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15 November 2019, Volume 38 Issue 6
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The Combined Application of SNP Array Detection and Chromosome Karyotype Analysis in Prenatal Diagnosis of High-Risk Gradivas ZENG Shu-hong，JIANG Yu-ying，WANG Yuan-bai，ZHUANG Jian-long 2019, 38 (6):  445-449.  Abstract ( 1987 )   PDF (940KB) ( 8826 )   Objective：To explore the combined application of single nucleotide polymorphism array (SNP array) and chromosome karyotype analysis in the prenatal diagnosis of pregnant women with different high-risk factors, and to understand the abnormal karyotype detection in different high-risk cases. Methods：A total of 356 pregnant women with high risks were included from January 2016 to June 2018. All of them underwent amniocentesis during the mid trimester of pregnancy. The aminotic cells were used for Karyotype analysis and SNP array. The results of SNP array were compared in the different groups with the high-risk factors including the advanced age, abnormal expression under ultrasound, adverse pregnancy history, chromosomal abnormality of couples, high-risk in serological screening, and two or more high-risk factors. Results：Six aminotic samples were failed to detect. The rate of abnormal chromosome karyotype was 6.29%, while the rate of copy number variation (CNV) in SNP array was 10.57% ( χ2=10.316, P=0.001). Interestingly, there were significant differences in the detection rate of pathogenic CNVs (pCNVs) among those pregnant women with different high-risk factors ( χ2=13.238, P=0.021). Meanwhile, the detection rate of pCNVs in pregnant women with two or more high-risk factors was significantly higher than the rates of pCNVs in other groups, and this rate was also higher than the rate of abnormal karyotype of traditional karyotype analysis ( χ2=4.167, P=0.031). Conclusions：SNP array can greatly increase the detection rate of pCNVs in those pregnant women with high-risk factors, while the application when combined with the routine karyotype analysis can detect the translocations and chimeras of chromosomes complementarily. This strategy can reduce the missed diagnosis and birth defects. We believe that SNP array can be used as the first choice of prenatal diagnosis in those pregnant women with two or more high-risk factors. References | Related Articles | Metrics

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Application of Next Generation Sequencing in Gene Diagnosis of Congenital Hydrocephalus PAN Lei，HE Zhi-ming，ZHANG Rui 2019, 38 (6):  450-453.  Abstract ( 1544 )   PDF (4867KB) ( 8859 )   Objective：To explore the application of next-generation sequencing in the gene diagnosis of congenital hydrocephalus. Methods：We collected a congenital hydrocephalus family, and designed the candidate gene panel according to the clinical characteristics and inheritance pattern. The next-generation sequencing was used to detect gene mutation. Results：L1CAM gene Exon6 mutation c.551G＞A(p.Arg184Gln) was detected in the proband. The proband′ mother and two aunts were c.551G＞A mutation carriers. Conclusions：For congenital hydrocephalus, the main strategy of genetic diagnosis is to screen the suspicious genes according to the clinical phenotype and genetic rules, and to design the gene panel for the next-generation sequencing. This strategy can quickly detect the genetic cause and improve the diagnostic efficiency. Prenatal diagnosis and effective genetic counseling may be provided for these families. References | Related Articles | Metrics

