Association of HOMA-IR with Ovarian Sensitivity Index in Women Undergoing IVF/ICSI: A Retrospective Cohort Study

Figures & data

Figure 1 Flowchart of data collection process.

Abbreviations: AMH, anti-mullerian hormone; AFC, antral follicle count; BMI, body mass index; COH, controlled ovarian hyperstimulation; PGT, preimplantation genetic testing.

Table 1 The Clinical Parameters of the Study Population

Variables	Groups of Cycles According to the Quartiles of HOMA-IR				P-value^a
	Q1 (<1.63)	Q2 (1.63–2.33)	Q3 (2.33–3.43)	Q4 (≥ 3.43)
Number	1959	1959	1959	1959
Age (y)	31.09 ± 3.70	30.35 ± 3.84	30.10 ± 3.83	29.55 ± 4.05	<0.001
BMI (kg/m^2)	21.68 ± 2.45	22.64 ± 2.70	23.91 ± 3.10	26.47 ± 3.71	<0.001
Infertile duration (y)	3.47 ± 2.65	3.45 ± 2.56	3.59 ± 2.49	3.75 ± 2.62	<0.001
Primary infertility	1009 (51.51%)	1010 (51.56%)	1057 (53.96%)	1138 (58.09%)	<0.001
Infertility factor
PCOS	205 (10.46%)	288 (14.70%)	356 (18.17%)	592 (30.22%)	<0.001
Tubal factor	1030 (52.58%)	1053 (53.75%)	1003 (51.20%)	875 (44.67%)	<0.001
Male factor	476 (24.30%)	403 (20.57%)	420 (21.44%)	328 (16.74%)	<0.001
Endometriosis	96 (4.90%)	88 (4.49%)	69 (3.52%)	47 (2.40%)	<0.001
Uterine factor	25 (1.28%)	28 (1.43%)	17 (0.87%)	19 (0.97%)	0.311
Unexplained	127 (6.48%)	99 (5.05%)	94 (4.80%)	98 (5.00%)	0.073
AMH (ng/mL)	4.24 ± 3.10	4.55 ± 3.32	4.52 ± 3.21	4.94 ± 3.44	<0.001
AFC	14.67 ± 5.39	15.37 ± 5.70	15.94 ± 5.86	17.98 ± 6.19	<0.001
Base FSH (mIU/mL)	6.54 ± 1.81	6.30 ± 1.72	6.17 ± 1.64	5.85 ± 1.53	<0.001
FINS (μU/mL)	5.86 ± 1.47	9.35 ± 1.24	13.06 ± 1.82	23.32 ± 10.29	<0.001
FPG (mmol/l)	4.61 ± 0.42	4.78 ± 0.44	4.89 ± 0.45	5.10 ± 0.51	<0.001
HOMA-IR	1.20 ± 0.29	1.97 ± 0.21	2.82 ± 0.31	5.28 ± 2.48	<0.001
GnRH agonist protocol	1606 (81.98%)	1644 (83.92%)	1618 (82.59%)	1658 (84.64%)	0.102
Initial Gn dose (IU)	152.09 ± 49.52	149.45 ± 45.06	154.06 ± 46.71	157.62 ± 46.67	<0.001
Total Gn dose (IU)	2054.60 ± 804.41	2033.60 ± 797.21	2171.02 ± 884.05	2487.81 ± 1097.77	<0.001
Duration of Gn (d)	10.83 ± 2.36	10.80 ± 2.47	11.03 ± 2.73	11.88 ± 3.16	<0.001
Dominant follicle count	7.70 ± 3.81	7.66 ± 3.80	7.57 ± 4.00	7.68 ± 4.04	0.391
Endometrium thickness (mm)	11.11 ± 2.67	11.17 ± 2.68	11.19 ± 2.76	11.14 ± 2.70	0.912
Retrieved oocytes	12.53 ± 6.35	12.47 ± 6.61	12.16 ± 6.63	11.72 ± 6.53	<0.001
MII oocytes	10.46 ± 5.65	10.44 ± 5.90	10.19 ± 5.89	9.80 ± 5.86	<0.001
No. of embryos	6.20 ± 4.09	6.12 ± 4.18	6.04 ± 4.13	5.72 ± 4.07	<0.001
High-quality Embryos’ no.	3.41 ± 2.96	3.40 ± 3.03	3.40 ± 3.03	3.22 ± 2.99	0.029
OSI	7.20 ± 5.08	7.25 ± 5.38	6.64 ± 4.99	5.68 ± 4.38	<0.001

Note: ^aA two-tailed P-value < 0.05 was considered statistically significant.

