Polycystic ovaries still a matter of contention in the diagnosis of PCOS

Published 23 November 2021

Substituting the ultrasound assessment of ovarian morphology with serum AMH measurement to diagnose PCOS according to the three Rotterdam criteria changed the number of women classified as having or not having PCOS – and ‘further blurs the diagnostic margins’.

When in 2004 a joint working group of ESHRE and ASRM finally agreed on a diagnostic definition of polycystic ovary syndrome, it seemed almost counterintuitive that polycystic ovaries were not listed as a necessary criterion for diagnosis.(1) The ‘Rotterdam’ criteria required the presence of any two of three diagnostic components, of which ovarian morphology ran alongside hyperandrogenism and oligo-amenorrhoea. Five years later a taskforce of the ‘Androgen Excess & PCOS Society’ in the USA declared that PCOS ‘should be defined by the presence of hyperandrogenism’, with polycystic ovaries now consigned to ‘ovarian dysfunction’ (along with ‘oligo-anovulation’) in support.(2)

Diagnosis was also one of several objectives of the recently published international guidelines on PCOS, in which ESHRE and ASRM were collaborating partners with Australia’s Centre for Research Excellence in PCOS, and which state clearly that ‘we endorse the Rotterdam PCOS diagnostic criteria in adults’.(3) Specifically, the international guidelines reaffirm all or two combinations of the three phenotypes recognised in the Rotterdam criteria: androgen excess, ovulatory dysfunction and polycystic morphology.

However, a new study on the assessment of ovarian morphology in the diagnosis of PCOS proposes that the diagnostic criteria for PCOS ‘are still poorly defined’ (with great variability in the syndrome’s clinical manifestations) and that the accurate determination of polycystic morphology requires high-resolution ultrasound, preferably transvaginal.(4) The Rotterdam criteria noted a follicle number per ovary of ≥12 (and ovarian volume of >10 cm3) as a diagnostic threshold with low resolution ultrasound, while later re-evaluations required a follicle number per ovary of ≥25 with high resolution technology. With such a range in recommendations adding further to diagnostic imprecision – and in the knowledge that transvaginal ultrasound may not be acceptable to all women – this latest study now asks if measurement of serum AMH as a diagnostic component of the syndrome might replace the ultrasound assessment of ovarian morphology.

Indeed, the authors report, AMH as a marker of follicular development has already been considered as a potential surrogate marker for ovarian morphology in the diagnosis of PCOS. However, the data were considered ‘insufficient’ for recommendation in the latest international guidelines.(5) Nevertheless, this review did conclude that, ‘once issues are addressed, AMH levels could replace more costly and less accessible ultrasound in PCOS diagnosis’ – notwithstanding the variable costs of AMH measurement now evident in many countries.

To address ‘the issues’ (low resolution ultrasound, infertile women in the comparison group, inconsistent AMH assays), this latest study used the Rotterdam criteria to diagnose PCOS in 163 women and confirming the status of ovarian morphology with high resolution ultrasound (applying a threshold of ≥25 follicles per ovary) and serum AMH measures with two validated assays.

Results from this cross-sectional study showed that those with an AMH measurement of ≥44.0 pmol/l identified 80.6% of women with ovarian morphology, and falsely identified 15.2% of women without PCOS morphology - a positive predictive value of 55.6% and negative predictive value of 94.9%. Further, when serum AMH was used in the place of ultrasound-assessed ovarian morphology for PCOS diagnosis, one of the two assays resulted in an additional seven women classified as having PCOS (and no longer classified one woman as having PCOS). For the other assay, eight additional and two fewer women were classified as having PCOS. Overall, both assays resulted in six more women being classified as having PCOS.

So where does that leave serum AMH as a surrogate for ultrasound assessment? With ovarian morphology still assumed the gold standard by which to evaluate the utility of AMH, the authors of this study still find an effect of misdiagnosis in application of the latter. They report: ‘The absolute number of women impacted by potential misdiagnosis in this study was 8 and 10 out of a sample of 163 women . . . or ~5% of the sample.’ They thus add that the use of serum AMH ‘further blurs the diagnostic margins’, and extends the risk of misdiagnosis. However, ‘whether the observed reclassification of some women using serum AMH constitutes misdiagnosis, or whether serum AMH offers a more accurate diagnostic criterion for PCOS is yet to be established’.

The bottom line of the study appears to be the inconsistency of AMH findings from the two different assays, and thus the conclusion that ‘universal cut-offs for serum AMH concentrations are not feasible for clinical practice’. Without the latter, the use of serum AMH as a substitute for follicle count seems likely to increase diagnoses of PCOS – even though generally ‘AMH concentrations are highly correlated with ovarian follicle numbers’.

The other caveat which the authors raise is the actual role of ovarian morphology in the diagnosis of PCOS, which, by the Rotterdam definition of ≥12 follicles per ovary, ‘is no longer considered abnormal’ and which alone is not a pathological condition. ‘Therefore,’ write the authors, ‘if [polycystic ovarian morphology] is not alone pathological, substantial caution is needed before an elevated AMH can be considered pathological.’ And this takes us back to our opening question of whether polycystic ovarian morphology is a diagnostic necessity for polycystic ovarian syndrome. The view here, as reflected in the latest international guidelines, suggests that a diagnosis of PCOS still depends on a trio of criteria, and that measurement of serum AMH – as yet – as a surrogate for morphological assessment by ultrasound may increase the likelihood of diagnosis.

* Not surprisingly, the report of the Rotterdam consensus on diagnostic criteria for PCOS remains the most cited paper in the 38-year history of Human Reproduction.

1. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop
Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004; 19: 41–47.
2. Aziz R, Carmina E, Dewally D, et al. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 2009; 91: 456-488. doi:10.1016/j.fertnstert.2008.06.035.
3. See https://www.eshre.eu/Guidelines-and-Legal/Guidelines/Polycystic-Ovary-Syndrome
4. Bell RJ, Islam RM, Skiba MA, et al. Substituting serum anti-Mullerian hormone for polycystic ovary morphology increases the number of women diagnosed with polycystic ovary syndrome: a community-based cross-sectional study. Hum Reprod 2021; doi.org/10.1093/humrep/deab232
5. Teede H, Misso M, Tassone EC, et al. Anti-Mullerian hormone in PCOS: a review informing international guidelines. Trends Endocrinol Metab 2019; 30: 467–478.

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