In view of the increasing problems of world over-population, it may be surprising to learn that human fertility is relatively poor. Compared, for example, with rodents, reproduction in people is very inefficient, and the fact that there are so many of us is due to improved survival rather than reproductive success. Even in couples who have already conceived (i.e. are of proven fertility) the average monthly chance of the woman getting pregnant is only 20–25%, and just by chance about 10% of these fertile couples will fail to conceive during their first year of trying. It is only after at least this period of time, during which their family doctor will have probably explained to them carefully how to maximise their chance of conceiving, that they are referred to a specialist fertility clinic.

The complete inability to conceive a child – infertility – is very rare. This would only be the case, for example, if the woman had completely blocked Fallopian tubes or premature menopause, or if the man had a complete lack of sperm. Absolute infertility in both partners who are of reproductive age means that there are no treatment options open to them, and their only means of having a family would be to adopt or foster children. The anxiety of wondering whether they will be acceptable as foster parents or adopters can be as stressful as the treatment for infertility.

Introduction

Four basic facts of life are:

1. organisms have no control over whether or not they become alive;

2. once alive they strive to say alive;

3. they have a strong and instinctive drive to reproduce (in humans this drive is fortified by a strong moral intuition);

4. they all eventually die.

The presumption in favour of life

Human beings, as organisms, are subject to these facts of life, but we are also able to rationalise and to moralise. We are able to recognise the basic instinct to preserve life in other people too, and appreciate that we have a moral duty to protect that instinct in them. This has been termed the ‘presumption in favour of life’, and for humans it is a fundamental fact of life: most people believe that matters relating to human life are of moral significance. As society has developed, this has become increasingly formalised in people's behaviour, to the extent that it is now enshrined in laws which are designed to protect life.

Reproduction is the single most distinguishing characteristic of life. It is the driving force of evolution, which is responsible for the diversity of plant and animal species on Earth. People are subjected to this force as much as any other organism, and a basic and powerful urge to reproduce is felt by most people at various times in their lives.

It has been said that the final aim of all human love relationships between men and women is more important than all other ends in life, because what it determines is nothing less than the composition of the next generation. It is perhaps no coincidence, then, that reproduction – involving, as it does, sexual intercourse – has come to occupy such an important part of our lives. It is the driving force of evolution, and hence generates the great variety of living organisms which inhabit, and have inhabited, the Earth, including, of course, ourselves. However, notwithstanding the power of evolution, or perhaps because of the force of it, sex has come to mean much more to us than reproduction.

Normal sexual intercourse has been defined as anything erotic which gives pleasure to both partners, who are consenting adults, and does not hurt anyone. This clearly holds good for a wide variety of sexual functions within loving relationships. In this context, the word love should be taken to mean the desire for the good of the other person; wishing for gain, or to exercise power over another person does not occur in a loving relationship.

Clearly, there are not only emotional but also physical risks associated with having a sexual relationship. Unwanted pregnancies and sexually transmitted diseases can all too easily follow from unprotected sexual intercourse (see chapter 6 for more information about contraception).

Unless they encounter each other and complete the process of fertilisation, the gametes – both sperm and oocyte – are destined to die quite quickly (sperm within 45 hours, oocytes within 24 hours). The oocyte, with its complex cytoplasm, is the only cell in the body which has the potential to become a new human being, but without the contribution of the sperm genome its development cannot proceed. Fertilisation, the union of male and female gametes to form a zygote, is not a single event, but a continuum of subtle interactions and their outcomes.

Final preparation of the gametes

Before they are able to join to form a zygote, the sperm and oocyte must undergo final changes which enable fertilisation to occur. The process of gametogenesis (chapter 2) has resulted in the production of sperm from the seminiferous tubules of the testis, and oocytes in the dictyate stage of developmental arrest.

Epididymal maturation of sperm

The epididymis (figures 2.4 and 3.1) is a long, much coiled duct lined with columnar epithelium which has both secretory and absorptive functions. When the sperm enter the head of the epididymis from the testis, they are immotile and unable to fertilise an oocyte. During their passage along the length of the epididymal duct, the sperm acquire twitching movements at first, followed by full motility with active forward progression. The mature sperm are stored in the tail of the epididymis until ejaculation.

