haematological malignancies, other diseases matured oocytes cryopreserved and AFC and serum AMH levels Sensitivity and specificity Dezellus et al. (2017) 249 IV Low Women with breast cancer Predicting ovarian function Baseline serum hormone values, grouped by menstrual status at follow-up Stochino-Loi et al. (2017) 180 IV Moderate Women with stage 3 and 4 endometriosis Predicting pregnancy Association of pre-surgery AMH with occurrence of pregnancy and pregnancy outcomes Hamy et al. (2016) 134 IV Moderate Women with breast cancer Predicting pregnancy Association of baseline AMH and AMH with occurrence of pregnancy Su et al. (2010) 127 IV Low Female breast cancer survivors Predicting ovarian function Median hormone values in patients with CRA vs hormone values in patients with no CRA on second follow-up Ruddy et al. (2014) 124 II Moderate Women with breast cancer Predicting ovarian function Baseline serum hormone values, grouped by menstrual status at follow-up Multivariate analysis, predicting ovarian function Su et al. (2014) 109 II Low Women with breast cancer Predicting ovarian function Pre-chemotherapy levels of AMH, FSH, inhibin B and E2, and unadjusted HRs of return of ovarian function Multivariate analysis predicting ovarian function Iwase et al. (2016) 58 IV Moderate Women with endometriosis Predicting pregnancy Serum hormone values at baseline and follow-up, grouped by pregnancy status at follow-up Anderson et al. (2013) 55 II Low Women with early breast cancer Predicting ovarian function Baseline serum hormone values, grouped by menstrual status at follow-up Multivariate analysis predicting ovarian function ROC curve D’avila et al. (2015) 47 IV Moderate Women with breast cancer Predicting ovarian function Baseline serum hormone values, grouped by menstrual status at follow-up ROC curve Chai et al. (2014) 42 IV Low Women with early breast cancer Predicting ovarian function Sensitivity and specificity ROC curve
Beneventi et al. () Italy Case series Quality: Low risk of bias N=135 female survivors treated for childhood malignant and non-malignant diseases and patients who had received BMT for thalassaemia major or sickle cell anaemia. 92 (68.1%) diagnosed before menarche 43 (31.85%) diagnosed after menarche Median age at enrolment = 19 years (IQR 16–21) Median age at start of treatment = 10 years (IQR 6–16) Median time since treatment = 9 years (IQR 6–12). Blood samples were collected in the early follicular phase in patients with spontaneous menstrual cycles, and in withdrawal bleeding in patients treated with oral contraceptives or HRT. AMH Gen II ELISA According to manufacturer’s instructions. Inhibin B Gen II ELISA According to manufacturer’s instructions Correlation: Spearman’s rank correlation test Biacchiardi et al. () Italy Case series Quality: Low risk of bias N=43 normo-ovulatory women aged 18–42 years who were affected by one or more ovarian endometriomas Mean age = 34.2 ± 5.4 years n=7 ASRM stage 2 n=26 ASRM stage 3 n=10 ASRM stage 4 Blood samples were drawn during the early follicular phase (day 3) of the month in which surgery was scheduled. Sera were frozen at -20°C for subsequent centralised testing EIA AMH/MIS assay Intra-assay and inter-assay CoV of 12.3% and 14.2%, respectively. AFC TVUS Transvaginal ultrasound examination was performed in the early follicular phase in order to estimate the AFC. AFC was determined by counting the follicles >3 mm diameter that were visible through a complete scanning of both ovaries. In order to avoid any operator-linked bias, all ultrasound examinations were done by the same investigators using the same equipment. Correlation: Pearson’s bivariate correlation test
Quality: Low/moderate/high risk of bias Treatment: ovarian endometrioma ablation. Inclusion criteria: deep infiltrating endometriosis or endometriomas measuring >3 cm, pregnancy intention before surgery, benefited from pre- and post-operative assessment of AMH, minimum 12 month follow-up. Exclusion criteria: women with superficial endometriosis and hydro salpinx. curves were done to estimate the probability of according to post-operative time and were compared using the log rank test. Follow-up period: >1 year. Post-operative follow-up was based on data from questionnaires completed at 1, 3, and 5 years after surgery. pregnancy Pregnancy outcomes (delivery, miscarriage, ectopic pregnancy, ongoing pregnancies) Conception mode (spontaneous or ART) Pregnancy rate AMH = anti-Müllerian hormone; ANOVA = analysis of variance; ART = assisted reproductive technology; CoV = coefficient(s) of variation; EIA = enzyme Immunoassay; ELISA = enzyme-linked immunosorbent assay; HCT = haematopoietic cell transplantation; NR = not reported
