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   Table of Contents - Current issue
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October-December 2019
Volume 3 | Issue 4
Page Nos. 195-259

Online since Thursday, January 2, 2020

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EXPERT REVIEW  

Clinical concern of the second pregnancy under the two-child policy p. 195
Zi-Jiang Chen
DOI:10.4103/2096-2924.274552  
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ORIGINAL ARTICLES Top

Extracellular vesicles in mouse testes elevate the level of serum testosterone p. 199
Da-Min Yun, Sheng Gao, Yu Lin, Xiao-Long Wu, A-Juan Liang, Fei Sun
DOI:10.4103/2096-2924.274549  
Objective: Testosterone plays an essential role in maintaining spermatogenesis and male fertility, and the primary known source of testosterone is testicular Leydig cells, which are regulated by luteinizing hormone (LH). However, whether any other ways of testosterone secretion exist still remains unknown. Methods: Transmission electron microscopy was used to detect testicular extracellular vesicles (EVs), which were isolated by an ultracentrifuge process. Separately, the concentrations of follicle-stimulating hormone (FSH), LH, and testosterone were measured by enzyme-linked immunosorbent assay. Results: Some EVs were found by tail vein injection to be present in mouse testes that elevate the circulating testosterone and LH levels in the blood, but do not affect FSH. Separately, they also promote testosterone production in the TM3 Leydig cell line in vitro. To determine whether the EVs from spermatogonia were involved in the secretion of testosterone, we used spermatogonial stem/progenitor cell line C18-4 cells and revealed that C18-4 cells promote production of testosterone in the TM3 Leydig cell line using the EVs. Conclusions: EVs in mouse testes likely originate from spermatogonia and involved in the regulation of the serum testosterone. Our results provide a new mechanism for the regulation of testosterone production.
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Retrospective cohort study of preimplantation genetic testing for aneuploidy with comprehensive chromosome screening versus nonpreimplantation genetic testing in normal karyotype, secondary infertility patients with recurrent pregnancy loss p. 205
Cai-Xia Lei, Jiang-Feng Ye, Yi-Lun Sui, Yue-Ping Zhang, Xiao-Xi Sun
DOI:10.4103/2096-2924.274544  
Objective: To evaluate whether preimplantation genetic testing for aneuploidy (PGT-A) with comprehensive chromosome screening increases live birth rate (LBR) in normal karyotype couples with recurrent pregnancy loss (RPL). Methods: A retrospective cohort follow-up study of 506 couples with RPL was conducted between April 2014 and March 2017. Couples were allocated to two groups according to their decision to choose PGT-A or not. The primary outcome was LBR per start/transfer cycle; secondary outcomes were ongoing pregnancy rate and miscarriage rate. Statistical analyses were conducted using univariate and multivariate logistic regression models adjusted for maternal age. Results: LBR per start (26.6% vs. 15.4%, relative risk [RR]: 2.66, 95% confidence interval [CI] [1.69–4.20], P < 0.0001; adjusted RR [aRR]: 2.40, 95% CI [1.49–3.86], P = 0.0004) and per transfer (44.9% vs. 25.1%, RR: 3.00, 95% CI [1.96–4.60], P < 0.0001; aRR: 2.64, 95% CI [1.68–4.14], P < 0.0001) was significantly higher in the PGT-A group than in the non-PGT-A group. The miscarriage rate was significantly lower in the PGT-A group compared to the non-PGT-A group (15.7% vs. 34.6%, RR: 0.27, 95% CI [0.13–0.57], P = 0.00005; aRR: 0.26, 95% CI [0.12–0.57], P = 0.0007). Conclusions: LBR per start cycle following PGT-A is significantly higher, and risk of miscarriage is significantly lower among infertile couples with RPL, irrespective of maternal age. PGT-A should be recommended to infertile couples with RPL.
