Value of follicular output rate in predicting ovarian response and pregnancy outcome of infertile patients

doi:10.3877/cma.j.issn.1673-5250.2018.06.013

Objective

To investigate clinical values of follicular output rate (FORT) in predicting ovarian response and pregnancy outcome of infertile patients with in vitro fertilization and embryo transfer (IVF-ET).

Methods

From January 1, 2010 to December 31, 2014, a total of 768 infertile patients who were treated with IVF-ET in Reproductive Medicine Center of Zhongnan Hospital of Wuhan University were collected as research subjects. In this study, FORT was the ratio of the number of preovulatory follicles (PFC) with a diameter of 3 to 8 mm and the antral follicle count (AFC) of 14 to 22 mm on the day of human chorionic gonadotropin (hCG) injection. According to FORT value, they were divided into 3 groups, low FORT value group (n=255, FORT value was lower than the 33rd percentile of the FORT value of all subjects, i. e. FORT value <0.36), middle FORT value group (n=277, FORT value was in the 33th to 67th percentile of the FORT value of all subjects, i. e. FORT value was 0.36 to 0.67), and high FORT value group (n=236, FORT value was higher than the 67th percentile of the FORT value of all subjects, i. e. FORT value >0.67). The general clinical data and related indicators of controlled ovulation hyperstimulation of 3 groups were collected by retrospective analysis. The age, body mass index (BMI), basal follicle stimulating hormone (FSH), AFC, total amount of gonadotropin (Gn), Gn use days, estradiol level on the day of hCG injection, PFC, number of ovums obtained, number of MⅡ ovums and number of embryos transferred were analyzed by one-way ANOVA analysis. The least significant difference(LSD) method was used to analyze AFC among three groups in further pairwise comparison. The duration of infertility, basic luteinizing hormone (LH) and basal estradiol levels were analyzed by Kruskal-Wallis H rank sum test. Chi-square test was used to analyze the ratio of different causes of infertility, high-quality embryos rate, embryo implantation rate, clinical pregnancy rate and live birth rate. Pearson correlation analysis was used to analyze the correlation between FORT and number of ovums obtained, number of available embryos, number of high quality embryos, age, basal FSH level and basal estradiol level, respectively. Influencing factors of clinical pregnancy rate in infertile patients were analyzed by multivariate unconditional logistic regression analysis. The procedures followed in this study were approved by the Ethics Committee of Zhongnan Hospital of Wuhan University (Approval Number: 2017109).

Results

①There were no significant differences among three groups in age, BMI, infertile duration, ratio of causes of infertility and other general clinical data (P>0.05). ② There were no significant differences in basal FSH, basal LH and basal estradiol levels among three groups (P>0.05). The number of AFC of low, middle and high FORT value group groups were 15.2±3.2, 14.3±3.7 and 13.8±3.5, respectively, and the difference was statistically significant (F=56.547, P<0.001). ③There were significant differences in estradiol level on the day of hCG injection, PFC, number of ovums obtained, number of MⅡ ovums, number of available embryos, double pronucleus fertilization rate, high quality embryo rate, embryo implantation rate, clinical pregnancy rate and live birth rate among three groups (F=64.974, 215.869, 26.344, 22.904, H=59.625, χ²=32.985, 16.532, 21.324, 14.319, 12.644; all P<0.001). However, there were no significant differences in total amount of Gn, Gn use days, and number of embryos transferred among three groups (P>0.05). ④Among all the infertile patients in this study, FORT had positive correlation with the number of ovums obtained (r=0.286, P<0.001), number of available embryos (r=0.327, P<0.001) and number of high quality embryos (r=0.252, P<0.001), but FORT had no correlation with age (r=0.021, P=0.063), basal FSH level (r=—0.019, P=0.169), basal estradiol level (r=0.023, P=0.088). ⑤ The results of multivariate unconditional logistic regression analysis on influencing factors of clinical pregnancy rate of infertile patients showed that FORT was the independent influencing factor on the clinical pregnancy rate of infertile patients (OR=1.023, 95%CI: 1.003-1.043, P=0.027).

Conclusions

FORT can be used as an effective index to predict ovarian antral follicles′ response to FSH and pregnancy outcome of infertile patients. However, because this study is just a retrospective study, the value of FORT in predicting ovarian response and pregnancy outcome in infertile patients remains to be confirmed by large, multicenter, prospective studies.

