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vo l u n ta ry a n d i n vo l u n ta ry s t e r i l i t y One of the most striking phenomena in Klinefelter’s syndrome is the marked underdevelopment of the testicles, which usually do not grow beyond the size of a pea. Other characteristics are a relatively short penis, the formation of mammary glands, greater than average height, sparse beard growth and little pubic hair, which in addition often has a female growth pattern, namely with a horizontal upper limit. A man with an extra x chromosome is bound to be effeminate, would seem to be the obvious assumption, but that is totally wrong.
And it is equally wrong to imagine that such a man is necessarily bisexual. If boys with Klinefelter’s syndrome receive testosterone treatment in puberty, they grow into very masculine men, quite able to hold their own sexually!
dna diagnosis
In recent years dna diagnosis has become a rapidly developing field: more and more syndromes are being shown to be genetically determined and in a number of diseases it has become clear that a small part of the chromosome, the gene, is not functioning properly. An example of this is cystic fibrosis, a genetic disorder affecting a gene of chromosome number seven. This poorly functioning gene causes thick sticky mucus in, for example, the airways and the pituitary gland. Blockages of these organs lead to chronic airway infections and growth problems.
In many cases the epididymides, the seminal duct and the seminal glands are affected by this ailment. Because sperms are actually being produced in the testicles it is sometimes possible for a sufferer of cystic fibrosis and his partner to achieve a pregnancy through icsi, though a child fathered in this way risks developing a form of cystic fibrosis. For this reason examination of the man and if necessary of the woman is necessary prior to such treatment.
Recently the gene important in sperm production, the azf gene, was found in the male chromosome. Minor writing errors in the order of the dna molecules lead to disruptions in sperm cell production.
Mutations in the azf gene are found in between 5 and 15 per cent of all men with poor sperm quality. In the event of successful assisted reproduction these will be passed on to male descendants. This is yet another reason in cases of very poor sperm quality to consult a clinical geneticist.
Azoospermia and Sertoli cell only
When investigating infertility one regularly encounters azoospermia, the condition where no sperm cells at all are present in the ejaculate.
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The number of new cases per year in the Netherlands is estimated at 300 to 400, of which two-thirds are caused by abnormalities in the production of sperm cells and about a third by a ‘kink’ in the duct system, or an obstruction.
The firm diagnosis of ‘obstructive azoospermia’ is made by microscopic examination of a section the size of a grain of rice from the larger of the two testicles. A Johnsen score is given, which is obtained by assessing the sperm-cell forming tubules for the degree of maturation from stem cell to ‘mature’ sperm cells. The presence of fully grown sperm cells gives a score of ten, nine or eight, the presence of spermatids, sperm cells that are not quite mature, gives a score of seven or six, spermatocytes five or four and only spermatogonia, sperm cells that are far from mature, a score of three. The Johnsen score has a strong correlation with the quality of the spermatogenesis. With a normal spermatogenesis the average score is 9.4.
The Sertoli cell-only syndrome is one of the commonest causes of non-obstructive azoospermia. ‘Sertoli cell-only’ refers to what the pathologists see on microscopic examination of a section of testicular tissue, that is sperm-cell forming tubules that are too small, have a thickened wall and are coated only with Sertoli cells. No germinating sperm cells are found, let alone fully mature ones. Patients with Sertoli cell-only have a normal male body, but often rather small testicles. With them the level of fsh, the hormone that from the hypophysis prompts the testicles to produce sperm cells, is too high. The cause of the syndrome is unknown. Very exceptionally in the testicular biopsy small areas of normal sperm cell production are found alongside the Sertoli cell-only picture.
Nowadays sperm cells can be obtained directly from the testicle or the epididymis, so that no spermatozoa need be present in the ejaculate.
