Changes in Serum Inhibin B Following Orchiopexy for Cryptorchidism: A Systematic Review and Meta-Analysis of Endocrine Recovery

Summary

This study aims to determine whether serum inhibin B can serve as a biomarker to evaluate the efficacy of orchiopexy in boys with cryptorchidism.

Abstract

This study evaluated the effects of pediatric orchiopexy on serum inhibin B concentrations, confirmed postoperative changes in endocrine parameters, and explored the potential utility of serum inhibin B as a marker of postoperative endocrine recovery. A systematic search of PubMed, Cochrane Library, Embase, Scopus, and Web of Science databases was conducted to identify self-controlled studies of boys with cryptorchidism who underwent orchiopexy. Relevant reference literature, related journals, and conference proceedings were also manually screened. Following quality assessment and data extraction, six studies involving 394 boys were included in the meta-analysis. In the primary analysis of studies reporting 6-month follow-up, serum inhibin B concentrations were significantly higher after orchiopexy than before surgery (MD, 14.03 pg/mL; 95% CI, 4.05–24.01 pg/mL; P = 0.014). Moderate-to-substantial heterogeneity was observed (I² = 67.5%). Evidence from 1- and 12-month follow-up studies was limited and yielded inconsistent findings. No significant postoperative changes were observed in follicle-stimulating hormone (FSH) (MD, −0.03 IU/L; 95% CI, −0.30 to 0.24 IU/L) or luteinizing hormone (LH) (MD, −0.02 IU/L; 95% CI, −0.07 to 0.04 IU/L). Orchiopexy was associated with a significant early increase in serum inhibin B, suggesting postoperative Sertoli cell recovery. Serum inhibin B may represent a potential short-term marker of endocrine recovery following orchiopexy, although further validation is required.

Introduction

Cryptorchidism is among the most common congenital abnormalities in boys, affecting approximately 2% to 4% of term infants and a substantially higher proportion of preterm infants. In addition to congenital cryptorchidism, acquired (or ascending) cryptorchidism, where a previously scrotally positioned testis gradually ascends out of the scrotum during childhood, represents a clinically relevant entity with a distinct natural history that may also warrant surgical correction¹. Persistence of the testis outside the scrotum is associated with impaired germ cell development, reduced fertility potential, testicular atrophy, and an increased risk of testicular malignancy later in life. Current guidelines therefore recommend orchiopexy during early childhood, preferably before 12 to 18 months of age, to preserve testicular development and optimize long-term reproductive outcomes^2,3,4.

Despite the widespread use of orchiopexy, assessment of postoperative testicular recovery remains challenging. Histological parameters obtained from testicular biopsy, including gonocyte and spermatogonial counts and the spermatogonia-to-tubule ratio, are considered important indicators of fertility potential⁴. However, testicular biopsy is invasive, unsuitable for routine follow-up, and may be associated with procedural complications. Consequently, there is considerable interest in identifying noninvasive biomarkers that reflect testicular function after surgical correction.

Inhibin B is a dimeric glycoprotein hormone composed of an α-subunit and a βB-subunit, produced predominantly by Sertoli cells. It represents the principal circulating marker of Sertoli cell function in prepubertal boys. Serum inhibin B concentrations correlate with seminiferous tubule development and are reduced in boys with cryptorchidism compared with healthy controls⁵. As a result, changes in serum inhibin B following orchiopexy have been proposed as a potential indicator of postoperative endocrine recovery. However, studies evaluating serum inhibin B before and after orchiopexy have reported inconsistent findings, and the magnitude and temporal pattern of postoperative changes remain uncertain^6,7.

This meta-analysis aims to quantify the effect of orchiopexy on serum inhibin B concentrations as a primary endpoint of Sertoli cell recovery. Its secondary objective is to explore whether the observed postoperative changes support the potential utility of inhibin B as a non-invasive marker for monitoring surgical efficacy, while acknowledging that current evidence remains insufficient to validate it as a surrogate for long-term fertility.

Protocol

This systematic review and meta-analysis was prospectively registered in the PROSPERO International Prospective Register of Systematic Reviews (registration number: CRD420261428789). This analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines.

Search strategy
A systematic search of PubMed, Embase, Cochrane Library, Scopus, and Web of Science was conducted from database inception through March 2025. The search strategy included the terms “cryptorchidism,” “undescended testis,” “orchiopexy,” “inhibin B,” “INHB,” “follicle-stimulating hormone,” “FSH,” “luteinizing hormone,” and “LH”.

