Journal of International Reproductive Health/Family Planning

Application of Increasing hCG Trigger Dose in Patients with Poor Ovarian Response

SONG Yun-jie, ZHANG Yuan, XIA Xin-ru, XIA Meng, WU Wei, HUANG Jie, DIAO Fei-yang, MAO Yun-dong, LIU Jia-yin, ZHANG Ru-yang, MA Xiang

2021, 40 (6): 441-445. doi: 10.12280/gjszjk.20210275

Abstract ( 2765 )

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Objective: To investigate whether increasing the trigger dose of human chorionic gonadotrophin (hCG) can improve the clinical outcome in patients with poor ovarian response who used gonadotropin releasing hormone agonist (GnRHa) long protocol in in vitro fertilization / intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cycle. Methods: The clinical data of 409 patients with poor ovarian response were analyzed retrospectively in our reproductive medicine center from January 2018 to March 2021. According to the trigger dose of hCG, 409 patients were divided into two groups. The conventional dosage group used 6 500 U hCG for trigger (n=337), and the increased dose group (n=72) used hCG 10 000 U or hCG 2 000 U combined with the hCG 6 500 U for trigger. The number of oocytes, the rate of oocyte retrieval, MⅡ rate, 2PN rate, the number of transplantable embryos, the rumber of high-quality embryos, the clinical pregnancy rate, embryo implantation rate, abortion rate and OHSS incidence were compared between the two groups. Results: There were no significant differences in the number of oocytes, the rate of oocyte retrieval, MⅡ rate, 2PN rate, the number of transplantable embryos, the number of high-quality embryos and the rate of abortion between the two groups (all P>0.05). The clinical pregnancy rate (55.56% vs. 42.73%,P=0.047) and the embryo implantation rate（50.51% vs. 37.88%,P=0.021）of the increased dose group was significantly higher than those of the conventional dose group. OHSS was not found in both groups. Conclusions: For the poor ovarian response population, increasing the dose of hCG for trigger can increase embryo implantation rate and the clinical pregnancy rate of fresh cycle transplantation using GnRHa long protocol, which is relatively safe and feasible. This is a recommendable scheme for trigger.

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Impacts of Female Low Body Mass Index on Pregnancy and Perinatal Outcomes of Frozen-Thawed Embryo Transfer

XIE Qi-jun, LI Xin, JIANG Wei, ZHAO Chun, LING Xiu-feng

2021, 40 (6): 446-451. doi: 10.12280/gjszjk.20210292

Abstract ( 2219 )

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Objective: To investigate the impacts of female low body mass index (BMI) on pregnancy and perinatal outcomes of frozen-thawed embryo transfer (FET). Methods: The clinical data of 5 952 women underwent FET in our center from January 2015 to June 2020 were retrospectively analyzed. These cases were divided into two groups according to BMI: group A (BMI<18.5 kg/m², 697 cases) and group B (BMI=18.5~23.9 kg/m², 5 255 cases). Then, group A and group B were subgrouped into A1 (1 embryo transferred, 178 cases) and A2 (2 embryos transferred, 519 cases), B1 (1 embryo transferred, 1 275 cases) and B2 (2 embryos transferred, 3 980 cases) according to the transferred embryos. ①The pregnancy outcomes were compared between A1 and A2 subgroup, A1 and B1 subgroup, A2 and B2 subgroup; ②The perinatal outcomes of singleton women were compared between group A and B group. Results: ①The embryo implantation rate (P=0.000), single live birth rate(P=0.000), gestational age (P=0.003) and neonatal birth weight (P=0.000) in subgroup A1 were significantly higher than those in subgroup A2, while the live birth rate of twins(P=0.000), preterm birth rate(P=0.004) and low birth weight rate(P=0.000) in subgroup A1 were significantly lower than those in subgroup A2. The neonatal birth weight in subgroup A1 was significantly lower than that in subgroup B1 (P=0.013). The embryo implantation rate(P=0.000), clinical pregnancy rate (P=0.000), live birth rate(P=0.000), single birth rate(P=0.006) and preterm birth rate (P=0.035) in subgroup A2 were significantly lower than those in subgroup B2. ②After adjusting the confounding factors through multiple logistic regression, the rates of macrosomia and large for gestational age (>90th) in A group was significantly lower than those in B group (aOR=0.493, 95%CI: 0.296-0.821, P=0.007; aOR=0.645, 95%CI=0.473-0.878, P=0.005). Conclusions: In FET cycle, transfering one embryo in the patients with low BMI can significantly reduce the preterm birth rate and multiple pregnancy rate with the advantages of increasing embryo implantation rate and neonatal birth weight and improving pregnancy and perinatal outcomes.

