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.

The effect of premature ovarian failure on inner ear function.

The aim of this study was to test whether hearing function is impaired in women with premature ovarian failure. Thirty (30) women with premature ovarian failure (POF), 30 women in menopause and 30 healthy controls were recruited in this study. Pure tone audiometric (PTA), transiently evoked otoacoustic emissions (TEOAEs) and distortion product otoacoustic emissions (DPOAEs) of the study participants were analysed. At PTA, 6 and 8 kHz were lower in menopause group compared with both women with POF and controls. At TEOAE 3 and 4 kHz and at DPOAE 1, 2, 4 and 6 kHz were lower in menopause group compared with the controls. At DPOAE 6 kHz was lower in the POF group compared with the controls. Women with POF comparing to menopause group at TEOAE 3, 4 kHz and at DPOAE 4 and 6 kHz were lower in the menopause group. Inner ear function of both women in menopause and women with POF was declined compared to the healthy controls. Clinically, evaluation of hearing status may be considered in women with POF.Impact statementWhat is already known on this subject: Premature ovarian failure (POF) affects 1%-2% of women, and it adversely effects on health status (such as cardiovascular, psychological and cognitive disorders). Previous studies suggested that a lack of oestrogen might play a role in hearing disorders in women. However, we do not know POF's adversely effect on cochlea and hearing.What the results of this study add: The present study demonstrates that lower serum oestrogen has a negative effect hearing in women with POF at DPOAE 6 kHz.What the implications are of these findings for clinical practice and/or further research: The women with POF must be evaluated for hearing status.

The effect of premature ovarian insufficiency on nasal mucociliary clearance time.

Premature ovarian insufficiency (POI) is a global health concern for women and affects several systems, such as cardiovascular system, autoimmune disease, and psychological status. The aim of this study was to investigate the effect of POI on nasal mucociliary clearance time via saccharin test by comparing postmenopausal women and healthy controls. Thirty-five (35) patients with POI, 35 healthy postmenopausal women and 35 healthy controls were recruited in this study. All study participants underwent measurements of nasal mucociliary clearance time via saccharine test. When women with POI and postmenopausal women compared with the controls, nasal mucociliary clearance time was longer in both women with POI and postmenopausal women. When women with POI were compared with postmenopausal women, the nasal mucociliary clearance time was not difference between two groups. There was a significant prolonged nasal mucociliary clearance time in the women with POI and postmenopausal women. Lower serum estradiol levels in women with POI as well as postmenopausal women had an adverse effect of nasal mucociliary clearance time.

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.

Renal cell carcinoma diagnosed during pregnancy: a case report and literature review.

Diagnosing cancer during pregnancy is uncommon. Although pregnancies with concomitant malignancies have been reported, urological tumours are possibly the most rarely identified tumours during pregnancy. Renal cell carcinoma appears to be the most common urological malignancy during pregnancy. In this case report, we discuss successful management of a patient who was diagnosed with renal cell carcinoma during the antenatal period.

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.

Face presentation at term: a forgotten issue.

AIM: To determine factors associated with face presentation of term fetuses delivered. METHODS: Of 34,480 consecutive, term deliveries of uncomplicated pregnancies within a 3-year period, all live, singleton term fetuses with cephalic presentation in which no lethal anomalies occurred that were diagnosed with a face presentation were studied. Factors that may have contributed to the etiology of the presentation including age, parity and fetal size were evaluated. Ultrasonographic evaluation was recorded. RESULTS: Fifty cases were diagnosed with an incidence of 0.14%. Parity was not associated with face presentation. Birthweight of 4000 g or more indicated an increased risk of approximately 2.9-fold, whereas fetuses weighing 3000-3499 g were found to have a relatively decreased risk of face presentation when compared with the general obstetrics group (P = 0.015 and 0.001, risk ratio = 2.948 and 0.450, respectively). With physical examination, only 70% were diagnosed correctly. CONCLUSION: Face presentation is a rare event and birthweight more than 4000 g was found to be associated with face presentation. Parity is not an associated factor.

Relationship between preterm labor and thrombophilic gene polymorphism: A prospective sequential cohort study.

OBJECTIVE: Premature labor is still the leading cause of infant mortality and morbidity worldwide. Multiple etiological factors including genetics and environment are held responsible for preterm birth. However, scientific data regarding the link between premature birth and genetics are limited. SUBJECTS AND METHODS: In this study, we included 50 women who had premature labor (group 1) but did not have any known risks for a premature delivery such as uterine anomaly, polyhydramnios, hypertension, and diabetes mellitus, and another 50 healthy women who had term labor as control (group 2). We compared these two patient groups for MTHFR C677T, MTHFR C1298T, prothrombin 20210A, factor V and ACE polymorphisms. RESULTS: We could not detect a statistical significance between groups for polymorphisms in MTHFR C677T, MTHFR C1298T, prothrombin 20210A, factor V and ACE polymorphisms. CONCLUSION: We investigated the relationship between premature and term labor and thrombophilic gene polymorphism. However, we found no associations with premature or term labor with the parameters included.

