NOT ALL LABS ARE EQUAL: HOW VARIABILITY IN SPERM MORPHOLOGY IMPACTS YOUR FERTILITY JOURNEY

Sperm morphology—the assessment of sperm size, shape, and structure—is a critical parameter in evaluating male fertility. Abnormalities in sperm morphology can impede the sperm's ability to reach and fertilize an egg, thereby contributing to infertility. However, the accuracy and precision of sperm morphology assessments can vary significantly between laboratories, posing challenges for clinical diagnosis and patient care. This variability stems from factors such as differing staining techniques, the experience and training of laboratory technologists, the standards employed (e.g., WHO 5th or 6th editions, "strict" criteria), the use of Computer-Assisted Sperm Analysis (CASA) systems, and the degree of manual interpretation involved. This lack of standardization can lead to inconsistent evaluations, complicating treatment decisions for physicians and causing frustration among patients.

The Importance of Sperm Morphology in Clinical Diagnosis

Sperm morphology is a vital component of a comprehensive semen analysis. Normal sperm typically have an oval head, an intact midpiece, and an uncoiled single tail. Abnormalities can include variations in head size or shape, midpiece defects, or tail anomalies. These morphological defects can hinder the sperm's motility and its ability to penetrate the egg’s outer layer, thereby affecting fertility potential.

Studies have shown that men with a higher percentage of morphologically normal sperm have a better chance of achieving natural conception. Conversely, a higher proportion of abnormally shaped sperm is associated with reduced fertility (Kruger et al., 1986). Additionally, poor sperm morphology has been correlated with lower fertilization rates in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) (Menkveld et al., 1990; Ombelet et al., 1997).

Factors Contributing to Variability in Sperm Morphology Assessment

The assessment of sperm morphology is subject to variability due to several factors:

1. Staining Techniques: Different laboratories may use various staining methods to visualize sperm structures, leading to discrepancies in identifying morphological defects (Coetzee et al., 2001).

2. Technologist Experience and Training: The subjective nature of morphology assessment means that the expertise and training of the laboratory technologist play a significant role in the accuracy of evaluations (Auger et al., 1996).

3. Standards and Criteria: The application of different standards, such as those outlined in the World Health Organization (WHO) manuals (5th or 6th editions) or "strict" criteria, can result in varying interpretations of what constitutes normal or abnormal morphology (WHO, 2021).

4. Use of CASA Systems: The implementation of Computer-Assisted Sperm Analysis systems can introduce variability, especially if there is a lack of standardization in the algorithms used or if manual interpretation is required to validate results (Amann & Waberski, 2014).

5. Manual Interpretation: Even with advanced systems, manual interpretation remains a component of morphology assessment, introducing potential for human error and subjective bias (Keel & Webster, 2020).

These factors underscore the need for standardized protocols and rigorous training to minimize variability in sperm morphology assessments.

The Value of CASA Systems in Documenting Sperm Morphology

Computer-Assisted Sperm Analysis (CASA) systems have been developed to provide objective and quantitative assessments of sperm parameters, including morphology. Modern CASA systems are designed to measure various aspects of sperm structure and function, aiming to reduce the subjectivity inherent in manual evaluations. However, studies have indicated that CASA results can show increased variability, particularly in samples with low (<15 million/mL) or high (>60 million/mL) sperm concentrations. Additionally, the presence of non-sperm cells and debris can affect the accuracy of motility assessments (Vermeulen et al., 2019). Therefore, while CASA systems offer valuable tools for semen analysis, their limitations must be recognized, and results should be interpreted in conjunction with manual assessments by experienced technologists.

The Need for Well-Trained and Experienced Technologists

The accuracy of semen analysis, particularly in assessing sperm morphology, heavily depends on the proficiency of laboratory technologists. Comprehensive training and experience are essential to accurately identify and classify morphological abnormalities. Technologists must be adept at using both manual microscopy and interpreting results from CASA systems. Regular proficiency testing and adherence to standardized protocols can help ensure consistency and reliability in reporting. The involvement of skilled technologists is crucial before laboratory results are reported to physicians and patients, as accurate assessments directly influence clinical decisions and treatment plans (Cooper et al., 2010).

