Treatment of male infertility

Treatment of male infertility

In the treatment of male infertility, we can distinguish several groups of procedures:
1. Lifestyle change
2. Pharmacological treatment
3. Surgical treatment
4. Assisted reproductive technologies
5. Alternative medicine therapy

Lifestyle

Infertility treatment in men should be started with changing the lifestyle in the first place. Currently, most people, and in particular men, don’t pay attention to proper nutrition. Stationary style of life, lack of regular physical exercise, alcohol consumption and cigarette smoking also contributes to the reduction of a man’s reproductive potential.

The best solution as regards nutrition is to have meals containing large amounts of vegetables, fruit and fish. These products are rich in polyunsaturated fatty acids, antioxidative vitamins and microelements. Studies show that a diet rich in vegetables and fruit improves semen parameters. At the same time, eating frequently meals containing fatty meats and milk may deteriorate the quality of semen (1, 2). Another study confirms the thesis that physical effort has positive impact on our bodies – in the fertility aspect, it improves semen parameters and positively influences hormone profile (3). Meanwhile men who spend too much time at the computer (more than 10 hours daily) increase their risk of abnormal spermiogram results (4). This is why it is so important to make patients aware of the importance of the proper lifestyle.

Pharmacological treatment

Male infertility can be treated pharmacologically only in some part as only in some patients we can apply causal treatment.

Hypogonadotropic hypogonadism

In this case, we encounter damaged or disturbed function of hypothalamic pituitary system. Hypogonadotropic hypogonadism can be caused by a genetic anomaly which leads to disorders of the migration of neurons secreting GnRH in the course of embryogenesis (Kallman’s syndrome); this disorder can be of idiopathic character but it can also be related to a hypothalamic or pituitary tumor or inflammatory process (5).

In the treatment of hypogonadotropic hypogonadism which is not related to a hypothalamic or pituitary tumor, GnRH analogs are administered in a pulsatile manner via special infusion pumps. Spermatogenesis should occur within a year from the initiation of treatment. However, due the simpler route of administration, much more often treatment with exogenous gonadotropins is applied, which in some part of patients simulates spermatogenesis (6). If we deal with hypogonadotropic hypogonadism beginning after puberty, a dose of 5,000 IU HCG twice a week should be effective. In case of the lack of therapeutic effect, we can add to the treatment recombinant FSH at a dose of up to 150 IU 3 times a week. (5).

In hypogonadotropic hypogonadism caused by hyperprolactinemia, we can apply treatment with dopamine agonists (naturally, having confirmed the causes of hyperprolactinemia). The treatment restores the normal levels of prolactin and, in consequence, also of testosterone. With this, libido rises, erection disorders are not observed and semen parameters improve (6).

Hypergonadotropic hypogonadism

Hypergonadotropic hypogonadism is related to primary testicular damage or caused by a systemic disease. Its typical features include increased levels of gonadotropins (in particular FSH), low testosterone level and spermatogenesis disorders. Currently there are no scientific studies which would confirm the efficacy of any pharmacological therapy improving semen parameters (6).

Normogonadotropic hypogonadism

Normogonadotropic hypogonadism is related to regressive changes in Leydig cells, dysregulation of hypothalamic pulse generator and increased SHBG (6). In this case, we can expect improvement in semen parameters after the application of the treatment with aromatase inhibitor. The best response to the above treatment is achieved in cases where we observe decreased testosterone (ng/dL) to estradiol (pg/dL) ratio. Studies confirming the efficacy of aromatase inhibitors were not randomized and placebo-controlled (7, 8).

Idiopathic abnormalities in semen analysis

In the case of low sperm count or motility as well as their morphology, therapies most often use substances commonly known as antiestrogens. In the treatment, clomiphene (25mg) and tamoxifen (20mg) are used (9, 10). However, the number of properly conducted studies which would confirm unquestionably the efficacy of antiestrogen treatment is too low.

Therapy with antioxidants such as vitamins E and C, coenzyme Q10, selenium is also applied. Based on the Cochrane database, it has been proved that treatment with antioxidants in men with reduced fertility increases the number of live births and pregnancy rate in couples subjected to assisted reproduction procedures (11).

Other compounds used to improve sperm motility are L-carnitine and acetyl L-carnitine. L-carnitine (plays main role in metabolic processes occurring in cell mitochondria). The significant role of L-carnitine in normal sperm maturation is suggested by high level of L-carnitine in epididymides and of acetyl L-carnitine in sperm (12).

