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15 January 2024, Volume 43 Issue 1
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Original Article
Case Report
Review


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Original Article

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Risk Factors of Unusable Embryos for IVF/ICSI in Older Women LIANG Jun-xia, YANG Yu-jie, ZHANG Li, GE Li-na, WANG Na-na, TIAN Ying, LIU Peng, YAN Meng 2024, 43 (1):  1-6.  doi: 10.12280/gjszjk.20230221 Abstract ( 573 )   HTML ( 46 )   PDF (1003KB) ( 522 )   Objective: To investigate the risk factors of unusable embryos after egg retrieval in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in older women. Methods: A total of 569 egg retrieval cycles of older women who underwent IVF/ICSI assisted pregnancy in the Reproductive Center of Hebei Reproductive Health Hospital from January 2015 to December 2021 were retrospectively analyzed, including 95 cycles with unusable embryos as the study group and 474 cycles with usable embryos as the control group. According to the age, each group was divided into three subgroups: G1 group aged 35 to 39 years, G2 group aged 40 to 42 years, and G3 group aged 43 to 45 years. Ovulation induction and laboratory indexes were compared. Results: The differences of age, infertility years, body mass index (BMI), basic follicle-stimulating hormone (FSH), basic estradio (E2), anti-Müllerian hormone (AMH) and antral follicle count (AFC) on the start day in the corresponding subgroups between the two groups were not statistically significant (all P>0.05). There were significant differences in the level of luteinizing hormone (LH) on the trigger day between G2 subgroups (P<0.05). On the trigger day, the differences in the E2 level and follicular output rate (FORT) between G1 and G2 subgroups of both groups were statistically significant (all P<0.05). The differences of preponderance follicle count (PFC) on the trigger day among the three subgroups of both groups were statistically significant (P<0.05). There were no significant differences in gonadotropin (Gn) dosage, Gn days, trigger action time, trigger day progesterone (P) level and trigger day E2/PFC among 3 subgroups of both groups (all P>0.05). Meanwhile, the differences in the number of eggs obtained, the number of MⅡ eggs, the total number of fertilization, the total number of cleavage, the number of 2PN and the number of 2PN cleavage statistically significant (all P<0.05). Interestingly, Logistic regression analysis showed that the infertility year was a risk factor of unusable embryos after egg retrieval, while PFC on the trigger day was a protective factor. Conclusions: In IVF/ICSI assisted pregnancy for older women, the occurrence of non-transplantable embryos will increase with the increase of infertility years, while the increase of PFC on the trigger day will reduce the risk of non-transplantable embryos. Figures and Tables | References | Related Articles | Metrics

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Stigma and Influencing Factors in Infertile Patients with Polycystic Ovary Syndrome LUO Li-yan, JIN Ye, SHI Li, HAN Mei, YU Ran, SONG Dong-hong 2024, 43 (1):  6-10.  doi: 10.12280/gjszjk.20230452 Abstract ( 541 )   HTML ( 29 )   PDF (946KB) ( 518 )   Objective: To investigate the status of stigma and influencing factors in infertile patients with polycystic ovary syndrome (PCOS). Methods: Using the convenience sampling method, infertile patients with PCOS diagnosed and treated in the Reproductive Medicine Center of Peking University Third Hospital were selected from January 2022 to March 2023. A cross-sectional study was conducted using the general information questionnaire, Infertility Stigma Scale (ISS) and Fertility Problem Inventory (FPI). Results: A total of 269 questionnaires were distributed on this occasion, in which 251 were deemed valid, resulting in an effectiveness rate of 93.3%. The total scores of ISS and FPI in infertility patients with PCOS were (61.49±23.25) and (148.32±31.02) respectively, with a positive correlation between ISS and FPI (r=0.719, P<0.001). Hierarchical multiple regression analysis showed that fertility stress was the influencing factor of stigma in infertile patients with PCOS, which explained 43.5% of the total variation. Conclusions: Stigma in infertile patients with PCOS is at the medium level. Clinical medical staff can focus on and identify patients with high fertility stress. Interventions should be developed according to the influencing factors to reduce the level of stigma. Figures and Tables | References | Related Articles | Metrics