Problems of subfertility affect both sexes approximately equally. Chapter 7 dealt with initial investigation and diagnosis of both female and male patients, and this chapter will discuss the options and treatment available to the subfertile couple in specialist centres and clinics. Many of the procedures of reproductive technology are surrounded with considerable moral and ethical controversy, and the final chapter of this book, chapter 9, is devoted to a discussion of the main issues.

Relatively speaking, less is known about causes and few remedies are available for problems of male subfertility, though it is the focus of an increasing amount of research. The study of male reproduction is called andrology.

Problems of gamete production

Treatment options for poor sperm quality

Techniques for improvement of sperm quality

Although a few cases of azoospermia (total lack of sperm in the semen) have been treated successfully by administering FSH and/or hCG, very little can be done at present about either azoospermia or asthenospermia (poor sperm quality), and the couple is usually advised to consider donor insemination (see below). Oligospermia (very low sperm concentration) can often be helped by taking general measures to improve health, such as losing weight, stopping smoking, reducing alcohol intake and avoiding stress. Some doctors and medical scientists have tried using various hormones and other chemical substances such as arginine, zinc and vitamin E for treating low sperm count and/or poor sperm quality but with very limited success.

Significance of viviparity

The oocyte is one of the biggest cells in the human body, and this is due mainly to the relatively large amount of cytoplasm which it contains. A major constituent of this ooplasm is yolk which is the main nutritional source for the embryo in its initial stage of development. Yolk is a mixture of lipids and proteins which provide the energy required for what is a very rapid period of biological change. The oocytes of all animals contain yolk, but the relative amount depends upon the degree of isolation of the embryo from other sources of nutrition. Birds and reptiles, for example, must complete all of their embryological development from zygote to hatchling within the confines of the egg shell, so they invariably have very yolky or teleolecithal eggs. Those species whose embryos derive their nourishment entirely from the egg yolk are described as oviparous.

The eggs of mammals contain relatively little yolk compared with the eggs of other vertebrate species. However, yolk is present in sufficient quantity to sustain the development of the early embryo through the period of cleavage. This term is used to describe the first few cell cycles of a multicellular organism developing from a single fertilised oocyte. Mammalian eggs are termed alecithal (figures 2.9 and 2.10).

In placental mammals, including of course humans, cleavage takes place as the embryo passes down the Fallopian tube towards the uterus. During this period, the embryo draws upon the reserves of yolk in the dividing cells.

Omnis cellula e cellula, ‘All cells from cells’ stated the German clinician Rudolf Virchow in 1855. From the beginning of evolution, the cells constituting the bodies of all life on Earth have come from pre-existing cells. More than any other characteristic of life, the ability to reproduce distinguishes the living from the non-living, and the process of reproduction is based on the cell cycle, the turn of which is dependent on cell division.

Cell cycle

Along with all other living things, except bacteria and cyanobacteria, the bodies of human beings are made up of eukaryotic cells. The vast majority of these cells are continually renewed and replaced by a form of cell division. This complex but ordered process involves duplication of the genetic material (DNA) in the nucleus of the cell, followed by its division into two equal portions, the migration of the portions to opposite sides of the cell (this part of the process is called mitosis), and finally the division and partition of the cytoplasm and its contents (cytokinesis).

A full cell cycle is that period from the end of one mitosis to the beginning of the next (figure 2.1). Division is the shortest phase of the cell cycle, and represents 5–10% of the total cell cycle time. Known as the M (or mitotic) phase, it is separated from the next M phase in the cycle by interphase, in which the cell is metabolically active and performs whatever functions for which it is adapted.

The capacity of a visual system to resolve fine spatial detail depends on several factors, some associated with the stimulus object, others with the eye, and still others with the central visual pathways. Sensitivity to spatial detail is commonly called acuity, but it is important to remember that this word is applied to several different performance measures. One reads, for example, of minimum separable acuity, grating acuity, vernier acuity, and stereoscopic acuity. The neural mechanisms that mediate these discriminative capacities are not necessarily all the same, despite the fact that the same word, “acuity,” is used for them. It should also be kept in mind that these measurements usually reflect performance at the extreme limit of some functional capacity, rather like determinations of the absolute threshold for detection of light. Thus, acuity measurements of all kinds can give misleading impressions of the sensory tasks in which the nervous system is routinely engaged.

