Is anti-müllerian hormone a determinant in unexplained recurrent miscarriage? Methods 1:2 case-control study with age matching, ancillary to the incident case-control study DÉFI, which was carried out from February, 2003 to October, 2008 in the Brest regional university hospital center : • 188 cases with a history of at least 3 UREM compared to • 376 controls from the general population with no history of miscarriage and having already given birth to a living child. Evaluation of OR was carried out by simultaneous AMH measurement in cases and controls (Immunotech*, Beckman-Coulter France). Results The two studied populations are in all points comparable apart from parity. When patients have already given birth: there is no significant difference in delivery term and weight at birth. ? Distribution of AMH levels according to the age of the total study population Dr Estelle LECLERCQ a , Dr Elisabeth PASQUIER b , Dr Marie-Thérèse LE MARTELOT a , Dr Sylvie ROCHE a , Dr Caroline BOHEC c , Pr Michel COLLET a a Service de gynécologie obstétrique et médecine de la reproduction CHRU Brest, b CIC CHRU Brest, c CH Pau [email protected]; [email protected] Discussion Limitations: • Blood sampling was randomly made during mentrual cycle. However, the distribution was similar between cases and controls. In addition, the literature is in favor of a low impact of the AMH intra cyclical variation; • Absence of ultrasound measurement of RO. Strengths: • Comparable descriptive characteristics of populations; • Simultaneous measurement of AMH in cases and controls; • Single assay kit. AMH is a marker of follicular activity pool and becomes a more reliable marker of the OR from the age of 25 years according to the latest publications. This explains why a lower AMH level is found in cases than in controls only after 25 years. However, the average and median measurements of these patients remained in the range of near-normal values for the age. It is therefore difficult to associate the miscarriages of these women with a single OR decline. PHRC régional 2002, bourse FARO It is now recognized that the secretion of AMH varies throughout the sexual life and the rate actually decreases from 25 years. This was showed by Kelsey in 2011 (curve attached). Thus, we analyzed our data according to these results. Histogram of the AMH blood levels Median = 3 Mean = 4.02 SD = 3.35 Median = 2.9 Mean = 3.61 SD = 2.96 CASES CONTROLS CASES N = 188 CONTROLS N = 376 Mean (M) Median +/- SD [Min-Max] M Median +/- SD [Min-Max] p Age 32.88 32.9 ± 5 [18.7 – 44.8] 32.3 32.99 ± 4.62 [18.5 - 44.7] NS Tobacco year packages 4.77 2.5 ± 6.073 [0 - 21] 4.41 1.3 ± 6.084 [0 - 38] NS BMI 23.0 21.8 ± 4.15 [17 - 44] 22.8 21.8 ± 3.30 [13 - 53] NS Menstrual cycle (days) 28.53 28 ± 2.98 [21- 45] 28.85 28 ± 3.3 [20 - 60] NS P = NS This is the FIRST case-control study with large samples (564), suggesting an association between the OR decrease and UREM in females over 25 years, not from an infertility consultation. It is possible that this OR decline is an early marker of deterioration of oocyte quality regardless of age. CASES N = 176 CONTROLS N = 358 M Median +/- SD [Min-Max] M Median +/- SD [Min-Max] p AMH ng/ml 3.51 2.8 ± 3 [0.1 – 18.8] 4.11 3.25 ± 3.4 [0.1 – 21.5] 0.046 Age 33.5 33.3 ± 4.4 [25 - 44.8] 33.5 33.3 ± 4.07 [25 – 44.7] 0.9 p AMH BMI Mother’s age 0.032 AMH Menstrual cycle Mother’s age 0.027 AMH Tobacco Mother’s age 0.039 AMH Mother’s age Menstrual cycle BMI Tobacco 0.031 R² linéaire = 0,0058 R² linéaire = 0,116 CASES N = 12 CONTROLS N = 18 M Median +/- SD [Min-Max] M Median +/- SD [Min-Max] p AMH ng/ml 5 5.7 ± 2.2 [1.4 – 7.8] 2.1 2.3 ± 0.9 [0.9 – 4.3] 0.011 Age 23 23,7 ± 2 [18.7- 24.9] 22.7 23.3 ± 2.02 [18 – 24.9] NS After age adjustment, the significant difference between cases and controls is the reverse of what is observed after 25 years but on a small population sample. In ≥ 25 year old females AMH levels si gnificantly lower in cases than in controls even after adjusting the variables stated above. AMH levels do not significantly differ between cases and controls even after adjusting mother's age, tobacco consumption, cycles and body mass index Introduction Maternal age and abnormalities of ovarian reserve (OR) is often considered among the etiologies of unexplained recurrent early miscarriage (UREM). Studies aiming at finding a relationship between UREM and abnormalities of OR show very discordant results due to major biases in most of them. Our case-control study aim to explore the role of OR in UREM by measuring the anti-müllerian hormone (AMH) serum levels. Distribution of AMH levels according to age (age ≥ 25 years) Comparison of cases and controls (age ≥ 25) by logistical multiple regression, step by step