比较卵裂球期鲜胚移植与全胚冷冻—冻胚移植的活产率的一项随机对照临床研究
发布时间：2018-09-18 19:32
【摘要】：目的:1.比较不孕症患者行体外受精/胞浆内单精子注射-胚胎移植(in vitro fertilization/intracytoplasmic sperm injection-embryo transfer,IVF/ICSI-ET)助孕过程中,卵裂球期行新鲜胚胎移植周期与全胚冷冻-冻胚移植周期的妊娠率、活产率、低出生体重儿比率、小于胎龄儿比率、新生儿并发症发生率、孕期并发症发生率及分娩并发症发生率。2.比较促性腺激素释放激素拮抗剂(gonadotropin releasing hormone antagonist,Gn RH-ant)方案与短效促性腺激素释放激素激动剂(gonadotropin releasing hormone agonist,Gn RH-a)长方案对胚胎质量及IVF/ICSI-ET助孕结局的影响。方法:第一部分为前瞻性随机对照临床试验,入组时间自2014年10月至2015年8月,首先按照纳入标准(1.不孕时间≥1年;2.年龄≥20岁且35岁;3.月经规律,具体定义为月经周期≥21天并≤35天;4.行第1周期IVF/ICSI-ET助孕治疗;5.因输卵管因素或男方因素行IVF/ICSI-ET助孕治疗;6.同意签署知情同意书)及排除标准(1.既往曾进行过一侧卵巢切除;2.符合多囊卵巢综合征(polycystic ovary syndrome,PCOS)的中国诊断标准;3.患有子宫异常疾病,包括子宫畸形[单角子宫、纵隔子宫、双子宫、双角子宫]、子宫腺肌症、黏膜下子宫肌瘤、宫腔粘连及瘢痕子宫;4.患者夫妇任一方的染色体核型有异常[不包括染色体多态性];5.反复自然流产[包括生化妊娠流产]2次及以上的病史;6.有辅助生殖技术[assisted reproductive technology,ART]及妊娠的禁忌症或患有对妊娠有明确影响的疾病:如高血压、有临床症状的心脏病、糖尿病、肝脏疾病、肾脏疾病、重度贫血、静脉血栓史、肺栓塞或脑血管事件史、恶性肿瘤病史;7.获卵数5枚)进行患者收集。随后,所有参试者采用统一Gn RH-ant方案进行控制性卵巢刺激(controlled ovarian stimulaton,COS)治疗。于取卵日对参试者进行随机分组,A组为新鲜胚胎移植组,B组为冷冻胚胎移植组。本试验共入组244人,其中A组124人,B组120人。胚胎移植后对患者妊娠情况进行跟踪随访,记录患者生化妊娠及临床妊娠情况,之后分别于孕12周、孕28周、孕37周、分娩时及产后6周进行电话随访,记录孕期、分娩、产后及新生儿情况。若首次移植未获活产,则继续随访后续冻胚移植情况。汇集整理试验数据,对两组间一般资料(年龄、不孕年限、体质指数[body mass index,BMI]、腰臀比、基础激素水平)、COS情况(促性腺激素[gonadotropin,Gn]时间、Gn总量、人绒毛膜促性腺激素[human chorionic gonadotropin,HCG]注射日子宫内膜厚度、卵泡数、成熟卵泡数及激素水平)、实验室指标(获卵数、获卵率、2PN受精数、2PN受精率、2PN卵裂数、2PN卵裂率、D3可移植胚胎数、可用胚胎数、可用胚胎率)、临床指标(生化妊娠率、临床妊娠率、持续妊娠率、胚胎种植率、异位妊娠率、流产率、活产率、早产率、足月分娩率、单胎分娩率、剖宫产率、活产儿数、男婴比率、低出生体重[low birth weight,LBW]比率、小于胎龄儿[small for gestational age,SGA]比率、新生儿并发症发生率、分娩并发症发生率及孕期并发症发生率)进行分析比较。第二部分同样按照第一部分收集参试者标准筛选出部分在2015年1月1日至2016年12月31日期间,于天津市中心妇产科医院生殖医学中心接受IVF/ICSI-ET短效Gn RH-a长方案助孕治疗,病例资料完整且首次移植2枚胚胎的患者,共计1929人。将进行新鲜周期胚胎移植者分为C组,共954人,将进行解冻周期胚胎移植者分为D组,共975人。通过查阅病例及随访记录等相关资料,回顾性分析在接受短效Gn RH-a长方案助孕治疗患者中,新鲜胚胎移植周期与全胚冷冻-冻胚移植周期的胚胎质量、妊娠率、活产率、LBW比率、SGA比率。并对比不同COS方案可能对胚胎质量及妊娠结局产生的影响。结果:1.采用统一Gn RH-ant方案进行COS治疗的244名参试者,冻胚移植组的生化妊娠率、临床妊娠率、持续妊娠率及胚胎种植率均高于鲜胚移植组(P0.05),活产率高于鲜胚移植组但差异无统计学意义(P0.05),异位妊娠率、流产率、早产率、新生儿并发症发生率、孕期并发症发生率及分娩并发症发生率与鲜胚移植组差异无统计学意义(P0.05)。更重要的是,冻胚移植组LBW比率和SGA比率均低于鲜胚移植组(P0.05)。2.采用短效Gn RH-a长方案进行COS治疗的1929名患者,鲜胚移植组的可用胚胎率高于冻胚移植组(P0.05)。而冻胚移植组生化妊娠率、临床妊娠率、持续妊娠率和胚胎种植率均高于鲜胚移植组(P0.05),异位妊娠率、流产率和早产率无统计学差异(P0.05),且冻胚移植组LBW比率及SGA比率均低于鲜胚移植组(P0.05)。3.在新鲜胚胎移植周期中,采用Gn RH-ant方案可获得更高的获卵率(P0.05),而可用胚胎率无差别(P0.05)。Gn RH-ant方案组生化妊娠率、临床妊娠率、持续妊娠率、胚胎种植率及活产率高于Gn RH-a长方案组,但无明显差异(P0.05)。而Gn RH-ant方案组所用Gn时间和Gn总量均少于Gn RH-a长方案组(P0.05)。4.在冷冻胚胎移植周期中,Gn RH-a长方案组获卵率高于Gn RH-ant方案组(P0.05),但可用胚胎率低于Gn RH-ant方案组(P0.05)。Gn RH-ant方案组生化妊娠率、临床妊娠率、持续妊娠率及胚胎种植率均较Gn RH-a长方案组高(P0.05)。更重要的是,Gn RH-ant方案组Gn时间及Gn总量显著少于Gn RH-a长方案组(P0.05)。结论:1.冻胚移植较鲜胚移植可获得更好的生化妊娠率、临床妊娠率、持续妊娠率及胚胎种植率。2.冻胚移植与鲜胚移植之间活产率、异位妊娠率、流产率、早产率、孕期并发症发生率、分娩并发症发生率及新生儿并发症发生率无明显差异。3.冻胚移植与鲜胚移植相比,LBW比率和SGA比率均低。4.Gn RH-ant方案较Gn RH-a方案Gn时间及Gn用量均少。5.Gn RH-ant方案对胚胎质量没有不利影响,甚至有优于Gn RH-a方案的倾向。6.Gn RH-ant方案较Gn RH-a方案在冻胚移植中有更好的妊娠结局。
