Journal of International Reproductive Health/Family Planning

Influence Factors of Pregnancy Outcomes in Frozen-Thawed Embryo Transfer Cycles Following Preimplantation Genetic Testing

HU Rui, WEI Cai-juan, JIA Dong-ling, MAO Bin, MA Xiao-ling, YANG Yuan

2023, 42 (1): 1-6. doi: 10.12280/gjszjk.20220344

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Objective: To analyze the influence of three common schemes of endometrial preparation on the pregnancy outcome and related influencing factors during the frozen-thawed embryo transfer (FET) cycle after preimplantation genetic testing (PGT), so as to provide a reference for the assisted reproduction treatment of PGT patients. Methods: The clinical data and pregnancy outcomes of 195 patients with 219 cycles of FET assisted by PGT from January 2017 to January 2022 at the First Clinical Medical College of Lanzhou University were analyzed retrospectively, including the cycles of PGT for aneuploidies (PGT-A), PGT for monogenetic (PGT-M), and PGT for structural rearrangements (PGT-SR). According to the endometrial preparation schemes, these cycles were divided into three groups: the natural cycle group (NC group, 56), the gonadotropin releasing hormone agonist (GnRHa) combined with hormone replacement therapy (HRT) cycle group (GnRHa+HRT group, 102) and the simple HRT cycle group (61). The general clinical data and pregnancy outcomes of the three groups were compared, and the influencing factors of live birth were analyzed by logistic regression. Results: The NC group, GnRHa+HRT group and HRT group all achieved higher clinical pregnancy rate (64.29%, 80.39%, 73.77%, P>0.05) and live birth rate (83.33%, 85.37%, 84.44%, P>0.05). The difference of PGT methods used in the three groups was statistically significant (P=0.002). The ratio of patients receiving PGT-SR in the NC group was higher than that in GnRHa+HRT group (P<0.05). The ectopic pregnancy rate in the NC group was higher than that in the other two groups (P<0.05). There were significant differences in the BMI, number of oocytes retrieved, number of transferable embryos and number of high-quality blastocysts between the live birth group and the non live birth group (P<0.05). In addition to the above four factors, the adverse pregnancy history and total number of blastocysts (P<0.2) of the two groups were included in the logistic regression analysis. It was found that only the number of high-quality blastocysts had an impact on the pregnancy outcomes, and that the number of high-quality blastocysts >2 was a protective factor for the outcome of live birth of PGT patients (OR=0.480, P<0.05). Conclusions: The clinical pregnancy rate and live birth rate of three FET endometrial preparation protocols are similar, but the ectopic pregnancy rate in the NC group is higher. It should be noted that the BMI, number of oocytes retrieved, number of transferable embryos and number of high-quality blastocysts may jointly affect the outcome of live birth of PGT patients, especially the number of high-quality blastocysts, so as to improve the live birth rate of PGT patients.

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Analysis of Affecting Factors on Clinical Pregnancy Outcomes in GnRH Antagonist Protocol

SHENG Jia-jia, DAI Zhi-jun, TANG Zhi-xia, YAN Chun, HONG Ming-yun

2023, 42 (1): 7-12. doi: 10.12280/gjszjk.20220342

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Objective: To investigate the factors influencing the clinical pregnancy outcomes of gonadotropin releasing hormone (GnRH) antagonist protocol. Methods: Data of 262 treatment cycles undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) in GnRH antagonist protocol at the Reproductive Medicine Center of Anhui Provincial Maternal and Child Health Hospital from January 2017 to March 2022 were retrospectively analyzed. According to clinical pregnancy outcomes, they were assigned to the clincial pregnant group and the non-pregnant group. Multiple logistic regression analysis and the receiver operating characteristic curve (ROC) were used to analyze the risk factors affecting clinical pregnancy outcomes, and the cut-off values were calculated. Results: The thickness of endometrium on the hCG trigger day was a protection factor affecting clinical pregnancy outcomes（OR=1.421, P<0.001). The cut-off value of endometrial thickness was 11 mm, and the area under the curve analysis of endometrial thickness was 0.702. Too thin endometrial thickness (<9 mm) was companied by the lowest implant rate. The clinical pregnancy rate in the 11 mm<x<15 mm group was significantly higher than that in the x<9 mm group and the 9 mm≤x≤11 mm group(P<0.05), but there was no significant difference with 15 mm≤x<20 mm (P>0.05). There was no significant difference in the miscarriage rate among these groups (P>0.05). The type of A endometrium on the hCG trigger day had better clinical pregnancy outcomes than the type B/C (OR=3.425, P=0.006). Conclusions: Endometrial thickness >11 mm and the Type A on the hCG trigger day were two protection factors affecting clinical pregnancy outcomes in GnRH antagonist protocol. The excessively thickened or thin endometrial thickness on the hCG trigger day should attract our attention.

