Journal of International Reproductive Health/Family Planning

The Influence of Perinatal Exposure of Low Dose of Bisphenol A on Spermatogenesis of Male Offspring Rats

BAI Yin-yang, XIONG Fang, ZHANG Yun, CHEN Jie, XU Li-shuang, WANG Min

2021, 40 (5): 353-358. doi: 10.12280/gjszjk.20210097

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Objective: To study the influence of perinatal exposure of bisphenol A (BPA) at a low dose on the spermatogenesis of male offspring rats. Methods: Pregnant rats were injected subcutaneously with BPA 2 μg/(kg·d) from gestation day 10 through lactation day 7, and the same volume of olive oil was used as the blank control. Their male offspring were served as the BPA group and the control group. Histological structure of the testis and the related regulation genes such as cyclin A1、cyclin B、c-jun and c-fos, as well as the FSH and LH, were tested, and the expressions POA-GnRH or ARC-kiss1 mRNAs were also examined in their male offspring during the postnatal day 18, 21, 24. Results: In comparison with the control group, the seminiferous tubular diameter, the number of round spermatids and the ratio of seminiferous tubule with round spermatids were significantly increased in PND24 BPA rats (P<0.05). The expression levels of cyclin A1, c-jun and c-fos mRNAs in the testes were significantly elevated in PND21 BPA rats (P<0.01). Similarly, the levels of plasma FSH and LH were increased in the PND21/24 BPA rats compared with the control rats (P<0.05). But the levels of plasma T and E₂ were no significant in the PND18/21/24 BPA rats and the control rats (P>0.05). In comparison with control group, the expression levels of POA-GnRH mRNA and ARC-kiss1 mRNA were significantly increased in PND21 BPA rats (GnRH: P<0.05; kiss1: P<0.01). Conclusions: In addition to the direct effect of BPA on the testes of male offspring, the perinatal exposure to a low dose of BPA promotes spermatogenesis via advancing the pubertal activation of ARC-kisspeptin, and via further enhancing the expressions of meiotic regulation genes in the testes of male offspring.

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Neonatal Outcomes of Single Delivery after Embryo Transfer at Blastocyst and Cleavage Stages in Fresh Cycles: A Meta-Analysis

ZHANG Hui, CHAI Liang-ting, LU Jing, WANG Chang-yan, CHANG Wen-liang

2021, 40 (5): 359-365. doi: 10.12280/gjszjk.20200741

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Objective: To evaluate systematically the neonatal outcomes of single delivery after embryo transfer at blastocyst and cleavage stages in the fresh cycles. Methods: A systematic search was performed on PubMed, Embase, Cochrane Library, Web of Science, CBM, CNKI, Wanfang and VIP databases (up to November 2020) to search the related studies on the neonatal outcomes of single birth after blastocyst and cleavage stage fresh embryo transfer. The evaluators screened the literature, evaluated the quality and extracted the data according to the inclusion and exclusion criteria. The RevMan 5.3 software was used for data analysis. Results: Thirteen studies were scrutinized for this meta-analysis. The overall showed that the incidences of very preterm birth (VPTB, RR=1.17, 95%CI: 1.08-1.26, P<0.000 1) and large for gestational age (LGA, RR=1.11, 95%CI: 1.04-1.19, P=0.002) were significantly increased, and the incidence of small for gestational age (SGA, RR=0.85, 95%CI: 0.78-0.93, P=0.000 6) was significantly decreased, in the single delivery after the blastocyst embryo transfer when compared with the embryo transfer at cleavage stage. There were no significant differences in the incidences of preterm birth (PTB, RR=1.10, 95%CI: 0.98-1.22, P=0.09), low birth weight (LBW, RR=1.00, 95%CI: 0.94-1.07, P=0.90) and very low birth weight (VLBW, RR=0.99, 95%CI: 0.89-1.10, P=0.88). Subgroup analysis showed that the incidence of neonatal PTB in the blastocyst group was significantly higher than that in the cleavage-embryo group (RR=1.28, 95%CI: 1.23-1.33, P<0.000 01). Conclusions: In the neonatal outcomes of single delivery in the fresh cycles, blastocyst transfer has the higher risks of VPTB and LGA and lower risk of SGA when compared with cleavage embryo transfer.

