Have antimüllerian hormone and antral follicle count been given the same opportunities?

30 05 2013

To the Editor:

We read with great interest the paper “Antimüllerian hormone in gonadotropin releasing-hormone antagonist cycles: prediction of ovarian response and cumulative treatment outcome in good-prognosis patients” (1) by Arce et al. In that paper the authors make a secondary analysis of the MEGASET study, concluding that antimüllerian hormone (AMH) can predict oocyte yield, categories of ovarian response, and live birth from IVF, and that AMH was associated with these outcomes, irrespective of the type of gonadotropin used. Moreover, as Nelson pointed out in the same issue of the journal (2), in Arce and colleagues’ analysis it was observed that the antral follicle count (AFC) was not associated with any of these outcomes.

There are two aspects that we would like to comment on. First, as already mentioned by Nelson, previous studies have observed that AMH and AFC were essentially equivalent in ovarian response prediction. We recently analyzed our population of oocyte donors (3) that presented similar inclusion criteria to that of the study by Arce (1): normal ovarian reserve (OR) by AFC and basal follicle-stimulating hormone (FSH). In this population treated with antagonists, AMH levels (analyzed by the Gen 2 ELISA) correlated significantly with the number of metaphase II oocytes (MII) retrieved. The AMH cutoff to predict a retrieval <6 MII was 2.31 ng/ml. AMH showed a mild capacity to discriminate poor response (AUC 0.675). We carried out a multiple regression analysis including age, AFC, and FSH in order to obtain a poor ovarian response prediction model and the AUC was 0.668 (95 % CI 0.540-0.796); if AMH was added to the model, the AUC was 0.713 (95% CI 0.596-0.830), slightly improving the prediction capacity. According to our results, measuring AMH is not an advantage for those reproductive medicine centers with easy access to AFC and FSH. In Arce’s paper, blood samples were analyzed at a central laboratory, whereas the AFC was performed at each investigational site by different observers, and a sonographer-dependent variability has been suggested. Read the rest of this entry »

Whatever its variability, AMH remains the most stable hormonal predictor

8 04 2013

To the Editor:

Dr. Hadlow and colleagues argue that antimüllerian hormone (AMH) levels decrease in the luteal phase and that the hormone should be measured in the follicular phase, since this variability may lead to misprediction of ovarian response in IVF. This assumption was made on the basis of few, not frequent, blood samples performed on a very limited sample of women (1).

In the study, the intra-individual variability of AMH was found to be similar to that of FSH. This finding is really surprising and points out a critical revision of the results obtained. Both of the largest available studies to date (2, 3) reported that 89% of the variation in AMH was due to between-subjects variation, while only 11% was due to true individual fluctuations. AMH may exhibit some variability, but the important point is that the fluctuations are randomly distributed throughout the menstrual cycle (4), raising the possibility that a fixed day for its measurement, as proposed, would be useless. The suggested cyclic moifications of AMH in Dr. Hadlow’s study need to be confirmed in studies investigating hormonal variability through more frequent samples and across at least two menstrual cycles. A logical and agreeable hypothesis explaining why AMH should reduce in the luteal phase needed to be formulated by the authors. If AMH is produced by antral follicles, the number of which shows no significant reduction in the luteal phase, and since AMH seems to be only marginally influenced by gonadotropins, why should its concentration reduce in the second part of the cycle? Read the rest of this entry »

Response to commentary of Drs. Rosenwaks and Reichman: “But isn’t AMH still better than FSH?”

27 03 2013

To the Editor:

We sincerely appreciate Drs. Rosenwaks’ and Reichman’s commentary (1) on our opinion piece. We are especially grateful for their explicit reporting of their program’s IVF outcomes in cases of low AMH levels, which is the largest experience yet reported. (Perhaps our admittedly provocative title spurred their useful and pertinent report of these results.) Finding that 6.2 eggs were retrieved from 1,052 patients with an AMH below 0.5 ng/mL, resulting in a 25.7% clinical pregnancy rate per retrieval, is reassuring. Perhaps more surprising is the 19% clinical pregnancy rate per retrieval among the 224 patients with AMH levels below the limit of detection (<0.16 ng/mL), who on average produced 3.9 eggs. Pertinent to our case, however, is the high cancellation rate they report for these groups: 26.1% for those with an AMH <0.50 ng/mL, and 38.8% when the AMH was <0.16 ng/mL.

We agree with Drs. Rosenwaks and Reichman that patients “should not be dissuaded from pursuing IVF solely because of a low AMH value,” as one of us (JPT) previously cautioned regarding elevated FSH values (2). Nonetheless, we do believe we have an obligation to warn that low AMH levels predict low ovarian response, higher cancellation rates, and lower pregnancy rates. We also continue to believe that AMH is a more sensitive and specific marker of low response than FSH ever was, so we still prefer it to FSH for this purpose.

James P. Toner, M.D., Ph.D.
Atlanta Center for Reproductive Medicine, Atlanta, GA
David B. Seifer, M.D., Ph.D.
Genesis Fertility and Reproductive Medicine, Brooklyn, NY


(1) Rosenwaks Z, Reichman DE. Use of antimüllerian hormone: the risks of interpreting ovarian reserve markers in isolation. Fertil Steril 2013, in press.

(2) Toner JP. Modest FSH elevations in young women: warn but don’t disqualify. Fertil Steril 2004; 81: 1493-5.

Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2012.04.045

Endocrine gland – derived vascular endothelial growth factor concentrations in follicular fluid and Serum may predict ovarian hyperstimulation syndrome

17 03 2011

To the Editor:

We read with great interest the article of Gao et al. (1). Gao et al. (1) had 17 patients that showed only mild to moderate signs and symptoms of OHSS using Golan classification system (2). A more recent classification reclassified OHSS into two groups (moderate and severe) stressing that mild OHSS signs are seen in most cases of controlled ovarian hyperstimulation that does not require special treatments (3), further reducing their OHSS patients number. Therefore, in the absence of severe OHSS cases, it is possible that the signs and symptoms of OHSS patients in their study may be similar to the non-OHSS group. Read the rest of this entry »

Re: The effect of surgical treatment for endometrioma on in vitro fertilization outcomes: a systematic review and meta – analysis.

2 09 2009

To the Editor:

We read the article by Tsoumpou et al. (1) with interest and commend the authors’ attempt to address this topical issue. The decision on what to do with regard to endometriomas in women having IVF remains an everyday challenge. The authors have done well to summarize the available data addressing this issue. Read the rest of this entry »