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   Table of Contents - Current issue
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July-September 2019
Volume 3 | Issue 3
Page Nos. 129-193

Online since Friday, September 27, 2019

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EXPERT REVIEW  

Application and challenge of preimplantation genetic testing in reproductive medicine p. 129
Xue-Li Liu, Chen-Ming Xu, He-Feng Huang
DOI:10.4103/2096-2924.268163  
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ORIGINAL ARTICLES Top

Knockdown of the premature ovarian insufficiency candidate gene NUP107 in ovarian granulosa cells affects cell functions, including receptor expression and estrogen synthesis p. 133
Xiao-Cheng Liu, Meng-Xin Han, Yan Xu, Hong-Yan Wang, Bin Li
DOI:10.4103/2096-2924.268158  
Objective: Mutations in NUP107 have been discovered in patients with premature ovarian insufficiency and may have tissue-specific effects in ovarian development. However, the role of NUP107 in human granulosa cell (GC) function and female fertility still remains unknown. In this study, we used RNA interference to investigate how NUP107 dysfunction influences GCs and ovarian development. Methods: Immunohistochemical staining was used to detect the expression of NUP107 in ovaries. Cell counting kit-8 assay, real-time cell analysis, and flow cytometry were used to explore cell proliferation and apoptosis, and an enzyme-linked immunosorbent assay was used to assess the estrogen concentrations. Quantitative real-time reverse transcription-quantitative polymerase chain reaction and Western blot analyses were used to determine the expression of NUP107 and functional receptors. Results: Knockdown of NUP107 expression had little effect on the growth and number of GCs. Further study confirmed that knockdown of NUP107 may interfere with estrogen synthesis in GCs and their sensitivity to the regulation of follicle-stimulating hormone (FSH) by decreasing the expression of estrogen synthesis-related genes AR, CYP17A1, CYP19A1, STAR, and NR5A1. Moreover, knockdown of NUP107 decreased the expression of AMHR2, FSHR, LHR, and ESR1 in GCs, but had no effect on the expression of ESR2. Conclusions: These data revealed that NUP107 may impede follicle growth and maturation by regulating hormone synthesis, sensitivity to follicle-stimulating hormone, and expression of functional receptors in GCs, and may, therefore, interfere with female fertility.
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Distinctive genes involved in steroidogenesis associated with follicular abnormal development in polycystic ovary syndrome model p. 141
Kai-Lun Yu, Xiu-Li Zhang, Xue-Mei Tan, Meng-Meng Ji, Yao Chen, Man-Man Liu, Zeng-Li Yu
DOI:10.4103/2096-2924.268157  
Objective: Polycystic ovary syndrome (PCOS), a heterogeneous endocrine disorder, affects female reproductive function, but its etiology has not been elucidated. In this study, we analyzed the differential genes related to ovarian steroid biosynthesis in patients with PCOS, to explore the mechanism of PCOS. Methods: The GSE59456 data were downloaded from the Gene Expression Omnibus database. We identified differentially expressed genes (DEGs) in ovaries between the female Sprague–Dawley rats those implanted with 5α-dehydrotestestrone (DHT) and those in control (CTL, implanted with empty capsule). Gene ontology, pathway enrichment analysis, and protein–protein interaction (PPI) network construction were subsequently performed. Results: In total, 530 upregulated DEGs and 522 downregulated DEGs were identified. The identified DEGs were mostly associated with steroid biosynthesis. In the PPI network, the module M1 was mainly related to steroid biosynthesis, and five genes (Hsd17b7, Tm7sf2, Idi1, Msmo1, and Sqle) of the module M1 were from the aforementioned group of upregulated genes. Furthermore, the 19 DEGs (Idi1, Cga, C1qb, Thy1, Gpx1, Ctss, Lpl, A2m, Cited2, Plppr4, Prkar2b, Slc44a1, Inha, Rbp4, Pla2g2a, Gata4, Fabp3, Cpa2, and Cpa1) between DHT and CTL groups were associated with the process of the transformation of primordial follicles to primary follicles. Conclusions: These DEGs, such as Hsd17b7, Tm7sf2, Idi1, Msmo1, Sqle, Rbp4, Gata4, Inha, and Cited2, may be used to elucidate the etiology of PCOS, which may provide new insights into the exploration of pathological mechanism and biomarkers for polycystic ovary.
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Fertility and sexual function after loop electrosurgical excision procedure in patients with high-grade squamous intraepithelial lesion p. 148
Meng Yu, Jing-Xin Ding, Ke-Qin Hua
DOI:10.4103/2096-2924.268164  
