Journal of International Reproductive Health/Family Planning

Effect of the Descend Range of Estradiol after Oocyte Retrieval in Antagonist Regimen on the Outcome of In Vitro Fertilization and Embryo Transfer

ZHOU Yu-xi, ZHANG Juan, ZHANG Juan-juan, LING Xiu-feng, ZHAO Chun

2022, 41 (4): 265-269. doi: 10.12280/gjszjk.20220104

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Objective: To study the effect of the descend range of estradiol (E₂) at 48 h after oocyte retrieval compared with 24 h before oocyte retrieval on the pregnancy outcomes of fresh embryo transfer in the antagonist regimen. Methods: A retrospective study was done on the clinical data from 413 cycles of fresh embryo transfer, from January 2017 to March 2021. According to the descend range of E₂ 48 h after oocyte retrieval compared with 24 h before oocyte retrieval, they were divided into four groups according to the quartile method. Group A: The descend range is 0-25.0% of the overall descend range; Group B: 25.1%-50.0%; Group C: 50.1%-75.0%; Group D: 75.1%-100.0%. The ovulation induction, embryological outcome and pregnancy outcomes were compared, and the relationship between E₂ reduction and live birth rates was analyzed by logistic regression. Results: There were significant differences in the total amount of Gn, days of antagonist use, live birth rates, implantation rates and clinical pregnancy rates among the four groups (all P<0.05). The live birth rate of group A was higher than group D, group B was higher than those of group C and group D, and the implantation rates of group A and group B were higher than group D (all P<0.008 3). After adjusting for the factors of differences among groups, the live birth rates of groups A and B were significantly higher than those of group D (OR=2.079, 95%CI: 1.138-3.799, P=0.017; OR=2.187, 95%CI: 1.213-3.944, P=0.009). Conclusions: In the antagonist regimen, the live birth rate of fresh embryo transfer in patients with a greater descend range of E₂ at 48 h after oocyte retrieval is lower than that in patients with less descend range of E₂.

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Bioanalysis of Non-Obstructive Azoospermia at Different Arrest Stages

WANG Wan-lun, LIU Tong-jia, ZHANG Ting, LI Shuo, BIAN Yan-chao, XIAO Rui

2022, 41 (4): 270-274. doi: 10.12280/gjszjk.20220167

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Objective: To screen the regulatory factors and the related pathways of non-obstructive azoospermia (NOA), and to explore the underlying molecular mechanisms by bioinformatics. Methods: The gene expression matrix of GSE45885 was obtained from GEO database. The samples of the NOA at the different arrest stages and the controls were screened, including 20 NOA samples and 4 normal samples. Among the 20 NOA patients, 2 patients were in the premeiotic arrest stage (PRE), 7 patients in the meiotic arrest stage (MEI) and 11 were in postmeiotic arrest stage (POST). The GEO2R online tool was used to identify the differentially expressed genes (DEGs). The data of three arrest stages of NOA in GEO chip were integrated and normalized, and then the intersection was obtained after correction. Gene Ontology（GO）enrichment analysis and Kyoto Encyclopedia of Genes and Genomes（KEGG）pathway enrichment analysis were performed for the differentially expressed genes and their target genes to obtain key pathways. Protein-protein interaction (PPI) network graph was constructed based on online tool (STRING). Finally, CytoHubba in Cytoscape was used to screen Hub genes. Results: 463 up-regulated genes and 12 down-regulated genes were screened in PRE. Two and three down-regulated genes were found in MEI and POST, respectively. There were no up-regulated genes in MEI and POST. The up-regulated genes in PRE participated in the regulation of spermatogenesis through some important pathways such as spermatogenesis, spermatid development, sperm motility, motile cilium and microtubule formation. Two common differential expression genes were screened out from the above three arrest stages of NOAs, two of them were microRNAs (miRNA), and two miRNAs had 58 common target genes. An online bioinformatics tool STRING was used to successfully construct a PPI network map of up-regulated genes in PRE, and Cytoscape was used to screen out the top 10 Hub genes in the network including DNAI1, DNAI2, PGK2, ROPN1L, ARMC4, DRC1, DNAAF3, CABYR, ZMYND10, CCDC65. Conclusions: The identification of Hub genes, common differential genes and their pathways will provide valuable references for the subsequent study on the mechanism of NOA. DRC1, ARMC4, MIR15A and MIR509-3 may serve as potential targets for subsequent studies on the etiological mechanism of NOA.