[Abstract]:Objective: 1. To compare the pregnancy rate, living rate, low birth weight infants during the cleavage global phase of fresh embryo transfer and whole embryo frozen-frozen embryo transfer cycles during in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) assisted pregnancy in infertility patients. Ratio, less than gestational age, neonatal complications, pregnancy complications and delivery complications. 2. Comparison of gonadotropin releasing hormone ant agonist (Gn RH-ant) regimen with short-acting gonadotropin releasing hormone agonist (Gn RH-ant) METHODS: The first part was a prospective randomized controlled clinical trial. The time of enrollment was from October 2014 to August 2015. Firstly, according to the inclusion criteria (1. Infertility time (> 1 year); 2. Age (> 20 years) and 35 years; 3. Menstrual cycle (> 21 days) and (< 35 days). IVF/ICSI-ET for the first cycle of pregnancy; 5.IVF/ICSI-ET for tubal or male factors; 6.Consent to sign informed consent; and exclusion criteria (1.Ovariectomy on one side has been performed in the past; 2.Compliance with the Chinese diagnostic criteria for polycystic ovary syndrome (PCOS); 3.Abnormal uterine disease, including a package Including uterine anomalies [unicornual uterus, mediastinal uterus, bicornual uterus], adenomyosis, submucosal myoma, intrauterine adhesion and scarred uterus; 4. Abnormal karyotype of either side of the couple [excluding chromosomal polymorphism]; 5. Repeated spontaneous abortion [including biochemical pregnancy and abortion] 2 times or more; 6. Assisted reproduction Techniques [assisted reproductive technology, ART] and contraindications of pregnancy or diseases with definite effects on pregnancy: hypertension, clinical symptoms of heart disease, diabetes, liver disease, kidney disease, severe anemia, history of venous thrombosis, pulmonary embolism or cerebrovascular events, history of malignancies; 7. 5 eggs retrieved) were collected. Subsequently, all participants were treated with controlled ovarian STIMULATON (COS) with a unified Gn RH-ant protocol. On the day of ovulation, participants were randomly divided into two groups: fresh embryo transfer group A and frozen embryo transfer group B. A total of 244 participants, 124 in group A and 120 in group B, were enrolled in the study. Pregnancy status was followed up, biochemical pregnancy and clinical pregnancy were recorded, followed by telephone follow-up at 12 weeks, 28 weeks, 37 weeks, delivery and 6 weeks postpartum. Pregnancy, delivery, postpartum and neonatal status were recorded. If the first transplantation did not achieve live birth, follow-up frozen embryo transplantation was continued. General information between the two groups (age, length of infertility, body mass index, BMI, waist-hip ratio, basal hormone level), COS (gonadotropin [Gn] time, total Gn, human chorionic gonadotropin [HCG] injection day endometrial thickness, follicle number, mature follicle number and hormone level), solid Laboratory indicators (number of eggs retrieved, rate of eggs retrieved, number of 2PN fertilization, 2PN fertilization rate, 2PN cleavage rate, number of D3 transplantable embryos, number of available embryos, available embryos rate), clinical indicators (biochemical pregnancy rate, clinical pregnancy rate, persistent pregnancy rate, embryo implantation rate, ectopic pregnancy rate, abortion rate, live birth rate, preterm birth rate, full-term delivery rate, single birth rate, cesarean section The uterine rate, the number of live births, the ratio of boys to babies, the