Objective: Loop electrosurgical excision procedure (LEEP) is the first choice for patients with high-grade squamous intraepithelial lesion (HSIL). This study aimed to investigate postoperative fertility and sexual function in patients with HSIL after LEEP. Methods: This cohort study included patients with HSIL enrolled at 11 obstetrics and gynecology hospitals between January 1, 2013, and December 31, 2015. The patients were treated with LEEP only. Ultimately, 760 patients meet our inclusion and exclusion criteria. Our research included two parts: The effect of LEEP on postoperative fertility and the effect of LEEP on postoperative sexual function. In the two different parts of the research, we chose different case series according to their follow up information. Results: In the LEEP group, 125 patients had successful deliveries and 27 were preterm (21.6%). The risk of preterm birth was significantly higher in the case group (relative risk [RR]: 2.634; 95% confidence interval [CI]: 1.689–4.108). As the cone depth and volume increased, the risk of preterm increased. In this study, the raw relative risk of cesarean section (CS) was increased in the LEEP group, however the constituent ratio of the indications in the LEEP group was not significantly different from that of the control group. With increased cone depth and volume, pain during postoperative sexual intercourse gradually increased. Conclusions: LEEP increases the risk of preterm birth. The risk increases as the cone depth and volume increases. LEEP could lead to pain during sexual intercourse.
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Therapeutic effect of metformin on patients with polycystic ovary syndrome with normal insulin sensitivity: A retrospective study p. 153
Wan-Wan Liu, Dong-Hai Li, Xue-Zhen Luo, Ling-Li Tang, Ying-Li Shi
DOI:10.4103/2096-2924.268160  
Objective: This study aimed at elucidating the therapeutic effectiveness of metformin in polycystic ovary syndrome (PCOS) patients with normal clinical indices of insulin sensitivity. Methods: This study was a retrospective cohort study. Based on their homeostasis model of assessment of insulin resistance (HOMA-IR) results, PCOS patients (n = 113) were allocated to either the IR Group (IR, HOMA-IR >2.69) or the non-IR Group (NIR, HOMA-IR ≤2.69). Metformin was administered to all patients, and their medical history, menstrual status, and endocrine and metabolic characteristics were obtained before and after treatment. The one-way analysis of variance was used to determine the differences between the IR and NIR groups. The paired t-test was used to determine the differences between pre- and posttreatment results. Results: Analyses of baseline characteristics showed that the incidence of IR and glycolipid metabolism is higher within elder PCOS patients. Metformin improved menstrual cycle and ovulation rate in NIR patients, similar to those in IR patients. In the NIR group, metformin decreased luteinizing hormone (LH) levels, free androgen index (FAI) levels, body mass index, and waist circumference, but had no obvious effect on glucose, insulin, and lipid profiles. Whereas in the IR group, metformin not only decreased LH and FAI levels, but also improved glycolipid metabolism. Conclusions: The effect of metformin on PCOS patients with normal insulin sensitivity index suggests that the mechanism of menstrual improvement may not be related to IR. In addition, metformin can improve glycolipid metabolism. Therefore, metformin is suitable for long-term treatment of PCOS and should be more widely used.
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Clomiphene citrate or medroxyprogesterone acetate with human menopausal gonadotropin in poor responders during In vitro fertilization/intracytoplasmic sperm injection treatments combined with embryo cryopreservation? p. 159
Lu Fang, Xiu-Juan Qi, Hong Zhu
DOI:10.4103/2096-2924.268162  
Objective: This study aimed to compare the efficacy of clomiphene citrate (CC) with human menopausal gonadotropin (hMG) and that of medroxyprogesterone acetate (MPA) with hMG in poor responders defined according to the Bologna criteria. Methods: The data of patients with poor ovarian response (POR) according to the Bologna criteria from September 2016 to November 2017 were retrospectively reviewed. All participants received either CC + hMG or the progesterone-primed ovarian stimulation protocol (PPOS) protocol. Results: A total of 340 patients and 563 in vitro fertilization cycles were analyzed in this study. The incidence of spontaneous luteinizing hormone (LH) surge and the mean LH level on trigger day were significantly lower in the PPOS group than in the CC + HMG group (0.04% vs. 3.49% and 4.26 ± 3.59 vs. 9.38 ± 6.92 mIU/mL, respectively, P < 0.05); however, the incidence of premature ovulation was similar between the two groups. The number of viable embryos harvested was not statistically different between the two groups (1.7 ± 1.1 vs. 1.5 ± 0.8, P = 0.06). The mean dose and duration of hMG were significantly higher in the PPOS group than in the CC + hMG group (908.7 ± 556.6 vs. 177.9 ± 214.5 IU and 6.0 ± 3.4 vs. 1.2 ± 1.5 days, respectively, P < 0.05). However, the number of oocytes retrieved, number of metaphase II oocytes, and fertilization rate were comparable between the two groups. Conclusions: The CC with low-dose gonadotropin strategy was superior to the MPA with hMG protocol for POR.
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REVIEW ARTICLES Top

