Lactoferrin and Iron in Seminal Plasma of Varicocele

Infertility is defined by World Health Organization (WHO) as a disease of reproductive system characterized by failure to achieve clinical pregnancy even after 12 months or more of regular unprotected sexual intercourse. It affects around 15% of all couples, that is 48.5 million couples worldwide.

Male infertility has emerged as an important cause of infertility worldwide. There are many factors affecting male fertility and research is going on to know impact of various factors on sperm functions.Male infertility affects 30:40% of cases.

Infertility could be due to different aetiologies. Among the possible causes are genetic factors, obstructive disorders (congenital absence of vas deferens), varicocele and testicular dysgenesis. However, some cases of male infertility are idiopathic.

Varicocele is considered as the second most common cause of infertility. In the general population, approximately 15% of adult men have varicocele, but in the population of infertile men, the prevalence rises to 40% of cases with primary infertility and 80% in secondary infertility .

Varicocele is characterised by dilated veins of the pampiniform plexus which are responsible for the testicular blood drainage.Varicocele can affect fertility through hypoxia of the testicular tissues, germ cell apoptosis, oxidative stress, reflux of toxic metabolites from the renal/adrenal tissues and hyperthermia of the testis.

Semen analysis is the gold standard diagnostic test for male infertility. Seminal plasma is considered a gold mine for male fertility as it contains molecules from male reproductive glands which play important role in sperm function.

Lactoferrin is an iron-binding globular glycoprotein that act as immunomodulator mainly at mucosal level. In general, lactoferrin plays important role in the regulation of iron absorption, the modulation of immune responses, and has anti-microbial, anti-viral, antioxidant, anticancer, and anti-inflammatory activities.

Lactoferrin is found in various exocrine fluids and blood plasma. It is secreted from the prostate and seminal vesicles in humans. The physiological role of the lactoferrin in the male reproductive tract remains unclear.

Few studies have investigated the effect of lactoferrin on semen quality in humans. A recent study has demonstrated that lactoferrin expression on cells of seminal fluid was associated with worse sperm concentration and morphology, considering it as a possible novel marker of male infertility. Other studies showed that seminal lactoferrin concentrations were raised in patient groups with oligozoospermia and oligoasthenozoospermia.

Iron is an essential trace nutrient that plays an important role in general health and fertility. It is not essentially toxic, but disturbances can appear due to prolonged intake of high doses or dysfunction in the regulatory mechanism.

Iron is one of the trace elements that present in semen.It participates in oxygenation and reduction processes, entering into the composition of many enzymes and metalloprotein compounds. It has been reported that iron can cause an increase in sperm damage.

The toxicity of iron could result from the formation of hydroxyl free radicals. Iron-induced oxidative stress may induce lipid peroxidation, which has been shown to result in deterioration of sperm morphology and motility. So, iron is highly toxic if accumulated in large quantities. Also,the excess or deficiency may lead to defective spermatogenesis and to fertility impairment.

Most of the previous researches on the effect of iron on sperm function have shown increased level of seminal iron in sub-fertile than fertile men. In addition, significant higher concentrations of seminal iron were detected in asthenozoospermic and teratozoospermic groups.

On the contrary, a study has demonstrated that iron level and other trace elements were significantly lower in seminal fluid of asthenozoospermic subjects in comparison with normozoospermic men. In that study, although higher levels of iron were detected in men with normal semen analysis, these higher levels adversely affected sperm motility in this group.

Eligibility Criteria:
Inclusion Criteria:

* Group I will include infertile patients with varicocele that is diagnosed clinically and by doppler scrotal ultrasonography.
* Group II will include infertile patients due to other causes than varicocele
* Group III will include fertile men with history of childbirth within the previous year.

Exclusion Criteria:

The patients will be excluded from the group I in the following conditions:

1. History or evidence of Genital tract infection.
2. History or evidence of hormonal/chromosomal abnormalities.
3. History or evidence of chronic debilitating diseases.
4. History of hormonal treatment or chemotherapy.
5. Low semen volume less than 1.5 ml.
6. Severe oligozoospermia less than 5x10\*6 /ml.
7. Azoospermia.