Journal of International Reproductive Health/Family Planning

A Nomogram Prediction Model for Gestational Hypertension after Frozen Embryo Transfer

LI Ning, ZHANG An-ni, HE Xiao-xia, ZHANG Xue-hong

2024, 43 (3): 177-184. doi: 10.12280/gjszjk.20240083

Abstract ( 372 )

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Objective: To explore the influencing factors of hypertensive disorders of pregnancy (HDP) after frozen embryo transfer (FET) by a predictive model of HDP. Methods: The clinical data of FET cycles in the Reproductive Medicine Center of the First Hospital of Lanzhou University from January 2019 to May 2023 were included. The cycles that meet the exclusion criteria were excluded. The general clinical data, FET-related data and HDP incidence of the included patients were statistically analyzed. The least absolute shrinkage and selection operator (LASSO) regression technique was used to select the predictors. According to the ratio of 7∶3, the final 4 079 cycles were randomly assigned to the training set (n=2 855) and the validation set (n=1 224). The nomogram prediction model of HDP incidence was established by multiple Logistic regression analysis and use a nomogram to represent it. The area under the curve (AUC), Hosmer-Lemeshow goodness-of-fit test and decision curve analysis (DCA) were used to evaluate this model. Results: Seven non-zero coefficient variables were selected according to LASSO regression analysis. After multivariate Logistic regression analysis, seven factors including endometrial preparation, polycystic ovary syndrome (PCOS), endometriosis, diminished ovarian reserve, family history of hypertension, body mass index, and number of intrauterine gestational sacs were used as the predictors to establish a model and displayed in a nomogram. The AUC of the training set was 0.728, and the AUC of the validation set was 0.734. The Hosmer-Lemeshow test showed that the model fitted well (P=0.867, mean absolute error=0.004). DCA suggested that when the threshold probability of clinical pregnancy was between 7% and 64%, the application of this nomogram could increase the net benefit. Conclusions: The prediction model of HDP after FET has a certain ability to distinguish, which can provide reference for clinical practice, but further development of more effective predictive factors is still necessary.

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Effect of Modified Flexible Antagonist Protocol on the Outcome of COH in Patients with Normal Ovarian Function

WANG Dong-xue, BAO Li-li, LIU Shan, YANG Bo

2024, 43 (3): 185-189. doi: 10.12280/gjszjk.20240023

Abstract ( 409 )

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Objective: To analyze the effect of modified flexible genadotropin releasing hormone antagonist (GnRH-ant) protocol on the pregnancy outcome of in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET） in patients with normal ovarian function. Methods: The retrospective analysis was performed on 124 IVF/ICSI-ET cycles in infertile patients with normal ovarian function from January to December 2020. According to whether GnRH-ant was added when LH<5 U/L on the trigger day, the cycles were divided into the modified flexible GnRH-ant group (modified group) and the fixed GnRH-ant group (fixed group), with 62 cycles in each group. The basic data, controlled ovarian hyperstimulation (COH)-related indicators and pregnancy outcomes of the two groups were compared. Results: There were no statistically significant differences in age, antral follide count, BMI, infertile duration and basal sexual hormone levels between the two groups (P>0.05). The gonadotropin (Gn) dosage, Gn days, GnRH-ant days and GnRH-ant total amount in the modified group were lower than those in the fixed group (all P<0.05). There was no significant difference in the endometrial thickness on the trigger day between the two groups (P>0.05). The LH level on the GnRH-ant day in the modified group was higher than that in the fixed group (P<0.05）. There were no significant differences in E₂ and progesterone levels on the GnRH-ant day, and LH, E₂ and progesterone levels on the trigger day between the two groups (all P>0.05). There were no significant differences in the number of follicle puncture, oocytes obtained, MⅡ oocytes, 2PN fertilization, available embryos, good-quality embryos, transferred embryos, oocyte retrieval rate, MⅡ oocyte rate, 2PN fertilization rate, 2PN cleavage rate, and high-quality embryo rate between the two groups (all P>0.05). No early ovulation of follicles or OHSS was found in the two groups of antagonist protocols. There were no statistically significant differences in the implantation rate, clinical pregnancy rate, biochemical pregnancy rate, abortion rate, and ectopic pregnancy rate between the two groups (all P>0.05). Conclusions: There were no significant differences in the clinical outcomes between the two groups of antagonist protocols. In terms of health and economy, the modified flexible GnRH-ant has obvious advantages, which is an ideal ovulation induction protocol for those patients with normal ovarian reserve.

