PRM1 variant rs35576928 (Arg>Ser) is associated with defective spermatogenesis in the Chinese Han population

Protamine genes play important roles in DNA packaging within the sperm nucleus. In order to evaluate the association of PRM1, PRM2, KIT and KITLG variants with susceptibility to severely defective spermatogenesis, 309 male infertility patients (199 cases with non-obstructive azoospermia and 110 cases with severe oligozoospermia) and 377 controls were recruited in the Chinese Han population. This study genotyped 38 single-nucleotide polymorphisms (SNP) in PRM1, PRM2, KIT and KITLG using Sequenom iplex. The results showed that PRM1 variant rs35576928 (p.R34S) was significantly associated with severe oligozoospermia and played a protective role against the disease (P = 0.0079, Bonferroni correction, OR 0.426). The dominant model (variant-containing genotypes) of the SNP was confirmed to protect against the occurrence of oligozoospermia (P = 0.0078, Bonferroni correction, OR 0.387). Haplotype analysis of PRM1 and PRM2 in combination exhibited that haplotype TACCGGC exhibited a significant protective effect against the occurrence of oligozoospermia when compared with controls (P = 0.002, Bonferroni correction, OR 0.602). Haplotype TACCTGC was strongly associated with risk of the clinical phenotype severe oligozoospermia (P = 0.002, Bonferroni correction, OR 2.716). The findings indicated that PRM1 variant rs35576928 (p.R34S) was associated with severely defective spermatogenesis in the Chinese Han population.Male spermatogenic failure may be associated with gene variants. We demonstrated whether such genetic variation of PRM1 and PRM2 affected clinicopathological characteristics and conferred susceptibility to this entity. In this study, we found that PRM1 variant rs35576928 (Arg>Ser) played a protective role against severe oligozoospermia. The dominant model analysis (variant-containing genotypes) confirmed that the SNP was a risk factor of a spermatogenesis defect. Haplotype analysis of PRM1 and PRM2 showed that TACCGGC was a common factor protecting against severe oligozoospermia, while the haplotype TACCTGC was strongly associated with the risk of the severe oligozoospmeria. Our findings indicate that the PRM1 variant rs35576928 (Arg>Ser) is associated with spermatogenesis defect in the Chinese Han population.     

Association of CLOCK gene variants with semen quality in idiopathic infertile Han-Chinese males

Recent experimental animal studies suggested that the circadian locomotor output cycles kaput protein gene (CLOCK) may play an important role in male reproduction. So far, such data for humans are not available. This study used single-nucleotide polymorphisms (SNP) to examine the association between CLOCK and semen quality in a human population with idiopathic infertility. Three-variant genotyping of CLOCK and semen analysis were performed in 478 men with idiopathic infertility by SNP genotyping assays and computer-aided sperm analysis. Subjects carrying a C allele at rs3749474 (CC and TC) presented significantly lower semen volume (P = <0.001 and 0.001, respectively) compared with the TT genotype. Subjects carrying the rs3749474 CC genotype had significantly lower sperm number per ejaculate (P = 0.026) and sperm motility (P = 0.021) than TT genotype carriers. rs1801260 TC genotype carriers had significantly lower sperm motility compared with the TT genotype (P = 0.028). For the rs3817444 genotypes, CA and AA genotype carriers presented significantly lower semen volume compared with the CC genotype (P = 0.022 and 0.001, respectively). The findings suggest, as far as is known for the first time, an association between CLOCK genetic variants and altered semen quality in a human population with idiopathic infertility.The gene encoding the circadian locomotor output cycles kaput protein (CLOCK) functions as an important positive enhancer of the circadian system. The observations reported in recent experimental animal studies suggested that CLOCK may play an important role in male reproduction. So far, such data for humans are not available. In this study, single-nucleotide polymorphisms (SNP) were used to examine the association between CLOCK and semen quality in human population with idiopathic infertility. Three-variant genotyping of CLOCK and semen analysis were performed in 478 males with idiopathic infertility by SNP genotyping assays and computer-assisted semen analysis. The results showed that the subjects carrying a C allele at rs3749474 (CC and TC) presented significantly lower semen volume compared with the TT genotype. For subjects carrying the CC genotype, sperm number per ejaculate and sperm motility were significantly lower compared with TT genotype carriers. The rs1801260 TC genotype carriers also had significantly lower sperm motility compared with the TT genotype. For the rs3817444 genotypes, the CA and AA genotype carriers presented significantly lower semen volume compared with the CC genotype. The findings suggested, as far as is known for the first time, an association between CLOCK genetic variants and altered semen quality in a human population with idiopathic infertility.     