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Evaluation of Psychological Status and Somatic Symptoms in Infertile Women Treated with Assisted Reproductive Technology in the Post-Epidemic Era of COVID-19

WANG Ling-yan, ZHOU Dan, YUE Yan, WANG Yu-yang

2021, 40 (5): 366-371. doi: 10.12280/gjszjk.20210057

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Objective: To investigate the application value of psychological status assessment in infertile women who received assisted reproductive technology (ART) in the post-epidemic era of COVID-19. Methods: From June 2020 to November 2020, infertile women who received ART treatment were investigated via the patient health questionnaire scale-15 (PHQ-15), generalized anxiety disorder scale-7 (GAD-7) and patient health questionnaire scale-9 (PHQ-9). The general situation, physical symptoms, anxiety, depression symptoms and other physical and mental health status were evaluated. Cronbach′s α coefficient, Spearman Brown half-split coefficient and two-week-retest reliability were used for the reliability analysis. Confirmatory factor analysis and Spearman correlation analysis were used to analyze the construct validity and criteria validity, respectively. Then the results of the three scales were converted into dichotomous variable (normal and positive results) as dependent variables.Together with patient′s demographic characteristics and infertility-related clinical characteristics which were added as independent variable into the univariate and multivariate logistic regression analysis, respectively(The entry criteria were P<0.1 in univariate analysis). Results: A total of 1 980 patients were included in the study, and the effective recovery rate was 89.6% (1 980/2 210). The Cronbach′s α coefficient and KMO value of PHQ-15, GAD-7 and PHQ-9 were 0.805, 0.863, 0.822 and 0.871, 0.909, 0.890, respectively. These results suggested that the reliability and validity of the three scales were good. Multivariate logistic regression analysis showed that the age of >35 years was the independent risk factor of anxiety, depression and physical symptoms for infertile women. College degree or above and husband smoking were two independent risk factors of anxiety and depression of infertile women. Owned one child was an independent protective factor for depressive symptoms (OR=0.63, 95%CI: 0.41-0.97, P=0.034) and somatic symptoms(OR=0.63, 95%CI: 0.42-0.94, P=0.022). Conclusions: PHQ-15, GAD-7 and PHQ-9 scales can be well used in evaluating the physical and mental health of infertile women who received ART treatment. Patients who were characterized by over 35 years old, college degree or above and husband smoking were vulnerable to anxiety, depression or physical symptoms.

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Prenatal Ultrasound Evaluation and Characteristic Analysis of Twin Reverse Arterial Perfusion Sequence

ZHOU Xun-dan, ZHANG Wen-ting, AN Pei-li, YANG Fang, HOU Xiao-xia

2021, 40 (5): 372-376. doi: 10.12280/gjszjk.20210098

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Objective: To analyze the characteristics of prenatal ultrasound in twin reversed arterial perfusion sequence (TRAPS). Methods: Retrospective analysis was conducted on the ultrasound characteristics of 22 cases of the TRAPS diagnosed in Northwest Women and Children′s Hospital from January 2015 to October 2020. Results: ①There were 13 cases with no heart and no head, no upper limbs, only part of the spine and lower limbs; 5 cases with head but no heart. The halo of skull or part of skull, limbs and spine could be seen, and no heart structure was found. The intracranial structure of these 5 cases was not clear or only part of brain tissue could be seen, or there were serious intracranial malformations; 4 cases of unformed centerlessness showed mass echo of irregular tissue without body structure. ②Concomitant deformity of centerlessness: 13 cases were accompanied with systemic edema, including 4 cases of lymphangioma, 1 case of whole forebrain, 1 case of forebrain with omphalocele, and 2 cases of hydrocephalus. ③In those pump twins, all of 22 cases were found fetal heart by ultrasound. One case showed NT thickening, double lung echo enhancement, intracardiac structural disorder, cardiothoracic ratio increase, pleural effusion, single umbilical artery, and no obvious abnormality was found in other fetuses. ④Color Doppler showed that those fetuses without cardiac malformation had the umbilical artery blood flow and reverse into the abdominal cavity. Conclusions: Prenatal ultrasound is an important means of TRAPS diagnosis. The early diagnosis of TRAPS is helpful to determine the prognosis and provide reliable reference for the treatment.