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Analysis on the Status Quo and Influencing Factors of Medical Treatment Delay in Infertility Patients Undergoing IVF-ET

ZHANG Ai-yu, LUAN Cui-yu, WANG Dong-mei, JIANG Shuai

2024, 43 (3): 190-194. doi: 10.12280/gjszjk.20240039

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Objective: To investigate the status quo of medical treatment delay in female infertility patients undergoing in vitro fertilization-embryo transfer (IVF-ET) and analyze the influencing factors. Methods: With the method of objective sampling, 203 female infertility patients who received IVF-ET for the first time at the Reproductive Medicine Center of Yantaishan Hospital from January to December 2022 were selected. According to the median time between the diagnosis of infertility and the first visit to IVF-ET, the subjects were divided into two groups: the medical treatment delay group and the non-medical treatment delay group. General information questionnaire, the Brief Illness Perception Questionnaire (BIPQ), the Perceived Social Support Scale (PSSS) and the Perceived Barriers to Health Care-seeking Decision in Chinese patients (PBHSD-C) were used to investigate. The differences of indexes between the two groups were compared, and the influencing factors of medical treatment delay were analyzed by Logistic regression. Results: The median interval between the diagnosis of infertility and the first treatment with IVF-ET in 203 patients was 18 months, and the quartile (P₂₅, P₇₅) was (6, 42) months, among which 121 patients (59.61%) were delayed in seeking medical treatment, and 82 patients were not delayed. There were statistically significant differences in the cultural level of couples, marital status of couples, monthly family income, BIPQ total score, PSSS total score, and PBHSD-C total score between two groups (all P<0.05). Logistic regression analysis showed that an increase in the BIPQ total score (OR=0.833, P=0.001) and PSSS (OR=0.887, P=0.002) was the protective factors for the delay in seeking medical treatment; an increase in the PBHSD-C total score (OR=1.754, P<0.001) was a risk factor for the delay in seeking medical treatment. Conclusions: The IVF-ET infertility patients generally have a high incidence of delay in seeking medical treatment. Patients with low disease perception, low perceived social support and high perceived disorder of medical treatment behavior are more likely to delay medical treatment. Medical staff should pay attention to the high-risk groups who are delayed in seeking medical treatment, improve their correct cognition and understanding of diseases, improve the level of social support, reduce the behavioral factors that hinder medical treatment, and promote timely medical treatment through the personalized medical treatment behavior guidance and universal pre-pregnancy health examination.

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Genetic Analysis of A Fetus with Chromosomal Abnormalities Caused by Sperm Generated by Adjacent-2 Segregation

CHEN Chun, DENG Guang-ming, CHEN Xi-min, WANG Jin, CHENG De-hua, QIN Sheng-fang, SONG Xiao

