Examining the ovaries by ultrasound for diagnosing hyperandrogenic anovulation: updating the threshold for newer machines

9 01 2014

To the Editor:

We enjoyed reading the article by Christ et al. (1). The discussion about ultrasound criteria, specifically where to put the threshold to distinguish between a polycystic and a normal ovary, has been ongoing for some time and will surely continue for a while yet. Although the results are somewhat predictable since this report is a reassessment of partial data from a previous study (2), the timing of this publication is important because it reinforces a recently published task force report (3). Change is long overdue, but we believe the recommendation of using ≥ 25 follicles per ovary (3) should be adopted promptly as it is clear that the former threshold of 12 follicles is obsolete due to the improvement in the resolution of ultrasound. However, physicians should be aware that a much lower threshold should be used when trying to identify women at high risk of having an excessive response to exogenous gonadotropins used in in vitro fertilization/intracytoplasmic sperm injection cycles. Women with a total antral follicle count (AFC) > 20, considering both ovaries, are already at a higher risk of ovarian hyperstimulation syndrome (4). Another important point to consider when choosing the best threshold are the differences observed in AFC during reproductive age (5). The question of using the same threshold or different thresholds depending on a woman’s age should be balanced between diagnostic test accuracy and ease of implementation.

We want to raise the question about an issue that we believe is no less important than the threshold: the misleading name given to the associated health condition. Such ovaries do not have cysts, only follicles. Several women are concerned about their “cysts” and frequently repeat ultrasound scans to examine whether the cysts are gone or even ask about the need to undergo surgery for removing them. In our opinion the best term for the health condition is hyperandrogenic anovulation, and the best term for the ovarian appearance would be multifollicular ovaries. These names are much easier to be properly explained and are much less likely to cause unnecessary harm.

We would like to highlight the fact that many sonographers who regularly perform gynecological ultrasound are able to subjectively recognize the typical appearance of ovaries from women with hyperandrogenic anovulation. The ovary is enlarged, its stroma is hyperechogenic relative to its cortex and highly vascular, and, above all, there are numerous, small follicles arranged around the periphery. We believe that pattern recognition should not be abandoned; even this study showed that the pattern of follicle distribution as well as the stromal area had significant diagnostic potential (1).

To summarize, we welcome the call to update the current criteria but we want to note that normative data should be the basis of further studies, as they are more appropriate when dealing with such variable values. Alongside this issue is an equally important need to change the misnomer given to this enigmatic health condition. Why not do both at the same time?

Martina Kollmann, M.D., Department of Obstetrics and Gynaecology, Medical University of Graz, Austria
Wellington P. Martins, M.D., Ph.D., Department of Obstetrics and Gynecology, Medical School of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil; School of Health Technology – Ultrasonography School of Ribeirao Preto (FATESA-EURP)
Nick Raine-Fenning, M.B.Ch.B., M.R.C.O.G., Ph.D., Division of Child Health, Obstetrics & Gynaecology, School of Medicine, University of Nottingham, Nottingham, UK

References

1. Christ JP, Willis AD, Brooks ED, Vanden Brink H, Jarrett BY, Pierson RA, et al. Follicle number, not assessments of the ovarian stroma, represents the best ultrasonographic marker of polycystic ovary syndrome. Fertil Steril 2014;101:280-7.

2. Lujan ME, Jarrett BY, Brooks ED, Reines JK, Peppin AK, Muhn N, et al. Updated ultrasound criteria for polycystic ovary syndrome: reliable thresholds for elevated follicle population and ovarian volume. Hum Reprod 2013 May;28:1361-8.

3. Dewailly D, Lujan ME, Carmina E, Cedars MI, Laven J, Norman RJ, et al. Definition and significance of polycystic ovarian morphology: a task force report from the Androgen Excess and Polycystic Ovary Syndrome Society. Hum Reprod Update 2013 Dec:In press.

4. Jayaprakasan K, Chan Y, Islam R, Haoula Z, Hopkisson J, Coomarasamy A, et al. Prediction of in vitro fertilization outcome at different antral follicle count thresholds in a prospective cohort of 1,012 women. Fertil Steril [Research Support, Non-U.S. Gov’t]. 2012 Sep;98:657-63.

