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Shattering the myths about male infertilityTreatment of male factors may be more successful and cost-effective than you thinkJay I. Sandlow, MD VOL 107 / NO 2 / FEBRUARY 2000 / POSTGRADUATE MEDICINE
CME learning objectives
This page is best viewed with a browser that supports tables Preview: Male factors play a role in up to half of subfertile couples, contrary to the myth that male factors rarely play a role. In this article, Dr Sandlow counters this and other myths about male infertility and suggests that primary care physicians can increase a couple's chance of conceiving by evaluating for male as well as female factors. This article will also help primary care physicians provide appropriate education and treatment, as well as determine when to make a referral to a male-infertility specialist.
In recent years, infertility has received increasing public attention. It is estimated that nearly 10% of couples are infertile (ie, unable to conceive after attempts over a span of at least 1 year) and that one of every five couples between the ages of 35 and 44 has difficulty conceiving. This article examines some of the myths associated with male infertility and subfertility and identifies the role of the primary care physician in managing the condition. Myth 1. Infertility is rarely the man's faultIn fact, up to 50% of infertile couples have male factor involvement (1). This group is typically split into 30% who have strictly male factors and 20% with both male and female factors. However, it is important that no blame is placed. Infertility is a problem of the couple and should be addressed as such. We assessed the utility of evaluation for male factors in 62 couples preparing to undergo assisted reproductive techniques because of male subfertility (2). The men involved were referred to our male infertility clinic for determination of the cause of subfertility. Fifty men (81%) were found to have identifiable infertility factors, and 47 (76%) were potentially treatable. We concluded that evaluation for male factors yields a significant, treatable cause in the majority of cases. Thus, we advocate evaluation for and, when indicated, treatment of male subfertility factors in couples considering assisted reproductive techniques. Identifiable factors in male subfertility include excurrent ductal obstruction, hypogonadism, ejaculatory dysfunction, varicoceles, and exposure to gonadotoxins.
Evaluation History: History taking is a crucial part of evaluation for male subfertility. Duration of infertility, number of previous pregnancies, and results of previous evaluations or treatments are key points. The sexual history, particularly with respect to potency and ejaculatory function, should be ascertained. Past medical history, including childhood history and adolescent development, should be gathered. Specifically, any history of torsion, cryptorchidism, or trauma may play a role. Systemic illness such as diabetes mellitus, neurologic disease such as multiple sclerosis, or previous cancer treatment such as chemotherapy or radiation therapy may be factors. Past surgeries may contribute to the problem, specifically retroperitoneal and bladder neck surgery. Previous hernia repair may cause vasal obstruction. Infections can affect fertility in several ways. Febrile episodes may decrease spermatogenesis, although usually this is self-limited and resolves within 3 to 6 months. Mumps in adolescence may lead to mumps orchitis. Sexually transmitted diseases, specifically chlamydial infection and gonorrhea, may cause ductal obstruction, as can any inflammatory condition within the testes, epididymides, or prostate. Gonadotoxins in the form of chemicals, medications (both prescription and nonprescription), tobacco, alcohol, and illicit drugs all affect spermatogenesis to some degree (table 1). The duration and amount of exposure often dictate the severity and reversibility of the spermatogenic dysfunction.