Minimum Separable Acuity and Minimum Angle of Resolution

When two dots or short line segments are made to approach each other in the visual field, a separation is reached at which the subject reports the presence of only one object. The critical angular spacing of the stimuli when they are just resolved is called the minimum angle of resolution (MAR) (Figure 9-1), a measure analogous to the two-point discrimination threshold in somatic sensation. The MAR is affected by many factors, including the brightness of the stimuli, the state of retinal adaptation, and the position of the stimuli on the retina.

One of the main tasks of vision is to distinguish objects from their backgrounds, which at a minimum requires detection of spatial differences in patterns of retinal illumination. This capability is greatly enhanced if the organism can also discern differences in the wavelengths of the light forming the retinal image. These spectral or chromatic patterns can also be useful in the identification, as well as the detection, of important objects such as food sources or predators. The spectral composition of the retinal image of a given object depends on the spectral content of the incident light, the object's reflectance characteristics, and to some extent the differential absorption of certain wavelengths in the ocular media before light reaches the retinal photoreceptors. It is the photoreceptors that first dissect the retinal image into its chromatic components, and in the vertebrate retina this process depends on the cones.

Color vision generally requires the presence in the retina of two or more photopigments with different spectral sensitivities. As described previously, the photopigments of all animals are composed of an opsin, a large, membrane-spanning protein, and the chromophore, 11-cis retinaldehyde. When the chromophore absorbs a light quantum, it changes shape and activates the opsin, which then functions as a catalyst for further reactions in the photoreceptor (see Chapter 5). Retinaldehyde by itself is colorless, but when combined with the opsin its geometry is modified, and the combination becomes a photopigment that absorbs light in the visible range. Changes in one amino acid group at critical points in the opsin can significantly alter the spectral sensitivity of the opsin-chromophore combination.

All information about the retinal image that is directly available to the brain is transmitted by the axons of retinal ganglion cells. In higher mammals, and particularly primates, the projection to the cortex via the lateral geniculate nucleus of the thalamus appears to be essential for conscious visual perception. Retinal axons also reach the hypothalamus, superior colliculus, pretectum, and various other nuclei of the brain stem and diencephalon that subserve a variety of functions, such as reflex orientation to visual stimuli, stabilization of gaze, and control of pupil diameter. This chapter focuses primarily on the retino-geniculate component of the projection to the cerebral cortex, but several of the principles dealt with here are relevant to brain-stem projections as well.

Parallel Processing of the Retinal Image and Classes of Ganglion Cells

Previous chapters have shown how the retinal circuitry establishes one channel to signal increments and another to signal decrements of illumination. These on and off channels encode complementary versions of the distribution of light on the retina and transmit them in parallel to the central nervous system. Also, as discussed earlier, other features of the retinal image, such as movement direction, can be signaled by specialized ganglion cells. Thus, the retinal image is not transmitted in raw form to the brain, but is analyzed in different ways by different ganglion cells, which then communicate their “Views” of the image along separate channels. Different animals segregate different aspects of the retinal image as part of this strategy of parallel processing.

Major Anatomic Features of the Eye

Figure 2.1 illustrates schematically the major components of the human eye, which resembles that of most other primates. The sclera is a tough outer coat that is fibrous in humans but contains bone or cartilage in some other vertebrate species. The cornea is continuous with the sclera and provides the first element of the refracting media that bend the light to form an image on the retina. The lens lies behind the iris and in front of the vitreous humor, which fills the greater part of the globe. Aqueous humor fills the posterior chamber (the space between the lens and iris) and the anterior chamber (the space between the iris and the cornea). The posterior and anterior chambers are continuous through the pupil, the aperture formed by the iris.

The general features of the retina, the multilayered neural structure lining the back of the eyeball, can be visualized in the living eye with an ophthalmoscope or special camera (Figure 2.2). Axons leave the retina through the optic disc or optic papilla and enter the optic nerve to reach the brain. At the posterior pole of the eye, the retina thins to form the fovea, an area specialized for high-acuity vision. The visual axis is an imaginary line from the fovea through the center of the pupil (Figure 2.1). Behind the retina is the pigment epithelium, which is separated from the sclera by the vascular choroid.

This chapter provides an overview of the projections from the retina to the brain in vertebrates and reviews the key terms used in describing the pathway. The major components of the pathway and their functions are examined in greater detail in subsequent chapters.