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Level of Benzo(a)pyrene Detected by High Performance Liquid Chromatography in Embryonic Tissues of Rat Early Pregnancy LIANG Jing，HOU Hai-yan，WANG Meng，SUN Yang，CHEN Ya-qiong 2019, 38 (6):  454-458.  Abstract ( 1297 )   PDF (1059KB) ( 8739 )   Objective：To establish a high performance liquid chromatography with fluorescence detection (HPLC-FLD) for the detection of Benzo(a)pyrene in the embryonic tissues of rat early pregnancy, so as to provide experimental data for future clinical application. Methods：The level of Benzo(a)pyrene in the embryonic tissues of rats was determined by Shimadzu HPLC with Shimadzu RF-535 fluorescence detector. The samples were extracted by acetonitrile, without cleaned-up. The chromatographic separation was performed using a column of Kromasil C18 (250 mm×4.6 mm, 5 μL) with a mobile phase consisting of methanol and water (95∶5, V/V) at the flow rate of 1.0 mL/min. Excitation wavelength (Ex) of fluorescence detection was 364 nm, the emission wavelength (Em) 427 nm, and the injection volume 20 μL. Results：The level of Benzo(a)pyrene in the tissues of rats was linear in the range of 0.002 μg/mL to 0.5 μg/mL. The regression equation of standard curve of extraction was ■=426 174x－316.95 with a correlation coefficient of 0.999 9. The average recovery for Benzo(a)pyrene standard spiked was more than 95% while the inter-day precision RSD was 3.38%, the intra-day precision RSD was 2.80%, and the stability (n=6) was 2.58%. The benzo(a)pyrene concentration of samples was in the range of 0-0.5837 μg/g. Conclusions：The HPLC-FLD method has the advantages of simple operation, low experiment cost, and coincident veracityand sensitivity. The process of sample extraction is simple and time-saving. We conclude that the HPLC-FLD may be a suitable way for the detection of benzo(a)pyrene in samples such as embryonic tissues in the clinical practice and research projects. References | Related Articles | Metrics

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Association between the Polymorphisms of IL-2 (rs6822844) and IL-2Ra (rs2104286) SNPs and the Unexplained Recurrent Spontaneous Abortion DENG Miao，ZHANG Hong-yan，WANG Chong，LIU Yuan-wei，SHENG Zhu-mei，ZHANG Zhi-fen 2019, 38 (6):  459-462.  Abstract ( 1155 )   PDF (7017KB) ( 8649 )   Objective：To investigate the association between the polymorphisms of single nucleotide polymorphisms (SNPs) of interleukin-2 gene (IL-2), IL-2 receptor α gene (IL-2Rα) and the susceptibility to unexplained recurrent spontaneous abortion (URSA). Methods：Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analysis SNPs of IL-2 (rs6822844) G/T and IL-2Rα (rs2104286) A/G in 145 URSA cases (URSA group) and 220 nomal controls (control group). Results：The frequencies of rs2104286 allele A and genotype A/A were higher in the URSA group when compared with the control group (P＜0.05). The carriers of rs2104286 allele A increased two times of the risk of URSA (OR=2.06, 95%CI: 1.34～3.16, P=0.001), so did the rs2104286 genotype AA (OR=2.27, 95%CI: 1.40～3.68, P=0.001). The frequencies of rs6822844 genotype G/G in the two groups were all 100% (P＞0.05). Conclusions：Allele A of IL-2Rα (rs2104286) might confer the susceptibility to URSA in Zhejiang. IL-2 (rs6822844) had no association with URSA. References | Related Articles | Metrics

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Recovery of Fertility after Removal of IUD: A Cohort Study ZHOU Jian，YANG Yue-hua，WANG Guan-rong，SHI Wen-hui，BA Lei，ZHANG Min，XU Hao-qin 2019, 38 (6):  463-466.  Abstract ( 1287 )   PDF (948KB) ( 8735 )   Objective：To investigate the effect of intrauterine device (IUD) on female fertility. Methods：From July 1, 2016 to September 30, 2017, two-way cohort study was used to observe the pregnancy within one year after using IUD as the observation cohort (1 361 cases) and condom women as the control cohort (1 307 cases) after giving birth to one child. The cumulative pregnancy rate of one year was calculated and the Cox proportional hazard model was used for multivariate analysis. Results：The average days of pregnancy in IUD group and control group were (144.1±96.86) days and (122.5±91.33) days, respectively. There was statistically significant difference between the two groups (P＜0.05). The cumulative pregnancy rate in IUD group was lower than that in control group. The difference was statistically significant (P＜0.05). The cumulative pregnancy rate of one year after removal of IUD for less than 5 years was 0.866 times higher than that of condom group (95%CI: 0.788～0.952). Multivariate Cox regression analysis showed that using of high copper IUD had a slighter effect on pregnancy (HR=0.826, 95%CI: 0.720～0.947) than using condoms. Conclusions：The cumulative pregnancy rate of one year after removal of high copper IUD was lower than that in condom group, and the pregnancy time was longer. It is suggested that if the subjects with using high copper IUD have plans for reproduction in the near future, IUD should be removed as early as possible to prepare for fertility. References | Related Articles | Metrics