Because of these new options it is necessary for the pathologist to make a careful distinction between a ‘complete’ and an ‘incomplete’ Sertoli cell-only syndrome. For this reason several biopsies are done in dif ferent directions. In Belgium by doing several ‘open’ testicular biopsies doctors succeeded in obtaining sperm cells from a third of these patients, which means that even with a serious disruption of sperm cell production, icsi (see below) is sometimes possible.
Defying Darwin
The oldest form of assisted reproduction is artificial insemination, in which a syringe or a pipette is used to bring the sperm into close proximity with the mouth of the womb. In 1780 the Italian scientist Spallanzini was the first to do this successfully, with a bitch. In 1799
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vo l u n ta ry a n d i n vo l u n ta ry s t e r i l i t y John Hunter was the first to carry out the procedure with a woman.
The sperm involved was that of a man with a deformation of the urethra, and Hunter injected it into the vagina of the man’s wife. The technique did not catch on: there was quite simply no one to be found who wanted to take on this ‘blasphemous’ process. It was 1866 before the American gynaecologist J. Marion Sims, later a celebrated figure, took up artificial insemination again, putting sperm directly into the womb. From that time on the treatment was used very sparingly, mostly with married couples where the husband had become infertile because of bilateral gonorrhaeal inflammation of the epididymis.
In his book Fertility in Marriage and Ways of Influencing It, Th. H.
van de Velde gives an account of how the pioneering American researcher Robert Latou Dickinson (1861–1950) conveyed the sperm directly to the Fallopian tube via the womb. H. Sellheim constructed an apparatus, the Tubenbesamer, with which the sperm could be blown into the Fallopian tubes; G. Fraenkel went even further: his advice was that if for any reason the abdomen had to be opened up, the ejaculate or punctuate from the epididymis should be brought into the immediate vicinity of the ovaries . . . Yet another gynaecologist suggested the idea of injecting sperm directly into the abdominal cavity from the back of the vagina, reasoning that by no means all sperm cells would immediately perish and that a few might even reach one of the ovaries.
Today artificial insemination is practised mainly by farmers. Approximately 90 per cent of cows and between 10 and 30 per cent of pigs are artificially inseminated. From the point of view of the breeder artificial insemination has many advantages over natural servicing, including the non-transmission of sexually transferable diseases.
Up to the mid-1970s artificial insemination was the only method of assisted reproduction available to help those suffering from involuntary childlessness. However, in the 1970s researchers and doctors developed a totally new kind of assisted fertilization: in-vitro fertilization (ivf). Two countries played a pioneering role – Australia and Great Britain – and four men are regarded as the founding fathers: the Britons Patrick Steptoe and Robert Edwards and the Australians Alan Troun-son and Carl Wood.
Ultimately it was the British pair who took the crown: in 1978
Steptoe and Edwards were able to present the first ‘test-tube baby’ to the world. The miracle baby’s name was Louise Brown. Incidentally, her sister Natalie, four years younger, was to be the first woman conceived by ivf herself to become a mother, only this time in the natural way. icsi is a complementary technique developed by Dr Gianpiero Palermo at the Free University of Brussels. In icsi a single living sperm cell is introduced into the ovum with a micropipette. The 229
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first experiments were carried out on mice, and in 1991 the first pregnancy was induced in a woman using icsi. By 2005 more than 400,000
had been born through icsi worldwide.
&
nbsp; As of 2007 in Western Europe it is estimated that one in forty children were born with the help of the test tube – over one million babies worldwide – and if one includes other fertility-enhancing treatments, the proportion rises to one in twenty: these figures are hard to dismiss.
Women not eligible for test-tube fertilization are those who are obese, those over the age of forty and those with ‘bad’ ovaries. The last condition can be tested by determining the level of fsh in the blood.
Assisted fertilization methods include iui, icsi, pesa, tese, tesa. The table below gives an overview.