Preeclampsia and cardiovascular disease share genetic risk factors on chromosome 2q22

ObjectiveFour putative single nucleotide polymorphism (SNP) risk variants at the preeclampsia susceptibility locus on chromosome 2q22; rs2322659 (LCT), rs35821928 (LRP1B), rs115015150 (RND3) and rs17783344 (GCA), were recently shown to associate with known cardiovascular risk factors in a Mexican American cohort. This study aimed to further evaluate the pleiotropic effects of these preeclampsia risk variants in an independent Australian population-based cohort.MethodsThe four SNPs were genotyped in the Western Australian Pregnancy Cohort (Raine) Study that included DNA, clinical and biochemical data from 1246 mothers and 1404 of their now adolescent offspring. Genotype association analyses were undertaken using the SOLAR software.ResultsNominal associations (P < 0.05) with cardiovascular risk factors were detected for all four SNPs. The LCT SNP was associated with decreased maternal height (P = 0.005) and decreased blood glucose levels in adolescents (P = 0.022). The LRP1B SNP was associated with increased maternal height (P = 0.026) and decreased maternal weight (P = 0.044). The RND3 SNP was associated with decreased triglycerides in adolescents (P = 0.001). The GCA SNP was associated with lower risk in adolescents to be born of a preeclamptic pregnancy (P = 0.003) and having a mother with prior preeclamptic pregnancy (P = 0.033).ConclusionsOur collective findings support the hypothesis that genetic mechanisms for preeclampsia and CVD are, at least in part, shared, but need to be interpreted with some caution as a Bonferroni correction for multiple testing adjusted the statistical significance threshold (adjusted P < 0.001).     

Quantitative trait analysis suggests human DAZL may be involved in regulating sperm counts and motility

A prospective study was carried out to identify the association of the DAZL (deleted in azoospermia-like) gene with major semen parameters in 210 men with normal and 467 men with abnormal semen parameters. Primer extension analysis for single nucleotide polymorphisms (SNP) of DAZL and quantitative trait analysis on the association of allele/genotype frequencies, linkage disequilibrium characteristics and DAZL haplotypes with semen parameters were investigated. Of five SNP (260A→G, 386A→G, 520+34c→a, 584+28c→t and 796+36g→a) screened, 386A→G was significantly correlated with sperm count (P < 0.0001) and motility (P < 0.005) and 584+28c→t was marginally correlated with sperm morphology. After excluding 520+34c→a, which was not in the Hardy–Weinberg equilibrium, the major haplotypes consisted of four SNP. One haplotype (260A→G (major allele), 386A→G (major allele), 584+28c→t (minor allele) and 796+36g→a (major allele)) was significantly associated with sperm count (P = 0.003) and motility (P = 0.04). This study suggests DAZL may be involved in regulating sperm counts, motility and possibly morphology.     

Haplotype analysis of TGF-β1 gene in a preeclamptic population of northern Mexico

ObjectiveTo determine the frequencies of −800G/A (rs1800468), −509C/T (rs1800469) and 869T/C (rs1800470) polymorphisms and their haplotypes in the TGF-β1 gene and their association with preeclampsia in a population of northern México.Design and methodsThis case-control study involved 175 preeclamptic and 253 normoevolutive pregnant women. The polymorphisms were genotyped by real time PCR.ResultsThe allele and genotype frequencies of polymorphisms showed no significant differences between cases and controls; the −800AA genotype had a very low frequency in cases (1%) and controls (0.4%). The TT genotype of the 869T/C polymorphism is a protective factor of severe preeclampsia (OR 0.56, 95% CI 0.32–0.98). The −509C/T and 869T/C polymorphisms were in linkage disequilibrium (D′ = .537, p = .009). The most common haplotypes in case and control groups were −800G/−509C/869C, 34.95% and 37.24%, respectively. We found no increased risk of preeclampsia by haplotype.ConclusionsOur results suggest that −800G/A, −509C/T and 869T/C polymorphisms of TGF-β1 gene or their haplotypes are not associated with preeclampsia and that only the TT genotype of 869T/C polymorphism is a protective factor of severe preeclampsia in a population of northern México.     

