Professor Robert McLachlan
MBBS(Hons) FRACP PhD
View Professor McLachlan’s profile here
The traditional definition of infertility is the absence of conception after one year of regular unprotected intercourse around the time of ovulation. These days we realise that couples come with fertility concerns before that time, or have specific issues, such as older female age, and require prompt evaluation so that they can plan their next step; this might be to keep trying for a natural conception or a move to some form of Assisted Reproductive Technologies (ART). These concerns are very common with about one in seven couples being affected by infertility, and one in 25 Australian children are now conceived by ART. When couples present with fertility concerns, there are some basic examinations and tests that should be conducted right away. If there is an issue, it can be identified, explained and managed as early as possible.
There are many factors that can cause infertility. In the past people focussed their attention on the female partner; but we now know that evaluation and management of the male partner is also essential in assessing a couple’s fertility prospects.
A similar amount of problems occur in female and male partners, and in about a third of cases there are issues for both partners. Therefore there is ‘gender equity’ in infertility and it should be considered a couple’s problem. Both partners need to be considered individually and collectively.
Male infertility is very common, one in 20 men are sub-fertile; meaning they have reduced fertility resulting in a prolonged period of a failure to conceive. In about two-thirds of cases we don’t actually know why the sperm quality is poor and this fact can be a major cause of frustration. What we can say is that half of all ART treatments involve sole or contributory male factor infertility.
The introduction of the Intracytoplasmic sperm Injection (ICSI) procedure over 20 years ago has revolutionised infertility management and has enabled many infertile men to father their own genetic children. This process was developed specifically for those men who did not have enough motile (or swimming) sperm that were capable of fertilising an egg in a dish, which is the original form of IVF.
ICSI involves the selection, by an embryologist, of a single motile sperm for microinjection into the egg. The procedure is undertaken with specialised microscopic equipment, as an egg measures approx. 0.1 of a millimetre. As an indication of scale, when you line up 10 eggs on a ruler side-by-side they would be ‘just’ visible, and sperm are many times smaller again, the head of a sperm is a similar size to a blood cell at 5 microns. If we are able to find a few live sperm in the semen or even in the testicles, with ICSI we can achieve pregnancy rates similar to other couples having standard IVF.
In essence, ICSI has really ‘levelled the playing field’ in lowering what is needed for conception from millions of sperm per ml of semen for natural conception to only needing one sperm for each of the eggs available to fertilise in ART.
At the time of the introduction of ICSI in 1993 it might have seemed that “as long as there is enough sperm to inject the eggs, we don’t need to worry about the male.” But it’s important to remember that the ICSI procedure is not a treatment; it is a bypass procedure that allows us to produce an embryo using only one sperm rather than millions of sperm. Secondly, there are several reasons it is essential the male be examined. The first question is always: “Can we restore natural fertility?” Our preferred option is for couples to get pregnant spontaneously, so if we can find a reversible form of infertility, we treat it and then allow nature to take its course. Next, we look for a reason for a man to have no sperm or a very low sperm count, and although we may not be able to fix it (such as genetic issues); at least we have a diagnosis and can relieve the anxiety of ‘not knowing why’. Finally, we look for other health problems more common in infertile men, such as a low testosterone or other diseases that may be affecting fertility.
How does the male reproductive system work?
The testicles have two jobs; to produce sperm for fertility and male hormones (called ‘androgens’, the major one being testosterone for virility. Fertility and virility is not the same thing and aren’t always affected at the same time. Thus a man could have very poor sperm production or sperm function and experience infertility and yet is virile with normal sex hormone levels. Some men however will have both; poor sperm production and infertility, and poor virility due to low hormone production.
The testicle is driven by the pituitary gland at the base of the brain. The pituitary gland produces two hormones Luteinising Hormone (LH) and Follicle Stimulating Hormone (FSH). Women produce the same hormones that stimulate the ovaries, but in men, they stimulate the testicles. The LH promotes the production of testosterone, which works together with the FSH on the Sertoli cells in the walls of the sperm tubules. These large cells wrap around and nurture the sperm cell division and their maturation into the characteristic ‘tadpole shape’.
A normal man matures a thousand sperm a second. This is tens of millions of sperm a day. The maturation process is a continuous production with a fresh crop each day; the sperm expelled today started its development 60 days ago, the sperm expelled tomorrow started 59 days ago etc.
After production, sperm delivery is the next level of complexity. Only 5% of the volume of semen actually comes from the testes; most of what you see is from the seminal vesicles and prostate at the base of the bladder. The testicles are connected through the epididymis, a fine coiled tube approx. 1.5 metres on the back of the testis which then becomes the vas defences (a much thinker tube you can feel going up into the groin) which connects into the urethra at the base of the bladder.
The DNA is packed into the tiny sperm head while the middle section houses the power packs (the mitochondria) that supply the energy needed to whip back and forth as a result of sliding between many pairs of fine ‘cables’ that run along its length. It is so powerful for its size (producing more power per unit mass than the space shuttle!); can survive for 6 days and transfers a wonderful amount of information. It’s been calculated that a normal ejaculation transfers 1.6 terabytes of information in just 3 seconds. ‘4G’ doesn’t get close to that! And these sperm know what they are doing; they know how to find an egg all the way up the female fallopian tubes, bind to it and burrow into it, and then chemically react with the egg to release its DNA.
