SAGE IVD recommended including the Follicle-Stimulating Hormone (FSH) test category in the third EDL:
• as a disease-specific IVD for use in clinical laboratories (EDL 3, Section II.b, within a new subsection for endocrine disorders);
• using an immunoassay format;
• to aid in the diagnosis of primary and secondary amenorrhoea, anovulation, gonadal dysfunction and precocious puberty; and
• to aid in the evaluation and management of infertility. The group requested that the FSH entry in the EDL include a link to the new WHO guidelines for diagnosing and managing infertility as and when these are published. The group further requested the addition of a note to the test category entry in the EDL stating that it is only recommended for use in specialized health care settings.

The consequences of infertility from a personal and social point of view can be dramatic. Fertility is considered a major public health issue by WHO. Testing FSH levels is part of several international guidelines and best practice for a large number of indications in fertility medicine, gonadal disorders, anovulation, amenorrhoea and menstrual irregularities. One of the medicines that is routinely used in fertility – clomiphene – is also included in the complementary list of the EML. There is, however, potential for overuse of the test, and little evidence base available to review for the clinical impact of FSH testing alone. SAGE IVD emphasized that FSH testing and result interpretation requires appropriate laboratory infrastructure and the availability of fertility or endocrinology specialists. The group also highlighted the importance of timing in sample collection (although timing requirements may vary depending on the condition being monitored). A WHO representative informed SAGE IVD that WHO is developing guidelines for diagnosing and managing infertility that will cover the nuances of sample collection for different conditions and circumstances. These are intended to be available later in 2020. SAGE IVD noted that while FSH testing is critical to evaluate and manage infertility, additional investigations may be needed for a definitive diagnosis.

This evidence portfolio makes clear the need for FSH testing in conjunction with other tests for the indication of infertility and ovarian reserves. It is primarily built on the predictive value of FSH for ovarian response and/or pregnancy after IVF (to tailor evaluation and management in women suspected of having hypothalamic-pituitary-ovarian (HPO) axis disorders impacting fertility). FSH appears to be an essential part in the test battery (together with LH and estrogen) with which to make these predictions. There are many assays; all showed adequate sensitivity and acceptable intra-assay variability. Standardized assays show high specificity (83–100%) for predicting poor response to stimulation (usually defined as < 2–3 follicles or %4 retrieved oocytes) using multiple cut-off points above 10 IU/L (10–20 IU/L). But because FSH is measured in conjunction with other laboratory tests, it is difficult to evaluate the value or impact of FSH testing separately. So the evaluation of this submission should be done in conjunction with the submissions for the other basic tests required (LH and estrogen). FSH testing is a basic element (alongside other laboratory tests) in tailoring the evaluation and management of women with infertility issues. There is evidence that the assays have significant inter- and intra-cycle variability, which limits their reliability. The overall correlation among different FSH assays is excellent, but absolute values can differ from one another. Clinicians may find it difficult to generalize FSH cut-off points reported in the medical literature to their practices unless they are using the very same assay and reference preparation. The accuracy in clinical practice depends on the cut-off point used.

World Health Organization. (‎2021)‎. The selection and use of essential in vitro diagnostics: report of the third meeting of the WHO Strategic Advisory Group of Experts on In Vitro Diagnostics, 2020 (‎including the third WHO model list of essential in vitro diagnostics)‎. World Health Organization. https://iris.who.int/handle/10665/339064