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Analysis of Relationship between Social Position of Strong Network and Depression Status in Women Undergoing IVF/ICSI Treatment

WANG Dan-ni, CHEN Ren, XU Qian-hua, WANG Jie-yu

2021, 40 (6): 452-455. doi: 10.12280/gjszjk.20210341

Abstract ( 2139 )

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Objective: To investigate the social capital and depression status in women undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET), and to analyze their relationship. Methods: 104 female patients were selected from the Reproductive Medicine Center of the First Affiliated Hospital of Anhui Medical University, who are planned the IVF/ICSI-ET treatment from December 2020 to February 2021. After the patients were trained in answering, the patients should answer the questions by themselves. The PHQ-9 scale was used to assess depression, and the "position generation method" was used to measure the social capital of patients′ strong social network. Use multiple linear regression to analyze the relationship between the social capital and depression status. Results: The median of treatment duration was 2 years in those women undergoing IVF/ICSI-ET treatment. The median of PHQ-9 score was 16.00, P₂₅ and P₇₅ scores were 15.00 and 18.00, and the self-reported depression symptoms rate was 52.9% (55/104). Our study defined strong social networks as spouse and relatives. The occupational value of the spouse (Median, 73.5 points) and the occupational accessibility of relatives (Median, 79 points) were associated with the increased depression level of those women undergoing IVF/ICSI treatment. Conclusions: The high social position of the strong social network of women undergoing assisted reproductive treatment is a risk factor of depression for these women. The targeted psychological interventions should be carried out to improve the quality of both fertility and life of these women and their families.

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Survey of Rare Diseases in Neonatal Intensive Care Unit between 2013 to 2020

SU Ai-ling, YU Zhang-bin, CHEN Yu-lin, ZHU Jin-gai, QIAN Miao

2021, 40 (6): 456-461. doi: 10.12280/gjszjk.20210153

Abstract ( 2164 )

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Objective: To understand the occurrence of rare diseases in the neonatal intensive care unit (NICU) of the Affiliated Maternity Hospital of Nanjing Medical University (our hospital), and judge the change trend of rare diseases. Methods: The critically ill newborns who were treated in our NICU between January 2013 and December 2020 were selected. Rare diseases were diagnosed by the tandem mass spectrometry screening of blood and urine samples, and genetic testing. The disease detection rate, clinical characteristics, genetic changes and prognostic follow-up of confirmed children were summarized by descriptive research methods. Results: The total number of newborns was 183 820, the annual deliveries increased from 18 863 to 26 511 year by year, and NICU inpatients from 2 312 to 2 871. A total of 34 children with rare diseases were screened out, and the annual NICU-detection rate increased from 0.43‰ to 4.39‰, showing an upward trend. Rare diseases included four neuromuscular-skeletal diseases, 18 genetic metabolic diseases, two endocrine diseases, six chromosome deletions or abnormalities, one immune system diseases and three others, with the highest proportion of genetic metabolic disorders (about 53%), followed by neuromuscular-skeletal diseases (about 11%). A total of 15 cases were diagnosed by conventional tandem mass spectrometry screening, and the remaining 19 were all confirmed by the exon sequencing technology. These rare diseases have their specific clinical manifestations. Of the 34 children with rare diseases, 8 children died, 18 children had basically normal growth and development, 7 children had backward growth and intellectual development, and one case was lost. Conclusions: In recent years, the detection rate of rare diseases in our hospital has increased year by year, mainly autosomal genetic metabolism. The proportion of mortality and late development is high. Strengthening the clinical understanding of rare diseases, expanding the scope of genetic and metabolic diseases screening, and strengthening prenatal counseling and genetic counseling are the key points of achieving prenatal and postnatal care and putting an reducing the harm of rare diseases.

