Objective:To explore whether the duration of oral estrogen treatment before progesterone application affects neonatal outcome in single frozen-thawed embryo transfer (FET) with artificial cycles.Methods:It was a retrospective cohort study. Patients who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), receiving single frozen blastocyst transfer with artificial cycle and delivering a single live birth in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University between January 2015 and December 2019 were included. All FET cycles were divided into four groups according to the estrogen treatment duration before progesterone application, ≤12 d ( n=306), 13-15 d ( n=620), 16-18 d ( n=471), and ≥19 d ( n=275). Primary outcome was the incidence of small for gestational age (SGA). Secondary outcomes were the incidence of preterm birth, low birth weight, macrosomia and large for gestational age (LGA). Results:A total of 1 672 single blastocyst transfer cycles were included. The incidence of SGA among the four groups was 7.8% (24/306), 4.8% (30/620), 5.7% (27/471), and 7.6% (21/275), respectively, with no statistically significant difference ( P=0.204). The results of multiple logistic regression analysis showed that the duration of estrogen used before progesterone application did not affect the incidence of SGA in singleton offspring (with ≤12 d as the reference, 13-15 d: a OR=1.37, 95% CI: 0.70-2.70, P=0.361; 16-18 d: a OR=0.74, 95% CI: 0.40-1.36, P=0.336; ≥19 d: a OR=0.81, 95% CI: 0.44-1.49, P=0.501). There were no significant differences in neonatal preterm birth rate ( P=0.204), low birth weight ( P=0.582), incidences of macrosomia ( P=0.201) and LGA infants ( P=0.335) among the four groups. Conclusion:In artificial FET cycle, the duration of oral estrogen treatment before progesterone application does not affect the outcome of singleton offspring after single blastocyst transfer.

目的 比较高孕酮状态下促排卵(progestin-primed ovarian stimulation,PPOS)方案中地屈孕酮和醋酸甲羟孕酮(medroxyprogesterone acetate,MPA)在卵巢低反应(poor ovarian response,POR)人群中的临床应用结局.方法 本研究属于单中心回顾性队列研究.纳入2019年1月至2021年9月期间在郑州大学第三附属医院生殖医学科行PPOS方案助孕的POR患者.根据使用的孕激素药物不同,分为地屈孕酮组和MPA组.以1∶3进行倾向性评分匹配(propensity score matching,PSM)校正混杂因素.观察指标为可利用胚胎数、获卵数、双原核(two pronuclei,2PN)数、优质胚胎数、全胚冷冻第一周期移植临床妊娠率和持续妊娠率.结果 共纳入1 962个周期,其中地屈孕酮组共494个周期,MPA组共1 468个周期.两组间不孕因素差异有统计学意义(P=0.045),余基础资料差异均无统计学意义(均P>0.05).地屈孕酮组的促性腺激素(gonadotropin,Gn)启动量[300(225,300)U]低于MPA组[300(300,300)U,P<0.001].Gn使用时间、Gn使用总量、早发黄体生成素峰、获卵数、2PN数、可利用胚胎数和优质胚胎数在组间差异均无统计学意义(均P>0.05).共有1 331个周期进行了第1次冻融胚胎移植,其中地屈孕酮组268个周期,MPA组1 063个周期.移植日子宫内膜厚度、移植胚胎数、移植胚胎阶段、子宫内膜准备方案组间差异均无统计学意义(均P>0.05).两组间的临床妊娠率和持续妊娠率差异均无统计学意义(均P>0.05).结论 对于POR患者,PPOS方案中地屈孕酮和MPA可获得相似的临床结局,表明地屈孕酮可作为PPOS方案有效的选择之一.

Objective:To investigate whether there is an association between season, temperature, as well as cumulative sunlight exposure on the day of oocyte retrieval and clinical outcomes of in vitro fertilization (IVF) and fresh embryo transfer. Methods:It was a retrospective cohort study, including patients who underwent IVF in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from August 2015 to October 2019. They were divided into four groups according to the oocyte retrieval date. Spring group: the oocyte retrieval date was from March to May. Summer group: the date of oocyte retrieval was from June to August. Autumn group: the date of oocyte retrieval was from September to November. Winter group: the date of oocyte retrieval was from December to February of the next year. The main outcome measures were clinical pregnancy rate and live birth rate. Binary logistic regression was used to explore the factors affecting clinical pregnancy rate and live birth rate.Results:There were no significant differences in the miscarriage rate and the live birth rate among the four groups (all P>0.05). The pairwise comparison between the groups indicated that the clinical pregnancy rate in the winter group [56.9% (816/1 435)] was lower than that in the summer group [61.5% (1 359/2 210), P=0.005]. Taking winter as the reference, the clinical pregnancy rate in summer was higher (a OR=1.25, 95% CI: 1.09-1.44, P=0.002). The clinical pregnancy rate in spring (a OR=1.14, 95% CI: 0.99-1.32, P=0.073) and autumn (a OR=1.09, 95% CI: 0.94-1.26, P=0.254) was not significantly different from winter. Binary logistic regression analysis showed that higher mean temperature was associated with higher clinical pregnancy rate (a OR=1.01, 95% CI: 1.00-1.01, P=0.005). Season, temperature and cumulative sunshine on the day of egg retrieval had no significant effect on the live birth rate. Conclusion:Summer and high temperature are independent and favorable influencing factors of clinical pregnancy rate. However, different seasons, temperatures and cumulative sunshine had no significant effect on live birth rate.

