胚龄对于CC级别单囊胚冻融移植周期妊娠结局的影响

doi:10.3969/j.issn.1674-8115.2021.04.014

摘要/Abstract

摘要：

目的·探讨单囊胚冻融移植周期中胚龄对CC级别囊胚妊娠结局的影响。方法·纳入2017年4月—2019年12月于上海永远幸妇科医院进行单个冻融囊胚移植的565例患者，分为高质量囊胚组（AA、AB、BA级，n=189）、中质量囊胚组（BB、AC、CA级，n=114）、低质量囊胚组（CB、BC级，n=140）和CC级别囊胚组（n=122）。其中，CC级别囊胚组按照胚龄进一步分为D5亚组（n=26）、D6亚组（n=81）和D7亚组（n=15）。对4个不同级别囊胚组及3个CC级别囊胚胚龄亚组的周期特征及妊娠结局进行比较。结果·高质量囊胚组、中质量囊胚组、低质量囊胚组、CC级别囊胚组的临床妊娠率（58.7% vs 54.4% vs 47.1% vs 25.4%，P=0.000）和活产率（46.2% vs 43.2% vs 36.2% vs 17.6%，P=0.000）依次降低。多元回归分析显示，胚胎质量与临床妊娠率显著相关。与高质量囊胚相比，CC胚胎的临床妊娠率较低（aOR=0.81，95%CI 0.71~0.93，P=0.003）。CC级别囊胚胚龄亚组分析显示，D5、D6和D7亚组的临床妊娠率（42.3% vs 23.5% vs 6.7%，P=0.040）和活产率（31.6% vs 15.6% vs 0，P=0.133）依次降低。多元回归分析显示，胚龄对CC级别囊胚移植临床妊娠率有显著影响。相较于D5的CC级别胚胎，D7的CC级别胚胎的临床妊娠率更低（aOR=0.69，95%CI 0.49~0.96，P=0.032）。结论·D5的CC级别囊胚具有很好的妊娠结局，临床价值高。D6的CC级别囊胚虽然妊娠率较低，但仍具有一定的临床价值，而D7的CC级别囊胚临床价值较小。

关键词: 囊胚质量, CC级别囊胚, 临床妊娠率, 单囊胚冻融移植

Abstract:

Objective· To assess the effect of embryonic age on the pregnancy outcomes of blastocyst graded as CC in single frozen-thawed blastocyst transfer cycles.

Methods· A total of 565 patients undergoing single frozen-thawed blastocyst transfer at Shanghai TOWAKO Hospital from April 2017 to December 2019 were included in this study, and they were divided into high-quality blastocyst group (grade AA, AB, and BA; n=189), medium-quality blastocyst group (grade BB, AC, and CA; n=114), low-quality blastocyst group (grade CB and BC; n=140) and CC grade blastocyst group (n=122). And the CC grade blastocysts were further divided into CC grade blastocysts of Day 5 (D5 subgroup, n=26), Day 6 (D6 subgroup, n=81) and Day 7 (D7 subgroup, n=15) according to the embryonic age. Thereafter, the cycle characteristics and pregnancy outcomes of the four groups and the three embryonic age subgroups of CC grade blastocysts were compared.

Results· The clinical pregnancy rate (58.7% vs 54.4% vs 47.1% vs 25.4%, P=0.000) and live birth rate (46.2% vs 43.2% vs 36.2% vs 17.6%, P=0.000) of the high-quality, medium-quality, low-quality, and CC grade blastocyst groups decreased sequentially. Multivariate analysis showed that embryo quality was significantly correlated with clinical pregnancy rate. Compared with high-quality blastocyst group, CC grade blastocyst group had a lower clinical pregnancy rate (aOR=0.81, 95%CI 0.71?0.93, P=0.003). The analysis of CC grade blastocyst embryonic age subgroups showed that the clinical pregnancy rate (42.3% vs 23.5% vs 6.7%, P=0.040) and live birth rate (31.6% vs 15.6% vs 0, P=0.133) of the D5, D6 and D7 subgroups also decreased sequentially. Multivariate analysis showed that the embryonic age had a significant impact on the clinical pregnancy rate of CC grade blastocyst transfer. Compared with the D5 subgroup, the D7 subgroup had a lower clinical pregnancy rate (aOR=0.69, 95%CI 0.49?0.96, P=0.032).

