Male Infertility Treatment & Management
- Author: Kassem Faraj; Chief Editor: Edward David Kim, MD, FACS more...
Limited numbers of medical treatments are aimed at improving chances of conception for patients with known causes of infertility.
A number of patients with hypogonadotropic hypogonadism respond to gonadotropin-releasing hormone (GnRH) therapy or gonadotropin replacement. Pulsatile GnRH therapy can be used in those with intact pituitary function. Gonadotropin replacement can be effective in hypothalamic and pituitary dysfunction.
Human chorionic gonadotropin (hCG) is a luteinizing hormone (LH) analogue that may be used alone or in combination with human menopausal gonadotropin (hMG) for Leydig cell stimulation. hCG is biologically similar to LH, but has a longer half life and is less costly than LH. hMG is a purified combination of follicle-stimulating hormone (FSH) and LH. When using hCG in combination with hMG or FSH, one should use hCG first, as it increases testosterone levels, which is essential for spermatogenesis and thus may better augment the overall effect of the therapy. FSH alone is not effective in inducing spermatogenesis, although recent studies suggest otherwise.
Estrogen modulators can also be of use. Aromatase inhibitors (eg, anastrozole) block the conversion of testosterone to estrogen, thus increasing the serum testosterone concentration.They are especially useful in improving semen parameters in patients with decreased testosterone:estradiol ratios.
Clomiphene citrate is a weak estrogen-receptor antagonist that works by blocking the negative feedback inhibition of estrogen on the anterior pituitary, thus increasing the release of FSH and LH. This will then result in increased testosterone production, ultimately augmenting spermatogenesis. Clomiphene citrate is effective in improving the semen parameters in patients with hypogonadotropic hypogonadism. Tamoxifen is another estrogen-receptor antagonist that, in combination with clomiphene, can increase sperm concentration, sperm motility, and pregnancy rates in males with idiopathic infertility.
Patients with congenital adrenal hyperplasia (CAH) may respond to therapy with glucocorticoids, while those with isolated testosterone deficiency may respond to testosterone replacement.
Exogenous testosterone decreases intratesticular testosterone production, thus inhibiting Sertoli cell function and spermatogenesis.
Treat patients with hyperprolactinemia with dopamine antagonists, such as bromocriptine or cabergoline.
Patients with antisperm antibody levels greater than 1:32 may respond to immunosuppression using cyclic steroids for 3-6 months. However, patients need to be aware of the potential side effects of steroids, including avascular necrosis of the hip, weight gain, and iatrogenic Cushing syndrome.
Imipramine or alpha-sympathomimetics, such as pseudoephedrine, may help close the bladder neck to assist in antegrade ejaculation. However, these medicines are of limited efficacy, especially in patients with a fixed abnormality such as a bladder neck abnormality occurring after a surgical procedure.
Alternatively, sperm may be recovered from voided or catheterized postejaculatory urine to be used in assisted reproductive techniques. The urine should be alkalinized with a solution of sodium bicarbonate for optimal recovery.
More recently, the injection of collagen to the bladder neck has allowed antegrade ejaculation in a patient who had previously undergone a V-Y plasty of the bladder neck and for whom pseudoephedrine and intrauterine insemination had failed.
Patients with poor semen quality or numbers may benefit from having their semen washed and concentrated in preparation for intrauterine insemination.
Couples with an abnormal postcoital test result due to semen hyperviscosity may benefit from a precoital saline douche or semen processing with chymotrypsin.
Patients should be encouraged to stop smoking cigarettes and marijuana and to limit environmental exposures to harmful substances and/or conditions.
Stress-relief therapy and consultation of other appropriate psychological and social professionals may be advised.
Infections should be treated with appropriate antimicrobial therapy.
Dietary supplements and vitamins
Safarinejad et al published a prospective, double-blind, randomized controlled trial assessing the effects of coenzyme Q 10 (ubiquinol) 200 mg po daily (n = 114 men) compared with placebo (n = 114 men) over 26 weeks. The authors found a statistically significant increase in sperm concentration, motility, and strict morphology in subjects who received ubiquinol compared to those who received placebo, and these effects gradually returned to baseline levels during the off-drug time period. While pregnancy rates were not tracked or reported, the study does appear to support the use of ubiquinol in men trying to achieve a pregnancy based on improvement in semen parameters.
Various techniques for varicocelectomy have been proposed and used, each with advantages and disadvantages.
The retroperitoneal approach may be performed as an open procedure or laparoscopically.
The inguinal approach (see image below) allows for ligation of individual veins with decreased risk of inadvertent arterial damage. A 3-5 cm incision is made over the inguinal canal and the spermatic cord is identified and elevated. The external veins parallel to the cord are ligated, followed by microscopic ligation of the spermatic veins Collateral vessels entering the cord distally may also be directly addressed with this technique. This is in contrast to the subinguinal approach, in which a greater number of arteries and veins are exposed and the dissection may be more difficult.
