Whither must spermatozoa wander? The future of laboratory seminology

Abstract

This commentary celebrates the publication of the 5th edition of the World Health Organization Laboratory Manual for the Examination and Processing of Human Semen. This is the most complete text to date on the creation of a conventional semen profile and includes invaluable reference limits for specific aspects of semen quality based on the analysis of over 1 900 recent fathers. The new edition of the manual also includes detailed protocols for monitoring different aspects of sperm function and new chapters on the preparation of spermatozoa for assisted conception and cryopreservation. Given that this publication is the definitive statement on how to perform a descriptive semen analysis, we might speculate on the future of this field and the sorts of tests that might feature in future editions of the manual. Cell biologists are currently being empowered by the 'omics revolution, which is placing at their disposal technologies of unprecedented power to examine the biochemical composition of cells such as spermatozoa. Indeed, spermatozoa are perfect vehicles for this kind of analysis because they can be obtained as extremely pure suspensions, exist naturally in isolation and can be induced to express their capacity for fertilization and the initiation of embryonic development in vitro. The application of 'omics technologies to these cells, in concert with detailed assessments of their functional competence, should provide insights into the biochemical basis of defective semen quality. This information will then help us understand the causes of male infertility and to develop rational methods for its treatment and possible prevention. Keywords: assisted conception, DNA damage, male infertility, miscarriage, semen, seminology, spermatozoa 1 In the beginning A long long time ago, when in vitro fertilization (IVF) was in its first flush of youth and Intracytoplasmic sperm injection (ICSI) had not driven seminology into the reproductive wilderness, the development of robust methods for the diagnosis and treatment of male infertility was regarded as a noble cause worthy of engagement.In those far-off days, the descriptive semen profile was the only means we had of determining the fertility of men attending infertility clinics. This profile focused on an analysis of sperm number, motility and morphology underpinned by the fundamental belief that fertility is essentially a war of attrition. According to this model, the ejaculate must contain more than a certain critical number of motile, morphologically normal spermatozoa in order to withstand the cellular carnage that inevitably accompanies the perilous transition from the point of insemination to the site of fertilization. In diagnostic terms, the concept that male fertility is essentially 'a numbers game' resulted in a preoccupation with threshold counts for sperm number, motility and morphology that define the conventional semen profile, even to this day. The belief that fertility is entirely dependent on sperm number was, ironically,

New WHO-reference limits—revolution or storm in a teapot?

“…Moreover, effective treatment needs the establishment of a nosologically sound diagnosis and this cannot be based on symptoms reflected by semen evaluation. 2 Relying exclusively on the latter has lead to conflicting results concerning the predictive value of semen analysis, e.g., the percentage of spermatozoa with normal morphology for in vitro fertilisation success. There is an ongoing debate whether sperm concentration, motility or morphology is most important for assessing male fertility or, more generally, whether semen evaluation is of any use at all.…”

“…Nevertheless, many studies have shown that even for this form of therapy, analysis of sperm chromatin integrity is important because DNA damage in human spermatozoa has been associated with adverse clinical outcomes, including poor fertilisation rates, impaired embryonic development, an increased risk of miscarriage and morbidity in the offspring, including childhood cancer. 2 Although many sperm function tests have been able to be superior to conventional semen analysis as predictors of both natural conception and in vitro fertilisation success, they have never achieved sufficient advances in discrimination to be incorporated into the andrological work-up as common practice. Tests should be able to detect underlying pathologies that can be referred to specific treatment.…”

“…Modern advances in diagnostic genomics might also help identify genotypes associated with specific defects in semen quality. 2,22 Such biomarkers could potentially be related not only to the clinical manifestation of male infertility, but also to patients' response to treatment. The variability in patient characteristics of infertility necessitates proven, personalized diagnostic approaches to optimized efficacy and safety outcomes.…”

“…Most importantly, there is a completely revised chapter on quality control. 2 The most striking changes in this new edition of the WHO manual, however, concern the reference values for semen quality. Whereas the previous reference values were based, more or less, on expert opinion, the new ones were acquired by analysing semen samples from 1800 recent fathers (time to pregnancy of f12 months) living in eight countries on three continents.…”

Genomics revolution on andrology: genetic testing for male infertility

“…In the Special Issue on Semen Analysis of Asian Journal of Andrology, Aitken [1] has extensively discussed the causes of male infertility, the past and the future developmental methods for its treatment and possible modes of prevention have been. The author stated that in the 21st century, molecular andrologists will have wide range of methods to examine the defective spermatozoa of infertile patients.…”