Tests Performed to Diagnose Male Infertility
A semen analysis is a vital investigation of male infertility that can be performed in the laboratory. This is a test where a man’s sperm and semen is examined under a microscope and important parameters are reported on including:
- Sperm count or concentration/ml
- Semen volume
- Motility information (how well sperm swim)
- Morphology (sperm shape, which affects their function)
Sperm production is sensitive to your general health. Sperm function may reflect this and can vary over time. For example, sperm number and function can temporarily become abnormal after a fever or significant illness. If a semen analysis returns an abnormal result, it should be repeated at a six-week interval, to assess if the abnormality is permanent or fluctuating. Repeated testing helps establish what a true average result is for an individual man.
Sperm Antibody Testing:
Tests for sperm antibodies should be measured routinely for all men presenting with infertility. Anti-sperm antibodies can be responsible for sperm movement disorders or can interfere with sperm-to-egg binding, impairing fertilization.
Age and Male Fertility
As a man gets older, his chances of conceiving and having a healthy baby may decline. It can also take longer for his partner to fall pregnant, and there is an increased risk of not conceiving at all.
Facts About Male Fertility and Age
- The quality of a man’s sperm decreases with age
- Whatever the age of the mother, the risk of miscarriage is higher if the father is over 45
- The children of older fathers are at greater risk of autism, mental health problems and learning difficulties
- For couples having IVF, the risk of not being able to have a baby is more than five times higher if the male partner is aged 41 or older
- The volume of a man’s semen and sperm motility (swimming power) decrease continually between the ages of 20 and 80
- Children with fathers aged over 40 are five times as likely to have an autism spectrum disorder than children fathered by men aged under 30
What Are the Causes of Male Infertility?
Azoospermia – Zero Sperm Count
Azoospermia is the total absence of sperm from the semen. Azoospermia is either caused by physical obstruction of sperm or occurs because of a sperm production problem. Some cases are reversible.
Oligospermia – Low Sperm Count
Sperm concentrations of less than 15 million/mL are classified as oligospermic. This figure represents the 5th percentile of a fertile male population. That is, 95% of fertile men have a higher sperm count.
Asthenospermia – Low Motility
Asthenospermia is defined as less than 40% sperm swimming or less than 32% rapidly swimming forwards. Complete asthenospermia is rare but can be associated with genetic causes or structural defects within the cells.
Teratospermia – Abnormal Sperm Shape/Morphology
Teratospermia is a reduced percentage (less than 4%) of sperm with normal morphology i.e. shape and appearance. The sperm’s ability to bind with the egg correlates strongly with normal morphology of the sperm head.
Microdeletions of The Y Chromosome – AZF Region Gene Mutation
Y chromosome infertility is caused by changes in the male’s Y chromosome. Genes within the Y chromosome are responsible for sperm production, and when abnormalities occur, men can experience problems with sperm production and fertility.
Deletions in the long arm of the Y chromosome that cause azoospermia or oligospermia occur in regions of the chromosome known as the azoospermia factor (AZF) regions. Such microdeletions are more common in men with severe primary sperm production (spermatogenic) disorders.
The AZF region is sub-divided into three regions: A, B, and C. Men with AZFA and AZFB deletions are unlikely to be able to find usable sperm for treatment, even with an open testicular exploration procedure.
When men with Y chromosome infertility conceive using ICSI (Intracytoplasmic Sperm Injection), these genetic mutations will inevitably be passed down to their sons.
Chromosomal Conditions & Gene Mutations
A karyotype is a chromosome analysis performed for men where clinical evidence of testicular failures suggests the possibility of Klinefelter’s syndrome, a chromosomal condition whereby men have an extra X chromosome.
Although most men with Klinefelter’s syndrome produce no sperm in the semen, sperm for IVF/ICSI may be obtained by testicular biopsy in more than 50% if patients. Children conceived from sperm retrieved from fathers with Klinefelter’s syndrome generally themselves have normal karyotypes.
Absent vas deferens (the duct that carries sperm from the testicles to the urethra) causing obstructive azoospermia can be a sign that a man either carries one or two copies of a gene mutation causing the autosomal recessive genetic condition cystic fibrosis. If a couple learns that their offspring are at risk of having cystic fibrosis, they can use IVF and preimplantation genetic diagnosis (PGD) to improve their chance of having healthy babies.
There are many other sperm production problems that at present, have no known cause. It’s likely that as further genetic disorders are discovered, more causes will be uncovered.
A varicocele is a scrotal varicose vein. Varicoceles are common, observed in 15% of the general male population. Most varicoceles do not cause symptoms, but some varicoceles can lead to increased scrotal/testicular baseline temperatures and cause oxidative stress associated with sperm problems. In the case that varicoceles are the cause of male factor infertility, they can be repaired through surgery and interventional radiology.
A scrotal ultrasound may also be recommended to assess for testicular tumours, causes of testicular obstruction or varicocoele.
Primary hypogonadism is defined as an inability of the testes to produce sufficient testosterone, due to a problem in the testicles. This condition is usually considered to be irreversible. Causes for primary hypogonadism include testicular damage, mumps orchitis, chemotherapy, and Klinfelter’s syndrome.