Successful varicocelectomy results in improvement in semen parameters in 60-70% of patients. The repair also typically halts further testicular damage and improves Leydig cell function.. Success with these repairs can be predicted by certain preoperative factors, such as younger patient age, greater sperm density, larger varicoceles, and high preoperative testosterone and lower FSH levels.[44, 45]
Persistent dilatation after repair is not unusual and does not necessarily represent surgical failure. Rather, the veins may remain clinically apparent owing to chronic stretching or thrombosis, even if venous reflux is no longer present. Semen analysis may show improvement as early as the 3-month follow-up visit.
Results from a prospective, randomized, controlled trial from Saudi Arabia provide an evidence-based endorsement of the superiority of subinguinal microsurgical varicocele repair over observation in infertile men with palpable varicoceles and impaired semen quality. Inclusion criteria included infertility lasting 1 year or longer, demonstration of a palpable varicocele, and presence of at least one impaired semen parameter (sperm concentration <20 million/mL, progressive motility <50%, or normal morphology <30%). A total of 145 participants had follow-up within 1 year; spontaneous pregnancy was achieved in 13.9% of controls compared with 32.9% of treated men (odds ratio, 3.04). In treated men, the mean of all semen parameters significantly improved on follow-up compared with baseline (p < 0.0001).
A meta-analysis that compared the various varicocelectomy approaches found that pregnancy rates increased in inguinal, subinguinal, open inguinal, and laparoscopic approaches. However, the subinguinal and inguinal groups had the lowest recurrence rates, highest pregnancy rates, greatest increases in sperm parameters, and lowest rate of hydrocele formation.
Interest in the use of robotic surgery has been growing across various medical fields, including varicocelectomy. The potential advantages of robotic-assisted microsurgery include the following :
Elimination of tremor
Scalability of motion
Multi-input visual interphases with multiple visual views
Ability to manipulate multiple instruments and cameras simultaneously
Robot-assisted subinguinal varicocelectomy has been shown to be safe and efficacious, with one group reporting improved sperm parameters in 76% of patients. Operative times are similar to those with microscopic inguinal varicocelectomy, although the robotic technique does have a learning curve.
Vasovasostomy or vasoepididymostomy
These microsurgical techniques are performed in patients with known epididymal or vasal obstruction, both congenital and acquired (eg, due to surgery, trauma, infection). Improved surgical techniques and the use of the operating microscope have improved the outcomes in patients requiring vasectomy reversal or those with primary vas obstruction. In a study by Fenig et al, the timing of a reversal along with a sperm granuloma identified during the patient’s physical examination have been identified as predictors of the need for epididymovasostomy.
In addition, men with increased follicle-stimulating hormone levels of >10 U/l may have an increased likelihood of needing assisted reproduction to achieve pregnancy after vasectomy reversal according to a study by the Goldstein group of Weill Cornell Medical College.
After scrotal exploration, the patency of the duct system proximal to the proposed site of anastomosis is confirmed by examination of expressed fluid for the presence of sperm. If no fluid is expressed, a 24-gauge angiocatheter with 0.1 mL of saline should be used to gently barbotage the proximal vas. If no sperm are observed, inspect the vasal fluid aspirated.
A thickened, white, toothpaste-like fluid usually contains no sperm or nonviable sperm fragments and is likely merely from the vasal epithelium, whereas a watery thin fluid often implies proximal patency. If viable sperm are observed, send an additional sample for cryopreservation prior to vasovasostomy. These sperm may be used for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) if the man remains azoospermic after the repair.
The patency of the distal duct system is confirmed by injecting 10 mL of sterile saline through the vas; if no resistance is encountered, the system is deemed patent. Alternatively, radiographic vasography or chromogenic vasography with methylene blue can be performed, with radiographic contrast visualized passing into the bladder or blue coloration of the urine proving patency, respectively. A 2-0 nylon suture can be passed into the vasal lumen to check the distance to obstruction if the above tests reveal distal blockage.
A vasovasostomy is generally performed in 2 layers, the inner lining with interrupted 10-0 nylon suture and the outer layer with interrupted 9-0 nylon suture (see image below). Optimally, a tension-free, mucosa-to-mucosa, watertight anastomosis is created.
A vasoepididymostomy is also closed in 2 layers (see image below). Factors that predict a more favorable outcome include a shorter time from the original injury/surgery, a vasovasostomy performed on one side rather than bilateral vasoepididymostomies, and reconstruction because of an infectious etiology rather than a surgical or idiopathic etiology.
When performing a vasoepididymostomy, an end-to-side technique is easier to perform and yields better outcomes than an end-to-end anastomosis. More recently, a triangular technique for vasoepididymostomy has been proposed. Although more motile sperm are present at the proximal epididymis in patients with ductal obstruction, the technique is easier and more successful if it is performed at the distal end.
