Limitations of semen analysis as a test of male fertility and anticipated needs from newer tests

Wang, Christina; Swerdloff, Ronald S.

doi:10.1016/j.fertnstert.2014.10.021

Cited by 240 publications

(173 citation statements)

References 57 publications

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“…Although a semen analysis is the best predictive test we have to date, it clearly falls short of a true diagnosis (5,6). Indeed, several studies have shown that men with sperm numbers (7)(8)(9), morphology (8,10), and motility (11)(12)(13)(14)(15)(16)(17) below the thresholds outlined by the WHO can be fertile. Furthermore, there are many instances of men with normal sperm parameters that are infertile (13, 18 -20).…”

mentioning

confidence: 99%

Deficiency in Outer Dense Fiber 1 Is a Marker and Potential Driver of Idiopathic Male Infertility

Hetherington

Schneider‐Futschik

Scott

et al. 2016

Molecular & Cellular Proteomics

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Globally, ϳ1 in 15 men of reproductive age are infertile, yet the precise mechanisms underlying their gamete failure are unknown. Although a semen analysis is performed to determine fertilizing potential, the diagnostic suitability of this analysis has been questioned in several reports, as many men, classified as infertile according to their semen analysis, subsequently turn out to be fertile. Herein, we have used a quantitative (phospho)-proteomic analysis, using enrichment on titanium dioxide followed by ion-trap mass spectrometry (LC-MS/MS), to compare the semen of infertile versus fertile males. One protein, namely outer dense fiber 1 (ODF1), was dramatically reduced in infertile males. Using specific antibodies, we then screened the gametes of a cohort of suspected infertile men and demonstrated a reduction in the amount of ODF1 compared with fertile controls. Stress treatment of sperm deficient in ODF1 caused the head to decapitate, suggesting why these gametes fail to initiate fertilization. Interestingly, electron micrographs of ODF1-deficient spermatozoa revealed an abnormal connecting piece, indicating several developmental defects with both the implantation plate and the thin laminated fibers. In some cases, the implantation plate appeared to be reduced in size or was overburdened by granular material near the connecting piece. Hence, a strong reduction ODF1 is a marker of idiopathic male infertility and a potential driver of this condition. Molecular & Cellular Proteomics 15: 10.1074/ mcp.M116.060343, 3685-3693, 2016.Globally, in excess of 80 million people suffer from infertility (1), with ϳ1 in every seven couples so affected (2). In at least half of these cases, a defect in one or more aspects of sperm function appears to be the cause (2). Understanding the contribution of each partner to a couple's infertility is critical in determining how this situation can be optimally addressed. In the case of the male, a semen analysis focusing on sperm motility, concentration, and morphology is often performed to determine the fertilizing potential. A set of guidelines for evaluating semen quality was originally published by the World Health Organization (WHO) in 1980 (3). However, so inadequate were these criteria in predicting infertility that revised values had to be released in 1987, 1992, 1999, and again in 2010 (4). Although a semen analysis is the best predictive test we have to date, it clearly falls short of a true diagnosis (5, 6). Indeed, several studies have shown that men with sperm numbers (7-9), morphology (8, 10), and motility (11-17) below the thresholds outlined by the WHO can be fertile. Furthermore, there are many instances of men with normal sperm parameters that are infertile (13, 18 -20). Thus, these traditional diagnostic tests are limited in the information they generate and are poor predictors of male-factor infertility.In order to define the cause of male infertility, attempts have been made to identify changes in the proteomic composition of normal and infertile spermatozoa (20...

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mentioning

confidence: 99%

Deficiency in Outer Dense Fiber 1 Is a Marker and Potential Driver of Idiopathic Male Infertility

Hetherington

Schneider‐Futschik

Scott

et al. 2016

Molecular & Cellular Proteomics

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“…Routine semen analysis is not a reliable method to determine the fertilising potential of spermatozoa and do not include the prediction of the changes that occur in the female reproductive tract before fertilisation. Thus, clinicians and researchers discuss that newer tests to predict the success of fertilisation are needed (Franken & Oehninger 2012, Wang & Swerdloff 2014). Indeed, current tests do not study spermatozoa ability to reach and fertilise the oocyte.…”

