Scholarly article on topic 'The relationship between Anti-müllerian hormone and the clinical, biochemical and sonographic parameters in women with polycystic ovarian syndrome'

The relationship between Anti-müllerian hormone and the clinical, biochemical and sonographic parameters in women with polycystic ovarian syndrome Academic research paper on "Clinical medicine"

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{"Polycystic ovary syndrome" / "Anti-müllerian hormone" / "Modified Ferriman Gallwey score" / "Mean ovarian volume" / "Antral follicle count"}

Abstract of research paper on Clinical medicine, author of scientific article — Ahmad Mahran

Abstract Background and aim of the study Anti-müllerian hormone (AMH) is a dimeric glycoprotein, which is secreted exclusively by granulose cells of primary, preantral, and small antral follicles (4–6mm). Women with polycystic ovary syndrome (PCOS) have a 2- to 3-fold increase in the serum AMH concentration, which corresponds to the 2- to 3-fold increase in the number of small follicles seen in PCOS. The aim of this study was to assess the relationship between AMH and the clinical, biochemical and sonographic parameters in women with PCOS. Study design In this prospective observational study, serum AMH was measured in 200 PCOS women attending 2 fertility clinics in Minia, Egypt. The relationship between AMH and the clinical, biochemical and sonographic parameters of PCOS was studied. Results AMH levels were found to have significant positive correlation with cycle length (r =0.706, P <0.01), modified Ferriman Gallwey (FG) score for hirsutism (r =0.329, P <0.01), mean ovarian volume (r =0.498, P <0.01), antral follicle count (AFC) (r =0.963, P <0.01) and total testosterone (r =0.272, P <0.01). Conclusion In conclusion, AMH is strongly correlated with the clinical, biochemical and sonographic features of PCOS.

Academic research paper on topic "The relationship between Anti-müllerian hormone and the clinical, biochemical and sonographic parameters in women with polycystic ovarian syndrome"

Middle East Fertility Society Journal (2015) xxx, xxx-xxx

Middle East Fertility Society Middle East Fertility Society Journal

www.mefsjournal.org www.sciencedirect.com

ORIGINAL ARTICLE

The relationship between Anti-müllerian hormone and the clinical, biochemical and sonographic parameters in women with polycystic ovarian syndrome

Ahmad Mahran

Department of Obstetrics & Gynaecology, Faculty of Medicine, Minia University, Minia, Egypt Received 29 September 2014; revised 3 June 2015; accepted 17 June 2015

KEYWORDS

Polycystic ovary syndrome; Anti-mullerian hormone; Modified Ferriman Gallwey score;

Mean ovarian volume; Antral follicle count

Abstract Background and aim of the study: Anti-mullerian hormone (AMH) is a dimeric glycoprotein, which is secreted exclusively by granulose cells of primary, preantral, and small antral follicles (4-6 mm). Women with polycystic ovary syndrome (PCOS) have a 2- to 3-fold increase in the serum AMH concentration, which corresponds to the 2- to 3-fold increase in the number of small follicles seen in PCOS. The aim of this study was to assess the relationship between AMH and the clinical, biochemical and sonographic parameters in women with PCOS.

Study design: In this prospective observational study, serum AMH was measured in 200 PCOS women attending 2 fertility clinics in Minia, Egypt. The relationship between AMH and the clinical, biochemical and sonographic parameters of PCOS was studied.

Results: AMH levels were found to have significant positive correlation with cycle length (r = 0.706, P < 0.01), modified Ferriman Gallwey (FG) score for hirsutism (r = 0.329, P < 0.01), mean ovarian volume (r = 0.498, P < 0.01), antral follicle count (AFC) (r = 0.963, P < 0.01) and total testosterone (r = 0.272, P < 0.01).

Conclusion: In conclusion, AMH is strongly correlated with the clinical, biochemical and sonographic features of PCOS.

© 2015 The Author. Production and hosting by Elsevier B.V. on behalf of Middle East Fertility Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-

nd/4.0/).

1. Introduction

E-mail address: ezzeldin_ahmad@yahoo.com Polycystic ovary syndrome (PCOS) is a common endocrinal

disorder affecting 6.6-8% of women of reproductive age (1). It is associated with 75% of the causes of anovulatory infertility (2). There has been much debate about the definition of PCOS. A refined definition was agreed at a recent joint

Peer review under responsibility of Middle East Fertility Society.

Production and hosting by Elsevier

http://dx.doi.org/10.1016/j.mefs.2015.06.003

1110-5690 © 2015 The Author. Production and hosting by Elsevier B.V. on behalf of Middle East Fertility Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Table 1 Clinical, Biochemical and sonographic characteristics of 200 PCOS patients.