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Clinicopathological Analysis of Nine Cases of Cervical Gastric-Type Adenocarcinoma

AN Chong-you, MA Yao-mei

2021, 40 (5): 377-381. doi: 10.12280/gjszjk.20210353

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Objective: To analyze the clinical and pathological characteristics of gastric-type adenocarcinoma (GAS), in order to diagnose and treat the disease early and improve the prognosis. Methods: The diagnosis, treatment, follow-up, pathological morphology, immunohistochemical characteristics and other data of 9 cases of cervical GAS in Tianjin Central Hospital of Gynecology Obstetrics from July 2013 to July 2017 were retrospectively analyzed, and relevant literatures were reviewed. Results: The median age of 9 patients was 44 years old. 6 patients were diagnosed in pre-operation, 2 in intra-operation and 1 was in post-operation. There were 3 cases of long-term abnormal vaginal discharge, 2 cases of intrauterine fluid and 5 cases of ovarian mass. The mean overall time to survival was 104.3 months (95%CI: 66.6-142.1 months). The survival rates at 12 months, 24 months and 36 months were 88.9%, 77.8% and 66.7% respectively. The cervical GAS mainly invaded towards the uterine body. The pathological microscope showed little difference from the normal gland. Immunohistochemical analysis of HIK1083, Mucin 6 (MUC6), cytokeratin7 (CK7), CDX2, villin, paired box gene-8 (PAX-8), CA-125, CA-19-9, P16 and carcinoembryonic antigen (CEA) showed high positive rates, while the positive rates of CK20, PAX-2 and P53 were low. Conclusions: Cervical GAS is rare and easy to be misdiagnosed. However, through the multidisciplinary combination of clinical, imaging and pathology, there is an opportunity to achieve the early diagnosis and treatment of GAS and improve the survival expectation.

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A Case Report of Prenatal Diagnosis of 69, XXX Homozygous Triploid

TIAN Xin-yuan, HUI Ling, ZHENG Lei, ZHANG Chuan, HAO Sheng-ju, ZHOU Bing-bo, CHEN Xue, WANG Lian

2021, 40 (5): 382-385. doi: 10.12280/gjszjk.20210215

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A case of 69, XXX homozygous triploid was reported. This is a 24-year-old, 21-week-pregnant woman with adverse pregnancy and childbirth history. The serum prenatal screening showed the high risk of 18-trisomy syndrome. The four-dimensional color ultrasound suggested some abnormality, and the non-invasive prenatal testing (NIPT) suggested the high risk of sex chromosome aneuploidy. After that, the in-depth genetic testing and analysis by the short tandem repeat (STR) fragment analysis and fetal chromosome karyotype analysis were done with the informed consent. In this case, the fetal chromosome karyotype was 69, XXX, and the STR fragment analysis showed fetal triploid. The possible cause of this case was double female fertilization, since no maternal contamination was found in amniotic fluid samples. Therefore, this fetal case was considered as the homozygous triploid. The pregnant woman chose to terminate the pregnancy after genetic counseling. In conclusion, the prenatal diagnosis combining with STR fragment analysis can not only eliminate the influence of maternal contamination, but also find chromosome number abnormalities.

