|Year : 2023 | Volume
| Issue : 1 | Page : 7-11
The Urological Society of India guidelines for the management of male infertility (Executive Summary)
Shivam Priyadarshi1, Raman Tanwar2, Vineet Malhotra3, KV Vinod4, Pramod Krishnappa5, Imdad Ali6, Amit Agrawal7, Vivek Sharma8
1 Department of Urology, SMS Medical College, Jaipur, Rajasthan, India
2 Jyoti Hospital and Urology Center, Gurugram, Haryana, India
3 Diyos Men's Health Center, New Delhi, India
4 Centre for Urological Research and Evaluation (CURE) & SK Hospital, Thiravantupuram, Kerala, India
5 Department of Urology, NU Hospitals and NU Fertility, Bengaluru, Karnataka, India
6 Department of Urology, Vijaynagar Institute of Medical Sciences, Ballari, Karnataka, India
7 Department of Urology, Command Hospital (Western Command), Panchkula, Haryana, India
8 Department of Urology, Government Medical College, Rewa, Madhya Pradesh, India
|Date of Submission||12-Jul-2022|
|Date of Decision||08-Oct-2022|
|Date of Acceptance||10-Dec-2022|
|Date of Web Publication||29-Dec-2022|
Department of Urology, SMS Medical College, Jaipur, Rajasthan
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Priyadarshi S, Tanwar R, Malhotra V, Vinod K V, Krishnappa P, Ali I, Agrawal A, Sharma V. The Urological Society of India guidelines for the management of male infertility (Executive Summary). Indian J Urol 2023;39:7-11
|How to cite this URL:|
Priyadarshi S, Tanwar R, Malhotra V, Vinod K V, Krishnappa P, Ali I, Agrawal A, Sharma V. The Urological Society of India guidelines for the management of male infertility (Executive Summary). Indian J Urol [serial online] 2023 [cited 2023 Apr 2];39:7-11. Available from: https://www.indianjurol.com/text.asp?2023/39/1/7/365890
These guidelines have been drafted by the Urological Society of India Male Infertility guidelines panel and address management of male infertility. The guidelines are intended for urologists and the recommendations are updated till January 2021. These will remain valid until the next update or for a maximum period of 5 years. The guidelines should not be regarded as a rigid clinical pathway for every patient and are not intended to replace clinical judgment. These guidelines should not be viewed as legal standards of care. This executive summary includes some salient aspects of the guidelines and the guideline statements. The complete guidelines document can be accessed from the Urological Society of India website at www.usi.org.in.
| Methodology|| |
A nonsystematic review of the literature available on the subject on PubMed and Google Scholar was performed. A total of 135,775 abstracts obtained from 1990 till present date using keywords “male infertility,” “Semen,” “Azoospemia,” “Oligospermia,” “Sperm retrieval,” “Hypogonadism,” “microlithiasis,” and “testicular cancer” were analyzed, and after removal of nonrelevant results and duplicates, a total of 833 articles were analyzed. Results of these studies and meta-analyses were combined in a simple narrative fashion. Articles published from India and pertaining to the Asian subpopulation were given a special attention. The recommendations are graded (GR) as strong where an action should or should not be undertaken because net benefit or net harm is substantial; moderate/optional where an action may or may not be undertaken because net benefit or net harm is equivocal; and weak or conditional/selective when net benefit or net harm of taking an action is justified only in selective circumstances. Clinical principle (CP) is a statement that is widely agreed upon by clinicians, for which there may or may not be evidence in the medical literature. Expert opinion is a statement agreed upon by the guidelines panel in the absence of evidence. Level of evidence (LE) was evaluated by the Centre for Evidence-Based Medicine method.
| Definition|| |
“Infertility is the inability of a sexually active, non-contracepting couple to achieve spontaneous pregnancy in 1 year.”