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Evaluation on the Application of Special Lectures about Scientific Contraception in Health Education in A University in Nanjing

YANG Yue-hua, SUN Zhi-ming

2022, 41 (4): 275-278. doi: 10.12280/gjszjk.20220126

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Objective: To evaluate the effect of special lectures about scientific contraception on the improvement of college students′ contraception knowledge, in order to provide evidence for health education in universities in China. Methods: 242 freshmen in a university in Nanjing at October 2021 were given a special lecture on scientific contraception. The questionnaire survey was conducted before and after the lecture, in order to compare the changes of college students′ contraceptive knowledge. Results: The lecture significantly improved the cognitive accuracy of college students′ contraceptive knowledge and their mastery of common contraceptive methods(both P<0.01). When choosing contraceptive methods, they will pay more attention to the internal characteristics of products such as contraceptive effect, side effects, convenient use and additional benefits (P<0.01), and the proportion of intentional choice of high-efficiency contraceptive methods has increased significantly (P<0.01). Conclusions: The special lecture on scientific contraception is simple and easy to operate, especially has obvious and immediate effect, so we think that it can be used as a method of health promotion in colleges and universities.

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A Clinical Analysis of 13 Cases of Ovarian Sertoli-Leydig Cell Tumor

XU Qian, CHENG Jiu-mei

2022, 41 (4): 279-283. doi: 10.12280/gjszjk.20220156

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Objective: To improve the diagnosis and treatment of ovarian Sertoli-Leydig cell tumor (SLCT). Methods: Thirteen cases of ovarian SLCT admitted between June 2014 and July 2021 were analyzed retrospectively, including their clinical characteristics, diagnosis, treatment and prognosis. Results: The median age of onset was 31 years (13-72 years) in 13 patients. Eight patients (61.5%) had the androgenic manifestations (due to the elevated levels of testosterone), 3 patients (23.1%) presented with abnormal uterine bleeding, and the other two patients (15.4%) had no obvious clinical symptoms. Imaging mainly showed cystic-solid tumors or solid tumors. All 13 patients underwent surgery, and diagnosed with ovarian SLCT by histopathology and immunohistochemistry. Eleven patients were at stage ⅠA, and 2 patients at stage ⅠC. Four patients underwent the complementary surgery to resect the affected adnexa and perform the multi-point pelvic and abdominal biopsy after 1-2 months of the initial operation and histopathological diagnosis. Two patients with SLCT at stage ⅠC underwent postoperative chemotherapy with the bleomycin + etoposide + cisplatin (BEP) regimen. The median follow-up time after surgery was 33 months. None of the 13 patients had a recurrence. Conclusions: Ovarian SLCT should be considered when women had abnormal endocrine symptoms and ovarian cystic-solid or solid masses. Surgery is main treatment for SLCT patient, and operative and postoperative histopathology will confirm the diagnosis of ovarian SLCT. Postoperative chemotherapy can be accordingly considered, and the postoperative multidisciplinary follow-up has been suggested.

