基于体外受精-胚胎移植助孕女性患者年龄对早期胚胎发育动力学参数及胚胎发育潜能影响的Time-lapse技术评估

doi:10.13481/j.1671-587X.20220221

Abstract

Abstract: Objective

To investigate the influence of age of patients in the kinetic parameters of early embryonic development and embryonic developmental potential， and to provide a theoretical basis for studying the relationship between patients’ age and embryo quality.

Methods

The clinical materials of infertile female patients who underwent in vitro fertilization-embryo transfer （IVF-ET） assisted fertility treatment in our department were retrospectively analyzed， and the patients were divided into <30 years old group （48 cases， 439 embryos）， 30 years old≤patients’ age<40 years old group （129 cases，1 019 embryos） and ≥40 years old group （48 cases， 176 embryos） according to their ages. All embryos were cultured in the Time-lapse culture system until Day 3； the developmental dynamics of early embryos were observed， and the number of eggs obtained， fertilization rates， cleavage rates， number of available embryos， number of excellent embryos， etc were compared among three groups； at the same time， the relationship between age and embryonic developmental arrest was also explored.

Results

Compared with≥40 years old group， the number of eggs obtained， the number of available embryos， and the number of high-quality embryos of the patients in <30 years old group and 30 years old≤ patient’s age<40 years old group were increased （P<0.05）； there were statistical differences in time from fertilization to division into 3 cells stages（t3）， time from fertilization to division into 4 cells stages（t4），fertilization time to division into 5 cells stages（t5），time from fertilization to division into 6 cells stages（t6）， time from 2 cells to 3 cells （cc2） among three groups （P<0.05）； the time from fertilization to division into 2 cells stages（t2） and t6 in 30 years old≤patients’ age<40 years old group were longer than those in <30 years old group （P<0.05）； t3 in ≥40 years old group was longer than that in <30 years old group and 30 years old ≤patients’ age<40 yeras old group （P<0.05）， and t3 in 30 years old ≤patients’ age <40 years old group were also longer than those in <30 years old group （P<0.05）； t4 and t5 in ≥40 years old group were longer than those in <30 years old group （P<0.05）， and cc2 in ≥40 years old group was longer than those in <30 years old group and 30 years old≤patients age<40 years old group （P<0.05）； there were no statistical differences in time from fertilization to the disappearance of the two pronucleis（tPNF），time from fertilization to division into 7 cells stages（t7）， time from fertilization to division into 8 cells stages（t8）， time from 3 cells to 4 cells（s2）， time from 5 cells to 8 cells（s3）， time from 3 cells to 5 cells（cc3） among three groups （P>0.05）.Compared with <30 years old group and 30 years old ≤patients’ age <40 years old group， the fragmentation rate of patients in ≥40 years old group was increased （P<0.05）， the incidence of other abnormal division events had a tendency to increase， but there were no statistically significant differences（P>0.05）； compared with <30 years old group and 30 years old≤patients’ age<40 years old group， the proportions of embryos developed to 5 cells， 6 cells， 7 cells and 8 cells in ≥40 years old group were decreased （P<0.05）.

Conclusion

The patients’ age has a certain influence in the developmental dynamics of embryos， with the increase of the patients’ age， the probability of developmental arrest of embryos increases.

Key words: In vitro fertilization, Age, Embryo, Morphokinetics, Developmental arrest

CLC Number:

R715.9

Dongyu YANG,Shan LU,Xiaojing CAO,Xulong CHEN,Sinan LI,Xinghong LU,Yunping NI,Yan XIE. Evaluation of Time-lapse technology on kinetic parameters of early embryonic development and embryonic development potential based on effect of age of female patients with in vitro fertilization-embryo transfer[J].Journal of Jilin University(Medicine Edition), 2022, 48(2): 436-443.

Figures/Tables 5

Tab.1

Tab.2

Parameters and outcome of treatment of patients in three groups"

Group	n	Starting dosage of Gn（IU）（ $x ˉ$ ±s）	Duration of Gn used （ $x ˉ$ ±s）	Total dosage of Gn used（IU）（ $x ˉ$ ±s）	Endometrial thickness on trigger day（l/mm）（ $x ˉ$ ±s）	No. of oocytes retrieved （ $x ˉ$ ±s）	2PN fertilization rate [η/%（n/N）]
<30 years old	48	137.5±42.8	11.0±1.8	1 576.8±585.6	10.0±2.7	12.9±6.5	70.7（439/621）
30 years old≤patients’ age<40 years old	129	176.7±63.1^*	11.0±2.3	1 939.2±836.9^*	10.4±3.0	11.4±6.8	69.3（1 019/1 471）
≥40 years old	48	220.6±65.0^*△	10.2±2.1	2 173.7±746.2^*	8.0±3.2^*△	4.7±3.3^*△	65.7（176/268）
F/χ²	—	7.387	2.410	7.383	10.905	24.416	2.218
P	—	<0.001	0.092	0.001	<0.001	<0.001	0.330
Group	n	Cleavage rate [η/%（n/N）]	Available embryos （ $x ˉ$ ±s）	No. of high-quality embryos （ $x ˉ$ ±s）	Average No. of embryos transferred （ $x ˉ$ ±s）	Embryo implantation rate[η/%（n/N）]	Clinical pregnancy rate[η/%（n/N）]
<30 years old	48	99.5（437/439）	7.8±3.9	3.5±2.4	1.4±0.5（32/23）	59.4（19/32）	73.9（17/23）
30 years old≤patients’ age<40 years old	129	99.7 （1 016/1 019）	6.5±4.4	2.7±2.5	1.5±0.5（107/70）	47.7（51/107）	62.9（44/70）
≥40 years old	48	97.7（172/176）^△	2.9±2.0^*△	1.1±1.2^*△	1.6±0.5（18/11）	27.8（5/18）	36.4（4/11）
F/χ²	—	10.822	21.775	15.572	1.039	4.611	4.488
P	—	0.004	<0.001	<0.001	0.358	0.100	0.106