| Epidemiology|| |
Infertility is the problem affecting 15% of married couples globally. The male factor contributes for about 20%–40%., As per the WHO, approximately 60–80 million couples suffer from infertility,,, and the prevalence varies from region to region. It is higher in countries with high fertility rate, which is termed as “barrenness amid plenty!.”,
As per a WHO multicentric study, 27% had etiological factors identified in both the male and the female, 20% only in male, 30% only in female and about 15% could not be clearly attributed to either. As per an Indian report, 50% of infertility results from reproductive diseases in men and 25% of infertility cases have no clearly defined etiology and are termed as unexplained infertility., Infertility varies widely among different Indian states. Its reported incidence is 3.7% in Uttar Pradesh, Himachal Pradesh, and Maharashtra, 5% in Andhra Pradesh, and 15% in Kashmir., In another multicentric study by the WHO, 45% of subfertile men had oligozoospermia or azoospermia.
| Guideline Statements|| |
Epidemiology and etiology
- To categorize infertility, both the partners should be investigated simultaneously (moderate recommendation)
- There are no reliable figures for the global prevalence of infertility. It is estimated to be 8%–12%, of which only the male partner accounts for 20%, females 38%, mixed 27% and unknown 15%. In India, it varies from 3.9% to 16.8% with wide variations not only in different states but also different castes and tribes of the same region
- The primary cause of infertility could be defined only in 40%. They are grouped as nonobstructive, obstructive, and coital. Reasons in 75% of cases of oligospermia remained unknown.
Evaluation and semen analysis
- Relevant reproductive clinical history and focused clinical examination should be done (strong recommendation)
- Perform semen analysis as per the WHO Laboratory Manual for the Examination and Processing of Human Semen (6th edn) reference criteria (strong recommendation)
- Offer blood endocrine profile only if semen analysis is abnormal on at least two occasions (strong recommendation)
- Offer ultrasound scrotum for patients who are obese, with previous scrotal surgery or have tight small scrotum (moderate recommendation)
- Transrectal ultrasound is offered only when ejaculatory duct obstruction (EDO) is suspected (Strong recommendation).
- For patients with nonpalpable vas, congenital bilateral absent vas deferens (CBAVD) must be suspected and CFTR mutation tested (strong recommendation)
- Diagnostic testicular biopsy should be done preferably in a center where there is a facility of sperm retrieval and cryopreservation (moderate recommendation)
- Vasography should not be used as a diagnostic procedure alone and only to be used intraoperatively before reconstructive surgery (strong recommendation)
- In men with female partners of good ovarian reserve, microsurgical vasovasostomy or epididymovasostomy for azoospermia due to obstruction in epididymis and vas, respectively, can be performed (strong recommendation)
- When the ovarian reserve of the partner is limited, sperm retrieval techniques such as MESA, TESE, PESA, TESA must be used in adjunct to reconstructive surgery (strong recommendation)
- For patients with irreparable reproductive tract, sperm retrieval techniques are preferred for ICSI/IVF (strong recommendation)
- Men with EDO and dilated ejaculatory ducts may benefit from transurethral resection of the ejaculatory ducts (TURED) (strong recommendation)
- Men with suspected EDO but normal transrectal ultrasound findings are likely to have a fibrous type of ejaculatory duct obstruction (postinfective). They are not candidates for TURED and will need PESA-ICSI (strong recommendation).
- Nonobstructive azoospermia (NOA) patients should undergo a comprehensive assessment including detailed medical history, hormonal profile, and genetic tests for assessing the etiology (strong recommendation)
- In men with AZFa and AZFb microdeletions, surgical sperm retrieval is contraindicated (strong recommendation)
- Microdissection TESE (mTESE) is the most efficient method for surgical sperm retrieval in NOA (strong recommendation)
- Male hypogonadotropic hypogonadism (HH) is the failure of the testes to produce androgens and sperms secondary to congenital or acquired diseases affecting the hypothalamus and/or the pituitary gland
- Diagnosis is confirmed by low serum FSH, LH, and testosterone levels. Imaging (MRI/CT) of the brain should be done (strong recommendation)
- Clinical features depend on the age of presentation
- Treatment requires androgen replacement therapy till/when fertility is not desired. For fertility, gonadotropins are started to stimulate spermatogenesis (strong recommendation)
- Testosterone replacement therapy must not be done for management of infertility (strong recommendation)
- HH is one of the rare conditions in which specific medical treatment can reverse infertility (strong recommendation).