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Prevalence of Retinopathy of Prematurity in China: A Meta-Analysis

REN Jun-li, YANG Liu, LI Yan, HUANG Li-juan, LI Xue-jiao, LI Hai-hong

2021, 40 (6): 462-467. doi: 10.12280/gjszjk.20210151

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Objective: To evaluate the prevalence of retinopathy of prematurity (ROP) in China by a meta-analysis. Methods: PubMed, Web of Science, Cochrane Library, Embase, CBM, CNKI, Wanfang Data and VIP databases were searched for cross-section studies on retinal disease of preterm infants in China from the date of establishment to December 2020. Two researchers screened the literature, extracted the data, and evaluated the risk of bias in the included studies. The meta-analysis was performed by using Stata12.0 software. Results: A total of 28 studies involving 75 572 patients were included. The results of meta-analysis showed that the prevalence of ROP in Chinese premature infant was 12.6% (95%CI: 11.1% to 14.1%), of which 16% (95%CI: 14% to 18%) for male and 16% (95%CI: 14% to 19%) for female. Grouped by gestational age, 38% (95%CI: 25% to 51%) for ≤30 weeks, 21% (95%CI: 13% to 29%) for 30-32 weeks, and 12% (95%CI: 3% to 20%) for ≥32 weeks. Grouped by body weight, ≤1.5 kg is 32% (95%CI: 28% to 35%), 1.5-2.0 kg is 11% (95%CI: 9% to 14%), ≥2.0 kg is 5% (95%CI: 4% to 7%). Grouped by region, 13% (95%CI: 12% to 14%) in the south, and 13% (95%CI: 12% to 15%) in the north. Subgroup analysis showed that the prevalence was higher in younger age, and the prevalence decreased with the increase of gestational age. The prevalence was the same in the south and the north. Conclusions: The prevalence of ROP in China is 12.6%. There are differences in this rate among preterm infants of different gestational age and body weight.

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A Case Report on Twin Fetuses Growth Restriction Caused by Both of Velamentous Cord Insertion after In Vitro Fertilization-Embryo Transfer

FAN Xue-yan, DONG Qu-long

2021, 40 (6): 468-470. doi: 10.12280/gjszjk.20210318

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Velamentous cord insertion(VCI) refers to the attachment of umbilical cord to the fetal membrane at the edge of placenta, which is more common in primiparas, multiple pregnancies and pregnant women who used human assisted reproductive technology. Because of its special anatomic position, VCI can lead to adverse pregnancy outcomes of both mother and infant. Mild cases show fetal growth retardation, and severe cases show intrauterine fetal death. In terms of treatment, there is no specific and effective drug intervention, and the clinical treatment mainly depends on the gestational age and intrauterine condition of the fetus. We reported a clinical case of twin fetuses growth restriction caused by both of VCI after in vitro fertilization-embryo transfer. We hope to improve the academic vision and the understanding of this disease in obstetricians and gynecologists.

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Research Progress in Metabolomics of Mammalian Follicles

MAO Fei, FENG Rui-zhi, QIAN Yun

2021, 40 (6): 471-475. doi: 10.12280/gjszjk.20210203

Abstract ( 2198 )

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The oocyte quality is one of the determining factors of successful assisted reproductive technology(ART) outcome. It is beneficial to establish a simple and reliable evaluation system of oocyte quality for improving the success rate of ART. Newly developed metabolomics is expected to provide a new method for evaluating oocyte quality. At present, metabolomics has been used in many relevant studies of female reproduction. By the qualitative and quantitative analysis of small and medium-sized molecules in oocytes, granulosa cells and follicular fluid samples, researchers have identified a variety of symbolic metabolites related to female infertility, which are involved in the metabolism of carbohydrate, lipid, amino acid and other substances. These studies have showed the potential application of metabolomics in the diagnosis and treatment of infertility. We review the research progress in the metabolomics of mammalian follicles.

