By Sovich Sankoh-Karmorh, MD, Clinical Embryologist and Fertility Specialist
What you should know about It?
Male factor sub-fertility is alarmingly becoming a red flag in the determination of pregnancy rate. Although almost half of infertility cases are female factor related, male factors account for 30% of these couples, with an additional 20% of couples with a combination of male and female factors, concluding that male factor infertility plays a significant 50% in all infertile cases.
During assisted reproduction, it is rational to state that all semen samples must be subjected to selection methods, regardless of the specific procedure of fertilization to perform. In the same way, the female reproductive tract itself, as nature puts it, serves as a stringent physiological selection platform for the ejaculate population. This dramatic reduction in numbers clearly emphasizes diverse hurdles sperm must overcome in order to reach its final destination before one fertilizes the egg.
Over the years as causes of sterility drifted from gynecological markers to andrological ones, this prompted researchers to better understand the physiology of the spermatozoon and what makes a sample of semen “incapable”. The rationale behind this is to come up with solutions that allow a higher recovery of motile and functional spermatozoa that would positively impact fertilization and increase pregnancy rate.
Recognizing Low Sperm count as the single most common factor of male sub-fertility, this article seeks to educate the readers and provide an understanding that would serve as a guideline in the evaluation of male sub-fertility. Moreover, it is essential to understand the endocrinology of spermatogenesis in order to appreciate its complexity and reach a conclusion. This will certify the proper diagnosis and treatment choice of male sterility based on semen characteristics.
Spermatogenesis (formation of sperm cells), in a nutshell, relies on the integrative functions of both the central nervous system (CNS) and the male reproductive system (brain and testes most importantly). Organs within the brain, such as the hypothalamus, release neurotransmitters called Gonadotropin which is responsible for releasing Hormones (GnRH) in a pulsatile way to enable the release of both Luteinizing and Follicle Stimulating Hormone (LH, FSH) from the anterior pituitary gland where they are produced. Consequently, in response to these secretions, two cell populations within the testes, Leydig and Sertoli cells are bonded to the hormones respectively through specific receptors. Testosterone, the major male secretory hormone of the testes, is produced in a positive response to this hypothalamic-pituitary-testes axis and functions also as a regulator of the secretion of LH in a negative feedback mechanism; simply put it, inhibits the continuous release of LH and its effect on the Leydig cells which ultimately leads to an increased level of FSH. Testosterone is further processed to another potent hormone called estrogen (androgen dihydrotestestorone) or estradiol.
On the other side of the equation, FSH is also under negative feedback control, however, not primarily by testosterone or other steroidal hormones, but rather Sertoli cells in response to FSH secrete, a glycoprotein called Inhibin which then suppresses FSH secretion in the pituitary. Consequently, there is no absolute requirement for Sertoli cell in the production of estrogen, and unlike in the females where estrogen is essential for fertility, it is not in males. Against this backdrop, we now understand the sperm formation has a lot to do with the brain and its workings as well as the response of the testes to these changes and the environment.
What constitutes a Normal Semen sample?
Now that we have literally given you a synopsis of semen endocrinology, if not bored you with all the chemistry, let’s have a look at what a normal semen sample constitutes.
When your fertility specialist requests you to do a semen analysis, he or she wants to assess the nature of your spermatozoa, (the actual living sperm cells), their vitality, motility, morphology as well as the composition of the fluid (semen) which is also important for sperm function. This method is potentially the most primary assessment tool for sterile males.
Most men will not know of their low sperm count condition and this is because the only sign of it is the inability to conceive a child with their female partners. Nevertheless, there may exist other obvious symptoms that could serve as a major concern, thus leading to a visit to a doctor and these may include problems with sexual function, for example: low sex drive (reduced libido) or difficulty maintaining an erection, pain, swelling or a lump in the testes and others may be concerned about decreased facial or body hair which represents a genetic and or hormonal abnormality.
Standard collection procedures are carried out in two ways: either at home during sexual intercourse, using a non-spermicidal condom or by masturbation within the medical facility. However, it is vital to note that the quality of the semen sample varies with how the ejaculation is produced and how it is preserved for evaluation which may influence the final results. According to research, ejaculation produced from masturbation and collected into a pre-weighted container can be of a lower quality than that which is collected at home into a non-spermicidal condom by sexual intercourse. This difference in quality is attributed to the period of time it requires to produce a sample during masturbation than that of the time of sexual arousal.
Several researchers have shown evidence that there are drawbacks to both methods of collection. During sexual intercourse, a good portion of the ejaculation, (the first portion may be lost) and the sperm rich seminal fluid is mixed with vaginal mucus whose pH may adversely influence spermatozoa ability to swim; additionally, the fraction of transport time plus transport temperature before reaching the facility all play adverse roles to the results obtained. The masturbation, population on the other hand is collected into one container where all spermatozoa are trapped into a protein-well and subsequently liquefies and increases osmolality.