Infections in infertility
- Infections have been associated with male infertility but direct causation has not been proven
- Antibiotics and anti-inflammatory agents (NSAIDs) for up to 3–6 weeks may have a role in the management of MAGI, especially in cases of complex of Prostatitis, prostatovesiculitis, and prostato-vesiculo-epididymitis (weak recommendation)
- Antioxidant therapy in the presence of epididymitis to restore ROS balance after resolving infections and inflammation may be used (weak recommendation).
Genetics in male infertility
- Elevated LH and FSH in men with azoospermia should prompt genetic testing (moderate recommendation)
- Sperm concentrations <10 million/mL (especially <5 million/ml) due to idiopathic spermatogenic defects should be referred for genetic counseling, karyotyping, and Y chromosome microdeletion (strong recommendation)
- NOA will often require microdissection TESE for best chance of sperm retrieval (moderate recommendation)
- In men with Klinefelter syndrome, the chances of sperm retrieval at microdissection TESE are around 22%–50% (moderate recommendation)
- The chances of transmission of Klinefelter syndrome to offspring are low
- Young men with AZFc deletions require genetic counseling regarding transmission to offspring. They have better chances of sperm retrieval (up to 55%) on microdissection TESE (moderate recommendation)
- Low-volume ejaculate, acidic pH and absent fructose suggests obstructive azoospermia, most commonly due to CBAVDs or EDO (Strong recommendation)
- CBAVD contributes to up to 30% of men with obstructive azoospermia
- CBAVD is a clinical diagnosis, made by absence of bilateral vasa on palpation (strong recommendation)
- The most common genetic evaluation for CBAVD is CFTR gene mutation evaluation (strong recommendation)
- Comprehensive testing in the couple is necessary to avoid CF child (strong recommendation)
- Sperm retrieval is successful in up to 97% of men with CBAVD by testicular sperm aspiration or epididymal aspiration (weak recommendation).
- Only clinically palpable varicocele requires treatment (strong recommendation)
- Microsurgical varicocelectomy is the preferred modality of treatment (strong recommendation).
- Unconsummated marriage may be due to erectile dysfunction (ED) or female factors such as vaginismus or dyspareunia and lack of understanding of reproductive anatomy (CP)
- Perform office sildenafil test to assess erectile function (weak recommendation)
- Consider office intracavernosal injection of vasoactive drug (ICIVAD) as the next step to identify vasculogenic ED, if unresponsive to oral PDE5i (moderate recommendation)
- In men with vasculogenic ED requiring ICIVAD or not responding to any nonsurgical options, shared decision-making should be done along with the patient for the role of penile prosthesis implantation as a treatment option (strong recommendation).
- Microlithiasis is associated with abnormal semen parameters but direct causation cannot be proven
- Testicular self-examination must be taught and encouraged in patients with microlithiasis (moderate recommendation)
Cancer and infertility
- Cryopreservation is mandatory and counseling should be done for all cases regarding fertility options (strong recommendation)
- Orchiectomy should not be delayed in the process of fertility preservation (moderate recommendation)
- Risk of hypogonadism should also be explained and baseline hormones should be established (moderate recommendation)
- Onco-TESE is an option in rare cases with azoospermia and bilateral testicular tumors (moderate recommendation).
- Testicular biopsy should be done during orchiopexy to rule out malignancy (moderate recommendation)
- Sperm retrieval with TESE may be done in cryptorchidism with azoospermia (moderate recommendation)
- Unilateral cryptorchidism shows paternity similar to that of normal individuals
- Orchiopexy done after 6–12 months has resulted in significant reduction of spermatogenesis, compared to those done before 6–12 months (moderate recommendation).
- Before labeling an infertile male as unexplained or idiopathic infertility, all other causes should be excluded (strong recommendation)
- Idiopathic and unexplained infertility do not have definitive treatment (moderate recommendation)
- Empirical medical treatment (EMT) consists of two broad categories, hormonal and antioxidants, which can be offered to these patients (moderate recommendation)
- EMT should be offered initially for at least 4–6 months (two spermatogenic cycles) before going for assisted reproductive techniques (weak recommendation)
- Patients with an abnormal T/E2 ratio may benefit from a cotreatment with aromatase inhibitors (moderate recommendation)
- 30%–80% of infertile men have elevated seminal ROS levels, a potentially treatable condition (weak recommendation)
- Oxidation–reduction potential is a better representative for oxidative stress (OS) as it provides an overall measure of the activity of both oxidants and reductants (weak recommendation).
