Exogenous hCG activity, but not endogenous LH activity, is positively associated with live birth rates in anovulatory infertility

Figures & data

Table I. Demographics and baseline characteristics.

Variables	rFSH (n = 79)	HP-hMG (n = 76)	All (n = 155)
Female age (years)	29.4 ± 3.8	29.4 ± 4.0	29.4 ± 3.9
BMI (kg/m^2)	25.2 ± 4.3	25.8 ± 5.1	25.5 ± 4.7
Waist-to-hip ratio	0.82 ± 0.09	0.83 ± 0.12	0.83 ± 0.10
Primary infertility (%)	65	55	60
Duration of infertility (years)	2.9 ± 1.9	2.9 ± 1.8	2.9 ± 1.9
Previous ovulation induction cycles	4.8 ± 2.5	4.7 ± 2.5	4.7 ± 2.5
Clomiphene citrate non-responders
Failure to ovulate* (%)	38	53	45
Failure to conceive^† (%)	62	47	55
Mean ovarian volume (cm^3)	8.2 ± 4.3	8.1 ± 4.1	8.1 ± 4.2
Antral follicle count	22 ± 14	23 ± 17	23 ± 16
LH (IU/l)	7.6 ± 4.5	7.2 ± 4.8	7.4 ± 4.6
LH > 10 IU/l (%)	23	22	23
FSH (IU/l)	5.4 ± 2.7	5.1 ± 1.3	5.2 ± 2.1
LH:FSH ratio	1.6 ± 1.2	1.5 ± 1.1	1.5 ± 1.1
Prolactin (μg/l)	12 ± 7	13 ± 15	12 ± 11
Androstenedione (nmol/l)	7.2 ± 3.5	8.0 ± 5.0	7.6 ± 4.3
Total testosterone (nmol/l)	1.6 ± 0.6	1.8 ± 0.7	1.7 ± 0.6
SHBG (nmol/l)	62 ± 43	57 ± 38	59 ± 40
Free androgen index	4.1 ± 3.3	4.9 ± 4.6	4.5 ± 4.0
Estradiol (pmol/l)	158 ± 63	156 ± 91	157 ± 77
Glucose (mmol/l)	5.1 ± 0.7	5.2 ± 0.7	5.1 ± 0.7
Insulin (pmol/l)	98 ± 101	109 ± 117	103 ± 109
Insulin:glucose ratio	2.8 ± 2.6	2.9 ± 2.7	2.8 ± 2.7

Variables expressed as mean ± SD, or %.

*At least 100 mg/day for at least 5 days.

^†After three cycles.

Table II. Serum concentrations of LH at baseline, and of LH and hCG at end of gonadotrophin stimulation.

LH activity	rFSH			HP-hMG
	No live birth (n = 63)	Live birth (n = 16)	p	No live birth (n = 63)	Live birth (n = 13)	p
Baseline
Endogenous LH (IU/l)	7.56 ± 4.42	8.00 ± 4.93	0.454	6.97 ± 4.04	8.54 ± 7.63	0.287
End of stimulation
Endogenous LH (IU/l)	14.5 ± 17.8*	9.41 ± 6.54	0.289	11.2 ± 9.91*	9.45 ± 9.11	0.666
Exogenous hCG (IU/l)	–	–	–	0.98 ± 0.35*	1.27 ± 0.39	0.010

The data are expressed as mean ± SD.

*57 women attended the end-of-stimulation visit.

Table III. Univariate logistic regression analysis of the association between live birth and clinical, sonographic and endocrinological parameters prior to start of ovarian stimulation and at end of stimulation.

Variables	rFSH (n = 79)			HP-hMG (n = 76)
	OR	95% CI	p-value	OR	95% CI	p-value
Baseline
Female age (years)	0.89	0.76–1.04	0.139	0.94	0.80–1.09	0.395
BMI (kg/m^2)	1.07	0.94–1.21	0.318	0.96	0.85–1.08	0.508
Waist-to-hip ratio	1.02	0.55–1.88	0.944	1.32	0.84–2.05	0.226
Menstrual cycle pattern*	3.75	0.78–18.03	0.098	6.00	0.73–49.3	0.095
Duration of infertility (years)	0.90	0.64–1.27	0.551	0.70	0.41–1.19	0.188
Failure to ovulate on cc	0.54	0.18–1.63	0.271	0.65	0.19–2.19	0.482
Failure to conceive on cc	1.86	0.62–5.65	0.271	1.55	0.46–5.26	0.482
Antral follicle count	1.02	0.99–1.06	0.192	1.03	1.00–1.07	0.070
Mean ovarian volume (cm^3)	1.02	0.90–1.15	0.761	0.99	0.85–1.16	0.948
LH (IU/l)	1.02	0.91–1.15	0.723	1.06	0.95–1.19	0.289
LH (≤10 IU/l vs. >10 IU/l)	0.59	0.17–2.02	0.397	0.48	0.12–1.87	0.289
FSH (IU/l)	0.58	0.38–0.90	0.015	1.08	0.69–1.70	0.733
Estradiol (pmol/l)	1.00	0.99–1.01	0.993	0.99	0.97–1.00	0.041
Prolactin (μg/l)	0.97	0.88–1.07	0.516	0.92	0.80–1.05	0.207
Androstenedione (nmol/l)	1.07	0.92–1.25	0.357	0.94	0.80–1.10	0.443
Total testosterone (nmol/l)	1.96	0.77–4.95	0.155	0.56	0.20–1.53	0.255
SHBG (nmol/l)	1.00	0.99–1.01	0.863	1.01	0.99–1.02	0.481
Free androgen index	1.14	0.98–1.33	0.090	0.86	0.69–1.09	0.208
Glucose (mmol/l)	0.67	0.28–1.60	0.361	0.60	0.24–1.52	0.282
Insulin (pmol/l)	1.00	1.00–1.01	0.811	0.99	0.98–1.00	0.205
Insulin: glucose ratio	1.05	0.87–1.27	0.629	0.77	0.50–1.16	0.210
End of stimulation
Follicular development (multiple vs. mono)	1.81	0.58–5.63	0.306	0.63	0.16–2.54	0.516
Duration of gonadotrophin (days)	1.04	0.93–1.17	0.507	1.02	0.93–1.12	0.675
Total dose of gonadotrophin (IU)	1.00	1.00–1.00	0.641	1.00	1.00–1.00	0.735
Endometrial thickness (mm)	1.25	0.98–1.61	0.078	0.90	0.67–1.20	0.461
Estradiol (pmol/l)	1.00	1.00–1.00	0.349	1.00	1.00–1.00	0.442
FSH (IU/l)	0.80	0.59–1.08	0.147	1.18	0.87–1.61	0.282
hCG (IU/l)	–	–	–	1.25	1.04–1.50	0.015
LH (IU/l)	0.97	0.92–1.02	0.273	0.98	0.91–1.05	0.568
LH (≤10 IU/l vs. >10 IU/l)	0.87	0.28–2.67	0.807	1.01	0.29–3.47	0.993