Treatment
What exactly is it?
iui
Intrauterine insemination
The injecting of sperm cells
into the uterus
ivf
In-vitro fertilization
Fertilization in the test tube
icsi
Intracytoplasmatic sperm
Injecting a sperm cell into an
injection
ovum
pesa
Percutaneous epididymal
Aspiration via the skin of
sperm aspiration
sperm cells from the epididymis
tese
Testicular sperm extraction
Obtaining sperm cells from
testicular tissue
One of the biggest problems in assisted reproduction techniques is the occurrence of multiple pregnancies. The risk of course increases in proportion to the number of embryos replaced. With multiple births delivery carries higher risks and there are frequent premature births, meaning that the babies not only spend a long period in hospital but also run the risk of, for example, retarded development. Doctors usually aim to replace as few embryos as possible.
Intracytoplasmatic sperm injection (icsi) is nothing more than a complement to in-vitro fertilization (ivf). In icsi a single living sperm cell is introduced into the ovum with a micropipette. Through the microscope the analyst selects a suitably mobile sperm cell, gives it a tap on the tail so that it is stunned for a second, then picks it up with a pipette and injects it into the ovum. As a potential parent you naturally hope that a Rolls Royce sperm cell is picked up, but the fact remains that you are defying Charles Darwin . . . In icsi at least, processes that play a part in natural fertilization are bypassed. In con-230
vo l u n ta ry a n d i n vo l u n ta ry s t e r i l i t y icsi.
trast to ivf, icsi requires only one mobile sperm cell per ovum. In cases of azoospermia through obstruction, pesa is the most common technique: with obstruction the number of properly mobile sperm cells is highest in the head of the epididymis, with a production problem the chance of finding mobile sperm cells is greatest in the tail.
In pesa a needle is inserted into the epididymis under local anaesthetic and withdrawn as suction continues. The needle is connected to a syringe via a tube, which is then injected with growing medium so that the content can be assessed by an analyst for the number of mobile sperm cells. This procedure can be repeated several times in a session.
Usually one starts on the side of the larger testicle, and if the count is low one can try the other side.
In a tese treatment sperm cells are taken from the testicle itself, and subsequently sperm cells are extracted in a laboratory from the section of testicular tissue removed. This has the advantage that a section of testicular tissue can immediately be obtained for the Johnsen score.
The treatment of fertility problems is generally felt to be very onerous. There are many stressful events, including (for women) daily hormone injections, blood samples, and diagnostic procedures such as exploratory operations, and masturbating to order and ‘epididymal sperm aspiration’ in men. Intercourse tends to become reproduction-led, potentially placing the desire for sex under pressure. In addition there is the situation of being constantly tossed back and forth between hope and fear. It becomes particularly burdensome when one wants to keep treatments secret from family, friends and colleagues. Taking time off work without letting colleagues in on the secret necessarily involves some fibbing.
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Freezing sperm cells
Freezing sperm cells, cryopreservation, is important mainly to young men with testicular cancer who after removal of the affected testicle face a course of chemotherapy. Occasionally a man presents for sterilization, while expressing the wish that his sperm be stored in advance of the procedure. Such a wish cannot be met with the normal health service, though he can have sperm frozen by commercial institutions.
Anyone thinking that sperm banks are a twentieth-century human invention is wrong: for several million years the male springtail has been consistently distributing scores of sperm droplets in the form of a chain. When the female insect’s eggs are mature, she goes to the sperm depot and takes one.
Simple freezing of sperm cells leads to shrinkage of the cell, loss of fluid and sometimes cracks, resulting in loss of function. There was a great step forward after the discovery of glycerol, which could counter the above processes. In freezing for cryopreservation liquid nitrogen is used, cooled to –196 degrees Celsius. One sperm sample can be used to fill between five and fifteen ampoules containing 0.3 millilitres.