Conclusion· D5 CC grade blastocysts predict good pregnancy outcome. Although the clinical pregnancy rate of D6 CC grade blastocysts is low, they are still useable. However, D7 CC grade blastocysts are of little clinical value.

Key words: blastocyst quality, blastocyst graded as CC, clinical pregnancy rate, single frozen-thawed blastocyst transfer

中图分类号:

R711.6

赵明, 黄亚, 杜通, 林嘉盈, 祁秀娟, 徐利, 陆文怡, 匡延平. 胚龄对于CC级别单囊胚冻融移植周期妊娠结局的影响[J]. 上海交通大学学报(医学版), 2021, 41(4): 502-508.

Ming ZHAO, Ya HUANG, Tong DU, Jia-ying LIN, Xiu-juan QI, Li XU, Wen-yi LU, Yan-ping KUANG. Effect of embryonic age on the pregnancy outcomes of blastocysts graded as CC in single frozen-thawed blastocyst transfer cycles[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(4): 502-508.

图/表 5

参考文献 25

1	Glujovsky D, Farquhar C, Quinteiro Retamar AM, et al. Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology[J]. Cochrane Database Syst Rev, 2016(6): CD002118.
2	Shoukir Y, Chardonnens D, Campana A, et al. The rate of development and time of transfer play different roles in influencing the viability of human blastocysts[J]. Hum Reprod, 1998, 13(3): 676-681.
3	Adler A, Lee HL, McCulloh DH, et al. Blastocyst culture selects for euploid embryos: comparison of blastomere and trophectoderm biopsies[J]. Reprod Biomed Online, 2014, 28(4): 485-491.
4	Fanchin R, Ayoubi JM, Righini C, et al. Uterine contractility decreases at the time of blastocyst transfers[J]. Hum Reprod, 2001, 16(6): 1115-1119.
5	Magli MC, Jones GM, Gras L, et al. Chromosome mosaicism in day 3 aneuploid embryos that develop to morphologically normal blastocysts in vitro[J]. Hum Reprod, 2000, 15(8): 1781-1786.
6	Mancuso AC, Boulet SL, Duran E, et al. Elective single embryo transfer in women less than age 38 years reduces multiple birth rates, but not live birth rates, in United States fertility clinics[J]. Fertil Steril, 2016, 106(5): 1107-1114.
7	Rodríguez Barredo DB, Tur Padro R, Mancini F, et al. Elective single embryo transfer and cumulative pregnancy rate: five-year experience in a Southern European Country[J]. Gynecol Endocrinol, 2012, 28(6): 425-428.
8	夏兰, 吴娴, 徐慧慧, 等. 胚胎质量对冻融周期中生化妊娠和胚胎早期停止发育的影响[J]. 上海交通大学学报(医学版), 2017, 37(3): 344-347.
9	Irani M, Reichman D, Robles A, et al. Morphologic grading of euploid blastocysts influences implantation and ongoing pregnancy rates[J]. Fertil Steril, 2017, 107(3): 664-670.
10	Oron G, Son WY, Buckett W, et al. The association between embryo quality and perinatal outcome of singletons born after single embryo transfers: a pilot study[J]. Hum Reprod, 2014, 29(7): 1444-1451.
11	倪晓蓓, 王珊珊, 张宁媛, 等. 单囊胚冷冻复苏周期中囊胚时期及质量与临床结局相关分析[J]. 生殖医学杂志, 2016, 25(10): 926-931.
12	Gardner DK, Lane M. Embryo culture systems[M]// Trounson AO, Gardner DK. Handbook of in vitro fertilization. 2nd ed. Boca Raton, FL: CRC Press, 2000: 205-264.
13	乔杰, 马彩虹, 刘嘉茵, 等. 辅助生殖促排卵药物治疗专家共识[J]. 生殖与避孕, 2015, 35(4): 211-223.
14	Kuang Y, Chen Q, Fu Y, et al. Medroxyprogesterone acetate is an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization[J]. Fertil Steril, 2015, 104(1): 62-70.e3.
15	黄亚, 徐利, 葛凤菊, 等. 激光辅助孵化完全去除透明带对冷冻单囊胚移植结局的影响[J]. 诊断学理论与实践, 2019, 18(3): 334-339.
16	van den Abbeel E, Balaban B, Ziebe S, et al. Association between blastocyst morphology and outcome of single-blastocyst transfer[J]. Reprod Biomed Online, 2013, 27(4): 353-361.
17	韩伟, 熊顺, 黄国宁. 体外受精胚胎发育潜能的形态学评估[J]. 生殖医学杂志, 2012, 21(2): 128-132.
18	Utsunomiya T, Ito H, Nagaki M, et al. A prospective, randomized study: day 3 versus hatching blastocyst stage[J]. Hum Reprod, 2004, 19(7): 1598-1603.
19	Kovalevsky G, Carney SM, Morrison LS, et al. Should embryos developing to blastocysts on day 7 be cryopreserved and transferred: an analysis of pregnancy and implantation rates[J]. Fertil Steril, 2013, 100(4): 1008-1012.
20	Du T, Wang Y, Fan Y, et al. Fertility and neonatal outcomes of embryos achieving blastulation on day 7: are they of clinical value?[J]. Hum Reprod, 2018, 33(6): 1038-1051.
21	Su Y, Li JJ, Wang C, et al. Aneuploidy analysis in day 7 human blastocysts produced by in vitro fertilization[J]. Reprod Biol Endocrinol, 2016, 14: 20.
22	Hashimoto S, Amo, Hama S, et al. Growth retardation in human blastocysts increases the incidence of abnormal spindles and decreases implantation potential after vitrification[J]. Hum Reprod, 2013, 28(6): 1528-1535.
23	Chen QJ, Wang Y, Sun LH, et al. Controlled ovulation of the dominant follicle using progestin in minimal stimulation in poor responders[J]. Reprod Biol Endocrinol, 2017, 15(1): 71.
24	Carney SK, Das S, Blake D, et al. Assisted hatching on assisted conception in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI)[J]. Cochrane Database Syst Rev, 2012, 12: CD001894.
25	洋歌德(Jagat Prasad Deep). 经阴道与经腹部超声引导下胚胎移植对IVF临床妊娠的影响[D]. 长沙: 中南大学, 2012.