Mean SEM Range

Age (years) 29.7 0.4 21-39

Cycle length (days) 56.9 4 28-180

BMI (kg/m2) 28.6 0.4 17.7-41.4

Modified FG score 8 0.5 0-30

Ovarian volume (cm3) 9.6 0.3 3.5-17

AFC 32.2 1.3 20-88

FSH (IU/l) 5.7 0.2 3.1-10.4

LH (IU/l) 9.5 0.4 5-19

Testosterone (ng/ml) 2.2 0.7 1.3-3.8

SHBG (ng/ml) 40.4 2.9 9.4-118

FAI 6.6 0.3 1-22

Fasting insulin(iU/ml) 19.5 4.6 2-72.8

Fasting glucose (mg/ml) 89 4.5 63-239.4

HOMA-IR 4.5 1.1 0.4-15.5

AMH (ng/ml) 4.5 0.2 1.4-10

Data are shown as mean ± SEM (standard error of the mean) and the range.

FG score = Ferriman Gallwey score, AFC = antral follicle count, FSH = follicle stimulating hormone, LH = luteinizing hormone, SHBG = sex hormone binding globulin, FAI = free androgen index, HOMA-IR = Homeostais Assessment model of insulin resistance, AMH = anti-müllerian hormone.

European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine (ESHRE/ASRM) consensus meeting. It depends upon the presence of two out of three criteria: oligo- and/or anovulation, hyperandrogenism (clinical and/or biochemical), polycystic ovaries, with the exclusion of other aetiologies (3). The pathophysiology of PCOS is likely to be multifactorial and polygenic. There is a significant body of evidence suggesting that excess ovarian androgen production is central in the pathogenesis of PCOS (4).

Anti-Mullerian hormone (AMH) is a dimeric glycoprotein, which is secreted exclusively by granulose cells of primary, pre-antral, and small antral follicles (4-6 mm). Its secretion gradually diminishes in the subsequent stages of follicle development and is practically undetectable in follicles greater than 8 mm (5). Serum AMH concentrations have been correlated with the number of small follicles and hence ovarian reserve. AMH has been shown to lower the sensitivity of follicles to circulating FSH (6).

Previous research has shown women with polycystic ovarian syndrome (PCOS) to have a 2- to 3-fold increase in the serum AMH concentration, which corresponds to the 2- to 3-fold increase in the number of small follicles seen in PCOS. This increase in AMH has been implicated in the pathogenesis of PCOS. It has been hypothesized that the high serum AMH levels in PCOS lower the follicular sensitivity to circulating FSH, thus preventing follicle selection, resulting in follicle arrest at the small antral phase with the failure of dominance (7,8).

In three recent studies involving women with PCOS, we have found high serum AMH levels to be associated with poor response to laparoscopic ovarian drilling (9), ovulation induction with clomiphene citrate (10), and gonadotrophins (11). It is clear from these findings that AMH can be an excellent

A. Mahran

predictor to response of PCOS women to different infertility treatment modalities.

We aim from this study to understand the relationship between AMH and other parameters in PCOS and to establish whether AMH can be used in the diagnosis of PCOS and assessment of its severity.

2. Materials and methods

This study involved 200 PCOS women among those attending

2 fertility units in Minia, Egypt, for fertility treatment. It was conducted between July 2012 and January 2014. The diagnosis of PCOS was based on the Rotterdam criteria, in which at least two of the following three criteria were met: (a) oligo or anovulation, (b) clinical or biochemical hyperandrogenaemia, (c) polycytic ovaries (>12 follicles < 10 mm and/or ovarian volume > 10 ml per ovary by vaginal ultrasound). Hyperprolactinaemia, thyroid dysfunction, Cushing's syndrome, congenital adrenal hyperplasia, an adrenal or ovarian tumour were excluded before enrollment in the study. The exclusion criteria include (a) use of hormonal therapy in the

3 months prior to the study, (b) absence of one ovary, (c) previous ovarian surgery, and (d) previous exposure to cytotoxic drugs or radiation therapy. The study was approved by the institutional review board of the faculty of Medicine, Minia University, Egypt. All subjects gave written informed consent prior to entering the study.

The degree of hirsutism in the study patients was assessed using modified Ferriman-Gallwey scoring system (12).