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The Differences between Cumulus Cells and Mural Granulosa Cells in Human Follicles

GAO Er-meng, CHIAN Ri-cheng

2021, 40 (5): 386-390. doi: 10.12280/gjszjk.20200731

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Granulosa cells (GC) are the somatic cells in the follicles. With the development of follicles, GCs are differentiated into two kinds of cells, in terms of location and function: cumulus cells and mural granulosa cells. The cumulus cells are surrounding the oocyte, while the mural granulosa cells (GCs) are lining at the follicular wall. Cumulus cells mainly provide nutrition and energy for the oocyte growth and development, while mural granulosa cells are mainly responsible for endocrine function. Up to date, the differences in metabolomics between human cumulus cells and mural granulosa cells have not been reported. The definitions and differences in function and gene expression between cumulus cells and mural granulosa cells are systematically discussed in this review. New conjectures about the differences in metabolic profiles are also proposed. Exploring the differences between the two kinds of cells may be helpful to evaluate oocyte quality and embryonic developmental potential, and may have important clinical value in predicting pregnancy outcome.

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DNA Damage and Repair during Ovarian Reserve Formation

ZHOU Zhi-xian, ZHU Fang, YIN Huan, SU Ye, CAI Hai-yi, FU Chun

2021, 40 (5): 391-396. doi: 10.12280/gjszjk.20210121

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In the process of the formation of ovarian reserve, the mammalian germ cells are in the active stage of DNA replication, exchange and recombination. DNA of this stage is sensitive to various internal and external damage factors, so it is predisposed to DNA damage. There are multiple pathways of DNA repair during this period. Homologous recombination (HR) pathway repairs DNA double-strand breaks, protects and restarts the stalled replication forks. Fanconi anemia (FA) pathway repairs interstrand crosslinks and promotes the replication forks to restart. Base excision repair (BER) pathway is an important mechanism of genome-wide epigenetic programming. Mismatch repair (MMR) pathway maintains the meiosis process and promotes the crossover formation and stabilization of the recombination process. Nucleotide excision repair (NER) pathway facilitates the repair of interstrand crosslinks. These pathways are essential for maintaining genomic stability of germ cell, reducing germ cell apoptosis, promoting germ cell proliferation and pluripotency expression to regulate the development of primordial germ cells so as to form ovarian reserve. To understand well the DNA damage and repair during ovarian reserve formation provides a theoretical basis for the etiological analysis of primary ovarian insufficiency (POI).

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Fertility Improvement Strategies for Patients with Premature Ovarian Insufficiency

DU Jie-bing, YANG Yi-hua

2021, 40 (5): 397-401. doi: 10.12280/gjszjk.20210001

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Premature ovarian insufficiency (POI) is defined as the decline of ovarian function in women before the age of 40. The main characteristics are amenorrhea or oligomenorrhea, symptoms of low estrogen, and decreased fertility. POI is different from menopause. It is not due to the complete decline of ovarian function. Patients with POI can still experience intermittent ovarian function recovery for a long time. Some POI patients have fertility needs, but the fertility treatments for those patients are limited, and the treatment effect is not ideal. It is need to optimize and personalize the fertility treatment for those POI patients with the fertility needs. This review summarizes some common fertility treatments for POI patients through relevant case reports and references, including drug treatment, surgery, in vitro activation of oocytes, stem cell transplantation, and injection of platelet-rich plasma. Meanwhile, the therapeutic principles, clinical efficacy, feasibility and limitations of clinical application were also reviewed.

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Research Progress on Oxidative Stress and Reproductive Related Diseases

JIANG Nan, MA Rui-hong, ZHAO Xiao-li, XIA Tian

2021, 40 (5): 402-406. doi: 10.12280/gjszjk.20210042

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Reactive oxygen species (ROS) is the product of the reaction between oxygen and electrons. The appropriate level of ROS and the oxidative stress balance play an important role in maintaining physiological function. When ROS was produced too much or the ability to eliminate ROS was weakened, the increased oxidative stress (OS) could lead to a variety of infertility-related diseases. OS is involved in the occurrence and development of polycystic ovary syndrome, endometriosis, recurrent abortion and other diseases, as well as the prognosis of these diseases. In addition to being involved in female reproductive-related diseases, OS can also reduce semen quality and affect male reproductive function. This article reviews the pathogenesis of oxidative stress and its effect on reproduction-related diseases.