ratio of low birth weight [LBW], the ratio of small for gestational age [SGA], the incidence of neonatal complications, the incidence of complications in childbirth and pregnancy complications were analyzed and compared. The second part was also selected according to the criteria of the first part. From January 1, 2015 to December 31, 2016, a total of 1929 patients received IVF/ICSI-ET short-acting Gn RH-a pregnancy-assisted treatment at the Reproductive Medical Center of Tianjin Central Obstetrics and Gynecology Hospital. The patients were divided into group C and 954 underwent thawing cycles. A total of 975 embryo transplant recipients were divided into group D. The embryo quality, pregnancy rate, live birth rate, LBW ratio and SGA ratio of fresh embryo transfer cycles and whole embryo cryopreservation-frozen embryo transfer cycles were analyzed retrospectively in patients receiving short-term Gn RH-a long-term regimen assisted pregnancy therapy by referring to case history and follow-up records. Results: 1. The biochemical pregnancy rate, clinical pregnancy rate, persistent pregnancy rate and embryo implantation rate in the frozen embryo transplantation group were higher than those in the fresh embryo transplantation group (P 0.05), but the live birth rate was higher than that in the fresh embryo transplantation group (P 0.05). The pregnancy rate, abortion rate, premature delivery rate, neonatal complications, pregnancy complications and delivery complications were not significantly different from those in the fresh embryo transplantation group (P 0.05). More importantly, the LBW ratio and SGA ratio in the frozen embryo transplantation group were lower than those in the fresh embryo transplantation group (P 0.05). 2. The COS treatment with short-term Gn RH-a regimen was performed in 1929. The biochemical pregnancy rate, clinical pregnancy rate, persistent pregnancy rate and embryo implantation rate of the frozen embryo transplantation group were higher than those of the fresh embryo transplantation group (P 0.05). There was no significant difference in ectopic pregnancy rate, abortion rate and premature delivery rate (P 0.05). The LBW and SGA rates of the frozen embryo transplantation group were lower than those of the frozen embryo transplantation group. Fresh embryo transfer group (P 0.05). 3. In the fresh embryo transfer cycle, the Gn RH-ant regimen can obtain a higher rate of eggs (P 0.05), but the available embryo rate has no difference (P 0.05). The biochemical pregnancy rate, clinical pregnancy rate, persistent pregnancy rate, embryo implantation rate and live birth rate of Gn RH-ant regimen group were higher than those of Gn RH-a long regimen group, but there was no significant difference (P 0.05). The Gn time and total Gn in the H-ant group were less than those in the Gn RH-a long-term group (P 0.05). 