Depending on the situation between one and three batches of sperm will be frozen. After freezing, one ampoule is defrosted in order to assess the mobility of the spermatozoa: the percentage of mobile sperm that continues to move after freezing or defrosting respectively varies from 5 to 50 per cent. With a concentration of mobile sperm of at least one million per millilitre in the initial sample, there is a reasonable chance of mobile sperm after the defrosting of the whole amount. This is important information when icsi is being considered, since only mobile sperm can be used.
The ampoules of frozen sperm are distributed across two vats in order to reduce the chance of loss as far as possible. It is impossible to assign every individual a deep-freeze vat of their own, so that the sperm of several men is stored in a single deep-freeze vat. Occasionally tiny cracks in the ampoules appear during freezing, so that the contents may come into contact with the liquid nitrogen. In this way viruses and microbes can in theory be released and come into contact with the frozen seed of other men. Because of this risk the man is required by law to be tested in advance for infectious diseases such as aids and hepatitis.
Sperm donorship
The first recorded sperm donation that took place in a medical center was carried out with few of the ethical considerations that are mandated in clinics today: it was performed in 1884 at Philadelphia medical 232
vo l u n ta ry a n d i n vo l u n ta ry s t e r i l i t y school for an infertile couple. Instead of taking the sperm from the husband, the doctor chloroformed the woman, then let his medical students vote which of them was the ‘best looking’, with that elected one providing the sperm for the insemination. After talking to the husband, they decided it was best not to let the woman know.
Sperm donation can be a morally contentious issue. Couples in heterosexual relationships considering sperm donation as a solution to childlessness may view it as preserving the sexual integrity of their relationship. However, sperm donation does not maintain the reproductive integrity of a relationship in that the woman’s sexual partner is not the biological father of her child, and it is the sperm donor, not the partner, who has reproduced himself.
However, others point out that the process is essentially a sexual one: a woman’s innate sexuality may be the reason why a child is wanted, the donor has to be screened for sexually transmitted diseases which could be passed on through the use of his sperm, and the donor has to sexually stimulate himself in order to produce the sperm samples which are used for achieving pregnancies in women to whom he is not related. Some would argue that it is impossible to distinguish sexuality from reproduction, and that the reason for preserving sexual integrity is to preserve reproductive integrity.
The use of sperm donation is increasingly
popular among unmarried women and single or coupled lesbians. Indeed, some sperm banks and fertility clinics, particularly in the us, Denmark and the uk have a predominance of women being treated with donor sperm who fall within these groups and their publicity is aimed at them. This produces many ethical issues around the ideals of conventional parenting and has wider issues for society as a whole, including the issues of the role of men as parents, the issue of family support for children, and the issue of financial support for women with children.
Some donor children grow up wishing to find out who their fathers were, but others may be wary of embarking on such a search since they fear they may find scores of half-siblings who have been produced from the same sperm donor. Even though local laws or rules may restrict the numbers of offspring from a single donor, there are no worldwide limitations or controls and most sperm banks will ‘onsell’ and export all their remaining stocks of vials of sperm when local maxima have been attained.
However, others would argue that sperm donation has liberated the way in which women can control their reproductive lives and that it has enabled many men as sperm donors to father children which they would not want or wish to support but which they know will fulfil a desperate biological and social need for the women who bear them.
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Many donees do not tell the child that they were conceived as a result of sperm donation, or, when non-anonymous donor sperm has been used, they do not tell the child until it is old enough for the clinic to provide the contact information about the donor.
For children who find out after a long period of secrecy, their main grief is usually not the fact that they are not the genetic child of the couple who have raised them, but the fact that the parent or parents have kept information from them or lied to them, causing loss of trust.
Furthermore, the overturning of their knowledge of who their parents are may cause a lasting sense of imbalance and loss of control.
However, there are certain circumstances where the child very likely should be told: when many relatives know about the insemination, so that the child might find it out from somebody else; when the husband carries a significant genetic disease, relieving the child from fear of being a carrier; or where the child is found to suffer from a genetically transmitted disorder and it is necessary to take legal action which then identifies the donor.
Manhood Page 29
