The past, present, and future of the semen analysis.

This month's Views and Reviews provides an added perspective to the World Health Organization laboratory manual for the examination and processing of human semen, which was recently published in the 6th edition. The first artice provides a historical context of the prior editions of the World Health Organization manuals and modifications adopted over the years. The next piece then provides additional perspectives on the methodologies used for the performance of semen analysis. The third article then examines some of the new semen analytic technologies and enhancements that have become more common over the years. Finally, the last article proposed where male reproductive testing will head in the coming years with emerging research and technologies.

Evolution of the WHO "Semen" processing manual from the first (1980) to the sixth edition (2021).

As stated clearly in all editions of the WHO Laboratory Manual for the Examination and Processing of Human Semen, the goal of the manual is to meet the growing needs for the standardization of semen analysis procedures. With constant advances in andrology and reproductive medicine and the advent of sophisticated assisted reproductive technologies for the treatment of infertility, the manual has been continuously updated to meet the need for new, evidence-based, validated tests to not only measure semen and sperm variables but also to provide a functional assessment of spermatozoa. The sixth edition of the WHO manual, launched in 2021, can be freely downloaded from the WHO website, with the hope of gaining wide acceptance and utilization as the essential source of the latest, evidence-based information for laboratory procedures required for the assessment of male reproductive function and health.

Breve visión histórica de la reproducción desde una óptica andrológica / An historical overview of reproduction from an andrological perspective

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Historical investigations into varicocele pathophysiology and sperm migration.

Stephenson JD, O'Shaughnessy EJ. Hypospermia and its relationship to varicocele and intrascrotal temperature. Fertil Steril 168;19(1):110-7. "There is a frequently observed, definite relationship between varicocele and hypospermia." Moghissi KS. Human and bovine sperm migration. Fertil Steril 1968;19(1):118-22. "Van Leeuwenhoek's discovery of motile spermatozoa led to the conclusion that their migration was due to their own propellant activity."

[Hypospadia and infertility of Henry II of France (1519-1559)]. / Die Hypospadie und Infertilität von Heinrich II von Frankreich (1519-1559).

Henry II (1519-1559) of France was the second son of Francis I (1494-1547) and Claude de France (1498-1524) born in 1519 in St. Germain-en-Laye. After his older brother's and his father's death in 1547, he was anointed the French king in Reims. In 1533 already, as a 14-year-old boy, for reasons of state, he was married to the same aged Catherine de Medici (1519-1589), as her uncle was Pope Clement VII (1478-1534). The marriage remained childless for 11 years since Henry, due to a distinct hypospadia and a completely sexually inexperienced wife was unable to conceive children with her. His existing liaison to Diane de Poitiers (1499-1566) - a 19-year-older maid of honor of his father Francis I from 1537 until his death - influenced his sexual life immensely.The blame for the childless marriage was placed primarily on his wife, as Henry had become father of an illegitimate daughter with a mistress. Catherine then underwent all possible medical and alchemical procedures to finally give birth to the hoped Dauphin. Ironically, her rival for the favor of her husband, Diane de Poitiers was one of her greatest allies. She made clear that the cause lay with Henry and not with his wife. This was confirmed by the added solid physician Jean Fernel (1497-1558). His treatment of Henry and the simultaneous training of the unexperienced Catherine by Diane de Poitiers led to success.The result was the birth of Francis II (1544-1560) in 1544, the first of 10 children in 12 years. Thus, the dynasty was saved. After the death of Henry in a tragic tournament accident in 1559, three of his sons became kings of France. But the line of Valois remained without further descendants and was continued by Henry IV, the first Bourbon king in 1589.

Henry VIII, McLeod syndrome and Jacquetta's curse.

The mental decline of King Henry VIII from being a jovial, charismatic and athletic young man into an increasingly paranoid, brutal tyrant in later life, ever more concerned at his lack of one or more male heirs, has attracted many medical diagnostic theories. Previous hypotheses have included diabetes, syphilis and hypothyroidism, among others. However, these inadequately explain Henry's failure to produce a male heir, despite multiple pairings. The latest postulated diagnoses for Henry are the coexistence of both Kell blood group antigenicity (possibly inherited from Jacquetta Woodville, Henry's maternal great grandmother) causing related impaired fertility, and McLeod syndrome, causing psychotic changes. As the mutated McLeod protein of the syndrome significantly reduces the expression, effectively inactivating the Kell antigen, we critically review this theory, examining in detail the pathophysiology of these conditions and assessing the genealogy of Henry VIII and its effect in subsequent generations.