2024, 43 (3): 195-200. doi: 10.12280/gjszjk.20230532

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The adjacent-2 segregation is a rare separation mode in the gametic formation of balanced translocation carriers. A fetus with severe fetal growth restriction (FGR) and chromosomal abnormalities is reported, and the prenatal diagnosis was performed by G-banding karyotype analysis, chromosomal microarray analysis (CMA), fluorescence in situ hybridization (FISH), quantitive fluorescent polymerase chain reaction (QF-PCR). The CMA result of amniotic fluid was arr[hg19]18p11.32q11.2(141,354-21,994,637)×3, 21q11.2q21.3(15,502,777-29,700,071)×1; Refer to the CMA results, the fetal karyotype was described as 46,XX, +der(18)t(18;21) (q11.2;q22.1),-21. In order to verify the source of abnormal karyotype, the chromosomes of parents′ peripheral blood were detected. The father′s karyotype was 46,XY,t(18;21)(q11.2;q22.1), and the pregnant woman had normal karyotype. FISH results showed that the amniotic fluid cells had two normal 18 chromosomes, one normal 21 chromosome and one derived 18 chromosome, and that the father was a cross-translocation carrier of the 18p and 21p. To rule out the possibility that the fetus′s two normal chromosomes 18 were uniparental disomy, this study used the results of identification of maternal blood contamination, and the results of short tandem repeat(STR) test confirmed that only one of the two normal chromosome 18 came from the mother. Therefore, the application of multiple detection techniques in the diagnosis of rare separation methods such as adjacent-2 segregation can help doctors to provide accurate prenatal genetic counseling for those balanced translocation carriers, and to identify the types of chromosomal abnormalities in their fetuses.

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Genetic Analysis of A Family with Recurrent Spontaneous Abortion Using FISH Combined with Chromosome Karyotype

ZHUANG Jian-long, JIANG Yu-ying, ZENG Shu-hong, CHEN Xin-ying

2024, 43 (3): 201-203. doi: 10.12280/gjszjk.20230409

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The etiology of spontaneous abortion is complex, including embryonic factors, maternal factors, environmental factors and abnormal immune function. Approximately 50%~60% abortions are related to fetal chromosomal abnormalities. We reported a case of twice spontaneous abortion. The couple were subject to both chromosome karyotype and fluorescence in situ hybridization (FISH) analysis. None of obvious abnormality was observed in the wife, while chromosome karyotype result showed 46,XY,t(1;11)(p36.2;q24) in the husband. The balanced translocation of t(1;11) carried by the husband may be the reason for recurrent spontaneous abortion in this family. The case indicated the application value of FISH technology in the verification of suspect subtelomeric rearrangements.

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A Case of Early Abdominal Pregnancy Rupture

XIA Meng-yao, YANG Ling, ZHAO Fei, GUO Lu-lu, WANG Feng-qing

2024, 43 (3): 204-206. doi: 10.12280/gjszjk.20230389

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Abdominal pregnancy is relatively rare in clinical practice, and can be divided into secondary abdominal pregnancy and primary abdominal pregnancy. The primary abdominal pregnancy is rarer than the secondary abdominal pregnancy. This paper reports a case of primary abdominal pregnancy with intraperitoneal hemorrhage. After an emergency laparoscopic exploration, it was found that the pregnancy tissue was implanted in the uterine sacral ligaments. The pregnancy tissue was removed under laparoscopy, and the level of β-human chorionic gonadotropin (β-hCG) reduced well after surgery. Clinical diagnosis of abdominal pregnancy is generally combined with the medical history，the level of β-hCG and gynecologic ultrasound, and can be combined with magnetic resonance imaging as a assisted method if necessary. It is worth noting that the diagnosis of ectopic pregnancy in this special site is difficult, and that abdominal pregnancy is often accompanied by intraperitoneal hemorrhage. The key method of definite diagnosis is laparoscopic exploration, and the key treatment of abdominal pregnancy is also mainly relied on surgical exploration, early detection and thorough removal of intra-abdominal pregnancy lesions to prevent the occurrence of secondary abdominal pregnancy. If necessary, low-dose methotrexate as a combined treatment can be added. To stop bleeding actively can prevent serious complications during the operation.