Role of decidual natural killer cells at the Maternal–Fetal interface during pregnancy p. 165
Shao-Liang Yang, Hai-Yan Wang, Da-Jin Li, Ming-Qing Li
DOI:10.4103/2096-2924.268161  
Pregnancy is a complicated process with intricate cell-to-cell crosstalk and immune regulation. Decidual natural killer (NK) cells account for 50%–70% of decidual immune cells in early pregnancy, suggesting that they play important roles in various events, such as embryo implantation and vascular remodeling. Many studies have shown that decidual NK cells interact with other cells either through direct contact or the secretion factors such as cytokines and chemokines. Hence, this review aimed to present the phenotypic characteristics, classification, and functions of decidual NK cells at the maternal–fetal interface during pregnancy.
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Role of oxidative stress and antioxidant therapies in endometriosis p. 170
Kalianee Devi Baboo, Zheng-Yun Chen, Xin-Mei Zhang
DOI:10.4103/2096-2924.268154  
Endometriosis (EMS) is a common gynecological disorder characterized by the presence of endometrial tissue outside the uterine cavity. It is commonly associated with pelvic pain and infertility. The exact pathogenesis remains unclear and many hypotheses have been suggested. In recent years, accumulating evidence indicates that oxidative stress (OS) plays a role in the development of EMS. The treatment of EMS remains a challenge. Antioxidant therapies for effective management of reactive oxygen species and inflammation have generated considerable research interest. Antioxidant agents such as Vitamins C and E, resveratrol, curcumin, melatonin, epigallocatechin-3-gallate, and others have been studied for the treatment of EMS. This review presents the role of OS in pathophysiology of EMS and the antioxidant therapies in its management.
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Cyclooxygenase-2 and decidual immune cells p. 177
Si-Yao Ha, Hui-Li Yang, Zhen-Zhen Lai, Lu-Yu Ruan, Jia-Wei Shi, Ming-Qing Li
DOI:10.4103/2096-2924.268155  
Cyclooxygenase-2 (COX-2) is a rate-limiting enzyme in arachidonic acid (AA) metabolism. COX-2 and its products (prostanoids) serve versatile biological functions during pregnancy. Numerous evidences demonstrate special reprogramming of COX-2-catalyzing AA metabolism in decidual immune cells (DICs), particularly in decidual macrophages, corresponding to special gestational phases. This review summarizes the reprogramming of COX-2-catalyzing AA metabolism in DICs as well as the immunoregulation of diverse COX-2-generating prostanoids in DICs during the different phases of gestation.
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Advances in genetic studies related to polycystic ovary syndrome in the post-genome-wide association studies era p. 185
Xian-Ling Cao, Zhen-Gao Sun
DOI:10.4103/2096-2924.268159  
Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by reproductive and metabolic dysfunction with a genetic predisposition evidenced by familial clustering and twin studies. Patients with PCOS often produce oocytes of poor quality, leading to lower rates of fertilization, cleavage, and implantation, but higher rates of miscarriages and long-term complications. However, the etiology of PCOS still remains uncertain due to unavailability of unified diagnostic criteria and prevalence of clinical heterogeneity. Owing to advances in technology and methods employed for research, large-scale genetic/other studies have provided many new insights into the genetic pathogenesis of PCOS. However, although genome-wide association studies have been conducted, we still need to evaluate the association between specific loci and their relevance in the manifestation of this disease. In this article, we have presented a review of the recent studies.
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CASE REPORT Top

The importance of endocervical curettage in an old post-loop electrosurgical excision procedure woman with abnormal cervical cytology and a normal punch biopsy histology: A case report and literature review p. 191
Luo-Pei Guo, Qing Cong, Hao Zhang, Long Sui
DOI:10.4103/2096-2924.268156  
Endocervical curettage (ECC) is an optional practice during colposcopy, and the indication for endocervical curettage (ECC) is controversial between Europe and the USA. Here, we explored the value of ECC in a specific situation. An elderly post-loop electrosurgical excision procedure woman, who had undergone a colposcopy 4 months before, went for her follow-up and abnormal cytology was found, and both the ECC and punch biopsy showed negative results. Then, a second ECC was performed, which led to the diagnosis of a high-grade squamous intraepithelial lesion. This case report shows that ECC is useful for diagnosing elderly women with Type 3 squamocolumnar junction.
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