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Comparison of Three Controlled Ovarian Hyperstimulation Protocols in Advanced-Age Infertile Patients with Diminished Ovarian Reserve

ZHAO Hai-jun, ZHANG Xi-hui, CHEN Jing, LU Jing, ZHANG Hong-feng, CHANG Wen-liang

2023, 42 (1): 13-17. doi: 10.12280/gjszjk.20220213

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Objective: To compare the application effects of three protocols of the controlled ovarian hyperstimulation in advanced-age patients with diminished ovarian reserve (DOR) when undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET). Methods: The data of 186 IVF/ICSI-ET cycles of advanced-age patients with DOR in the Department of Reproductive Medicine in Handan Central Hospital from June 2016 to January 2020 were retrospectively analyzed. According to the protocols of ovarian stimulation, the included subjects were divided into three groups: the progestin-primed ovarian stimulation (PPOS) group (n=61), the microstimulation group (n=65) and the GnRH antagonist (GnRH_A) group (n=60). The differences in general conditions, treatment indicators and pregnancy outcomes were compared. Results: Compared with the microstimulation group, the PPOS group and GnRH_A group had the prolonged duration of gonadotropin (Gn) and the increased total dosage of Gn, while both groups had the higher levels of serum E₂ on hCG day (all P<0.05). The numbers of oocytes retrieved were significantly increased, the numbers of available embryos and high-quality embryos increased, and the cycle cancellation rates were significantly decreased, the effective frozen-thawed embryo transfer (FET) cycle rate increased, in the PPOS group and GnRH_A group when compared with the microstimulation group. Understandably, the cumulative pregnancy rates and the cumulative live birth rates in the PPOS group and GnRH_A group were significantly higher than those in the microstimulation group (both P<0.05). The serum level of LH on hCG day in the microstimulation group and PPOS group was higher than that in the GnRH_A group (P<0.05). The effective FET cycle rate in the PPOS group was significantly higher than that in the GnRH_A group(P<0.05). Conclusions: Those advanced-age patients with DOR can receive a good pregnancy outcome by using either PPOS protocol or GnRH_A protocol during their IVF/ICSI-ET treatment cycles. Both of the two protocols are of feasible choice.

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IVF/ICSI Outcomes in Infertility Patients with Uterine Septum after Transcervical Resection of Septum

ZHANG Yu-ting, ZHU Yuan, ZHOU Jian-jun

2023, 42 (1): 18-22. doi: 10.12280/gjszjk.20220170

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Objective: To analyze the clinical outcomes of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment in those patients after transcervical resection of septum (TCRS). Methods: The data of 183 patients with uterine septum who underwent IVF/ICSI in our Center from January 2013 to July 2020 were collected. The pregnancy outcomes of the patients treated by TCRS(TCRS group, 156 cases) or no TCRS (unTCRS group, 27 cases) were analyzed. Results: There were 247 embryo transfer cycles in total. The clinical pregnancy rate was 64.0% and the live birth rate 49.0% in fresh embryo transfer cycles. In frozen embryo transfer cycles, the clinical pregnancy rate was 51.0% and the live birth rate 40.1%. There were no significant differences between the two groups in the implantation rate, clinical pregnancy rate, spontaneous abortion rate, premature birth rate, live birth rate and birth weight of newborn with single pregnancy (all P>0.05). Compared with the TCRS group, the unTCRS group had higher rate of twin pregnancy (77.8% vs. 27.3%, P=0.006), the smaller gestational week of delivery (P=0.049) and the lower newborn birth weight (P=0.005) in fresh embryo transfer cycles. There were no significant differences in above related indexes between the two groups in frozen embryo transfer cycles (all P>0.05). Conclusions: For infertility patients with uterine septum without abnormal pregnancy history, before IVF/ICSI, can be not treated by TCRS. Single embryo transfer is recommended to improve their clinical outcome.

