Contribution of recruitable follicles to circulating anti-Müllerian hormone levels following maximal gonadotrophin stimulation in patients with limited ovarian reserve.

In women, the majority of anti-Müllerian hormone (AMH) measured in serum originate from small antral follicles measuring 2-10 mm. In gonadotrophin-stimulated cycles prior to assisted reproductive technology (ART), most of the recruitable follicles develop beyond 10 mm in size and thus lose their AMH secretion capacity causing declining serum AMH levels. The aim of this study was to define the residual serum AMH level after elimination of the AMH producing recruitable follicles following maximal gonadotrophin stimulation. We measured serum AMH and number of follicles according to size at several time points during a cycle of maximal gonadotrophin stimulation (fixed dose of 300 IE HP-hMG) in 107 women with low AMH (median AMH 5 pmol/L, interquartile range (IQR) 3.3-8.3). We found that AMH decreased gradually and reached a minimum level of -55.4% (95% CI -59.6; -50.7) of the baseline value four days after ovulation trigger. Our findings suggest that the residual AMH production origins from pre-antral and small antral follicles not visible by sonography and that they account for up to 40% of the circulating AMH.

Serum anti-Müllerian hormone concentration before and after salpingectomy for ectopic pregnancy.

RESEARCH QUESTION: Does salpingectomy for ectopic pregnancy affect the ovarian reserve measured by changes in pre- and post-operative levels of anti-Müllerian hormone (AMH)? DESIGN: This is a prospective observational multicentre study of 64 women treated with salpingectomy for an ectopic pregnancy. AMH was measured in serum samples collected at admission before salpingectomy and at follow-up (median time to follow-up [interquartile range] was 3 [3-4] months). Changes in serum AMH levels were investigated using Wilcoxon signed-rank test and the relationship between changes in AMH and age, time to follow-up, and pre-operative serum AMH level was investigated using linear regression analysis. The biological variation of AMH was also calculated. RESULTS: Serum AMH levels did not differ significantly before and after salpingectomy (median ∆AMH [follow-up value minus admission value] 0.40 pmol/l, interquartile range -2.0 to 4.0 pmol/l). ΔAMH was independent of age, time to follow-up and pre-operative serum AMH level. The intra-individual biological variation for AMH ranged from 12.1% to 26.3%, depending on time between the two samples. CONCLUSIONS: This is the first paired study to investigate serum AMH values before and after salpingectomy in an unselected population of women presenting with an ectopic pregnancy, including both patients who conceived naturally and following fertility treatment. It was found that salpingectomy for ectopic pregnancy had no short-term effect on serum AMH levels, and changes in AMH levels were independent of age, time to follow-up, and pre-operative serum AMH level. Furthermore, the study demonstrated a 6-month biological variation of AMH of less than 30%.

The use of anti-Müllerian hormone for controlled ovarian stimulation in assisted reproductive technology, fertility assessment and -counseling.

Ovarian reserve can be determined by serum anti-Müllerian hormone (AMH) level and/or antral follicle count before controlled ovarian stimulation. The aim of controlled ovarian stimulation is to achieve an appropriate number of mature follicles and avoid complications such as ovarian hyperstimulation syndrome. Measurement of the ovarian reserve is useful for clinicians as it predicts the ovarian response to controlled ovarian stimulation. Further, it assists in giving the patient realistic expectations regarding the treatment. By determining the ovarian reserve, the most appropriate stimulation protocol and gonadotropin dose can be chosen specifically for each woman enabling so-called "individualized treatment" in line with the personalized treatment concept. Many benefits come with using AMH as a biomarker for ovarian reserve; the hormone is considered fairly cycle independent apart from a small decrease in the late follicular phase and there is no inter-observer variance. However, the use of AMH also has limitations; since the implementation of AMH in fertility treatment several AMH assays have been developed. This has made direct comparisons of AMH serum levels complicated. Currently, no international standardized assays exist. AMH is a valid predictor of the ovarian response to controlled ovarian stimulation and to some extent the chance of pregnancy in relation to assisted reproductive technology, but AMH is less optimal in prediction of spontaneous pregnancy and live birth after assisted reproductive technology. Accordingly, AMH can be used to optimize gonadotropin stimulation in fertility treatment, but is not recommended as a screening tool in the general population.

[The use of anti-Müllerian hormone in fertility treatment].

The need for fertility treatment in Denmark is increasing, one of the main causes being postponed parenthood. Ovarian reserve is determined by the anti-Müllerian hormone (AMH) level and by antral follicle count. Both tests can predict the ovarian response to gonadotropin treatment prior to in vitro fertilization (IVF) and are used to individualize ovarian stimulation to achieve an appropriate number of follicles and to avoid ovarian hyperstimulation. A new assay detects low values of AMH and may predict who will benefit from IVF, and who should be referred directly to oocyte donation.