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Analysis of the predictive factors for the recurrence of deep infiltrating endometriosis: A 2-year prospective study p. 213
Yun-Xi Zheng, Qi Cheng, Kai-Kai Chang, Jing-Yao Ruan, Qi Tian, Shou-Xin Gu, Yun Chen, Xiao-Fang Yi
DOI:10.4103/2096-2924.274543  
Objective: To investigate factors that may be associated with the recurrence of deep infiltrating endometriosis (DIE) and DIE-related symptoms. Methods: Starting in September 2014, women with a confirmed diagnosis of DIE based on surgical and histological findings were included in the prospective study with a 2-year follow-up in our hospital. A total of 84 consecutive patients were included, all of whom underwent laparoscopic surgery. The data were obtained from the medical records of the patients. Follow-up data, including presence of pain as assessed using the visual analog scale (VAS) score and ultrasonography/magnetic resonance imaging findings, were obtained at 3, 6, 9, 12, and 24 months postoperatively. Variables, such as age, body mass index, severity and duration of symptoms, size and location of the lesion, and pre- and postoperative medical treatment, were evaluated using univariate and multivariate analyses to identify factors correlated to recurrence. Results: A total of 11 (13.1%) patients presented with recurrence, with a mean time to recurrence of 14.2 months. The univariate analysis showed that the longer duration of menstruation (7.4 vs. 6.0, P = 0.010), the more advanced revised American Fertility Society (rAFS) stage (Stages I and II vs. III and IV, χ2 = 9.964, P = 0.001), the higher VAS score for dysmenorrhea (9.4 vs. 5.2, P = 0.001), and the more severe pain during defecation (7.8 vs. 4.8, P = 0.016) were positively correlated to DIE recurrence. However, the multivariate analysis also revealed that a more severe dysmenorrhea and advanced rAFS stage were the independent factors associated with the recurrence of DIE, with an odds ratio of 1.895 (confidence interval [CI]: 1.061–3.385, P = 0.031) and 4.310 (CI: 1.091–17.028, P = 0.037), respectively. Conclusions: More than 10% of patients presented with recurrence of DIE 2 years after surgery. Recurrence of DIE was more common in patients who complained of more severe dysmenorrhea and had an advanced rAFS stage.
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Effects of carbophos on rat testopathy following resveratrol administration: An experimental study p. 222
Cyrus Jalili, Shiva Roshankhah, Azita Faramarzi, Mohammad Reza Salahshoor
DOI:10.4103/2096-2924.274545  
Objective: Carbophos (CAR) is an organophosphate that is most capable of producing free radicals and inducing alteration in some of the male reproductive parameters. Resveratrol (RES) is an herbal polyphenol and exerts beneficial antioxidant effects. This study aimed to evaluate the effects of RES against CAR-induced alteration in reproductive parameters of male rats. Methods: In this experimental study, 48 male rats were randomly assigned to eight groups: Group 1: Normal control (saline) group; Group 2: CAR control (250 mg/kg) group; Groups 3–5: 2, 8, and 20 mg/kg RES, respectively, groups; Groups 6–8: CAR plus 2, 8, and 20 mg/kg RES, respectively, groups. The agents were administered intraperitoneally and by gavage daily for 65 days. Sperm parameters, testis malondialdehyde (MDA) levels, total antioxidant capacity, testosterone levels, and germinal layer height were evaluated and compared among these groups. Results: No significant alterations were observed in RES groups (with different doses) compared to the normal control group (P > 0.05). The levels of all parameters except MDA (which decreased) significantly increased in the CAR plus RES (with different doses) groups compared to the CAR control group (P < 0.01). Conclusions: RES attenuates the toxic effect of CAR on some of the male reproductive parameters.