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Prenatal Diagnosis and Clinical Genetic Analysis of Chromosome 22q11.2 Microduplications

LI Yan-qing, SU Jing-ming, CHEN Geng-bo, JIANG Yu-ying, WANG Yuan-bai, XIAO Shan-shan, ZHUANG Jian-long

2023, 42 (1): 23-26. doi: 10.12280/gjszjk.20220351

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Objective: To analyze the prenatal ultrasonographic and genetic characteristics in fetuses with chromosome 22q11.2 microduplications. Methods: A total of 13 cases with 22q11.2 microduplications from Prenatal Diagnosis Center of Quanzhou Women′s and Children′s Hospital from January 1, 2018 to June 30, 2021 were included. Prenatal ultrasonographic characteristics, genetic causes and follow-up results were collected. Single nucleotide polymorphism array (SNP-array) and karyotype analysis were performed using amniotic fluid and umbilical cord blood. Results: The results of prenatal ultrasound demonstrated that case 1 had congenital diaphragmatic hernia and nuchal translucency (NT) thickening and choroid plexus cyst, and that case 2 and case 8 had the aberrant right subclavian artery. The results of SNP-array showed the microduplication fragments in 22q11.2 region range from 801.1 kb to 3.8 Mb in the enrolled 13 cases. Parental SNP-array verification indicated that two cases of microduplications were inherited from normal parents and that two of microduplications were de novo. At last, ten families chose to continue their pregnancies. Among them, 8 fetuses were followed up after birth without obvious abnormality, and 2 fetuses lost follow-up after birth. Conclusions: Interpretation of the clinical significance of prenatal 22q11.2 microduplications should be careful; the combination of prenatal ultrasonography and parental SNP-array verification will be helpful for the selection of pregnancy outcomes.

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Occult LH Peak in GnRH Antagonist Protocol: A Case Report and Literature Review

WANG Ying-xin, ZHANG Ning, XU Shu-ning

2023, 42 (1): 27-30. doi: 10.12280/gjszjk.20220439

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GnRH antagonist protocol, as a common clinical ovulation protocol, has the advantages of flexibility, economy and safety. However, the early-onset LH peak due to inadequate dosing or inappropriate timing of antagonist addition can ultimately affect pregnancy outcomes. We review the clinical data of a patient who developed an occult LH peak during the antagonist regimen. The patient showed an increased level of progesterone and a decreased level of estradiol during her ovulation with the antagonist regimen, suggesting the occurrence of an occult LH peak. She also had a premature ovulation during the oocyte retrieval procedures. In the second cycle, the long-lasting luteal phase regimen was used to effectively reduce the appearance of endogenous LH peak, and 8 eggs were successfully obtained. We also discuss the diagnosis and prevention of occult LH peak occurring in antagonist regimens in this paper.

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A Case Report on Cervical Pregnancy Combined with Ovarian Pregnancy after IVF-ET

WANG Shu-fang, HU Meng-ying, DONG Qu-long, WANG Hua, CHEN Juan, YANG Zhen-hua

2023, 42 (1): 31-34. doi: 10.12280/gjszjk.20220469

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The pregnancy with both cervical pregnancy and ovarian pregnancy is a special type of ectopic pregnancy. The incidence is far lower than that of tubal pregnancy. However, the risk is relatively high, and untimely diagnosis and treatment may cause serious adverse consequences. It is necessary to identify, diagnose and treat as early as possible. In recent years, with the progress of assisted reproductive technology, the incidence of this type of ectopic pregnancy has increased. The color ultrasound technology is helpful to the early diagnosis. In 2022, a woman diagnosed with cervical pregnancy combined with ovarian pregnancy after in vitro fertilization-embryo transfer was diagnosed in the department of gynecology at the Characteristic Medicine Center of the Chinese People′s Armed Police Forces. In this extremely rare and special case, because of the early diagnosis, the woman was cured with minimized side injury, cost and pain by the method of individualized drug and curettage of cervical canal, without any invasive operations such as surgery or arterial embolism. The outcome was very satisfactory.