XRCC1 Arginine194Tryptophan and GGH-401Cytosine/Thymine polymorphisms are associated with response to platinum-based neoadjuvant chemotherapy in cervical cancer

ObjectiveThe objective of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) of genes which are involved in DNA synthesis and repair with the response to platinum-based neoadjuvant chemotherapy (NAC) and disease-free survival (DFS) in patients with cervical cancer who were treated with NAC followed by radical hysterectomy.MethodsA retrospective review was performed on 66 patients with cervical cancer who were treated with NAC followed by radical hysterectomy in our institute between January 1999 and February 2007. DNA was extracted from the paraffin-embedded, formalin-fixed tissue blocks of hysterectomy specimens. The genotypes of SNPs (MTHFR 677Cytosine/Thymine, XRCC1 Arginine194Tryptophan, GGH-401Cytosine/Thymine, and GSTP1 Isoleucine105Valine) were determined using a single base primer extension assay. The association of SNP genotypes with the response to NAC, which was measured by physical and colposcopic examinations, was evaluated. In addition, DFS based on SNP genotypes was examined.ResultsThe genotypes of XRCC1 Arginine194Tryptophan and GGH-401Cytosine/Thymine were significantly associated with the response to NAC (P =  0.023 for XRCC1 Arginine194Tryptophan; P =  0.046 for GGH-401Cytosine/Thymine). However, the genotypes of MTHFR 677Cytosine/Thymine and GSTP1 Isoleucine105Valine were not associated with the response to NAC. In subgroup analysis with 39 patients who were treated with regimens containing 5-fluorouracil (5-FU), the genotypes of GGH-401Cytosine/Thymine were significantly associated with the response to NAC (P =  0.039). In multifactor dimensionality reduction (MDR) analysis, the combination of XRCC1 Arginine194Tryptophan and GGH-401Cytosine/Thymine genotypes was associated with the response to NAC (P < 0.001). However, no SNP genotypes were associated with DFS, but the cisplatin dose intensity of NAC was associated with DFS.ConclusionsThe genotypes of XRCC1 Arginine194Tryptophan and GGH-401Cytosine/Thymine were associated with the response to NAC in patients with cervical cancer. However, no SNP genotypes were associated with DFS.     

Phosphatidylserine translocation in human spermatozoa from impaired spermatogenesis

The aim of the present study was to evaluate phosphatidylserine translocation in specific patient groups and compare the rates of apoptosis between ejaculated and testicular spermatozoa. Fifty-six patients undergoing infertility treatments were included in the present study. Semen samples (n = 37) were obtained from cases with normozoospermia (n = 9) and abnormal semen parameters (n = 28). Testicular biopsy was performed in 19 patients, eight with obstructive and six with non-obstructive (hypospermatogenesis) azoospermia, and in five patients without azoospermia (anejaculation and oligozoospermia). Phosphatidylserine externalization was assessed using annexin-V binding and fluorescence microscopy, and propidium iodide exclusion tests were used to distinguish live from dead cells. In semen, oligoasthenoteratozoospermia showed significantly increased rates of sperm apoptosis (60.3 ± 12.9) than normozoospermia (47.5 ± 10.2). In testis, hypospermatogenesis (63.3 ± 10.3) and obstructive azoospermia (63.6 ± 15.1) showed significantly increased rates of sperm apoptosis than non-azoospermic patients (49.6 ± 25.5). Comparisons between semen and testis showed that oligozoospermia had significantly higher rates of sperm apoptosis in semen (57.9 ± 11.9) than in testis (29.4 ± 1.1). The results suggest the presence of a post-testicular apoptotic induction factor and the potential beneficial use of testicular spermatozoa in clinical treatments.     

Valores extremos del IMC materno: factores determinantes de peores resultados obstétricos y perinatales

ObjectiveTo study the influence of maternal body mass index (BMI) at the beginning of pregnancy on obstetric-perinatal outcomes.Material and methodsObservational-ambispective study. We recruited 1407 patients with singleton gestations and deliveries of foetuses > 24 weeks between 01/12/2017 and 31/07/2019. The sample was stratified according to their BMI following the WHO classification. Variables on pre-pregnancy, gestational disease, obstetric care, and maternal-perinatal outcomes were analysed and compared between the studied groups. The statistical program has been R Core Team 2020, version 3.6.3. P ≤ .05 was considered significant.ResultsClass II-III (BMI 35-39 and BMI ≥ 40 respectively) obese women have a higher risk of chronic arterial hypertension (OR 53.54, 95% CI 18.21-229.02), gestational diabetes (OR 5.24, 95% CI 2.87-9.51) and preeclampsia (OR 2.38, 95% CI 0.95-5.51 with P = .049). The underweight women had more intrauterine growth restriction diagnoses (OR 3.09, 95% CI 1.46-6.17). Inductions of labour and caesarean sections increase as BMI increases (P = .006). Low weight patients also had a higher risk of caesarean section (OR 2.46, 95% CI 1.06-5.20). Neonatal admissions were more frequent in obese and underweight women (OR 2.68, 95% CI 1.39-5.00 and OR 2.56, 95% CI 1.10-5.44 respectively). Obese women had a higher risk of neonatal weight > 4000 g (OR 3.06, 95% CI 1.57-5.77) and low weight pregnant women had a higher risk of neonatal weight < 2500 g (OR 2.94, 95% CI 1.54-5.41).ConclusionExtreme values of maternal BMI at the beginning of gestation are determining factors for an adverse obstetric-perinatal outcome.     