Objective:To investigate the timing of the first frozen-thawed embryo transfer (FET) on clinical and perinatal outcomes in whole embryo freezing patients, who used the medroxyprogesterone acetate (MPA) in progestin primed ovarian stimulation (PPOS).Methods:A retrospective cohort study was conducted to analyze the clinical data of patients with the first FET after ovulation induction by PPOS protocol in Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University from January 2015 to November 2021. According to the time interval between the day of oocytes retrieved and the day of the first FET in the ovulation induction cycle, they were divided into two groups. Group A: transplantation was performed during the first menstrual cycle after oocyte retrieval (time interval ≥24 d and <45 d, n=80), group B: transplantation was performed at least one month apart after oocytes retrieved (time interval ≥45 d, n=1 040). After propensity score matching (PSM), the general data, clinical excretion promotion, embryo laboratory indicators, indicators related to the first FET cycle, clinical and perinatal outcomes were compared between the two groups. Results:Before PSM, the age of group A was significantly higher than that of group B [38 (35, 41) years vs. 37 (32, 40) years, P=0.020]. After PSM, there were no significant differences in general data, ovulation induction cycle data, embryo laboratory indicators, clinical pregnancy rate, live birth rate and perinatal outcomes between the two groups (all P>0.05). Conclusion:Compared with FET at least one month after oocytes retrieval, FET during the first menstrual cycle after PPOS does not affect clinical or perinatal outcomes. FET can be performed as early as possible after oocytes retrieval according to the condition of patients to shorten the time to reach their first live birth.

目的:探讨胚胎植入前遗传学检测(PGT)中滋养外胚层细胞活检对新生儿出生体质量及围产期结局的影响.方法:回顾分析2017 年1 月至2021 年12 月在郑州大学第三附属医院生殖医学中心行冻胚移植(FET)并获得单胎活产患者的临床资料.纳入行胚胎植入前行遗传学检测的患者 221 例(PGT组)和同期行卵胞质内单精子注射(IC-SI)的患者756 例(ICSI组),利用倾向性评分匹配(PSM)进行1:2 匹配后得到PGT组191例和ICSI组363 例,比较匹配前后两组患者基线数据及新生儿出生体质量等围产期及新生儿结局的差异,采用多因素线性回归分析单胎活产新生儿出生体质量的影响因素.结果:匹配前两组患者的孕产次、不孕年限及移植日内膜厚度比较,差异有统计学意义(P<0.05),匹配后两组患者基线数据差异均无统计学意义(P均>0.05).匹配前后,两组的妊娠期高血压疾病、妊娠期糖尿病、胎膜早破、前置胎盘、剖宫产率、分娩孕周、新生儿出生体质量及新生儿身长比较,差异均无统计学意义(P均>0.05).多因素线性回归分析结果显示,滋养外胚层细胞活检与新生儿出生体质量无关,女方BMI、移植日子宫内膜厚度、分娩孕周和新生儿性别显著影响新生儿出生体质量(P均<0.05).结论:PGT中滋养外胚层活检可能不会影响新生儿出生体质量,也不增加母婴不良并发症发生风险.

Objective:To explore the impact on the fertility and outcomes of females with squamous intraepithelial lesion (SIL) undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and obstetric outcomes after local treatment. Methods:Patients with SIL undergoing IVF/ICSI were set as the SIL group in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2020. While, control group was matched using the propensity scoring method in a 1∶3 ratio in accordance with the age, body mass index, and basic follicle-stimulating hormone, antral follicle count and the oocytes retrieval time. Pregnancy outcomes were compared by analyzing the basic conditions of the two groups, the index of the IVF/ICSI cycles, the clinical pregnancy rate and the implantation rate of the fresh cycles, the cumulative pregnancy rate, the cumulative live birth rate, and obstetric outcomes of patients giving live birth after local treatment were also analyzed.Results:The demographic characteristics were of no significant differences between the SIL group and control group (all P>0.05). As for the IVF/ICSI results, no significant differences were observed in the duration of gonadotropins (Gn) used, total dosage of Gn used, No. of oocytes retrieved, normal fertilization rate, No. of available embryos, No. of high-quality embryos, and No. of blastocyst formation between the two groups (all P>0.05). For fresh embryo transfer cycles, the number of transferred embryos was lower, the clinical pregnancy rate and the implantation rate in the SIL group were higher than those in control group, while the differences were not significant (all P>0.05). The differences of time to pregnancy,the cumulative pregnancy rate and the cumulative live birth rate between SIL group and control group were not statistically significant (all P>0.05). There were no statistically significant differences in delivery methods, gestational age, newborn birth weight, and incidence of pregnancy complications between the two groups (all P>0.05). According to local surgical treatment, 79 patients with SIL who achieved live birth were divided into cold knife conization subgroup, loop electrosurgical excisional procedure subgroup, and no-operation subgroup. There were no statistically significant differences in delivery methods, gestational age, newborn birth weight and incidence of pregnancy complications among the three subgroups (all P>0.05). Conclusion:SIL did not affect fertility of patients or assisted pregnancy outcomes of IVF/ICSI, and local surgical treatment does not increase the risk of preterm birth, low birth weight infants.