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Effect of Irisin on Endometrial Function in Obese Rats ZHOU Li，LI Cheng-gang，ZHAO Yu-juan，CHEN Li 2019, 38 (6):  467-470.  Abstract ( 1225 )   PDF (8879KB) ( 8556 )   Objective：To investigate the effect of Irisin on the endometrial function in obese rats. Methods：Female SD rats were treated with high-fat diets to induce obesity, while the normal-control group (n=16) was treated with normal diets. The obese rats were randomly divided into the model-control group (n=16) and the irisin group (n=16). The rats in the irisin group were injected intraperitoneally with recombinant irisin [100 ng/（g·d）×14 days], while the rats in the two control groups were injected with normal saline. Then, female rats in estrus were mated with male rats. Eight rats were sacrificed in each group on the day 5 and day 10 of pregnancy. The pregnancy rate, average number of blastocyst and embryo morphology were observed. The expressions of leukemia inhibitory factor (LIF) and integrin αvβ3 in the implantation sites were determined. Results：The body weight in the irisin group after treatment was significantly lower than that in the model-control group (P=0.035), and the average number of blastocyst in the model-control group were significantly lower than that in the irisin group and the normal-control group (both P＜0.05). The endometrium of the normal-control group was full, and the embryo was well developed. The uterine cavity in the model-control group was large, and the embryonic development was poor. The endometrium of the irisin group was closed, and the embryonic development was well improved. The expression levels of LIF and integrin αvβ3 mRNAs and proteins in the model-control group were significantly lower than those in the normal-control group and the irisin group (all P＜0.05). Conclusions：Irisin can improve the endometrial receptivity of obese rats by increasing the expressions of LIF and integrin αvβ3 in endometrium. References | Related Articles | Metrics

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Correlation between FSH and Metabolic Syndrome in Postmenopausal Women: A Meta-Analysis MA Ting，SUN Xiao-yan，YU Xiao，ZHANG Xue-hong 2019, 38 (6):  471-477.  Abstract ( 1317 )   PDF (1492KB) ( 8716 )   Objective：To investigate the correlation between metabolic syndrome (MS) and serum follicle-stimulating hormone (FSH) level in postmenopausal women. Methods：PubMed, Web of Science, CNKI and VIP databases were searched to collect observational studies on the relationship between FSH level and MS in postmenopausal women. The retrieval time was from the establishment of the database to March 31, 2019, and the languages were Chinese and English. RevMan 5.3 software was used for Meta analysis. Results：A total of 6 case-control studies and 2 cross-sectional studies were included in the meta-analysis, including 494 cases of post-menopausal women with MS and 603 cases of post-menopausal women without MS. There was no significant difference in FSH level between postmenopausal women with MS and without MS. The subgroup analysis also showed that there was no significant difference in the FSH level detected by enzyme-linked immunoassay between above two groups (SMD=-0.29, 95%CI: -0.93～0.35, P=0.38). However, the FSH level detected by chemiluminescence (SMD=-0.72, 95%CI: -1.03～-0.41, P＜0.000 01), or by radioimmunoassay (SMD=-0.38, 95%CI: -0.65～-0.11, P=0.006), in MS postmenopausal women was significantly lower than that in non-MS post-menopausal women. In addition, FSH levels in early and middle menopausal MS women were lower than those in non-MS menopausal women. After sensitivity analysis, FSH level of post-menopausal MS women was significantly lower than that of post-menopausal non-MS women (SMD=-0.44, 95%CI: -0.77～-0.11, P=0.009). Conclusions：The lowered level of FSH may be a risk factor of MS in postmenopausal women. References | Related Articles | Metrics