Effect of 2 referral intervals on diagnostic discordance between cytology and histology at a colposcopy clinic

ObjectiveTo determine the effect of the time interval between cervical cytology screening and histology at treatment on grade of cervical disease.MethodsIn a retrospective cross-sectional study at a colposcopy clinic in Soweto, Johannesburg, South Africa, data were compared from women with cytologic abnormalities referred for colposcopy between April 2003 and June 2010 to determine whether early (≤ 180 days) or late (> 180 days) referral had an impact on dysplasia grade.ResultsIn the early and late referral groups, there were 213 (13.43%) and 201 (14.63%) women, respectively, with upgrading of cervical dysplasia (P = 0.35), and 1373 (86.57%) and 1173 (85.37%) women, respectively, with downgrading or no change (P = 0.35). Risk factors for upgrading were HIV infection (odds ratio [OR], 1.63; P < 0.001) and condom use (OR, 1.30; P = 0.02). Four cases (0.68%) of invasion among women with low-grade squamous intraepithelial lesion (LSIL) and 50 cases (2.11%) among women with high-grade SIL (HSIL) were not detected by cytology. Risk factors for invasive disease on histology were age (OR, 1.09 per year; P < 0.001), parity (OR, 1.32 per pregnancy; P < 0.001), and HSIL on cytology (OR, 3.17; P = 0.03).ConclusionThere was no difference in the up- or downgrading of cervical dysplasia between the 2 referral groups.     

Association of AQP8 in women with PCOS

Aquaporin 8 (AQP8) has been identified as a novel gene participating in female reproductive physiology. The present study was designed to determine whether an association exists between AQP8 and polycystic ovary syndrome (PCOS). This study recruited 192 women with PCOS and 191 controls. High-resolution melting and sequencing were employed to investigate the genotypes of six single-nucleotide polymorphisms within AQP8 (rs7198838, rs1076973, rs1076974, rs2287797, rs2287798 and rs2287796). A significant difference was found in rs2287798 between PCOS cases and controls (P = 0.0007). Possible associations between AQP8 genotypes and three different phenotypes of this syndrome were investigated. The results support the earlier evidence for a possible role of AQP8 in the pathogenesis of PCOS. Further studies are still needed to elucidate its functional role.Aquaporin 8 (AQP8) has been identified as a novel gene participating in female reproductive physiology. The present study was designed to determine whether there is an association between AQP8 and polycystic ovary syndrome (PCOS). This study recruited 192 women with PCOS and 191 controls. High-resolution melting and sequencing were employed to investigate the genotypes of six single-nucleotide polymorphisms within AQP8 (rs7198838, rs1076973, rs1076974, rs2287797, rs2287798 and rs2287796). We observed a significant difference in allele frequency of rs2287798 between PCOS cases and controls (P = 0.0007). The possible association between AQP8 genotypes and three different phenotypes of this syndrome in this locus were investigated. Our results support the earlier evidence for a possible role of AQP8 in the pathogenesis of PCOS. Further studies are still needed to elucidate its functional role.     

A pilot study of the effectiveness of reflexology in treating idiopathic constipation in women

ObjectivesConstipation is a common problem in the UK, affecting up to 20% of the population. Reflexologists claim that reflexology can be beneficial in the treatment of constipation. The aim of this exploratory pilot study was to determine the effectiveness of reflexology in treating idiopathic constipation in women and it is the first study of the effectiveness of reflexology for the treatment of women with idiopathic constipation defined according to Rome II criteria.MethodsNineteen female patients referred to a specialist biofeedback service with idiopathic constipation defined by Rome II criteria were recruited. A course of reflexology treatment (weekly for six weeks) was given. Patients' subjective perception of constipation was recorded as well as the Hospital Anxiety and Depression Scale (HAD), the Short form 36 (SF36), whole gut transit and the Holistic Complementary and Alternative Medicine Questionnaire (HCAMQ) before and after the intervention.ResultsAll participants completed the intervention and none were lost to follow-up. Ninety-four percent of participants identified their constipation to be improved to some extent. Ten participants had improved colonic transit times and two patients had normalised colonic transit. Ten patients (53%, p = 0.19) demonstrated an improved anxiety score and 11 participants (58%, p = 0.14) demonstrated an improved depression score on the HAD scales. Improvement was seen in general health, mental health and vitality on the SF36 scale, with vitality improving significantly (p < 0.05). Sixty-three percent of participants had a more positive attitude (p = 0.03) towards CAM and holistic health following treatment.ConclusionsThis study shows that in this sample reflexology has potential benefit for treating idiopathic constipation in women. Further randomised trials are required.     