Tales of healthy men: male reproductive bodies in biomedicine from 'Lebensborn' to sperm banks.

Using the example of 'sperm tales', borne out of the biomedical technologies that went hand in hand with the establishment of the 'science of man' (andrology), the article engages with the epistemic evolution of interrelated biomedical theories and concepts of what constitutes a 'healthy' reproductive male body. The article asks: how has the normative ideal male body been either perpetuated or interrogated through these tales of male reproduction at the interface between scientific and medical technologies? And how were changes to the normalization of male bodies central to clinical practices and cultural understandings of health and illness? With many aspects of the medical history of male reproduction in the 20th century still unexplored, this article will focus on the growing intervention of biomedicine to 'treat' male infertility by way of the classification, standardization and normalization of male corporeality, focusing in particular on the representation and construction of men and the male body, as reflected in medical science and practice from the second half of the 20th century onwards in Germany. The article analyses the rise in importance of sperm in biomedical investigation, including a consideration of the construction of infertility as the defining force behind concepts of 'healthy men', and examines the related conceptualization of male reproductive bodies at the crossroad between 'healthy' and 'normal'. It is argued that the ideal of male reproduction as being inherently healthy has lost ground. By the late 20th century, male bodies have become vulnerable, at least as represented in medical science and technology.

Development and current applications of assisted fertilization.

Since the very early establishment of in vitro insemination, it became clear that one of the limiting steps is the achievement of fertilization. Among the different assisted fertilization methods, intracytoplasmic sperm injection emerged as the ultimate technique to allow fertilization with ejaculated, epididymal, and testicular spermatozoa. This work describes the early steps that brought forth the development of intracytoplasmic sperm injection and its role in assisted reproductive techniques. The current methods to select the preferential male gamete will be elucidated and the concerns related to the offspring of severe male factor couples will be discussed.

Fertility preservation: definition, history, and prospect.

Exposure to gonadotoxic agents for treating cancer and other diseases or postponement of maternity jeopardize the prospects of genetic parenthood and are major factors driving the development of fertility preservation technologies. Although its mainstays, cryopreservation and vitrification, have been adopted from infertility medicine for fertility preservation purposes, there is a need for additional specialized procedures, protocols, and biomedical devices. As its multidisciplinary character and aims diverge compared with other branches of reproductive medicine, we are witnessing the emergence of a field in its own right.

[Sterility in medieval noblemen]. / Männliche Zeugungsunfähigkeit im mittelalterlichen Adel.

The social competence of the medieval nobleman was closely associated with his male sense of honour. One essential aspect of his masculinity was the ability to produce progeny. The childlessness of a good ruler needed special justification, the childlessness of a bad ruler was seen as God's punishment. In terms of canon law, the inability to procreate was irrelevant as long as the marriage could be consummated. Considering the importance of the procreative capacity and its symbolic significance one must ask to what extent it was possible to ascertain sterility in the Middle Ages. In the case of noblemen one can assume that they could obtain certainty about their fertility through their premarital and extramarital intercourse. This might explain why some rulers and nobles accepted a childless marriage without deeming it necessary to take another wife (or plan their itinerary in a way that enabled them to produce progeny).

[History of spermatozoon and changing views]. / Histoire du spermatozoïde et mobilité des idées.

With Ham, Leeuwenhoek discovered animalcules in human semen in 1677, without theoretical interpretations. Discussions focused on the respective role of ovum and animalcules during two centuries with erroneous doctrines. Modern ideas on status and origin of animalcules are associated with the development of the cell theory. Animalcules became spermatozoa. In 1875, Hertwig observed that the head of spermatozoon becomes a pronucleus and combines with the female pronucleus, thus establishing the concept that fertilization is the conjugation of two cells. During the first half of 20th century, endocrinology and genetics influenced management of infertile couples. Cryopreservation, analyses of ultrastructural morphology improved knowledges of normal and abnormal male gametes. In Vitro Fertilization and more IntraCytoplasmic Sperm Injection opened new views on the role of spermatozoa in human generation. Genetics and procreation were more and more so linked that each perspective of further advances shocked ethical considerations as transgression of natural biology. The future of spermatozoon in human reproductive programs remains a mystery according to, for example, experimental development using stem cell cultures.