The Visual Fields

The central projections of the two eyes map the visible world onto the brain. To understand this process, it is important to know how the visual field of each eye is described and how the projections from the two eyes are combined in the central pathways. The retina of each eye is conventionally divided into nasal and temporal parts, on the basis of proximity to the nose or temporal bone, respectively. Similarly, the visual field of each eye is divided into nasal and temporal parts, and because of the inversion of the retinal image by the eye's optics, the nasal visual field is imaged on the temporal retina, and the temporal field on the nasal retina. Figure 4.1 schematizes the projections of the visual fields in an animal whose eyes are located at the sides of its head. In such lateral-eyed animals, the axons from one retina generally cross completely in the optic chiasm, so that the input from that eye is directed at the contralateral hemisphere of the brain.

Figure 4.2 illustrates diagrammatically the monocular visual fields as they would appear to a frontal-eyed human observer, left eye (oculus sinister, O.S.) on the left, right eye (oculus dexter, O.D.) on the right.

When the eyes face the front, the central part of the visual field is imaged on both retinas (see Figure 4.4). This bestows certain advantages for depth perception, but also creates a formidable problem for the brain: how to ensure that the two retinal images are transformed to yield a unified perception of the part of the visual field seen by both eyes. Failure to achieve this, which sometimes happens in pathological conditions of the nervous system, results in diplopia, the perception that there are two objects when there really is only one. Diplopia can be demonstrated by pushing gently on the skin at the side of one eye to misalign the two visual axes.

Binocular Single Vision

The encoding of the two retinal images of a single object to yield a unique perception results in perceptual fusion of the two images. In discussing fusion, it is important to distinguish between it and two other phenomena, fixation and focus. If the visual axis of one eye is directed at an object so that the image is positioned on the fovea, the eye is said to fixate the object. It is possible to deliberately place an image outside the fovea, but the term “fixation” is generally used to mean foveal fixation. The fixated object will be in focus only if its distance from the eye and the power of the eye's optics permit the formation of a crisp retinal image.

Morphologic and physiologic studies have identified many regions of the cerebral cortex that are involved in vision. All of these are, in some sense, “Visual cortex,” but this term also has more restricted meanings. “Primary visual cortex” refers to a region of distinctive cytoarchitecture that the anatomist Brodmann designated area 17. In primates, this is the principal target of the geniculo-cortical projection. Echoing this fact, as well as its appellation of primary visual cortex, area 17 is sometimes designated VI. The term “striate cortex” arises from the presence in humans of the stria of Gennari, a prominent horizontal band in area 17 that stains heavily for myelin and is visible to the naked eye in fresh tissue. It is also called the calcarine cortex because it lies adjacent to the calcarine sulcus. Visually responsive regions outside area 17 are collectively called extrastriate areas and will be treated later in this chapter.

Effects of Lesions in Striate Cortex

Humans with complete destruction of the striate cortex on one side cease to perceive stimuli in the contralateral visual field. Partial lesions result in localized scotomata, which may be more or less “dense” depending on how much function remains. Sometimes vision is reduced to detection of motion or the presence of light. When the striate cortex and nearby regions are ablated in nonhuman primates, severe deficits are observed in tasks that presumably require visual perception. Ablation of visual cortex in other animals does not always produce such striking deficits.

This textbook is an attempt to answer a question: What would I want a student to know about the visual system before beginning work in my laboratory? Draft versions have been used for several years in an undergraduate course at Brown University. Inevitably, the content and approach of the book have been colored by my expectations of students in that course and by my own particular interests. It is assumed that students will have had an introductory course on the nervous system and will be acquainted with the fundamentals of cellular neurophysiology and the general organization of the vertebrate central nervous system. Minimal knowledge of physics is assumed, so some time will be spent on the elementary principles of optics as they apply to visual systems. Although the book is intended primarily for undergraduates, it can provide useful background for beginning graduate students if supplemented by material from the research literature.

The text is organized into three parts. Part I treats the eye as an imageforming organ and provides an overview of the projections from the retina to key visual structures of the brain. Part II examines the functions of the retina and its central projections in greater detail, building on the introductory material of Part I. Part III treats certain special topics in vision that require this detailed knowledge of the structure and properties of the retina and visual projections.