Abbreviations: HOMA-IR, homeostatic model assessment of insulin resistance; BMI, body mass index; PCOS, polycystic ovary syndrome; AMH, anti-mullerian hormone; AFC, antral follicle count; FSH, follicle-stimulating hormone; FINS, fasting serum insulin; FPG, fasting plasma glucose; COH, controlled ovarian hyperstimulation; GnRH, gonadotropin-releasing hormone; Gn, gonadotropin; MII, metaphase II; OSI, ovarian sensitivity index.

Figure 2 Association between Ln HOMA-IR and Ln OSI. All adjusted for age, BMI, AMH, AFC, initial Gn dose, basal FSH, PCOS, COH protocol, infertility type. Red line represents the smooth curve fit between variables and the blue dotted curves represents the 95% of confidence interval.

Table 2 Association of Ln HOMA-IR with Ln OSI

Variables	Crude Model		Adjusted Model I^a		Adjusted Model II^b
Ln HOMA-IR	β (95% CI)	P-value	β (95% CI)	P-value	β (95% CI)	P-value
Continuous	−0.18 (−0.21, −0.16)	<0.0001	−0.09 (−0.12, −0.07)	<0.0001	−0.12 (−0.15, −0.09)	<0.0001
Categories
Quartile 1	0 (reference)		0 (reference)		0 (reference)
Quartile 2	−0.00 (−0.05, 0.04)	0.8995	−0.00 (−0.04, 0.04)	0.9460	−0.02 (−0.06, 0.02)	0.4078
Quartile 3	−0.10 (−0.15, −0.06)	<0.0001	−0.04 (−0.08, −0.00)	0.0358	−0.07 (−0.11, −0.03)	0.0007
Quartile 4	−0.27 (−0.31, −0.22)	<0.0001	−0.14 (−0.19, −0.10)	<0.0001	−0.18 (−0.22, −0.13)	<0.0001
P for trend	< 0.001		< 0.001		< 0.001

Notes: ^aAdjusted: age, BMI, AMH, AFC, initial Gn dose. ^bAdjusted: age, BMI, AMH, AFC, initial Gn dose, basal FSH, PCOS, COH protocol, infertility type.

Abbreviations: HOMA-IR, homeostatic model assessment of insulin resistance; Ln, log e transformation; β, regression coefficient; CI, confidence interval.

Table 3 Subgroup Analysis of the Relationship Between Ln HOMA-IR and Ln OSI

Subgroups	Subjects n (%)	Ln OSI		P-value for Interaction^b
		β (95% CI)	P-value^a
PCOS diagnosis				< 0.0001
PCOS	1441 (18.39%)	−0.18 (−0.26, −0.11)	< 0.0001
Non-PCOS	6395 (81.61%)	−0.10 (−0.13, −0.07)	< 0.0001
Tubal				0.6371
Tubal factor	3961 (50.55%)	−0.12 (−0.15, −0.08)	< 0.0001
Non-tubal factor	3875 (49.45%)	−0.13 (−0.17, −0.09)	< 0.0001
Male				0.5504
Male factor	1627 (20.76%)	−0.12 (−0.17, −0.06)	< 0.0001
Non-male factor	6209 (79.24%)	−0.12 (−0.16, −0.09)	< 0.0001
Age (y)				0.0798
< 35	6721 (85.77%)	−0.11 (−0.14, −0.08)	< 0.0001
≥ 35	1115 (14.23%)	−0.11 (−0.18, −0.04)	0.0032
BMI categories				< 0.0001
Normal weight	3833 (48.92%)	−0.06 (−0.10, −0.02)	0.0028
Overweight/obese	4003 (51.08%)	−0.23 (−0.27, −0.19)	< 0.0001
COH protocol				0.1935
GnRH agonist	6526 (83.28%)	−0.11 (−0.14, −0.08)	< 0.0001
GnRH antagonist	1310 (16.72%)	−0.15 (−0.22, −0.08)	< 0.0001

Notes: ^aMultivariate linear regression model: adjusted for age, BMI, AMH, AFC, initial Gn dose, basal FSH, PCOS status, COH protocol, infertility type. ^bLog likelihood ratio test to obtain a P-value for interaction in each subgroup.

Abbreviations: OSI, ovarian sensitivity index; BMI, body weight index; PCOS, polycystic ovary syndrome; COH, controlled ovarian hyperstimulation; GnRH, gonadotropin releasing hormone; Ln, log e transformation; β, regression coefficient; CI, confidence interval.