5. Wiser A, Shalom-Paz E, Hyman JH, Sokal-Arnon T, Bantan N, Holzer H, et al. Age-related normogram for antral follicle count in women with polycystic ovary syndrome. Reprod Biomed Online 2013 Oct;27:414-8.

Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2014.01.012

The authors respond:

We appreciated reading the thoughtful commentary by Kollmann and colleagues in response to our article. They brought forth several issues relating to the definition and significance of polycystic ovarian morphology (PCOM) that warrant further and more widespread dialogue. First, they too acknowledge the urgent need to implement a higher follicle threshold for PCOM than the outdated value of ≥12 follicles per ovary, which unfortunately continues to be recommended (1). Similar to others (2), our data using newer imaging technology clearly support a substantially higher follicle threshold—26 versus 12 follicles—to distinguish between the normal and polycystic ovary syndrome (PCOS) condition (3). Indeed, in our recent review of follicle counts reported for healthy women of reproductive age (4), there is evidence of a technology-dependent increase in the number of follicles that are now visible using higher frequency transducers (≥8MHz), which afford better image resolution.

Second, Kollmann et al. recommend that thresholds for PCOM be based on normative data. This is consistent with the approach taken by the Androgen Excess and PCOS Society whose recently proposed threshold of ≥25 follicles per ovary was based on the estimated 95th percentile of follicle counts made in >1000 healthy women of which our control series was included (4). We agree that a comprehensive evaluation of ovarian morphology in healthy women across all ages is urgently needed in light of advancements in imaging technology. As for proposing thresholds based on an upper-limit of normal, this is certainly an acceptable approach if and when the control population is carefully defined. Unlike the receiver operating characteristic curve analysis we employed, this approach is limited by a pre-selected false-positive rate and no indication of the sensitivity of the marker to detect the diseased condition. However, we acknowledge that in the case of PCOS, where there is controversy regarding the actual clinical spectrum of PCOS, consideration of a normative series may be most prudent.

Third, they urge that follicle patterning continue to be considered in the detection of PCOM. We agree that a peripheral distribution of follicles can be reliably assessed and is highly predictive of PCOS. However, our study did not show this marker to have greater specificity than follicle counts nor did it add appreciable diagnostic power when coupled with other sonographic markers. Moreover, follicle patterning lacked sensitivity to detect PCOS (only 27%). This might have reflected the broad definition for hyperandrogenism employed by our study (that is, either biochemical or clinical hyperandrogenism was sufficient). However, this hypothesis was not tested. Last, while there is the potential for follicle patterning to be less variable than follicle counts across the lifespan, we are unaware of any study that has prospectively evaluated this notion.

In closing, we agree that the term “polycystic ovary” should be abandoned for a more appropriate description of the actual anatomical anomaly. The ovary is multi- or poly-follicular, and we must continue to educate our peers and patients on this point until there is sufficient consensus to support a name change for PCOS—which at present, seems looming (5).

Marla E. Lujan, M.Sc. Ph.D., Human Metabolic Research Unit, Division of Nutritional Sciences, Cornell University, Ithaca, New York

References

1. Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, Pasquali R, et al. Diagnosis and treatment of polycystic ovary syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2013; 98:4565-92.

2. Dewailly D, Gronier H, Poncelet E, Robin G, Leroy M, Pigny P, et al. Diagnosis of polycystic ovary syndrome (PCOS): revisiting the threshold values of follicle count on ultrasound and of the serum AMH level for the definition of polycystic ovaries. Hum Reprod 2011;26:3123-9.

3. Lujan ME, Jarrett BY, Brooks ED, Reines JK, Peppin AK, Muhn N, et al. Updated ultrasound criteria for polycystic ovary syndrome: reliable thresholds for elevated follicle population and ovarian volume. Hum Reprod 2013;28:1361-8.

4. Dewailly D, Lujan ME, Carmina E, Cedars MI, Laven J, Norman RJ, et al. Definition and significance of polycystic ovarian morphology: a task force report from the Androgen Excess and Polycystic Ovary Syndrome Society. Hum Reprod Update 2013;Dec 16: In press.

5. Teede H, Gibson-Helm M, Norman RJ, Boyle J. Polycystic ovary syndrome: perceptions and attitudes of women and primary health care physicians on features of PCOS and renaming the syndrome. J Clin Endocrinol Metab 2014;99:E107-11.

Published online in Fertility and Sterility doi: 10.1016/j.fertnstert.2014.01.013

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