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Research Progress on the Function of MicroRNA in Decidualization

LI Hong-wanyu, YANG Jie-qiong, ZHANG Cong

2021, 40 (6): 476-480. doi: 10.12280/gjszjk.20210363

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Decidualization is the process of morphological and functional changes of the endometrium from the secretory period to embryo implantation after ovulation. It is very important for the establishment and maintenance of pregnancy and the cyclical changes of endometrium. The transformation of endometrial stromal cell is most important, which is driven by progesterone and cAMP signals and is accompanied by changes in the expressions of a series of marker molecules. MicroRNAs (miRNAs) play an extensive role in the post transcriptional regulation. A large number of studies have shown that miRNAs are involved in the regulation of decidualization related genes, such as IGFBP1, PRL, KLF12 and HOXA10. This article summarizes the role of miRNA synthesis related enzymes and miRNAs in the process of decidualization, which provides more information for the study of decidualization and related diseases such as repeated implantation failure, endometriosis, preeclampsia and other female diseases.

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The Major Signaling Pathways in Early Embryonic Development

CHEN Ran-ran, SONG Dian-rong

2021, 40 (6): 481-485. doi: 10.12280/gjszjk.20210213

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Embryonic development begins from the zygote. After multiple cleavages, the embryonic morphology changed, and the internal cells differentiated into the different lineages that laid the foundation for the subsequent formation of gastrula. The various signal pathways participate in the fine regulation of early embryonic development. For example, the differential activation of Hippo signal pathway leads to the differentiation of trophectoderm (TE) and inner cell mass (ICM); fibroblast growth factor/extracellular signal-regulated kinase (FGF/ERK) signaling pathway further differentiated ICM into primitive endoderm (PE) and epiblast (EPI); bone morphogenetic protein (BMP) signaling pathway and classic Wnt signaling pathway are not only related to the pluripotent of embryonic cells, but also play an important role in the establishment of hypocotyls; Notch signaling pathway and Nodal signaling pathway are mainly involved in the formation of left-right asymmetry of embryos. Here we review the role and regulation mechanism of the main signal pathways in early embryonic development, so as to provide reference for the in-depth understanding of the process of early embryonic development and regulation.

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In Vitro Activation of Primordial Follicles in Patients with Primary Ovarian Insufficiency

SONG Wen-guang, FU Hao, GUO Min, HU Chun-xiu

2021, 40 (6): 486-489. doi: 10.12280/gjszjk.20210343

Abstract ( 2770 )

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Primary ovarian insufficiency (POI) is one of the important causes of female infertility. At present, the main treatment to realize fertility is the egg donation. However, due to egg source and ethical problems, patients need to face many difficulties. The development of in vitro follicular activation technology brings new treatment ideas for the treatment of POI. The hippopotamus signaling pathway, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, mammalian target of rapamycin complex 1 (mTORC1) signaling pathway and other follicle development-related signaling pathways can be in vitro activated by pharmacological or non-pharmacological means, to promote primordial follicle development. The ovarian tissue containing primordial follicles will be subsequently implanted back into the patient, and patients ultimately may achieve the fertility goal. We review the research progress of IVA of primordial follicles in patients with POI, so as to provide reference for the clinical treatment strategy of POI.

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The Mechanism of Platelet-Rich Plasma Therapy in Thin Endometrium

ZHENG Xiu-dan, YIN Lan-lan, WANG Yan-bo, MA Tian-zhong

2021, 40 (6): 490-494. doi: 10.12280/gjszjk.20210162

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Thin endometrium can lead to the decreased rates of clinical pregnancy and live birth. At present, there is no optimal plan to improve endometrial thickness in patients with thin endometrium. As an auxiliary method for emerging endometrial preparation, platelet-rich plasma (PRP) perfusion therapy may have a complex mechanism in the treatment of thin endometrium. The platelet concentration in PRP is higher than that in whole blood. The basic principle and therapeutic potential of high concentration platelets are based on their ability to provide superphysiological quantities of essential growth factors for regenerative stimulation and to promote tissue repair with low healing potential. Based on the research progress of PRP, this paper focuses on the growth factors in PRP to promote cell proliferation, migration, and to regulate the proliferation and apoptosis of endometrial cells through NF-κB signaling pathway. The discussion will provide a reference for further study of the molecular basis and exact mechanism of PRP therapy.

