- Email: [email protected]
Frequency of the Male Infertility Evaluation: Data from the National Survey of Family Growth
Frequency of the Male Infertility Evaluation: Data from the National Survey of Family Growth Michael L. Eisenberg,* Ruth B. Lathi, Valerie L. Baker, Lynn M. Westphal, Amin A. Milki and Ajay K. Nangia From the Departments of Urology (MLE), and Obstetrics and Gynecology (MLE, RBL, VLB, LMW, AAM), Stanford, California, and Department of Urology, Kansas University School of Medicine (AKN), Kansas City, Kansas
Abbreviations and Acronyms IVF ⫽ in vitro fertilization NSFG ⫽ National Survey of Family Growth Accepted for publication August 13, 2012. * Correspondence: Department of Urology, Stanford University School of Medicine, 300 Pasteur Dr., Stanford, California 94305-5118 (telephone: 650-723-5700; FAX: 650-498-5346; e-mail: [email protected]).
Purpose: An estimated 7 million American couples per year seek infertility care in the United States. A male factor contributes to 50% of cases but it is unclear what proportion of infertile couples undergoes male evaluation. Materials and Methods: We analyzed data from cycles 5 to 7 of the National Survey of Family Growth performed by the Centers for Disease Control to determine the frequency of a male infertility evaluation, and associated reproductive and demographic factors. Results: A total of 25,846 women and 11,067 men were surveyed. Male evaluation was not completed in 18% of couples when the male partner was asked vs 27% when female partners were asked. This corresponds to approximately 370,000 to 860,000 men in the population who were not evaluated at the time of infertility evaluation. Longer infertility duration and white race were associated with increased odds of male infertility evaluation. The male and female samples showed no change in the receipt of male examination with time. Conclusions: Many men from infertile couples do not undergo male evaluation in the United States. Given the potential implications to reproductive goals and male health, further examination of this pattern is warranted. Key Words: testes; ovary; infertility, male; infertility, female; questionnaires
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www.jurology.com
AN estimated 7.3 million American couples seek infertility care in the United States.1 Evaluation revealed that 50% of cases have a female factor, 20% have a male factor and 30% have combined factors.2 Thus, 50% of infertile couples have an element of male factor infertility. The diagnosis and treatment of male infertility can lead to a lower intensity of infertility treatment, possibly associated with improved success and decreased treatment costs.3,4 For this reason the American Society of Reproductive Medicine advocates evaluating the female and male members of infertile couples during standard infertility
evaluation.5,6 Recent data show that IVF cycles are increasing in the United States but other data suggest that male infertility surgical procedures may be decreasing.7 In addition to the impact on family building, male infertility may be associated with increased risks of testis and prostate cancer.8-10 Childless men may be at higher risk for cardiovascular mortality later in life.11 Also, Jensen et al suggested that men with impaired semen parameters are even at higher risk for overall mortality.12 In fact, when examining the medical records of 1,200 men evaluated for infertility at 2 American male reproduc-
0022-5347/13/1893-1030/0 THE JOURNAL OF UROLOGY® © 2013 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
http://dx.doi.org/10.1016/j.juro.2012.08.239 Vol. 189, 1030-1034, March 2013 RESEARCH, INC. Printed in U.S.A.
AND
FREQUENCY OF MALE INFERTILITY EVALUATION
tive health centers, Honig et al found that 1% of all men referred for infertility had a serious medical pathology diagnosed on evaluation, including genetic disorders, endocrine disease and malignancy.13 Importantly, semen analysis alone could not identify men at highest risk for disease. Furthermore, Kolettis and Sabanegh found that 6% of all men referred for infertility harbored a serious disease.14 Given the importance of a male evaluation in the treatment of an infertile couple, we determined the rate of male infertility evaluation in the United States using NSFG data.
MATERIALS AND METHODS Study Population We analyzed data from NSFG cycles 5 (1995), 6 (2002) and 7 (2006 to 2008). A total of 10,847 women, representing the population of the United States living in households, were surveyed in 1995, while 4,928 men and 7,643 women were surveyed in 2002. Cycle 7 was designed as a continuous survey. The first data release, representing 6,139 men and 7,356 women, was analyzed in the current report. The NSFG is a multistage probability sample designed to represent the household population of 15 to 45-year-old American women and men. The survey is done to produce nationally representative data with the ability to combine data sets for analysis. In each household 1 member within the required age range was randomly selected for recruitment. All subjects provided written consent for participation. The survey was available in English and Spanish. The overall survey response rate was 75% to 79%.1,15,16 Institutional review board approval was not required for this secondary analysis of a de-identified national data set.