4. In the frozen embryo transfer cycle, the oocyte retrieval rate in the Gn RH-a long-term group was higher than that in the Gn RH-ant group (P 0.05), but the available embryo rate was lower than that in the Gn RH-ant group (P 0.05). The biochemical pregnancy rate, clinical pregnancy rate, persistent pregnancy rate and embryo implantation rate in the Gn RH-ant group were lower than those in the Gn RH-ant group. More importantly, Gn time and total Gn in Gn RH-ant group were significantly less than those in Gn RH-a long-term group (P 0.05). Conclusion: 1. Frozen embryo transplantation can obtain better biochemical pregnancy rate, clinical pregnancy rate, persistent pregnancy rate and embryo implantation rate. 2. The survival rate between frozen embryo transplantation and fresh embryo transplantation is different. There were no significant differences in pregnancy rate, abortion rate, premature delivery rate, complications during pregnancy, delivery rate and neonatal complications. 3. Compared with fresh embryo transfer, frozen embryo transfer had lower LBW ratio and SGA ratio. 4. Gn RH-ant regimen had less Gn time and Gn dosage than Gn RH-ant regimen. 5. Gn RH-ant regimen had no adverse effects on embryo quality. Gn RH-ant regimen has a better pregnancy outcome than Gn RH-a regimen.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R714.8
本文编号：2248906
[Abstract]:Objective: 1. To compare the pregnancy rate, living rate, low birth weight infants during the cleavage global phase of fresh embryo transfer and whole embryo frozen-frozen embryo transfer cycles during in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) assisted pregnancy in infertility patients. Ratio, less than gestational age, neonatal complications, pregnancy complications and delivery complications. 2. Comparison of gonadotropin releasing hormone ant agonist (Gn RH-ant) regimen with short-acting gonadotropin releasing hormone agonist (Gn RH-ant) METHODS: The first part was a prospective randomized controlled clinical trial. The time of enrollment was from October 2014 to August 2015. Firstly, according to the inclusion criteria (1. Infertility time (> 1 year); 2. Age (> 20 years) and 35 years; 3. Menstrual cycle (> 21 days) and (< 35 days). IVF/ICSI-ET for the first cycle of pregnancy; 5.IVF/ICSI-ET for tubal or male factors; 6.Consent to sign informed consent; and exclusion criteria (1.Ovariectomy on one side has been performed in the past; 2.Compliance with the Chinese diagnostic criteria for polycystic ovary syndrome (PCOS); 3.Abnormal uterine disease, including a package Including uterine anomalies [unicornual uterus, mediastinal uterus, bicornual uterus], adenomyosis, submucosal myoma, intrauterine adhesion and scarred uterus; 4. Abnormal karyotype of either side of the couple [excluding chromosomal polymorphism]; 5. Repeated spontaneous abortion [including biochemical pregnancy and abortion] 2 times or more; 6. Assisted reproduction Techniques [assisted reproductive technology, ART] and contraindications of pregnancy or diseases with definite effects on pregnancy: hypertension, clinical symptoms of heart disease, diabetes, liver disease, kidney disease, severe anemia, history of venous thrombosis, pulmonary embolism or cerebrovascular events, history of malignancies; 7. 