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SIDDHARTHA CHATTERJEE*, R G CHOWDHURY**, B KHAN***
Management of male infertility is always difficult task. In recent years booming of artificial reproductive technologies (ART) has put infertologists in front of a mil ion dol ar question whether to treat the person or the gametes. A basis andrology laboratory at present has become part and parcel of an infertility clinic. Hence treatment of male infertility has become institutional and col ective for clinicians and basic scientists. The basic approach towards management of male infertility includes confirmation of diagnosis and to find out the cause for which pathological, endocrinological and biochemical tests are essential. In this series specific defects causing seminopathy has been found 18% cases where treatments is straightforward and towards the cause. The main bulk of idiopathic seminal defects (82%) real y poses chal enge to the infertologists so far management is concerned. In this study commonest seminal defect has been found to be oligoasthenozoospermia which amounts 63% cases. For medical management purpose drugs commonly used are clomiphene, gonadotrophins, bromocriptine, L-thyroxine , vitamin E, B12, etc. When they fail the main approach remains to be intra-uterine insemination (IUI) and ART eg, in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI). Keywords: Male infertility, artificial reproductive technologies, medical management.
Rising incidence of male infertility has become a burning problem to infertility practitioners. For successful management sound knowledge in genito-urinary physiology, medicine as well as endocrinology is essential. In recent year dramatic advancement in ART brought new hope regarding fatherhood to couples, suffering from severe male factor problem. This has changed the whole scenario. The importance of basic science and laboratory techniques are being valued more and more. The common practice of offering empirical treatment with hormonal and non-hormonal drugs is abating day by day. The main problem which the clinician treating for male infertility is facing today is whether to bank on conventional treatment or manipulation of semen in the laboratory followed by ART. However, the expenditure needed for this type of sophisticate treatment is out of reach to many patients, especially in developing countries like ours. The conventional treatment of which the major component is medical management is by far the cheapest and least troublesome for the couple concerned. Moreover improvement of male factor by medical treatment causes tremendous psychological well- being in both the partners. Medical management of male infertility includes hormonal and non- hormonal drugs. In the present study, it has been tried to evaluate the role of medical treatment in the Between January’01 and October’03, 970 couples attended the clinic. Seminal pathology could be found in 323 (33%) of them. They were treated with drugs, which are grouped as: (i) Simulative-Gonadot- rophin (hMG/hCG), clomiphene, androgens. (ii) Suppressive –Bromocriptine, androgens. (iii) Replacement –hMG/hCG, L-thyroxine, androgens. (iv) Emperical –Above drugs, vitamins, proteins, All these cases were re-evaluated with an aim to confirm diagnosis, which involved repeat semen analysis after every 4 weeks, over a period of 6 months with 3days abstinence, keeping a close watch on quality of collection container used to avoid contamination by toxic materials. After seminopathy was confirmed the aetiology was investigated. Sperm survival, sperm function tests, hormone estimations, biochemical evaluation starting from sugar to basic tests of renal function were performed. In only 10-15% cases cause of seminopathy could be detected. The major bulk of 85-90% Depending on above findings treatment protocol was selected for particular patient. For patients with specific defects Selection of treatment is not difficult. For hypogonadotrophic hypogonadism (low FSH and LH), replacement therapy with MG/hCG is the treatment of choice, bromocriptine and L-thyroxine for hyperprolactinaemia and indicated. For maturation arrest in spermatogenesis, gonadotrophin and androgens are also drugs of choice. For inflammatory and infective condition antibiotics and anti-inflammatory drugs are of immense value. For idiopathic group of infertile patients the clinical presentations where oligozoospermia, asthenozoospermia, oligoasthenzoospermia, pyospermia and combination of them. For oligozoospermia the degree was to be found out. In severe group (less than 10 million/ml), partial obstruction needed to be ruled out as low count with normal motility is mostly due to this. Sometimes for moderate (10-15 million/ml and) (15-19 million/ ml) oligozoospermia support with vitamins and nutrients are of help. In all cases clomiphene was considered. Gonadotrophin alone or in combination was also useful. Asthenozoospermia presented real challenge to us. Severe asthenozoospermia sometimes improved with androgens and or hCG. For mild and moderate group vitamin E, androgens were helpful. In this series treatment was selected according to above criteria. For oligoasthenzoospermia combination of clomiphene with hCG, androgens with hCG, vitamins or clomiphene alone were considered. Idiopathic pyospermia may not respond to usual treatment. For all above conditions IUI or ART was also considered. For mild to moderate group of oligoasthenozoospermia semen wash, sperm preparation in suitable medium (Ham F-10, Earle’s) and incubation in 5% CO2 atmosphere followed by IUI was advocated. Sample obtained after layering and swim up was used for IUI. Azoospermia needs separate mention. All cases of azoospermia do not mean complete absence of spermatogenesis. Obstructive group may respond to surgery. Sometimes epididymal sperm aspiration may be helpful. In testicular atrophy or failure, donor insemination becomes the method of choice. In recent years even in later cases THESE and ICSI produce some success. It was stated previously that incidence of male infertility in this series was 33% amongst all infertile couples. The number of cases having detectable factor ie, with known