Variable	High-quality blastocyst	Midian-quality blastocyst	Low-quality blastocyst	CC grade blastocyst	P value
Number of case/n	189	114	140	122	?
Maternal age/year	33 (30, 37)	34 (31, 36)	35 (32, 39)	37 (32, 41)	0.000
Body mass index/(kg·m^-2)	21.30 (19.50, 22.90)	21 (19.35, 23.00)	21.25 (19.60, 23.00)	21.00 (19.80, 23.40)	0.826
Infertility duration/year	3 (2, 5)	3 (2, 5)	3 (3, 5)	3 (2, 6)	0.527
Infertility type/n (%)					0.056
Primary infertility	92 (48.7)	45 (39.5)	69 (49.2)	70 (57.4)
Secondary infertility	97 (51.3)	69 (60.5)	71 (50.7)	52 (42.6)
Previous transfer attempt/n	0 (0, 0)	0 (0, 0)	0 (0, 1)	0 (0, 0)	0.051
Basal FSH/(IU·L^-1)	7.30 (6.20, 8.85)	7.55 (6.03, 8.70)	8.20 (6.70, 10.40)	8.10 (6.80, 10.80)	0.001
AMH/(ng·mL^-1)	3.13 (1.47, 5.32)	2.34 (1.25, 4.39)	1.69 (0.61, 2.91)	1.25 (0.54, 2.62)	0.000
Ovarian stimulation protocol/n (%)					0.357
PPOS	76 (40.2)	37 (32.5)	61 (43.6)	46 (37.7)
Mild stimulation	54 (28.6)	31 (27.2)	43 (30.7)	36 (29.5)
GnRH-ant	42 (22.2)	39 (34.2)	28 (20.0)	35 (28.7)
Natural cycle	14 (7.4)	7 (6.1)	6 (4.3)	3 (2.5)
Long protocol	2 (1.1)	0 (0)	2 (1.4)	2 (1.6)
Luteal stimulation	1 (0.5)	0 (0)	0 (0)	0 (0)
Fertilization method/n (%)					0.011
IVF	135 (71.0)	87 (75.5)	86 (60.9)	72 (58.3)
ICSI	54 (29.0)	27 (24.5)	54 (39.1)	50 (41.7)
Embryonic age/n (%)					0.000
D5	150 (79.4)	65 (57.0)	66 (47.1)	26 (21.3)
D6	39 (20.6)	45 (39.5)	69 (49.3)	81 (66.4)
D7	0 (0)	4 (3.5)	5 (3.6)	15 (12.3)
Endometrial preparation/n (%)					0.470
Hormone therapy cycles	75 (39.7)	49 (43.0)	52 (37.1)	38 (31.1)
Mild stimulated cycles	49 (25.9)	30 (26.3)	34 (24.3)	31 (25.4)
Natural cycles	65 (34.4)	35 (30.7)	54 (38.6)	53 (43.4)
Endometrial thickness on ET day/mm	8.60 (8.50, 11.40)	8.85 (8.40, 10.80)	8.50 (8.20, 11.00)	8.50 (8.12, 10.78)	0.671