A varicocelectomy and vasovasostomy should never be performed at the same time because of a risk of testicular atrophy.
Robotic vasovasostomy has been shown to yield similar patency rates as the microsurgical approach, but no difference in pregnancy rates (~60%). The mean operating times for robotic vasovasostomy and vasoepididymostomy have also been shown to be comparable to the microsurgical approaches.
Robotic assistance also permits microsurgical procedures to be used in areas that are normally difficult to access. For example, in patients who have a vasal obstruction as a result of a prior inguinal hernia repair, robotic-assisted intra-abdominal vasovasostomy has been effectively employed. It provides an advantage to these patients because it requires very small inguinal incisions to mobilize the external vas and it allows for tension-free anastomosis because the testicular vas is brought into the pelvis for the procedure.
Transurethral resection of the ejaculatory ducts
Patients with a known or suspected obstruction of the ejaculatory ducts may be eligible for transurethral resection of the ejaculatory ducts (TURED), which durably improves semen quality in patients with ejaculatory duct obstruction.
In the operating room, with patients under spinal or general anesthesia, the resectoscope with a 24F cutting loop is used to excise the verumontanum of the prostate. Using the O'Connor drape to enable placement of a finger in the rectum to elevate the prostate may be helpful.
Resection is performed with care to avoid injuring the bladder neck or external sphincter.
Risks with this procedure include watery (urine) ejaculate, chemical or bacterial epididymitis due to reflux, bleeding, and retrograde ejaculation.
Sperm retrieval techniques
Testicular sperm extraction (TESE) is performed at the time of testicular biopsy or as a separate procedure using the same technique. In a study spanning 15 years, TESE from men with azoospermia followed by cryopreservation was more effective at fertilization than fresh sperm from biopsies (62% vs 47% for all diagnoses).[58, 59]
Microscopic TESE (microTESE) has been shown to improve sperm retrieval rates with minimal tissue excision.During microdissection, the surgeon can identify sperm-producing areas in the testicles, as opposed to standard TESE, where this is not possible. Robotic-assisted TESE (ROTESE) has been employed in select studies and has been shown to be safe and feasible for sperm retrieval. An advantage of ROTESE over microTESE is that ROTESE can provide surgeons with multiple imaging modalities to use during the procedure, which may assist in identifying tubules that have sperm.
Testicular sperm aspiration (TESA) is less invasive than TESE but yields fewer sperm and is suboptimal in cases of nonobstructive azoospermia.
Microsurgical epididymal sperm aspiration (MESA) involves directly retrieving sperm from the epididymis. Sperm in the epididymis are more mature than that in the testis. Using a microscope, the epididymis is uncovered and incised to express sperm. Epididymal fluid is aspirated into a tuberculin syringe primed with human tubal fluid (HTF).
Percutaneous epididymal sperm aspiration (PESA) involves direct sperm aspiration from the epididymis. This procedure can be performed under local anesthesia in the office setting. While effective in sperm retrieval, this does not allow sampling from multiple sites and is associated with an increased risk of epididymal and testicular injury and secondary epididymal obstruction.
An autogenous spermatocele can be created in patients with an unreconstructable ductal system. A buttonhole is created within the viscera, and repeated percutaneous aspirations of sperm can be performed using ultrasonographic guidance. An intact tunica vaginalis with no adhesions is needed, so it is ideal for use in patients with normal spermatogenesis and a congenital absence of the vas. This procedure is rarely used.
An alloplastic spermatocele uses an artificial silicone sperm reservoir in place of the tunica vaginalis for sperm storage and subsequent retrieval. This technique has been unsuccessful so far.
Under general anesthesia, an unlubricated Foley catheter is placed in the bladder and a buffer (ie, human tubal fluid [HTF] medium) is instilled through the catheter. A rectal probe is inserted with its electrodes positioned against the posterior seminal vesicles. Electrical stimulation is begun at 3-5 volts and increased as necessary. Electroejaculation achieves up to a 90% sperm retrieval rate.
The penile vibratory stimulator has been shown to be a useful alternative to electroejaculation in select patients. The US Food and Drug Administration (FDA) has approved this device for home use, using 2.2 mm at 100 Hz. This is associated with fewer adverse effects and lower cost than electroejaculation. In addition, collection may take place at home instead of in the operating room.
Artificial insemination (AI) involves the placement of sperm directly into the cervix (ie, intracervical insemination [ICI]) or the uterus (ie, intrauterine insemination [IUI]). AI is most useful for couples in whom the postcoital test indicated no sperm, those who have very low sperm density or motility, or those who have unexplained infertility.
IUI allows the sperm to be placed past the inhospitable cervical mucus and increases the chance of natural fertilization. This results in a 4% pregnancy rate if used alone and a pregnancy rate of 8-17% if combined with superovulation. Both processes require semen processing.
