促性腺激素释放激素拮抗剂灵活方案中促黄体生成素一过性早升对新鲜周期IVF/ICSI-ET患者妊娠结局的影响

doi:10.13481/j.1671-587X.20220623

摘要/Abstract

摘要：

目的比较拮抗剂灵活方案中促黄体生成素（LH）一过性早期升高（早升）和未出现LH早升对新鲜周期体外受精/卵胞浆内单精子注射-胚胎移植（IVF/ICSI-ET）患者的妊娠结局，探讨一过性LH早升是否对妊娠结局有不良影响。方法回顾性分析行拮抗剂灵活方案促排卵的145例IVF/ICSI-ET患者的临床资料。根据LH是否出现一过性早升分为无LH早升组（n=105）和LH早升组（n=40）。比较2组患者基本情况、促排卵情况、实验室指标及临床妊娠结局等指标。结果 2组患者平均年龄、不孕年限、体质量指数（BMI）、基础卵泡刺激素（FSH）水平、基础 LH 水平、基础雌二醇（E₂）水平、抗苗勒管激素（AMH）水平、基础窦卵泡（AFC）数、卵巢低储备患者百分率和多囊卵巢综合征（PCOS）患者百分率比较差异均无统计学意义（P>0.05）。LH早升组患者添加拮抗剂日的促性腺激素（Gn）天数、添加拮抗剂日LH水平和添加拮抗剂日E₂水平均大于无LH早升组（t=－3.251，P=0.001；t=－10.198，P<0.001；t=3.233，P=0.002），而拮抗剂使用天数少于无LH早升组（t=3.090，P=0.003）。2组患者添加拮抗剂日卵泡直径、扳机日E₂和孕酮（P）水平、扳机日子宫内膜厚度、获卵数、成熟卵数（率）、正常受精数（率）、第3天（D3）可用胚胎数（率）、D3优质胚胎数（率）、胚胎种植率、临床妊娠率及继续妊娠率组间比较差异无统计学意义（P>0.05）。多因素Logistic回归分析，添加拮抗剂的Gn天数和添加拮抗剂当日E₂水平是采用新鲜IVF/ICSI-ET周期拮抗剂灵活方案中患者出现LH早升的危险因素［OR （95%CI）=1.516（1.128~2.038），P=0.006；OR（95%CI）= 2.424（1.345~4.371），P=0.003］。结论采用拮抗剂灵活方案患者在超促排卵过程中出现一过性的LH早升不影响妊娠结局，但需要及时控制升高的LH并注意添加拮抗剂的时机。

关键词: 拮抗剂方案, 促黄体生成素, 妊娠结局, 体外受精/卵胞浆内单精子注射-胚胎移植

Abstract:

Objective To compare the pregnant outcomes of the patients with and without transient premature of luteinizing hormone （LH） in gonadotrophin releasing hormone（GnRH） antagonist flexible protocols who underwent fresh in vitro fertilization / intracytoplasmic sperm injection-embryo transfer （IVF/ICSI-ET） cycles， and to explore whether transient premature had adverse effect on the pregnancy outcomes. Methods The clinical data of 145 IVF/ICSI-ET patients who received flexible antagonist regimen to promote ovulation were analyzed retrospectively. They were divided into non-transient premature of LH group （n=105） and transient premature LH group （n=40）according to whether the patients had the transient premature of LH.The clinical indicators， laboratory indicators and clinical pregnancy outcomes of the patients were compared between two groups. Results There were no significant differences in the average age， infertility years，body mass index（BMI）， basic follicular stimulating hormone（FSH）， basic LH， basic estradiol（E₂）， anti-Mullerian hormone（AMH）， number of basic antral follicles（AFC）， percentages of the patients with poor ovarian reserve and polycystic ovarian syndrome（PCOS） patients between two groups （P>0.05）.The gonadotropin（Gn）days， LH level and E₂ level on the initial day of antagonists of the patients in transient premature of LH group were higher than those in non-transient premature of LH group （t=－3.251， P= 0.001； t=－10.198，P<0.001； t=3.233，P=0.002）， while the days of antagonist use were less than those in non-transient premature of LH group （t=3.090， P=0.003）. There were no significant differences in follicular diameter on the initial day of antagonists， E₂ and progesterone（P）levels and endometrial thickness on the trigger day， number of available oocytes， numbers（rates） of MⅡ oocytes， numbers（rates） of normal fertilization， numbers（rates） of D3 available embryos， numbers（rates） of D3 high-quality embryos， embryo implantation rates， clinical pregnancy rates and ongoing pregnancy rates of the patients between two groups （P>0.05）. The multivariate Logistic regression analysis results showed that the Gn days and E₂ level on the initial day of antagonists were the risk factors for the transient premature of LH of the patients underwent fresh IVF/ICSI-ET cycle antagonist flexible protocol［OR （95%CI）=1.516（1.128－2.038），P=0.006；OR（95%CI）=2.424（1.345－4.371），P=0.003］. Conclusion The transient premature of LH of the patients with antagonist flexible protocol during superovulation does not affect the pregnancy outcomes， but it is necessary to control the increased LH level in time and pay attention to the timing of adding antagonists.

