE) Society definition (n=504) and women with normoandrogenemic PCOS (n=183). Anthropometrics, lipid profile, glucose, insulin, oral glucose tolerance test (OGTT), and reproductive hormone levels were evaluated. RESULTS: Women with PCOS diagnosed according to the AE Society had a significantly higher prevalence of metabolic syndrome compared with the normoandrogenemic PCOS phenotype: odds ratio (OR) 2.95 [95% confidence interval (CI) 1.21-7.21]. There was no significant difference in the prevalence glucose intolerance test between the groups [OR: 2.15, 95% CI 0.71-6.56]. The prevalence of low high density lipoprotein (HDL)-cholesterol in the group under the AE-PCOS Society criteria was higher than that of the normoandrogenemic PCOS group [OR: 2.82, 95%CI 1.29-3.36]. CONCLUSION: The risks of metabolic syndrome and cardiovascular disease may vary among the phenotypes of PCOS based on the Rotterdam criteria. This new data may be of reference in informing women with PCOS, although further prospective studies are needed to validate this proposition.

Prokineticin 1 and leukemia inhibitory factor mRNA expression in the endometrium of women with idiopathic recurrent pregnancy loss.

OBJECTIVE: To determine the expression patterns of prokineticin 1 (PROK1) and leukemia inhibitory factor (LIF) mRNA differ in peri-implantation endometrial tissue of women with idiopathic recurrent pregnancy loss (RPL) from normal fertile women. DESIGN: A case-control study. SETTING: University-based tertiary care center. PATIENT(S): 30 women with idiopathic RPL and 30 fertile controls. INTERVENTION(S): Endometrial biopsies. MAIN OUTCOME MEASURE(S): Real-time polymerase chain reaction analysis for expression of PROK1 and LIF mRNA. RESULT(S): The expression of PROK1 and LIF was statistically significantly increased in the endometrium of the women with idiopathic RPL compared with the controls. Furthermore, increased LIF expression was observed in the endometrium of women with idiopathic RPL compared with controls. CONCLUSION(S): An increased mRNA expression of PROK1 and LIF could be one of the several abnormalities characterizing the endometrium in women with RPL.

Association of folic acid receptor α in maternal serum with neural tube defects.

OBJECTIVE: To evaluate whether serum folic receptor α levels are changed in women whose previous pregnancies were complicated with neural tube defects (NTDs). METHODS: This was a case-control study that included 41 women as the control group who had previously had at least one healthy pregnancy and 37 women as the study group who had a previous pregnancy complicated with NTDs. Blood samples were obtained from all of the participants six weeks after the termination of pregnancy or delivery of a baby. Serum folate receptor α concentrations were analyzed using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: The mean concentrations of serum folate receptor α were significantly lower in the NTD cases compared to those in the control group (p = 0.02). There was no significant difference in mean serum folate titers between the NTD cases and the control group (p = 0.07). CONCLUSION: Low serum folic acid receptor α levels in the current study did not appear to be a regulatory marker of maternal folate homeostasis per se but rather a factor that contributed to the development of NTDs.

Amniotic fluid urocortin-1 concentrations for the prediction of preterm delivery.

AIM: The aim of this study was to analyze whether urocortin-1 concentration in midtrimester amniotic fluid could serve as an indicative marker of preterm labor. MATERIAL AND METHODS: A retrospective cohort study was conducted. Urocortin-1 concentrations in midtrimester amniotic fluid were measured in 22 pregnant women with preterm deliveries and 45 women who delivered at term using enzyme-linked immunosorbent assay. RESULTS: The median amniotic fluid urocortin-1 concentration was significantly lower in the women with preterm birth (40.06 pg/mL; range, 13.77-67.58 pg/mL) than in the women who gave birth at term (49.56 pg/mL; range, 26.25-175.9 pg/mL; P = 0.022). The result of receiver-operator curve analysis indicates that an amniotic fluid urocortin-1 concentration ≤ 57.88 pg/mL had an area under the curve of 0.673 (95% confidence interval, 0.55-0.78; P = 0.01) with a sensitivity of 81.8%, specificity of 40.0%, positive predictive value of 40%, and a negative predictive value of 82% in identifying which of the patients subsequently delivered prematurely. CONCLUSIONS: These results suggest that low urocortin-1 concentration in midtrimester amniotic fluid could be used as an indicative marker of preterm birth.

Maternal and fetal adropin levels in gestational diabetes mellitus.

AIM: To evaluate maternal and cord blood serum adropin concentrations in pregnant women with gestational diabetes mellitus (GDM). STUDY DESIGN: Twenty pregnant women with GDM and 20 gestational age-matched healthy pregnant women participated in the study. Maternal serum and cord blood adropin levels were assessed using an enzyme immunosorbent assay, at the time of birth. The relation of maternal serum and cord blood adropin levels with metabolic parameters were also assessed. RESULTS: The mean maternal and cord serum adropin in the GDM group were significantly lower than those of the control women (P=0.01 and P<0.001, respectively). Maternal serum adropin levels did not correlate with either fetal serum adropin levels or maternal metabolic values. CONCLUSION: The data suggest that low adropin levels may contribute to the underlying pathogenesis of GDM.

Salusins, newly identified regulators of hemodynamics and mitogenesis, increase in polycystic ovarian syndrome.

In the current study, we aimed to investigate whether serum salusin α and ß levels are different in PCOS subjects. Fifty women with PCOS and 50 healthy, age- and body mass index matched controls were included to the prospective cross-sectional study. All subjects underwent venous blood drawing on the early follicular phase after an overnight fasting. Serum salusin α and ß levels were measured with EIA, and ELISA respectively. The relationships between serum salusin levels and anthropometric and metabolic parameters were also assessed. Plasma salusin α and ß levels were higher in women with PCOS compared to control group. Serum salusin α level correlated positively with salusin ß and fasting serum insulin levels. The serum salusin ß levels were correlated positively with HOMA-IR, TG, LDL-C, LH, FSH, and total testosterone levels. Our results indicate that salusins, newly identified regulators of hemodynamics and mitogenesis, are increased within the serum of women with PCOS.

Surgical removal of endometrioma decreases the NF-kB1 (p50/105) and NF-kB p65 (Rel A) expression in the eutopic endometrium during the implantation window.

We aimed to investigate whether the surgical removal of endometrioma alters the nuclear factor-kappa B1 (NF-kB1; p50/105) and NF-kB p65 (Rel A) expression in the eutopic endometrium of infertile women with endometrioma before and after laparoscopic removal of the ovarian endometrioma during the mid-secretory phase. Infertile women with endometrioma (n = 15) were enrolled. Infertile patients with nonendometriotic ovarian cyst (n = 10) and healthy fertile women (n = 10) were recruited as controls. Endometrial samples were obtained before and 3 months after the laparoscopic cystectomy. The NF-kB1 (p50/105) levels were analyzed by enzyme-linked immunosorbent assay (ELISA) in the endometrium of all groups before and after laparoscopic ovarian cystectomy during implantation window. Expression of NF-kB1 (p50/105) in eutopic endometrium was significantly higher in infertile women with endometrioma compared to nonendometriotic cyst and fertile controls (P < .05). Laparoscopic cystectomy resulted in a significant decrease in NF-kB1 expression in women with endometrioma. The NF-kB p65 (Rel A) immunoreactivity of eutopic endometrium decreased significantly subsequent to the surgical removal of the endometrioma. In conclusion, increased endometrial NF-kB expression may contribute to endometriosis-associated infertility.