The rate of high ovarian response in women identified at risk by a high serum AMH level is influenced by the type of gonadotropin

Figures & data

Table 1. Demographics and baseline, end-of-stimulation, oocyte and embryo data of the women grouped by the AMH concentration at start of stimulation (quartiles 1–3 versus quartile 4).

	Long GnRH agonist protocol			GnRH antagonist protocol
	AMH Q1-Q3	AMH Q4		AMH Q1-Q3	AMH Q4
Variable	≤75th (≤5.2 ng/ml) (n = 468)	>75th (>5.2 ng/ml) (n = 155)	p Value*	≤75th (≤5.2 ng/ml) (n = 561)	>75th (>5.2 ng/ml) (n = 188)	p Value*
Clinical characteristics
Age (years)	31 (29, 34)	30 (28, 32)	<0.001	31 (29, 33)	30 (28, 32)	<0.001
BMI (kg/m^2)	21.9 (20.3, 24.0)	21.3 (20.1, 23.5)	0.113	21.9 (20.3, 23.8)	21.8 (20.5, 23.5)	0.868
Cycle length (days)	28 (28, 29)	29 (28, 30)	<0.001	28 (28, 29)	29 (28, 30)	<0.001
First treatment cycle, n (%)	327 (70%)	104 (67%)	0.517	427 (76%)	134 (71%)	0.186
Day 1 (before start of stimulation)
Ovarian volume (ml)	8.5 (6.0, 11.8)	10.4 (7.7, 14.3)	<0.001	10.6 (8.0, 14.2)	13.2 (9.6, 16.8)	<0.001
AFC (n)	10 (7, 14)	11 (8, 18)	<0.001	14 (11, 17)	18 (15, 22)	<0.001
AMH (ng/ml)	3.0 (2.1, 4.0)	7.0 (5.8, 8.5)	<0.001	2.4 (1.4, 3.6)	6.9 (6.0, 8.7)	<0.001
FSH (IU/l)	3.8 (3.0, 4.9)	3.4 (2.7, 4.4)	0.003	7.2 (6.2, 8.5)	6.5 (5.7, 7.6)	<0.001
End-of-stimulation
Estradiol (nmol/l)	5.5 (4.0, 7.3)	8.5 (6.2, 13.0)	<0.001	5.7 (4.1, 8.2)	8.7 (6.3, 13.3)	<0.001
Progesterone (nmol/l)	2.6 (2.0, 3.4)	3.2 (2.4, 3.9)	<0.001	2.5 (1.9, 3.2)	2.9 (2.1, 3.8)	<0.001
Progesterone/estradiol ratio	0.46 (0.35, 0.63)	0.36 (0.24, 0.49)	<0.001	0.42 (0.30, 0.60)	0.32 (0.21, 0.44)	<0.001
Follicles ≥12 mm (n)	10 (8, 13)	15 (12, 19)	<0.001	10 (7, 13)	15 (11, 18)	<0.001
Endometrial thickness (mm)	11 (9, 12)	11 (10, 12)	0.079	10 (9, 12)	11 (10, 12)	0.039
Endometrial echogenicity pattern  (hypo, iso, hyper) (%)	39, 49, 13	34, 51, 15	0.544	40, 51, 9	36, 54, 10	0.668
Cycle cancellation for ovarian hyper-response, n (%)	2 (<1%)	7 (5%)	0.001	1 (<1%)	1 (<1%)	0.439
Early OHSS (moderate/severe), n (%)	1 (<1%)	7 (5%)	<0.001	4 (<1%)	8 (4%)	0.003
Intervention for ovarian  hyper-response, n (%)	2 (<1%)	11 (7%)	<0.001	16 (3%)	19 (10%)	<0.001
Oocyte retrieval
Women with oocyte retrieval, n (%)	446 (95%)	145 (94%)	0.392	537 (96%)	185 (98%)	0.088
Oocytes retrieved (n)	9 (6, 12)	14 (10, 18)	<0.001	8 (5, 11)	12 (9, 17)	<0.001
Women with ≥15 oocytes  retrieved, n (%)	76 (16%)	65 (42%)	<0.001	63 (11%)	76 (40%)	<0.001
Fertilisation and embryo data
Fertilisation rate (%)	60 (33, 75)	52 (29, 70)	0.091	60 (43, 75)	58 (42, 71)	0.193
Embryos on day 3 (n)	2 (1, 5)	3 (2, 6)	0.029
Women with top-quality embryo(s)  on day 3, n (%)†	199 (45%)	73 (50%)	0.229
Blastocysts on day 5 (n)				2 (1, 4)	3 (1, 6)	<0.001
Women with good-quality blastocyst(s)  on day 5, n (%)‡				266 (50%)	106 (57%)	0.068
Women with transfer, n (%)¶	397 (89%)	122 (84%)	0.119	462 (86%)	159 (86%)	0.976

Values are median (IQR) unless otherwise indicated.

*Wilcoxon test (continous data); Chi-Square test or Fisher's exact test (categorial data).

†Top-quality embryos were defined as 4–5 cells on day 2, ≥7 cells on day 3, equally-sized blastomeres and ≤20% fragmentation on day 3 and no multinucleation.

‡Good-quality blastocysts were defined as blastocysts with expansion and hatching score ≥4 and with inner cell mass and trophectoderm grades of A or B, using the definitions described by Gardner & Schoolcraft [23].

¶Among women with oocytes retrieved.

Table 2. Comparison of baseline, end-of-stimulation, oocyte and embryo characteristics between HP-hMG- and rFSH-treated women with potential for being high-responders by a high AMH at start of stimulation.