D Table 88 Evidence profile table for the analytical validity of AMH testing for girls or women undergoing gonadotoxic treatment Outcome No. of participants, no. of studies and study design Risk of bias Inconsistency Indirectness Other Results for AMH testing Results for comparator test Analytical validity QoE Importance Analytical validity of AMH tests compared with clinical reference standard n=30 k=1 Case series 0 Low risk of bias NA -1 No evidence of incremental value of AMH was provided -1 Only one small study No There was a 40-fold difference in level of detectable AMH between the two AMH tests. Predictably, more samples had undetectable levels with the less sensitive EIA AMH/MIS assay (53 samples) compared with the pico-AMH ELISA (33 samples). NA ⨁⨀⨀⨀ Very low quality Important (to know if different AMH assays are comparable) AUC of AMH to discriminate between women with and without menses n=56 k=1 Case series 0 Low risk of bias NA -1 No evidence of incremental value of AMH was provided -1 Only one small study No AUC of AMH ≤ 25 pg/ml was 0.71 Comparator AUCs: AFC (total 2–10 mm) <1: 0.82 FSH ≥40IU/L: 0.72 Inhibin B ≤5 pg/ml: 0.63 AFC <1 + AMH ≤25 pg/ml: 0.87 AFC <1 + FSH ≥40IU/L: 0.87 AMH ≤25 pg/ml + FSH ≥40IU/L: 0.74 ⨁⨀⨀⨀ Very low quality Not important (unknown how to use this evidence in clinical practice) Sensitivity of AMH compared to other ovarian reserve tests in distinguishing n=56 k=1 Case series 0 Low risk of bias NA -1 No evidence of incremental value of AMH was provided -1 Only one small study, No Sensitivity AMH ≤ 25 pg/mL 76%. Sensitivities comparators: AFC (total 2–10 mm) < 1: 79% ⨁⨀⨀⨀ Very low quality Not important (unknown how to use this evidence in clinical
CRA no CI reported FSH ≥ 40IU/L: 78% Inhibin B ≤ 5pg/ml: 54% practice) Specificity of AMH compared to other ovarian reserve tests in distinguishing CRA n=56 k=1 Case series 0 Low risk of bias NA -1 No evidence of incremental value of AMH was provided -1 Only one small study, no CI reported No Specificity AMH ≤25 pg/mL 60%. Specificities comparators: AFC (total 2–10 mm) <1: 89% FSH ≥40IU/L: 64% Inhibin B ≤ 5pg/ml: 64% ⨁⨀⨀⨀ Very low quality Not important (unknown how to use this evidence in clinical practice) Correlation between different AMH tests n=98 k=2 Case series 0 Low risk of bias 0 -1 No evidence of incremental value of AMH was provided -1 Low number of patients included No AMH Gen II ELISA versus Ansh Labs AMH ELISA: rho=0.964, p<0.0001 AMH Gen II ELISA versus Ultrasensitive AMH ELISA: rho=0.92, p<0.001 AMH Gen II ELISA vs ELISA: rho=0.92, p<0.001 Ultrasensitive AMH ELISA vs pico-AMH ELISA: rho = 0.99, p<0.001 NA ⨁⨀⨀⨀ Very low quality Important (to know if different AMH assays are comparable) Concordance between AMH and FSH n=53 k=1 Case series 0 Low risk of bias NA -1 No evidence of incremental value of AMH was provided -1 Low number of patients only one No The overall, positive and negative per cent agreements between low AMH and high FSH levels were 77.4%, 57.1% and 67.6%, respectively. See results for AMH testing’ column ⨁⨀⨀⨀ Very low quality Not important (unknown how to use this evidence in clinical practice)
study Correlation between AMH and AFC n=366 k=5 Case series 0 Low risk of bias 0 All positive moderate to strong correlations -1 No evidence of incremental value of AMH was provided 0 No Correlation (range): Positive: 0.62 (0.44–0.83), k=4 Pre-cancer: 0.48 (0.44–0.52), k=2 Post-cancer: 0.72, k=1 Post-childhood cancer: 0.83, k=1 Pre-endo surgery: 0.842 (k=1) See results for AMH testing’ column ⨁⨀⨀⨀ Very low quality Not important (unknown how to use this evidence in clinical practice) Correlation between AMH and FSH n=462 k=7 Case series 0 Low risk of bias -1 Inconsistent results between studies -1 No evidence of incremental value of AMH was provided -1 and results No Negative: -0.50 (-0.52, -0.47; k=2), NS (k=3) Pre-cancer: -0.47, k=1, NS, k=2 Post-cancer: NS, k=1 Post-childhood cancer: -0.52, k=1 Serum AMH versus serum FSH levels: NS, k=3 Detectable AMH versus serum FHS: -0.55, k=1 See results for AMH testing’ column ⨁⨀⨀⨀ Very low quality Not important (unknown how to use this evidence in clinical practice) Correlation between AMH and E2 n=331 k=4 Case series 0 Low risk of bias -1 Inconsistent results between studies -1 No evidence of incremental value of AMH was provided -1 and results No Positive: 0.30 (0.15–0.44), k=2 Negative: -0.64, k=1 Pre-cancer -0.64 and 0.15, k=2 Positive post-cancer: 0.44, k=1 Pre- and post-cancer: NS (k=1) See results for AMH testing’ column ⨁⨀⨀⨀ Very low quality Not important (unknown how to use this evidence in clinical practice)