Purpose This study aimed to investigate the effect of male semen quality, occupational exposure, and lifestyle on recurrent pregnancy loss (RPL). Methods Information on couples' occupational exposure and lifestyle was collected using a detailed questionnaire from 68 RPL couples and 63 randomly selected healthy controls. Semen parameters were estimated by computer-assisted sperm analysis, and sperm nuclear status was detected with aniline blue (AB) staining. Results Patients in the RPL group had significantly lower viability, normal morphology, and total progressive motility of sperm, and a higher mean percentage of AB staining positive sperm compared with those of controls (P <0.05). There were no differences in sperm concentration, and motility between the groups (P >0.05). Significant odds ratio (OR) was found when occupational exposure and unhealthy habits were superimposed (OR: 11.965, P =0.005). Conclusions In addition to standard female factors for evaluating the risk for RPL, the use of male factors should also be taken into consideration. We found that sperm quality, occupational exposure, and lifestyle are factors that affect RPL. Consequently, occupational exposure and lifestyle factors should constitute an important section of questionnaires given to patients, and these factors should be evaluated by a clinician or trained staff.

5,10-Methylenetetrahydrofolate reductase (MTHFR) catalyzes the metabolism of folate and nucleotides, which are essential for DNA synthesis and methylation. It is highly polymorphic, and its variant genotypes result in lower enzymatic activity and higher plasma homocysteine. Previous studies have provided evidence that a high prevalence of MTHFR gene polymorphisms is frequently detected in patients with autoimmune disease, suggesting a novel genetic association with autoimmune disorders. However, the genetic association between MTHFR and Graves' disease (GD), one of the most common autoimmune diseases, has not been studied. Here, we designed a clinic-based case-control study including 199 GD cases and 235 healthy controls to examine the associations between three common MTHFR polymorphisms (i.e., C677T, A1298C, and G1793A) and GD. Surprisingly, logistic regression analysis shows MTHFR 677CT + TT genotypes are associated with an approximately 42% reduction in the risk of GD in women (adjusted OR = 0.58, 95% CI = 0.3-0.9), compared to the CC genotype, indicating a significant protective effect of 677CT + TT genotypes. Our result provides epidemiological evidence that MTHFR mutation (C677T) protects women from GD. The protective effect, possibly obtained by influencing DNA methylation, should be confirmed in a large number of cohorts.

Genetic abnormalities could account for 10% to 15% of male infertility cases, so increasing attention is being paid to gene mutations in this context. DNAH1 gene polymorphisms are highly correlated with astheno-teratozoospermia, but limited information has been reported on pathogenic variations in DNAH1 in the Chinese population. We explored 4 novel variations of the DNAH1 gene in Chinese infertile patients. Mutation screening of the DNAH1 gene was performed on 87 cases of asthenozoospermia with targeted high-throughput sequencing technology; another 200 nonobstructive azoospermia cases were further analyzed to investigate the prevalence of DNAH1 variations. The effects of the variations on protein function were further assessed by bioinformatic prediction. For carriers of DNAH1 variations, genetic counseling should be considered. Assisted reproductive technologies should be performed for these individuals and microsurgery should be considered for patients with azoospermia. DNAH1 variations were identified in 6 of 287 patients. These included 8 heterozygous variations in exons and a splicing site. Among these, 4 variations (g.52400764G>C, g.52409336C>T, g.52430999_52431000del, g.52412624C>A) had already been registered in the 1000 Genomes and Exome Aggregation Consortium databases. The other 4 novel variations (g.52418050del, g.52404762T>G, g.52430536del, g.52412620del) were all predicted to be pathogenic by in silico analysis. The variations g.52418050del and g.52430999_52431000del were detected in 1 patient who was more severe than another patient with the variation g.52430999_52431000del. Physicians should be aware of genetic variants in male infertility patients and DNAH1 mutations should be considered in patients with asthenospermia or azoospermia.

These results revealed that the kinds of fetal abnormalities, numbers of abortions, and chromosomal abnormality rates increased with increasing maternal age. The most common trisomy types in spontaneous abortions were closely related to maternal age. We hypothesize whether the larger probability of chromosomal abnormalities is due to increased mutation rate with maternal age, or due to a worse in-utero conditions.

Background and objectiveDirect-acting antivirals (DAA) facing resistance continue to be used in some areas worldwide. Thus, identifying hepatitis C virus (HCV) genotypes/subtypes and loci with certain prevalent resistance-associated substitutions (RASs) deserves attention. We investigated the global and regional frequencies of naturally occurring RASs among all confirmed HCV subtypes (n=86) and explored co-occurring and mutually exclusive RAS pairs within and between genes NS3, NS5A, and NS5B.MethodsA total of 213,908 HCV sequences available as of July 10, 2019 were retrieved from the NCBI nucleotide database. After curation, 17,312 NS3, 8,478 NS5A, and 25,991 NS5B sequence fragments from DAA-naïve patients were screened for RASs. MEGA 6.0 was used to translate aligned nucleotide sequences into amino acid sequences, and RAS pairs were identified by hypergeometric analysis.ResultsRAS prevalence varied significantly among HCV subtypes. For example, D168E, highly resistanct to all protease inhibitors except voxilaprevir, was nearly absent in all subtypes except in 43.48% of GT5a sequences. RASs in NS3 exhibiting significantly different global distribution included Q80K in GT1a with the highest frequency in North America (54.49%), followed by in Europe (22.66%), Asia (6.98%), Oceania (6.62%), and South America (1.03%). The prevalence of NS3 S122G in GT1b was highest in Asia (26.6%) and lowest in Europe (2.64%). NS5A L28M, R30Q, and Y93H in GT1b, L31M in GT2b, and NS5B C316N in GT1b was most prevalent in Asia. A150V in GT3a, associated with sofosbuvir treatment failure, was most prevalent in Asia (44.09%), followed by Europe (31.19%), Oceania (24.29%), and North America (19.05%). Multiple mutually exclusive or co-occurring RAS pairs were identified, including Q80K+R155K and R155K+D168G in GT1a and L159F+C316N and R30Q (NS5A)+C316N (NS5B) in GT1b.ConclusionOur data may be of special relevance for those countries where highly effective antivirals might not be available. Considering the specific RASs prevalence will help the clinicians to make optimal treatment choices. The RASs pairs would benefit anti-HCV drug development.