Arterial stiffness during controlled ovarian hyperstimulation and early pregnancy in women exposed to assisted reproduction

Figures & data

Table 1. Description of digital pulse wave analysis (DPA) variables and effects of physiological conditions.

DPA variables	Physiological interpretation	Conditions with high values	Conditions with low values
Cardiac ejection elasticity index (EEI)	Indicates left ventricular ejection capacity or compliance of central arteries	Large artery compliance, increased left ventricle ejection power	Large artery stiffness, atherosclerosis, decreased left ventricular ejection power
Dicrotic index (DI)	Indicates level of resistance in the peripheral circulation	Peripheral vasoconstriction	Peripheral vasodilatation
b/a	Indicates left ventricular ejection power or central artery compliance	Low central artery compliance, increased cardiovascular risk, atherosclerosis, increases by age	High compliance of central arteries; young age, athletic constitution
d/a	Reflects the intensity of the reflecting pulsewave from peripheral arteries, indicative of afterload	Young age, peripheral vasodilatation	A longer negative d peak develops by advancing age, atheriosclerosis, peripheral vasoconstriction
Aging index (AI)	AI = (b-c-d-e)/a, representing the global vascular stiffness, i.e. “vascular age”	Atheriosclerosis, increases by age	Young age, athletic constitution

Table 2. Demographic data of the study population.

	n = 68
	Median (range)	Mean (SD)
Age (years)	36 (26–44)	36 (5)
BMI (kg/m^2)	24 (18–35)	24 (4)
MAP (mmHg)	86 (68–134)	87 (10)
HR (bpm)	68 (42–87)	67 (10)
Parity (n)	1 (0–4)	–
FSH (IU)	1875 (822–5850)	2114 (989)
Follicles (n)	12 (2–28)	13 (6)
Oocytes (n)	10 (2–23)	10 (6)
OSI (n × 1000/IU)	4.8 (0.67–21.9)	5.9 (4.4)
Infertility factor	(n)
Male	22
Anovulation	6
Tubal	4
Endometriosis	4
Unidentified	32
IVF protocol	(n)
Agonist	11
Antagonist	57

SD, standard deviation; BMI, body mass index; MAP, mean arterial pressure; HR, heart rate; FSH, follicle stimulating hormone; OSI, ovarian sensitivity index (number of retrieved oocytes x 1000 divided by the cumulative FSH dose); IVF, in vitro fertilization.

Table 3. Associations at baseline measurements between DPA variables and maternal age, heart rate, logarithmic value of ovarian sensitivity index (logOSI) and grade of ovarian response at controlled ovarian hyperstimulation.

	Maternal age		Heart rate		LogOSI		Ovarian response
DPA variables	p^a	Tau^a	p^a	Tau^a	p^a	Tau^a	Poor Median (95% CI)	Normal Median (95% CI)	High Median (95% CI)	Poor vs. normal vs. high^c	Poor vs. normal^d	Normal vs. high^d	Poor vs. high^d
EEI	<0.0001^b	−0.40	0.045^b	0.17	0.0002^b	0.31	0.45 (0.30, 0.57)	0.60 (0.49, 0.69)	0.66 (0.56, 1.08)	0.013	0.044	0.12	0.001
b/a	0.0001^b	0.32	0.70	–	<0.0001^b	−0.34	−0.53 (−0.58, −0.39)	−0.60 (−0.65, −0.54)	−0.63 (−0.75, −0.60)	0.010	0.046	0.12	0.0002
DI	0.016^b	0.20	<0.0001^b	−0.51	0.34	–	0.80 (0.71, 0.90)	0.74 (0.68, 0.79)	0.74 (0.57, 0.85)	0.23	N/A	N/A	N/A
d/a	0.0003^b	−0.30	0.79	–	0.029^b	0.18	−0.18 (−0.31, −0.14)	−0.17 (−0.20, −0.14)	−0.13 (−0.20, −0.06)	0.12	N/A	N/A	N/A
AI	0.0002^b	0.31	0.68	–	0.0004^b	−0.29	−0.36 (−0.45, −0.04)	−0.54 (−0.61, −0.32)	−0.53 (−0.82, −0.43)	0.039	0.092	0.24	0.001

DPA, digital pulse wave analysis; EEI, cardiac ejection elasticity index; DI, dicrotic index; AI, aging index; OSI, ovarian sensitivity index; N/A, not applicable.

^a Statistics with Kendal tau rank correlation analysis.

^b p < 0.05 confirmed with simple linear regression analysis.

^c Statistics with Kruskal-Wallis test.

^d Statistics with Mann-Whitney U test.

Table 4. Hemodynamic effects of oocyte stimulation and pregnancy, compared with basal measurements before conception. For details, see text. Digital pulse wave analysis values are indices without quantitative measures.

	Basal n = 68	Stimulation n = 59			Embryo transfer n = 52			Pregnancy n = 19
	Median (95% CI)	Median (95% CI)	p	Effect^a	Median (95% CI)	p	Effect^a	Median (95% CI)	p	Effect^a
MAP (mmHg)	86 (84, 90)	84 (83, 86)	0.57	–	89 (85, 93)	0.007	Increase	85 (80, 90)	0.91	–
HR (bpm)	68 (65, 71)	72 (68, 75)	0.0003	Increase	75 (72, 79)	<0.0001	Increase	77 (73, 85)	0.003	Increase
EEI@75	0.630 (0.562, 0.691)	0.630 (0.535, 0.692)	0.66	–	0.533 (0.459, 0.688)	0.021	Increased large artery stiffness, decreased LV power	0.501 (0.477, 0.590)	0.75	–
b/a	−0.600 (−0.630, −0.550)	−0.585 (−0.650, −0.535)	0.86	–	−0.563 (−0.625, −0.490)	0.035	Increased large artery stiffness, decreased LV power	−0.530 (−0.600, −0.505)	0.15	–
DI@75	0.691 (0.652, 0.715)	0.692 (0.642, 0.702)	0.77	–	0.710 (0.676, 0.737)	0.003	Peripheral vasoconstriction	0.705 (0.592, 0.773)	0.16	–
d/a	−0.170 (−0.190, −0.145)	−0.165 (−0.190, −0.145)	0.65	–	−0.198 (−0.235, −0.140)	0.15	–	−0.195 (−0.265, −0.110)	0.30	–
AI	−0.455 (−0.565, −0.360)	−0.460 (−0.545, −0.375)	0.37	–	−0.355 (−0.480, −0.205)	0.008	Increased global arterial stiffness	−0.350 (−0.470, −0.230)	0.14	–

HR, heart rate; MAP, mean arterial pressure; EEI@75 ejection elasticity index corrected to heart rate 75 bpm; DI@75, dicrotic index corrected to heart rate 75 bpm; AI, aging index; LV, left cardiac ventricle.

^a Effect compared to basal measurement, statistics performed with Wilcoxon matched-pairs signed-rank test.

Figure 1. Boxplots showing cardiovascular changes after administration of follicle-stimulation hormone (Stim), at embryo transfer (ET) and in early pregnancy (Gravid) compared to baseline values (Basal). Gray boxes indicate significant changes (p < 0.05) compared with basal measurements, and star symbols denote values outside the panel boxes. HR, heart rate; MAP, mean arterial pressure; AI, aging index; EEI@75, cardiac ejection elasticity index adjusted to heart rate 75 bpm; DI@75, dicrotic index adjusted to heart rate 75 bpm.