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Modium-Low Differentiation Sertoli-Leydig Cell Tumor of the Ovary: A Case Report and Literature Review

LIU Shu-jie, LI Ming-ze, ZHANG Hai-yan

2024, 43 (3): 207-211. doi: 10.12280/gjszjk.20230455

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The medium-low differentiation Sertoli-Leydig cell tumor (SLCT) has the tendency to become a malignant tumor. A case of SLCT in an 18-year-old young woman was reported. Amenorrhea was the first symptom. Within then 10 months, she gradually developed defeminizing symptoms of breast atrophy, as well as signs of virilization such as protruding Adam′s apple, growth of lip beard, deep voice, and clitoral hypertrophy. She had a medical history of thyroid nodule surgery 6 years ago, and the function of thyroid was normal. A large cystic-solid tumor of the left ovary was found under the laparotomic exploration, approximately 10 cm in diameter. Operation was performed, including left adnexectomy, right ovary biopsy, bilateral para-colonic sulcus peritoneal biopsy and greater omentum biopsy. The postoperative pathological diagnosis indicated the medium-low differentiation of SLCT. The patient subsequently recovered well after 4 cycles of chemotherapy with paclitaxel liposome and carboplatin, and was successful childbirth. For women of childbearing age who exhibit de feminization or even masculinization, the possibility of ovarian SLCT should be considered. Fertility preserving surgery and radical surgery should be individualized according to the tumor grading. Patients with high risk of postoperative recurrence should receive timely chemotherapy to reduce the risk of secondary surgery and death.

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Small Cell Neuroendocrine Carcinoma of the Endometrium: A Case Report and Literature Review

WANG Jing, WANG Xiao-hui

2024, 43 (3): 212-215. doi: 10.12280/gjszjk.20230490

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A case of small cell neuroendocrine carcinoma originating in the endometrium was reported. The patient was a 59-year-old woman with postmenopausal vaginal bleeding and no significant abnormalities in the level of serum tumor markers. Pelvic magnetic resonance imaging (MRI) showed the thickening of endometrium with abnormal signals, the increased signals of fundus uteri, the uterine body junction zone and myometria with limited diffusion. On September 14, 2023, the patient underwent the single-hole transumbilical laparoscopic transabdominal total hysterectomy+transabdominal bilateral salpingotomy+transabdominal bilateral oophorectomy+retroperitoneal abdominal paraaortic lymph node dissection+transabdominal bilateral pelvic lymph node dissection+pelvic adhesion release+umbilical plastic surgery. As of December 2023, the patient has received four times of chemotherapy, the general condition was good, and no recurrence and metastasis were found. Endometrial small cell neuroendocrine carcinoma has a high degree of malignancy and poor prognosis, with non-specific clinical manifestations. Diagnosis mainly relies on pathological and immunohistochemical examinations. Early detection, diagnosis and personalized treatment are key to improving patient prognosis.

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Research Progress in Single-Cell Omics of Human Endometrium

JIANG Le-ran, ZHANG Yuan, WANG Lin, DIAO Fei-yang

2024, 43 (3): 216-221. doi: 10.12280/gjszjk.20240094

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The expression and function of various subtypes of cells in the endometrium are crucial for maintaining normal endometrial function and providing an environment for embryo implantation. In recent years, the single-cell omics has gradually become an important tool for the basic research and clinical application related to endometrium, as it can perform the high-throughput sequencing of endometrium from different sources and stages at the single-cell level. This article provides a systematic review of existing studies on the single-cell omics related to the endometrium, including the physiological status of the endometrium, as well as the single-cell differences and intercellular interactions in pathological conditions such as recurrent spontaneous abortion, endometriosis, adenomyosis, thin endometrium, intrauterine adhesions, repeated implantation failures and endometrial cancer. The deeper understanding of the application of single-cell omics of endometrium is helpful for us to reveal the pathophysiological mechanisms of the endometrium-related diseases.

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Research Progress on the Cryopreservation of Small Numbers of Human Sperm

WU Zhu-lian, WANG Cai-zhu, ZHOU Hong, CHEN Huan-hua, LIN Ruo-yun, SHU Jin-hui

2024, 43 (3): 222-227. doi: 10.12280/gjszjk.20230512

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The samples of small numbers of human sperm are not only difficult to obtain (testicular/epididymal puncture surgery or microsurgical sperm extraction), but also few in number and poor in quality. Both the sperm recovery rate and the retrieval rate are low using traditional freezing methods. The existing technology of sperm cryopreservation has been improved in many aspects in order to enhance the cryopreservation effect of small numbers of sperm. The newly developed freezing vectors have made great progress in improving the recovery rate of motile sperm, the recovery rate of sperm and the convenience of operation. The cofactors of cryophosphate, such as antifreeze proteins, lecithin, nanoparticles and antioxidants, improved the cryophosphate effect to some extent. Sperm vitrification cryopreservation technology has gradually shown its development potential. This paper reviews the research progress of cryopreservation of small numbers of sperm, focusing on the optimization of cryopreservation vectors, cryopreservation protectant and cryopreservation program.