Variables Outcome. The infertility diagnosis was assessed by several questions administered in the NSFG. Women were asked, “During any of your relationships, have you or your (husband or) partner at the time ever been to a doctor or other medical care provider to talk about ways to help you become pregnant?” For men the survey asked, “Did you or your wife ever go/Have you or your wife ever been/During any of your relationships, have you or your (wife or) partner at the time ever been to a doctor or other medical care provider to talk about ways to help you have a baby together?” Infertility was coded as a dichotomous variable (yes/no). Participants were then asked, “Who was it that had infertility testing? Was it you, him [or her] or both of you?” Women were also queried on the infertility services used. Insurance coverage during infertility pursuits was also queried. Men were asked about the infertility services used. The diagnosis of a sperm problem or varicocele was also asked. Given that reproductive options for nonheterosexual respondents are often driven by sexual orientation, only heterosexual participants were included in the current
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analysis. Sexual orientation data were only available on cycles 6 and 7. Exposure. Demographic and socioeconomic characteristics were analyzed to assess associations with fertility pursuit. Potential mediating and confounding variables were selected a priori based on items in the literature found to be associated with infertility. Variables analyzed included age (less than 30, 30 to 39 and 40 years or greater), marital status (dichotomous, that is yes/no), selfreported race/ethnicity (white, black, Hispanic or other), educational attainment (categorical, including less than high school, high school/general education diploma or more than high school) and income level (dichotomous, including less vs greater than $75,000). Because only female surveys queried about the date of initial infertility services use, age and marital status at evaluation were only definitely known for women. Data analysis. Relationships between male infertility evaluation and survey sociodemographic characteristics or period were determined using chi-square analysis. We developed a multivariable logistic regression model to assess the relationship with male infertility evaluation. Given that it was sometimes difficult to determine when the evaluation began, several sociodemographic variables can change. Thus, analysis was performed using the male and female samples but only respondent characteristics were analyzed. All analyses accounted for the complex survey design of the NSFG. All tests were 2 sided with p ⬍0.05 considered statistically significant. All calculations were performed using STATA® 10.
RESULTS Male Sample In the most recent male sample (cycle 7) approximately 8.0% of respondents indicated they had used infertility services, representing approximately 4.1 million men in the American population. When analyzing data on cycles 6 and 7, 51.9% of the men who had used infertility services indicated who in the relationship had undergone fertility testing. Of these respondents 18% indicated that only the female partner was evaluated and 8% indicated that only the male partner was evaluated. There was no difference in the reported rates of male and female evaluation from 2002 to 2008 (p ⫽ 0.55). In the most recent cycle approximately 370,000 of the men from infertile couples reported that they did not undergo infertility evaluation, while 110,000 of their partners were not evaluated for infertility (see table). Supplementary table 1 (jurology.com) lists socioeconomic characteristics of the men in the sample who provided data on infertility evaluation. Older men and those who lived in more highly populated areas were more likely to undergo infertility evaluation. Also, trends suggested that greater educational attainment and income also increased the
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FREQUENCY OF MALE INFERTILITY EVALUATION
Fertility evaluations reported by respondents to NSFG cycles 5 to 7 Female*
1995: Female Male Female 2002: Female Male Female 2006: Female Male Female Overall: Female Male Female
Male*
No. Pts (%)
Count ⫻ 10 (95% CI)
No. Pts (%)
Count ⫻ 104 (95% CI)
⫹ male
125 (27.4) 57 (12.6) 271 (60.0)
70 (56–84) 32 (23–41) 150 (140–170)
⫹ male
76 (24.7) 27 (8.0) 197 (67.4)
69 (50–88) 22 (12–32) 190 (160–220)
22 (18.9) 11 (9.5) 68 (71.6)
36 (20–53) 18 (5.4–31) 137 (91–184)
⫹ male
86 (30.2) 29 (12.3) 191 (57.6)
86 (52–120) 35 (16–54) 160 (130–200)
26 (16.7) 16 (5.1) 118 (78.2)
37 (16–58) 11 (4.1–19) 174 (126–221)
⫹ male
287 (27.4) 113 (10.9) 659 (61.7)
220 (180–270) 89 (66–110) 500 (450–560)
48 (17.7) 27 (7.2) 186 (75.1)
73 (47–100) 30 (15–44) 311 (250–372)
4
* Percents account for complex survey design in which certain groups were over sampled to obtain adequate subjects for analysis and counts represent weighted population sizes.