Key words: Fertilization in vitro, Embryo transfer, Follicular output rate, Ovarian response, Controlled ovarian hyperstimulation, Pregnancy outcome, Antral follicle count, Preovulatory follicle, Infertility, female

表1 3组不孕患者一般临床资料比较

组别	例数	年龄(岁，±s)	BMI(kg/m²，±s)	不孕年限[年，M(P₂₅～P₇₅)]	不孕原因[例数(%)]
组别	例数	年龄(岁，±s)	BMI(kg/m²，±s)	不孕年限[年，M(P₂₅～P₇₅)]	输卵管及子宫因素	排卵障碍	男方因素	不明原因
低FORT值组	255	30.8±4.4	21.8±3.0	4(2～6)	164(64.3)	10(3.9)	75(29.4)	6(2.4)
中FORT值组	277	30.5±4.3	22.0±3.4	4(2～6)	172(62.1)	6(2.2)	88(31.8)	11(4.0)
高FORT值组	236	30.4±4.4	21.9±3.0	3(2～6)	151(64.0)	9(3.8)	72(30.5)	4(1.7)
检验值	?	F＝1.289	F＝0.417	H＝3.273	χ²＝4.464
P值	?	0.428	0.709	0.195	0.365

表1 3组不孕患者一般临床资料比较

组别	例数	年龄(岁，±s)	BMI(kg/m²，±s)	不孕年限[年，M(P₂₅～P₇₅)]	不孕原因[例数(%)]
组别	例数	年龄(岁，±s)	BMI(kg/m²，±s)	不孕年限[年，M(P₂₅～P₇₅)]	输卵管及子宫因素	排卵障碍	男方因素	不明原因
低FORT值组	255	30.8±4.4	21.8±3.0	4(2～6)	164(64.3)	10(3.9)	75(29.4)	6(2.4)
中FORT值组	277	30.5±4.3	22.0±3.4	4(2～6)	172(62.1)	6(2.2)	88(31.8)	11(4.0)
高FORT值组	236	30.4±4.4	21.9±3.0	3(2～6)	151(64.0)	9(3.8)	72(30.5)	4(1.7)
检验值	?	F＝1.289	F＝0.417	H＝3.273	χ²＝4.464
P值	?	0.428	0.709	0.195	0.365

表2 3组不孕患者激素水平及窦卵泡计数比较

组别	例数	基础FSH水平(mIU/mL，±s)	基础LH水平[mIU/mL，M(P₂₅～P₇₅)]	基础雌二醇水平[pg/mL，M(P₂₅～P₇₅)]	AFC(个，±s)
低FORT值组	255	7.9±2.2	4.2(3.1～5.5)	39(27～52)	15.2±3.2
中FORT值组	277	7.6±2.3	3.8(2.8～5.3)	39(23～55)	14.3±3.7
高FORT值组	236	7.7±2.1	4.2(3.4～5.6)	36(26～49)	13.8±3.5
检验值		F＝1.973	H＝8.056	H＝1.815	F＝56.547
P值	?	0.139	0.847	0.404	<0.001

表2 3组不孕患者激素水平及窦卵泡计数比较

组别	例数	基础FSH水平(mIU/mL，±s)	基础LH水平[mIU/mL，M(P₂₅～P₇₅)]	基础雌二醇水平[pg/mL，M(P₂₅～P₇₅)]	AFC(个，±s)
低FORT值组	255	7.9±2.2	4.2(3.1～5.5)	39(27～52)	15.2±3.2
中FORT值组	277	7.6±2.3	3.8(2.8～5.3)	39(23～55)	14.3±3.7
高FORT值组	236	7.7±2.1	4.2(3.4～5.6)	36(26～49)	13.8±3.5
检验值		F＝1.973	H＝8.056	H＝1.815	F＝56.547
P值	?	0.139	0.847	0.404	<0.001

表3 3组不孕患者促排卵指标、实验室相关结果及妊娠结局比较

组别	例数	Gn总量(U，±s)	Gn使用时间(d，±s)	注射hCG当日雌二醇水平(pg/mL，±s)	PFC(个，±s)	获卵数(个，±s)	MⅡ卵子数(个，±s)	可利用胚胎数(个，±s)
低FORT值组	255	31.8±12.0	9.6±1.6	2 830.1±495.9	6.3±1.9	7.4±3.5	6.1±2.3	4(2～7)
中FORT值组	277	30.5±10.8	9.7±1.5	4 631.7±981.8	9.1±2.8	10.2±3.8	9.3±2.5	6(4～8)
高FORT值组	236	30.3±10.1	9.9±1.4	5 824.4±1 234.7	10.3±2.4	11.5±3.6	10.4±2.7	7(4～11)
检验值	?	F＝1.504	F＝1.891	F＝64.974	F＝215.869	F＝26.344	F＝22.904	H＝59.625
P值	?	0.205	0.367	<0.001	<0.001	<0.001	<0.001	<0.001
组别	例数	移植胚胎数(个，±s)	双原核受精率[%(n/n′)]	优质胚胎率[%(n/n′)]	胚胎种植率[%(n/n′)]	临床妊娠率[%(n/n′)]	活产率[例数(%)]
低FORT值组	255	1.8±0.5	61.6(1 328/2 156)	58.2(778/1 337)	22.0(121/549)	33.7(86/255)	76(29.8)
中FORT值组	277	1.9±0.3	64.6(1 909/2 955)	65.4(1 069/1 635)	24.7(140/566)	40.1(111/277)	104(37.5)
高FORT值组	236	1.9±0.4	66.4(1 770/2 665)	67.3(1 272/1 890)	32.6(166/509)	50.4(119/236)	107(45.3)
检验值	?	F＝0.465	χ²＝32.985	χ²＝16.532	χ²＝21.324	χ²＝14.319	χ²＝12.644
P值	?	0.204	<0.001	<0.001	<0.001	<0.001	<0.001