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Advancements of MiR-202 in Reproductive Modulation

LIANG Yue, DONG Jie, XIAO Xi-feng, WANG Xiao-hong

2024, 43 (3): 228-233. doi: 10.12280/gjszjk.20240080

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MicroRNAs (miRNAs) have emerged as key regulators of diverse biological processes, including cell proliferation, differentiation, apoptosis, and metabolism. They are also actively involved in the reproductive and developmental processes of organisms. Among the let-7 family, miR-202 stands out owing to its high conservation across different species, implying the potential shared functions and regulatory roles. Substantial evidence from numerous studies underscores the involvement of miR-202 in a wide range of pathophysiological processes. Notably, it exerts significant inhibitory effects on tumor cell proliferation, migration, and invasion. Moreover, miR-202 plays a critical role in modulating the differentiation of T cell and exhibits the implications in the regulation of neurodevelopment and neurodegenerative diseases. The increasing evidence have indicated that miR-202 plays a crucial role in gamete development and the regulation of reproductive physiology. In this article, we review the regulatory roles of miR-202 in key reproductive processes, namely spermatogenesis, follicle development, and reproductive endocrine regulation.

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Research Progress on Sleep Disorders in Patients Receiving Assisted Reproductive Technology and Non-Pharmacological Intervention

HE Qing-wen, LI Xi-hong

2024, 43 (3): 234-237. doi: 10.12280/gjszjk.20230466

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The patients undergoing the treatment of assisted reproductive technology, as a special group that is different from other groups of diseases, are prone to sleep disorders due to the impact of physiological and psychosocial factors. In this review, the current status, assessment tools, and non-pharmacological intervention of sleep disorders in patients undergoing assisted reproductive technology were introduced. The appropriate tools were used to evaluate the degree of sleep disorders effectively. The appropriate intervention measures can improve the sleep quality of patients, including digital cognitive behavioral therapy, mindfulness-based stress reduction, music therapy, aerobic and resistance exercises and progressive muscle relaxation. This review will provide a reference for the evaluation of sleep disorders and non-pharmacological intervention for those patients undergoing assisted reproductive technology for pregnancy.

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The Role of Gut Microbiota in Patients with Polycystic Ovary Syndrome

SHI Bai-chao, CHANG Hui, WANG Yu, LU Feng-juan, WANG Kai-yue, GUAN Mu-xin, MA Liang, WU Xiao-ke

2024, 43 (3): 238-242. doi: 10.12280/gjszjk.20240078

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Gastrointestinal microbiome is a rich collection of microorganisms that exist in the human intestine, which affects the life activities of the body via various pathways such as nerve, endocrine, and participates in the process of many diseases. Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-aged women. Gastrointestinal microbiome may be a potential pathogenic factor for the development of PCOS, and the change of its composition is correlated with clinical features such as insulin resistance, hyperandrogenism, chronic inflammation and obesity. Similarly, the metabolites of gastrointestinal microbiome such as bile acids and short-chain fatty acids are involved in the pathological process of PCOS. In this context, the agents of fecal microbiota transplantation, probiotics, prebiotics and synbiotics, as well as the natural products including alkaloids, flavonoids and polyphenols, can change the composition of gastrointestinal microbiome and the level of metabolites, and regulate the function of gastrointestinal microbiome to improve the endocrine and metabolic diseases of PCOS. Therefore, the research progress on gastrointestinal microbiome is reviewed in order to provide a reference for clinical therapeutic approaches of PCOS.