A family history of fertility problems or disorders, such as cystic fibrosis and androgen receptor deficiency, may suggest a genetic cause. Finally, a review of systems may suggest a cause. Impaired visual fields, galactorrhea, frequent respiratory infections, or anosmia may help identify either congenital or acquired causes of infertility. Physical examination: The physical examination should be thorough, yet focused. About 1% of men with subfertility have an underlying medical condition, such as testicular cancer, endo-crine dysfunction, or a genetic disorder (3). The general examination should include body habitus, secondary sexual characteristics, gynecomastia, and lymphadenopathy. The penis should be examined for curvature, location of the meatus, and phimosis or paraphimosis. Testicular examination should focus on size and volume, symmetry, consistency, and presence of masses. Asymmetry of the testes may signify a focal process as well as varicocele. The epididymides should be examined for presence of the entire gland, continuity with the vas deferens, induration, and tenderness. Examination of the spermatic cord, with special attention to the presence or absence of the vas deferens or varicoceles, is important. A rectal examination to detect prostatic infection or palpable seminal vesicles may rule out ejaculatory duct or seminal vesicle obstruction. Laboratory tests: Selective use of laboratory studies may be a cost-effective adjunct to history taking and physical examination. All patients should have at least two seminal fluid analyses. Ejaculatory abstinence should be maintained for 3 to 5 days, and samples should be collected 1 to 2 weeks apart. Sperm counts normally vary in an individual, so if the two seminal fluid analyses are dissimilar, a third should be obtained. Although many variables may be examined, the most important are sperm density (million per milliliter), motility (percentage of moving sperm), volume and pH of ejaculate, speed of sperm movement, and total number of motile sperm in the ejaculate. Other factors include agglutination, viscosity, and morphology. The spermatogenic cycle is about 70 days in the human male, with another 15 to 20 days of transit through the ductal system. Therefore, it takes about 90 days for any therapeutic intervention to be reflected in the seminal fluid analysis. Other assessments include analysis of postejaculate urine to rule out significant retrograde ejaculation, evaluation for autosperm antibodies, and functional analyses, such as sperm penetration assay, cervical mucous migration, postcoital test, and hemizona assay. Many of these are laboratory-dependent in terms of availability and consistency of interpretation and beyond the scope of this discussion. Hormonal evaluation should be limited to men with severe oligospermia (<10 million per milliliter). Studies have shown that it is extremely rare to detect significant endocrine abnormalities in men with mild to moderate oligospermia and normal results on physical examination (4). Endocrine studies should include measurement of total testosterone level (to evaluate Leydig's cell function) and level of follicle-stimulating hormones (to evaluate Sertoli's cell function). Luteinizing hormone, estradiol, and prolactin values may also be obtained, although these studies are not routine and are usually done using a pooled sample if results of random testosterone studies are abnormal. Myth 2. Nothing can be done to improve sperm countsAlthough numerous studies have demonstrated the efficacy of treatment of the male partner to increase fertility (as manifested by improved sperm counts or pregnancy), some clinicians still believe that not much can be done for male factor infertility (5-8). Indeed, many of the causes of male infertility are progressive, and treatment is needed to halt further damage or dysfunction (9). In some patients, subfertility is the first sign of systemic disease, such as pituitary tumor or testicular cancer (3). Additionally, although detection of genetic aberrations associated with infertility may not cause physicians to alter the approach because these conditions are not reversible, patients should be informed about results of genetic and other diagnostic tests before proceeding to the in vitro fertilization (IVF) process (10). Our previously cited study (2) suggests that although identification and treatment of male factors in infertility do not result in pregnancy in all couples, significant improvement of the sperm count is common, resulting in increased success. In this study, 47 of 62 men (76%) were found to have potentially correctable causes. Of these, 28 (60%) underwent corrective treatment. Spontaneous pregnancy occurred in 9 (32%) of these couples, and an additional 12 (43%) had improvement in seminal parameters. Thus, one third of the couples were able to conceive without the use of assisted reproductive techniques, and a significant percentage were able to avoid IVF for less invasive techniques.
Management Primary care physicians may also be instrumental in diagnosing potentially correctable disorders, such as genital tract infections, erectile dysfunction, and hormonal abnormalities. Therefore, it is imperative that primary care physicians be involved in the process of evaluating for male factors. The treatment of endocrinopathy can have a huge impact on the outcome of a couple's quest for children. Endocrinopathy may be a harbinger of more serious medical problems (3). Once such problems have been ruled out, treatment may be undertaken. In almost all men with hypogonadotropic hypogonadism--in which little or no gonadotropin-releasing hormone is present, thus leading to nearly nondetectable levels of luteinizing and follicle-stimulating hormones--injection of gonadotropins results in the return of spermatogenesis, with the majority of couples achieving pregnancy (11). Success rates after treatment of the male partner include improved seminal parameters in up to 70% of men, with a 35% to 40% unassisted pregnancy rate (12). Correction of obstructions, whether from vasectomies or other factors, results in return of sperm to the ejaculate in 50% to 95% of men. Pregnancy rates as high as 65% have been obtained, although a more realistic value is probably closer to 30% to 50% (13). Myth 3. Varicoceles don't cause infertilityThe most common cause of male infertility is varicocele. A varicocele is an abnormal dilation of the pampiniform plexus of the internal spermatic vein and is typically identified on the left side. This condition has been found to be a contributing factor in up to 40% of cases of primary and up to 80% of cases of secondary male subfertility. Varicoceles have also been identified in up to 15% of the general population (14). In the healthy state, the intratesticular temperature is maintained at several degrees below body temperature by means of a countercurrent temperature system. The spermatic arteries are surrounded by the multiple veins of the pampiniform plexus. The warm arterial blood is cooled by convection from these veins. Varicoceles are thought to increase the intratesticular temperature through the loss of venous valvular function. This leads to pooling of the warm blood in the testis, thus causing altered spermatogenesis, Leydig's cell dysfunction, and subsequent infertility (15).