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Two Cases of Induced Labor after Missed Diagnosis of Cornual Pregnancy and Literature Review

SONG Jian-ming, KONG Wei-min

2023, 42 (1): 35-39. doi: 10.12280/gjszjk.20220360

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The clinical data of 2 cases of cornual pregnancy were reported. The clinical characteristics and treatment plan were summarized, and were analyzed in detail combined with literature review. The etiology of cornual pregnancy may be related to pelvic inflammatory disease, abnormal uterine morphology or uterine space occupying, assisted reproductive technology and other factors. However, it is not clear until now. Cornual pregnancy is prone to misdiagnosis and missed diagnosis during early pregnancy. Ultrasound and magnetic resonance imaging can improve the accuracy of diagnosis. Laparoscopic surgery and laparoscopic direct vision tissue aspiration of cornual pregnancy can be performed before the vital signs are stable or the lesions are not ruptured or bleeding heavily. If the patient has suffered from intraperitoneal hemorrhage and shock, or has serious abdominal adhesions, or has a bigger gestational age or a bigger fetus, open surgery should be performed as soon as possible. After treatment of cornual pregnancy, the strict follow-up is required. For those with cornual wedge resection or cornual perforation during uterine aspiration, strict contraception is required for at least 6 months, and for the best being 2 to 3 years. Watch out for recurrent cornual pregnancy, uterine rupture and placenta implantation after a second pregnancy.

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Successful Treatment of Acute Pulmonary Embolism in the Third Trimester of Pregnancy: A Case Report

WU Nan, TONG Yu, XU Xiu-hua

2023, 42 (1): 40-43. doi: 10.12280/gjszjk.20220260

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Pulmonary embolism (PE) is a clinical syndrome in which the pulmonary artery or its branches are obstructed by endogenous or exogenous emboli, resulting in circulatory abnormalities and cardiac dysfunction. A case of acute pulmonary embolism in the third trimester of pregnancy was successfully treated. The patient was admitted to our hospital because of "threatened preterm labor". Venous thromboembolism assessment on admission did not indicate high risk. However, the patient developed palpitation, chest tightness and dyspnea after forced defecation on the fourth day of admission. The patient had the increased heart rate, decreased blood oxygen, normal blood pressure, and increased D-dimer, and no other obvious abnormalities. Electrocardiogram showed the moderate ST depression and abnormal T wave. Ultrasound examination showed a very slow flow rate of deep veins of both lower limbs, mild pulmonary hypertension, and slightly enlarged right ventricle. Other ultrasound examination showed no obvious abnormalities. After multidisciplinary consultation and discussion, the acute pulmonary embolism during pregnancy was considered. This disease was characterized by acute onset and rapid progress. Therefore, the patient after the emergency cesarean section of the lower uterine segment was transferred to the ICU of the general hospital for treatment. After the transfer, the patient had respiratory failure and mechanical ventilation could not maintain oxygenation. The patient was treated with veno-venous extracorporeal membrane oxygenation (V-V ECMO) to maintain oxygenation, and then received symptomatic treatment such as thrombectomy and thrombolysis. After active treatment, the patient had a good prognosis. The purpose of this case report is to improve the awareness and alertness of pulmonary embolism during pregnancy, and to remind clinicians that the risk factors should be dynamically and individually assessed, to achieve early detection and timely prevention, so as to save the lives of mothers and infants and reduce the fatality.

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Research Progress of Proteins Related to Sperm Acrosome Development

CHANG Tian-qing, WU Hua, FENG Rui-zhi, QIAN Yun

2023, 42 (1): 44-49. doi: 10.12280/gjszjk.20220506

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Fertilization is the first step of a new life, in which a diploid zygote is formed by the fusion between the sperm haploid genetic material and the ovular haploid genetic material. The process of mammalian fertilization involves a series of complex and delicate activities, such as sperm hyperactivation and capacitation, acrosome reaction and sperm-egg binding. Sperm acrosome is a special membrane organelle with a cap-like structure that covers the anterior part of the sperm nucleus, which plays a key role in the process of fertilization. Acrosome formation mainly includes vesicle formation, vesicle transport, vesicle fusion, and the binding of acrosome to the nucleus, etc. The unique protein transport mechanism requires the coordination of endoplasmic reticulum, Golgi apparatus and other organelles as well as some special structures. Acrosome formation is a key step in the transformation of a spermatid into a spermatozoon, which is finely regulated by multiple genes. Defects in acrosome formation are associated with a variety of male infertility, including globozoospermia. This review summarizes the sequence of major biological events during sperm acrosome development and the related proteins, and introduces the recent research on the role of autophagy-related proteins in acrosome development, in order to provide new ideas for the diagnosis and treatment of male infertility.