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Isolated Torsion of Fallopian Tube Complicating Pregnancy: A Case Report and Literature Review WANG Yan，QI Yue，ZHA Wen-hui，CHEN Yang，WU Fu-ju 2019, 38 (6):  478-482.  Abstract ( 1266 )   PDF (6654KB) ( 8776 )   Tube torsion refers to a gynecological acute abdominal disease, in which the fallopian tube rotates on its own axis, without ipsilateral ovarian torsion. The incidence is very low, only 1/1 500 000. Clinical symptoms are not typical, easy to cause misdiagnosis. Tube torsion during pregnancy is even rarer, accounting for 12% of all cases of tubal torsion. Due to the lack of specific examination methods, the diagnoses are often delayed, even resulting in peritonitis and thereby endangering the life of the mother and baby. A case of pregnancy complicated with tubal torsion in our hospital was reported as follows, with a review of literatures, in order to explore the clinical characteristics and treatment methods of this rare and complex disease, so as to improve our ability of diagnosis and treatment. References | Related Articles | Metrics

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Ovarian Micropapillary Serous Borderline Tumor: A Case Report and Literatures Review GU Lu-lu，WU Fei，HUANG Zhi-ling，LENG Jia-li，ZHANG Li-hui 2019, 38 (6):  480-482.  Abstract ( 1680 )   PDF (6730KB) ( 8806 )   Micropapillary serous borderline tumor (MPSC) is a very rare type of ovarian cancers. Although it does not show the destructive invasive growth, it is associated with other malignant behaviors of ovarian cancer. Compared with the serous lesions without micropapillary structure, ovarian MPSC has the high probability of bilateral tumor and surface involvement, and the high incidence of invasive intraperitoneal implantation, which is equivalent to the non-invasive low-grade serous carcinoma. Until now, there are no clear clinical norms or guidelines for the treatment of MPSC. There is some controversy to the effect of micropapillary structure on the prognosis of those patients with serous borderline ovarian tumor. Combined with a case of ovarian MPSC with noninvasive intraperitoneal implantation from our hospital, this article mainly discusses the treatment of MPSC in order to improve the clinicians′ understanding. References | Related Articles | Metrics

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Ovarian Growing Teratoma Syndrome: A Case Report with Mini Review YAO Ying-chun，WANG Ling，HAN Li-ying 2019, 38 (6):  483-485.  Abstract ( 1395 )   PDF (6688KB) ( 8807 )   Ovarian growing teratoma syndrome (GTS) , as a rare complication, is characterized by the increase in tumor size or tumor number, or both, with the normalization of tumour markers during or after chemotherapy or radiological therapy. Histopathological test showed a mature teratoma without any malignant component. Although the diagnosis is clear, many oncologists often misinterpret because of its rarity. The exact etiology and pathogenesis of this disease are still unclear. Surgery is the best treatment as this disease is resistant to chemotherapy and radiation. We reported a case of GTS, and reviewed relevant literatures, to provide a reference for clinical diagnosis and treatment. References | Related Articles | Metrics

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Congenital Adrenal Hyperplasia Combined with Male Infertility: A Case Report WANG Li，CHEN Yong，JIANG Wen-hui，TIAN Er-po 2019, 38 (6):  486-488.  Abstract ( 1637 )   PDF (831KB) ( 8703 )   Congenital adrenal hyperplasia (CAH), an autosomal recessive disease, is characterized by the adrenocortical steroid hormone synthesis disorder. The most common type is 21-hydroxylase deficiency. This disease is generally accompanied with male infertility, which is mainly due to adrenal residual tumors and the change of gonadotropins. The diagnosis of CAH is often missed due to its rarity and atypical symptoms. The early diagnosis and treatment in childhood can improve the reproductive function of male patients in adults. CAH is mainly treated with glucocorticoid, and some of adult male patients can restore their fertility. For those male patients who can not restore their natural fertility, the assisted reproductive technology can be recommended. Meanwhile, if the diagnosis of CAH in adults was definite, the sperm cryopreservation should be done as soon as possible. In this article, we report a case of CAH with male infertility and provide a short review. References | Related Articles | Metrics

