Can Ultrasensitive Anti-Müllerian Hormone Testing Predict Failed Response to Ovarian Stimulation?

BackgroundAnti-Müllerian hormone (AMH) has emerged as a marker of ovarian reserve with prognostic value for ovarian response to gonadotropin stimulation. However, a minimum AMH value below which no response to ovarian stimulation can be expected has not been established, and many patients whose AMH was below the detectable range of traditional AMH assays have experienced successful follicle development and oocyte retrieval. A commercially available picoAMH ELISA assay from AnshLabs has a lower threshold of detection of 10 pg/mL, but the clinical utility of this test has not been fully described.ObjectiveThe purpose of this study was to determine whether use of an ultrasensitive AMH assay can predict successful oocyte retrieval in a population of women with diminished ovarian reserve (DOR).Materials and MethodsA database of successful in vitro fertilization (IVF) cycles (2008 to 2012) was interrogated for patients with diminished ovarian reserve (early follicular FSH of ≥10 IU/L), whose first cycle resulted in aspiration of at least 3 oocytes (n=24). Our SART database was also interrogated for patients with cancelled first IVF cycles during the same period, and patients who were cancelled for lack of ovarian response (<3 follicles) were included (n=24). Demographic information and ovarian reserve markers were recorded. Frozen serum samples were analyzed for AMH using the AnshLabs picoAMH ELISA. For results above the detectable range, samples were reanalyzed using the traditional AnshLabs AMH assay.ResultsNo demographic differences were found between groups. Two patients had AMH below the minimum limit of detection for traditional AMH assay (73 pg/mL); 17 patients had AMH above the maximum threshold for picoAMH. The successful group had higher antral follicle count (8.5 vs 6, p=0.003), higher AMH (847 vs 406 pg/mL, p=0.008), and higher FSH (13.1 vs 9.8 IU/L, p=0.009). AMH correlated with AFC (R=0.61, p<0.0001) but not with FSH. By ROC analysis, AMH >500 pg/mL has 83.3% sensitivity and 70.8% specificity to detect patients likely to successfully proceed to oocyte retrieval. Below AMH of 100 pg/mL, no patients achieved oocyte retrieval.ConclusionsDue to a lower threshold of detection, the PicoAMH assay may be able to predict successful ovarian stimulation among women with DOR using a threshold of 500 pg/mL, with good sensitivity and specificity. No participants with AMH <100 pg/mL achieved successful oocyte retrieval. Providers should consider measuring picoAMH in patients with DOR prior to attempting ovarian stimulation for IVF.SupportTable 1Demographics, patient characteristics, and results by groupSuccessfuln=24Droppedn=24p-valueAge (years)39.5 (32-45)40.5 (29-44)0.72BMI (kg/m2)22.3 (19.1-37.7)23.2 (15.4-36)0.55Gravidity0 (0-4)0 (0-5)0.86Parity0 (0-2)0 (0-3)0.15Additional infertility diagnosis Tubal Factor2 (8.3)2 (8.3)1.00 Endometriosis1 (4.2)0 (0)1.00 Uterine Factor3 (12.5)1 (4.2)0.61 Fertility Preservation1 (4.2)2 (8.3)1.00AMH (pg/mL)846 (142-2750)405 (35-2220)0.008*Day 3 FSH (IU/L)13.08 ± 2.519.83 ± 4.240.004*AFC8.5 (4-13)6 (2-18)0.003* Open table in a new tab BackgroundAnti-Müllerian hormone (AMH) has emerged as a marker of ovarian reserve with prognostic value for ovarian response to gonadotropin stimulation. However, a minimum AMH value below which no response to ovarian stimulation can be expected has not been established, and many patients whose AMH was below the detectable range of traditional AMH assays have experienced successful follicle development and oocyte retrieval. A commercially available picoAMH ELISA assay from AnshLabs has a lower threshold of detection of 10 pg/mL, but the clinical utility of this test has not been fully described. Anti-Müllerian hormone (AMH) has emerged as a marker of ovarian reserve with prognostic value for ovarian response to gonadotropin stimulation. However, a minimum AMH value below which no response to ovarian stimulation can be expected has not been established, and many patients whose AMH was below the detectable range of traditional