Utility of anti-Mullerian hormone in clinical decision making in BRCA mutation carriers

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Objectives: BRCA1/2 mutations increase cancer risk and may also confer risk for reduced fertility potential, posing a dilemma for BRCA mutation carriers desiring future fertility. On December 19, 2016, the FDA approved the use of Anti-Mullerian Hormone (AMH) assay for use in the assessment of ovarian reserve. AMH serum concentration accurately reflects the size of the pool of antral follicles, representing the quantity of the remaining primordial follicles and is not dependent on timing in the menstrual cycle. The purpose of this study is to determine the frequency of AMH testing to monitor ovarian reserve and utility in clinical decision making among patients with BRCA1/2 mutations. Methods: BRCA1/2 mutation carriers were retrospectively identified from electronic medical records using ICD-10 codes, and BRCA1/2 mutation carriers between the ages of 18 and 50 seen between January 1, 2017 and August 1, 2020 were included in the study. CPT codes were used to identify patients with prior AMH testing; for patients who received testing, AMH levels and clinical data were abstracted from medical records. AMH levels were categorized as low or normal based on reported age-dependent reference ranges1. Referral to REI and cryopreservation were outcomes of interest and were compared between patients with low vs. normal AMH levels using Fisher's exact test. Results: Of 1,186 BRCA1/2 mutation carriers of reproductive age seen at NYU Langone Health, 73 (6.2%) received AMH laboratory testing. Of the 73 patients who had AMH testing, 39 (53.4%) had BRCA1 mutation and 36 (49.3%) had BRCA2 mutations; two patients (2.7%) carried mutations on both genes. AMH tests were ordered by the following providers: 64 (87.7%), gynecologic oncologists; 7 (9.6%), general gynecologist; and 2 (2.7%), reproductive endocrinologists (REI). Of the 73 women, 53 (72.6%) were interested in future fertility and 11 (15.1%) were unsure. The median age at the time of AMH testing was 30 years (Interquartile range [IQR] 27-34 years), and the median AMH level was 3.6 ng/mL (IQR 1.9-6.0 ng/mL). Twenty-nine patients (39.7%) had low AMH levels and of patients with low AMH levels, 14 (48.3%) received REI referrals and 9 (31.0%) patients were seen by REI. Significantly more patients with low AMH underwent cryopreservation compared to patients with normal AMH (17.2% vs 2.3%, p=0.03). One patient decided to undergo risk reducing surgery following a very low AMH value of Conclusions: Only 6% of BRCA1/2 mutation carriers of reproductive age at our institution received AMH testing. Incorporation of AMH monitoring into the screening and preventative care of BRCA1/2 mutation carriers desiring future fertility may help guide patient decision making regarding oocyte cryopreservation and timing of risk reducing surgery; further prospective evaluation in needed to better assess the role of AMH in these patients.