High sperm DNA fragmentation

In the case of abnormal result of sperm DNA fragmentation test, the use of antioxidants is recommended. Antioxidants protect sperm DNA and, thereby, reduce the percentage of abnormalities (13).

Retrograde ejaculation

In the case of retrograde ejaculation, treatment with imipramine 25 mg twice daily or pseudoephedrine 3 mg twice daily is used. These preparations improve the function of internal urethral sphincter and induce normal ejaculation. However, their efficacy is limited (5).

Leukocytospermia

Leukocytospermia often accompanies infections of reproductive organs. Therefore, it is worth carrying out semen culture if leukocytes in semen are found. If any pathogenic bacteria are found, causal treatment is introduced. However, according to some studies, even when the amount of leukocytes in semen is low (200 thousand – 1 million/mL), semen parameters improve after the introduction of empirical antibiotic treatment. Anti-inflammatory drugs should be given simultaneously (14, 15). However, there are studies which do not confirm the efficacy of such treatment (16).

Erectile dysfunction. Decreased libido

This is a large group of disorders. The accurate medical interview is very important here as the cause of disorders often has psychological background or results from comorbidities and drugs taken by a patient. Given the specifics of this problem, it should be dealt with by an experienced sexologist. Depending on the cause, phosphodiesterase type 5 inhibitors, testosterone or dopamine antagonists are used (6).

Surgical treatment

Varicocele treatment

Most often it is not recommended, but in exceptional cases laparoscopic method is used. Laparoscopic surgery is performed transperitoneally and consists in testicular vein ligation with special clips. This method allows to preserve normal function of arteries and lymphatic ducts. According to some studies, the efficacy of this method in improving semen parameters in patients with clinically definite varicoceles is confirmed in as many as 60-70% of patients. The efficacy of this method should be assessed not earlier than after 3 months from surgery (17, 18).

Treatment of vasal and epididymal obstruction

In patients with the obstruction of the vas deferens or epididymis, which can be congenital or acquired – e.g. in connection with inflammatory condition, trauma or vasectomy carried out for contraceptive purposes, microsurgical techniques can be applied. They aim at obtaining or restoring the patency of vasa deferentia. The procedures are carried out under microscope and require broad experience from the operator. The results of treatment of the post-vasectomy condition presented in the study by Belker indicate high efficacy of the procedure described above (19). Further treatments include the connection of the severed vas deferens to the epididymis (vasoepididymostomy – VEA). The indication for this treatment is the absence or blockage of the lumen of the vas deferens or unsuccessful vasovasostomy (22). Meanwhile, currently available aggregated results indicate low efficacy of such treatment (<1%).

Transurethral resection of the ejaculatory duct

Ejaculatory duct obstruction may be caused by the chronic inflammation of the penis or pressure from prostatic cysts or seminal vesicles. However, the most common cause is birth defect. These disorders can be treated with transurethral resection of the ejaculatory duct (5).

Assisted reproductive technologies

Intrauterine insemination

In many cases of reduced reproductive potential in a man, a useful solution may be using sperm in intrauterine insemination procedure (IUI). IUI is also applied in cases of hypospadias, retrograde ejaculation and impotence.

In men with retrograde ejaculation, sperm is obtained from urine after centrifugation. In order to eliminate the harmful effect of acidic urine environment on sperm, urine is alkalized with sodium bicarbonate.

The efficacy of insemination ranges from 5 to 10% per cycle. The maximum number of attempts at IUI recommended in Great Britain is 6, in U.S. – 12 and in other countries – 3.

Testicular or epididymal biopsy

All methods described above are used in order to obtain sperm for use in in vitro fertilization. We can obtain sperm with TESA (testicular sperm aspiration), TESE (testicular sperm extraction), MESA (microsurgical epididymal sperm aspiration), percutaneous epididymal sperm aspiration, open testicular biopsy. After the application of ICSI, normal pregnancies have been achieved also in other cases of sperm retrieval in patients with testicular failure, azoospermia after chemotherapy and Klinefelter’s syndrome.

Good prediction of the presence of sperm in testicles is provided by the assessment of FSH and inhibin B levels. Low levels of inhibin B and high levels of FSH correlate with the lower chance of sperm retrieval in biopsy (21, 6).