AMH assays have experienced successful follicle development and oocyte retrieval. A commercially available picoAMH ELISA assay from AnshLabs has a lower threshold of detection of 10 pg/mL, but the clinical utility of this test has not been fully described. ObjectiveThe purpose of this study was to determine whether use of an ultrasensitive AMH assay can predict successful oocyte retrieval in a population of women with diminished ovarian reserve (DOR). The purpose of this study was to determine whether use of an ultrasensitive AMH assay can predict successful oocyte retrieval in a population of women with diminished ovarian reserve (DOR). Materials and MethodsA database of successful in vitro fertilization (IVF) cycles (2008 to 2012) was interrogated for patients with diminished ovarian reserve (early follicular FSH of ≥10 IU/L), whose first cycle resulted in aspiration of at least 3 oocytes (n=24). Our SART database was also interrogated for patients with cancelled first IVF cycles during the same period, and patients who were cancelled for lack of ovarian response (<3 follicles) were included (n=24). Demographic information and ovarian reserve markers were recorded. Frozen serum samples were analyzed for AMH using the AnshLabs picoAMH ELISA. For results above the detectable range, samples were reanalyzed using the traditional AnshLabs AMH assay. A database of successful in vitro fertilization (IVF) cycles (2008 to 2012) was interrogated for patients with diminished ovarian reserve (early follicular FSH of ≥10 IU/L), whose first cycle resulted in aspiration of at least 3 oocytes (n=24). Our SART database was also interrogated for patients with cancelled first IVF cycles during the same period, and patients who were cancelled for lack of ovarian response (<3 follicles) were included (n=24). Demographic information and ovarian reserve markers were recorded. Frozen serum samples were analyzed for AMH using the AnshLabs picoAMH ELISA. For results above the detectable range, samples were reanalyzed using the traditional AnshLabs AMH assay. ResultsNo demographic differences were found between groups. Two patients had AMH below the minimum limit of detection for traditional AMH assay (73 pg/mL); 17 patients had AMH above the maximum threshold for picoAMH. The successful group had higher antral follicle count (8.5 vs 6, p=0.003), higher AMH (847 vs 406 pg/mL, p=0.008), and higher FSH (13.1 vs 9.8 IU/L, p=0.009). AMH correlated with AFC (R=0.61, p<0.0001) but not with FSH. By ROC analysis, AMH >500 pg/mL has 83.3% sensitivity and 70.8% specificity to detect patients likely to successfully proceed to oocyte retrieval. Below AMH of 100 pg/mL, no patients achieved oocyte retrieval. No demographic differences were found between groups. Two patients had AMH below the minimum limit of detection for traditional AMH assay (73 pg/mL); 17 patients had AMH above the maximum threshold for picoAMH. The successful group had higher antral follicle count (8.5 vs 6, p=0.003), higher AMH (847 vs 406 pg/mL, p=0.008), and higher FSH (13.1 vs 9.8 IU/L, p=0.009). AMH correlated with AFC (R=0.61, p<0.0001) but not with FSH. By ROC analysis, AMH >500 pg/mL has 83.3% sensitivity and 70.8% specificity to detect patients likely to successfully proceed to oocyte retrieval. Below AMH of 100 pg/mL, no patients achieved oocyte retrieval. ConclusionsDue to a lower threshold of detection, the PicoAMH assay may be able to predict successful ovarian stimulation among women with DOR using a threshold of 500 pg/mL, with good sensitivity and specificity. No participants with AMH <100 pg/mL achieved successful oocyte retrieval. Providers should consider measuring picoAMH in patients with DOR prior to attempting ovarian stimulation for IVF. Due to a lower threshold of detection, the PicoAMH assay may be able to predict successful ovarian stimulation among women with DOR using a threshold of 500 pg/mL, with good sensitivity and specificity. No participants with AMH <100 pg/mL achieved successful oocyte retrieval. Providers should consider measuring picoAMH in patients with DOR prior to attempting ovarian stimulation for IVF.