Older age in the male has been associated with lower pregnancy rates and higher rates of subsequent spontaneous abortions in patients undergoing IUI.[62, 63] Patients in whom IUI has failed 3-6 times should consider proceeding to IVF.
Assisted reproduction techniques
Patients with severe oligospermia, azoospermia, unexplained infertility, or known defects that preclude fertilization by other means are candidates for assisted reproduction techniques. Assisted reproduction techniques use donated or retrieved eggs that are fertilized by the male partner's sperm or donor sperm. The fertilized embryos are then replaced within the female reproductive tract. These techniques result in a 15-20% delivery rate per cycle and may eventually be successful in 50% of cases. However, the high cost and technical difficulty of the procedures generally preclude their routine use as first-line therapy.
In vitro fertilization
IVF involves fertilization of the egg outside the body and reimplantation of the fertilized embryo into the woman's uterus. Indications for IVF include previous failures with IUI and known conditions of the male or female precluding the use of less-demanding techniques.
IVF generally requires a minimum of 50,000-500,000 motile sperm. Harvesting eggs initially involves down-regulating the woman's pituitary with a GnRH agonist and then performing controlled ovarian hyperstimulation.
Follicular development is monitored by ultrasonographic examination and by checking serum levels of estrogen and progesterone. When the follicles are appropriately enlarged, a transvaginal follicular aspiration is performed.
A mean of 12 eggs are typically retrieved per cycle, and they are immediately placed in an agar of fallopian-tube medium. After an incubation period of 3-6 hours, the sperm are added to the medium using approximately 100,000 sperm per oocyte. After 48 hours, the embryos have usually reached the 3- to 8-cell stage. Two to 4 embryos are usually implanted in the uterus, while the remaining embryos are frozen for future use. Pregnancy rates are 10-45%.
Overall, IVF is a safe and useful procedure. Risks include multiple pregnancies and hyperstimulation syndrome, as well as a slightly higher rate of major birth defects. Additionally, an increased risk of hypospadias occurs in boys (1.5% vs 0.3%), probably because of the increased maternal progesterone used for egg harvesting.
Finally, the use of this technology has led to many ethical issues, such as the fate of embryos after divorce.
Gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT)
These procedures allow the placement of semen (GIFT) or a fertilized zygote (ZIFT) directly into the fallopian tube by laparoscopy or laparotomy. Success rates have been estimated to be 25-30% using these techniques. Unfortunately, these procedures require general anesthesia and have associated risks. Fertilization and implantation within the uterus are not guaranteed, and these procedures cannot be performed in patients with fallopian tube obstruction. GIFT and ZIFT are rarely used as a therapeutic option.
Intracytoplasmic sperm injection
ICSI involves the direct injection of a sperm into an egg under microscopy (see image below). It is indicated in patients who have failed more conservative therapies or those with severe abnormalities in which no other treatment would be effective, including patients with sperm extracted directly from the epididymis or testicle.
Sperm samples are collected either via masturbation or surgically. Surgical extraction may be more useful in cases of persistent necrozoospermia, due to the high DNA fragmentation rates in ejaculated sperm. Sperm can then be evaluated microscopically in terms of their motility, morphology, DNA quality, and/or the ability to bind a hyaluronic acid assay. The embryologist then chooses the most adequate sperm for the procedure.
Oocytes are processed with hyaluronidase to remove the cumulus mass and corona radiata. A micropipette is used to hold the egg while a second micropipette injects the sperm. The oocyte is positioned with the polar body at the 6-o'clock or 12-o'clock position, and the sperm is injected at the 3-o'clock position to minimize the risk of chromosomal damage in the egg. After incubation for 48 hours, the embryo is implanted in the woman.
Van Steirteghem et al reported a 59% fertilization rate and a 35% pregnancy rate with the use of ICSI in 1409 oocytes. Fresh sperm and cryopreserved sperm appear to have similar success rates. In female partners of men with infertility who are undergoing ICSI, diminished ovarian reserve may adversely affect the success of TESE (ie, reduce the clinical pregnancy rate).[58, 59] Some studies also suggest that a direct correlation exists between endometrial thickness and pregnancy rates after ICSI.
The potential complications, ethical issues, and high costs of ICSI must be considered and individualized.
A genetics consultation may be indicated in patients with a known or suspected genetic cause of infertility and in patients with nonobstructive azoospermia or severe oligospermia (< 5 million sperm/mL). In addition, in the era of IVF and ICSI, determining the risks of passing on chromosomal abnormalities to a potential offspring is important.
Use a peripheral karyotype and a PCR-based evaluation of the Y chromosome to evaluate for microdeletions. Patients with nonobstructive azoospermia have a 13-17% chance of genetic abnormalities, 4-16% of which are due to Klinefelter syndrome and 9% are due to a partial Y deletion.