Case Report

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45,X/47,XYY Disorders of Sex Development: A Case Report and Literature Review TIAN Wen-yan, LUO Ying, LI Xiao-yan, YAN Qi, XUE Feng-xia, WANG Ying-mei, ZHANG Hui-ying 2024, 43 (1):  11-16.  doi: 10.12280/gjszjk.20230352 Abstract ( 601 )   HTML ( 30 )   PDF (6520KB) ( 512 )   45,X/47,XYY sexual dysplasia is a disorder of abnormal sexual development due to a rare chromosomal abnormality. We report a case of 45,X/47,XYY mosaicism disorders of sex. The patient presented with primary amenorrhea and masculinization, as well as Turner syndrome. Laparoscopic exploration showed gonadal type for one side the cord-like gonads, one side the ovoid structure. The pathological condition was cryptorchidism type gonadal gland. Bilateral appendages were surgically removed, artificial cycle therapy was given, and then the patient had menstruation. In this paper, we summarized a total of 11 cases, including this case and other ten cases with the female phenotype reported in the literature, seeing a doctor for primary amenorrhea were found. The clinical manifestations, diagnosis and treatment of this disease were summarized as follows: women with phenotype 45,X/47,XYY sexual dysplasia have various clinical manifestations, most of which are Turner syndrome combined with masculinization. It should be early detection and removal of dysplasia gonads, to prevent the occurrence of gonadal tumors and masculine effects. Long-term alternative hormone therapy and psychological counseling should be performed after surgery. Figures and Tables | References | Related Articles | Metrics

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A Case of Oocyte Maturation Arrest Caused by Heterozygous Variation of TUBB8 Gene c.154-156del WEN Xing-xing, CHAI Meng-han, YANG Ni, ZOU Hui-juan, ZHANG Zhi-guo, LI Lin, CHEN Bei-li 2024, 43 (1):  17-19.  doi: 10.12280/gjszjk.20230220 Abstract ( 561 )   HTML ( 26 )   PDF (3896KB) ( 461 )   Whole exome sequencing was carried out in a patient with oocyte maturation arrest, and the suspected pathogenic variants were screened by bioinformatics and verified by Sanger sequencing on the patient and her family members. A heterozygous deletion variant of the TUBB8 gene c.154-156del(p.52del) was identified in the patient, but was not found in her parents, brother, sister and niece. Both her brother and sister gave birth. This variant co-segregated with the phenotype. The c.154-156del(p.52del) heterozygous deletion variant of the TUBB8 gene may be the genetic cause of this patient with oocyte maturation arrest. TUBB8 gene mutation accounts for about 30% of patients with oocyte maturation arrest. For the patients with oocyte maturation arrest, TUBB8 gene test can be routinely performed in genetic counseling. The patients caused by TUBB8 gene mutation can only conceive through oocyte donation. Figures and Tables | References | Related Articles | Metrics

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A Case of 45,X/46,XY Chromosomal Mosaic Infertility ZHANG Xiao-cui, YU Li-fei, YANG Yue-wei, LIU Yun-jing, HUANG Wei-dong, YI Jiang-yan, ZHANG Xue-ping 2024, 43 (1):  20-23.  doi: 10.12280/gjszjk.20230265 Abstract ( 516 )   HTML ( 12 )   PDF (1974KB) ( 560 )   45,X/46,XY chromosomal mosaic is a relatively rare disease in clinical. Patients with this type of chromosomal mosaic manifest either male or female external characteristics, with clinical features resembling Turner syndrome but milder in severity. We report a case of male phenotype patient who sought medical attention for infertility. Through G-banding chromosome karyotype analysis and whole-genome copy number variation (CNV) analysis of peripheral blood DNA, the patient was diagnosed with 45,X/46,XY chromosomal mosaic. A total of 50 chromosome karyotypes from peripheral blood lymphocytes were analyzed, revealing a karyotype diagnosis of 45,X[27]/46,XY[23]. Whole-genome CNV analysis detected a mosaic pattern with partial loss of the Y chromosome (64%), while Y chromosome microdeletion analysis did not show any noticeable abnormalities. The cases of 45,X/46,XY chromosomal mosaic with male phenotype are relatively uncommon. In this specific case, the patient exhibited a short stature and genital deformity, representing a milder clinical phenotype. Figures and Tables | References | Related Articles | Metrics

