促性腺激素释放激素激动剂在体外受精-胚胎移植患者黄体支持中的应用

doi:10.13481/j.1671-587X.20210321

摘要/Abstract

摘要： 目的

探讨体外受精-胚胎移植（IVF-ET）患者应用多剂量间断给予促性腺激素释放激素激动剂（GnRH-a）用于黄体支持对妊娠结局及患者子代安全的影响，指导IVF-ET患者科学应用GnRH-a。

方法

前瞻性纳入106例首次进行IVF-ET的患者，采用随机区组分配方法分为对照组（n=53）和多剂量GnRH-a组（n=53）。对照组和多剂量GnRH-a组患者均给予标准的黄体支持治疗，多剂量GnRH-a组则在标准的黄体支持治疗基础上于取卵后的第2、5和8天加用GnRH-a治疗。比较2组患者妊娠结局（妊娠率、临床妊娠率和活产率）和分娩结局（子代早产率、低出生质量儿率和出生缺陷率）。比较2组患者血清黄体酮水平。对患者子代进行随访，采用Bayley婴儿发展量表（Bayley Ⅲ）和儿童行为检查表（CBCL）对患者子代运动、认知、语言及行为发育情况进行评价，得出Bayley Ⅲ评分和CBCL评分。

结果

多剂量GnRH-a组患者妊娠率、临床妊娠率和活产率均明显高于对照组（P<0.05）。2组患者间子代早产率、低出生质量儿率和出生缺陷率比较差异无统计学意义（P>0.05）。胚胎移植第14天，多剂量GnRH-a组患者血清黄体酮水平明显高于对照组（P<0.05）。亚组分析，胚胎移植第14天，多剂量GnRH-a组患者中成功妊娠和非妊娠患者血清黄体酮水平分别高于对照组（P<0.05）。2组患者子代24个月时Bayley Ⅲ评分与CBCL评分比较差异均无统计学意义（P>0.05）。

结论

在标准黄体支持治疗的基础上多剂量间断给予GnRH-a可获得更好的妊娠结局，且长期安全性良好。

关键词: 促性腺激素释放激素激动剂, 体外受精, 胚胎移植, 黄体支持, 妊娠结局

Abstract: Objective

To evaluate the effect of multiple-dose gonadotropin-releasing hormone agonist（GnRH-a） addition to luteal support in pregnancy outcomes and safety of the patients with first in-vitro fertilization-embryo implantation （IVF-ET） and their offsprings， and to guide the IVF-ET patients to use GnRH-a scientifically.

Methods

A total of 106 patients with the first IVF-ET were randomly assigned into control group （n=53） and multiple-dose GnRH-a group （n=53）. The patients in control group were given standard luteal support treatment， while the patients in multiple-dose GnRH-a were given standard luteal support plus GnRH-a at day 2， day 5 and day 8 after egg retrieval. The pregnancy outcomes including pregnancy rates， clinical pregnancy rates and live birth rates of the patients were compared between two groups， and the delivery outcomes included premature birth rate， low-birth weight birth rate and birth defect rate of the patients were compared between two groups. The serum progesterone levels of the patients in two groups were detected. The offsprings of the patients were followed up，and the Bayley Infant Development Scale （Bayley Ⅲ） and Child Behavior Checklist （CBCL） were used to evaluate the exercise， cognitive abilities， language and behavioral development of the children.

Results

The pregnancy rate， clinical pregnancy rate， and live birth rates of the patients in multiple-dose GnRH-a group were statistically higher than those in control group （P<0.05）. There were no significant differences in the rates of premature birth， low-birth weight and birth defects of the patients between two groups （P>0.05）.On the 14th day after embryo implantation， the serum progesterone level of the patients in multiple-dose GnRH-a group was significantly higher than that in control group （P<0.05）.The subgroup analysis results showed that on the 14th day after embnyo implantation，the serum progesterone levels of the pregnancy and non-pregnant patients in multiple-dose GnRH-a group were significantly higher than those in control group， respectively （P<0.05）.There were no significant differences in Bayley Ⅲ score and CBCL score of the patients between two groups at 24th month （P>0.05）.