Diagnosis and treatment The primary indications for treatment of a varicocele are (1) male subfertility, usually detected by abnormal findings on seminal fluid analysis, although abnormal function or morphology may be the only evident factor; (2) adolescent testicular growth retardation that is persistent during a 6-month observation period; and (3) intractable pain that is not attributable to other intrascrotal causes. Although some controversy remains about the utility and effectiveness of repairing varicoceles, most investigators agree that treating a varix in a subfertile male improves seminal parameters and yields higher pregnancy rates than does no treatment (21). It was originally reported that varix size did not affect the improvement seen postoperatively (22), but more recent reports have contradicted this finding (23). Furthermore, in two studies (24,25), morphology of the sperm as judged by Kruger's criteria (26) was increased by varicocele repair. Myth 4. It's cheaper to proceed directly to assisted reproductive techniquesIn a study of treatment costs, Comhaire (27) examined the cost per delivered baby for various treatments of subfertility. Varicocele repair was found to be the least expensive option ($1,700 per delivery), as compared with intrauterine insemination (IUI; $2,566 per delivery) and IVF ($11,667 per delivery with intracytoplasmic sperm injection [ICSI] and $18,333 without). Although, obviously, parameters and factors differed from group to group (for instance, many of the couples who had ICSI might never have achieved pregnancy with the other methods), Comhaire concluded that evaluation and treatment of male factors is cost-effective. Schlegel (28) analyzed treatment costs of varicoceles versus IVF/ICSI, citing a huge savings in cost, as well as in potential complications, when the primary cause of male factor infertility is addressed. He found the cost per delivery after varicocelectomy to be $26,268, as compared with $62,263 after IVF/ICSI (based on the highest published IVF/ICSI success rate). He also pointed out that potential complications of IVF, such as hyperstimulation, would increase the cost further. Finally, he reasoned that the actual cost for IVF/ICSI would be even higher, because the added cost of multiple births associated with assisted reproductive techniques was not factored into the final analysis. Donovan and associates (29) compared the cost of repeated vasectomy reversal procedures to that of sperm aspiration in conjunction with IVF. The pregnancy rate following repeated reversals was 44%, with a cost per delivered baby of $14,892. The pregnancy rate following sperm aspiration with IVF was 67%, but the cost per delivered baby was $35,570. It was calculated that a pregnancy rate of 81% would be necessary to achieve a comparable cost per delivery. This study illustrates that microsurgical reconstruction is worthwhile in many men and may be more cost-effective than sperm aspiration with IVF. These studies confirm that a significant percentage of couples can avoid unnecessary costs and risks of IVF simply by treatment of factors in the male partner. ConclusionInfertility affects about 10% of couples. Although one or both partners may have factors that contribute to the difficulty in achieving conception, ultimately the outcome is dependent on both the man and the woman. Therefore, evaluation and treatment should be goal-directed. The workup and treatment of the subfertile male is an important part of this goal. Significant male factors are involved in nearly 50% of infertile couples. Identification and correction of these factors yield excellent results, often allowing the couple the opportunity to conceive naturally, thus bypassing more expensive and invasive treatments. Through patient education, as well as diagnosis and treatment of correctable factors, the primary care physician can play a key role in helping a couple achieve fertility. References
Dr Sandlow is assistant professor, department of urology, and director of the section of male infertility, University of Iowa College of Medicine, Iowa City. Correspondence: Jay I. Sandlow, MD, Department of Urology, University of Iowa College of Medicine, 200 Hawkins Dr, 3241 RCP, Iowa City, IA 52242-1089. E-mail: jay-sandlow@uiowa.edu.
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