Sexual Complaints,Pelvic Floor Symptoms,and Sexual Distress in Women over Forty

IntroductionThe American Psychiatric Association recommends considering sexually related personal distress when assessing female sexual dysfunction. Currently, there is little data regarding the impact of sexual complaints on sexual distress.AimTo investigate the association between sexual complaints and perceived sexual distress in a population of ambulatory adult women.MethodsUsing the short forms of the Personal Experiences Questionnaire and Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire, we assessed sexual complaints among 305 women seeking outpatient gynecologic care. Depressive symptoms were quantified using the Center for Epidemiologic Studies Depression (CESD) score. Sexual distress was measured using the Female Sexual Distress Scale (FSDS). Using multivariable logistic regression, we compared sexual complaints between distressed and nondistressed women.Main Outcome MeasuresSexual distress, defined by FSDS score ≥15.ResultsFSDS scores were available for 292/305 participants. Seventy-six (26%) scores reflected distress. Distressed women were more likely to be younger (55.2 ± 1.0 years vs. 56.7 ± 0.8 years, P = 0.017); have higher CESD scores (16.6 vs. 9.5, P = 0.001); and report decreased arousal (56.8% vs. 25.1%, P = 0.001), infrequent orgasm (54% vs. 28.8%, P = 0.001), and dyspareunia (39.7% vs. 10.6%, P = 0.001). Women with sexual distress were also more likely to report sexual difficulty related to pelvic floor symptoms, including urinary incontinence with sexual activity (9% vs. 1.3%, P = 0.005), sexual avoidance due to vaginal prolapse (13.9% vs. 1%, P = 0.001), or sexual activity restriction due to fear of urinary incontinence (14.9% vs. 0.5%, P = 0.001). After multivariate analysis, sexual distress was significantly associated with dyspareunia (odds ratio [OR] 3.11, P = 0.008) and depression score (OR 1.05, P = 0.006), and inversely associated with feelings of arousal during sex (OR 0.19, P = 0.001).ConclusionOur results indicate that sexually related personal distress is significantly associated with dyspareunia, depressive symptoms, and decreased arousal during sexual activity. This contributes to our understanding of how sexual complaints may adversely affect women's quality of life. Knoepp LR, Shippey SH, Chen CCG, Cundiff GW, Derogatis LR, and Handa VL. Sexual complaints, pelvic floor symptoms, and sexual distress in women over forty.     

Centrally Mediated Erectile Dysfunction in Rats with Type 1 Diabetes: Role of Angiotensin II and Superoxide

IntroductionErectile dysfunction is a serious complication of diabetes mellitus. Apart from the peripheral actions, central mechanisms are also responsible for penile erection.AimThis study aims to determine the contribution of angiotensin (ANG) II in the dysfunction of central N-methyl-D-aspartic acid (NMDA)- and nitric oxide (NO)-induced erectile responses in streptozotocin-induced type 1 diabetic (T1D) rats.MethodsThree weeks after streptozotocin injections, rats were randomly treated with the angiotensin-converting enzyme inhibitor-enalapril, or the ANG II type 1 receptor blocker, losartan, or the superoxide dismutase mimetic, tempol, or vehicle via chronic intracerebroventricular infusion by osmotic mini-pump for 2 weeks.Main Outcome MeasureCentral NMDA receptor stimulation or the administration of the NO donor, sodium nitroprusside (SNP)-induced penile erectile responses and concurrent behavioral responses were monitored in conscious rats.ResultsTwo weeks of enalapril, losartan, or tempol treatment significantly improved the erectile responses to central microinjection of both NMDA and SNP in the paraventricular nucleus (PVN) of conscious T1D rats (NMDA responses—T1D+enalapril: 1.7 ± 0.6, T1D+losartan: 2.0 ± 0.3, T1D+tempol: 2.0 ± 0.6 vs. T1D+vehicle: 0.6 ± 0.3 penile erections/rat in the first 20 minutes, P < 0.05; SNP responses—T1D+enalapril: 0.9 ± 0.3, T1D+losartan: 1.3 ± 0.3, T1D+tempol: 1.4 ± 0.4 vs. T1D+vehicle: 0.4 ± 0.2 penile erections/rat in the first 20 minutes, P < 0.05). Concurrent behavioral responses including yawning and stretching, induced by central NMDA and SNP microinjections, were also significantly increased in T1D rats after enalapril, losartan, or tempol treatments. Neuronal NO synthase expression within the PVN was also significantly increased, and superoxide production was reduced in T1D rats after these treatments.ConclusionsThese data strongly support the contention that enhanced ANG II mechanism/s within the PVN of T1D rats contributes to the dysfunction of central NMDA-induced erectile responses in T1D rats via stimulation of superoxide. Zheng H, Liu X, and Patel KP. Centrally mediated erectile dysfunction in rats with type 1 diabetes: Role of angiotensin II and superoxide. J Sex Med 2013;10:2165–2176.     