Patients with CBAVD nearly uniformly have a mutation in the CFTR gene. An estimated 50-82% of men with CBAVD have a genital-only form of CF, which may manifest in patients with only one copy of the abnormal CF gene. In contrast, patients with clinical CF usually have two copies of the abnormal gene.
As for men who do have the digestive and pulmonary complications of CF, technology is allowing them to live longer. These men are now candidates for assisted reproductive techniques. The female partner must be evaluated for a CFTR gene mutation before attempted fertilization to determine the risk of producing offspring with CF, which is an autosomal recessive trait.
Patients with severe oligospermia or azoospermia should be evaluated with a hormonal evaluation.
Patients with unexplained hypogonadism or hyperprolactinemia should undergo a CT scan or MRI of the sella turcica to evaluate for a pituitary tumor.
Abnormalities may indicate the need for a formal endocrinology consultation.
See the list below:
A diet high in antioxidants such as vitamin C and vitamin E has been proposed to improve the quality of sperm by decreasing the number of free radicals that may cause membrane damage.
Additionally, the use of zinc, fish oil, and selenium has been shown to be of benefit in some studies. 
See the list below:
Patients should limit the use of potentially spermatotoxic substances such as cigarettes, marijuana, and anabolic steroids. Environmental exposures to harmful substances and/or conditions should be minimized.
The optimal timing to perform intercourse for conception is every 2 days at mid cycle.
The use of spermatotoxic lubricants should be avoided.
Palermo G, Joris H, Devroey P, Van Steirteghem AC. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet. 1992 Jul 4. 340(8810):17-8. [Medline].
Matorras R, Diez J, Corcóstegui B, Gutiérrez de Terán G, García JM, Pijoan JI, et al. Spontaneous pregnancy in couples waiting for artificial insemination donor because of severe male infertility. Eur J Obstet Gynecol Reprod Biol. 1996 Dec 27. 70(2):175-8. [Medline].
Carlsen E, Giwercman A, Keiding N, Skakkebaek NE. Evidence for decreasing quality of semen during past 50 years. BMJ. 1992 Sep 12. 305(6854):609-13. [Medline].
Mulcahy N. Male infertility increases overall cancer risk. Medscape Medical News. June 21, 2013; Accessed July 30, 2013. Available at http://www.medscape.com/viewarticle/806619.
Eisenberg ML, Betts P, Herder D, Lamb DJ, Lipshultz LI. Increased risk of cancer among azoospermic men. Fertil Steril. 2013 Jun 12. [Medline].
Ventimiglia E, Capogrosso P, Boeri L, Serino A, Colicchia M, Ippolito S, et al. Infertility as a proxy of general male health: results of a cross-sectional survey. Fertil Steril. 2015 Jul. 104 (1):48-55. [Medline].
Baker HW. Reproductive effects of nontesticular illness. Endocrinol Metab Clin North Am. 1998 Dec. 27(4):831-50. [Medline].
Alshahrani S, Ahmed AF, Gabr AH, Abalhassan M, Ahmad G. The impact of body mass index on semen parameters in infertile men. Andrologia. 2016 Feb 5. [Medline].
Jacobsen KD, Ous S, Waehre H, Trasti H, Stenwig AE, Lien HH, et al. Ejaculation in testicular cancer patients after post-chemotherapy retroperitoneal lymph node dissection. Br J Cancer. 1999 Apr. 80(1-2):249-55. [Medline].
Gundersen TD, Jørgensen N, Andersson AM, Bang AK, Nordkap L, Skakkebæk NE, et al. Association Between Use of Marijuana and Male Reproductive Hormones and Semen Quality: A Study Among 1,215 Healthy Young Men. Am J Epidemiol. 2015 Sep 15. 182 (6):473-81. [Medline].
El Osta R, Almont T, Diligent C, Hubert N, Eschwège P, Hubert J. Anabolic steroids abuse and male infertility. Basic Clin Androl. 2016. 26:2. [Medline].
Wang C, McDonald V, Leung A, Superlano L, Berman N, Hull L, et al. Effect of increased scrotal temperature on sperm production in normal men. Fertil Steril. 1997 Aug. 68(2):334-9. [Medline].
Schatte EC, Orejuela FJ, Lipshultz LI, Kim ED, Lamb DJ. Treatment of infertility due to anejaculation in the male with electroejaculation and intracytoplasmic sperm injection. J Urol. 2000 Jun. 163(6):1717-20. [Medline].
Brackett NL, Lynne CM, Aballa TC, Ferrell SM. Sperm motility from the vas deferens of spinal cord injured men is higher than from the ejaculate. J Urol. 2000 Sep. 164(3 Pt 1):712-5. [Medline].
da Silva BF, Meng C, Helm D, Pachl F, Schiller J, Ibrahim E, et al. Towards understanding male infertility after spinal cord injury using quantitative proteomics. Mol Cell Proteomics. 2016 Jan 26. [Medline].
