Follicle Stimulating Hormone is an accurate predictor of azoospermia in childhood cancer survivors

Funding: RTM is supported by a Wellcome Trust Intermediate Clinical Fellowship (grant no: 098522), https://wellcome.ac.uk/what-we-do/directories/intermediate-clinical-fellowships-people-funded. TWK is supported by Engineering and Physical Sciences Research Council grant EP/P015638/1, http://gow.epsrc.ac.uk/NGBOViewGrant.aspx?GrantRef=EP/P015638/1.The accuracy of Follicle Stimulating Hormone as a predictor of azoospermia in adult survivors of childhood cancer is unclear, with conflicting results in the published literature. A systematic review and post hoc analysis of combined data (n = 367) were performed on all published studies containing extractable data on both serum Follicle Stimulating Hormone concentration and semen concentration in survivors of childhood cancer. PubMed and Medline databases were searched up to March 2017 by two blind investigators. Articles were included if they contained both serum FSH concentration and semen concentration, used World Health Organisation certified methods for semen analysis, and the study participants were all childhood cancer survivors. There was no evidence for either publication bias or heterogeneity for the five studies. For the combined data (n = 367) the optimal Follicle Stimulating Hormone threshold was 10.4 IU/L with specificity 81% (95% CI 76%–86%) and sensitivity 83% (95% CI 76%–89%). The AUC was 0.89 (95%CI 0.86–0.93). A range of threshold FSH values for the diagnosis of azoospermia with their associated sensitivities and specificities were calculated. This study provides strong supporting evidence for the use of serum Follicle Stimulating Hormone as a surrogate biomarker for azoospermia in adult males who have been treated for childhood cancer.Publisher PDFPeer reviewe

Follicle Stimulating Hormone is an accurate predictor of azoospermia in childhood cancer survivors

The accuracy of Follicle Stimulating Hormone as a predictor of azoospermia in adult survivors of childhood cancer is unclear, with conflicting results in the published literature. A systematic review and post hoc analysis of combined data (n = 367) were performed on all published studies containing extractable data on both serum Follicle Stimulating Hormone concentration and semen concentration in survivors of childhood cancer. PubMed and Medline databases were searched up to March 2017 by two blind investigators. Articles were included if they contained both serum FSH concentration and semen concentration, used World Health Organisation certified methods for semen analysis, and the study participants were all childhood cancer survivors. There was no evidence for either publication bias or heterogeneity for the five studies. For the combined data (n = 367) the optimal Follicle Stimulating Hormone threshold was 10.4 IU/L with specificity 81% (95% CI 76%–86%) and sensitivity 83% (95% CI 76%–89%). The AUC was 0.89 (95%CI 0.86–0.93). A range of threshold FSH values for the diagnosis of azoospermia with their associated sensitivities and specificities were calculated. This study provides strong supporting evidence for the use of serum Follicle Stimulating Hormone as a surrogate biomarker for azoospermia in adult males who have been treated for childhood cancer

Sensitivity and specificity of FSH-based azoospermia diagnosis for a range of threshold values.

<p>Median and 95% CI are calculated from 2,000 stratified bootstrap replicates of the combined data (n = 367).</p

Receiver-operator characteristic (ROC) curve analysis of FSH as predictor of azoospermia (combined cohort: n = 367).

<p>Area under the curve: 0·89 (95% CI 0·85–0·92. The optimal diagnostic threshold is 10.4 mIU/mL, with sensitivity 0.814 and specificity 0.823.</p

Forest plot of 95% confidence limits for the log-adjusted diagnostic odds ratio for the five studies listed in Table 1.

<p>The vertical dashed line denotes the line of no effect. Visual inspection shows that each study is statistically significant in its own right, that the intervals overlap to a great extent, and that therefore the studies are unlikely to be heterogeneous.</p

Flow-chart of systematic search methodology.

<p>n = number of studies; N = number of childhood cancer survivors fulfilling criteria.</p

Funnel plots for specificity (upper panel) and sensitivity (lower panel) relating study size to reported diagnostic accuracy for the five studies listed in Table 1.

<p>The Chi-squared statistical test for funnel plot asymmetry did not reach statistical significance (p = 0.32 for sensitivity; p = 0.17 for specificity), suggesting a lack of publication bias.</p

Characteristics of the included studies.

<p>Characteristics of the included studies.</p