Comparison of clinical outcomes between different down-regulation protocols in in vitro fertilization-embryo transplantation patients

doi:10.3877/cma.j.issn.1673-5250.2018.03.011

Objective

To compare the clinical outcomes in pregnancy between the infertility patients receiving long-term protocol and ultra-long-term down-regulation protocol who underwent in vitro fertilization-embryo transfer (IVF-ET) .

Methods

From July 1, 2012 to January 31, 2017, a total of 386 infertility patients who underwent IVF-ET or intracytoplasmic sperm injection-embryo transfer (ICSI-ET) in Department of Reproductive Medicine, Jining No.1 People′s Hospital were selected as research subjects. According to the different down-regulation protocols they received, they were divided into long-term down-regulation protocol group (n=249), and ultra-long-term down-regulation protocol group (n=137). In long-term down-regulation protocol group and ultra-long-term down-regulation protocol group, there were 192 cases and 30 cases of patients ≤30 years old, 21 cases and 68 cases of patients >30-35 years old, 36 cases and 39 cases of patients ≥35 years old, respectively. The following items of all subjects were collected, including age, body mass index (BMI), the dosage of gonadotropins (Gn), the duration of Gn treatment, the number of embryos transferred, the number of oocytes retrieved, and rates of biochemical pregnancy, clinical pregnancy, spontaneous miscarriage and ectopic pregnancy. The age, BMI, the dose of Gn, and the number of embryos transferred between two groups with different age stages were compared by independent-samples t test, respectively. The number of oocytes retrieved between two groups with different age stages were compared by rank sum test, respectively. The rates of biochemical pregnancy, clinical pregnancy, spontaneous miscarriage and ectopic pregnancy between two groups with different age stages were compared by chi-square test, respectively.

Results

①There were no statistical differences between two groups with different age stages in the terms of age and BMI, respectively (P>0.05). ②Among infertility patients ≥30 years old, the dosage of Gn, duration of Gn treatment and the number of embryos transferred in ultra-long-term down-regulation protocol group were (3 290.0±1 113.6 ) g, (12.3±2.3) d, and (2.1±0.3), respectively, which were all greater or longer than those in long-term down-regulation protocol group [(1 848.2±684.8 ) g, (9.7±1.9) d, and (2.0±0.2)], and all the differences were statistically significant (t=5.489, P<0.001; t=6.254, P<0.001; t=3.072, P=0.016). The spontaneous miscarriage rate of patients in ultra-long-term down-regulation protocol group was 3.3%, which was significantly lower than that of long-term down-regulation protocol group 20.6% (χ²=4.969, P=0.026). ③Among infertility patients >30-35 years old, the dosage of Gn, duration of Gn treatment of patients in ultra-long-term down-regulation protocol group were (3 800.0±1 310.5) g and (12.7±2.9) d, respectively, which were greater or longer than those in long-term down-regulation protocol group [(2 149.0±603.8) g, (9.5±1.9) d], and both the differences were statistically significant (t=5.632, 4.991; P<0.001). ④Among infertility patients ≥35 years old, the dosage of Gn and duration of Gn treatment of patients in ultra-long-term down-regulation protocol group were (3 991.7±944.5) g and (12.4±2.9) d, respectively, which were greater or longer than those in long-term down-regulation protocol [(2 701.7±987.3) g, (9.7±1.8) d], while the number of oocytes retrieved of patients in ultra-long-term down-regulation protocol group was 7 (4-9), which was significantly lower than those in long-term down-regulation protocol group [10 (8-15)], and all the differences were statistically significant (t=7.226, t=4.872, Z=5.121; P<0.001).

Conclusions

Infertility patients ≤ 30 years old are recommended to be treated with ultra-long-term down-regulation protocol for IVF-ET treatment. There is no obvious advantage for patients >30-35 years old to apply ultra-long-term down-regulation protocol, so it is suggested to apply long-term down-regulation protocol. Patients ≥ 35 years old are suggested to use ultra-long-term down-regulation protocol for IVF-ET treatment carefully.