	Long GnRH agonist protocol			GnRH antagonist protocol
	AMH Q4: >75th (>5.2 ng/ml)			AMH Q4: >75th (>5.2 ng/ml)
Variable	HP-hMG (n = 76)	rFSH (n = 79)	p Value*	HP-hMG (n = 87)	rFSH (n = 101)	p Value*
Clinical characteristics
Age (years)	30 (28, 32)	30 (28, 32)	0.743	30 (28, 33)	30 (28, 31)	0.039
BMI (kg/m^2)	22.5 (20.7, 23.8)	20.8 (19.8, 22.8)	0.002	22.1 (21.0, 23.9)	21.6 (20.1, 23.0)	0.022
Cycle length (days)	29 (28, 30)	29 (28, 30)	0.682	29 (28, 30)	29 (28, 31)	0.382
First treatment cycle, n (%)	52 (68%)	52 (66%)	0.731	57(66%)	77 (76%)	0.105
Day 1 (before start of stimulation)
Ovarian volume (ml)	10.3 (7.9, 13.9)	10.5 (7.7, 14.8)	0.807	13.4 (9.1, 17.0)	13.0 (9.9, 16.7)	0.885
AFC (n)	12 (8, 20)	11 (8, 16)	0.486	18 (15, 22)	18 (15, 22)	0.934
AMH (ng/ml)	7.0 (5.9, 8.5)	7.0 (5.7, 8.4)	0.912	7.1 (6.2, 8.7)	6.8 (6.0, 8.3)	0.347
FSH (IU/l)	3.2 (2.6, 4.4)	3.6 (2.8, 4.4)	0.257	6.7 (5.6, 7.7)	6.4 (5.7, 7.5)	0.251
End-of-stimulation
Estradiol (nmol/l)	8.7 (6.4, 13.0)	8.4 (6.1, 12.8)	0.736	9.7 (6.8, 14.8)	7.8 (5.5, 12.4)	0.012
Progesterone (nmol/l)	2.7 (1.9, 3.6)	3.6 (2.8, 4.5)	<0.001	2.8 (2.1, 3.9)	3.0 (2.1, 3.8)	0.857
Progesterone/estradiol ratio	0.31 (0.21, 0.42)	0.43 (0.30, 0.52)	<0.001	0.26 (0.20, 0.41)	0.34 (0.24, 0.47)	0.011
Follicles ≥12 mm (n)	15 (12, 18)	16 (13, 19)	0.274	14 (11, 18)	16 (12, 19)	0.064
Endometrial thickness (mm)	11 (10, 12)	11 (10, 12)	0.522	11 (10, 12)	11 (10, 12)	0.478
Endometrial echogenicity pattern  (hypo, iso, hyper) (%)	44, 43, 13	24, 60, 17	0.033	31, 58, 11	41, 50, 9	0.386
Cycle cancellation for ovarian  hyper-response, n (%)	3 (4%)	4 (5%)	1.000	0 (0%)	1 (<1%)	–
Early OHSS (moderate/severe), n (%)	3 (4%)	4 (5%)	1.000	3 (3%)	5 (5%)	0.727
Intervention for ovarian  hyper-response, n (%)	5 (7%)	6 (8%)	1.000	7 (8%)	12 (12%)	0.470
Oocyte retrieval
Women with oocyte retrieval, n (%)	72 (95%)	73 (92%)	0.555	85 (98%)	100 (99%)	0.475
Oocytes retrieved (n)	12 (9, 16)	15 (11, 20)	0.007	12 (8, 15)	14 (10, 19)	0.033
Women with ≥15 oocytes retrieved, n (%)	25 (33%)	40 (51%)	0.025	27 (31%)	49 (49%)	0.015
Fertilisation and embryo data
Fertilisation rate (%)	50 (27, 73)	56 (35, 69)	0.826	57 (43, 69)	60 (41, 73)	0.663
Embryos on day 3 (n)	3 (2, 6)	4 (2, 6)	0.806
Women with top-quality embryo(s)  on day 3, n (%)†	38 (53%)	35 (48%)	0.561
Blastocysts on day 5 (n)				3 (1, 6)	3 (1, 6)	0.969
Women with good-quality blastocyst(s)  on day 5, n (%)‡				55 (65%)	51 (51%)	0.060
Women with transfer, n (%)¶	61 (85%)	61 (84%)	0.848	72 (85%)	87 (87%)	0.655

Values are median (IQR) unless otherwise indicated.

*Wilcoxon test (continous data); Chi-Square test or Fisher's exact test (categorial data).

†Top-quality embryos were defined as 4–5 cells on day 2, ≥7 cells on day 3, equally-sized blastomeres and ≤20% fragmentation on day 3 and no multinucleation.

‡Good-quality blastocysts were defined as blastocysts with expansion and hatching score ≥4 and with inner cell mass and trophectoderm grades of A or B, using the definitions described by Gardner & Schoolcraft [23].

¶Among women with oocytes retrieved.

Figure 1. (A) Occurrence of high ovarian response (≥15 oocytes retrieved) and (B) live birth rates (LBR) among the women classified as potential high responders by a high initial AMH level. Values within bars are n/total. p Values are based on the Chi-Square test.

Gardner DK, Schoolcraft WB. In-vitro culture of human blastocysts. In: Jansen R, Mortimer D, eds. Towards reproductive certainty: fertility and genetics beyond 1999. New York: The Parthenon Publishing Group; 1999:378–88

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