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Male Azoospermia Caused by Compound Heterozygous Mutation in CYP21A2 Gene and Multi-Gene Mutations: A Case Report and Literature Review

GONG Yi-xin, DING Yu, LUO Si-hui, ZHENG Xue-ying

2022, 41 (4): 284-288. doi: 10.12280/gjszjk.20220207

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CYP21A2 mutation causes 21-hydroxylase deficiency (21-OHD), leading to congenital adrenal hyperplasia and gonadal dysplasia. There is heterogeneity in clinical phenotype due to the different gene mutation sites. Infertility appears to be the leading cause for adult 21-OHD outpatients. The complicated cases of the CYP21A2 mutation combined with multiple gene mutations were rarely reported in the worldwide. We reported a case of male azoospermia with the compound heterozygous mutation of c.518T>A/c.293-13A>G coding CYP21A2. Interestingly, this case was complicated with DNAJB13/DNAI1/QRICH2J/FSIP2/HYDIN multi-gene mutations. The clinical phenotype was male infertility, and spermatogenesis was established by the treatment with glucocorticoid for three months. This case report enriched the genotypes of male infertility, and provided us with experience in the clinical diagnosis and treatment of these diseases.

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Two Cases of 21-Hydroxylase Deficiency in Reproductive Age Misdiagnosed as Polycystic Ovary Syndrome and Literature Review

CHI Xue-xiu, GUO Bao-qiang, YU Shan, HE Dong-hua

2022, 41 (4): 289-293. doi: 10.12280/gjszjk.20210611

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21-hydroxylase deficiency (21-OHD) is one of the most common congenital adrenal hyperplasia. The clinical symptom in part of patients with 21-OHD is atypical, so that 21-OHD is easy to be misdiagnosed or missed diagnosis. In this paper, we report 2 cases of 21-OHD that was misdiagnosed as polycystic ovary syndrome (PCOS) due to menstrual disorder, infertility and hyperandrogenemia. Sanger sequencing showed that one patient carried c.374G>A (p.Arg125His) and c.518T>A (p.Ile173Asn) heterozygous missense mutations, confirming that the mutant gene came from her parents. Another patient carried homozygous missense mutation of c.518T>A (p.Ile173Asn), and the source of mutation was not clear because her relatives were not detected. With the treatment of oral dexamethasone, 2 patients were restored the regular menstruation, and improved the symptoms of hyperandrogenism. One patient got successful pregnancy and childbirth. When women of childbearing age with infertility and hyperandrogenemia were diagnosed as PCOS, and the treatment effect is not good, 21-OHD should be considered. The combination of 17-OHP assay, ACTH excitation test and gene mutation test will be helpful for the definite diagnosis and differential diagnosis.

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A Case of Successful Delivery in An Infertile Patient with Ovarian Resistance Syndrome: Treated with Antagonist Protocol and Fresh-Embryo Transfer

CHEN Ya-nan, GUO Jia-li, LI Ze-wu, YANG Ai-jun

2022, 41 (4): 294-297. doi: 10.12280/gjszjk.20210634

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Resistant ovarian syndrome (ROS) is a reproductive endocrine disorder of unknown etiology, with a low incidence and mainly leading to infertility. The complicated treatment and long procedure cause the anxiety of ROS patients. In this paper, we report a case of an infertile patient with ROS, who underwent in vitro fertilization and embryo transfer (IVF-ET) for successful pregnancy. The patient had failed to conceive after several in vitro fertilization treatments at an outside hospital because of her primary infertility, ineffective ovulation treatment, and low response to exogenous gonadotropin (Gn). In the following treatment in our hospital, we adjusted her Gn level and finally obtained a live birth after fresh embryo transfer with an antagonist regimen. Through a retrospective analysis of the relevant literatures, we hope to explore the possible reasons for the successful treatment of this ROS case, and to provide new ideas for the clinical management of ROS patients, so that we can achieve a more satisfactory pregnancy outcome while reducing the cost of treatment.