likelihood of male infertility evaluation. On multivariable modeling after adjusting for age, income, education, Metropolitan Statistical Area status and race, only nonwhite ethnicity was significantly associated with a lower likelihood of male evaluation (OR 0.34, 95% CI 0.12– 0.96). There were no significant differences in male infertility evaluation based on treatment (supplementary table 2, jurology.com). In contrast, men with sperm problems were more likely to undergo infertility evaluation (p ⬍0.01). Men who reported a varicocele diagnosis also reported male infertility evaluation. Overall, 14% and 5% of men who reported using infertility services also reported sperm problems and varicocele, respectively. Of those who reported male evaluation 31% also reported sperm problems and 10% reported varicocele. To help assess the respondent definition of male infertility evaluation, we examined men from couples that had last visited a clinic for infertility services within the last 12 months. We determined which of these men had reported infertility evaluation as well as testicular examination within the last 12 months. Of the men who reported a history of male evaluation 81% also reported testicular examination in the last 12 months. Female Sample In the cycle 7 female sample approximately 9.4% of respondents indicated that they had used infertility services, representing approximately 5 million women. When analyzing data on cycles 6 and 7, 56.5% of those women who had used infertility services indicated who in the relationship had undergone fertility testing, including 27% who indicated that only the female partner was evaluated and 10%
who reported that only the male was evaluated. There were no differences in the reported rate of male or female evaluation from 1995 to 2008 (p ⫽ 0.49). In cycle 7 approximately 350,000 women from infertile couples reported that they did not undergo infertility evaluation, while 860,000 of their partners did not (see table). Supplementary table 2 (jurology.com) lists socioeconomic characteristics of the women in the sample who provided data on infertility evaluation. Couples with a white female partner were more likely to undergo male evaluation. In addition, longer infertility duration for the couple increased the likelihood of male evaluation. On multivariable modeling after adjusting for age, income, education, Metropolitan Statistical Area status and infertility duration only infertility duration increased the odds of male evaluation. Compared to couples with less than 12 months of infertility, those with 12 to 23 months (OR 4.33, 95% CI 1.84 –10.21) and 24 months or greater (OR 8.08, 95% CI 2.87–22.78) of infertility had significantly higher odds of male evaluation. When examining infertility treatment, couples that used medication, intrauterine insemination or IVF were more likely to undergo male evaluation (supplementary table 2, jurology.com). Fewer men from couples that used donor sperm were evaluated than those that used male partner sperm. In all 5 couples that used donor sperm but did not undergo male evaluation the male partner had undergone prior vasectomy.
DISCUSSION The current study shows that infertile couples do not undergo male evaluation 18% to 27% of the time.
FREQUENCY OF MALE INFERTILITY EVALUATION
This corresponds to between 370,000 and 860,000 men from infertile couples who did not undergo male evaluation. Indeed, most studies estimate a 15% incidence of infertility and yet only 8% of couples undergo evaluation.17 Current American Society of Reproductive Medicine guidelines advocate the evaluation of each partner during infertility assessment.5,6 The current report indicates the low rate of a complete evaluation of both members of an infertile couple. Prior research indicated that sociodemographic indicators, such as income, education and race, are associated with the intensity and duration of infertility service use.18-21 While unadjusted analysis suggested possible relationships with age, race, income and education, our study shows that after multivariable adjustment only race was significantly associated with male evaluation. The reason for the association is uncertain but it may reflect cultural biases in regard to fertility, as is also seen in varied use of surgical sterilization among races.22 In addition, socioeconomic influences could also explain the etiology even if it is not captured adequately in the NSFG. In the female sample infertility duration was most associated with a couple undergoing male evaluation, suggesting that as unmet reproductive goals persist, the couple explores all possible explanations. In fact, other data support that male evaluation is often explored after other reproductive interventions have been attempted, which has hampered recruitment for trials aimed at male infertility.23 Any delay in male evaluation may lead to delayed treatment and resultant increased maternal age. Women who receive advice on fertility without knowledge of male fertility have incomplete data. Evaluation of and treatment for male infertility can improve fertility outcomes by lowering treatment costs and allowing some couples to avoid assisted reproductive technology. Indeed, studies show that vasectomy reversal represents a more cost-effective option than IVF.4 In addition, studies suggest that surgical varicocelectomy can lower treatment costs compared to those of primary assisted reproductive technologies.4,24 Cayan et al noted that varicocelectomy can lead to improved semen parameters, qualifying couples for a lower level of assisted reproductive technology.3 In addition to cost savings, growing evidence suggests that the reproductive and overall health of the offspring conceived using IVF may be compromised.25,26 It remains uncertain whether the etiology of adverse offspring health effects is related to the technology or to the inherent infertility of the parents. Nevertheless, a reasoned approach to the evaluation and treatment of male infertility is clearly warranted.