Study eligibility criteria
The review was structured according to the PICO framework: Population—boys diagnosed with cryptorchidism; Intervention—orchiopexy; Comparator—preoperative baseline status (self-controlled); Outcome—changes in serum inhibin B concentrations.

Studies were eligible if they met the following criteria: (1) included boys diagnosed with cryptorchidism who underwent orchiopexy; (2) reported serum inhibin B concentrations before and after surgery; (3) provided sufficient data for quantitative synthesis; and (4) were prospective or retrospective cohort studies. Studies were eligible regardless of cryptorchidism laterality, surgical approach, or postoperative follow-up duration, provided they reported the required endocrine data pre- and post-surgery.

Studies were excluded if they were reviews, editorials, letters, case reports, conference abstracts without sufficient data, animal or laboratory studies, studies involving adult populations, non-English publications, or duplicate publications.

The reference lists of included studies and relevant review articles were screened to identify additional eligible studies. Two investigators independently conducted the literature search and data extraction. Disagreements were resolved through discussion or consultation with a third reviewer.

Data extraction
Two reviewers independently screened studies and extracted data using a standardized form. Extracted information included study characteristics, participant characteristics, orchiopexy method, follow-up duration, postoperative complications, and endocrine outcomes. The primary outcome was serum inhibin B concentration. For each study, serum inhibin B concentrations before and after orchiopexy, together with measures of variability, were extracted. Data on serum follicle-stimulating hormone and luteinizing hormone concentrations were also collected when available.

Quality assessment
Nonrandomized studies were evaluated using the Methodological Index for Non-Randomized Studies instrument⁸, whereas the randomized controlled trial was assessed using the Cochrane Risk of Bias 2 tool⁹. MINORS scores of 13–16 were considered high quality, 9–12 moderate quality, and ≤8 low quality. The certainty of evidence for the primary outcome was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework¹⁰.

Statistical analysis
The primary outcome was the mean difference in serum inhibin B concentration before and after orchiopexy. Pooled mean differences with corresponding 95% confidence intervals were calculated using a random-effects model. For the primary analysis, the mean and standard deviation of paired differences were extracted when directly reported. For studies reporting only separate preoperative and postoperative summary statistics, the standard deviation of the mean change was calculated using the following equation:

Where SD_diff is the standard deviation of the paired difference, SD_pre and SD_post are the standard deviations of the preoperative and postoperative measurements, respectively, and r is the within-subject correlation coefficient. A conservative value of r = 0.5 was assumed when the actual correlation was not reported.

Heterogeneity was assessed using the I² statistic. Because of the limited number of included studies, formal subgroup analyses and meta-regression were not performed. Publication bias was not formally assessed because fewer than 10 studies were available. Leave-one-out sensitivity analyses were performed to evaluate the influence of individual studies on the pooled effect estimate.

All statistical analyses were performed using R version 4.4.1. Statistical significance was defined as a two-sided P value < 0.05.

Results

Study selection and search results
A total of 789 records were identified through the database searches (PubMed, Cochrane, Embase, Scopus, and Web of Science). After removing 446 duplicate records, 343 articles remained for initial screening. Two reviewers independently screened the titles and abstracts of these 343 articles and excluded 306 records that were clearly irrelevant to the study topic or did not meet the eligibility criteria (e.g., animal experiments, case reports, reviews, conference abs...

Discussion

In this systematic review and meta-analysis, serum inhibin B concentrations at 6 months after orchiopexy were significantly higher than preoperative levels in boys with cryptorchidism. Although the magnitude of change varied across studies, the overall findings indicate that postoperative increases in inhibin B are consistently observed following surgical correction. These results provide quantitative evidence that orchiopexy is associated with favorable changes in a circulating marker of Sertoli cell function and testic...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Cochrane RoB 2 Tool	Higgins et al., 2011	N/A	Risk of bias assessment tool for randomized controlled trials
FSH ELISA Kit	N/A	N/A	For quantitative measurement of serum follicle-stimulating hormone
GRADE Framework	Izcovich et al., 2023	N/A	Certainty of evidence assessment framework
Human serum samples	N/A	N/A	Collected from pediatric patients pre- and post-orchiopexy
Inhibin B ELISA Kit	N/A	N/A	For quantitative measurement of serum inhibin B
LH ELISA Kit	N/A	N/A	For quantitative measurement of serum luteinizing hormone
MINORS Instrument	Slim et al., 2003	N/A	Methodological quality assessment tool for non-randomized studies
R software	R Foundation for Statistical Computing	Version 4.4.1	Statistical analysis software for meta-analysis