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Application of Follicular Phase Long-Acting GnRH Agonist Long Protocol in IVF

LI Wen-shu, LIU Xue-mei

2021, 40 (5): 407-410. doi: 10.12280/gjszjk.20210039

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Gonadotropin-releasing hormone agonist (GnRHa) has been widely used in the pituitary downregulation of in vitro fertilization and embryo transfer (IVF-ET), in which a variety of the controlled ovarian stimulation protocols were derived. The follicular phase long-acting GnRH agonist long protocol has been gradually used in the patients with endometriosis, polycystic ovary syndrome and poor ovarian response, as well as some patients with normal ovarian reserve in recent years. This protocol has the advantages of higher embryo implantation rate and clinical pregnancy rate by improving endometrial receptivity and embryonic quality, when compared with other protocols.

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Application Value of Hysteroscopy in Diagnosis of Adenomyosis

CHEN Chao, ZHANG Ying

2021, 40 (5): 411-414. doi: 10.12280/gjszjk.20210040

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Adenomyosis is a high incidence of disease which seriously endangers women′s health. It is difficult to diagnosis in the early stage. Hysteroscopy can be used to identify specific or nonspecific lesions in the uterine cavity of patients with adenomyosis, sometimes being subtle and characteristic lesions. These lesion include endometrial invagination, vascular hyperplasia, endometritis, uterine compression and cystic adenomyosis. Therefore, hysteroscopy plays an important role in the diagnosis of adenomyosis. Hysteroscopy combined with ultrasound can improve the diagnostic rate of hysteroscopy for adenomyosis, and help to determine the size, location and depth of lesions. Under the guidance of ultrasound, hysteroscopic biopsy can obtain the tissue of the endometrial-myometrial interface for histopathology, which is the most valuable minimally invasive diagnostic method for adenomyosis. This method provides the possibility of individualized treatment for those adenomyosis patients with fertility requirements or desire to preserve the uterus.

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Influencing Factors Related to Endometrial Disease Caused by Polycystic Ovary Syndrome

CAO Jing, SU Rui, WANG Xiao-hui

2021, 40 (5): 415-419. doi: 10.12280/gjszjk.20210137

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Polycystic ovary syndrome (PCOS) is a reproductive endocrine and metabolic disease caused by multiple etiologies. It is clinically manifested as hirsutism, acne, ovulation disorders, oligomenorrhea and amenorrhea. The long-term complications of PCOS include metabolism syndrome, cardiovascular disease, endometrial carcinoma (EC), etc. Endometrial disease refers to the irregular vaginal bleeding, prolonged menstrual period and increased menstrual flow caused by endocrine disorders. Endometrial disease includes endometrial hyperplasia (EH) and EC. The risk of endometrial disease in PCOS patients is increased due to their endocrine and metabolic disorders (including the disorder of estrogen and androgen secretion, insulin resistance and hyperinsulinemia), inflammation, microsatellite instability, miRNA expression disorders and their long-term comorbidities ( such as obesity, diabetes, etc.). The EH and EC in PCOS patients affect their physical and mental health. This article summarizes the research progress of PCOS-related endometrial disease and influencing factors.

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Kisspeptin, Pregnancy and Related Diseases

HAN Xin-yu, WU Tian-qiang, FENG Xiao-ling

2021, 40 (5): 420-426. doi: 10.12280/gjszjk.20210122

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Kisspeptin, a neuropeptide encoded by kiss-1 gene, has been considered to inhibit tumor metastasis and regulate reproductive endocrine. Kisspeptin and its receptors are widely distributed in the brain, pituitary gland, ovary, uterus, placenta and other tissues. The expression of kisspeptin in the endometrium changes periodically, which is significantly increased in the endometrial stromal cells of the late secretion period. The concentration of kisspeptin in placenta and maternal plasma also increases sharply in the first trimester. Recent studies have shown that kisspeptin plays an important role in regulating the physiological processes of pregnancy such as decidualization, placenta formation and embryo implantation. Kisspeptin is also involved in the maintenance of glucose homeostasis during pregnancy. The abnormal level of kisspeptin is associated with pregnancy-related diseases such as recurrent abortion, preeclampsia and gestational diabetes mellitus. In this paper, the role of kisspeptin and the mechanism in the physiological pregnancy and the pregnancy-related diseases are reviewed.