Genetic polymorphisms in the Fas and FasL genes are associated with epithelial ovarian cancer risk and clinical outcomes

AimIn this study, we evaluated whether functional polymorphisms within the Fas and FasL genes were associated with the risk of developing epithelial ovarian cancer (EOC) and survival of patients with EOC.MethodsA case–control study was performed in 342 EOC patients and 344 control women. The genotypes of three promoter region polymorphisms (Fas ? 1377G/A, ? 670A/G and FasL ? 844T/C) were determined using ligase detection reaction-polymerase chain reaction (LDR-PCR). The clinical outcomes in 202 EOC patients were compared across genotypes.ResultsThe genotype frequencies of the FasL ? 844 T/C polymorphism were significantly different between the case and control groups (P = 0.034). Compared to the T/T and T/C genotypes, the C/C genotype significantly increased the risk of developing EOC (OR = 1.46, 95% CI = 1.08–1.99). The survival analysis showed that the Fas ? 1377G/A and ? 670A/G polymorphisms were related to prognosis in EOC patients. Compared with patients with the G/G genotype of the ? 1377G/A polymorphism, patients carrying the A allele had a shorter PFS and OS, as determined by univariate and multivariate analysis (HR = 1.81, 95% CI = 1.26–2.62 and HR = 1.86, 95% CI = 1.15–3.00, respectively). Similarly, Kaplan–Meier and Cox proportional hazard model analyses indicated that patients carrying the G allele of Fas ? 670A/G polymorphisms had shorter PFS and OS than those carrying the AA genotype (HR = 1.67, 95% CI = 1.15–2.42 and HR = 1.80, 95% CI = 1.10–2.94, respectively).ConclusionsFunctional polymorphisms in the Fas and FasL genes may be involved in epithelial ovarian cancer development and progression in northern Chinese women.     

Eclampsia: Maternal and neonatal outcomes

The objective of our study is to define the maternal and neonatal outcomes associated with eclampsia. This retrospective cohort study was performed using the Consortium on Safe Labor, database from 12 clinical centers, including 19 hospitals, from 2002–2008. All patients admitted with a diagnosis of eclampsia or seizure in labor and delivery or postpartum were included in the analysis. Patients with history of seizure disorder were excluded. Maternal and neonatal outcomes were compared to outcomes of women with preeclampsia and their neonates. Statistical analyses were performed using SAS. Chi square and t-test were used for categorical and continuous variables, respectively. Logistic regression and general linear regression were used to calculate odds ratios and 95% confidence intervals. p < 0.05 was considered significant. The eclampsia prevalence was 0.08% (n = 191) in our population; the preeclampsia cohort had 7012 women. There were significantly more eclamptic women (49%) delivered by cesarean section, as compared to preeclamptic women (36%), OR 1.7 (1.28–2.28). These women were more likely to have an ICU admission OR 12.9 (7.0–23.7). The mean gestational ages and birthweights were lower in the neonates of the eclampsia group. A multivariate analysis revealed that low cord arterial pH, low 5 min Apgar score, respiratory distress syndrome OR 5.5, (1.11–27.66) and seizures OR 10.3 (3.12–33.68), p < 0.05, were significantly elevated in the eclampsia cohort. The prevalence of eclampsia in our contemporary obstetrics population was 0.08%. Both mothers as well as neonates of eclamptics are at significant risk for complications due to their illness.     

Septate,subseptate and arcuate uterus decrease pregnancy and live birth rates in IVF/ICSI