Key words: Fertilization in vitro, Embryo transfer, Sperm injections, intracytoplasmic, Gonadotropins, Abortion, spontaneous, Female

表1 年龄≤30岁的2组受试者一般临床资料及妊娠结局比较

组别	例数	年龄(岁，±s)	BMI(kg/m²，±s)	Gn使用剂量(g，±s)	Gn使用时间(d，±s)	获卵数[个，M(P₂₅～P₇₅)]
长方案组	192	26.6±2.4	22.9±3.9	1 848.2±684.8	9.7±1.9	13(9～17)
超长方案组	30	27.1±2.2	22.7±3.8	3 290.0±1 113.6	12.3±2.3	11(7～16)
检验值	?	t＝1.023	t＝0.922	t＝5.489	t＝6.254	Z＝0.982
P值	?	0.336	0.821	<0.001	<0.001	0.110
组别	例数	移植胚胎数(个，±s)	生化妊娠[% (n/n′)]	临床妊娠[% (n/n′)]	自然流产[% (n/n′)]	异位妊娠[% (n/n′)]
长方案组	192	2.0±0.2	58.3(112/192)	53.1(102/192)	20.6(21/102)	1.0(1/102)
超长方案组	30	2.1±0.3	53.3(16/30)	50.0(15/30)	3.3(1/30)	0(0/30)
检验值	?	t＝3.072	χ²＝0.266	χ²＝0.102	χ²＝4.969	—
P值	?	0.016	0.606	0.750	0.026	1.000

表1 年龄≤30岁的2组受试者一般临床资料及妊娠结局比较

组别	例数	年龄(岁，±s)	BMI(kg/m²，±s)	Gn使用剂量(g，±s)	Gn使用时间(d，±s)	获卵数[个，M(P₂₅～P₇₅)]
长方案组	192	26.6±2.4	22.9±3.9	1 848.2±684.8	9.7±1.9	13(9～17)
超长方案组	30	27.1±2.2	22.7±3.8	3 290.0±1 113.6	12.3±2.3	11(7～16)
检验值	?	t＝1.023	t＝0.922	t＝5.489	t＝6.254	Z＝0.982
P值	?	0.336	0.821	<0.001	<0.001	0.110
组别	例数	移植胚胎数(个，±s)	生化妊娠[% (n/n′)]	临床妊娠[% (n/n′)]	自然流产[% (n/n′)]	异位妊娠[% (n/n′)]
长方案组	192	2.0±0.2	58.3(112/192)	53.1(102/192)	20.6(21/102)	1.0(1/102)
超长方案组	30	2.1±0.3	53.3(16/30)	50.0(15/30)	3.3(1/30)	0(0/30)
检验值	?	t＝3.072	χ²＝0.266	χ²＝0.102	χ²＝4.969	—
P值	?	0.016	0.606	0.750	0.026	1.000

表2 年龄>30～35岁的2组受试者一般临床资料及妊娠结局比较

组别	例数	年龄(岁，±s)	BMI(kg/m²，±s)	Gn使用剂量(g，±s)	Gn使用时间(d，±s)	获卵数[个，M(P₂₅～P₇₅)]
长方案组	21	32.5±1.0	23.7±4.4	2 149.0±603.8	9.5±1.9	12(8～16)
超长方案组	68	32.9±1.0	24.0±4.5	3 800.0±1 310.5	12.7±2.9	9(6～13)
检验值	?	t＝1.632	t＝0.937	t＝5.632	t＝4.991	Z＝0.753
P值	?	0.100	0.810	<0.001	<0.001	0.097
组别	例数	移植胚胎数(个，±s)	生化妊娠[% (n/n′)]	临床妊娠[% (n/n′)]	自然流产[% ( n/n′)]
长方案组	21	1.9±0.3	71.4(15/21)	57.1(12/21)	16.3(7/43)
超长方案组	68	1.9±0.4	67.7(46/68)	63.2(43/68)	8.3(1/12)
检验值	?	t＝0.822	χ²＝0.106	χ²＝0.252	χ²＝0.052
P值	?	0.080	0.744	0.615	0.820