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Research Progress of Bisphenol A on Female Reproductive Function Injury and Drug Intervention

CHANG Xiao-ying, SHEN Hao-fei, YU Xiao, ZHANG Xue-hong

2023, 42 (1): 50-53. doi: 10.12280/gjszjk.20220510

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Bisphenol A (BPA) as an organic compound widely existing in the environment can interfere with the normal metabolism of the body and participate in the occurrence and development of a variety of diseases. High dose BPA exposure has an acute toxic effect on the reproductive system. Long-term exposure to BPA has more significant damage to the reproductive system, and can even produce intergenerational effects, affecting the growth and development of offspring. BPA damages female reproductive function and reduces female fertility through a variety of mechanisms. Therefore, it is particularly important to develop related drugs to alleviate this adverse reaction. This paper reviews the effects of BPA on female reproductive system, and introduces the research progress of antioxidants, probiotics, vitamins and traditional Chinese medicine on alleviating the effects of BPA on reproductive system. However, the clinical application of related drugs still needs the support of evidence-based medical evidence.

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The Detrimental Effects of Chronic Periodontitis on Human Reproductive Health

ZHOU Chuang, ZHANG Chen-ji, CHEN Xuan-ning, FENG Yi-sheng, DING Zhi-de

2023, 42 (1): 54-59. doi: 10.12280/gjszjk.20220477

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Chronic periodontitis is a kind of periodontal disease caused by microbial plaque that involves periodontal tissues. Recently, several studies have shown an association between periodontitis and various systemic diseases in humans, including reproductive diseases. For example, periodontitis may induce female reproductive diseases such as infertility, polycystic ovary syndrome, endometriosis, etc. For males, periodontitis is closely correlated to erectile dysfunction, infertility and prostate diseases. Therefore, periodontitis may have detrimental effects on the human fertility. The periodontitis-related endometriosis and followed malignant lesions, as well as prostate cancer, may also bring a entail underestimated survival pressure on the patients and a heavy economic burden on the society. In this paper, we discuss the detrimental effects of periodontitis on human reproduction, and the potential improving effects of the prevention and treatment of chronic periodontitis on the reproductive health of childbearing-age population.

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The Pathogenesis of Chronic Endometritis: A Review

XIONG Yu-jing, LUO Wan-bin, AI Xi-xiong, XU Yan-wen

2023, 42 (1): 60-65. doi: 10.12280/gjszjk.20220294

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Chronic endometritis (CE), a persistent endometrial inflammation caused by pathogen infection, is related to adverse pregnancy outcomes. However, there are still disagreement in the diagnosis and treatment of CE. Exploring the inflammatory mechanism of CE is helpful to improve the diagnosis and treatment of CE. The occurrence and development of CE is closely related to the activation of inflammatory pathways, such as TLR and NLR pathways. The metabolic changes of endometrial immune cells, dysregulation of microRNAs and alteration of DNA methylation patterns can abnormally regulate the generation of inflammatory mediators that are related to the pathogenesis and development of CE. The inflammatory mechanism of CE was reviewed in this article, providing a valuable information for understanding in-depth the pathogenesis and pathophysiological changes of CE, and for seeking more standardized and effective diagnostic and treatment measures of CE.