OR, odds ratio; CI, confidence interval.

*Amenorrhea and oligomenorrhea vs. anovulatory cycles.

Table IV. Demographics, baseline and stimulation characteristics by hCG concentration at end of HP-hMG stimulation.

Variables	hCG (IU/l)			p-value*
	≤P25	>P25–P75	>P75
	n = 18	n = 35	n = 17
Baseline
Female age (years)	30.1 ± 3.6	29.3 ± 3.9	28.6 ± 4.7	0.561
BMI (kg/m^2)	27.8 ± 4.1	26.0 ± 5.5	24.3 ± 5.3	0.099
Waist-to-hip ratio	0.83 ± 0.06	0.83 ± 0.12	0.86 ± 0.17	0.759
Duration of infertility (years)	3.0 ± 1.5	2.7 ± 2.1	2.7 ± 1.3	0.432
Primary infertility	39%	61%	53%	0.251
Antral follicle count	17 ± 11	27 ± 15	21 ± 24	0.028
Mean ovarian volume (cm^3)	8.2 ± 3.5	8.4 ± 4.2	7.3 ± 4.5	0.468
LH (IU/l)	5.3 ± 2.0	6.9 ± 4.0	9.1 ± 7.4	0.452
FSH (IU/l)	5.4 ± 1.4	4.7 ± 1.3	5.4 ± 1.3	0.174
Estradiol (pmol/l)	132 ± 40	176 ± 114	151 ± 78	0.237
Progesterone (nmol/l)	3.1 ± 1.3	4.7 ± 10.0	2.9 ± 2.3	0.545
Prolactin (μg/l)	16.6 ± 27.3	11.9 ± 6.6	10.5 ± 6.3	0.533
Androstenedione (nmol/l)	7.7 ± 3.7	7.9 ± 4.7	9.2 ± 7.2	0.974
Total testosterone (nmol/l)	1.7 ± 0.5	1.8 ± 0.6	1.8 ± 1.0	0.583
SHBG (nmol/l)	43.3 ± 25.8	60.2 ± 38.1	61.5 ± 47.0	0.200
Glucose (mmol/l)	5.3 ± 0.7	5.2 ± 0.8	5.0 ± 0.6	0.714
Insulin (pmol/l)	135 ± 132	120 ± 136	74 ± 57	0.099
Insulin:glucose ratio	3.6 ± 3.0	3.2 ± 3.2	2.1 ± 1.5	0.133
End of stimulation
Subjects with monofollicular development (%)	67	69	59	0.466
Number of follicles ≥12 mm	2 ± 1	2 ± 2	2 ± 2	0.780
Duration of gonadotrophin (days)	9.9 ± 2.6	13.6 ± 5.3	19.9 ± 7.7	<0.001
Total dose of gonadotrophin (IU)	746 ± 198	1225 ± 669	2014 ± 1102	<0.001
Last gonadotrophin dose (IU)	75 ± 0	97.5 ± 27.6	121.3 ± 33.9	<0.001
Endometrial thickness (mm)	9.6 ± 1.8	9.5 ± 2.2	9.5 ± 2.6	0.964
Estradiol (pmol/l)	831 ± 247	1455 ± 1524	1644 ± 1552	0.017
FSH (IU/l)	8.4 ± 2.5	9.1 ± 1.2	11.6 ± 0.90	<0.001
hCG (IU/l)	0.6 ± 0.1	1.0 ± 0.2	1.5 ± 0.2	<0.001
LH (IU/l)	14.8 ± 10.9	8.8 ± 6.6	10.9 ± 12.6	0.053
Subjects with LH > 10 IU/l (%)	56	29	41	0.156

Variables expressed as mean ± SD, or %.

*Kruskal–Wallis test for continuous and chi-square test for categorical data.

Figure 1.  Live birth rate according to the ≤P25, >P25–P75 and >P75 percentiles of serum hCG concentrations at end of HP-hMG stimulation. Seventy women attended the end-of-stimulation visit.