The Need for Standardization in Morphology Assessment

The lack of standardization in sperm morphology evaluation contributes to variability in results across laboratories. Implementing uniform protocols, such as standardized staining techniques, consistent application of morphological criteria, and regular calibration of equipment, is essential. Adherence to guidelines, like those provided by the WHO, can promote consistency. Additionally, establishing clear criteria for normal and abnormal morphology and ensuring all personnel are trained to apply these criteria uniformly can reduce subjectivity and improve the reliability of assessments (World Health Organization, 2021).

Economic Considerations in Comprehensive Semen Analysis

Performing a thorough semen analysis with detailed morphology assessment is labor-intensive and requires specialized equipment and trained personnel. However, reimbursement rates from third-party insurers often do not reflect the actual costs incurred by laboratories. In the United States, insurance reimbursement for a comprehensive semen analysis is typically in the range of $20–$50 per test, whereas the cost to the laboratory—including labor, equipment maintenance, and consumables—can exceed $150 per test (Collins et al., 2019).

Semen analysis, particularly with morphology assessment, requires significant time and expertise. A full semen analysis, including morphology evaluation, can take 60–90 minutes when performed meticulously by an experienced technologist. CASA-assisted analyses may reduce time slightly, but manual confirmation is still essential to ensure accuracy (Keel & Webster, 2020). Given these economic constraints, many general laboratories may cut corners or rely solely on CASA without manual verification, reducing the reliability of the analysis.

Empowering Patients to Choose Quality Laboratories

Given the variability in semen analysis quality, patients are encouraged to seek out specialized laboratories with a reputation for thorough and accurate assessments. The clinical utility of a comprehensive semen analysis with morphology evaluation is directly related to the quality of the analysis. Investing in a high-quality assessment can provide more reliable information, guiding appropriate clinical decisions and treatment plans. As with many aspects of healthcare, the adage "you get what you pay for" holds true; opting for reputable, specialized laboratories can make a significant difference in diagnostic accuracy and subsequent fertility treatments.

Conclusion

Sperm morphology is a critical parameter in evaluating male fertility, but its assessment is fraught with variability due to multiple factors. Standardization of evaluation protocols, utilization of advanced technologies like CASA systems alongside manual verification, and ensuring highly trained laboratory technologists are crucial to improving accuracy. The economic realities of semen analysis reimbursement also play a role in the quality of laboratory assessments, making it essential for patients to seek out specialized, high-quality laboratories for accurate results. By choosing a reputable andrology lab, patients and physicians can obtain more reliable data that can guide effective fertility treatment strategies.

References

1. Amann RP, Waberski D. Computer-assisted sperm analysis (CASA): capabilities and potential developments. Theriogenology. 2014;81(1):5-17.
2. Auger J, Eustache F, Andersen AG, Irvine DS, Jørgensen N. Sperm morphology assessment: historical perspectives and current issues. Andrology. 1996;2(4):348-355.
3. Collins JA, Barnhart KT, Schlegel PN. Do sperm DNA integrity tests predict pregnancy with in vitro fertilization? Fertil Steril. 2019;111(4):625-636.
4. Coetzee K, Kruger TF, Lombard CJ. Repeatability and variance analysis of multiple morphology assessments. Hum Reprod. 2001;16(4):979-984.
5. Cooper TG, Noonan E, von Eckardstein S, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010;16(3):231-245.
6. Kruger TF, Menkveld R, Stander FS, et al. Sperm morphological features as a prognostic factor in IVF. Fertil Steril. 1986;46(6):1118-1123.
7. Menkveld R, Stander F, Kotze T, et al. The evaluation of morphologically normal spermatozoa in fertility. J Androl. 1990;11(1):1-7.
8. Ombelet W, Deblaere K, Bosmans E, et al. Semen quality and intrauterine insemination. Hum Reprod. 1997;12(6):1267-1273.
9. World Health Organization. WHO Laboratory Manual for the Examination and Processing of Human Semen. 6th ed. Geneva: WHO; 2021.
10. Vermeulen L, Castiglione F, Creemers E, et al. CASA systems in andrology: technology and diagnostic applications. Andrology. 2019;7(3):479-493.

Please send your questions or comments to Bruce R Gilbert, MD, PhD, HCLD, ALD