Financial support and sponsorship: Nil.
Conflicts of interest: There are no conflicts of interest.
| References|| |
Sharlip ID, Jarow JP, Belker AM, Lipshultz LI, Sigman M, Thomas AJ, et al
. Best practice policies for male infertility. Fertil Steril 2002;77:873-82.
George SS, Fernandes HA, Irwin C, Chandy A, George K. Factors predicting the outcome of intracytoplasmic sperm injection for infertility. Natl Med J India 2003;16:13-5.
Sigman M, Lipshultz LI, Howards SS. Evaluation of the Subfertile Male. In: Lipshultz LI, Howards SS, editors. Infertility in the Male. St. Louis, Missouri: Mosby-Year Book; 1997. p. 173.
Mascarenhas MN, Cheung H, Mathers CD, Stevens GA. Measuring infertility in populations: Constructing a standard definition for use with demographic and reproductive health surveys. Popul Health Metr 2012;10:17.
Boivin J, Bunting L, Collins JA, Nygren KG. International estimates of infertility prevalence and treatment-seeking: Potential need and demand for infertility medical care. Hum Reprod 2007;22:1506-12.
Rutstein, Shea O. and Iqbal H. Shah. 2004. Infecundity, Infertility, and Childlessness in Developing Countries. DHS Comparative Reports No. 9. Calverton, Maryland, USA: ORC Macro and the World Health Organization.
Sciarra J. Infertility: An international health problem. Int J Gynaecol Obstet 1994;46:155-63.
Population Council. Infertility. In: Looking Back, Looking Forward: A Profile of Sexual and Reproductive Health in India. New Delhi: Population Council; 2004. p. 67-72.
van Balen F, Gerrits T. Quality of infertility care in poor-resource areas and the introduction of new reproductive technologies. Hum Reprod 2001;16:215-9.
World Health Organization. Towards more objectivity in diagnosis and management of male infertility. Int J Androl 1987;7:1-53.
Zargar AH, Wani AI, Masoodi SR, Laway BA, Salahuddin M. Epidemiologic and etiologic aspects of primary infertility in the Kashmir region of India. Fertil Steril 1997;68:637-43.
Kumar TC. Fertility and in-vitro
fertilization in India. Curr Sci 2004;86:254-6.
Dabaja AA, Schlegel PN. Medical treatment of male infertility. Transl Androl Urol 2014;3:9-16.
World Health Organization. Infecundity, Infertility, and Childlessness in Developing Countries. DHS Comparative Reports No 9. Calverton, Maryland, USA: ORC Macro and the World Health Organization; 2004.
Punab M, Poolamets O, Paju P, Vihljajev V, Pomm K, Ladva R, et al.
Causes of male infertility: A 9-year prospective monocentre study on 1737 patients with reduced total sperm counts. Hum Reprod 2017;32:18-31.
Katole A, Saoji AV. Prevalence of Primary Infertility and its Associated Risk Factors in Urban Population of Central India: A Community-Based Cross-Sectional Study. Indian J Community Med. 2019 Oct-Dec; 44 (4):337-341. doi: 10.4103/ijcm.IJCM_7_19. PMID: 31802796; PMCID: PMC6881900.
Irvine DS. Epidemiology and aetiology of male infertility. Hum Reprod 1998;13 Suppl 1:33-44.
Raheem AA, Ralph D. Male infertility: Causes and investigations. Trends Urol Men's Health 2011; 2 (5):8-11.
Gautam G, Kumar R, Gupta NP. Factors predicting the patency of two-stitch invagination vasoepididymal anastomosis for idiopathic obstruction. Indian J Urol 2005;21:112-5. [Full text]
Surya BV, Washecka R, Glasser J, Johanson KE. Cysts of the seminal vesicles: Diagnosis and management. Br J Urol 1988;62:491-3.