Causes of Male Infertility
The natural conception process is a wonderfully complex but also delicate process; and unfortunately some parts fail in infertile men. The four major types are:
1. Deficiency of FSH and LH secretion due to pituitary problems
The rarest and occurs in less than 1% of cases.
This can be treated through injections of LH and FSH and will restore natural function to allow a spontaneous or natural pregnancy.
2. Blocked vas deferens or other tubes
These account for about 25% of cases. It can be a congenital problem (present from birth) or following surgery (esp. vasectomy) or severe trauma or infections.
In some cases blockages can be fixed and some vasectomies reversed but for many, sperm can be taken from above the blockage and used for ICSI.
3. Sexual difficulties
Occurs about 10% of cases, couples have difficulties in having regular ejaculatory sex; some diabetic men, those with spinal cord injury, certain medications and psychosexual problems mean that they can’t ejaculate at the ‘right time in the right place’. Some men can’t be helped to achieve this goal but for others, ART treatment is a very effective option.
4. Sperm Production
This is by far the most common cause of male infertility; sperm production is faulty so that not enough sperm are made, or they don’t swim or work. Sometimes, we have an explanation, for example we know that cancer treatment can affected production, and some genetic problems may be the cause, but, often we don’t actually know. Sadly when we don’t know the cause, we don’t have effective treatment to boost sperm number or quality. ART treatments will be the only treatment options in these cases.
When you present for assessment, the doctor will go through your general health, medication, drug use, as well as your reproductive history such as:
- prior paternity
- sexual issues (erectile, ejaculation, sex frequency and timing)
- undescended testes
- genital infection, trauma
- previous pelvic surgery
- symptoms of testosterone deficiency
Physical examination will be required, and require a brief examination of the genitals. This it is not painful and includes assessment of testes, epididymis and vas. Note is taken of scarring or previous injury. The size, shape and texture of the testes is noted and compared with the expected normal range (15-35ml in adulthood). Reduced testicular volume could indicate poor sperm production.
Some health problems are more common in infertile men, particularly testicular cancer in men with a history of undescended testes, and testosterone deficiency
In addition to examination and medical history, routine tests often include a blood test to determine the FSH, LH and testosterone levels and semen analysis. When sperm production fails due to a testicular problem, the pituitary gland ‘knows’ to make high levels of FSH to stimulate more output. Therefore the finding of a low sperm count, small testicles and high level of FSH indicates there is something wrong in the testes ability to produce sperm.
Testosterone deficiency is also more common in men with poor sperm production; about 10% will eventually need testosterone therapy. But it is important to note that you do not commence testosterone treatment in an infertile man until his fertility concerns are addressed, such as by storage of sperm, or IVF treatment and storage of embryos. This is because testosterone is effectively a male contraceptive, as it turns off LH and FSH secretion and sperm production. Men who use testosterone to grow muscles (androgen abuse); have small testes and a low or zero sperm count for this reason.
One can consider sperm as army of soldiers committed to fertilising an egg yet in the end it only takes one soldier. In the semen analysis, we count the number of soldiers (as concentration per ml and total in the ejaculate) and the speed at which they march – their motility. The more you have out there ‘actively looking’, the better the chances! One important thing we can’t test well is whether the soldier can shoot. The scientists look at the sperm shape (morphology) under the microscope, as a pointer to its functional ability. If the sperm are perfectly ‘kitted up’ (perfect shape) this suggest (but can’t assure) he is a competent soldier! Thus morphogy is fairly weak surrogate marker of function and not a direct measurement of function.
The World Health Organization (WHO) semen test reference limits (last updated 2009) specifies only 4% or more of sperm are need to be normal shaped, so you don’t need to have many normal shaped sperm to be considered potentially fertile. And some men will cause a natural pregnancy with a sperm count, motility of morphology well below the reference ranges. So although semen quality is important, it is not the “be all end all”.
Management of male infertility
The overall strategy for managing male infertility is to first strive to achieve a natural pregnancy. Starting with the simple things first which is timing of sex, this includes ensuring the partner is ovulating and knows when her fertile window is; and encouraging sex at least every two days during this period. From this point, there are three ascending options for treatment:
1. Artificial insemination
The process of timing the artificial insemination with partners semen into the female partners uterus during ovulation.
2. Traditional IVF
The process where 30,000 sperm are introduced to the egg in a dish to encourage fertilisation
3. Microinjection ICSI
The process of selecting one single sperm and injecting it straight into the egg to promote fertilisation
Professor Rob McLachlan is a consultant andrologist to the Monash IVF program, a past President of the Fertility Society of Australia, a consultant to the World Health Organization on male fertility regulation and Director of Andrology Australia which is a Federal government initiative, based at Monash, that is committed to research and community and professional education in male reproductive health.
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