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A Case of Spontaneous Ovarian Hyperstimulation Syndrome in Pregnancy

ZHOU Duo, LI Heng-jing, LU Guang-mei, HUANG Qiu-fang, ZHANG Yi

2022, 41 (4): 298-301. doi: 10.12280/gjszjk.20210541

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Ovarian hyperstimulation syndrome is a common complication in assisted reproductive technology. It usually occurs after two weeks or more of induced ovulation. However, the spontaneous ovarian hyperstimulation syndrome (sOHSS) is extremely rare. Some clinical cases showed that the etiology of sOHSS was related to the mutations of follicle stimulating hormone receptor gene, the high level of human chorionic gonadotropin (hCG), the high level of thyroid-stimulating hormone (TSH), and gonadotropin pituitary adenoma. In this paper, we report a case of twin pregnancy complicated with sOHSS, and further study the possible etiology, diagnosis and treatment of sOHSS.

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Clinical Treatment Strategies of Repeated Implantation Failure

WANG Yan, MENG Qing-xia

2022, 41 (4): 302-307. doi: 10.12280/gjszjk.20220171

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The rapid development of assisted reproductive technology has enabled many infertile patients to get successful pregnances through in vitro fertilization and embryo transfer and its derivative technology. However, there are still some patients who have failed to obtain a clinical pregnancy after transferring high-quality embryos for many times. This is called repeated implantation failure (RIF). RIF is a difficult problem in assisted reproductive technology, which increases the economic burden of patients and aggravates their physical and mental trauma. How to improve embryo quality, to intervene maternal factors (such as improving thin endometrium, improving endometrium receptivity, inhibiting uterine contraction, improving hypercoagulability, immunosuppressive therapy) and to change embryo transfer methods so as to improve pregnancy outcomes, are hot spots in clinical research. The research progress of clinical treatment strategies of RIF due to different etiologies was reviewed in order to provide reference and treatment ideas for clinical workers.

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Injury Factors of Vitrification Cryopreservation and Transplantation of Ovarian Cortex

HUANG Shao-feng, NIU Xiang-li, LIN Zhong, ZHU Xue-hong, BIN Li, LIU Shu-cen

2022, 41 (4): 308-312. doi: 10.12280/gjszjk.20220115

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The cryopreservation and transplantation of ovarian tissue is technically feasible, and the effectiveness is improved with the development of technology. It can be used to preserve female fertility, especially to preserve the fertility of prepubertal women with cancer who will have radiotherapy and chemotherapy. Vitrification is considered to be one of the most promising methods for cryopreservation of ovarian tissue, but its safety and efficacy need to be further verified. Cryogenic injury and transplantation ischemia-reperfusion injury are two problems of further development of cryopreservation and transplantation, in which the difficulty and focus are how to preserve follicles effectively. The existing freezing and transplantation conditions and effects are evaluated from six aspects of cryoprotectant, ovarian tissue size, cryocarrier, antioxidants, promoting angiogensis and hormones, in order to advance the project of female fertility preservation.

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Autophagy Participated in Pathological Mechanism of Premature Ovarian Insufficiency

YAO Ting, YANG Hong-mei, CUI Li-hua, MENG Qing-fang

2022, 41 (4): 313-316. doi: 10.12280/gjszjk.20220133

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The combination of factors of premature ovarian insufficiency (POI) may include chromosomal abnormalities, autoimmune diseases, chemotherapy, environmental pollutants and so on. Autophagy as a kind of important mechanisms for maintaining cellular homeostasis and energy balance is associated with the occurrence and development of POI. The autophagy defect related to chromosomal abnormalities and gene mutations may lead to a large number of primordial follicles loss and the restraint of granulosa cell differentiation, which injures ovarian function, and finally leads to POI. The excessive activation of autophagy caused by stimulation of adverse factors in ovarian cells, such as autoimmune diseases, chemotherapy and environmental pollutants, leads to the apoptosis of ovarian cells and the increase of atresia follicles, which reduces primordial follicles, and finally leads to POI. In this paper, the effect of autophage in the pathogenesis of POI was reviewed, in order to discusse how to improve ovarian function of POI patients in clinical practice.