Tab.2

Tab. 3

Tab.4

Tab.5

References 21

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Group	n	Age of female（year）	Age of male （year）	BMI （kg·m^—2）	AFC
<30 years old	48	27.2±1.7	30.0±3.3	21.4±2.4	22.6±11.2
30 years old≤patients’ age<40 years old	129	34.0±2.8^*	36.7±5.3^*	22.2±3.1	17.2±11.1^*
≥40 years old	48	41.6±2.8^*△	42.6±4.1^*△	23.4±3.4^*△	7.1±4.4^*△
F	—	370.371	88.971	5.437	29.962
P	—	<0.001	<0.001	0.005	<0.001
Group	Duration of infertility （year）	bFSH [λ_B/（IU·L^—1）]	bLH [λ_B/（IU·L^—1）]	AMH [λ_B/（IU·L^—1）]	bE2 [ρ_B/（pmol·L^—1）]
<30 years old	2.4±1.5	6.6±1.7	7.2±4.2	5.2±3.8	161.7±77.3
30 years old≤patients’ age<40 years old	3.7±2.9^*	8.1±8.3	6.8±5.5	3.8±3.3^*	167.2±88.1
≥40 years old	4.7±3.4^*	8.4±3.4	5.5±2.6	1.4±1.1^*△	202.4±88.1
F	8.527	1.111	1.808	18.120	2.421
P	<0.001	0.331	0.166	<0.001	0.091

Group	No.of embryos	tPNF	t2	t3	t4	t5	t6
<30 years old	439	25.3±3.4	28.0±3.9	37.7±5.1	40.4±5.5	51.3±7.0	54.4±6.0
30 years old≤patients’ age<40 years old	1 019	25.8±3.9	28.6±4.4^*	38.9±5.9^*	41.3±6.3	52.3±7.6	55.4±6.5^*
≥40 years old	176	25.6±4.0	28.8±4.7	40.0±6.8^*△	42.2±6.2^*	53.5±7.4^*	55.7±6.8
F	—	2.658	3.384	10.353	5.076	1.137	3.08
P	—	0.070	0.034	<0.001	0.006	0.016	0.046
Group	No.of embryos	t7	t8	s2(t4-t3)	s3(t8-t5)	cc2(t3-t2)	cc3(t5-t3)
<30 years old	439	56.3±5.6	57.8±5.3	2.8±4.5	8.5±6.3	9.8±4.1	14.0±5.7
30 years old≤patients’ age<40 years old	1 019	57.1±5.7	58.3±5.5	2.6±4.5	7.5±6.4	10.4±4.2	14.2±5.6
≥40 years old	176	57.7±5.0	59.8±5.1	2.4±3.9	8.8±6.6	11.7±4.9^*△	14.9±6.5
F	—	2.803	3.01	0.654	1.996	10.137	1.096
P	—	0.061	0.050	0.520	0.137	<0.001	0.334

Group	No.of embryos	Reverse division	1 cell → 3 cells	2 cells → 5 cells	Fragmentation
<30 years old	439	7.3（32/439）	3.4（15/439）	2.7（12/439）	11.4（50/439）
30 years old≤patient age<40 years old	1 019	7.0（71/1 019）	3.5（36/1 019）	3.2（33/1 019）	13.8（141/1 019）^*
≥40 years old	176	10.2（18/176）	6.8（12/176）	6.8（12/176）^*△	19.8（35/176）^*
χ²	—	2.337	4.481	6.728	14.585
P	—	0.311	0.096	0.035	0.001

Group	No. of embryos	2 cells	3 cells	4cells
<30 years old	439	97.5(428/439)	92.0(404/439)	87.7(385/439)
30 years old≤patient age<40 years old	1 024	96.2(985/1 024)	90.4(926/1 024)	86.1(882/1 024)
≥40 years old	176	99.4(175/176)	90.3(159/176)	80.7(142/176)
χ²	—	5.961	1.004	5.191
P	—	0.051	0.606	0.075
Group	5 cells	6 cells	7 cells	8 cells
<30 years old	77.0(338/439)	70.2(308/439)	60.8%(267/439)	45.3(199/439)
30 years old≤patient age<40 years old	73.6(754/1 024)	67.4(690/1 024)	56.1(574/1 024)	39.9(409/1 024)
≥40 years old	61.4(108/176)^*△	53.4(94/176)^*△	43.2(76/176)^*△	33.5(59/176)^*
χ²	15.892	16.555	15.871	7.901
P	<0.001	<0.001	<0.001	0.019

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Evaluation of Time-lapse technology on kinetic parameters of early embryonic development and embryonic development potential based on effect of age of female patients with in vitro fertilization-embryo transfer

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