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Clinical Application of PPOS Protocol and Its Safety YU Xiao，MA Ting，ZHANG Xue-hong 2019, 38 (6):  489-492.  Abstract ( 1787 )   PDF (893KB) ( 8928 )   It is essential to block the adverse effects of premature LH surge on developmental oocyte in the process of the controlled ovulation stimulation. The traditional protocols of ovulation induction, such as gonadotropin-releasing hormone agonist and antagonist, have some disadvantages of increasing incidence of ovarian hyperstimulation syndrome, high cost and inconvenience. In 2015, Professor Kuang YP proposed the progestin primed ovarian stimulation protocol (PPOS), in which exogenous progesterone was used to inhibit LH peak, and to combine with human menopausal urinary gonadotropin (hMG) to stimulate ovulation. PPOS protocol had been proved to be effective in inhibiting premature LH peak, obtaining good quality embryos and satisfactory clinical outcomes in women with all kinds of ovarian reactions. At present, progesterone drugs used in PPOS protocol include medroxyproges acetate, utrogestan and dydrogesterone. It is also necessary to concern the security of PPOS protocol. We reviewed the mechanism of PPOS protocol, the application population, the effeciency of different progesterone drugs, the effects on the quantity and quality of oocytes retrieved and the clinical outcomes, as well as the safety of newborn. References | Related Articles | Metrics

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Regulation of the Cytokins from Mesenchymal Stem Cells on Oxidative Stress LIU Han-wen，QIN Lian-ju，CUI Yu-gui 2019, 38 (6):  493-497.  Abstract ( 1248 )   PDF (1025KB) ( 8810 )   The pathophysiological process of diseases is mostly accompanied by the elevated level of oxidative stress, including those reproductive endocrine diseases such as polycystic ovary syndrome, decrease ovarian reserve and premature ovarian failure. Stem cells have been used in the cell therapy or clinical trials of many diseases including endometrial adhesion, polycystic ovary syndrome and premature ovarian failure, in which mesenchymal stem cells (MSC) have distinct advantages over embryonic stem cells (ESC) and induced pluripotent stem cells (iPS). Numerous cytokines secreted by MSC have a regulatory effect on oxidative stress in tissues and cells. It has been found that interleukin-6 (IL-6) and brain-derived neurotrophic factor (BDNF) decrease the level of oxidative stress by the activated Nrf2 pathway. In this paper, the anti-oxidative stress of the cytokins from mesenchymal stem cells is reviewed, as well as its possible intracellular mechanism, so as to provide a new idea for the further clinical trial of the cell therapy with mesenchymal stem cells. References | Related Articles | Metrics

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Progress on the Ovarian Cryopreservation and Transplantation WANG Sheng-cun，LI Bi-chun 2019, 38 (6):  498-503.  Abstract ( 1243 )   PDF (920KB) ( 8749 )   There are a large number of eggs in the ovaries of mammals, which is a resource pool of female germ cells. It is expected to restore maternal fertility, and to maintain normal levels of hormones, by the cryopreservation of healthy ovarian tissue, rapid resuscitation and then orthotopic transplantation to the pelvic cavity or heterotopic transplantation to the subcutaneous and renal capsule and other parts. The success of ovarian tissue transplantation depends on the size of graft, the duration of local ischemia, exogenous antioxidants and angiogenic factors. At present, there have been a few reports of human ovarian cryopreservation and transplantation, and the success of live births. More animal experiments confirmed this possibility. In this paper, the research progress on the ovarian cryopreservation and transplantation is reviewed. References | Related Articles | Metrics

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Research Progress of BMI in Female Infertility ZHANG Qian-qian，HE Yu-jie 2019, 38 (6):  504-509.  Abstract ( 1330 )   PDF (947KB) ( 8720 )   Obesity causes the ovulation disorder, difficulty conceiving naturally and infertility. With the incidence of infertility in obese women increasing, the number of people seeking assisted reproductive technology is also rising. Obesity increases the days and doses of Gn, decreases the number of eggs obtained, and reduces the clinical pregnancy rate and live birth rate. Obesity affects oocyte quality, preimplantation embryo quality and endometrial receptivity. Obesity affects oocyte quality by altering follicular fluid metabolites and gene expression, increasing lipotoxicity and adiponectin, and intervening telomere morphology. The model of diet induced obesity (DIO) showed that the delayed development of oocyte and the change of cell composition affected the quality of embryo. Animal models showed that obesity impaired endometrial decidualization. The endometrial receptivity array (ERA) and sequence analysis showed that the abnormal gene expression in endometrium of implantation window affected endometrial receptivity. Obese pregnancies increase the risk of obstetric complications. Obesity in mothers increases the risk of metabolic disorders in multigenerations, which is an intergenerational effect. Weight loss methods includes lifestyle improvement, drug intervention, surgery and so on. In clinic, obese couples are advised to lose weight timely and reasonably according to their age and ovarian reserve. References | Related Articles | Metrics