Heterogeneous appearance of VEGF (vascular endothelial growth factor) immunopositivity in cyst capsules of endometrioma.

The aim of the research was to reveal vascular endothelial growth factor (VEGF) immunolocalization in endometrioma cysts and endometrial tissues. The study group (group1) included 15 patients laparoscopically operated on for endometrioma and the control group (group 2) included 13 patients prepared for diagnostic laparoscopy for primary infertility. Biopsies from endometrioma cyst capsules, disease-free peritoneum and pipelle biopsies from the endometrium were taken from group 1. Biopsies from parietal peritoneum and endometrium were taken from group 2. Results showed VEGF immunoreactivity of peritoneal biopsies of group 1 was more intense than that of the control biopsies. A positive correlation was seen between the diameter of cyst capsules and VEGF labeling intensity and as the size of cyst enlarged, the appearance of non-homogeneous distribution of VEGF immunolocalization became more frequent. We conclude that the variation of VEGF immunolocalization in endometrioma cysts may be attributed to other possible angiogenic molecules in the pathogenesis and may cause unexpected responses to anti-angiogenic therapies.

Is leptin a significant predictor of bone mineral density in postmenopausal Turkish women?

The objective of the present study was to investigate the relationship between leptin and bone mineral density in postmenopausal Turkish women. A total of 122 healthy postmenopausal women were enrolled in this cross-sectional study. Blood samples were obtained for analysis of serum leptin. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at the lumbar spine, femoral neck and trochanter on the same day. Leptin levels was significantly correlated with BMD of L(1-4) (P = 0.04), but not of femoral neck (P = 0.13), and trochanter (P = 0.39). However, Z scores of L(1-4) (P = 0.009), femur neck (P = 0.009), and femur trochanter (P = 0.025) were positively correlated with leptin levels. In multiple linear regression analysis, leptin was not found to be a statistically significant independent predictor for BMD. Leptin was associated with BMD and Z scores at various body sites; however, it was not an independent predictor of BMD.

The effect of retained embryos on pregnancy outcome in an in vitro fertilization and embryo transfer program.

OBJECTIVE: The purpose of this study was to determine the incidence of retained embryos and its impact on pregnancy outcome in the absence of known risk factors like blood and mucus in the transfer catheter. The factors that could be associated with embryo retention were also investigated. STUDY DESIGN: The results of all embryo transfer procedures performed at Ankara IVF Center between January 2003 and December 2005 were analyzed retrospectively. Three hundred and five embryo transfers, in which the transfer catheter was contaminated with blood or mucus, were excluded and the remaining 1,454 embryo transfers, with clean catheter, were enrolled into the study. Both fresh (n=1,422) and frozen (n=32) embryo transfers were included. RESULTS: The overall incidence of retained embryos during study period was 2.8% (41/1,454) following a clean initial embryo transfer. The mean age of the female partner, mean number of retrieved oocytes, MII oocytes, fertilized oocytes and the embryos transferred were similar in patients with and without retained embryos. The 1,454 embryo transfers performed during the study period resulted in 712 pregnancies (49%), of which 639 proved to be clinical pregnancies with a rate of 44%. The implantation rate was 22.8%. Pregnancy outcomes including positive beta-hCG (58.5% versus 48.7%), biochemical (4.7% versus 5.1%) and clinical pregnancy rates (53.6% versus 43.6%), implantation rate (24% versus 22.7%) and multiple pregnancy rate (36.3% versus 44.7%) were not significantly different between patients with and without retained embryos. An influence of individual physicians and embryologists on the frequency of retained embryos was not detected. The type of embryo transfer catheter used did not show any difference in terms of embryo retention. The cleavage stages of embryos were not different between groups. Although it was not statistically significant, the number of embryos transferred appeared to be a potentially confounding factor for retained embryos (p=0.053) and it might be significant in a slightly larger sample. When transfer of one or two embryos was compared to three or more embryos, the likelihood of retained embryos increased from 1.2% (4/321) to 3.2% (37/1,133). CONCLUSION: Retained embryos in the transfer catheter and immediate retransfer of them have no adverse impact on clinical pregnancy and implantation rates unless other previously reported signs of difficult transfer are also observed.