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Triplet Pregnancy Complicated by Twin Reversed Arterial Perfusion Sequence after Assisted Reproductive Technology: A Case Report and Literature Review LI Ting-ting, TAN Xiao-fang, SHI Wei-hong 2024, 43 (1):  24-27.  doi: 10.12280/gjszjk.20230208 Abstract ( 559 )   HTML ( 19 )   PDF (1362KB) ( 472 )   Twin reversed arterial perfusion sequence (TRAPS) is a rare and severe complication of monochorionic twin pregnancies, due to abnormal placental-fetal vascular anastomosis, which is characterized by absence of heart or loss of normal cardiac structure in one twin. We reported a case of triplet pregnancy complicated by TRAPS after assisted reproductive technology. Two cleavage-stage frozen embryos were transferred, one of which developed into monochorionic twin pregnology. The TRAPS was diagnosed by ultrasound at 8+5 weeks. However, due to personal factors, the patient did not intervene in a timely manner and the pump twin died. Another single fetus developed normally until full term delivery. If the treatment is needed, as for the technique of choice to interrupt the vascular supply to the acardiac twin, the radiofrequency ablation of the intrafetal vessel is usually the preferred approach. However, the best timing of intervention is still debated. Figures and Tables | References | Related Articles | Metrics

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A Case of Tubal Ectopic Pregnancy with Hydatidiform Mole and Intraperitoneal Hemorrhage ZHANG Tong, YE Hong 2024, 43 (1):  28-31.  doi: 10.12280/gjszjk.20230250 Abstract ( 588 )   HTML ( 24 )   PDF (7774KB) ( 500 )   Tubal ectopic pregnancy with hydatidiform mole is extremely rare in clinical practice, and preoperative diagnosis is often difficult. The diagnosis is mainly based on the postoperative histopathology results. This article reports a 38-year-old woman whom underwent laparoscopic right fallopian tube resection in an emergency due to rupture of right fallopian tube pregnancy. The postoperative pathology revealed completeness hydatidiform mole. The patient recovered well after surgery, with a satisfactory decrease in serum human chorionic gonadotropin (hCG) during the follow-up period. There were no symptoms of vaginal bleeding, coughing, hemoptysis, or related lesion metastasis. Tubal pregnancy with hydatidiform mole often manifests as acute abdominal disease. Therefore, for patients with acute abdominal disease, the possibility of hydatidiform mole should be paid to. The treatment is mainly based on surgery, and chemotherapy should be performed if necessary. After surgery, close follow-up is required, and doctors should be noting the possibility of lesion erosion and malignancy too. Figures and Tables | References | Related Articles | Metrics

Review

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Pathways of Insulin Resistance in Ovarian Granulosa Cells of Polycystic Ovary Syndrome Patients REN Lu-lu, REN Wen-chao, ZHANG Xiao-xuan, REN Chun-e 2024, 43 (1):  32-37.  doi: 10.12280/gjszjk.20230330 Abstract ( 627 )   HTML ( 22 )   PDF (1009KB) ( 506 )   Insulin resistance (IR) is associated with the genesis and development of polycystic ovary syndrome (PCOS). The abnormity of insulin-related signaling pathways causes metabolism disorder, which affects follicle development and quality. In ovarian granulosa cells of PCOS, the classical pathways of insulin include phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK). The pathways related with inflammation include Toll-like receptor (TLR)/nuclear factor-κB (NF-κB), and the pathways of oxidative stress include nuclear factor-erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) and GTPase of immunity-associated protein 7 (GIMAP7)/ sonic hedgehog (SHH). There are multiple pathways related with metabolism, such as the lipid metabolism-related pathway of activating transcription factor 4 (ATF4). Therefore, clarifying the IR-related signal transduction pathway and molecular mechanism in ovarian granulosa cells of PCOS patients can supplement the knowledge of PCOS pathogenesis, and further provide new ideas for the treatment of PCOS. References | Related Articles | Metrics