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Effect of Circadian Rhythm Disorder on Ovarian Function

WANG Zi-xin, SONG Jia-yi, XIA Tian

2022, 41 (4): 317-321. doi: 10.12280/gjszjk.20220089

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Circadian rhythm as an endogenous timing mechanism regulates the sleep, diet and reproductive rhythm of human body. With the changes of life and work patterns, the disorder of circadian rhythm has become a health problem of general concern. Ovarian function reflects the growth and development ability of basic follicles in ovarian cortex, including the number and quality of follicles, and reflects women′s reproductive potential. More and more studies have shown that there is a correlation between circadian rhythm and ovarian function. Circadian rhythm disorder affects ovarian function by changing the secretion of reproductive hormones, ovulation, the number of oocytes, the level of melatonin and the expression of clock genes. This review expounds the influence of circadian rhythm disorder on ovarian function, so as to provide ideas for clinical research and diagnosis and treatment.

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Advances of Stem Cell Therapy for Endometrial Injuries

SHEN Yan-qing, CHEN Huang, CHEN Ye

2022, 41 (4): 322-326. doi: 10.12280/gjszjk.20220179

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Endometrial injuries caused by infection or intrauterine hinders the implantation and development of embryos, and seriously affects women′s physical and mental health and their fertility. However, the current treatment approaches are limited and ineffective. Stem cells play an important role in repairing the damaged tissue due to their self-renewal capacity and differentiation potential. The cells used in the stem cells therapy, such as bone mesenchymal stem cells (MSCs), umbilical cord mesenchymal stem cells (UC-MSCs), endometrial stem cells (EnScs), adipose-derived stem cells (ASCs) and human amniotic epithelial cells (hAECs) have been shown the great potential for endometrial injury treatment in the animal models and clinical studies. Stem cell therapy promotes the regeneration of endometrial cells, thereby improving the endometrial thickness and microvessel density, as well as increasing the conception rate and improving the fertility outcome. Stem cell therapy may improve the endometrium morphologically and functionally, and help to restore the menstrual and reproductive functions, providing a new therapeutic strategy for endometrial injuries.

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Leukemia Inhibitory Factor Related to Endometrial Receptivity

ZHANG Xiao-xuan, ZHAI Chao, LI Guang-can, REN Chun-e

2022, 41 (4): 327-331. doi: 10.12280/gjszjk.20220168

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Endometrial receptivity plays a key role in embryo implantation, and 2/3 of embryo implantation failures are due to poor endometrial receptivity. Leukemia inhibitory factor (LIF) is an important biological marker of endometrial receptivity. The expression of LIF is highly upregulated in the endometrial glandular epithelium during the implantation window. LIF participates in the regulation of signal transduction of endometrial epithelial cells during embryo implantation, which may transform the endometrium from a non-receptive state to a receptive state. Abnormal expression of LIF impaires endometrial receptivity, which is closely related to the occurrence of infertility. Studies have showed that the expression of LIF is steroid-dependent, and that the expression can also be regulated by a variety of cytokines and growth factors. This paper describes the expression of LIF, signal transduction pathway and influencing factors of LIF expression in the establishment of endometrial receptivity, embryo implantation and decidualization, providing new ideas for the diagnosis and treatment of endometrial receptivity.

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Advance of Pierson Syndrome

LIAO Zhen-hua, YANG Feng-xun, JIANG Hong-kun, LU Yu

2022, 41 (4): 332-336. doi: 10.12280/gjszjk.20220193

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Pierson syndrome is an autosomal recessive genetic disease caused by the mutations of LAMB2 gene encoding laminin β2, which is characterized by congenital nephrotic syndrome, early-onset renal failure and bilateral small cornea. It is often accompanied by diffuse mesangial sclerosis, serious other ocular abnormalities and nervous system abnormalities, and often rapidly progresses to renal failure. Pierson syndrome is rare in clinic, which is difficult to diagnose according to clinical phenotype, and is easy to be missed and misdiagnosed. It needs to be differentiated from other disorders that can cause renal abnormalities with or without extrarenal abnormalities. At present, there is no specific therapy for Pierson syndrome, and the treatment methods are mainly targeted in the supportive care. The prognosis of Pierson syndrome is poor. We review the research progress of Pierson syndrome to improve clinicians′ understanding.