Talebi AR, Khalili MA, Vahidi S, Ghasemzadeh J, Tabibnejad N. Sperm chromatin condensation, DNA integrity, and apoptosis in men with spinal cord injury. J Spinal Cord Med. 2013 Mar. 36 (2):140-6. [Medline].
Takihara H, Sakatoku J, Fujii M, Nasu T, Cosentino MJ, Cockett AT. Significance of testicular size measurement in andrology. I. A new orchiometer and its clinical application. Fertil Steril. 1983 Jun. 39(6):836-40. [Medline].
Bouloux P, Warne DW, Loumaye E; FSH Study Group in Men's Infertility. Efficacy and safety of recombinant human follicle-stimulating hormone in men with isolated hypogonadotropic hypogonadism. Fertil Steril. 2002 Feb. 77(2):270-3. [Medline].
Whitten SJ, Nangia AK, Kolettis PN. Select patients with hypogonadotropic hypogonadism may respond to treatment with clomiphene citrate. Fertil Steril. 2006 Dec. 86(6):1664-8. [Medline].
Rucker GB, Mielnik A, King P, Goldstein M, Schlegel PN. Preoperative screening for genetic abnormalities in men with nonobstructive azoospermia before testicular sperm extraction. J Urol. 1998 Dec. 160(6 Pt 1):2068-71. [Medline].
Yoshida A, Miura K, Nagao K, Hara H, Ishii N, Shirai M. Sexual function and clinical features of patients with Klinefelter's syndrome with the chief complaint of male infertility. Int J Androl. 1997 Apr. 20(2):80-5. [Medline].
Aiman J, Griffin JE, Gazak JM, Wilson JD, MacDonald PC. Androgen insensitivity as a cause of infertility in otherwise normal men. N Engl J Med. 1979 Feb 1. 300 (5):223-7. [Medline].
Davis-Dao CA, Tuazon ED, Sokol RZ, Cortessis VK. Male infertility and variation in CAG repeat length in the androgen receptor gene: a meta-analysis. J Clin Endocrinol Metab. 2007 Nov. 92 (11):4319-26. [Medline].
Vicdan A, Vicdan K, Günalp S, Kence A, Akarsu C, Isik AZ, et al. Genetic aspects of human male infertility: the frequency of chromosomal abnormalities and Y chromosome microdeletions in severe male factor infertility. Eur J Obstet Gynecol Reprod Biol. 2004 Nov 10. 117(1):49-54. [Medline].
Colombo JB, Naz RK. Modulation of insulin-like growth factor-1 in the seminal plasma of infertile men. J Androl. 1999 Jan-Feb. 20 (1):118-25. [Medline].
Naderi G, Mohseni Rad H, Tabassomi F, Latif A. Seminal insulin-like growth factor-I may be involved in the pathophysiology of infertility among patients with clinical varicocele. Hum Fertil (Camb). 2015 Jun. 18 (2):92-5. [Medline].
Tollner TL, Venners SA, Hollox EJ, Yudin AI, Liu X, Tang G, et al. A common mutation in the defensin DEFB126 causes impaired sperm function and subfertility. Sci Transl Med. 2011 Jul 20. 3 (92):92ra65. [Medline].
Diao R, Fok KL, Chen H, Yu MK, Duan Y, Chung CM, et al. Deficient human β-defensin 1 underlies male infertility associated with poor sperm motility and genital tract infection. Sci Transl Med. 2014 Aug 13. 6 (249):249ra108. [Medline].
Smith HC. Fertility in men with cystic fibrosis assessment, investigations and management. Paediatr Respir Rev. 2010 Jun. 11 (2):80-3. [Medline].
Zahalsky MP, Berman AJ, Nagler HM. Evaluating the risk of epididymal injury during hydrocelectomy and spermatocelectomy. J Urol. 2004 Jun. 171(6 Pt 1):2291-2. [Medline].
Purohit RS, Wu DS, Shinohara K, Turek PJ. A prospective comparison of 3 diagnostic methods to evaluate ejaculatory duct obstruction. J Urol. 2004 Jan. 171(1):232-5; discussion 235-6. [Medline].
Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010 May-Jun. 16(3):231-45. [Medline].
Pierik FH, Dohle GR, van Muiswinkel JM, Vreeburg JT, Weber RF. Is routine scrotal ultrasound advantageous in infertile men?. J Urol. 1999 Nov. 162(5):1618-20. [Medline].
Raman JD, Nobert CF, Goldstein M. Increased incidence of testicular cancer in men presenting with infertility and abnormal semen analysis. J Urol. 2005 Nov. 174(5):1819-22; discussion 1822. [Medline].
Yanagimachi R, Yanagimachi H, Rogers BJ. The use of zona-free animal ova as a test-system for the assessment of the fertilizing capacity of human spermatozoa. Biol Reprod. 1976 Nov. 15(4):471-6. [Medline].