Objective:To evaluate the cumulative live birth rate (CLBR) of mild stimulation and conventional stimulation in Poseidon 4 group for progestin-primed ovarian stimulation protocols (PPOS).Methods:It was a single-center, retrospective cohort study. The study included the first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 2017 to March 2020, and included patients met the criteria of Poseidon 4 group and accepted PPOS. According to the different starting dosage of gonadotropin (Gn), it was divided into mild stimulation group and conventional stimulation group. In mild stimulation group, Gn starting dosage was 150 U, and in conventional stimulation group Gn starting dosage was 300 U. The primary outcome measure was CLBR. Secondary observation indicators were No. of oocytes retrieved, No. of two pronuclei (2PN), No. of available embryos, No. of high-quality embryos and cumulative pregnancy rate. Results:A total of 1 334 cycles met the inclusion and exclusion criteria. After 1∶3 propensity score matching (PSM) model, 116 cycles of mild stimulation and 348 cycles of conventional stimulation were included for analysis. The total dosage of Gn used in the conventional ovarian stimulation group was significantly higher than that in the mild stimulation group [2 700.00 (2 400.00, 3 300.00) U vs. 1 500.00 (918.75, 2 456.25) U, P<0.001]. The number of oocytes retrieved [3.00 (2.00, 4.00)], 2PN [2.00 (1.00, 3.00)], available embryos [1.00 (1.00, 2.00)] and high-quality embryos [1.00 (0.00, 1.00)] in the conventional stimulation group were significantly higher than those in the mild stimulation group [2.00 (1.00, 3.00), P<0.001; 1.00 (1.00, 2.00), P=0.002; 1.00 (0.00,2.00), P=0.002; 0.00 (0.00, 1.00), P=0.025]. There was no statistical difference in the cumulative pregnancy rate between mild stimulation and conventional stimulation [15.52% (18/116) vs. 19.54% (68/348), P=0.334]. The CLBR of the mild stimulation group was 11.21% (13/116), and the CLBR of the conventional stimulation group was 14.08% (49/348), with no significant difference between the two groups ( P=0.431). Conclusion:Conventional stimulation increased the dosage of Gn used, and the number of oocytes retrieved and available embryos were more than those in mild stimulation, but the CLBR was similar between the two protocols. Therefore, mild stimulation is also an important clinical option for patients with low ovarian prognosis.

Objective:To compare the cumulative live birth rate (CLBR) of gonadotropin-releasing hormone (GnRH) antagonist protocol, medroxyprogesterone (MPA) protocol and clomiphene citrate (CC) protocol in low prognosis population with decreased ovarian reserve.Methods:It was a retrospective cohort study. Patients who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 2015 to May 2018 were recruited. Including POSEIDON group 3 and group 4, GnRH-antagonist protocol, MPA, and CC protocol were used for ovulation stimulation. The basic data and clinical outcomes of the three protocols were analyzed. The main outcome measure was CLBR. With the GnRH-antagonist group as the reference, the adjusted odds ratio ( aOR) and 95% confidence interval ( CI) of the MPA group and the CC group were calculated. Results:In the POSEIDON group 3, the CLBR of the three protocols was not statistically different. After logistic regression analysis, the ovulation stimulation protocols did not affect the CLBR of POSEIDON 3 group ( P=0.226, P=0.468). In the POSEIDON group 4, the CLBR of the MPA group was higher than that of the CC group (10.7% vs. 5.4%, P=0.002). Using binary logistic regression and GnRH-antagonist group as the control, the CLBR of the MPA protocol was higher (a OR=2.22, 95% CI=1.17-4.24, P=0.021), the CLBR of the CC protocol was not significantly different from the GnRH-antagonist group (a OR=0.95, 95% CI=0.48-1.85, P=0.868). Conclusion:For patients under 35 years old with low ovarian reserve, the clinical outcomes of the three ovulation stimulation protocols were similar. For patients who are 35 years or older with low ovarian reserve, the CLBR of the MPA protocol was higher.