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The Role of CircRNAs in Follicular Granulosa Cells of Patients with Endometriosis Infertility

GAO Zhao-yang, ZHANG Ning-qing, CHEN Qiong-hua, WU Rong-feng

2024, 43 (3): 243-248. doi: 10.12280/gjszjk.20230529

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The abnormal follicular development is one of the pathological mechanisms of infertility in patients with endometriosis (EMs). In recent years, the role of circular RNA (circRNA) in the development of endometrium-related diseases has attracted more attention. However, the research on the role of circRNAs in EMs is still at the early stage, and the role of circRNA in the development of EMs follicles is especially unclear. It is currently known that circRNAs can participate in the occurrence and development of EMs by affecting the proliferation and apoptosis of granulosa cells, epithelial-mesenchymal transition, microenvironment of follicular fluid and hormone regulation, which further lead to infertility. This review aims to elucidate the research progress on the potential impact of circRNAs on follicular granulosa cells leading to adverse pregnancy outcomes, and to explore the possibility of circRNAs as a biomarker for EMs, so as to provide new ideas and methods for clinical diagnosis and treatment.

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Research Progress on the Correlation between the Endometrial Cancer Associated with Type 2 Diabetes Mellitus and the Intestinal Flora

WANG Fang, WAN Tao, YANG Yong-xiu

2024, 43 (3): 249-253. doi: 10.12280/gjszjk.20240034

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Type 2 diabetes mellitus (T2DM) is related to the higher incidence and the increased invasiveness of endometrial cancer (EC). Hyperglycemia, hyperinsulinemia, insulin resistance and obesity in patients with T2DM have been widely studied as potential pathogenesis of EC, and the imbalance of intestinal flora may be the key factor of T2DM-related EC. This paper summarizes the relationships between T2DM and EC, T2DM and intestinal flora, T2DM-related EC and intestinal flora, including the abnormal expression of microRNA, mitochondrial dysfunction, inflammation and adiponectin level, and the progress of intestinal flora in treating T2DM-related EC, in order to provide a reference for the prevention and treatment of T2DM-related EC from the perspective of intestinal flora.

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Progress in the Diagnosis and Treatment of Obstetric Antiphospholipid Syndrome

LI Yan-lin, HE Yin-fang

2024, 43 (3): 254-259. doi: 10.12280/gjszjk.20240073

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Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disease characterized by persistent positivity of antiphospholipid antibody (aPL) and pathological pregnancy, with clinical manifestations such as recurrent spontaneous abortion, fetal death, fetal growth restriction, preeclampsia, and premature delivery. Early diagnosis and appropriate management of the patients with OAPS can significantly reduce the incidence of pregnancy complications. Currently, the first-line therapeutic option is aspirin combined with low molecular weight heparin, which improves the pregnancy outcome in most patients. The second-line therapeutic medications, such as hydroxychloroquine and glucocorticoid, can be used as a complement to the first-line therapeutic option. The emerging therapeutic medications, such as biologics and statins, are still at the exploratory stage of clinical application. In this article, we review the advances in the diagnosis and treatment of OAPS.

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Clinical Research Progress of Vulvar Lichen Sclerosus

CHENG Shi-yu, SHI Jie, LI Yan-li, GAO Han

2024, 43 (3): 260-264. doi: 10.12280/gjszjk.20240048

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Vulvar lichen sclerosus (VLS) is a chronic inflammatory skin disease with female vulvar itching as the main clinical manifestation. It mainly affects the female anogenital area, such as the labia and the perianal region. VLS can affect women of all ages, but predominantly pre-pubertal girls and post-menopausal women present to hospital with persistent vulvar itching, burning pain or discomfort during intercourse. The exact pathogenesis of VLS is still unknown. Genetic, metabolic abnormalities, autoimmune and other factors may be involved. If the lesions are not treated effectively, they can eventually progress to irreversible anatomical changes in the vulva and malignant tumors, seriously endangering the physical and psychological health of the patient. According to the severity of VLS, the individualized treatment should be adopted, mainly including psychological counseling, physical intervention and surgical treatment.

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