Introduction
Anti-Müllerian hormone (AMH) is widely used as a biomarker of ovarian reserve and is clinically applied to estimate the quantitative follicle pool and guide counseling and treatment in reproductive medicine, including assisted reproduction and fertility preservation [
1,
2]. Because AMH has relatively low intra-cycle variability compared with gonadotropins, it is often considered a practical marker for assessment across the menstrual cycle [
2]. However, professional guidance emphasizes that ovarian reserve markers, including AMH, should not be interpreted as direct measures of current fertility potential, particularly in individuals without proven infertility [
2].
In the context of delayed childbearing and persistently low fertility, interest in fertility assessment and reproductive life planning has increased. At the same time, direct-to-consumer (DTC) fertility testing has expanded, and AMH is frequently marketed as a ‘fertility test.’ However, a content analysis of websites selling DTC AMH tests found that marketing claims may overstate the ability of AMH testing to predict natural fertility, underscoring the need for accurate information and appropriate counseling when AMH tests are offered outside specialist settings [
3]. Recent population-based and trial data further suggest that women’s interest in AMH testing decreases when evidence-based information about the test’s limitations is provided [
4,
5].
Venipuncture remains the conventional approach for serum AMH testing, but it may pose practical barriers in decentralized care models, including travel, limited access to phlebotomy services, and discomfort associated with needle-based sampling. Capillary blood sampling by fingerstick is minimally invasive and may facilitate decentralized sample collection, potentially expanding access to fertility-related testing in telemedicine and remote care settings.
Previous studies have reported strong concordance between fingerstick or capillary and venous sampling for AMH and other fertility-associated hormones, supporting the feasibility of capillary sampling for ovarian reserve assessment [
6-
8]. Nevertheless, agreement may be influenced by preanalytical factors, such as collection devices and tube additives, as well as assay-specific performance characteristics [
8,
9]. Evidence specific to Korean reproductive-aged women and the automated fluorescence immunoassay system (AFIAS) AMH assay (Boditech Med) remains limited. Therefore, this study compared serum AMH concentrations measured in paired capillary fingerstick and standard venous samples and evaluated participant tolerability of fingerstick sampling.
Methods
1. Study design and participants
This prospective method-comparison study was conducted at Korea University Anam Hospital, Seoul, Republic of Korea, from October 26 to 30, 2023. The study protocol was approved by the Institutional Review Board of Korea University Anam Hospital (Approval No. 2023AN0427), and all participants provided written informed consent before enrollment.
Reproductive-aged women attending the outpatient clinic were eligible for inclusion. Women were excluded if they were currently pregnant, had a history of ovarian surgery, or had a major systemic illness that could materially affect ovarian function. Demographic and relevant clinical information, including hormonal contraceptive use and the presence of polycystic ovary syndrome, were collected when available.
2. Sample collection and handling
During a single clinic visit, paired blood samples were obtained from each participant: venous blood collected by standard venipuncture and capillary blood collected by fingerstick using a commercially available collection kit. Fingerstick sampling followed standardized instructions, and the order of venipuncture and fingerstick sampling was recorded.
Approximately 0.5 mL of capillary blood was collected into a microcollection tube suitable for serum preparation, and approximately 5 mL of venous blood was collected into a routine serum tube in line with institutional practice. Samples were processed according to the manufacturer’s instructions and institutional standard operating procedures to obtain serum, and AMH testing was performed as soon as feasible after collection. Paired samples from the same participant were analyzed on the same assay platform.
3. AMH assay
Serum AMH concentrations were quantified using the AFIAS AMH assay, an automated fluorescent immunoassay. All laboratory analyses were performed at EONE Laboratories, Republic of Korea. According to the manufacturer, the reportable range for the AFIAS AMH assay is 0.02 to 15 ng/mL [
10]. Quality control and instrument maintenance were performed in accordance with the manufacturer’s recommendations. No postanalytical correction factor or conversion equation was applied; AMH concentrations from fingerstick and venous samples were analyzed as directly measured by the AFIAS AMH assay.
4. Outcomes
The primary outcome was agreement between venous and fingerstick serum AMH measurements. Secondary outcomes were participant-reported pain associated with each sampling method and qualitative feedback on acceptability and preference. Pain was assessed immediately after each procedure using an 11-point numeric rating scale (NRS; 0=no pain, 10=worst pain imaginable).
5. Statistical analysis
Method-comparison analyses were performed using Passing–Bablok regression with the cumulative sum (CUSUM) test for linearity and Bland–Altman analysis to assess agreement and potential systematic bias between sampling methods [
11,
12]. For the Bland–Altman analysis, differences were calculated as venous minus fingerstick values, and the 95% limits of agreement were defined as the mean difference ±1.96 standard deviations. Correlation was assessed using Pearson and Spearman correlation coefficients. Agreement was further summarized using the intraclass correlation coefficient (ICC), calculated with a two-way mixed-effects model and an absolute-agreement definition for single and average measures. Pain scores were compared between procedures using the Wilcoxon signed-rank test. Analyses were conducted using complete-case data; the analytic sample size varied by outcome due to missing paired measurements, such as missing pain scores. A two-sided p-value <0.05 was considered statistically significant. Analyses were performed using IBM SPSS Statistics for Windows ver. 27.0 (IBM Corp.).
Results
Paired venous and capillary fingerstick AMH measurements were available for 90 participants. Participants were 25–46 years old (mean age, 31.5). Mean serum AMH concentrations were 2.74 ng/mL in venous samples (range, 0.11 to 9.99; median, 2.15) and 3.42 ng/mL in fingerstick samples (range, 0.17 to 11.55; median, 3.14).