5 eggs retrieved) were collected. Subsequently, all participants were treated with controlled ovarian STIMULATON (COS) with a unified Gn RH-ant protocol. On the day of ovulation, participants were randomly divided into two groups: fresh embryo transfer group A and frozen embryo transfer group B. A total of 244 participants, 124 in group A and 120 in group B, were enrolled in the study. Pregnancy status was followed up, biochemical pregnancy and clinical pregnancy were recorded, followed by telephone follow-up at 12 weeks, 28 weeks, 37 weeks, delivery and 6 weeks postpartum. Pregnancy, delivery, postpartum and neonatal status were recorded. If the first transplantation did not achieve live birth, follow-up frozen embryo transplantation was continued. General information between the two groups (age, length of infertility, body mass index, BMI, waist-hip ratio, basal hormone level), COS (gonadotropin [Gn] time, total Gn, human chorionic gonadotropin [HCG] injection day endometrial thickness, follicle number, mature follicle number and hormone level), solid Laboratory indicators (number of eggs retrieved, rate of eggs retrieved, number of 2PN fertilization, 2PN fertilization rate, 2PN cleavage rate, number of D3 transplantable embryos, number of available embryos, available embryos rate), clinical indicators (biochemical pregnancy rate, clinical pregnancy rate, persistent pregnancy rate, embryo implantation rate, ectopic pregnancy rate, abortion rate, live birth rate, preterm birth rate, full-term delivery rate, single birth rate, cesarean section The uterine rate, the number of live births, the ratio of boys to babies, the ratio of low birth weight [LBW], the ratio of small for gestational age [SGA], the incidence of neonatal complications, the incidence of complications in childbirth and pregnancy complications were analyzed and compared. The second part was also selected according to the criteria of the first part. From January 1, 2015 to December 31, 2016, a total of 1929 patients received IVF/ICSI-ET short-acting Gn RH-a pregnancy-assisted treatment at the Reproductive Medical Center of Tianjin Central Obstetrics and Gynecology Hospital. The patients were divided into group C and 954 underwent thawing cycles. A total of 975 embryo transplant recipients were divided into group D. The embryo quality, pregnancy rate, live birth rate, LBW ratio and SGA ratio of fresh embryo transfer cycles and whole embryo cryopreservation-frozen embryo transfer cycles were analyzed retrospectively in patients receiving short-term Gn RH-a long-term regimen assisted pregnancy therapy by referring to case history and follow-up records. Results: 1. The biochemical pregnancy rate, clinical pregnancy rate, persistent pregnancy rate and embryo implantation rate in the frozen embryo transplantation group were higher than those in the fresh embryo transplantation group (P 0.05), but the live birth rate was higher than that in the fresh embryo transplantation group (P 0.05). The pregnancy rate, abortion rate, premature delivery rate, neonatal complications, pregnancy complications and delivery complications were not significantly different from those in the fresh embryo transplantation group (P 0.05). More importantly, the LBW ratio and SGA ratio in the frozen embryo transplantation group were lower than those in the fresh embryo transplantation group (P 0.05). 