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Expanding research also suggests that aberrations in reproductive fitness may be a harbinger of disease in men. Indeed, 1% to 6% of men evaluated for infertility have significant medical pathology, including malignancy, even when they have a socalled normal semen analysis.13,14 Moreover, male infertility is often associated with depression and erectile dysfunction.27,28 Investigators also found that impaired semen production or male infertility is associated with testis cancer and high grade prostate cancer years after infertility evaluation.8,9 Importantly, recent studies linked semen quality and fatherhood with cardiovascular and overall mortality.11,12 With the growing understanding of the link between male infertility and male health, it is imperative that all men from infertile couples undergo complete evaluation. While the focus of our report is on men, notably 8% to 12% of women underwent no evaluation for infertility. Similar to their male counterparts, some causes of infertility may have serious health implications for women. For example, primary ovarian insufficiency is associated with early onset osteopenia, increased total mortality and increased mortality due to ischemic heart disease.29 Moreover, the pregnancy outcome may also be compromised if conditions that affect fertility as well as pregnancy outcome, eg uterine cavity abnormalities, are not treated before conception. Interestingly, male and female participants reported different rates of no male evaluation (18% vs 27%). While the reason for the discrepancy is not clear, it may be related to recall bias. Indeed, only 51% of men and 56.5% of women who used infertility services reported who was evaluated. Moreover, since only 1 member per household completed the survey, recollections may have been incomplete without the partner. In addition, the definition of a male evaluation in the NSFG is uncertain. While respondents were asked who underwent evaluation, no criteria were applied to define a proper male evaluation. Whether semen analysis alone or a complete history, or physical or laboratory evaluation was performed is not known. Indeed, 20% of the men who reported male evaluation in the last year had not had a testicular examination during that period, which would certainly represent a complete examination. Thus, we may underestimate the number of men who failed to receive male evaluation, defined as a complete medical history and physical examination, semen analysis and indicated blood tests. Other important limitations warrant mention. The NSFG is a cross-sectional study that surveys participants at a single time point, often several years after the use of infertility services. While race
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remains constant, other variables could conceivably change with time, such as educational level or income. Such misreporting would likely occur randomly, leading to regression to the mean and favoring the null hypothesis. Nevertheless, the current
report suggests that many men from infertile couples do not undergo male evaluation. In conclusion, given the potential implications to reproductive goals, and male and offspring health, further examination of this pattern is warranted.
REFERENCES 1. Chandra A, Martinez GM, Mosher WD, et al: Fertility, family planning, and reproductive health of U.S. women: data from the 2002 National Survey of Family Growth. National Center for Health Statistics. Vital Health Stat 23 2005; 25: 1. 2. Thonneau P, Marchand S, Tallec A et al: Incidence and main causes of infertility in a resident population (1,850,000) of three French regions (1988 –1989). Human Reprod 1991; 6: 811. 3. Cayan S, Erdemir F, Ozbey I et al: Can varicocelectomy significantly change the way couples use assisted reproductive technologies? J Urol 2002; 167: 1749. 4. Meng MV, Greene KL and Turek PJ: Surgery or assisted reproduction? A decision analysis of treatment costs in male infertility. J Urol 2005; 174: 1926. 5. Practice Committee of American Society for Reproductive Medicine: Optimal evaluation of the infertile female. Fertil Steril, suppl., 2006; 86: S264. 6. Male Infertility Best Practice Policy Committee of the American Urological Association and Practice Committee of the American Society for Reproductive Medicine: Report on optimal evaluation of the infertile male. Fertil Steril, suppl., 2006; 86: S202.