Going forward, most labs would prefer a sample collected by masturbation at the clinic for obvious reasons stated, rather than by coitus except wherein the patient demonstrates an inability to produce sample by masturbation. Additionally, the gold standard of normal semen parameters as recommended by WHO, 5th edition Laboratory manual, 2010 should include but not wholly controlled by the following: 1.5 ml volume with a concentration of 15×106 per ml, motility total 40% with progressive motility at 32%, vitality 58% and morphology or normal forms 4%. A pH of 7.2, white blood cells count 1×106 per ml, immunobead test 50% and MAR (mixed antiglobulin reaction) 50% are also recommended. It is important to note that some laboratories may have varying ranges based on equipment calibrations and specific research conformity.
Nevertheless, semen specimen can be produced by masturbation after an abstinence of 2 to 7 days, and be maintained at a temperature of 20-37C to allow liquefaction and analysis within an hour of production. As observed, there are large variations within semen parameters even in healthy, fertile men; therefore it is advisable not to conclude on a single semen analysis but rather review with caution and repeat on 2 or 3 occasions 3 months apart, as new spermatozoa are produced continually and takes about 42 to 76 days to mature. A reasonable conclusion can be drawn from the average of 4 samples within one standard deviation of the mean.
After being diagnosed by your doctor as having low sperm count or oligozoospermia, it is essential to note that your diagnosis could be correlated to problems associated with abnormal shapes of the sperm cell (teratozoospermia), movement or motility (oligoasthenozoopermia), absent sperm cells (azoospermia), bacterial infection represented by increased wbc (leukospermia) or its function. Often the cause may originate from a known medical illness or health issues, nevertheless, 15% of times, the cause is idiopathic.
Causes could categorically range from medical or health issues to environmental and lifestyle ones. These may include chronic illnesses such as metabolic diseases; diabetes, for example, long-standing malignancies and cancer therapy, viral and bacterial infections: orchitis (mumps, gonococcal); structural issues such as blockage of any of the tubes that carry the sperm or undescended testes. It could also stem from inflammation of the testes (varicoceles), and previous vasectomy and other self-induced sterile procedures to name a few. Hormonal imbalances such as increased gonadotrophins (FSH) and persistent Muellerian duct may be diagnosed after careful physical examination and laboratory investigation. Genetic diseases such as Klinefelter’s Syndrome make up a small portion of this population of males since 1 in every 500 males are born with the disorder. Some environmental risk factors are evident in patients who work within industrial settings with overexposure to heavy metals.
Hyperthermia of scrotal skin as a cause of oligospermia represents an essential reversible condition that has long been understated. Few researches have in recent past conducted studies in this regard and have concluded same. One of such researchers, Setchell, along with several other authors believed that increase scrotal skin temperature results in impairment of spermatogenesis and that hyperthermia is a modern life style condition. Such condition being associated with tight fitting, thermally insulating clothing, sedentary work ( prolonged vehicle driving), obesity, use of laptop and computers and exposure to electro-magnetic waves raise scrotal temperature leads to an increased metabolic and oxygen demand that cannot be met by the limited blood flow to the scrotum. This results into hypoxia (low oxygen to the tissue)and generation of reactive oxygen species (ROS), consequently leading to decrease sperm output.
Risk factors linked to low sperm count may be inter-related to the problems that cause it, whether direct or indirect. Some of these factors have been researched and evidence tested, such as obesity, usage of illicit drugs, having past or present infections, being exposed to toxins, trauma to the testes, excessive alcohol consumption, cigarette smoking, undergoing cancer therapy especially radiation and importantly being born with a fertility disorder or having a blood-male relative (father or brother) with a fertility disorder.
Whatever the cause leading to the diagnosis, low sperm count has an associative infertility complication that can be stressful to both you and your partner. These complications may also result to months of empirical treatment, invasive procedures such as surgery or other less invasive treatment such as intrauterine insemination (IUI), invitro fertilization (IVF) or ICSI. Other times, the couple could be counseled properly to use a sperm donor or if not collectively agree to adoption. No matter the decision reached to finally bring the anticipated result, male-factor infertility itself is a stressor that can one way or the other affect your quality of life as well as your social wellbeing. Consequently, it is important that you include your partner within the decision making and ensure that a suitable resolution is reached together with your doctor. Remember that any man can father a child, with the right information, testing and counseling, no matter the mechanism used. Breaking the social norms and barriers could be a way forward for male-factor infertility and an eye-opener to a world of conception opportunities. Biomedical technology has evolved to include many neo-reproductive reforms that have been proven and tested safe.
This article has been peer reviewed by Journal of Reproduction.