A retrospective matched-control study to evaluate the effect of uterine anomalies on pregnancy rates after 2481 embryo transfers in conventionally stimulated IVF/intracytoplasmic sperm injection (ICSI) cycles. The study group of 289 embryo transfers before and 538 embryo transfers following hysteroscopic resection of a uterine septum was compared with two consecutive embryo transfers in the control group. Groups were matched for age, body mass index, ovarian stimulation, embryo quality, IVF or ICSI and infertility aetiologies. Number of embryos transferred, embryo quality and absence of uterine anomalies significantly predicted the pregnancy rates in the study group: odds ratios (OR) 1.7, 2.6 and 2.5, respectively (P < 0.001). Pregnancy rates after embryo transfer before hysteroscopic metroplasty were significantly lower, both in women with subseptate and septate uterus and in women with arcuate uterus compared with controls. If two or three embryos with at least one best-quality embryo were transferred, the differences were 9.6% versus 43.6%, OR 7.3 (P < 0.001) and 20.9% versus 35.5%, OR 2.1 (P < 0.03), respectively. Differences in terms of live birth rates were even more evident: 1.9% versus 38.6%, OR 32 (P < 0.001) and 3.0% versus 30.4%, OR 14 (P < 0.001). After surgery, the differences disappeared.This retrospective matched control study evaluated the influence of septate, subseptate and arcuate uterus on pregnancy and live birth rates after 2481 in conventionally stimulated IVF/intracytoplasmic sperm injection (ICSI) cycles. The study group included 827 embryo transfers (289 embryo transfers before and 538 embryo transfers following hysteroscopic resection of uterine septum ans was compared with two consecutive mebryo transfers in the control group. Both groups were matched by age, body mass index, stimulation protocol, quality of embryos, use of IVF or ICSI, and infertility aetiologies. Multivariate logistic regression analysis of the study group showed that the number of embryos, embryo quality and the absence of uterine anomalies significantly predicted the pregnancy rates: odds ratios (OR) 1.7, 2.6, and 2.5, respectively (P < 0.001). The pregnancy and live birth rates before surgery were lower compared with controls, both in women with subseptate or septate uterus and in women with arcuate uterus. If two or three embryos with at least one best quality embryo were transferred, the differences in terms of pregnancy rates were 9.6% versus 43.6%, OR = 7.3 (P < 0.001) and 20.9% versus 35.5%, OR = 2.1 (P < 0.03), respectively. The differences in terms of live birth rates were even more evident: 1.9% versus 38.6%, OR = 32 (P < 0.001) and 3.0% versus 30.4%, OR = 14 (P < 0.001). After surgery, the differences disappeared. Negative impact of uterine anomalies on pregnancy and on live birth rates are two important arguments for treating uterine anomalies in infertile women.     

Transforming growth factor beta-1 (TGF-β1) gene single nucleotide polymorphisms (SNPs) and susceptibility to pre-eclampsia in Iranian women: A case–control study

ObjectivesPre-eclampsia (PE) is a disorder of pregnancy characterized by high blood pressure and proteinuria. Transforming growth factor beta-1 (TGF-β1) is an important replicated PE candidate gene, and few studies have evaluated the direct association of TGF-β polymorphisms and risk to PE. The aim of this study was to investigate the association between three SNPs of TGF-β1 and serum level of this cytokine in PE patients and controls.Design and methodsIn this study the polymorphisms of the TGF-β1 gene at the coding region, and positions 29T→C (Leu 10 Pro), 74G→C (Arg 25 Pro) and 788C→T (Thr 263 Ile) were studied in 123 PE and 120 normal subjects using PCR-restriction fragment length polymorphism PCR-(RFLP) and amplification refractory mutation system (ARMS)-PCR methods. Moreover, serum TGF-β1 was determined by enzyme-linked immunosorbent assay (ELISA) technique.ResultsAt positions 74G→C and 29T→C the genotypes and allele frequencies showed no significant differences between PE patients and normal controls (P = 0.3 and P = 0.5 respectively). While in the case of position 788C→T both genotypes and allele frequencies were significantly different between PE patients and controls (P = 0.02). Haplotype analysis on three polymorphic sites showed no significant differences between PE and control individuals (P = 0.8). TGC and CGC haplotypes were the most frequent in both studied groups. The mean serum TGF-β1 level was significantly higher (62.73 ng/ml) in PE patients compared with pregnant (47.01 ng/ml) and non-pregnant (40.68 ng/ml) control groups (P = 0.0001).ConclusionsThe results of this study suggest that TGF-β1 gene 788C→T polymorphism is an important factor mediating the casual pathway of preeclampsia.     

Adverse pregnancy outcomes in cases involving extremely young maternal age

ObjectiveTo assess pregnancy outcomes among adolescent girls 16 years old or younger and their newborns.MethodsA cohort study was carried out at Siriraj Hospital, Mahidol University, Bangkok, Thailand, using completed charts for 1061 girls aged 16 years or younger (study group) and 1100 women aged 20 to 29 years (reference group) delivered at that hospital between January 1, 2006, and December 31, 2010. Demographic data, maternal laboratory investigations, maternal complications, placental complications, medications administered in hospital, and neonatal outcomes were recorded.ResultsAnemia (odds ratio [OR], 1.86; confidence interval [CI], 1.52–2.26); heart disease (OR, 0.38; CI 0.15–0.90), thyroid disorder (OR, 0.054; CI, 0.01–0.40), pulmonary disease (OR, 0.89; CI, 0.41–1.93); medical and obstetrics complications including gestational diabetes mellitus (OR, 0.04; CI, 0.01–0.29), placenta previa (OR 1.04, CI 0.06–16.60), preterm labor (OR, 1.98; CI, 1.55–2.53), as well as mean neonatal weight (2830.77 ± 81.31 g and 3038.53 ± 482.23 g; P = 0.001) were different in the 2 groups and the differences were statistically significant.ConclusionAdverse maternal and neonatal outcomes were common in the study group. Extensive education about contraception and safe sex on the one hand, and an effective care plan if pregnancy occurs, should be provided to teenage girls to reduce these poor outcomes.     