10. Walsh TJ, Croughan MS, Schembri M et al: Increased risk of testicular germ cell cancer among infertile men. Arch Intern Med 2009; 169: 351.
20. Eisenberg ML, Smith JF, Millstein SG et al: Predictors of not pursuing infertility treatment after an infertility diagnosis: examination of a prospective U.S. cohort. Fertil Steril 2010; 94: 2369.
11. Eisenberg ML, Park Y, Hollenbeck AR et al: Fatherhood and the risk of cardiovascular mortality in the NIH-AARP Diet and Health Study. Hum Reprod 2011; 26: 3479.
21. Smith JF, Eisenberg ML, Glidden D et al: Socioeconomic disparities in the use and success of fertility treatments: analysis of data from a prospective cohort in the United States. Fertil Steril 2011; 96: 95.
12. Jensen TK, Jacobsen R, Christensen K et al: Good semen quality and life expectancy: a cohort study of 43,277 men. Am J Epidemiol 2009; 170: 559. 13. Honig SC, Lipshultz LI and Jarow J: Significant medical pathology uncovered by a comprehensive male infertility evaluation. Fertil Steril 1994; 62: 1028. 14. Kolettis PN and Sabanegh ES: Significant medical pathology discovered during a male infertility evaluation. J Urol 2001; 166: 178. 15. Abma JC, Chandra A, Mosher WD et al: Fertility, family planning, and women’s health: new data from the 1995 National Survey of Family Growth. Vital Health Stat 23 1997; 19: 1. 16. Chandra A, Mosher WD, Copen C et al: Sexual behavior, sexual attraction, and sexual identity in the United States: data from the 2006 –2008 National Survey of Family Growth. Hyattsville: National Center for Health Statistics 2011; p36.
7. Ketefian A, Hu J, Bartolucci AA et al: Fifteen-year trend in the use of male reproductive surgery: analysis of the Healthcare Cost and Utilization Project data. BJU Int 2011; 107: 1118.
17. Chandra A and Stephen EH: Infertility service use among U.S. women: 1995 and 2002. Fertil Steril 2010; 93: 725.
8. Walsh TJ, Schembri M, Turek PJ et al: Increased risk of high-grade prostate cancer among infertile men. Cancer 2010; 116: 2140.
18. Farley Ordovensky Staniec J and Webb NJ: Utilization of infertility services: how much does money matter? Health Serv Res 2007; 42: 971.
9. Jacobsen R, Bostofte E, Engholm G et al: Risk of testicular cancer in men with abnormal semen characteristics: cohort study. BMJ 2000; 321: 789.
19. Anderson JE, Farr SL, Jamieson DJ et al: Infertility services reported by men in the United States: national survey data. Fertil Steril 2009; 91: 2466.
22. Eisenberg ML, Henderson JT, Amory JK et al: Racial differences in vasectomy utilization in the United States: data from the national survey of family growth. Urology 2009; 74: 1020. 23. Trussell JC, Christman GM, Ohl DA et al: Recruitment challenges of a multicenter randomized controlled varicocelectomy trial. Fertil Steril 2011; 96: 1299. 24. Schlegel PN: Is assisted reproduction the optimal treatment for varicocele-associated male infertility? A cost-effectiveness analysis. Urology 1997; 49: 83. 25. Kallen B, Finnstrom O, Lindam A et al: Cancer risk in children and young adults conceived by in vitro fertilization. Pediatrics 2010; 126: 270. 26. Jensen TK, Jorgensen N, Asklund C et al: Fertility treatment and reproductive health of male offspring: a study of 1,925 young men from the general population. Am J Epidemiol 2007; 165: 583. 27. Smith JF, Walsh TJ, Shindel AW et al: Sexual, marital, and social impact of a man’s perceived infertility diagnosis. J Sex Med 2009; 6: 2505. 28. Shindel AW, Nelson CJ, Naughton CK et al: Sexual function and quality of life in the male partner of infertile couples: prevalence and correlates of dysfunction. J Urol 2008; 179: 1056. 29. Nelson LM: Clinical practice. Primary ovarian insufficiency. N Engl J Med 2009; 360: 606.
Abbreviations and Acronyms IVF ⫽ in vitro fertilization NSFG ⫽ National Survey of Family Growth Accepted for publication August 13, 2012. * Correspondence: Department of Urology, Stanford University School of Medicine, 300 Pasteur Dr., Stanford, California 94305-5118 (telephone: 650-723-5700; FAX: 650-498-5346; e-mail: [email protected]).
