An analysis of male fertility should include the following:

1. A semen analysis for accurate measurement of sperm motility and count. Sperm morphology is assessed employing “Kruger criteria.” Semen should also be cultured for UreaplasmaUrealyticum, Chlamydia, Gonococcus and for aerobic/anaerobic pathogens.

2. A blood test for the presence of antisperm antibodies (ASA). Immunity to sperm, whether in the male or female, is not an absolute cause of infertility. Sperm antibodies-small proteins that can be produced by immune cells to attach to sperm-reduce fertility, but do not invariably prevent conception. Rather, the effects are graduated; the larger the immunologic response, the less likely it is that a pregnancy will occur.

Under normal conditions, blood cells that produce antibodies and sperm do not mix.  Direct contact between the two is prevented by a cellular wall within the testicles.  This barrier is formed by Sertoli cells, which abut very closely against each other, forming tight junctions that separate the developing sperm cells from the blood and prevent immunologic stimulation.  However, the blood/testis barrier can be broken as a result of injury or infection.  When this barrier is breached, immunologic attack on sperm can occur.

Once sperm antibodies have formed, they can affect sperm in several different ways.  Some antibodies will cause sperm to stick together (agglutinating antibodies).  Agglutinated sperm clump together in huge masses and are unable to migrate through the cervix and uterus.  Other antibodies mark the sperm for attack by Natural killer (NK) cells of the body’s immune system (opsonizing antibodies).  Some antibodies cause reactions between the sperm membrane and the cervical mucus preventing the sperm from swimming through the cervix (immobilizing antibodies).  Antibodies can also block the sperm’s ability to bind to the zonapellucida of the egg, a prerequisite for fertilization.  Finally, there is evidence that the fertilized egg shares some of the same antigens that are found on the sperm.  It is possible that sperm antibodies present in the mother can react with the early embryo, resulting in its destruction before it is able to implant and develop.

Sperm antibodies occur in about 7% of infertile women and are even more common in men, especially those who have previously undergone reproductive surgery such as vasectomy or vasectomy reversal.  In fact, when vasectomy was performed more than ten years prior was, more than was >70% of such men will have high concentrations of sperm antibodies, representing a severe form of male infertility.  The treatment that is most effective at overcoming sperm antibodies is intracytoplasmic sperm injection (ICSI) where each egg is injected with a single sperm.

3. If IVF is being considered, the man should also undergo blood testing for Hepatitis B surface antigen, Hepatitis C antibodies, RPR (Syphilis) and HIV.

4. A Sperm DNA Integrity Assay (SDIA). The SDIA, like the Sperm Chromatin Structure Assay (SCSA) is a tool for measuring clinically important properties of sperm chromosomes. The results correlate well with the potential of sperm from a given male to produce embryos that would be sufficiently “competent to produce a live birth.” The SDIA utilizes a specially designed DNA probe and a high tech machine that can then sort out according to properties that are even more integral to their ability to create an embryo than their physical appearance under the microscope. Instead, the SDIA measures DNA damage.

The degree of abnormalities in the genetic material of the sperm is expressed numerically as the DNA Fragmentation Index (DFI). DNA damage may be present in sperm from both fertile and infertile men. Therefore, this sperm DNA damage analysis may reveal a hidden abnormality of sperm DNA in infertile men classified as unexplained based on apparently normal standard sperm parameters.  Infertile men with abnormal sperm characteristics exhibit increased levels of DNA damage in their sperm.  Sperm from infertile men with normal-appearing sperm may have DNA damage to a degree comparable to that of infertile men with abnormal-appearing sperm. An abnormal SDI assay is more likely to occur in cases of abnormal semen parameters. Since SDIA is independent of conventional semen parameters, results may identify male patients for whom IVF and intracytoplasmic sperm injection (ICSI) will be far less likely to result in a viable pregnancy.

Cancer treatments are well known to adversely affect male fertility.  Sperm production often drops as a result of the effects of chemotherapy or radiation intended to treat the cancer. Sometimes even if the sperm stem cells survive, they may be damaged in a way that affects the sperm that they produce.  The effects of this damage can range from infertility to pregnancy with inevitable miscarriage.  SDI assays serve as predictors of the probability to conceive and carry the pregnancy to viability.