Electrostimulation of ejaculation and penile vibratory stimulation

A large group of men with spinal cord injuries and some neurological diseases is infertile in connection with erectile disorders, ejaculation disorders and abnormal semen parameters. In patients with lack of ejaculation, in order to obtain sperm, apart from testicular/epididymal biopsy electrostimulation of ejaculation and penile vibratory stimulation can be applied. In this way, it is possible to obtain sperm which, depending on their number, can be used in intrauterine insemination (IUI) or in vitro fertilization procedures. The effectiveness of IVF/ICSI with the use of sperm acquired by means of both of the sperm acquisition methods described above is comparable (23).

IVF z IMSI-MSOME / ICSI +FAMSI

In patients with abnormal results of MSOME (Motile sperm organelle morphology examination) and normal sperm DNA fragmentation, treatment with IVF with IMSI-MSOME (IMSI-Intracytoplasmatic Morphology Selected Sperm Injection) can be proposed – sperm injection to an egg cell with precisely assessed morphology at a magnification of at least 600x (sperm head structure evaluation with regard to the number and quality of organelles). In patients with additional abnormal sperm DNA fragmentation, it is suggested to carry out sperm sorting and ICSI +FAMSI (functional fine, acrosome activated, morphologically selected sperm injection). In the case of FAMSI, sperm is selected both with regard to its normal morphology, shape and optimal vital functions. This technique differs from MSOME because it takes into account additional criteria during the assessment of a sperm cell introduced to the egg cell. At the same time, it allows to reduce the risk of selecting a spermatozoon with aneuploidies.

Alternative medicine therapy

Acupuncture, moxibustion, herbalism

There are studies discussing the use of acupuncture and moxibustion (technique which involves skin cauterization with a wormwood cigar). According to the most of them, significant improvement in semen parameters is achieved, especially when the therapy is applied for the whole cycle of spermatogenesis (25). Also the use of the traditional Chinese herbalism improves semen parameters by influencing endocrine system (24, 25, 26).

Conclusion

It must be kept in mind that, to a large extent, we are able to prevent the reduction of fertility in men. We should make children pay attention to healthy style of life from their earliest years. As of today, pharmacological treatment in some cases is hardly effective. For this reason, assisted reproductive technologies provide invaluable advantages.

Authors of the article: Mariusz Łukaszuk, MD; Professor Krzysztof Łukaszuk, PhD, MD, Chief of INVICTA Fertility Clinics.