Variable	High-quality blastocyst	Midian-quality blastocyst	Low-quality blastocyst	CC grade blastocyst	P value
Number of case/n	189	114	140	122	?
Maternal age/year	33 (30, 37)	34 (31, 36)	35 (32, 39)	37 (32, 41)	0.000
Body mass index/(kg·m^-2)	21.30 (19.50, 22.90)	21 (19.35, 23.00)	21.25 (19.60, 23.00)	21.00 (19.80, 23.40)	0.826
Infertility duration/year	3 (2, 5)	3 (2, 5)	3 (3, 5)	3 (2, 6)	0.527
Infertility type/n (%)					0.056
Primary infertility	92 (48.7)	45 (39.5)	69 (49.2)	70 (57.4)
Secondary infertility	97 (51.3)	69 (60.5)	71 (50.7)	52 (42.6)
Previous transfer attempt/n	0 (0, 0)	0 (0, 0)	0 (0, 1)	0 (0, 0)	0.051
Basal FSH/(IU·L^-1)	7.30 (6.20, 8.85)	7.55 (6.03, 8.70)	8.20 (6.70, 10.40)	8.10 (6.80, 10.80)	0.001
AMH/(ng·mL^-1)	3.13 (1.47, 5.32)	2.34 (1.25, 4.39)	1.69 (0.61, 2.91)	1.25 (0.54, 2.62)	0.000
Ovarian stimulation protocol/n (%)					0.357
PPOS	76 (40.2)	37 (32.5)	61 (43.6)	46 (37.7)
Mild stimulation	54 (28.6)	31 (27.2)	43 (30.7)	36 (29.5)
GnRH-ant	42 (22.2)	39 (34.2)	28 (20.0)	35 (28.7)
Natural cycle	14 (7.4)	7 (6.1)	6 (4.3)	3 (2.5)
Long protocol	2 (1.1)	0 (0)	2 (1.4)	2 (1.6)
Luteal stimulation	1 (0.5)	0 (0)	0 (0)	0 (0)
Fertilization method/n (%)					0.011
IVF	135 (71.0)	87 (75.5)	86 (60.9)	72 (58.3)
ICSI	54 (29.0)	27 (24.5)	54 (39.1)	50 (41.7)
Embryonic age/n (%)					0.000
D5	150 (79.4)	65 (57.0)	66 (47.1)	26 (21.3)
D6	39 (20.6)	45 (39.5)	69 (49.3)	81 (66.4)
D7	0 (0)	4 (3.5)	5 (3.6)	15 (12.3)
Endometrial preparation/n (%)					0.470
Hormone therapy cycles	75 (39.7)	49 (43.0)	52 (37.1)	38 (31.1)
Mild stimulated cycles	49 (25.9)	30 (26.3)	34 (24.3)	31 (25.4)
Natural cycles	65 (34.4)	35 (30.7)	54 (38.6)	53 (43.4)
Endometrial thickness on ET day/mm	8.60 (8.50, 11.40)	8.85 (8.40, 10.80)	8.50 (8.20, 11.00)	8.50 (8.12, 10.78)	0.671