Conclusion

Addition of multiple-dose GnRH-a to standard lutal support treatment can achieve better pregnancy outcomes with sustained better safety.

Key words: gonadotrophin-releasing hormone agonist, in-vitro fertilization, embryo implantation, luteal support, pregnancy outcome

中图分类号:

R711.6

曲丹妮, 王鹏, 李媛. 促性腺激素释放激素激动剂在体外受精-胚胎移植患者黄体支持中的应用[J]. 吉林大学学报(医学版), 2021, 47(3): 701-706.

Danni QU, Peng WANG, Yuan LI. Application of gonadotropin-releasing hormone agonist inluteal support of patientswith in⁃vitro fertilization-embryo implantation[J]. Journal of Jilin University(Medicine Edition), 2021, 47(3): 701-706.

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Group	Maternal age（year）	BMI （kg·m^－2）		Duration of infertility （year）		Menstrual cycle (t/d)		Type of infertility [n(η/%)]
Group	Maternal age（year）	BMI （kg·m^－2）		Duration of infertility （year）		Menstrual cycle (t/d)		Primary infertility		Secondary infertility
Control	32.6±4.9	22.6±7.5		3.5±0.7		29.3±4.2		31(58.5)		27(50.9)
Multiple-dose GnRH-a	32.9±5.3	23.1±7.3		3.7±0.9		29.1±3.5		22(41.5)		26(49.1)
t/χ²	0.303	0.348		1.277		0.266		0.609
P	0.763	0.729		0.204		0.791		0.435
Group	Infertility cause [n(η/%)]
Group	Tubal abnormality		Male factor		Ovulation failure		Endometriosis		Unexplained
Control	24(45.3)		9(17.0)		4(7.5)		14(26.4)		2(3.8)
Multiple-dose GnRH-a	19(35.8)		11(20.8)		5(9.4)		15(28.3)		3(5.7)
χ²	1.127
P	0.890

Group	FSH[λ_B/(IU·L^－1)]	Retrieved oocytes	Transferred embryos	Gn duration (t/d)	Gn dose (λ_B/U)	Endometrial thickness (l/mm)
Control	8.9±1.3	12.2±3.2	1.8±0.6	10.5±2.2	1 979.7±516.2	10.2±1.9
Multiple-dose GnRH-a	8.6±1.5	12.9±3.1	1.7±0.5	10.2±1.9	1 959.1±515.3	10.7±1.6
t	1.100	1.144	0.932	0.751	0.206	1.465
P	0.274	0.255	0.353	0.454	0.837	0.146

Group	Pregnancy rate[n(η/%)]	Clinical pregnancy rate[n(η/%)]	Live birth rate[n(η/%)]
Group	Pregnancy rate[n(η/%)]	Clinical pregnancy rate[n(η/%)]	Singleton pregnancy	Twin pregnancy
Control	20(37.7)	19(35.8)	12(22.6)	1(1.9)
Multiple-dose GnRH-a	27(50.9)	26(49.1)	19(35.8)	1(1.9)
χ²	1.873	1.892	2.156
P	0.047	0.047	0.033
Group	Number of fetuses	Preterm birth rate[n(η/%)]	Low birth quality infant rate[n(η/%)]	Birth defect rate[n(η/%)]
Control	14	1(7.1)	2(14.3)	0(0)
Multiple-dose GnRH-a	21	1(4.8)	2(9.5)	0(0)
χ²		－	－	－
P		0.647	0.530	1.000

Variable	Number of fetuses	Bayley score		CBCL score
Variable	Number of fetuses	Exercise development	Cognition and language development	CBCL score
Control	14	101.9±20.3	103.3±19.5	46.8±9.5
Multiple-dose GnRH-a	21	107.5±23.2	101.7±22.3	49.1±9.7
t		0.755	0.225	0.696
P		0.455	0.824	0.491

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