Secondary hypogonadism exists when there is inadequate central stimulation of fundamentally normal testes. Men with this condition can be treated with hormonal medications to “switch on” or improve their testosterone and sperm production. Causes of secondary hypogonadism include Kallman syndrome, or pituitary insufficiency due to tumours, infections, surgery or radiation.
Erection and ejaculation problems can contribute to infertility. For some couples, IUI (Intrauterine Insemination) or IVF can be used to get pregnant when these problems are central and cannot be overcome with simple treatments.
Obstruction (Obstructive Azoospermia)
Approximately 6% of infertile men have blockages in the genital tract that prevent the passage of sperm out of the testes, which results in the absence of sperm in the semen.
There are three major groups of causes of male genital tract blockages:
- Development disorders of the epididymis (the coiled tube that lies on the back aspect of each testicle); vas deferens (the duct that carries sperm from the testicles to the urethra); and seminal vesicles (the gland that mixes the sperm to form semen)
- Scarring from inflammation (E.g. sexually transmitted infections like gonorrhoea)
- Previous vasectomy
In these instances, it is possible to obtain sperm by a surgical procedure called TESA (Testicular Sperm Aspiration Procedure) or PESA (Percutaneous Epidydimal Sperm Aspiration) to use for IVF/ICSI.
PESA is a procedure that involves passing a fine needle into the epididymis to obtain sperm. TESA involves passing a fine needle directly into the testes in order to retrieve a small number of the seminiferous tubules (tubes where sperm are made).
About 15% of infertile men have no sperm in their semen (azoospermia). This may be due to the wrong hormonal signals being present, which can halt sperm production. Occasionally, correcting a man’s hormones can reverse the problem.
Testicular failure can occur when sperm producing cells in the testes either did not develop or have been irreversibly destroyed. This may be caused by chromosomal or genetic disorders, inflammation of the testes (e.g. after a mumps infection) or treatment with certain drugs (e.g. chemotherapy). It may also be associated with failure of the testes to descend into the scrotum during infancy (cryptorchidism).
For couples in this category who wish to have a family, having a testicular biopsy is a reasonable primary approach to assess whether sperm can be found. If sperm can be retrieved, it can be used for IVF/ICSI. In cases where sperm cannot be found, using a sperm donor may be their only realistic alternative.
Who Are These Procedures Used For?
PESA/TESA may be used to diagnose whether sperm production is occurring in cases of obstructive and non-obstructive azoospermia.
It is often used in cases where the male partner has one of the following issues:
- Primary testicular problems with deficient sperm production
- Irreversible obstruction of the genital tract (possibly caused by a previous infection or surgery)
- Congenital bilateral absence of the vas deferens (CBAVD)
- Post-vasectomy or failed vasectomy reversal
How Is PESA / TESA Sperm Used?
Sperm retrieved using PESA/TESA can be used to attempt to achieve a pregnancy using a laboratory technique called intracytoplasmic sperm injection (ICSI). In order to use testicular sperm to conceive, the female partner must undergo IVF treatment and egg collection. Her egg collection procedure is usually performed on the same day as the PESA/TESA. A single sperm that has been isolated during a PESA/TESA can then be injected into each egg collected from the female partner.
ICSI treatment using testicular sperm retrieved using PESA/TESA is a commonly performed procedure and has similar success rates to routine IVF.
Vasectomy & Fertility
When men undertake a vasectomy procedure it is because at the time, they felt their family was complete. About three percent of men who have had a vasectomy will later on consider having more children. This most commonly occurs in the context of a new relationship.
Men who have had a vasectomy can conceive either by having a vasectomy reversal or by using IVF/ICSI with testicular sperm retrieval techniques such as TESA or PESA.
Vasectomy reversal is a procedure performed by a urologist and involves re-joining the cut ends of the vas deferens usually by microsurgery (using an operating microscope). The operation is much more complex than the original vasectomy and is usually done under general anaesthetic. The procedure can take several hours.
How Successful Is a Vasectomy Reversal?
In 60-90% of vasectomy reversals, sperm returns to the ejaculate. The chance is lower if:
- The vasectomy was performed a long time ago
- A large segment of vas deferens was removed originally
- The vas was cut near the epididymis
- Other blockages have since developed in the epididymis
- 10-15 years after a vasectomy, reversal is less likely to be successful
Even after technically successful surgery, pregnancy is not guaranteed. Only about 40% of couples achieve a pregnancy 2-3 years after vasectomy reversal. The chance of pregnancy is lower when the woman is older or where the couple may have other fertility issues. Sperm antibodies may have developed which adversely affect sperm function. Sperm antibodies occur when a man’s immune system mistakes the man’s own sperm for a foreign tissue and mounts an immune attack. About four in five men develop sperm antibodies after vasectomy.
Sperm Antibodies and Vasectomy
Low levels of sperm antibodies do not cause problems. However, in men with high levels of sperm antibodies, antibodies can interfere with the ability of sperm to swim, and to attach to and fertilise the egg. This can stop pregnancy from happening, even if the vas deferens is successfully re-joined.