Variable	High-quality blastocyst	Midian-quality blastocyst	Low-quality blastocyst	CC grade blastocyst	P value
Number of case/n	189	114	140	122	?
Biochemical pregnancy /n(%)	126 (66.7)	68 (59.6)	94 (67.1)	43 (35.2)	0.000
Clinical pregnancy/n(%)	111 (58.7)	62 (54.4)	66 (47.1)	31 (25.4)	0.000
Early miscarriage/n(%)	21 (18.9)	12 (19.4)	13 (19.7)	10 (32.3)	0.417
Ectopic pregnancy/n(%)	3 (2.7)	1 (1.6)	0 (0)	0 (0)	0.620
Ongonging pregnancy/n(%)	87 (46.0)	49 (43.0)	53 (37.9)	21 (17.2)	0.000
Late miscarriage^①/n(%)	3 (2.1)	0 (0)	1 (1.0)	1 (1.1)	0.619
Live birth^①/n(%)	67 (46.2)	41 (43.2)	38 (36.2)	16 (17.6)	0.000
Gestational age^①/week	39 (38, 40)	39 (37, 40)	39 (38, 40)	39 (39, 40)	0.481
Birth weight^①/kg	3 400 (3 100, 3 705)	3 350 (3 000, 3 600)	3 300 (3 000, 3 600)	3 475 (3 000, 3 710)	0.669

Variable	High-quality blastocyst	Midian-quality blastocyst	Low-quality blastocyst	CC grade blastocyst	P value
Number of case/n	189	114	140	122	?
Biochemical pregnancy /n(%)	126 (66.7)	68 (59.6)	94 (67.1)	43 (35.2)	0.000
Clinical pregnancy/n(%)	111 (58.7)	62 (54.4)	66 (47.1)	31 (25.4)	0.000
Early miscarriage/n(%)	21 (18.9)	12 (19.4)	13 (19.7)	10 (32.3)	0.417
Ectopic pregnancy/n(%)	3 (2.7)	1 (1.6)	0 (0)	0 (0)	0.620
Ongonging pregnancy/n(%)	87 (46.0)	49 (43.0)	53 (37.9)	21 (17.2)	0.000
Late miscarriage^①/n(%)	3 (2.1)	0 (0)	1 (1.0)	1 (1.1)	0.619
Live birth^①/n(%)	67 (46.2)	41 (43.2)	38 (36.2)	16 (17.6)	0.000
Gestational age^①/week	39 (38, 40)	39 (37, 40)	39 (38, 40)	39 (39, 40)	0.481
Birth weight^①/kg	3 400 (3 100, 3 705)	3 350 (3 000, 3 600)	3 300 (3 000, 3 600)	3 475 (3 000, 3 710)	0.669

Variable	aOR (95%CI)	P value
Blastocyst quality
High-quality blastocyst	Reference
Midian-quality blastocyst	0.96 (0.85?1.09)	0.562
Low-quality blastocyst	0.92 (0.82?1.04)	0.175
CC grade blastocyst	0.81 (0.71?0.93)	0.003
Maternal age
≤29 year	Reference
30?35 year	1.04 (0.92?1.18)	0.538
≥36 year	0.78 (0.68?0.90)	0.000
Body mass index
<18.5 kg·m^-2	Reference
18.5?24 kg·m^-2	1.08 (0.93?1.25)	0.295
>24 kg·m^-2	1.07 (0.90?1.27)	0.454
Infertility duration
≤2 year	Reference
3?5 year	0.94 (0.85?1.04)	0.262
≥6 year	0.90 (0.79?1.02)	0.092
Infertility type
Primary infertility	Reference
Secondary infertility	1.01 (0.92?1.11)	0.835
Basal FSH	0.99 (0.99?1.00)	0.011
AMH	0.99 (0.98?1.00)	0.254
Previous transfer attempt	1.00 (0.97?1.04)	0.914
Ovarian stimulation protocol
PPOS	Reference
Mild stimulation	1.00 (0.89?1.12)	0.964
GnRH-ant	1.06 (0.95?1.19)	0.287
Natural cycle	1.02 (0.84?1.24)	0.860
Long protocol	1.61 (0.94?2.76)	0.087
Luteal stimulation	0.61 (0.24?1.54)	0.299
Fertilization method
IVF	Reference
ICSI	1.00 (0.91?1.10)	0.980
Embryonic age
D5	Reference
D6	0.92 (0.84?1.01)	0.097
D7	0.87 (0.69?1.11)	0.272
Endometrial preparation
Natural cycles	Reference
Hormone therapy cycles	1.10 (1.00?1.22)	0.044
Mild stimulated cycles	1.09 (0.95?1.24)	0.214
Endometrial thickness on ET day
<8 mm	Reference
8?15 mm	1.15 (1.00?1.34)	0.058
>15 mm	1.64 (1.23?2.17)	0.000