Purpose: An estimated 7 million American couples per year seek infertility care in the United States. A male factor contributes to 50% of cases but it is unclear what proportion of infertile couples undergoes male evaluation. Materials and Methods: We analyzed data from cycles 5 to 7 of the National Survey of Family Growth performed by the Centers for Disease Control to determine the frequency of a male infertility evaluation, and associated reproductive and demographic factors. Results: A total of 25,846 women and 11,067 men were surveyed. Male evaluation was not completed in 18% of couples when the male partner was asked vs 27% when female partners were asked. This corresponds to approximately 370,000 to 860,000 men in the population who were not evaluated at the time of infertility evaluation. Longer infertility duration and white race were associated with increased odds of male infertility evaluation. The male and female samples showed no change in the receipt of male examination with time. Conclusions: Many men from infertile couples do not undergo male evaluation in the United States. Given the potential implications to reproductive goals and male health, further examination of this pattern is warranted. Key Words: testes; ovary; infertility, male; infertility, female; questionnaires
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www.jurology.com
AN estimated 7.3 million American couples seek infertility care in the United States.1 Evaluation revealed that 50% of cases have a female factor, 20% have a male factor and 30% have combined factors.2 Thus, 50% of infertile couples have an element of male factor infertility. The diagnosis and treatment of male infertility can lead to a lower intensity of infertility treatment, possibly associated with improved success and decreased treatment costs.3,4 For this reason the American Society of Reproductive Medicine advocates evaluating the female and male members of infertile couples during standard infertility
evaluation.5,6 Recent data show that IVF cycles are increasing in the United States but other data suggest that male infertility surgical procedures may be decreasing.7 In addition to the impact on family building, male infertility may be associated with increased risks of testis and prostate cancer.8-10 Childless men may be at higher risk for cardiovascular mortality later in life.11 Also, Jensen et al suggested that men with impaired semen parameters are even at higher risk for overall mortality.12 In fact, when examining the medical records of 1,200 men evaluated for infertility at 2 American male reproduc-
0022-5347/13/1893-1030/0 THE JOURNAL OF UROLOGY® © 2013 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
http://dx.doi.org/10.1016/j.juro.2012.08.239 Vol. 189, 1030-1034, March 2013 RESEARCH, INC. Printed in U.S.A.
AND
FREQUENCY OF MALE INFERTILITY EVALUATION
tive health centers, Honig et al found that 1% of all men referred for infertility had a serious medical pathology diagnosed on evaluation, including genetic disorders, endocrine disease and malignancy.13 Importantly, semen analysis alone could not identify men at highest risk for disease. Furthermore, Kolettis and Sabanegh found that 6% of all men referred for infertility harbored a serious disease.14 Given the importance of a male evaluation in the treatment of an infertile couple, we determined the rate of male infertility evaluation in the United States using NSFG data.
MATERIALS AND METHODS Study Population We analyzed data from NSFG cycles 5 (1995), 6 (2002) and 7 (2006 to 2008). A total of 10,847 women, representing the population of the United States living in households, were surveyed in 1995, while 4,928 men and 7,643 women were surveyed in 2002. Cycle 7 was designed as a continuous survey. The first data release, representing 6,139 men and 7,356 women, was analyzed in the current report. The NSFG is a multistage probability sample designed to represent the household population of 15 to 45-year-old American women and men. The survey is done to produce nationally representative data with the ability to combine data sets for analysis. In each household 1 member within the required age range was randomly selected for recruitment. All subjects provided written consent for participation. The survey was available in English and Spanish. The overall survey response rate was 75% to 79%.1,15,16 Institutional review board approval was not required for this secondary analysis of a de-identified national data set.