When Is IVF Used After Vasectomy?
Men who have had a vasectomy reversal but their partner has been unable to get pregnant can turn to IVF. Some couples decide not to go down the road of vasectomy reversal and go straight to IVF to have a baby. This decision will depend on the couple’s individual circumstances.
Male Infertility Treatment Options
Intrauterine Insemination (IUI)
Also referred to as artificial insemination, this fertility procedure involves placing concentrated laboratory-optimised sperm high up inside a woman’s uterus to facilitate fertilization. The goal of IUI is to increase the number of motile and normally shaped sperm that reach the egg and thereby increase the chance of fertilization and conception.
While IUI gives the sperm a head start, it still requires the sperm to reach and fertilize the egg on its own. It’s a less invasive and less expensive option compared with IVF, and may be suitable where a man has a mild sperm problem or erectile dysfunction. IUI can also allow a woman to conceive using donor sperm.
ICSI has revolutionised the treatment for couples where there is severe male infertility. With ICSI, a single healthy sperm is selectively injected into the egg. This effectively causes fertilization to occur. Even in men with extremely low sperm counts or with ultra low numbers of normal looking sperm, ICSI can be very successful.
IMSI is a form of ICSI performed using digital ultra-high magnification of sperm to examine not only for general morphology, but also for more subtle changes in sperm ultrastructure. IMSI may be recommended for those with severe male factor infertility, such as very low numbers of sperm, a high proportion of abnormal looking sperm, or if more standard ICSI procedures have been unsuccessful in the past.
IMSI may not be suitable for all patients requiring ICSI for several reasons: IMSI is a new technology, and is not covered by Medicare and therefore adds extra expenses to IVF treatment. While current international evidence shows IMSI early outcomes may be promising, more evidence is needed to conclusively demonstrate improved live birth outcomes compared to more standard ICSI techniques alone.
Testicular Sperm Retrieval
Men with obstructive azoospermia require surgical sperm retrieval to conceive, but this technique may also benefit other men with severe male factor infertility associated with high levels of sperm DNA fragmentation or damage contributing to poor IVF outcomes.
Hormonal Induction of Spermatogenesis
This is a treatment for male hypogonadotropic hypogonadism, which can correct oligospermia and azoospermia in men where there is insufficient production of male hormones, causing infertility.
Fertility Preservation for Male Patients
When young men are diagnosed with a cancer, future fertility may be easily overlooked in the desire to quickly commence treatment. Chemotherapy can temporarily or permanently destroy developing sperm cells. Radiotherapy for testicular or other cancers near the testes can also damage the testis, leaving permanent problems with sperm production. Radiotherapy such as total body irradiation can cause problems too.
Up to two thirds of male patients become azoospermic (zero sperm count) following chemotherapy. Recovery of sperm production is strongly dependent upon the chemotherapy and radiation therapy regimen they have been exposed to and also will depend on the patient’s baseline reproductive function.
Men who are about to have cancer treatments may have sperm cryopreserved before commencing treatment. Semen collected during chemotherapy or radiotherapy must not be used as the effects of toxic drug exposure may be dangerous.
How Does Sperm Quality Affect Embryo Quality and Overall IVF Success?
Poor-quality sperm may lead to the production of poor-quality embryos. Sperm DNA damage can be increased by cigarette smoking, environmental toxin exposure, genital tract infections and previous chemotherapy or radiotherapy.
Sperm DNA damage is associated with poor embryo development, recurrent IVF failure, and increased risk of miscarriage. There is increasing interest in sperm DNA integrity testing to predict IVF outcomes.
Medical treatments for sperm DNA damage include oral antioxidant treatment (which includes fresh colourful fruit and vegetables, or vitamin supplements such as zinc, Vitamin C, Coenzyme Q 10, Vitamin D and melatonin); and lab selection of sperm with low levels of DNA damage.
The use of testicular sperm in couples with repeated implantation failure where the man has high levels of sperm DNA fragmentation has been reported to result in higher pregnancy rates.
What Can Be Done to Prevent Male Infertility?
- Quit smoking or don’t smoke to begin with
- Avoid unnecessary exposures to drugs or toxins
- Take antioxidants – natural dietary sources are the best
- Have your children at a younger age where you and your sperm are more healthy
- Keep the scrotum a few degrees cooler than core body temperature
- Don’t make your partner wait too long to have children – older eggs are less adept at repairing sperm DNA damage
- Use condoms with new partners – STIs can cause infertility
- Carefully consider your options and future choices before having a vasectomy
Common Misconceptions About Male Infertility
There are many misconceptions surrounding male infertility. Given that male factor infertility is present in around 50% of cases of couples struggling to conceive, it’s important to know what factors contribute to infertility, and some simple steps that can be taken to improve fertility.
Myth #1 – Age does not affect male fertility
Myth #2 – My smoking won’t affect my partner’s chance of conception
Myth #3 – My general health doesn’t affect my sperm
Myth #4 – Losing weight won’t help my sperm
Myth #5 – Fresh fruit and vegetables can’t help my sperm
Myth #6 – Alcohol isn’t an issue for men trying to conceive