Clementini E, Palka C, Iezzi I, Stuppia L, Guanciali-Franchi P, Tiboni GM. Prevalence of chromosomal abnormalities in 2078 infertile couples referred for assisted reproductive techniques. Hum Reprod 2005;20:437-42.
Arshad MA, Majzoub A, Esteves SC. Predictors of surgical sperm retrieval in non-obstructive azoospermia: Summary of current literature. Int Urol Nephrol 2020;52:2015-38.
Shah R, Gupta C. Advances in sperm retrieval techniques in azoospermic men: A systematic review. Arab J Urol 2018;16:125-31.
Fraietta R, Zylberstejn DS, Esteves SC. Hypogonadotropic hypogonadism revisited. Clinics (Sao Paulo) 2013;68 Suppl 1:81-8.
Young J, Xu C, Papadakis GE, Acierno JS, Maione L, Hietamäki J, et al.
Clinical management of congenital hypogonadotropic hypogonadism. Endocr Rev 2019;40:669-710.
Hayes FJ, Seminara SB, Crowley WF Jr. Hypogonadotropic hypogonadism. Endocrinol Metab Clin North Am 1998;27:739-63.
Ohlander SJ, Lindgren MC, Lipshultz LI. Testosterone and male infertility. Urol Clin North Am 2016;43:195-202.
Han TS, Bouloux PM. What is the optimal therapy for young males with hypogonadotropic hypogonadism? Clin Endocrinol (Oxf) 2010;72:731-7.
Jung JH, Kim MH, Kim J, Baik SK, Koh SB, Park HJ, et al
. Treatment of leukocytospermia in male infertility: A systematic review. World J Mens Health 2016;34:165-72.
Behre HM, Bergmann M, Simoni M, Tüttelmann F. Primary testicular failure. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, et al
., editors. Endotext. South Dartmouth (MA): MDText.com, Inc.; 2000.
Okutman O, Rhouma MB, Benkhalifa M, Muller J, Viville S. Genetic evaluation of patients with non-syndromic male infertility. J Assist Reprod Genet 2018;35:1939-51.
Greco E, Scarselli F, Minasi MG, Casciani V, Zavaglia D, Dente D, et al.
Birth of 16 healthy children after ICSI in cases of nonmosaic Klinefelter syndrome. Hum Reprod 2013;28:1155-60.
Baazeem A, Belzile E, Ciampi A, Dohle G, Jarvi K, Salonia A, et al
. Varicocele and male factor infertility treatment: A new meta-analysis and review of the role of varicocele repair. Eur Urol 2011;60:796-808.
Ding H, Tian J, Du W, Zhang L, Wang H, Wang Z. Open non-microsurgical, laparoscopic or open microsurgical varicocelectomy for male infertility: A meta-analysis of randomized controlled trials. BJU Int 2012;110:1536-42.
Mahafza WS, Alarini MY, Awadghanem AF, Odwan G, Juweid ME. Testicular microlithiasis: Correlation with Doppler sonography of testicular arteries and sperm function. J Clin Ultrasound 2016;44:474-9.
Gupta AA, Edelstein K, Albert-Green A, D'Agostino N. Assessing information and service needs of young adults with cancer at a single institution: The importance of information on cancer diagnosis, fertility preservation, diet, and exercise. Support Care Cancer 2013;21:2477-84.
Trost LW, Brannigan RE. Oncofertility and the male cancer patient. Curr Treat Options Oncol 2012;13:146-60.
Carrasquillo R, Sávio LF, Venkatramani V, Parekh D, Ramasamy R. Using microscope for Onco-testicular sperm extraction for bilateral testis tumors. Fertil Steril 2018;109:745.
Hamada A, Esteves SC, Nizza M, Agarwal A. Unexplained male infertility: Diagnosis and management. Int Braz J Urol 2012;38:576-94.
Attia AM, Abou-Setta AM, Al-Inany HG. Gonadotrophins for idiopathic male factor subfertility. Cochrane Database Syst Rev 2013; 23 (8): CD005071.
Tremellen K. Oxidative stress and male infertility – A clinical perspective. Hum Reprod Update 2008;14:243-58.