目的:比较不同体重指数(BMI)预期卵巢正常反应患者在早卵泡期长效长方案(长长方案)体外受精/卵胞浆内单精子注射-胚胎移植(IVF/ICSI-ET)中应用尿促卵泡激素(uFSH)和基因重组人促卵泡激素(rFSH)临床结局的差异.方法:回顾性收集2015年9月至2019年12月在郑州大学第三附属医院生殖医学中心行长长方案IVF/ICSI-ET助孕且预期卵巢正常反应的患者,按照BMI分为偏瘦或正常组(BMI<24 kg/m2,1056例)、超重组(24 kg/m2≤BMI<28 kg/m2,554例)和肥胖组(BMI≥28 kg/m2,112例).在3组不同BMI的患者中,分别对使用uFSH或rFSH进行超促排卵IVF/ICSI-ET助孕的两组患者以年龄、窦卵泡数、不孕年限、基础FSH和抗米勒管激素(AMH)进行1:1倾向性评分匹配,对匹配后患者的数据进行分析.比较两组患者Gn启动量、Gn时间、Gn总量、Gn费用,HCG日内膜厚度、LH、E2、P、≥14 mm卵泡数、获卵数、可利用胚胎数以及两组患者优质胚胎率、中重度卵巢过度刺激(OHSS)综合征发生率、胚胎着床率、临床妊娠率、流产率、活产率、累积妊娠率和累积分娩率的差异.结果:3组不同BMI的患者rFSH组和uFSH组比较,获卵数、中重度OHSS发生率、临床妊娠率、活产率差异均无统计学意义(P>0.05),uFSH组的Gn启动量均高于rFSH组(P均<0.05),而Gn费用低于rFSH组(P<0.05);偏瘦或正常组和超重uFSH组的Gn总量均高于rFSH组(P<0.05);肥胖组中uFSH组的优质胚胎率(44.03％)高于rFSH组(32.10％),差异有统计学意义(P<0.001).结论:uFSH的临床有效性不低于rFSH,控制性卵巢刺激有效性低于rFSH;uFSH成本低,更具有经济学优势;肥胖患者可能更适合选用uFSH进行超促排卵.

目的 评价生长激素(GH)对体外受精/卵胞浆内单精子显微注射(IVF/ICSI)治疗中胚胎质量欠佳患者再次助孕时的胚胎质量及助孕结局的影响.方法 通过回顾性自身前后对照,选取2016年1月—2019年3月在本中心行IVF/ICSI助孕失败后再次助孕时添加GH并采用相同促排卵方案的112例患者为研究对象,根据GH使用天数分为<35 d组和≥35 d组,根据是否添加GH分为自身对照组和GH实验组,自身对照组采用本中心常规促排方案,移植后未获得持续性妊娠;GH实验组促排方案不变,于不同时间添加GH(2 IU/d或4 IU/d)直至取卵日,取卵后行常规IVF或ICSI,比较GH不同用药时间前后两次促排周期的临床及实验室指标.结果 无论GH使用天数<35 d或≥35 d,GH实验组在促性腺激素(Gn)总用量、获卵数及双原核(2PN)受精率与自身对照组相比,差异均无统计学意义;而GH实验组的人绒毛膜促性腺激素(hCG)日子宫内膜厚度、可利用胚胎率及优质胚胎率均显著高于自身对照组(P<0.05);同时在GH使用天数<35 d组中,GH实验组流产率(26.7％)与自身对照组(100％)差异无统计学意义;在GH使用天数≥35 d组中,GH实验组的流产率(7.7％)显著低于自身对照组(100％,P=0.001).结论 在IVF/ICSI助孕中,对于因胚胎质量欠佳助孕失败的患者,再次助孕时添加小剂量的GH(2 IU/d或4 IU/d),可以改善胚胎质量,提高临床妊娠率.

Objective:To explore the effect of thin endometrial thickness (EMT) on the low birth weight (LBW) of singleton in fresh embryo transfer cycle.Methods:It was a retrospective cohort study. The data of singleton deliveries achieved after fresh cleavage embryo transfer in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 2015 to February 2019 were included. A total of 2247 cycles were included and were divided into three groups depending on the EMT: group A≤7.5 mm, group B 7.6-12.0 mm and group C>12.0 mm. The major outcome measure was LBW. Binary logistic regression was performed to correct for confounding factors.Results:Singleton birthweight was lower in group A [3000(2525, 3350) g] compared with group B and group C [3350(3050, 3650) g, 3400(3100, 3690) g, all P<0.001]. The incidence of LBW in group A [24.7% (20/81)] was significantly higher than that in groups B and C [4.0% (57/1414), 5.3% (40/752), all P<0.001], while there was no statistical difference between groups B and C ( P>0.05). Body mass index ( P=0.029), estrogen level on the human chorionic gonadotropin (hCG) trigger day ( P=0.027), EMT ( P<0.001), gestational age ( P<0.001) and the gender of the newborn ( P<0.001) were independent factors of LBW. The incidence of LBW increased when the body mass index and gestational age were smaller and estrogen level on the hCG trigger day was ≥4000 ng/L. Taking group B as control group, the incidence of LBW in group A increased significantly and was an independent risk factor for LBW (a OR=4.39, 95% CI=1.85-10.46, P<0.001), while the incidence of LBW in group C had no significant difference (a OR=0.90, 95% CI=0.51-1.59, P=0.723). Conclusion:In the fresh cleavage stage embryo transfer cycle, singleton birth weight was lower in thin EMT group. And thin EMT was an independent risk factor for LBW of singleton delivery.

目的 研究英文文献汇报在生殖医学研究生中应用效果.方法 选取2019年12月至2020年6月生殖医学科一、二、三年级研究生参与英文文献汇报,于完成7个月的文献汇报后,向全程参与的25名研究生发放问卷,调查英文文献汇报对其产生的影响.结果 所有评价均认为,英文文献阅读和汇报对自己有一定的帮助.没有研究生进行负面评价,99.4％的学生给予了比较有帮助的积极评价.结论 英文文献汇报对于提高生殖医学研究生英语水平和科研能力有一定作用.