Finkel DM, Phillips JL, Snyder PJ. Stimulation of spermatogenesis by gonadotropins in men with hypogonadotropic hypogonadism. N Engl J Med. 1985 Sep 12. 313 (11):651-5. [Medline].
Santi D, Granata AR, Simoni M. FSH treatment of male idiopathic infertility improves pregnancy rate: a meta-analysis. Endocr Connect. 2015 Sep. 4 (3):R46-58. [Medline].
Pavlovich CP, King P, Goldstein M, Schlegel PN. Evidence of a treatable endocrinopathy in infertile men. J Urol. 2001 Mar. 165 (3):837-41. [Medline].
Whitten SJ, Nangia AK, Kolettis PN. Select patients with hypogonadotropic hypogonadism may respond to treatment with clomiphene citrate. Fertil Steril. 2006 Dec. 86 (6):1664-8. [Medline].
Chua ME, Escusa KG, Luna S, Tapia LC, Dofitas B, Morales M. Revisiting oestrogen antagonists (clomiphene or tamoxifen) as medical empiric therapy for idiopathic male infertility: a meta-analysis. Andrology. 2013 Sep. 1 (5):749-57. [Medline].
Reynolds JC, McCall A, Kim ED, Lipshultz LI. Bladder neck collagen injection restores antegrade ejaculation after bladder neck surgery. J Urol. Apr 1998. 159(4):1303. [Medline].
Safarinejad MR, Safarinejad S, Shafiei N, Safarinejad S. Effects of the reduced form of coenzyme q(10) (ubiquinol) on semen parameters in men with idiopathic infertility: a double-blind, placebo controlled, randomized study. J Urol. 2012 Aug. 188(2):526-31. [Medline].
Binsaleh S, Lo KC. Varicocelectomy: microsurgical inguinal varicocelectomy is the treatment of choice. Can Urol Assoc J. 2007 Sep. 1 (3):277-8. [Medline].
Huang HC, Huang ST, Chen Y, Hsu YC, Chang PC, Hsieh ML. Prognostic factors for successful varicocelectomy to treat varicocele-associated male infertility. Reprod Fertil Dev. 2014 Mar. 26 (3):485-90. [Medline].
Kondo Y, Ishikawa T, Yamaguchi K, Fujisawa M. Predictors of improved seminal characteristics by varicocele repair. Andrologia. 2009 Feb. 41 (1):20-3. [Medline].
Al Bakri A, Lo K, Grober E, Cassidy D, Cardoso JP, Jarvi K. Time for improvement in semen parameters after varicocelectomy. J Urol. 2012 Jan. 187(1):227-31. [Medline].
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. 2010 Dec 21. [Medline].
Wang J, Xia SJ, Liu ZH, Tao L, Ge JF, Xu CM, et al. Inguinal and subinguinal micro-varicocelectomy, the optimal surgical management of varicocele: a meta-analysis. Asian J Androl. 2015 Jan-Feb. 17 (1):74-80. [Medline].
Parekattil SJ, Gudeloglu A. Robotic assisted andrological surgery. Asian J Androl. 2013 Jan. 15 (1):67-74. [Medline].
Trost L, Parekattil S, Wang J, Hellstrom WJ. Intracorporeal robot-assisted microsurgical vasovasostomy for the treatment of bilateral vasal obstruction occurring following bilateral inguinal hernia repairs with mesh placement. J Urol. 2014 Apr. 191 (4):1120-5. [Medline].
Gudeloglu A, Brahmbhatt JV, Parekattil SJ. Robotic microsurgery in male infertility and urology-taking robotics to the next level. Transl Androl Urol. 2014 Mar. 3 (1):102-12. [Medline].
Belker AM, Thomas AJ, Fuchs EF. Results of 1,469 microsurgical vasectomy reversals by the Vasovasostomy Study Group. J Urol. 1991 Mar. 145(3):505-11. [Medline].
Fenig DM, Kattan MW, Mills JN, et al. Nomogram to preoperatively predict the probability of requiring epididymovasostomy during vasectomy reversal. J Urol. 2012 Jan. 187(1):215-8. [Medline].
Hsiao W, Sultan R, Lee R, Goldstein M. Increased Follicle-Stimulating Hormone is Associated With Higher Assisted Reproduction Use After Vasectomy Reversal. J Urol. 2011 Jun. 185(6):2266-71. [Medline].
Anger JT, Goldstein M. Intravasal "toothpaste" in men with obstructive azoospermia is derived from vasal epithelium, not sperm. J Urol. 2004 Aug. 172(2):634-6. [Medline].
Berger RE. Triangulation end-to-side vasoepididymostomy. J Urol. 1998 Jun. 159(6):1951-3. [Medline].
Hauser R, Yogev L, Paz G, Yavetz H, Azem F, Lessing JB, et al. Comparison of efficacy of two techniques for testicular sperm retrieval in nonobstructive azoospermia: multifocal testicular sperm extraction versus multifocal testicular sperm aspiration. J Androl. 2006 Jan-Feb. 27(1):28-33. [Medline].