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Advances in the Role of IL-33 in Pregnancy-Related Diseases

CAO Xiao-wan, CHEN Li, SONG Zhen-zhen, ZHANG Guo-ying

2021, 40 (5): 427-430. doi: 10.12280/gjszjk.20210110

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Interleukin 33 (IL-33) belongs to the IL-1β family and is a newly discovered nuclear localization factor with dual anti-inflammatory and pro-inflammatory effects. Studies have shown that IL-33 can maintain normal pregnancy by participating in the process of regulating maternal-fetal immune tolerance. At the same time, IL-33 plays an important role in a variety of pregnancy-related diseases. Abnormal expression or dysfunction of IL-33 in early pregnancy can lead to miscarriage. The decrease of IL-33 in the placenta leads to trophoblast dysfunction, which is related to poor placental function of preeclampsia patients. Decreased expression of IL-33 or dysfunction in the decidua in the middle and late stages of pregnancy plays an important role in the occurrence and development of preterm birth. Although IL-33 can trigger calcium flux in a variety of cells and increase the level of calcium ions in cells, and calcium ions play an important role in uterine smooth muscle contraction, the research on IL-33 in uterine smooth muscle has not been in-depth. The occurrence of preterm birth is ultimately accompanied by uterine smooth muscle contraction, therefore, study on the role of IL-33 in pregnancy-related diseases and the contraction of smooth muscle cells will help to further study the mechanism of occurrence and development of preterm birth, thereby providing new ideas for the diagnosis and treatment of preterm birth.

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Adipokines and Gestational Diabetes Mellitus and Glucose Lipid Metabolism

ZHENG Kai, YUAN Jing

2021, 40 (5): 431-435. doi: 10.12280/gjszjk.20200617

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Gestational diabetes mellitus (GDM) is one of the major complications during pregnancy. With the implementation of the two-child policy, the improvement of living standard and the change of marriage concept, the incidence of GDM has been increasing year by year under the influence of high risk factors such as obesity, age and genetic susceptibility. At present, the specific pathogenesis of GDM is not clear, which may be related to insulin resistance and dysfunction of insulin β cell. The disorder of glucose metabolism in pregnant women with GDM will further lead to the disorder of lipid metabolism, leading to adverse pregnant outcomes. Adipokines, such as betatrophin, chemerin, C1q/tumor necrosis factor related protein (CTRP9) and leptin, may play a role in the pathogenesis of GDM. This article reviews the roles of adipokines in the regulation of glucose and lipid metabolism, and the pathogenesis of GDM.

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Potential Application of Glucagon-Like Peptide-1 Receptor Agonists in the Treatment of Polycystic Ovary Syndrome and Infertile Patients with Obesity

YANG Ze-xin, WANG Jun-chao

2021, 40 (5): 436-440. doi: 10.12280/gjszjk.20210103

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Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenemia, oligo/anovulation, polycystic ovarian changes and impaired fertility. It is the most common cause of anovulatory infertility in women of childbearing age. Most of PCOS patients are accompanied by obesity, while obesity also has a negative impact on fertility. Glucagon-like peptide-1 (GLP-1) as an important gastrointestinal hormone plays an important role in the obesity and progression of PCOS. This review summarizes the mechanism of PCOS and infertility with obese/ overweight and the change of secretion pattern of GLP-1 in those PCOS women with obese. This review will provide the references that GLP-1 receptor agonists (GLP-1RA) can be used in the treatment of PCOS and infertile patients with obesity.

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