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Postpartum hemorrhage following cesarean delivery in women with a scarred uterus: A retrospective cohort study p. 230
Bing-Nan Chen, Di Wang, Jia-Po Li, Li-Yang Zhang, Chong Qiao
DOI:10.4103/2096-2924.274548  
Objective: To develop a model to predict the risk of postpartum hemorrhage (PPH) following cesarean delivery in women with a scarred uterus. Methods: A total of 4,637 pregnant women with scarred uterus who underwent a cesarean delivery at a large hospital between January 2014 and December 2017 were enrolled. The women were divided into PPH (n = 287) and non-PPH (n = 4,350) groups. A model to predict PPH (blood loss ≥1,000 mL within 24 h following cesarean delivery) was developed using multivariate logistic regression analysis. Receiver operating characteristic curve was drawn, and the area under curve (AUC) was calculated. Results: The incidence of PPH was 6.19% (287 of 4,637 women). Seven independent risk factors were associated with PPH: maternal age (odds ratio [OR] = 1.42, 95% confidence interval [CI]: 1.02–1.97), previous gravidity (OR = 1.24, 95% CI: 1.01–1.50), placental location (posterior wall of uterus, OR = 0.69, 95% CI: 0.47–1.02; other locations, OR = 1.21, 95% CI: 0.81–1.80), placenta previa (incomplete placenta previa, OR = 10.51, 95% CI: 5.99–18.42; complete placenta previa, OR = 31.65, 95% CI: 21.07–47.54), placenta accreta (OR = 6.39, 95% CI: 4.02–10.16), hypertensive disorders of pregnancy (OR = 2.27, 95% CI: 1.40–3.68), and fetal position (breech position, OR = 2.07, 95% CI: 1.19–3.60; transverse position, OR = 1.07, 95% CI: 0.48–2.41). A predictive model with AUC of 0.89 was developed (95% CI: 0.86–0.91, P < 0.001). Conclusions: A model was developed to predict PPH following cesarean delivery in women with a scarred uterus.
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Carrier rate analysis of single-gene disorders based on 1000 genome project and exome aggregation consortium data p. 235
Meng-Meng Duan, Hua-Jun Zheng
DOI:10.4103/2096-2924.274546  
Objective: Screening variants underlying the single-gene disorder in the general population can help reduce the incidences of birth defects. To determine the most prevalent pathogenic variants causing autosomal recessive diseases, we investigated the frequencies of these variants in six major geographic ancestry groups from Exome Aggregation Consortium (ExAC) database and 26 populations from the 1,000 Genome Project, including three Chinese ethnic groups. Methods: We selected 64 autosomal recessive diseases and collected corresponding causal genes and variants from ClinVar for the analysis. The RS (reference single-nucleotide polymorphism) IDs of these variants were used to search the corresponding VCF file from the 1,000 Genomes Project and ExAC databases. We calculated the frequencies of heterozygotes of each disease variants in the 1,000 Genomes Project and ExAC samples and compared the distribution of disease alleles among different populations. Results: Our analysis revealed that 1,151/212 variants were carried by 60,706/2,504 individuals sequenced in the ExAC/1,000 Genomes Project. The average number of autosomal recessive disease alleles carried by samples from ExAC and 1,000 Genomes Project were 0.53 and 0.68, respectively. These disease alleles showed differential distribution among populations, and some disease alleles were significantly enriched in certain ethnic groups. In addition, 1–2 main pathogenic variants were identified in each disease. Meanwhile, several ClinVar variants with relatively high frequency (>1%) in the samples were found to be benign instead of “conflicting evaluations of pathogenicity.” Conclusions: Our observations revealed that main pathogenic variants existed in certain autosomal recessive disease, suggesting that screening of disease hypermutations in different populations is valuable in reducing the occurrence of birth defects.
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REVIEW ARTICLES Top

Advances on the metabolism of cohesin in age-related chromosomal aneuploidy p. 243
Li-Yuan Tian, Bin Zhang
DOI:10.4103/2096-2924.274547  
Age-related chromosomal aneuploidy is associated with the reduction of cohesin in meiosis. There are many complicated factors affecting the metabolism of cohesion, including the hyperactive separase, abnormal Shugoshin protein degradation, oxidative damage, increased intracellular pH in oocytes, abnormal metabolism of spindle assembly checkpoint, anaphase-promoting complex, and age-related reproductive hormones, which are summarized in the review.