It is important to add that most current data available on the significance of abnormal SDIA results in infertile couples seeking treatment has emanated from non-IVF pregnancies. Within a few months, a large database of information on the clinical role of the SDIA in patients undergoing IVF will be available through research currently underway at SIRM. In the interim, our preliminary data suggests the following:

The viable (>12 weeks) IVF pregnancy rate (and thus presumably also the birth rate) could be as much as 2 times lower in women under 33 years of age, whose partners have abnormal SDI assays (with a DFI of <30%). Results become progressively worse with advancing maternal age such that at 35 years+, the viable pregnancy rate could be as much as 3-4 times lower.

Although it is possible for abnormal SDIA results to sometimes spontaneously revert back to normal, this likely occurs quite infrequently.

Although abnormal SDIA results are detected in men with apparently normal semen analyses, abnormal results are more commonly seen in cases of men who have abnormal sperm parameters (abnormal sperm count, motility and/or morphology)

There is some suggestion that the use of antioxidant therapy (pycnogenol 200mg daily, L-Carnitine 3 grams per day, acetyl carnitine 500mg per day, Vitamin C 1,000mg  per day and Vitamin E 800IU per day) taken for 6-8 weeks, can cause the SDI assay to revert to normal in many cases.

There is some suggestion that men who have varicoceles ( a collection of distended veins in the scrotum) associated with an abnormal SDI assay may experience a reversion of the SDI assay back to normal, 3-6 months following surgical or radiological ablation of the varicoceles.

In summary, an abnormal SDI assay augurs poorly for the outcome of fertility treatment in general  – and IVF/ICSI in specific. In such cases, the fertilization rate and pregnancy rates are reduced and the chance of early pregnancy loss appears to be increased significantly.  An abnormal SDIA result does not totally preclude a successful pregnancy. The prognosis worsens progressively as the age of the egg provider advances beyond 33 years.  Selective surgical ligation of a varicocele and medical anti-oxidant treatment may be effective in restoring the SDIA to normal.

Immunity to sperm, whether in the male or female, is not an absolute cause of infertility.  Sperm antibodies-small proteins that can be produced by immune cells to attach to sperm-reduce fertility, but do not invariably prevent conception. Rather, the effects are graduated; the larger the immunologic response, the less likely it is that a pregnancy will occur.

Under normal conditions, blood cells that produce antibodies and sperm do not mix.  Direct contact between the two is prevented by a cellular wall within the testicles.  This barrier is formed by Sertoli cells, which abut very closely against each other, forming tight junctions that separate the developing sperm cells from the blood and prevent immunologic stimulation.  However, the blood/testis barrier can be broken as a result of injury or infection.  When this barrier is breached, immunologic attack on sperm can occur.

Once sperm antibodies have formed, they can affect sperm in several different ways.  Some antibodies will cause sperm to stick together (agglutinating antibodies).  Agglutinated sperm clump together in huge masses and are unable to migrate through the cervix and uterus.  Other antibodies mark the sperm for attack by Natural killer (NK) cells of the body’s immune system (opsonizing antibodies).  Some antibodies cause reactions between the sperm membrane and the cervical mucus preventing the sperm from swimming through the cervix (immobilizing antibodies).  Antibodies can also block the sperm’s ability to bind to the zonapellucida of the egg, a prerequisite for fertilization.  Finally, there is evidence that the fertilized egg shares some of the same antigens that are found on the sperm.  It is possible that sperm antibodies present in the mother can react with the early embryo, resulting in its destruction before it is able to implant and develop.

Sperm antibodies occur in about 7% of infertile women and are even more common in men, especially those who have previously undergone reproductive surgery such as vasectomy or vasectomy reversal.  In fact, when vasectomy was performed more than ten years prior was, more than was >70% of such men will have high concentrations of sperm antibodies, representing a severe form of male infertility.  The treatment that is most effective at overcoming sperm antibodies is intracytoplasmic sperm injection (ICSI) where each egg is injected with a single sperm.