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Roles of Growth Differentiation Factor 15 in Gestational Diseases

SHI Zi-yun, LIANG Jing, ZHANG Ying

2022, 41 (4): 337-341. doi: 10.12280/gjszjk.20220004

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Gestational diseases are a series of diseases related to the abnormal physiological function of maternal and fetus during pregnancy, which seriously impair the health of maternity and infant. Recent studies have shown that the highly-specifical expression of growth differentiation factor 15(GDF15) in placental tissue is crucial to maintain gestation and to promote normal fetal development, and the expression of GDF15 is abnormal in the placental tissue of various gestational diseases, including hyperemesis gravidarum, abortion, pregnancy anemia, gestational diabetes and gestational hypertension, etc. GDF15 as a multifunctional cytokine could participate in the regulation of energy metabolism during pregnancy by regulating insulin resistance and glucose tolerance. GDF15 could also play an important role in the regulation of immune balance during pregnancy by regulating the functions of macrophages, dendritic cells and other immune cells. We review the roles of GDF15 in the pathogenesis and pathophysiology of gestational diseases.

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Research Progress of High-Risk Human Papillomavirus Negative Cervical Cancer

LI Yu-lan, LIU Xiao, HAN Feng-jiao, YUE Ling, XU Fei-xue

2022, 41 (4): 342-346. doi: 10.12280/gjszjk.20220163

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Cervical cancer is the most common malignant tumor of female reproductive system, and the persistent infection of high-risk human papillomavirus (HR-HPV) is a necessary factor of cervical intraepithelial neoplasia and canceration. Currently, the early screening methods for cervical cancer include HPV testing, cervical exfoliation cytology and colposcopy. Clinically, most patients with cervical cancer are of HR-HPV positive, but less than 1% of cervical cancer patients are of HR-HPV negative. Compared with the HR-HPV positive cervical cancer patients, the HR-HPV negative cervical cancer patients have poor prognosis. Therefore, the most urgent issues are to find the pathogenesis of HR-HPV negative cervical cancer, and to explore the specific biomarkers and new therapeutic targets. In this paper, the pathogenesis, clinical characteristics and molecular biology research progress of HR-HPV negative cervical cancer are described, in order to provide new clinical ideas and basis for the diagnosis and treatment of HR-HPV negative cervical cancer.

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Interpretation of "2021 ACOG Clinical Consensus: Pharmacologic Stepwise Multimodal Approach for Postpartum Pain Management"

WANG Bin, GUAN Bo-yang, TIAN Yun, SUN Ying, ZHUANG Guo-li

2022, 41 (4): 347-352. doi: 10.12280/gjszjk.20220031

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Postpartum pain is a common problem for pregnant women. Improper treatment may lead to adverse consequences such as greater opioid use, postpartum depression, and development of persistent pain. Therefore, ACOG put forward clinical consensus about the recommendations on pharmacologic stepwise multimodal approach for postpartum pain management in 2021, especially for acute perineal, uterine and incisional pain. In addition, it also provides advices for the treatment of postpartum pain when breastfeeding or discharge, and emphasizes the principle of individualized medication. The recommended clinical medication can follow the step-by-step administration of "non-opioid analgesics (such as acetaminophen and non-steroidal anti-inflammatory drugs) - weak opioids - strong opioids (if necessary)". Those can be combined reasonably. We tried to interpreted the main viewpoints of this clinical consensus in this review.

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