Document Type : Original Article
Authors
1 Department of Biochemistry and Molecular Biology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
2 Department of Biochemistry, International Campus of Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Abstract
Keywords
One of the main causes for infertility is decreased ovarian reserve. Ovarian reserve is the number of good quality oocytes that remain within the ovaries. As a woman’s age increases, her ovarian reserves decline (
Few studies have assessed the levels of FSH and AMH at various ages in infertile women, therefore our aim was to investigate the changes in serum concentrations of AMH and FSH at different ages and its correlation with ovarian reserves in infertile women.
This cross-sectional study was performed at the Research Center of Infertility, Shahid Sadoughi University, Yazd, Iran between May 2010 and September 2012. We assessed serum AMH and FSH levels on days 2 or 3 of the menstrual cycles of 197 infertile women with problem decreasing ovarian reserve and 176 healthy controls, without decreasing ovarian reserve and age 19-47 years, who were admitted to infertility clinic to investigate infertility. Inclusion criteria were: no history of gynecological surgical procedures, presence of a regular menstrual cycle, no signs of hyper-androgenemia, and normal sonographic appearance of the ovaries. Infertile women were excluded if they were using fertility drugs or had any autoimmune, genetic, or iatrogenic conditions, autoimmune endocrinopathies, radiation therapy or pelvic surgery, or polycystic ovary syndrome as these factors have been shown to alter serum AMH levels (
Patients were stratified into the following age categories: <25, 25-29.9, 30-34.9, 35-39.9, 40-45 and ≥45 years. Ethical approval for the study was received from the Women’s and Medical Ethics Committee.
This approval allowed for measurement of serum AMH levels in stored routine clinical samples without the need for the patient’s written permission in order to produce an age-related normal range data for AMH levels. All 197 patients and 176 healthy controls were asked to provide their consent in order to link their AMH results with IVF outcome.
Serum AMH levels were assessed in serum by the enzyme linked immunosorbent assay ( ELISA ) method ( Beckman Coulter, USA ). The sensitivity of the assay is 0.08 ng/ml with a reference range of 12.6 ng/ml. Interand intra-assay coefficients of variation ( CV ) are <7.7% and <5.8%, respectively. Luteinizing hormone ( LH ) and FSH levels were assessed in serum by the electrochemiluminescent immunoassay ( ECLIA ) method ( Cobas, England ). The assay sensitivity for FSH is <0.1 mIU/ml with interand intraassay CVs of <7.7% and <5.8%, respectively. Sample collection was performed by random sampling at days 3-5 of a spontaneous menstrual cycle. The serum was separated one hour after sampling and frozen at -20˚C until assayed.
The data were presented as mean±standard deviation as calculated in each group by SPSS software version 16 ( SPSS Inc., Chicago, IL, USA ). The student’s t test was used to assess differences between mean values of AMH, FSH and LH in the infertility and control groups with a confidence level of 95% and p value <0.05.
Table 1 shows the mean AMH, FSH and LH levels according to the six age categories. Overall there was a significantly lower mean AMH serum level in infertile women compared to the control group (
Mean serum FSH levels consistently increased with increasing age in both the infertile and control groups.
However, this increase was higher in the infertile group (
Changes in anti-Mullerian hormone (AMH), follicle stimulating hormone (FSH) and luteinizing hormone (LH) serum concentrations for different ages of women in the infertile and control groups
Age (Y) | Infertile Mean±SD | Fertile Mean±SD | P value | |
---|---|---|---|---|
n=197 | n=176 | |||
BMI (kg/m2) | 27±2 | 27±6 | ||
AMH (ng/ml) | 0.32±0.2 | 1.85±0.19 | 0.002 | |
FSH (mIU/ml) | 21.36±4.28 | 9.79±4.38 | 0.03 | |
LH (mIU/ml) | 11.68±2.05 | 8.66±2.16 | 0.32 | |
n=17 | n=15 | |||
BMI (kg/m2) | 28±3 | 27±5 | ||
AMH (ng/ml) | 0.55±0.16 | 2.04±0.21 | 0.000 | |
FSH (mIU/ml) | 17.27±2.36 | 5.02±4.39 | 0.002 | |
LH (mIU/ml) | 9.2±1.25 | 5.54±1.23 | 0.2 | |
n=29 | n=27 | |||
BMI (kg/m2) | 26±2 | 27±4 | ||
AMH (ng/ml) | 0.39±0.23 | 2.06±0.24 | 0.001 | |
FSH (mIU/ml) | 20.41±4.49 | 6.7±3.35 | 0.04 | |
LH (mIU/ml) | 12.32±2.54 | 8.98±1.35 | 0.27 | |
n=38 | n=32 | |||
BMI (kg/m2) | 28±1 | 26±7 | ||
AMH (ng/ml) | 0.41±0.21 | 1.91±0.17 | 0.000 | |
FSH (mIU/ml) | 29.3±3.24 | 13.21±5.26 | 0.02 | |
LH (mIU/ml) | 14.76±1.81 | 9.39±2.49 | 0.35 | |
n=22 | n=57 | |||
BMI (kg/m2) | 27±5 | 28±1 | ||
AMH (ng/ml) | 0.34±0.18 | 1.78±0.21 | 0.000 | |
FSH (mIU/ml) | 27.48±5.62 | 7.02±1.66 | 0.004 | |
LH (mIU/ml) | 12.38±2.53 | 6.89±3.39 | 0.55 | |
n=61 | n=31 | |||
BMI (kg/m2) | 28±6 | 26±3 | ||
AMH (ng/ml) | 0.29±0.25 | 1.72±0.26 | 0.032 | |
FSH (mIU/ml) | 29.32±3.59 | 13.23±6.34 | 0.023 | |
LH (mIU/ml) | 7.22±2.3 | 6.32±2.12 | 0.34 | |
n=30 | n=14 | |||
BMI (kg/m2) | 27±2 | 28±4 | ||
AMH (ng/ml) | 0.25±0.22 | 1.35±0.14 | 0.012 | |
FSH (mIU/ml) | 32.54±6.42 | 17±5.32 | 0.043 | |
LH (mIU/ml) | 10.61±1.87 | 8.34±2.43 | 0.21 | |
BMI; Body mass index.
Mean±standard deviation in anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH) and luteinizing hormone (LH) in both fertile and infertile women.
Mean±standard deviation values for anti-Müllerian hormone (AMH) over the reproductive age range in control group and infertile women.
Mean±standard follicle stimulating hormone (FSH) values for the reproductive age range in control and infertile group women.
Mean±standard deviation values for follicle luteinizing stimulating hormone (LH) over the reproductive age range in fertile and infertile women.
In this study infertile women had higher FSH levels and lower AMH levels than fertile women. The range of AMH observed in infertile women was <1 whereas in the control group it was approximately 1 to 3. Mean serum AMH levels steadily decreased with increasing age in the age range of 19 to 47 years. In addition, mean FSH level approximately increased with increasing age in this range ( 19 to 47 years ) and was attributed to reduced ovarian reserve. Since AMH are produced by preantral and antral follicles (
We observed good correlation between serum AMH and FSH levels with ovarian reserve. These results supported those of previous studies in terms of the connections between low AMH serum levels and poor ovarian response (
La Marca et al. (
With increasing age AMH levels decrease due to reduced ovarian reserves. Hence AMH can be used as a marker for the assessment of ovarian reserves in the follicular and luteal phases.