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Changes of Human Body Composition in Perimenopausal Women: A Review

YAO Li-jun, WANG Li-na, ZHANG Hui-ying

2021, 40 (6): 495-498. doi: 10.12280/gjszjk.20210273

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Perimenopause is an important period of the changes in women′s body composition. Body weight and body fat percentage increase during this period, while bone and muscle mass decrease. These changes increase the risk of many diseases. The human body composition analysis can effectively evaluate the composition of human body under both physiological and pathological conditions, and compare the changes of body composition with the lifestyle. We review the change of body composition in perimenopausal women and the effect of lifestyle intervention and hormone replacement therapy on body composition. It is recommended that perimenopausal women optimize diet, engage in continuous and regular physical activity during mid-life to prevent weight gain and abdominal fat deposition, increase muscle mass, and slow down bone loss, so as to offset the adverse changes in body composition associated with menopause. The behavioral changes during perimenopausal period is the main therapy to prevent the adverse change in body composition. It is also necessary to study furtherly the efficacy and long-term safety of estradiol formulations.

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Genital Tract Microbiota and Endometrial Polyps

WANG Li-na, YAO Li-jun, ZHANG Hui-ying

2021, 40 (6): 499-503. doi: 10.12280/gjszjk.20210244

Abstract ( 2018 )

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Endometrial polyps (EPs) is a kind of pathological changes of endometrium, which is composed of endometrial glands and endometrial stroma containing blood vessels. Although EPs is a common gynecologic disease, the pathogenesis is still unclear. With the wide use of hysteroscopy, the diagnosis and treatment level of EPs has been significantly improved. Many studies using molecular biology and sequencing technology have shown that microbiota exists in the upper and lower genital tract of healthy women, and that the composition of microbiota is different. Recent studies have found that the change of genital tract microbiota is closely related to female reproductive health. The correlation between the genital tract microbiota and the pathogenesis of EPs is one of the research hotspots. The genital tract microbiota may participate in the development of EPs by affecting local immune regulation, causing inflammatory response, changing hormone levels, increasing the number of pathogenic microbiota and affecting cell proliferation/apoptosis. Here we review the correlation between the genital tract microbiota and EPs, which can provide a reference to explore the pathogenesis of EPs.

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Environmental Heavy Metal Exposure and Endometriosis

SHEN Ling-chao, JI Dong-mei

2021, 40 (6): 504-508. doi: 10.12280/gjszjk.20210136

Abstract ( 1968 )

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The etiological and pathophysiological mechanisms of endometriosis (EMs) include endocrine, genetic, immune and environmental factors. Environmental pollution can lead to the accumulation of a large number of heavy metal elements, such as iron, nickel and cadmium, in water, soil and air. If women were exposed to this kind of environment, a lot of these heavy metals could enter into their bodies. After that, these heavy metals were combined with some organic compounds in body to form the metallic integration or metal-protein complex that promote the production of harmful reactive oxygen species (ROS). Many studies have showed that ROS promotes the proliferation of endometrial cells and the invasion of ectopic lesions by activating the mitogen-activated protein kinase (MAPK) pathway and aggravating oxidative stress. Some heavy metals, such as cadmium and nickel, can specifically bind with estrogen receptor (ER) in the body, by which the estrogen-like effects were induced so as to interfere with endocrine and metabolism, and to increase the risk of EMs in women. This paper reviews the correlation between the environmental heavy metal exposure and the pathophysiological mechanism of EMs, as well as the research progress, as to add a new reference for us to explore the etiology and pathophysiology of EMs.

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Circular RNA in Pathophysiology of Polycystic Ovary Syndrome

HUANG Ling-li, FENG Rui-zhi, QIAN Yun

2021, 40 (6): 509-513. doi: 10.12280/gjszjk.20210307

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Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine diseases in women of childbearing age, and the incidence of PCOS increased year by year. The clinical manifestations of PCOS are highly heterogeneous, leading to different degrees of decline in the life quality of patients. There is growing evidence that PCOS may be a complex polygenetic disease with strong epigenetic and environmental influences. Some studies conducted high-throughput sequencing or gene chip analysis on ovarian tissues and placental tissues of PCOS patients found multiple differentially expressed circRNA, such as hsa_circ_0006877, hsa_circ_0118530. These differentially expressed circRNA may affect oocyte development and reproductive endocrine balance through their involvement in the ovarian granulosa cell proliferation and apoptosis, androgen synthesis and release. This article reviews the role of circRNA in the occurrence and development of PCOS.