aetiology, were 58 (18%). Idiopathic group was the largest being 82% (Table 1). The commonest type found in this series was oligoasthenozoospermia followed by oligozoospermia, asthenzoospermia and others (Table 1). according to Detectable/Idiopathic Factors Detectable/idiopathic factors No. of cases (%) Improvement in semen parameters after clomiphene treatment was found in 26 cases (45%) out of 58 but pregnancy could be achieved in only 12% case. This cannot be attributed only to clomiphene but in some cases female factors were also responsible. Gonadotrophin on the other hand showed improvement rate 14 cases (46%) out of 31 with very poor pregnancy rate of 7%. Androgens showed improvement in 27 cases (34%) with very poor pregnancy outcome of 1%. Vitamins ie, vitamin E and B12 yielded better results where improvement was in more than 110cases (52%) and pregnancy achieved in 18% cases. From the above4 results vitamins were found to be fairly useful. It is clear that oligoasthenozoospermia is the commonest aberration in the males. For mild to moderate groups of oligoasthenozoospermia IUI with processed sperm suspension gave encouraging results. Motility of spermatozoa were fortified by washing and incubation in suitable medium. Concentration by centrifugation technique relatively increased live sperm count/ml. Layering followed by swim up helped to avoid contamination of sperm cells. In severe oligozoospermia IVF and oligasthenozoospermia ICSI are the ways out. Isolated asthenozoospermia is rare disorder. Selection of treatment protocol for idiopathic groups needs much expertise. Drugs are ineffective for idiopathic oligozoospermia’. Vitamins could improve oligosthenozoospermia in about 52% cases but pregnancy rate (18%) was not highly However, vitamin has come out to be little more useful than other age4nts in the treatment of male infertility. This is in contrary to the existing belief. What we have observed is vitamin E alone or in combination with vitamin B12 worked under in improvement of sperm motility2. So asthenozoospermic patients do better with vitamins. This happens because of improved membrane stability due to removal of oxygen free radicals or peroxidation of phospholipids by vitamin E. These are the products from leucocytes particularly macrophages3. On the other hand vitamin B12 acts as coenzyme in many biochemical reactions in the synthesis of spermatozoa and also its precursor and stem cells. This helps in improving sperm motility really count too. In certain cases which are not hormone dependent anti- oestrogens as stimulating agent may be successful4. The main problem of clomiphene is standradisation of dose. It acts by stimulation of FSH secretion which is not dose dependent to clomiphene in the males. The anti-oestrogenic action of high dose clomiphene may precipitate prostatic dysfunction as well as spermatid dysfunction on its prolonged use. In the females the response t clomiphene treatment can be judged by folliculometry and oestradiol estimation very shortly after the medicine. But in the males monitoring of treatment takes prolonged period of 72-90 days when repeat semen analysis determines the efficacy. In fact is many solutions sperm count may increase with clomiphene but not fertility. In some studies5.6 that did include control, the investigations have concluded that clomiphenc could be considered as an effective agent. The use of gonadrotrophin in regular basis is extremely costly, though theoretically this is the ideal treatment of hypogonadotrophic hypogonadism. It is recognized now-a- days that 25% cases of idiopathic oligoasthenozoospermia is due to inadequate gonadotrophin activity (IGA) when FSH and LH and LH levels are normal in circulation. This is one of the main indications of gonadotrophin use. But the problem is the difficulty in confirmation of IGA and it requires very high dose Androgens particularly in low close continuous treatment are helpful in many occasions. Treatment with high close testosterone which leads to complete suppression of spermatogenesis and thereafter rebound stimulation of sperm production following stoppage is also advocated but with little improvement of fertility. Reproducibility of the rebound phenomenon is also reported. The difficulties are the selection of treatment modality androgens for particular patients as there is no clear criterion In mild to moderate seminopathy IUI which close not come under medical treatment strictly gives better results than others. In cases with severe seminopathy several semen samples can be collected and stored in liquid nitrogen (frozen sperm) and thereby sperm pool can be made. On the day of insemination the pooled frozen semen can be thawed and be used as a whole for IUI. In conclusion this is important t realize that a lot remains to be understood about the male factors of infertility. Better understanding of the pathophysiology of male factor may indicate the research in the field of male infertility and its pharmacology. If investigations to find out the causative factor can be made properly and carefully medical management can be of help to a section of patients suffering from 1. Templeton A- Infertility – epidemiology, aetiology and effective management. Health Bull 2. Engle S, Der Einflug van a Tokopherolazetal auf die spermienmotilitat. Dermatologische 3. Kurzawa R- Modualtion of peritoneal macrophage function: effect of selected drugs on their activity and sperm phagocytosis. Ann Acad Med Stetin 1997; 43: 79-97 4. Haidl G, Schill WB – Guidelines of drug treatment of male infertility. Drugs 1991; 4: 60-8. 5. Micic S, Dotlic R- Evaluation of sperm parameters in clinical trial with clomiphene citrate of oligospermic men. J urol 1985; 133: 221-2. 6. Wang C, Chan CW Wong KK, Yeung KK- comparison of the effectiveness of placebo, clomiphene citrate, mesterolone, pentoxifylline and testosterone rebound therapy for the treatment of idiopathic oligospermia. Fertil Steril 1983; 40: 385-65. 7. Winters SJ Troen P – Gonadoatrophin therapy in male infertility. IN Bain J, Schill WB Schwarzstein L, editors. Treatment of Meal Infertility. Berlin: Springer, 1982: 85-97.

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