Objective:To investigate the embryo transfer strategies of early follicular phase prolonged protocol, to reduce the risk of multiple birth rate while achieving a higher live birth rate.Methods:It was a retrospective cohort study. Patients who underwent gonadotropin-releasing hormone (GnRH) agonist protocols in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 2017 to February 2019 were included. According to the type of embryos transferred, we divided all cycles into four groups, fresh cycle cleavage stage embryo transfer group (group A), fresh cycle blastocyst transfer group (group B), freeze-thaw cleavage stage embryo transfer group (group C), freeze-thaw blastocyst transfer group (group D). The main outcome measures were live birth rate and multiple birth rate. Binary logistic regression was used to correct confounding factors.Results:The risk of moderate to severe ovarian hyperstimulation syndrome (OHSS) in group A [4.8% (110/2283)] was higher than that in group C [1.0% (6/614), P<0.001] and group D [2.1% (16/762), P<0.001]. The risk of moderate to severe OHSS in group B [3.8% (42/1116)] was higher than that in group C ( P<0.001). The multiple birth rate of the two embryos transfer group [group A 23.4% (535/2283), group C 20.8% (128/614) ] was significantly higher than that of the one blastocyst transfer group [group B 1.4% (16/1116), group D 0.9% (7/762)], and the difference was statistically significant ( P<0.001). The clinical pregnancy rate [68.7% (767/1116)] and the live birth rate [59.6% (665/1116)] of group B were higher than those of group A [63.5% (1449/2283), P=0.003; 54.8% (1250/2283), P=0.008], group C [60.1% (369/614), P<0.001; 51.6% (317/614), P=0.001] and group D [62.7% (478/762), P=0.007; 52.8% (402/762), P=0.003], but there was no statistical difference among group A, group C and group D. Taking group B as a reference, the live birth rate of group A (a OR=0.86, 95% CI=0.74-0.99, P=0.044), group C (a OR=76, 95% CI=0.62-0.93, P=0.008) and group D (a OR=0.79, 95% CI=0.65-0.95, P=0.013) was lower than that of group B. Conclusion:For the early follicular phase prolonged protocol, based on the control of OHSS, fresh cycle single blastocyst transplantation is preferred. While obtaining a higher live birth rate, the multiple birth rate is significantly reduced.

Objective:To investigate the effect of long-acting growth hormone (GH) pretreatment on the clinical outcome and safety of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) in women of advanced age. Methods:It was a prospective, self-controlled study. The patients who underwent IVF/ICSI-embryo transfer (ET) in the Department of Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from May 2018 to November 2019 were included. The patients with age between 35 and 39 years, number of unilateral basal antral follicles ≥5, the basic follicle-stimulating hormone (FSH) <10 IU/L, and ≥50% of the embryos in the previous IVF/ICSI-ET cycle belong to Ⅳ grade embryos were collected in group A1, and in the next IVF/ICSI cycle, GH was added for more than 6 weeks of pretreatment (group A2). The parallel control group was selected for IVF/ICSI during the same period, the criteria for inclusion in the group are the same as above, group B1: the first cycle of routine IVF/ICSI without GH treatment; group B2: adopt the same controlled ovarian hyperstimulation (COH) protocol as the first cycle, without GH treatment. The main outcome measure was the cumulative live birth rate (CLBR).Results:The duration of gonadotropin (Gn) used, the thickness of the endometrium on human chorionic gonadotropin (hCG) injection day, the levels of estrogen and progesterone on hCG injection day, and IVF ratio were not statistically significantly different between before and after self-control groups ( P>0.05). The dosage of Gn used in group A2 was higher than that in group A1 [(3 880.4±902.0) IU vs. (3 485.6±1 054.0) IU, P=0.012], and the dosage of Gn used in group B2 was higher than that in group B1 [(3 377.7±899.2) IU vs. (3 117.8±891.3) IU, P=0.025]. Available embryo rate[55.17% (160/290)], high-quality embryo rate [21.38% (62/290)], clinical pregnancy rate of frozen-thawed embryo transfer [60.87% (14/23)], cumulative pregnancy rate [61.11% (22/36)] and CLBR [50.00% (18/36)] of group A2 were significantly higher than those of group A1 [45.98% (120/261), P=0.031; 12.64% (33/261), P=0.007; 17.39% (4/23), P=0.003; 17.50% (7/40), P<0.001; 2.50% (1/40), P<0.001], the difference was statistically significant. Comparing group B2 with group B1, there were no statistical differences in available embryo rate, high-quality embryo rate, clinical pregnancy rate of fresh cycle, and clinical pregnancy rate of frozen-thawed embryo transfer (all P>0.05). The cumulative pregnancy rate [34.21% (13/38) vs. 12.50% (5/40), P=0.023] and CLBR [26.32% (10/38) vs. 2.50% (1/40), P=0.003] were significantly different. Compared with group B2, available embryo rate [55.17% (160/290) vs. 45.56% (113/248), P=0.026], high-quality embryo rate [21.38% (62/290) vs. 13.31% (33/248), P=0.014], cumulative pregnancy rate [61.11% (22/36) vs. 34.21% (13/38), P=0.021] and CLBR [50.00% (18/36) vs. 26.32% (10/38), P=0.036] in group A2 were significantly higher, and the differences were statistically significant. The group A2 had no significant difference in the incidence of ovarian hyperstimulation syndrome (OHSS), the rate of multiple pregnancy, and the rate of ectopic pregnancy compared with group A1, but the abortion rate of group A2 was significantly lower than that of group A1 [18.18% (4/22) vs. 71.43% (5/7), P=0.016]. There were no significant differences in fasting blood glucose before the use of GH on Gn start day and oocyte retrieval day in group A2 ( P>0.05). Conclusion:GH may improve the outcome of assisted pregnancy in advanced age patients. The clinical application of GH is relatively safe.