Section: Discussionmentioning

confidence: 99%

Obesity, energy balance and spermatogenesis

Oliveira¹,

Sousa²,

Silva³

et al. 2017

Reproduction

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Obesity has grown to pandemic proportions. It affects an increasing number of children, adolescents and young adults exposed to the silent comorbidities of this disorder for a longer period. Infertility has arisen as one important comorbidity associated with the energy dysfunction promoted by obesity. Spermatogenesis is a highly regulated process that is determined by specific energetic requirements. The reproductive potential of males relies on hormonal-dependent and -independent stimuli that control sperm quality. There are conflicting data concerning the impact of male overweight and obesity on sperm quality, as well as on the possible paternal-induced epigenetic trait inheritance of obesity. In addition, it remains a matter of debate whether massive weight loss induced by lifestyle interventions, drugs or bariatric surgery may or may not benefit obese men seeking fatherhood. Herein, we propose to discuss how energy balance may modulate hormonal signalling and sperm quality in overweight and obese men. We also discuss some molecular mechanisms that mediate obesity-related dysfunction in male reproductive system and how paternal obesity may lead to trait inheritance. Finally, we will discuss how lifestyle modifications and sustained weight loss, particularly the loss achieved by bariatric surgery, may revert some of the deleterious effects of obesity in men and their offspring.Reproduction (2017) 153 R173-R185

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“…While the analyses conducted herein have been used to search for associations in chronic diseases and biomarkers such as serum lipids (Patel et al ., 2012), we are not aware of any published work focusing on human fecundity or related impairments such as conception delay or pregnancy loss. To this end, we cannot interpret our findings in the context of earlier work, but data‐driven techniques can be extended to include emerging biomarkers of male fecundity, such as sperm function tests or in vitro capacitation tests (Wang & Swerdloff, 2014). …”

Section: Discussionmentioning

confidence: 90%

A data‐driven search for semen‐related phenotypes in conception delay

2016

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SummarySperm count, morphology, and motility have been reported to be predictive of pregnancy, although with equivocal basis prompting some authors to question the prognostic value of semen analysis. To assess the utility of including semen quality data in predicting conception delay or requiring >6 cycles to become pregnant (referred to as conception delay), we utilized novel data‐driven analytic techniques in a pre‐conception cohort of couples prospectively followed up for time‐to‐pregnancy. The study cohort comprised 402 (80%) male partners who provided semen samples and had time‐to‐pregnancy information. Female partners used home pregnancy tests and recorded results in daily journals. Odds ratios (OR), false discovery rates, and 95% confidence intervals (CIs) for conception delay (time‐to‐pregnancy > 6 cycles) were estimated for 40 semen quality phenotypes comprising 35 semen quality endpoints and 5 closely related fecundity determinants (body mass index, time of contraception, lipids, cotinine and seminal white blood cells). Both traditional and strict sperm phenotype measures were associated with lower odds of conception delay. Specifically, for an increase in percent morphologically normal spermatozoa using traditional methods, we observed a 40% decrease in conception delay (OR = 0.6, 95% CI = 0.50, 0.81; p = 0.0003). Similarly, for an increase in strict criteria, we observed a 30% decrease in odds for conception delay (OR = 0.7, 95% CI = 0.52, 0.83; p = 0.001). On the other hand, an increase in percent coiled tail spermatozoa was associated with a 40% increase in the odds for conception delay (OR = 1.4, 95% CI = 1.12, 1.75; p = 0.003). However, our findings suggest that semen phenotypes have little predictive value of conception delay (area under the curve of 73%). In a multivariate model containing significant semen factors and traditional risk factors (i.e. age, body mass index, cotinine and ever having fathered a pregnancy), there was a modest improvement in prediction of conception delay (16% increase in area under the curve, p < 0.0002).

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Limitations of semen analysis as a test of male fertility and anticipated needs from newer tests

Cited by 240 publications

References 57 publications

Deficiency in Outer Dense Fiber 1 Is a Marker and Potential Driver of Idiopathic Male Infertility

Deficiency in Outer Dense Fiber 1 Is a Marker and Potential Driver of Idiopathic Male Infertility

Obesity, energy balance and spermatogenesis

A data‐driven search for semen‐related phenotypes in conception delay

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