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Research Progress on Post-Translational Modification in Polycystic Ovary Syndrome LIU Yi-ran, FENG Rui-zhi, QIAN Yun 2024, 43 (1):  38-42.  doi: 10.12280/gjszjk.20230372 Abstract ( 605 )   HTML ( 16 )   PDF (908KB) ( 474 )   Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women, but its pathogenesis is unknown. Current researches suggested that the disease may be influenced by a variety of factors, including epigenetic and environmental factors. In recent years, the incidence of PCOS has been increasing, leading to a decline in the quality of life of patients. Therefore, it is necessary to actively explore new treatments. Post-translational modification (PTM) is an important way to regulate protein function. Most studies have found that phosphorylation is closely related to insulin resistance of PCOS, acetylation is mainly focused on the quality of PCOS oocytes, and methylation is closely related to PCOS lipid metabolism. Exploring the role of PTM in the occurrence and development of PCOS may provide new ideas for targeted treatment of this disease. References | Related Articles | Metrics

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The Relationship between Intestinal Flora, Intestinal Metabolites and Polycystic Ovary Syndrome ZHOU Xin-yue, LI Ning, WEI Lin-fei, ZHANG Xue-hong 2024, 43 (1):  42-47.  doi: 10.12280/gjszjk.20230383 Abstract ( 562 )   HTML ( 15 )   PDF (907KB) ( 462 )   Human gut microbiota is rich and diverse, among which gut microbiota can affect host metabolism, immunity and other processes through the brain-gut axis pathway, and then is related to the occurrence and development of a variety of diseases. The changes of intestinal flora in patients with polycystic ovary syndrome (PCOS) are related to clinical features and complications such as insulin resistance, hyperandrogenism, chronic inflammation and metabolic syndrome. Recent studies have shown that intestinal flora may also affect the pathogenesis and pathological process of PCOS through intestinal metabolites such as bile acids, short-chain fatty acids, ceramides and trimethylamine derivatives. In addition, some studies have explored the application of fecal microbiota transplantation, supplementation of probiotics and synbiotics to regulate intestinal flora, in order to provide a theoretical basis for improving the clinical manifestations and related complications of PCOS. References | Related Articles | Metrics

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Low-Grade Chronic Inflammation in Polycystic Ovary Syndrome Women QU Hui-ying, GUI Wen-wu 2024, 43 (1):  48-52.  doi: 10.12280/gjszjk.20230359 Abstract ( 616 )   HTML ( 17 )   PDF (868KB) ( 462 )   Polycystic ovary syndrome (PCOS) is characterized by ovulatory dysfunction, insulin resistance, and hyperandrogenemia, and is one of the main causes of female infertility. Its etiology is complex, and many studies in recent years have shown that its pathogenesis may be related to low-grade chronic inflammation. Systemic low-grade chronic inflammation is often associated with obesity, insulin resistance and hyperandrogenemia. Inflammation in the ovaries can affect follicular development and ovulation. In addition to affecting reproductive function, inflammation also increases the risk of other diseases, such as non-alcoholic fatty liver disease. This article provides a detailed overview of the complex relationship between obesity, insulin resistance, hyperandrogenemia, and inflammation in PCOS patients, and outlines how inflammation is involved in ovulatory disorders and the diseases outside the reproductive system. References | Related Articles | Metrics

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Advances of Endoplasmic Reticulum Stress in Polycystic Ovary Syndrome LI Wen-ya, ZHANG Qiao-li, YANG Xiao-kui 2024, 43 (1):  53-57.  doi: 10.12280/gjszjk.20230410 Abstract ( 499 )   HTML ( 13 )   PDF (869KB) ( 442 )   Polycystic ovary syndrome (PCOS) is a prevalent gynecological endocrine disorder characterized by menstrual disorders, infertility, hirsutism, acne and obesity. The precise pathogenesis of PCOS remains unclear. Recent evidence has demonstrated the involvement of endoplasmic reticulum stress in its pathological process, suggesting the potential of endoplasmic reticulum stress as a novel therapeutic target for PCOS. Endoplasmic reticulum stress refers to the state where the endoplasmic reticulum is in a state of steady imbalance and the accumulation of incorrectly folded or unfolded proteins in the endoplasmic reticulum. Moderate endoplasmic reticulum stress contributes to the development and maturation of follicles. Sustained endoplasmic reticulum stress leads to the abnormal follicle development, hormonal and insulin synthesis and secretion disorders in PCOS patients by inducing granulosa cell apoptosis and mediating processes such as steroid hormone metabolism, glucose metabolism and lipid metabolism, thereby impairing female fertility. This paper provides an overview of the relationship between endoplasmic reticulum stress and various pathogenic factors associated with PCOS, to offer fresh insights into its etiology and treatment. References | Related Articles | Metrics