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Cesarean Scar Diverticulum and Treatment Options ZHANG Yi-xin，YANG Qing 2019, 38 (6):  510-513.  Abstract ( 1504 )   PDF (901KB) ( 8960 )   Cesarean scar defect (CSD), a long-term complication of cesarean section, is defined as the localized dilation and cystic protrusion of the intimal layer to the extramuscular process in the scar with poor healing. The main manifestations of CSD are irregular vaginal bleeding, dysmenorrhea, chronic pelvic pain, secondary infertility and so on. Current treatments include drug therapy, hysteroscopic diverticulum removal and transvaginal/laparoscopic diverticulum repair. The most suitable treatment option should be personalized for CSD patients with different conditions, which is the emphasis of clinical research. Especially, for those CSD patients with fertility requirements, the focuses on treatment option are whether to undergo surgical repair before the next pregnancy, what kind of operation to be the most appropriate, and whether the outcome of pregnancy after surgical repair to be well improved. References | Related Articles | Metrics

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Advances in the Diagnosis and Treatment of Chronic Endometritis YE Hai-hua，LU Li-mei，DAI Yu-jing，LIANG Yan-chun 2019, 38 (6):  514-518.  Abstract ( 1501 )   PDF (962KB) ( 8765 )   Chronic endometritis (CE) as the chronic and persistent inflammation of endometrium is characterized by the infiltration of plasma cell in the matrix of endometrium. The clinical symptoms of CE is mild and atypical. As a result, CE is easy to be neglected. CE is closely related to abnormal uterine bleeding, uterine adhesion, infertility, recurrent implantation failure and recurrent miscarriage. The diagnostic methods of CE include hysteroscopy, histopathological examination of endometrium and microorganism culture of endometrium. Recently, researchers propose that immunohistochemical staining of CD138 can specifically recognize plasma cell in the matrix of endometrium and improve the clinical diagnosis rate of CE. In addition, the detection of microorganism by reverse transcription polymerase chain reaction (RT-PCR) also helps the diagnosis of CE. Specific microRNAs in the blood and endometrium are also used as the potential diagnostic markers of CE. However, the diagnostic criteria of CE is still not standardized. The first line treatment of CE is antibiotics (such as doxycycline, ciprofloxacin, ofloxacin, metronidazole, etc.), with a high cure rate. And the treatment of CE improves the pregnancy outcomes of those women with infertility, recurrent implantation failure, and recurrent miscarriage. References | Related Articles | Metrics

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Diagnosis and Treatment of Adenomyosis SHEN Hao-fei，JIA Tian-yu，WANG Yi-xiang，HE Xiao，ZHANG Xue-hong 2019, 38 (6):  519-522.  Abstract ( 1396 )   PDF (917KB) ( 8654 )   Adenomyosis (AD) as a benign uterine disease is characterized by ectopic endometrial glands and stroma in the myometrium. The pathomechanism of AD is still unclear. This disease often occurs in women of childbearing age from 30 to 50 years old. Clinical manifestations may be asymptomatic, hypogastralgia or abnormal uterine bleeding. Transvaginal ultrasound and magnetic resonance imaging are helpful in the diagnosis of AD. Although diagnostic methods have been improved, there is not a uniform classification of AD. The patients′ understanding is still insufficient. Currently, the therapy drug for this disease includes gonadotropin-releasing hormone agonist and levonorgestrel intrauterine sustained release system. The conservative surgery includes uterine artery embolization, lesion resection and high intensity focused ultrasound. Studies have shown that AD has a negative impact on female fertility, with high risks of miscarriage and obstetric complications. After the effective treatment, the fertility can be improved. It is necessary to develop a lifelong health management plan for those AD patients. References | Related Articles | Metrics