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Endometriosis pathoetiology: The role of micrornas in the dysregulation of endometrial functions p. 247
Jiahui Zhang, Isabelle Baptista, Ping Xia, Bhuchitra Singh
DOI:10.4103/2096-2924.274551  
Endometriosis is a common gynecological disorder characterized by pelvic pain, heavy menstruation, and infertility. The clinical diagnosis of endometriosis is often delayed 8–10 years after the onset of symptoms due to the lack of an effective and reliable noninvasive diagnostic method. In recent years, a number of research studies have reported using microRNAs (miRNAs) as potential noninvasive biomarkers for diagnosing endometriosis. Because miRNAs regulate gene expression, the differential expression of miRNAs in endometriosis patients also provides insight on dysregulated gene expressions in the pathogenesis of endometriosis. In this review, a number of global profiling studies (published through July 2019) that investigated the differential expression of miRNAs in endometriosis were identified. Based on these findings, the role of miRNAs in the pathogenesis of endometriosis, particularly with regard to the dysregulation of endometrial functions, cell cycle regulation, proliferation of endometrial stromal cells, and angiogenesis, was discussed. The potential of these miRNAs as noninvasive diagnostic biomarkers of endometriosis was also discussed.
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The cumulus cells and oocytes: A systematic review of extended culture for intracytoplasmic sperm injection p. 252
Sharon Kim Truong, Bhuchitra Singh, Ping Xia
DOI:10.4103/2096-2924.274550  
Currently-placed protocols for extended culture for in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are not uniformly standardized in determining the optimal stage of oocyte maturation for maximizing clinical outcomes. The objective of this systematic review is to elucidate the relationship between extended cumulus-oocyte culture and its effect on the clinical outcomes of IVF/ICSI. We included an electronic search on PubMed Central as well as the Journal of Fertility and Sterility to yield seven studies on extended oocyte culture for IVF/ICSI. Four of the seven investigations illustrate the promising beneficial relationship of extended culture with conditioned or supplemented media to mimic physiological uterine conditions. Three studies did not capture beneficial relationships between extended oocyte culture and clinical outcomes with unconditioned, unsupplemented maturation medium. Improvement in fertilization rates, oocyte development, and live birth rates may be achieved by extended culture with the addition of supplemental biochemicals. The usage of follicular fluid, cumulus cells, and meiotic inhibitors imitates the physiological in vivo conditions, whereas extended oocyte culture imitates in vivo temporal conditions. The conjunction of extended oocyte culture with supplemented metabolites, either added in maturation media manually or secreted by cumulus-oocyte complexes, mimics natural uterine physiological conditions to improve clinical outcomes for patients seeking IVF/ICSI.
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CASE REPORT Top

46,XY,9(p24)dup(2q35q37.3) with cryptorchidism: A case report and literature review p. 256
Han-Zhi Wu, Chao Lou, Li Liu, Cui-Yun Qin, Hongmin Yan, Rong Qiang
DOI:10.4103/2096-2924.274542  
A young boy with a facial abnormality was brought to our genetics clinic. Physical examination found bilateral cryptorchidism. Several clinical genetic tests, including chromosome microarray analysis (CMA), karyotyping, and azoospermia factor (AZF) microdeletions on the Y chromosome, were used to identify the genetic basis for this abnormality. The karyotype showed a duplication of the chromosome 2q35q37.3 fragment attached to chromosome 9(p24); CMA revealed 2q35q37.3(220,558,895-243,006,013)x3; the Y chromosome showed no AZF microdeletions; and the parent karyotypes were normal. Surgery has been planned to correct cryptorchidism a year after the original examination. A similar case was found previously.
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