Questions faced by gynaecologist while treating infertile couples with semen abnormalities.
The ideal abstinence interval suggested by World Health Organisation (WHO) before semen is given for testing is between 2 to 7 days. There is some impact of ejaculatory abstinence on semen analysis parameters which has been reviewed in various studies. It has been seen that longer abstinence is associated with increase in semen volume and count. However, effect of abstinence or motility, morphology, and DNA fragmentation rate are contradictory and inconclusive. Nevertheless, a trend appears towards improvement in these para metres with shorter abstinence. It is also important to note that the first fraction of an ejaculation is the most effective part for conception as the sperms are more numerous, move more and present better-quality DNA than those which come through the second ejaculate. Even in men suffering from an-ejaculation (it is the pathological inability to ejaculate in men with or without orgasm) first ejaculation obtained by electro ejaculation is much better than the quality of the second electro ejaculation. Therefore, it is obvious that repeated procedures of sperm collection by electro ejaculation are not justified for improving the sperm quality in an-ejaculatory neurologically intact men.
When we see several different reports from good laboratories it may become difficult to decide which report to believe as correct. This becomes more important if one report shows normal semen parameters and the other sub-normal. It is important to note what is written in the column of morphological characteristic of sperms. Generally, more than 4% of normal sperms constitute a morphologically normal semen sample. If we find a technician who has reported 80% of normal forms or even 30% of normal sperms it indicates that the technique of doing the semen analysis is not the standard technique or the technician is not trained adequately to do a semen analysis. Most of the laboratories have technicians who have good experience in blood and urine testing but are very poorly trained regarding semen analysis which is quite different from the above two. Mostly technicians working in fertility centres which offer semen analysis, are more proficient in the assessment of semen samples. A beautifully typed report from a leading laboratory does not qualify the report to be correct.
Normal semen analysis which was redefined by WHO in 2010 shows differences from the standard semen para metres which were followed earlier ever since the reference values were defined by WHO in 1998. The semen volume from 2 ml to 1.5 ML is now considered normal, sperm concentration of 15 million/ml from 20 million/ml and progressive motility now of 32% instead of 50% is now redefined by WHO as normal. Sperm morphology 4% or above is considered normal and is generally not above 14% to 20%.
Whenever an infertile couple comes, and the man carries a semen analysis report which shows mild oligo-astheno-terato-zoospermia (OATs) along with an ultrasound report showing grade 1 varicocele how should we proceed. If the varicocele is only demonstrated by ultrasound on standing and coughing and not palpable clinically then it is grade 1, and a case of subclinical varicocele which is defined as a non-palpable enlargement of the venous plexus of the spermatic cord which can be diagnosed only by imaging techniques. No surgical repair is recommended in such case, as studies have shown that, there is no increase in the sperm parameters nor in the pregnancy rate post operatively. Diagnosis of varicocele which is can easily be made by physical examination of scrotal palpation in upright position or in lying down position is truly clinical varicocele and comes under grade 2 and 3 respectively. These are the cases which may sometimes benefit from surgical varicocelectomy hence needs to be referred either to a urologist or infertility/IVF specialist.
Azoospermia is defined as ‘absence of spermatozoa in the sediment of a centrifuged semen sample of a man’ and crypto-zoospermia is as ‘extremely low spermatozoa concentration (≤1 million/mL) in the ejaculate of a man’ according to WHO. These situations are generally diagnosed during a routine male infertility investigation. Azoospermia is seen approximately in 1% of the male population and may be as high as 20% among male infertility cases.
The first thing to be noted from the semen analysis report is the volume of the semen. If this is found lower than normal one needs to rule out history of spillage of the sample while collection. If there has been no history of spillage, the pathological causes of low semen volume are many, such as retrograde ejaculation, an-ejaculations, and hypogonadism. Even anatomical causes contribute to low semen volume such as ejaculatory duct obstruction or congenital absence of the vas/seminal vesicles which can be ruled out by further investigations, for which the man needs to be referred to a urologist/andrologist. If this was not the case, then a repeat semen analysis is recommended after 7 days requesting the laboratory for centrifugation of the sample. If we find sperms in the sediment this is possibly a case of crypto-zoospermia. All these cases of azoospermia or crypto-zoospermia need further investigations and should be referred to an ART clinic.
Obesity is a possible cause of secondary hypogonadism associated infertility in some men. The mechanism by which this happens is as following. Enzyme aromatase is highly expressed in peripheral fat tissue and converts testosterone to oestradiol, causing increased peripheral oestradiol production. High levels of oestradiol inhibit secretion of LH and FSH from the pituitary by negative feedback mechanism. Reduced levels of LH and FSH in turn lead to a reduction in testosterone synthesis and sperm production leading to infertility. To counteract the physiological effect of elevated oestradiol, use of aromatase inhibitors have seen to normalise serum testosterone by stopping its conversion to oestradiol thus its effect on spermatogenesis. The commonly available aromatase inhibitors available are letrozole which is used in doses of 2.5 mg/day or anastrozole given in the doses of 1 mg/day for a period of 3 to 6 months. Generally, with the use of aromatase inhibitors the serum oestradiol levels fall, and the total testosterone levels increase and so does sperm concentration.
Antioxidants are extensively used in the treatment of subnormal semen para metres in male subfertility. There are many vitamins and micronutrients used as antioxidants in practice. One of the most used antioxidants is vitamin C which is found in abundance in the semen of fertile men. It is known to protect sperm’s DNA from free radical damage by virtue of which it improves sperm quality. It is given in doses of 1000 milligrams per day orally for 3 to 6 months. Vitamin E protects sperm cell membrane from damage therefore improve sperm motility and is used at a dosage of 600 mg per day for 3 to 6 months. Other micronutrients like selenium is used as 200 µg a day, glutathione 400 mg per day, and L-acetyl cysteine 3 g per day to increase sperm concentration and sperm motility. Lot of controversy exists regarding long term use of antioxidants. Recent clinical trials have shown that antioxidants do not appear to improve semen para metres or DNA fragmentation among men with male factor infertility. Therefore, limited and judicious use of these drugs is recommended in male infertility and if no improvement is seen in semen parameters in 3 to 4 months or a pregnancy does not occur within 6 months, one must resort to methods of ART to assist in conception.
To conclude, it is important to remember that there is limited role of medical management in male infertility. What a gynaecologist needs to know is to be able to recognise a sub-normal semen report and to know with certainty when to refer the patient further to an ART clinic or andrologist. However, there are conditions causing subfertility in men which can be managed medically and should be treated before referring the patient to a specialist. Nevertheless, there are a few more conditions like male accessory gland infections (MAGI) and hypo-gonadotropic hypogonadism in men which can be treated success fully by medical management but require either a good local genital examination or hormonal and genetic workup, respectively. These patients need to be referred further without wasting time so that they get the correct treatment and their families can be completed within a stipulated time frame.