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Research Progress of Cyclosporine A Treatment of Recurrent Spontaneous Abortion

GE Meng-di, ZHAO Xiao-xuan, ZHAO Yan, FENG Xiao-ling

2021, 40 (6): 514-518. doi: 10.12280/gjszjk.20210233

Abstract ( 2008 )

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Recurrent spontaneous abortion (RSA) is a common gynecological and obstetric disease. The etiology of RSA is complex, while the etiology of some RSA patients is still unclear, which may be closely related to abnormal immune factors. The therapeutic effect of cellular immunosuppressant cyclosporine A (CsA) in recurrent abortion has been gradually revealed. It has been found that CSA can regulate the maternal-fetal immune tolerance and trophoblast proliferation, migration and invasion, which provides evidence support for its use as a drug related to RSA. In this paper, we expound the embryonic protection mechanism of CsA from the various aspects. CsA participates in regulating the balance of maternal and fetal immune tolerance cytokines, alleviating the immune stress injury of trophoblast, enhancing the proliferation and invasion of trophoblast and reducing trophoblast apoptosis. Combined with the latest clinical reports on the CsA combined with traditional Chinese medicine in the treatment of RSA, we discuss the treatment application of CsA in RSA diseases, and provide ideas for further research on CsA in the treatment of RSA.

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Polymorphism of Folic Acid Carrier Gene and Fetal Neural Tube Malformation

PEI Jiao-jiao, XIE Jiang-yan, WU Xiao-li

2021, 40 (6): 519-523. doi: 10.12280/gjszjk.20210128

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Folic acid is the natural form of a group of water-soluble vitamins (vitamin B₉). As a coenzyme of a one-carbon unit transferase system, folic acid provides important raw materials for methylation and nucleic acid synthesis in vivo. Its derivatives are also the substrates of many one-carbon unit transfer reactions. Dietary sources of folic acid include leafy green vegetables, legumes and fortified cereal products. The bioavailability of folic acid depends not only on dietary intake but also on the cellular mechanisms that regulate folic acid absorption and metabolism, as well as the genetic polymorphism of key carriers in folic acid metabolic pathways. The risk of neural tube defect (NTD) is different among individuals with the same eating habits, and the contribution of the same folic acid concentration to red blood cells is also different. It is more and more important to understand the mechanism of NTD through the study of folic acid absorption and transport. The gene polymorphism of folic acid carrier is an excellent candidate for studying the mechanism of NTD, which provides a theoretical basis for a scientific and individual supplement of folic acid that is easy to absorb.

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Progress on Diagnosis and Treatment of Ovarian Immature Teratoma

WANG An-sheng, DU Yuan-yuan, YANG Yang

2021, 40 (6): 524-528. doi: 10.12280/gjszjk.20210105

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Immature teratoma of the ovary is a germ cell tumor of the ovary, which is most frequent in women of childbearing age. It is very easy to relapse and metastasize, but the malignant degree can be reversed after recurrence by reoperation. Its origin is thought to be related to meiotic errors and epigenetic disorders. The symptoms and signs of immature teratoma of the ovary are lack of specificity. In addition to the traditional examination methods, neuronspecific enolase test, ¹⁸F-FDG PET/CT and other examination methods have been approved. It is a relatively rare disease, so there is not a clinical guideline for the treatment of ovarian immature teratoma and follow-up management in those adult and child patients. The current mainstream treatment is surgery, not chemotherapy unless it has to be, and to protect the fertility as far as possible. Due to its relatively easy relapse, postoperative follow up is very important. The follow up frequency should be the same as other malignant tumors. Growing teratoma syndrome is a relatively few complication of ovarian immature teratoma. Surgery is the main treatment method for it, and targeted drug therapy also has some progress. The research progress of the source, diagnosis, treatment and complications of ovarian immature teratoma in recent years was reviewed in order to provide a reference for clinical diagnosis and treatment.

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