Objective:To investigate the optimal number of oocytes retrieved of early follicular phase prolonged protocol and to reduce the risk of ovarian hyperstimulation syndrome (OHSS) while achieving a high cumulative live birth rate (CLBR).Methods:It was a retrospective cohort study. Patients who underwent the first in vitro fertilization or intracytoplasmic sperm injection in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 2014 to December 2017 were included. According to the number of oocytes retrieved, we divided all patients into 5 groups, group A: 1-5 oocytes, group B: 6-10 oocytes, group C: 11-15 oocytes, group D: 15-20 oocytes, group E: >20 oocytes. The basic and clinical data of 5 groups were analyzed. The main outcome measures were CLBR and the incidence of OHSS. Binary logistic regression was used to correct confounding factors to analyze the factors affecting the CLBR and the incidence of OHSS. We calculated the CLBR and the incidence of OHSS in each group. Results:The maternal age (a OR=0.93, 95% CI=0.90-0.97, P<0.001) and body mass index (a OR=0.95, 95% CI=0.92-0.99, P=0.02) were risk factors for CLBR. The number of oocytes retrieved was the protection factor for CLBR (a OR=1.27, 95% CI=1.20-1.35, P<0.001). The maternal age (a OR=0.94, 95% CI=0.91-0.97, P<0.001), body mass index (a OR=0.96, 95% CI=0.93-0.99, P=0.04), and increase in the number of oocytes retrieved (a OR=1.84, 95% CI=1.64-2.06, P<0.001) were the independent risk factors of the incidence of OHSS. With the increase of the number of oocytes retrieved (group A to group C), CLBR increased significantly [51.6% (157/304), 64.8% (869/1314), 75.2% (1334/1774), P<0.001], while the differences among groups C, D and E were not statistically significant ( P>0.05). With the increase in the number of oocytes retrieved (group A to group E), the incidence of OHSS increased significantly [0.3% (1/304), 3.3% (44/1314), 5.0% (88/1774), 9.8% (104/1065), 15.4% (77/499), P<0.001], especially when the number of oocytes retrieved was >15. Conclusion:For the early follicular phase prolonged protocol, the optimal number of oocytes retrieved is 11-15, which can obtain higher CLBR, and reduce the incidence of OHSS.

目的 分析来曲唑联合羟乙基淀粉注射液在卵巢过度刺激综合征(OHSS)高危患者中的应用效果.方法 于2016年1月至2018年12月,根据用药方案将于该院行取卵术和全胚冷冻的OHSS高危患者206例分为观察组(103例)与对照组(103例),对照组患者术后予以羟乙基淀粉注射液治疗,观察组患者术后予以来曲唑联合羟乙基淀粉注射液治疗,比较患者治疗前后血清雌二醇(E2)水平,以及轻度、中度、重度OHSS发生率.结果 治疗前(人绒毛膜促性腺激素注射日),E2水平组间比较差异无统计学意义(P>0.05).治疗后,观察组E2水平明显下降并低于对照组(P<0.05).与对照组相比,观察组轻度OHSS发生率较高,中度OHSS发生率较低(P<0.05),但重度OHSS发生率组间比较差异无统计学意义(P>0.05).结论 OHSS高危患者取卵术后行来曲唑联合羟乙基淀粉注射液治疗,可降低雌激素水平,促使中度OHSS轻度化,降低中度OHSS发生率,具有较好的OHSS防治效果.

