Male factors
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In assessing male fertility, in addition to semen analysis, the patient’s medical history is also of great importance.
In the case of a problem or an IVF failure associated with exceptionally low fertilization or with poor quality Day 4 or 5 embryos, a visit to a Specialist Urologist or Andrologist is recommended.
If pathological causes of male infertility are excluded, there are other screening tests that may shed light on the problem. It should be noted that a normal semen analysis does not necessarily guarantee male fertility.
There are situations where, despite the fact that there is a normal number of spermatozoa with good morphology and mobility in the sample, their DNA is abnormal. Today, there are a number of criteria to assess DNA quality, eg DNA fragmentation index (DFI), etc.
Peripheral blood karyotype
A peripheral blood karyotype determines whether the number of chromosomes in the cells is normal (46, XY in males and 46, XX in females).
If this number is not normal or if there are structural chromosome abnormalities, the sperm is then a carrier of abnormal genetic material. In such cases, the resulting embryos have genetic anomalies that impede a successful pregnancy, resulting in infertility or multiple miscarriages.
Therefore, depending on their medical history, a karyotype analysis may be recommended to a couple before they undergo treatment with assisted reproductive techniques.
If the karyotype is abnormal, there are two options: a genetic analysis of embryos prior to embryo transfer (preimplantation genetic diagnosis, PGD) or the use of donor sperm.
DNA fragmentation
As the term implies, sperm DNA can break into small pieces or fragments. Should this occur, the prognosis is not good, although it should be noted that oocytes are able to repair and compensate for this fragmentation to some extent. The better the oocyte quality, the greater its ability to repair.
Different factors can cause DNA fragmentation in sperm:
- Internal factors (primary fragmentation). Fragmentation is the result of abnormal maturation of spermatozoa in the epididymis or abnormalities that are not eliminated by the control mechanisms within the testes. In men older than 45, there may be an increased frequency of DNA fragmentation.
- External factors (secondary fragmentation). There are several factors that may cause DNA fragmentation. In some cases, the damage is permanent, as after radiotherapy or chemotherapy. In other cases, it may be temporary, as can happen in the case of varicocele, exposure to high temperatures (due to profession, high fever, etc), infection or inflammation of the testicles (orchitis).
The DNA is a structure with two protein chains that form a helix. Fragmentation can affect only one or both of these chains, with a worse prognosis in the latter case. When the percentage of sperm with fragmented DNA exceeds 25%, the patient's reproductive capacity may deteriorate if left untreated.
Measurement of DNA fragmentation (DNA Fragmentation Index, DFI) is recommended in the following cases:
- Repeated failure of assisted reproductive techniques
- Failure of blastocyst formation
- Recurrent miscarriages
- High percentage of oligo-azoo-terato-spermia (ie < 5 million/cm3, < 10 % motility, <1% normal morphology)
- Varicocele
- Urogenital infections
- Men over 45 years old
- Exposure to toxins or very high temperatures
Various options are available to address the fragmentation:
- Suppression of the cause (treatment of fever, varicocele surgery, etc).
- Medication with antioxidants. Fragmentation is produced by a cellular oxidation process as a by-product associated with inflammation. Treatment with antioxidants may be effective in a large number of cases.
- Collect sperm directly from the testes with a biopsy (Testicular Sperm Extraction, TESE). The semen is collected before passing the zone where DNA fragmentation occurs (the epididymis).
- Intracytoplasmic Μorphologically-selected Sperm Injection (IMSI): allows the selection of sperm with a lower risk of fragmentation.
Due to the ease of treatment, the lack of side effects and the overall health benefits to the patient, the administration of oral antioxidants (vitamins C and E, coenzyme Q10, carnitine, etc.) for 2-3 months prior to IVF treatment, particularly for men at high risk of DNA fragmentation, is recommended.
Abnormalities of meiosis
Sometimes, genetic errors occur during the process of meiosis. In women, errors during meiosis are the cause of the increased risk of miscarriage after a certain age or birth defects (eg Down's syndrome).
Abnormalities during meiosis can also occur in men. They are generally associated with an abnormal semen analysis (especially in the case of oligo-zoospermia), although sometimes these patients have a normal semen analysis.
In these cases, two options have proven to be effective: the genetic screening of embryos before transfer (preimplantation genetic diagnosis, PGD) or the use of donor sperm.
Other pathologies
During infertility investigation, some problems that may be revealed include male sexual dysfunction or varicocele.
Sexual dysfunction
The most common problem in men is erectile dysfunction, although problems such as decreased libido can often affect the couple.
Sexual intercourse during the woman’s fertile days is essential in order to achieve a pregnancy. Any factor that reduces the frequency of intercourse or prevents it, also reduces the fertility of the couple.
Sexual dysfunction may be caused by physical (diabetes, neurological disorders, toxins or other substances, etc.) or psychological problems (anxiety, stress, depression, etc.).
A thorough investigation of infertility based on both Andrology and Psychology may provide the key to effective treatment, be that surgical or pharmaceutical intervention.
Varicocele
Varicocele is defined by the presence of enlarged veins in the spermatic cord. It is responsible for up to 40% of male infertility.
Varicocele is sometimes associated with pain or heaviness in the testes, although it is often asymptomatic.
In cases where there are very few or no symptoms or minimal clinical findings, it is controversial whether surgery improves fertility.
Medium and high degree of varicocele is associated with an increased risk of DNA fragmentation and should therefore be treated with embolization or surgery. Although embolization is a simple technique, its success rate is lower than that of surgery.
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