Key words: Antagonist regimen, Luteinizing hormone, Pregnancy outcome, In vitro fertilization/intracytoplasmic sperm injection-embryo transfer

中图分类号:

R714.8

高红,林莉,颜晓红,陶萍,李友筑. 促性腺激素释放激素拮抗剂灵活方案中促黄体生成素一过性早升对新鲜周期IVF/ICSI-ET患者妊娠结局的影响[J]. 吉林大学学报(医学版), 2022, 48(6): 1566-1573.

Hong GAO,Li LIN,Xiaohong YAN,Ping TAO,Youzhu LI. Effect of transient prematur of luteinizing hormone in gonadotropin releasing hormone antagonist flexible protocols on pregnancy outcomes of patients underwent fresh IVF/ICSI-ET cycles[J]. Journal of Jilin University(Medicine Edition), 2022, 48(6): 1566-1573.

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Group	n	Age (year)	Duration of infertility（year）	BMI(kg·m^－2)		AMH[ρ_B/(g·L^－1)]	Basic FSH [λ_B/(IU·L^－1)]
Non-tansient premature of LH	105	32.4±4.8	2(1,4)	21.69±2.02		2.34(1.36,3.84)	7.43±2.52
Tansient premature of LH	40	33.2±5.6	2.5(1.5,4)	22.64±3.73		2.93(1.47,5.80)	7.46±3.80
t/Z/χ²		－0.864	－0.793	－0.297		－1.163	－0.058
P		0.389	0.427	0.686		0.245	0.954
Group	n	Basic LH [λ_B/(IU·L^－1)]	Basic E₂[ρ_B/(ng·L^－1)]	No.ofAFC	Percentage of poorovary reserve(η/%)		Percentage of PCOS(η/%)
Non-tansient premature of LH	105	4.41±2.16	51.92±18.07	11.9±6.7	27（25.7）		10（9.5）
Tansient premature of LH	40	5.07±1.94	52.26±17.97	13.6±9.0	10（25）		7（17.5）
t/Z/χ²		－1.694	－0.102	－1.090	0.008		1.781
P		0.092	0.919	0.280	0.930		0.182

Group	n	Gn duration untill antagonist starting day（t/d）	E₂ level on antagonist use day E₂[ρ_B/(pg·L^－1)]	D level on antagonist use day P[ρ_B/（μg·L^－1）]	Dominant follicle diameter on antagonistuse day （l/mm）	Antagonist use duration (t/d)
Non-tansient premature of LH	105	6.62±1.39	0.92±0.57	0.64±0.42	13.83±1.75	4.42±1.53
Tansient premature of LH	40	7.49±1.34	1.40±0.86	0.75±0.44	13.98±1.63	3.78±0.92
t		－3.251	－3.233	－1.424	－0.443	3.090
P		0.001	0.002	0.157	0.658	0.003
Group	n	Gn use dosage(IU)	Gn use duration(t/d)	E₂ level on hCGinjection day [ρ_B/(pg·L^－1)]	P level on hCG injection day [ρ_B/(μg·L^－1)]	Endometrial thickness on hCG injection day（l/mm）
Non-tansient premature of LH	105	1 822.93±590.77	9.3±1.8	2.61±1.34	0.73±0.37	11.22±2.53
Tansient premature of LH	40	1 954.69±582.15	9.5±1.4	3.12±1.54	0.73±0.38	11.70±2.49
t		－1.213	－0.521	－1.972	0.120	－1.025
P		0.229	0.603	0.051	0.905	0.307

Group	n	No. of available oocytes	No. of MⅡ oocytes	No. of 2PN	No.of D3 available embryos	No.of D3 high-quality embryos
Non-tansient premature of LH	105	9.2±5.1	7.7±4.1	6.3±3.7	4.8±3.3	3.9±3.0
Tansient premature of LH	40	10.3±6.1	8.5±5.0	6.8±4.3	5.2±3.6	3.9±3.4
t/χ²		－1.086	－0.943	－0.604	－0.564	－0.020
P		0.279	0.348	0.547	0.575	0.984
Group	n	Mature oocytes [n(η/%)]	Normal fertilization [n(η/%)]	Available embryos[n(η/%)]	High-quality embryos[n(η/%)]
Non-tansient premature of LH	105	804(83.6)	666(82.8)	507(76.1)	407(61.1)
Tansient premature of LH	40	340(82.9)	271(79.7)	208(76.8)	157(57.9)
t/χ²		0.087	1.580	0.042	0.812
P		0.768	0.209	0.838	0.368

Group	n	No.of transferred embryos	Transferred blastocysts[n(η/%)]	Implanted embryos[n(η/%)]	Clinical pregnancy[n(η/%)]	Ongoing pregnancy [n(η/%)]
Non-tansient premature of LH	105	2（1,2）	33（31.4）	68（42.0）	60（57.1）	51（48.6）
Tansient premature of LH	40	1.5（1，2）	12（30.0）	22（36.7）	19（47.5）	15（37.5）
Z/χ²		－0.355	0.028	0.512	1.086	1.432
P		0.245	0.868	0.474	0.297	0.231

Variable	Assignment
Premature LH surge	No=0；Yes=1
Basic LH	Quantitative data
Gn duration untill antagonist starting day	Quantitative data
E₂ level on antagonist use day	Quantitative data
Follicle diameter on antagonist use day	Quantitative data