Objective:To investigate clinical outcomes and safety of the early follicular phase prolonged protocol and gonadotropin-releasing hormone antagonist (GnRH-A) protocol of patients with expected high ovarian response.Methods:A retrospective cohort analysis of the expected high ovarian response patients during in vitrofertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) was performed in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from September 2015 to May 2019, including 1855 gonadotropin-releasing hormone agonist (GnRH-a) cycles and 720 GnRH-A cycles. The main outcome measures were the clinical outcomes, the incidence of moderate to severe ovarian hyperstimulation syndrome (OHSS), the pregnancy outcome of the first cycle of whole embryo freezing, cumulative pregnancy rate per oocytes retrieval cycle and time to pregnancy (TTP). And a self-controlled study was performed to compare the clinical outcomes of the patients who underwent early follicular phase prolonged protocol previously and underwent GnRH-A protocol or early follicular phase prolonged protocol later. Results:1) There was no statistical difference between GnRH-a group and GnRH-A group in maternal age, body mass index (BMI), basal follicle-stimulating hormone (bFSH), anti-Müllerian hormone (AMH) and intima thickness on the human chorionic gonadotropin (hCG) trigger day ( P>0.05). Compared with the Gn start-up [(170.12±53.94) IU], No. of obtained oocytes (20.60±9.92), No. of available embryos (10.96±6.59), and No. of high-quality embryos (6.47±4.97) in the GnRH-A group, the gonadotropins (Gn) start-up [(135.11±36.61) IU], No. of obtained oocytes (17.79±7.80), No. of available embryos (9.08±5.56), and No. of high-quality embryos (5.18±4.56) in the early follicular phase prolonged protocol group were significantly reduced correspondingly ( P<0.001, P<0.001, P<0.001, P=0.012), while Gn used duration [(14.3±3.23) d], total Gn used dosage [(2 322.08±1 020.48) IU], incidence of moderate to severe OHSS after hCG trigger (9.54%) and fresh cycle clinical pregnancy rate (69.44%) increased significantly ( P<0.001). 2) The clinical pregnancy rate and the abortion rate of the first cycle of whole embryo freezing were not statistically different between the two groups ( P>0.05). 3) There was no statistically significant difference in the cumulative pregnancy rate between the two groups ( P>0.05); the TTP of GnRH-A after fresh embryo transfer [(47.67±3.18) d] and frozen embryo cycle [(140.33±45.43) d] were significantly less than those in the early follicular phase prolonged protocol group [(81.25±3.72) d, (185.19±46.52) d, P<0.001]. But there was no significant difference in TTP between the two groups in the total transplantation period ( P>0.05). 4) The comparison of early follicular phase prolonged protocol and GnRH-A protocol self-control showed that No. of available embryos (5.79±3.14) and No. of high-quality embryos (2.78±1.50) in early follicular phase prolonged protocol were significantly lower than those in GnRH-A group (10.14±4.74, 5.70±3.50) ( P=0.027, P=0.005), and the total Gn used dosage [(2 535.80±1 212.17) IU] and moderate to severe OHSS incidence rate (4.55%) were significantly higher ( P=0.049, P=0.043). 5) The comparison of early follicular phase prolonged protocol and self-control of early follicular phase prolonged protocol protocol again showed that the BMI assisted by the early follicular phase prolonged protocol again [(24.63±2.99) kg/m 2] was lower than that of the early follicular phase prolonged protocol in the first cycle [(25.01±3.12) kg/m 2, P=0.049], while the No. of high-quality embryos (4.00±3.58) and the clinical pregnancy rate of early follicular phase prolonged protocol again (52.10%) were significantly higher than those of the first cycle (2.56±2.12, 29.41%) ( P=0.046, P=0.004). Conclusion:For patients with high expected response, the GnRH-A protocol can significantly reduce the duration of Gn used, the dosage of Gn used and the incidence of moderate to severe OHSS, increase the No. of oocytes, the No. of available embryos and the No. of high-quality embryos. The clinical pregnancy rate of the fresh cycle was lower in GnRH-A protocol, and whole embryo freezing can be considered. For the previous early follicular phase prolonged protocol patients, GnRH-A protocol can be considered next time, and the early follicular phase prolonged protocol can be selected again based on improvement of the basic state and prevention of OHSS.

目的:观察3种降调长方案对卵巢储备功能正常不孕患者IVF/ICSI助孕治疗的促排卵效果及临床结局.方法:选取2016年1月至2018年9月于郑州大学第三附属医院生殖医学中心接受长方案IVF/ICSI助孕的卵巢储备正常患者共5846个周期;根据年龄(≤35岁组、>35岁组)分为:短效长方案组(A组)、长效长方案组(B组)和长长方案组(C组),观察不同年龄组3种方案间的实验室及临床的各项指标.结果:年龄≤35岁组和>35岁组中:C组的Gn用量及使用天数、获卵数、ICSI成熟卵数、2 PN受精率和优质胚胎率、HCG日P水平和因P值升高行全胚冷冻率均最高,A组最低(P<0.05);A组在Gn启动日及HCG日的LH和E2水平均高于其他两组(P<0.05),但HCG日内膜厚度最低(P<0.05).年龄≤35岁组中:B组和C组的着床率和临床妊娠率明显高于A组(P<0.05),B组和C组无明显差异(P>0.05);年龄>35岁组:A、B、C组的着床率和临床妊娠率均无明显差异(P>0.05).结论:对拟行IVF/ICSI助孕卵巢功能正常的不孕患者:年龄≤35岁者应用长效GnRH-a长方案(长长方案、长效长方案)较短效GnRH-a长方案(短效长方案)更能获得良好的助孕结局;对于年龄>35岁的不孕患者,3种降调长方案的助孕结局无明显差异,短效长方案可明显减少Gn用量及时间.