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Research Progress on the Relationship between Endometriosis and Intestinal Flora Imbalance

ZHANG Hai-xia, FENG Xiao-ling

2023, 42 (1): 66-71. doi: 10.12280/gjszjk.20220468

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Endometriosis (EMs) is a common hormone-dependent disease in gynecology, which is most common in women of reproductive age. Although EMs is a benign disease, it has the properties of adhesion, invasion, metastasis and other malignant tumors, and it is prone to repeated attacks. EMs seriously affects the daily life and physical and mental health of female patients. The specific pathogenesis of EMs is still unclear. Many studies have demonstrated that the imbalance of intestinal flora plays an important role in the pathogenesis of EMs. The impact of intestinal flora imbalance on the pathogenesis of EMs may be related to the mechanisms involved in immune regulation, lipopolysaccharide generation, inflammatory factors and angiopoietin release, and sex hormone metabolism. In this review, the intestinal flora imbalance and mechanism related to the pathogenesis of EMs were summarized.

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Effects of Branched-Chain Amino Acids on Metabolism and Reproduction in Polycystic Ovary Syndrome

FENG Xiao-ling, CHEN Yao, WANG Ying

2023, 42 (1): 72-76. doi: 10.12280/gjszjk.20220391

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Polycystic ovary syndrome(PCOS) is a common reproductive endocrine disease in women of childbearing age. Patients are often accompanied by clinical manifestations such as insulin resistance, obesity, infertility and poor pregnancy outcome, which seriously affect women′s physical and mental health. Recent studies have shown that some patients with PCOS have the metabolic abnormality of branched-chain amino acids (BCAA), and that BCAA may be used as a marker to predict the risk of PCOS related complications. As an essential amino acid of human body, BCAA plays an important role in maintaining the homeostasis of the body by participating in the regulation of insulin secretion, and fat generation and differentiation. The change of BCAA level will affect the reproductive function of women. In addition, the excessive level of serum BCAA in PCOS patients is related to the disorders of glucose and lipid metabolism, the insulin resistance and obesity, and the adverse effect on ovulation and pregnancy in those patients of childbearing age. In this paper, the roles of BCAA in the metabolism of glucose and lipid and reproduction, as well as research progress, were reviewed, so as to provide new ideas for the diagnosis and treatment of metabolic and reproductive diseases in PCOS patients.

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Clinical Characteristics and Treatment of Microsatellite Instability Type of Endometrial Cancer

CHEN Xi, YANG Yong-xiu

2023, 42 (1): 77-82. doi: 10.12280/gjszjk.20220442

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In recent years, the incidence of endometrial cancer (EC) has been on the rise, and the traditional pathological tissue typing cannot accurately guide the individual treatment and evaluate the prognosis of patients. The molecular typing of EC based on molecular biology technology came into being. This molecular typing has an important guiding role in postoperative chemoradiotherapy, immunotherapy and targeted therapy for EC patients. The microsatellite instability (MSI) type of EC is one of the molecular types of The Cancer Genome Atlas (TCGA). MSI type of EC has unique clinical and pathological features. In addition, it is different from other types of EC in terms of treatment and prognosis. Molecular classification has been integrated into the Guideline from European Society of Gynaecological Oncology. Recent studies have shown that the patients with MSI type of EC do not get more benefit from chemotherapy, but they can get benefits from immunotherapy. The immune therapy combined with anti-angiogenesis drugs therapy has been recommended for those patients. However, there are still some controversy on the pathological characteristics, prognosis and therapy of MSI type of EC. Several therapy protocols of the combined drugs are still under study. It is true that the individualized treatment according to the molecular classification of EC will be the research focus.

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Research Progress of Transform Growth Factor-β1 in Intrauterine Adhesions

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

2023, 42 (1): 83-88. doi: 10.12280/gjszjk.20220466

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Intrauterine adhesion (IUA) is a disease of the endometrial fibrosis caused by the damaged endometrial basal layer. The common clinical manifestations of IUA are menstrual change，infertility and pregnancy failure and repeated embryo implantation failure. Therefore, IUA seriously affects the reproductive health of women of reproductive age. The evolution of IUA is more complex and variable, which is controlled by a multifactorial and multilevel combination. Transform growth factor-β1 (TGF-β1) as a cytokine plays an important role in regulating cell growth, differentiation and apoptosis. TGF-β1 is involved in the pathological progression of many human diseases. It is believed that TGF-β1 is closely related to the tissue fibrosis, and that its overexpression promotes the endometrial fibrosis and aggravates the degree of IUA. In this article, we describe the research progress of TGF-β1 and its related pathways in IUA.

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