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Research Progress in the Pathophysiological Features and Treatment of Thin Endometrium REN Yuan, MENG Yu-shi 2024, 43 (1):  58-62.  doi: 10.12280/gjszjk.20230357 Abstract ( 567 )   HTML ( 14 )   PDF (990KB) ( 506 )   The good receptivity of the endometrium is crucial for successful pregnancy, and a thin endometrium can lead to the impaired receptivity and adverse pregnancy outcomes. It is urgent issue in the field of reproductive medicine how to treat thin endometrium, improve endometrial receptivity, and to increase the embryo implantation rate. Understanding the pathophysiological characteristics of thin endometrium can make clinical treatment more targeted. The impaired proliferation of epithelial cells and macrophages, the decreased expression of ovarian steroid hormones and their receptors, the excessive deposition of extracellular matrix and the cellular senescence are all involved in the development of thin endometrium. There are various clinical treatments for thin endometrium, such as the use of estrogen, aspirin, tamoxifen and other adjuvant drugs, pelvic floor neuromuscular electrical stimulation, stem cell transplantation, intrauterine infusion of granulocyte colony-stimulating factor, platelet-rich plasma, etc. However, some patients with refractory and difficult-to-treat thin endometrium still have poor response to these treatment methods. This review summarizes the pathophysiological characteristics of thin endometrium and the progress in clinical treatment. References | Related Articles | Metrics

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Relationship between Uric Acid and Female Reproductive Disorders and Pregnancy Outcomes WANG Jie, MA Xiang 2024, 43 (1):  63-67.  doi: 10.12280/gjszjk.20230415 Abstract ( 566 )   HTML ( 13 )   PDF (872KB) ( 533 )   Uric acid is the end product of endogenous and exogenous purine metabolism. Under normal conditions, the synthesis and excretion of uric acid in the body are in a state of dynamic balance. Studies have shown that the level of serum uric acid is strongly associated with female reproductive disorders and pregnancy outcomes. The patients with polycystic ovary syndrome (PCOS) have a higher risk of hyperuricemia than those women of non-PCOS. In women with PCOS undergoing IVF or ICSI, the elevated level of serum uric acid is associated with the decreased rates of clinical pregnancy and live birth, and with the increased risk of low birthweight. Interleukin-1β is a possible connecting bridge between serum uric acid and endometriosis, causing the dysfunction of endometrial metaplasia and infertility. Furthermore, the elevated uric acid in pregnant women can cause gestational hypertension, pre-eclampsia and gestational diabetes mellitus, which can lead to adverse pregnancy outcomes such as premature delivery and low birth weight of offspring. In this article, we review the relationship between uric acid and female reproductive disorders and pregnancy outcomes, to provide a reference for clinical diagnosis and treatment strategies. References | Related Articles | Metrics

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Application Progress of Progestin-Primed Ovarian Stimulation LI Cai-hua, GUO Pei-pei, JIANG Xiao-hua, FANG You-yan, ZHOU Ping, WEI Zhao-lian 2024, 43 (1):  68-73.  doi: 10.12280/gjszjk.20230476 Abstract ( 548 )   HTML ( 14 )   PDF (900KB) ( 533 )   In assisted reproductive technology, it is very important to prevent the premature endogenous luteinizing hormone (LH) peak in process of controlled ovarian stimulation. Traditional controlled ovarian stimulation protocols with gonadotropin-releasing hormone (GnRH) analogues (GnRH agonists or antagonists) to inhibit the level of endogenous LH have many disadvantages such as high cost and inconvenient use. Progestin-primed ovarian stimulation (PPOS) protocol has been proved to achieve good clinical outcomes in various populations by the negative feedback effect of exogenous progesterone on pituitary gland to inhibit LH level, and its offspring safety has also been preliminarily confirmed. In this paper, the mechanism of PPOS, application of different exogenous progesterone drugs, application effects of different populations and offspring safety of PPOS were reviewed. References | Related Articles | Metrics