Passing–Bablok regression (
Figure 1) demonstrated a linear relationship between methods (y=0.123+1.175x, where y represents fingerstick AMH and x represents venous AMH), with an intercept of 0.1233 (95% confidence interval [CI], 0.0345 to 0.2637) and a slope of 1.1753 (95% CI, 1.1248 to 1.2404). The CUSUM test showed no significant deviation from linearity (
p=0.07).
Using a two-way mixed-effects model with an absolute-agreement definition, agreement between methods was excellent (single-measure ICC, 0.930 [95% CI, 0.267 to 0.980]; average-measure ICC, 0.964 [95% CI, 0.422 to 0.990]). The ICC was significantly greater than zero (F[90, 90]=79.255, p<0.001).
Correlation analyses showed strong associations between venous and fingerstick AMH values (Spearman ρ=0.979 [95% CI, 0.968 to 0.986], p<0.0001; Pearson r=0.9822 [95% CI, 0.9731 to 0.9883], p<0.0001).
Bland–Altman analysis (
Figure 2) showed a mean bias, calculated as venous minus fingerstick AMH, of −0.67 ng/mL, with 95% limits of agreement from −1.62 to 0.28 ng/mL. The dispersion of differences increased at higher mean AMH concentrations.
Pain scores were low for both procedures, with mean NRS scores of 2.36 for venipuncture and 2.91 for fingerstick sampling. In paired comparisons, fingerstick sampling was associated with significantly higher pain than venipuncture (Wilcoxon signed-rank test, n=90; Z=2.451; p=0.014).
Discussion
In this prospective paired-sample comparison study, serum AMH concentrations measured in capillary fingerstick samples showed high agreement with those measured in venous samples using the AFIAS AMH assay. Regression analysis suggested proportional bias, with fingerstick values tending to be higher than venous values, and Bland–Altman plots indicated that discrepancies became more apparent at higher AMH concentrations.
These findings are consistent with prior studies supporting the feasibility of capillary sampling for AMH measurement. Burke et al. [
6] reported high concordance between fingerstick and venipuncture AMH measurements in a clinical cohort. In a separate validation study of at-home serum AMH testing, Silliman et al. [
7] demonstrated high concordance between home-collected and clinic-collected samples when appropriate collection and processing procedures were used. Alternative microsampling approaches, such as dried blood spots, have also shown promising correlations with serum AMH, although matrix effects and processing steps may affect analytical performance [
8].
Several mechanisms may have contributed to the observed proportional differences. Capillary sampling may be sensitive to preanalytical factors, including sample volume, clotting time, and tube additives; these factors may have a greater impact at higher analyte concentrations and as the reportable range is approached. In addition, AMH values are known to vary across assay platforms and calibrations, underscoring the importance of assay-specific evaluation and cautious interpretation when methods or specimen types are changed [
9]. Notably, the AFIAS AMH assay has been analytically evaluated against established automated platforms and has demonstrated strong correlation in serum samples [
9].
Although overall agreement was high, proportional bias was observed, with fingerstick values tending to be slightly higher than venous values. Therefore, the two sampling methods should not yet be considered fully interchangeable without further calibration and external validation, particularly near clinical decision thresholds and at extreme AMH levels. Because no correction equation was derived or validated in this study, the findings support analytical comparability rather than direct replacement of venous testing.
From a clinical perspective, fingerstick-based sampling may improve access to ovarian reserve assessment in settings where venipuncture is inconvenient, such as telemedicine consultations or fertility preservation counseling. Because AMH testing is typically used for elective ovarian reserve evaluation rather than emergency decision-making, the potential value of fingerstick sampling lies primarily in improving accessibility rather than urgency. A simplified capillary sampling approach may therefore be useful in decentralized care settings or in situations where access to venipuncture or phlebotomy services is limited. However, the expanding availability of DTC AMH testing raises issues related to interpretation: marketing materials may overstate the predictive value of AMH for natural fertility [
3], and evidence-based information about AMH testing can substantially alter women’s perceptions and interest [
4,
5]. Accordingly, decentralized AMH testing should be accompanied by appropriate clinical interpretation and counseling, consistent with professional recommendations that ovarian reserve markers should not be used as stand-alone 'fertility tests' in individuals without proven infertility [
2]. Importantly, this sampling approach is intended to expand access to clinician-guided AMH testing rather than position AMH as a stand-alone fertility test.
This study has several limitations. First, it was conducted at a single center with a modest sample size, which may limit generalizability. Second, few participants had AMH values at the extreme low or high ends of the distribution. Because disagreement appeared greater at higher AMH concentrations, and because even small absolute differences may be clinically meaningful at very low AMH levels, the clinical interchangeability of fingerstick and venous sampling at the extremes remains uncertain. Third, unsupervised home collection, shipping conditions, and delayed processing were not evaluated, although all are relevant to real-world at-home testing. Fourth, some participants used hormonal contraception, which may influence AMH concentrations and could have introduced additional variability. Because of the modest sample size, adequately powered stratified analyses according to contraceptive use could not be performed [
13]. Finally, no correction equation was derived or externally validated; therefore, the present data support overall analytical agreement rather than direct replacement of venous testing across all clinical contexts. Future studies should include larger and more diverse cohorts, incorporate testing of preanalytical conditions, including delayed processing and shipping simulations, and evaluate clinically relevant decision thresholds and classification agreement, such as low, normal, and high AMH categories, rather than relying solely on continuous agreement metrics.
In conclusion, fingerstick sampling showed high overall agreement with venipuncture for AMH measurement using the AFIAS AMH assay and may improve access to clinician-guided ovarian reserve assessment in decentralized settings. However, fingerstick values tended to be higher than venous values, and further validation, potentially including assay-specific calibration, is needed before the two methods can be considered clinically interchangeable, especially at the extreme low and high ends of the AMH range.