2. The COS treatment with short-term Gn RH-a regimen was performed in 1929. The biochemical pregnancy rate, clinical pregnancy rate, persistent pregnancy rate and embryo implantation rate of the frozen embryo transplantation group were higher than those of the fresh embryo transplantation group (P 0.05). There was no significant difference in ectopic pregnancy rate, abortion rate and premature delivery rate (P 0.05). The LBW and SGA rates of the frozen embryo transplantation group were lower than those of the frozen embryo transplantation group. Fresh embryo transfer group (P 0.05). 3. In the fresh embryo transfer cycle, the Gn RH-ant regimen can obtain a higher rate of eggs (P 0.05), but the available embryo rate has no difference (P 0.05). The biochemical pregnancy rate, clinical pregnancy rate, persistent pregnancy rate, embryo implantation rate and live birth rate of Gn RH-ant regimen group were higher than those of Gn RH-a long regimen group, but there was no significant difference (P 0.05). The Gn time and total Gn in the H-ant group were less than those in the Gn RH-a long-term group (P 0.05). 4. In the frozen embryo transfer cycle, the oocyte retrieval rate in the Gn RH-a long-term group was higher than that in the Gn RH-ant group (P 0.05), but the available embryo rate was lower than that in the Gn RH-ant group (P 0.05). The biochemical pregnancy rate, clinical pregnancy rate, persistent pregnancy rate and embryo implantation rate in the Gn RH-ant group were lower than those in the Gn RH-ant group. More importantly, Gn time and total Gn in Gn RH-ant group were significantly less than those in Gn RH-a long-term group (P 0.05). Conclusion: 1. Frozen embryo transplantation can obtain better biochemical pregnancy rate, clinical pregnancy rate, persistent pregnancy rate and embryo implantation rate. 2. The survival rate between frozen embryo transplantation and fresh embryo transplantation is different. There were no significant differences in pregnancy rate, abortion rate, premature delivery rate, complications during pregnancy, delivery rate and neonatal complications. 3. Compared with fresh embryo transfer, frozen embryo transfer had lower LBW ratio and SGA ratio. 4. Gn RH-ant regimen had less Gn time and Gn dosage than Gn RH-ant regimen. 5. Gn RH-ant regimen had no adverse effects on embryo quality. Gn RH-ant regimen has a better pregnancy outcome than Gn RH-a regimen.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R714.8
【参考文献】
相关期刊论文 前10条
1 罗丹;丁晓芳;李璐璐;舒德峰;朱燕;钟少红;高颖;;卵巢过度刺激综合征高风险患者行全胚冷冻的临床应用价值研究[J];临床急诊杂志;2016年09期
2 张静雯;马文敏;黄建洲;池霖生;;卵母细胞玻璃化冷冻技术在体外受精-胚胎移植中的应用[J];中国优生与遗传杂志;2016年03期
3 郑群;程兆俊;邹立波;陈浩浩;;玻璃化冷冻法和程序化冷冻法对人卵裂期胚胎冷冻复苏效果及临床结局的比较[J];中国优生与遗传杂志;2016年01期
4 张秀萍;张烁;杨晓丽;;卵巢储备功能预测指标的临床价值[J];中国优生优育;2014年03期
5 赵亚琼;金锐;王莹;杨芳;;全胚冷冻在预防OHSS中的价值探讨[J];宁夏医学杂志;2013年09期
6 黄永刚;黄朝霞;侯晓红;肖宇;吕杰强;;全胚冷冻后行冻融胚胎移植预防卵巢过度刺激综合征的临床观察[J];中国妇幼保健;2012年33期
7 柳倩茹;马文敏;邓伟芬;罗国群;;全胚冷冻预防卵巢过度刺激综合征42例分析[J];中国妇幼保健;2012年25期
8 叶尔登切切克;腊晓琳;;卵巢过度刺激综合征发病机制的研究进展[J];医学综述;2012年10期
9 陈明晖;李洁;苗本郁;何科;周灿权;;早发型与晚发型卵巢过度刺激综合征的特点[J];中山大学学报(医学科学版);2012年01期
10 龚斐;宗豫容;张顺吉;朱文兵;蔡素芬;陆长富;卢光t;林戈;;全胚冷冻后行FET避免IVF/ICSI—ET助孕治疗中、重度OHSS发生风险[J];中国现代医学杂志;2011年34期
相关硕士学位论文 前1条
1 饶腾子;影响IVF结局的临床因素分析及IVF成功抱婴预测模型初步探讨[D];南方医科大学;2012年
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