Objective To observe the effect of ovarian stimulation during continuous luteal phase after mini-stimulation protocol in patients with poor ovarian response (POR) receiving in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET).Methods A study of 144 cases following IVF/ICSI-ET was performed in the Third Affiliated Hospital of Zhengzhou University from June 2016 to December 2017.All patients received mini-stimulation regimen (mini-stimulation group).After ovulation,continuous luteal phase stimulation was performed (luteal phase group).According to the semen condition of the male,IVF or ICSI was selected.All the available embryos could be frozen and transferred in the next cycle.The clinical and laboratory indicators and pregnancy outcomes of the two ovulation-promoting protocols were compared.Results 1) In the luteal phase group,the estradiol [(1 043.28±744.77) ng/L vs.(672.47±586.67)ng/L] and progesterone levels [(6.29 ± 0.73) IU/L vs.(1.21 ± 0.94) IU/L] on the human chorionic gonadotropin (hCG) injection day were higher than those of the mini-stimulation group,and the luteinizing hormone (LH) levels on the hCG injection day [(3.74 ± 2.93) IU/L vs.(8.45 ± 5.81) IU/L] were lower than those of the mini-stimulation group,differences were statistically significant (P＜0.001).Between luteal phase group and mini-stimulation group,there were no significant differences in gonadotropin (Gn) used dosage [(2 117.85±1 047.26) IU/L vs.(2 213.64±877.03) IU/L] and ovulation days [(7.76±3.56) d vs.(8.03±2.63) d](P＞0.05).2) The number of retrieved oocytes in the mini-stimulation group and the luteal phase group presented a non-normal distribution,which was expressed by the median and quartile spacing.The number of retrieved oocytes were divided into 0-1,2-3,＞3,and the corresponding cases were 70 vs.45,53 vs.64,21 vs.35.Non-parametric rank sum test was applied,and the results showed that the number of retrieved oocytes in the luteal phase group was higher than that in the mini-stimulation group,and the difference was statistically significant (P=0.022).Available embryos [1.0(0.0,2.0) vs.1.0(0.0,2.0)],two pronucleus (2PN) fertilization rate (70.7％ vs.65.3％),high-quality embryo rate (40.3％ vs.38.9％),premature ovulation rate (6.3％ vs.9.0％) were not statistically different between the two protocols (P＞0.05).3) The number of transplanted embryos (1.53 ± 0.51 vs.1.57± 0.54),the clinical pregnancy rate (18.4％ vs.28.3％) and the miscarriage rate (22.2％ vs.23.5％) were not statistically different between the two groups (P＞0.05).Conclusion Patients with POR can obtain more oocytes,increase available embryos and promote cumulative pregnancy rate.Moreover,the lower level of LH on the hCG injection day during luteal phase ovarian stimulation indicated that the high progesterone level in the luteal phase plays a significant role in down regulation,which is a safe and feasible program.

Objective To investigate the relationship between supraphysiologic estradiol levels on the human chorionic gonadotropin (hCG) injection day and small for gestational age (SGA) and low birth weight (LBW). Methods It was a retrospective cohort study. Patients with singleton pregnancies with delivered after transfer of fresh embryos during the period of July 2008 to July 2017 at the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University were included. According to the serum estradiol level on the day of hCG trigger, we divided all patients into 6 groups. Group A: estradiol≤2000 ng/L (referent group), group B: estradiol 2001-3000 ng/L, group C: estradiol 3001-4000 ng/L, group D: estradiol 4001-5000 ng/L, group E: estradiol 5001-6000 ng/L, group F: estradiol>6000 ng/L. The outcome measures were SGA, LBW, very low birth weight (VLBW), preterm birth (PT) and full-term LBW. We compared the odds ratio (OR) of SGA, LBW, VLBW, PT and full-term LBW among the groups. Then multivariable logistic regression [age, parity, body mass index (BMI), infertility time, type of infertility, cause of infertility, endometrial thickness of hCG injection day, mode of assisted pregnancy, stage of embryo transfer, the number of transplanted embryos, the sex of the newborn] was used to analyze whether these outcome measures could be explained by the estradiol level on the hCG trigger day. Results Compared with group A, the incidence of SGA, LBW and term LBW in group D, group E and group F increased significantly. However, the incidence of VLBW and PT did not change significantly with the increase of estradiol levels (P=0.70, P=0.85). After adjusting for confounding factors by logistic regression analysis, estradiol ≥ 4001 ng/L was an independent risk factor for SGA (group D: aOR=1.69, 95% CI=1.03-2.75, P=0.04; group E: aOR=1.94, 95% CI=1.12-3.36, P=0.02; group F: aOR=2.31, 95% CI=1.38-3.87, P<0.001), LBW (group D: aOR=1.95, 95% CI=1.11-3.44, P=0.02; group E: aOR=2.57, 95% CI=1.38-4.78, P<0.001; group F: aOR=3.36, 95% CI=1.89-5.98, P<0.001), and full-term LBW (group D: aOR=5.36, 95% CI=2.00-14.37, P<0.001; group E: aOR=7.35, 95% CI=2.64-20.49, P<0.001; group F: aOR=12.02, 95% CI=4.55-31.78, P<0.001). At the same time, we also found that BMI was associated with the incidence of SGA, patients with lower BMI had a higher risk of SGA (aOR=0.88, 95% CI=0.83-0.90, P<0.001). Conclusion Supraphysiological serum estradiol level was an independent risk factor for SGA, LBW and full-term LBW birth of fresh embryo transfer. Key words: Estradiol; Small for gestational age; Fresh embryo transfer; Low birth weight