is anti-müllerian hormone a determinant in unexplained ... · introduction maternal age and...
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Is anti-müllerian hormone a determinant in unexplained recurrent miscarriage?
Methods1:2 case-control study with age matching, ancillary tothe incident case-control study DÉFI, which was carriedout from February, 2003 to October, 2008 in the Brestregional university hospital center :
• 188 cases with a history of at least 3 UREMcompared to
• 376 controls from the general population with nohistory of miscarriage and having already given birth toa living child.
Evaluation of OR was carried out by simultaneous AMHmeasurement in cases and controls (Immunotech*,Beckman-Coulter France).
ResultsThe two studied populations are in all points comparableapart from parity. When patients have already givenbirth: there is no significant difference in delivery termand weight at birth.
?Distribution of AMH
levels according to the age of the total study
population
Dr Estelle LECLERCQa, Dr Elisabeth PASQUIERb, Dr Marie-Thérèse LE MARTELOTa, Dr Sylvie ROCHEa , Dr Caroline BOHECc, Pr Michel COLLETa
a Service de gynécologie obstétrique et médecine de la reproduction CHRU Brest, b CIC CHRU Brest, c CH [email protected]; [email protected]
DiscussionLimitations:
• Blood sampling was randomly made during mentrualcycle. However, the distribution was similar between casesand controls. In addition, the literature is in favor of a lowimpact of the AMH intra cyclical variation;• Absence of ultrasound measurement of RO.
Strengths:
• Comparable descriptive characteristics of populations;• Simultaneous measurement of AMH in cases andcontrols;• Single assay kit.
AMH is a marker of follicular activity pool and becomes amore reliable marker of the OR from the age of 25 yearsaccording to the latest publications. This explains why alower AMH level is found in cases than in controls onlyafter 25 years. However, the average and medianmeasurements of these patients remained in the range ofnear-normal values for the age. It is therefore difficult toassociate the miscarriages of these women with a singleOR decline.
PHRC régional 2002, bourse FARO
It is now recognized that the secretion of AMHvaries throughout the sexual life and the rateactually decreases from 25 years. This wasshowed by Kelsey in 2011 (curve attached). Thus,we analyzed our data according to these results.
Histogram of the AMH blood levels
Median = 3 Mean = 4.02SD = 3.35
Median = 2.9Mean = 3.61SD = 2.96
CASES CONTROLS
CASES N = 188 CONTROLS N = 376
Mean(M)
Median +/- SD[Min-Max]
MMedian +/- SD
[Min-Max]p
Age 32.8832.9 ± 5
[18.7 – 44.8] 32.3
32.99 ± 4.62[18.5 - 44.7]
NS
Tobaccoyear packages
4.772.5 ± 6.073
[0 - 21]4.41
1.3 ± 6.084[0 - 38]
NS
BMI 23.021.8 ± 4.15
[17 - 44]22.8
21.8 ± 3.30 [13 - 53]
NS
Menstrual cycle (days)
28.5328 ± 2.98
[21- 45]28.85
28 ± 3.3 [20 - 60]
NS
P = NS
This is the FIRST case-control study with largesamples (564), suggesting an associationbetween the OR decrease and UREM in femalesover 25 years, not from an infertilityconsultation. It is possible that this OR decline isan early marker of deterioration of oocytequality regardless of age.
CASES N = 176 CONTROLS N = 358
MMedian +/- SD
[Min-Max]M
Median +/- SD[Min-Max]
p
AMHng/ml
3.512.8 ± 3
[0.1 – 18.8]4.11
3.25 ± 3.4 [0.1 – 21.5]
0.046
Age 33.533.3 ± 4.4[25 - 44.8]
33.533.3 ± 4.07[25 – 44.7]
0.9
p
AMHBMIMother’s age
0.032
AMHMenstrual cycle Mother’s age
0.027
AMH TobaccoMother’s age
0.039
AMHMother’s ageMenstrual cycle BMITobacco
0.031
R² linéaire = 0,0058 R² linéaire = 0,116
CASES N = 12 CONTROLS N = 18
MMedian +/- SD
[Min-Max]M
Median +/- SD[Min-Max]
p
AMHng/ml
55.7 ± 2.2[1.4 – 7.8]
2.12.3 ± 0.9[0.9 – 4.3]
0.011
Age 2323,7 ± 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 femalesAMH levels significantly 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
IntroductionMaternal age and abnormalities of ovarian reserve (OR) is often considered among the etiologies of unexplained recurrent early miscarriage (UREM). Studies aiming atfinding 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 explorethe 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 logisticalmultiple regression, step by step