表3 3组不孕患者促排卵指标、实验室相关结果及妊娠结局比较

组别	例数	Gn总量(U，±s)	Gn使用时间(d，±s)	注射hCG当日雌二醇水平(pg/mL，±s)	PFC(个，±s)	获卵数(个，±s)	MⅡ卵子数(个，±s)	可利用胚胎数(个，±s)
低FORT值组	255	31.8±12.0	9.6±1.6	2 830.1±495.9	6.3±1.9	7.4±3.5	6.1±2.3	4(2～7)
中FORT值组	277	30.5±10.8	9.7±1.5	4 631.7±981.8	9.1±2.8	10.2±3.8	9.3±2.5	6(4～8)
高FORT值组	236	30.3±10.1	9.9±1.4	5 824.4±1 234.7	10.3±2.4	11.5±3.6	10.4±2.7	7(4～11)
检验值	?	F＝1.504	F＝1.891	F＝64.974	F＝215.869	F＝26.344	F＝22.904	H＝59.625
P值	?	0.205	0.367	<0.001	<0.001	<0.001	<0.001	<0.001
组别	例数	移植胚胎数(个，±s)	双原核受精率[%(n/n′)]	优质胚胎率[%(n/n′)]	胚胎种植率[%(n/n′)]	临床妊娠率[%(n/n′)]	活产率[例数(%)]
低FORT值组	255	1.8±0.5	61.6(1 328/2 156)	58.2(778/1 337)	22.0(121/549)	33.7(86/255)	76(29.8)
中FORT值组	277	1.9±0.3	64.6(1 909/2 955)	65.4(1 069/1 635)	24.7(140/566)	40.1(111/277)	104(37.5)
高FORT值组	236	1.9±0.4	66.4(1 770/2 665)	67.3(1 272/1 890)	32.6(166/509)	50.4(119/236)	107(45.3)
检验值	?	F＝0.465	χ²＝32.985	χ²＝16.532	χ²＝21.324	χ²＝14.319	χ²＝12.644
P值	?	0.204	<0.001	<0.001	<0.001	<0.001	<0.001

表4 不孕患者临床妊娠率影响因素的多因素非条件logistic回归分析结果

影响因素	B	SE	Wald值	P值	OR值	OR值95%CI
年龄	0.007	0.024	0.567	0.754	1.007	0.962～1.055
可利用胚胎数	0.032	0.063	0.183	0.611	1.033	0.912～1.169
优质胚胎数	－0.027	0.074	0.114	0.721	0.974	0.842～1.126
优质胚胎率	0.758	0.484	0.451	0.118	2.134	0.826～5.515
双原核受精率	1.108	0.860	0.059	0.198	3.029	0.561～16.350
AFC	－0.064	0.051	0.153	0.211	0.940	0.851～1.038
PFC	－0.158	0.093	7.149	0.088	0.843	0.703～1.010
FORT	0.022	0.010	8.735	0.027	1.023	1.003～1.043

表4 不孕患者临床妊娠率影响因素的多因素非条件logistic回归分析结果

影响因素	B	SE	Wald值	P值	OR值	OR值95%CI
年龄	0.007	0.024	0.567	0.754	1.007	0.962～1.055
可利用胚胎数	0.032	0.063	0.183	0.611	1.033	0.912～1.169
优质胚胎数	－0.027	0.074	0.114	0.721	0.974	0.842～1.126
优质胚胎率	0.758	0.484	0.451	0.118	2.134	0.826～5.515
双原核受精率	1.108	0.860	0.059	0.198	3.029	0.561～16.350
AFC	－0.064	0.051	0.153	0.211	0.940	0.851～1.038
PFC	－0.158	0.093	7.149	0.088	0.843	0.703～1.010
FORT	0.022	0.010	8.735	0.027	1.023	1.003～1.043

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