• Download: Treatment of male infertility

Bibliography:
1. Mendiola J, Torres-Cantero AM, Moreno-Grau JM, Ten J, Roca M, Moreno-Grau S, Bernabeu R. Food intake and its relationship with semen
quality: a case-control study. Fertil Steril. 2009 Mar;91(3):812-8. Epub 2008 Mar 7.
2. Zampieri N, Zamboni C, Ottolenghi A, Camoglio FS. The role of lifestyle changing to improve the semen quality in patients with varicocele..
Minerva Urol Nefrol. 2008 Dec;60(4):199-204.
3. Vaamonde D, Da Silva-Grigoletto ME, García-Manso JM, Barrera N, Vaamonde-Lemos R. Physically active men show better semen parameters
and hormone values than sedentary men.Zhonghua Nan Ke Xue. Eur J Appl Physiol.
4.Semen analysis of sterile patients among occupational computermen. 2012 Jan 11 2008 Oct;14(10):914-6.He J, Liu HC, Yu WZ, Zou HY.Source
Institute of Clinical Medicine, PLA Technological Center for Healthy Birth & Child Care, Urumqi General Hospital of Lanzhou Military Region,
Urumqi, Xinjiang 830000, China. hejiang8770@163.com
5.Sperfoff L. Kliniczna endokrynologia ginekologiczna i niepłodność. Medipage 2007; 1346-1355
6. Zgliczyński W. Endokrynologia. Medical Tribune Polska. 2011; 647-649
7. Ramasamy R, Stahl PJ, Schlegel PN.Medical therapy for spermatogenic failure. Asian J Androl. 2012 Jan;14(1):57-60. doi: 10.1038/aja.2011.63.
Epub 2011 Dec 19.
8. Cakan M, Aldemir M, Topcuoglu M, Altuğ U. Role of testosterone/estradiol ratio in predicting the efficacy of tamoxifen citrate treatment in
idiopathic oligoasthenoteratozoospermic men. Urol Int. 2009;83(4):446-51. Epub 2009 Dec 8.
9. Vandekerckhove P, Lilford R, Vail A, Hughes E. Clomiphene or tamoxifen for idiopathic oligo/asthenospermia. Cochrane Database Syst Rev
2000; (2): CD000151.
10. Sterzik K, Rosenbusch B, Grab D, Heyden M, Lichtenberger K, Wolf A.The treatment of oligozoospermia with tamoxifen does not improve
sperm quality. Zentralbl Gynakol. 1991;113(12):683-8.
11. Showell MG, Brown J, Yazdani A, Stankiewicz MT, Hart RJ. Antioxidants for male subfertility. Cochrane Database Syst Rev. 2011 Jan
19;(1):CD007411.
12. Balercia G, Regoli F, Armeni T, Koverech A, Mantero F, Boscaro M. Placebo-controlled double-blind randomized trial on the use of L-carnitine,
L-acetylcarnitine, or combined L-carnitine and L-acetylcarnitine in men with idiopathic asthenozoospermia. Fertil Steril. 2005 Sep;84(3):662-71.
13. Armand Zini, 1,2 Maria San Gabriel,1 and Abdulaziz Baazeem1. Antioxidants and sperm DNA damage: a clinical perspective. J Assist Reprod
Genet. 2009 August; 26(8): 427–432.
14. Hamada A, Agarwal A, Sharma R, French DB, Ragheb A, Sabanegh ES Jr.Empirical treatment of low-level leukocytospermia with doxycycline
in male infertility patients. Urology. 2011 Dec;78(6):1320-5.
15. Branigan EF, Spadoni LR, Muller CH.J Reprod Med. Identification and treatment of leukocytospermia in couples with unexplained
infertility.1995 Sep;40(9):625-9.
16. Tomlinson MJ, Barratt CL, Cooke ID. Fertil Steril. Prospective study of leukocytes and leukocyte subpopulations in semen suggests they are not
a cause of male infertility.1993 Dec;60(6):1069-75.
17. Al Bakri A; Lo K; Grober E; Cassidy D; Cardoso JP; Jarvi K. Time for improvement in semen parameters after varicocelectomy.J Urol. 2012;
187(1):227-31
18. Abdel-Meguid TA, Al-Sayyad A, Tayib A, Farsi HM. Does Varicocele Repair Improve Male Infertility? An Evidence-Based Perspective From a
Randomized, Controlled Trial. Eur Urol. Dec 21 2010;
19. Belker AM, Thomas AJ Jr, Fuchs EF, Konnak JW, Sharlip ID Department of Surgery, University of Louisville School of Medicine, Kentucky.The
Journal of Urology [1991, 145(3):505-11]
20. Jezek D, Knuth UA, Schulze W. Successful testicular sperm extraction (TESE) in spite of high serum follicle stimulating hormone and
azoospermia: correlation between testicular morphology, TESE results, semen analysis and serum hormone values in 103 infertile men. Hum
Reprod. 1998 May;13(5):1230-4.
21. von Eckardstein S, Simoni M, Bergmann M, Weinbauer GF, Gassner P, Schepers AG, Nieschlag E. Serum inhibin B in combination with serum
follicle-stimulating hormone (FSH) is a more sensitive marker than serum FSH alone for impaired spermatogenesis in men, but cannot predict the
presence of sperm in testicular tissue samples. J Clin Endocrinol Metab.1999 Jul;84(7):2496-501.
22.Semczuk M. Andrologia PZWL 416-417.
23. Kathiresan AS, Ibrahim E, Aballa TC, Attia GR, Ory SJ, Hoffman DI, Maxson WS, Barrionuevo MJ, Lynne CM, Brackett NL. Comparison of in
vitro fertilization/intracytoplasmic sperm injection outcomes in male factor infertility patients with and without spinal cord injuries. Fertil Steril. 2011
Sep;96(3):562-6.
24. Tempest HG, Homa ST, Routledge EJ, Garner A, Zhai XP, Griffin DK Syst Biol Reprod Med. 2008 Jul-Aug;54(4-5):185-95. Plants used in
Chinese medicine for the treatment of male infertility possess antioxidant and anti-oestrogenic activity.
25. Crimmel AS, Conner CS, Monga M. Withered Yang: a review of traditional Chinese medical treatment of male infertility and erectile dysfunction.
J Androl. 2001 Mar-Apr;22(2):173-82.
26. . Zheng RL, Zhang H. Effects of ferulic acid on fertile and asthenozoospermic infertile human sperm motility, viability, lipid peroxidation, and
cyclic nucleotides.Free Radic Biol Med. 1997;22(4):581-6.