表2 年龄>30～35岁的2组受试者一般临床资料及妊娠结局比较

组别	例数	年龄(岁，±s)	BMI(kg/m²，±s)	Gn使用剂量(g，±s)	Gn使用时间(d，±s)	获卵数[个，M(P₂₅～P₇₅)]
长方案组	21	32.5±1.0	23.7±4.4	2 149.0±603.8	9.5±1.9	12(8～16)
超长方案组	68	32.9±1.0	24.0±4.5	3 800.0±1 310.5	12.7±2.9	9(6～13)
检验值	?	t＝1.632	t＝0.937	t＝5.632	t＝4.991	Z＝0.753
P值	?	0.100	0.810	<0.001	<0.001	0.097
组别	例数	移植胚胎数(个，±s)	生化妊娠[% (n/n′)]	临床妊娠[% (n/n′)]	自然流产[% ( n/n′)]
长方案组	21	1.9±0.3	71.4(15/21)	57.1(12/21)	16.3(7/43)
超长方案组	68	1.9±0.4	67.7(46/68)	63.2(43/68)	8.3(1/12)
检验值	?	t＝0.822	χ²＝0.106	χ²＝0.252	χ²＝0.052
P值	?	0.080	0.744	0.615	0.820

表3 年龄≥35岁的2组受试者一般临床资料及妊娠结局比较

组别	例数	年龄(岁，±s)	BMI(kg/m²，±s)	Gn使用剂量(g，±s)	Gn使用时间(d，±s)	获卵数[个，M(P₂₅～P₇₅)]
长方案组	36	37.3±2.3	23.7±2.2	2 701.7±987.3	9.7±1.8	10(8～15)
超长方案组	39	38.6±2.1	23.5±2.8	3 991.7±944.5	12.4±2.9	7(4～9)
检验值	?	t＝1.924	t＝0.944	t＝7.226	t＝4.872	Z＝5.121
P值	?	0.061	0.802	<0.001	<0.001	<0.001
组别	例数	移植胚胎数(个，±s)	生化妊娠[% (n/n′)]	临床妊娠[% (n/n′)]	自然流产[% (n/n′)]	异位妊娠[% (n/n′)]
长方案组	36	2.3±0.5	55.6(20/36)	41.7(15/36)	20.2(3/15)	13.3(2/15)
超长方案组	39	2.3±0.6	43.6(17/39)	41.0(16/39)	25.0(4/16)	0(0/16)
检验值	?	t＝0.739	χ²＝1.072	χ²＝0.003	χ²＝0.000^a	—
P值	?	0.110	0.300	0.955	1.000	0.226

表3 年龄≥35岁的2组受试者一般临床资料及妊娠结局比较

组别	例数	年龄(岁，±s)	BMI(kg/m²，±s)	Gn使用剂量(g，±s)	Gn使用时间(d，±s)	获卵数[个，M(P₂₅～P₇₅)]
长方案组	36	37.3±2.3	23.7±2.2	2 701.7±987.3	9.7±1.8	10(8～15)
超长方案组	39	38.6±2.1	23.5±2.8	3 991.7±944.5	12.4±2.9	7(4～9)
检验值	?	t＝1.924	t＝0.944	t＝7.226	t＝4.872	Z＝5.121
P值	?	0.061	0.802	<0.001	<0.001	<0.001
组别	例数	移植胚胎数(个，±s)	生化妊娠[% (n/n′)]	临床妊娠[% (n/n′)]	自然流产[% (n/n′)]	异位妊娠[% (n/n′)]
长方案组	36	2.3±0.5	55.6(20/36)	41.7(15/36)	20.2(3/15)	13.3(2/15)
超长方案组	39	2.3±0.6	43.6(17/39)	41.0(16/39)	25.0(4/16)	0(0/16)
检验值	?	t＝0.739	χ²＝1.072	χ²＝0.003	χ²＝0.000^a	—
P值	?	0.110	0.300	0.955	1.000	0.226

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