2.1. Biochemical assay

Blood samples were collected on day 2-3 of spontaneous menstrual cycle or after progesterone induced withdrawal bleeding. Testing for hormonal profiles (i.e.: FSH, LH, sex hormone binding globulin (SHBG), testosterone, and prolactin) was done routinely as per unit protocol. Serum samples were assayed for AMH in duplicate using an ELISA kit (Uscan), which is a sandwich enzyme immunoassay for the in vitro quantitative measurement of AMH in serum, plasma, and other biological fluids. This kit has an intra- and inter assay coefficient of variation of less than 10% and less than 12%, respectively. The minimum detectable level of human AMH by this kit was typically greater than 0.046 ng/mL, with a detection range of 0.156-10 ng/mL. The assay has high sensitivity and excellent specificity for detection of human AMH with no significant cross-reactivity or interference.

Insulin resistance (IR) was calculated using the Homeostasis Assessment model (HOMA) as follows: HOMA IR = fasting insulinaemia (lIU/ml) x fasting glucose (mmol/l)/22.5 (13).

2.2. Transvaginal ultrasound

Ultrasound examination was performed on the same day of blood testing by the IVF specialists in the 2 units with a 7 MHz transvaginal probe. Ovarian volume was calculated according to simplified formula for an ellipsoid (0.5 x length x width x thickness) (14). The antral follicle count (AFC) was assessed by counting all antral follicles of 2-9 mm diameter in the transverse section in both ovaries.

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Figure 1 Correlation between AMH and cycle length (A), FG score (B), mean ovarian volume (C), AFC (D), total testosterone (E) and FSH (F).

2.3. Statistical analysis

Data were entered into Statistical Package for Social Science version 17 (SPSS Inc). In Table 1, the data are presented as mean ± SEM. The correlation between AMH and various parameters was evaluated using two-tailed Pearson correlation coefficient. A P value of 60.5 was considered significant.

3. Results

The clinical, biochemical and sonographic characteristics of the subjects are summarized in Table 1.

Serum AMH levels showed a statistically significant positive correlation with cycle length (r = 0.706, P < 0.01), modified Ferriman Gallwey score for hirsutism (r = 0.329, P < 0.01), mean ovarian volume (r = 0.498, P < 0.01), AFC (r = 0.963, P < 0.01) and total testosterone (r = 0.272, P < 0.01) (see Fig. 1).

Serum AMH levels showed a positive correlation with FAI and serum LH; however that failed to reach a statistical significance. On the other hand, there was a statistically significant negative correlation with serum FSH (r = 0.24, P < 0.1). There was a weak negative correlation between serum AMH levels and age, BMI, fasting glucose levels, serum insulin and HOMA-IR.

4. Discussion

Polycystic ovary syndrome (PCOS) is a heterogeneous collection of symptoms and signs forming together a spectrum of a disorder with a mild presentation in some and severe disturbance of reproductive, endocrine and metabolic function in others. There are three hallmarks of PCOS upon which, the diagnosis of PCOS is based. These hallmarks are oligo or anovulation, hyperandogenaemia, and ultrasonographic features.

In the present study, we measured the baseline serum AMH in 200 infertile PCOS women and we studied the relationship between AMH and the clinical, biochemical and sonographic features of the study population.

Regarding the clinical features, we demonstrated a statistically significant positive correlation between serum AMH and cycle length and modified Ferriman Gellway (FG) score of hir-sutism. Cycle length can be considered as a reflection to the degree of anovulation and FG score can is considered as a reflection to the degree of hyperandrogenaemia which plays a crucial role in the pathogenesis of PCOS. A not surprising result we found was the positive correlation between serum AMH and both total Testosterone and FAI. Similar association was demonstrated in the studies done by (15,16).

Serum AMH was shown in this study to be positively correlated with AFC and mean ovarian volume. This is a logic finding as AMH is produced by the granulose cells of pre-antral and small antral follicles. This is in agreement with other studies (8,15,17,18). It is also shown that in patients with PCOS, granulose cells secrete more AMH (19).

In the present study, we established a weak negative correlation between serum AMH levels and patients' chronological age and BMI. These findings are in accordance with the studies done by (20-22).

A. Mahran

The relationship between AMH and insulin resistance has been a matter of controversy among different studies. (23) observed a negative association between AMH and HOMA-IR, while (24) discovered an independent relationship between HOMA-IR and AMH in women without PCOS. In the present study, we found a negative but weak correlation between AMH and HOMA-IR.

In conclusion, AMH is strongly correlated with the clinical, biochemical and sonographic features of PCOS. Further studies are required to find out AMH can be used either as an adjuvant or a substitute for these characteristics in diagnosis of PCOS.

Conflict of Interest

Author states that there is no conflict of interest. Acknowledgment

The author is quite grateful to the entire medical, laboratory and nursing staff of Minia infertility research unit and Minia IVF centre for their kind support for his work.

References

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