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Research Progress of Cuproptosis in Gynecologic Malignant Tumor GAO Ya-ting, WANG Fang, MA Jian-hong, MA Yi-tong, LIU Chang 2024, 43 (1):  74-78.  doi: 10.12280/gjszjk.20230334 Abstract ( 550 )   HTML ( 15 )   PDF (1325KB) ( 506 )   Copper ion as an important coenzyme participates in a wide range of metabolic processes, including aerobic respiration, peptide amidation, iron transport, superoxide dismutase and extracellular matrix biosynthesis. Copper homeostasis is an important mechanism to maintain cell activity. Cuproptosis is a form of cell death caused by the accumulation of copper ions, which is characterized by the imbalance of copper homeostasis, the accumulation of copper in cells, the selective disturbance of tricarboxylic acid cycle, the aggregation of fatty acylated mitochondrial enzymes and the loss of iron-sulfur protein, the protein stress of mitochondria, the cell membrane cracking, and finally the cell death. Gynecological malignant tumors are important causes of cancer death in women. It is found that cuproptosis is closely related to the occurrence, development, prognosis and drug resistance of gynecological malignant tumors. Some cuproptosis regulators can inhibit tumor metastasis and recurrence by inhibiting angiogenesis and regulating drug resistance of cancer cells. Therefore, cuproptosis is a valuable research direction for the treatment of gynecological malignant tumors. Figures and Tables | References | Related Articles | Metrics

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Fatty Acid Synthase and Its Inhibitors in Endometrial Cancer FENG Ya-ru, LI Xue, ZHANG Hui-ying 2024, 43 (1):  79-82.  doi: 10.12280/gjszjk.20230328 Abstract ( 543 )   HTML ( 11 )   PDF (905KB) ( 454 )   Fatty acid synthase (FASN) is a key enzyme in the fatty acid synthesis that catalyzes the de novo synthesis of lipids. Most of the fatty acids are of food origin in normal tissues, while fatty acids are dependent on the de novo synthesis of lipids in endometrial cancer cells. Previous studies have shown that FASN expression is associated with the development, progression and poor prognosis of endometrial malignancies. The overexpression of FASN is correlated with mitogen extracellular kinase (MEK)/ extracellular signal-regulated kinase (ERK)/ mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) signaling pathways. Specific blockade of its activity can significantly inhibit the growth and proliferation of tumor cells. We review the action of FASN and mechanism in endometrial malignancies and the progress of FASN inhibitors such as C75, C93, orlistat and so on, in endometrial cancer or other tumors, with the aim of providing new ideas for the treatment of endometrial tumors. References | Related Articles | Metrics

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Effect of Immune Cells and Immune Factors in Endometrial Cancer HE Ling, KUAI Dan, ZHANG Yan-fang, TIAN Wen-yan, WANG Ying-mei, ZHANG Hui-ying 2024, 43 (1):  83-88.  doi: 10.12280/gjszjk.20230386 Abstract ( 544 )   HTML ( 11 )   PDF (884KB) ( 466 )   Endometrial cancer is a common gynecological malignant tumor, which seriously threatens the quality of life and health of women. Recent studies have shown that in the immune microenvironment of endometrial cancer, the interaction between immune cells such as dendritic cells and immune-enhancing factors can enhance the anti-tumor immune effect, while immune cells such as tumor-associated macrophages and immunosuppressive factors can exert tumor-promoting immune effects by inhibiting immune responses. This article reviews the research progress on the effects of some immune cells, immunosuppressive factors and immune enhancing factors in the immune microenvironment of endometrial cancer, and provides new ideas for further study of the pathogenesis and immunotherapy of endometrial cancer. References | Related Articles | Metrics