Somatic copy number alterations predict response to platinum therapy in epithelial ovarian cancer

ObjectivePlatinum resistance remains an obstacle in the treatment of epithelial ovarian cancer (EOC). The goal of this study was to profile EOCs for somatic copy number alterations (SCNAs) as predictive markers of platinum response.MethodsSCNAs were assessed in a discovery (n = 86) and validation cohort (n = 115) of high risk stage I or stage II-IV EOCs using high-resolution SNP arrays. ASCAT and GISTIC identified all significantly overrepresented amplified or deleted chromosomal regions. Cox regression and univariate analysis assessed which SCNAs correlated with overall survival (OS), progression-free survival (PFS), platinum-free interval (PFI) and platinum response. Relevant SCNAs were also assessed in a pooled analysis involving both cohorts and published SCNA data from The Cancer Genome Atlas (TCGA; n = 227).ResultsWe identified 53 regions to be significantly overrepresented in EOC. Of these, 6 were associated with OS, PFS or PFI in the discovery cohort at P < 0.05. In the validation cohort, amplifications of chromosomal region 14q32.33, which contains AKT1 as a potential driver gene, also correlated with OS (OR = 1.670; P = 0.018). In a pooled analysis of 428 tumors, involving the discovery, validation and TCGA cohorts, 14q32.33 amplifications significantly reduced OS, PFS and PFI (HR = 2.69, P = 1.7 × 10^− 4; HR = 1.82, P = 1.9 × 10^− 2 and HR = 1.80, P = 2.2 × 10^− 2 respectively). Moreover, AKT1 mRNA expression correlated with the number of chromosomal copies of the 14q32.33 region (P = 2.8 × 10^− 11;R² = 0.26).ConclusionsWe established that amplifications in 14q32.33 were associated with reduced OS, PFS, PFI and platinum resistance in three independent cohorts, suggesting that AKT1 amplifications act as a potentially predictive marker for EOC treated with platinum-based chemotherapy.     

Pregnancy on long term follow up in endometriosis patients with evidence of altered peritoneal fluid oxidative stress status

ObjectiveThe aim is to assess whether women with endometriosis, idiopathic infertility, and tubal ligation have different levels of reactive oxygen species (ROS), total antioxidant capacity (TAC), and ROS–TAC score in their peritoneal fluid, and to assess whether the ROS–TAC score is a better predictor of endometriosis and pregnancy than the ROS and TAC scores alone.Materials and methodsPeritoneal fluid from 108 women: 60 with endometriosis, 38 with tubal ligation/reanastomosis and 10 with unexplained infertility was obtained. ROS was measured by the chemiluminescence assay using luminol as the probe and TAC was measured using the colorimetric assay. We compared the three groups on their ROS, TAC, and ROS–TAC scores using Kruskal–Wallis test, and compared the ability of ROS, TAC and the ROS–TAC scores to predict endometriosis vs. idiopathic and tubal, and pregnancy using the DeLong non-parametric method of comparing two dependent ROC curves.ResultsEndometriosis patients had significantly higher ROS values compared with tubal ligation/reanastomosis patients (P = 0.005). Peritoneal fluid TAC levels were not different across the three groups. Significantly lower ROS–TAC score [indicative of higher oxidative stress (OS)] was observed in endometriosis and unexplained infertility patients compared to tubal ligation/reanastomosis patients (overall P = 0.003). There is no evidence that the ROS–TAC score (AUC = 0.71, 95%; CI = 0.60, 0.81) is significantly better at predicting endometriosis diagnosis than either TAC alone (AUC = 0.73, 95%; CI = 0.63, 0.82) or ROS alone (AUC = 0.73, 95%; CI = 0.63, 0.83). Fifty-four patients with endometriosis attempted to become pregnant. Those that became pregnant (20%, 11/54) had significantly lower levels of ROS values (P = 0.001), higher levels of TAC (P = 0.021), and higher ROS–TAC scores (P = 0.002) than endometriosis patients who did not get pregnant.ConclusionEndometriosis patients with lower peritoneal fluid ROS and higher TAC levels were more likely to get pregnant.