Lewis R. Freezing sperm a viable option in azoospermic men. Medscape Medical News. August 12, 2013. [Full Text].
Omurtag K, Cooper A, Bullock A, et al. Sperm recovery and IVF after testicular sperm extraction (TESE): effect of male diagnosis and use of off-site surgical centers on sperm recovery and IVF. PLoS One. 2013. 8(7):e69838. [Medline]. [Full Text].
Schlegel PN. Testicular sperm extraction: microdissection improves sperm yield with minimal tissue excision. Hum Reprod. 1999 Jan. 14 (1):131-5. [Medline].
Belker AM, Sherins RJ, Dennison-Lagos L, Thorsell LP, Schulman JD. Percutaneous testicular sperm aspiration: a convenient and effective office procedure to retrieve sperm for in vitro fertilization with intracytoplasmic sperm injection. J Urol. 1998 Dec. 160(6 Pt 1):2058-62. [Medline].
Mathieu C, Ecochard R, Bied V, Lornage J, Czyba JC. Cumulative conception rate following intrauterine artificial insemination with husband's spermatozoa: influence of husband's age. Hum Reprod. 1995 May. 10 (5):1090-7. [Medline].
Bellver J, Garrido N, Remohí J, Pellicer A, Meseguer M. Influence of paternal age on assisted reproduction outcome. Reprod Biomed Online. 2008 Nov. 17 (5):595-604. [Medline].
Olson CK, Keppler-Noreuil KM, Romitti PA, Budelier WT, Ryan G, Sparks AE, et al. In vitro fertilization is associated with an increase in major birth defects. Fertil Steril. 2005 Nov. 84(5):1308-15. [Medline].
Silver RI, Rodriguez R, Chang TS, Gearhart JP. In vitro fertilization is associated with an increased risk of hypospadias. J Urol. 1999 Jun. 161(6):1954-7. [Medline].
Jakab A, Sakkas D, Delpiano E, Cayli S, Kovanci E, Ward D, et al. Intracytoplasmic sperm injection: a novel selection method for sperm with normal frequency of chromosomal aneuploidies. Fertil Steril. 2005 Dec. 84 (6):1665-73. [Medline].
Van Steirteghem AC, Liu J, Joris H, Nagy Z, Janssenswillen C, Tournaye H, et al. Higher success rate by intracytoplasmic sperm injection than by subzonal insemination. Report of a second series of 300 consecutive treatment cycles. Hum Reprod. 1993 Jul. 8(7):1055-60. [Medline].
Wald M, Ross LS, Prins GS, Cieslak-Janzen J, Wolf G, Niederberger CS. Analysis of outcomes of cryopreserved surgically retrieved sperm for IVF/ICSI. J Androl. 2006 Jan-Feb. 27(1):60-5. [Medline].
Rehman R, Fatima SS, Hussain M, Khan R, Khan TA. Effect of endometrial thickness on pregnancy outcome after intracytoplasmic sperm injection. J Pak Med Assoc. 2015 May. 65 (5):448-51. [Medline].
Scott R, MacPherson A, Yates RW, Hussain B, Dixon J. The effect of oral selenium supplementation on human sperm motility. Br J Urol. 1998 Jul. 82(1):76-80. [Medline].
Klemetti R, Gissler M, Sevon T, Koivurova S, Ritvanen A, Hemminki E. Children born after assisted fertilization have an increased rate of major congenital anomalies. Fertil Steril. 2005 Nov. 84(5):1300-7. [Medline].
Agbugui JO, Omokhudu O. Posterior urethral valve: an unusual cause of primary male infertility. J Reprod Infertil. 2015 Apr-Jun. 16 (2):113-5. [Medline].
Mechlin C, Mccullough A. V1590 robotic microsurgical varicocele repair: initial experience and surgical outcomes from a single academic center. J Urol. 2013. 189:e652-3. [Full Text].
|Ejaculate volume||Low (< 1.5 mL)||Postejaculation urine (retrograde ejaculation)
TRUS (absence of vas deferens)
Hormonal evaluation (hypogonadism)
|High (>5 mL)||Likely contaminant|
|Semen quality||Does not coagulate||TRUS (ejaculatory duct obstruction)|
|Does not liquefy||Hormonal analysis|
|Sperm density||Oligospermia (< 20 million per mL)
Severe oligospermia (< 5 million per mL)
|TRUS (partial ejaculatory duct obstruction)
Antisperm antibody evaluation
Physical examination for varicocele
|Azoospermia||Sperm centrifuged to verify azoospermia
Postejaculation urine (retrograde ejaculation)
Testicular biopsy (testicular failure)
TRUS (ejaculatory duct obstruction)
Physical examination for varicocele
|*All semen analyses with abnormal results should be repeated.|