Variables Outcome. The infertility diagnosis was assessed by several questions administered in the NSFG. Women were asked, “During any of your relationships, have you or your (husband or) partner at the time ever been to a doctor or other medical care provider to talk about ways to help you become pregnant?” For men the survey asked, “Did you or your wife ever go/Have you or your wife ever been/During any of your relationships, have you or your (wife or) partner at the time ever been to a doctor or other medical care provider to talk about ways to help you have a baby together?” Infertility was coded as a dichotomous variable (yes/no). Participants were then asked, “Who was it that had infertility testing? Was it you, him [or her] or both of you?” Women were also queried on the infertility services used. Insurance coverage during infertility pursuits was also queried. Men were asked about the infertility services used. The diagnosis of a sperm problem or varicocele was also asked. Given that reproductive options for nonheterosexual respondents are often driven by sexual orientation, only heterosexual participants were included in the current
1031
analysis. Sexual orientation data were only available on cycles 6 and 7. Exposure. Demographic and socioeconomic characteristics were analyzed to assess associations with fertility pursuit. Potential mediating and confounding variables were selected a priori based on items in the literature found to be associated with infertility. Variables analyzed included age (less than 30, 30 to 39 and 40 years or greater), marital status (dichotomous, that is yes/no), selfreported race/ethnicity (white, black, Hispanic or other), educational attainment (categorical, including less than high school, high school/general education diploma or more than high school) and income level (dichotomous, including less vs greater than $75,000). Because only female surveys queried about the date of initial infertility services use, age and marital status at evaluation were only definitely known for women. Data analysis. Relationships between male infertility evaluation and survey sociodemographic characteristics or period were determined using chi-square analysis. We developed a multivariable logistic regression model to assess the relationship with male infertility evaluation. Given that it was sometimes difficult to determine when the evaluation began, several sociodemographic variables can change. Thus, analysis was performed using the male and female samples but only respondent characteristics were analyzed. All analyses accounted for the complex survey design of the NSFG. All tests were 2 sided with p ⬍0.05 considered statistically significant. All calculations were performed using STATA® 10.
RESULTS Male Sample In the most recent male sample (cycle 7) approximately 8.0% of respondents indicated they had used infertility services, representing approximately 4.1 million men in the American population. When analyzing data on cycles 6 and 7, 51.9% of the men who had used infertility services indicated who in the relationship had undergone fertility testing. Of these respondents 18% indicated that only the female partner was evaluated and 8% indicated that only the male partner was evaluated. There was no difference in the reported rates of male and female evaluation from 2002 to 2008 (p ⫽ 0.55). In the most recent cycle approximately 370,000 of the men from infertile couples reported that they did not undergo infertility evaluation, while 110,000 of their partners were not evaluated for infertility (see table). Supplementary table 1 (jurology.com) lists socioeconomic characteristics of the men in the sample who provided data on infertility evaluation. Older men and those who lived in more highly populated areas were more likely to undergo infertility evaluation. Also, trends suggested that greater educational attainment and income also increased the
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FREQUENCY OF MALE INFERTILITY EVALUATION
Fertility evaluations reported by respondents to NSFG cycles 5 to 7 Female*
1995: Female Male Female 2002: Female Male Female 2006: Female Male Female Overall: Female Male Female
Male*
No. Pts (%)
Count ⫻ 10 (95% CI)
No. Pts (%)
Count ⫻ 104 (95% CI)
⫹ male
125 (27.4) 57 (12.6) 271 (60.0)
70 (56–84) 32 (23–41) 150 (140–170)
⫹ male
76 (24.7) 27 (8.0) 197 (67.4)
69 (50–88) 22 (12–32) 190 (160–220)
22 (18.9) 11 (9.5) 68 (71.6)
36 (20–53) 18 (5.4–31) 137 (91–184)
⫹ male
86 (30.2) 29 (12.3) 191 (57.6)
86 (52–120) 35 (16–54) 160 (130–200)
26 (16.7) 16 (5.1) 118 (78.2)
37 (16–58) 11 (4.1–19) 174 (126–221)
⫹ male
287 (27.4) 113 (10.9) 659 (61.7)
220 (180–270) 89 (66–110) 500 (450–560)
48 (17.7) 27 (7.2) 186 (75.1)
73 (47–100) 30 (15–44) 311 (250–372)
4
* Percents account for complex survey design in which certain groups were over sampled to obtain adequate subjects for analysis and counts represent weighted population sizes.
likelihood of male infertility evaluation. On multivariable modeling after adjusting for age, income, education, Metropolitan Statistical Area status and race, only nonwhite ethnicity was significantly associated with a lower likelihood of male evaluation (OR 0.34, 95% CI 0.12– 0.96). There were no significant differences in male infertility evaluation based on treatment (supplementary table 2, jurology.com). In contrast, men with sperm problems were more likely to undergo infertility evaluation (p ⬍0.01). Men who reported a varicocele diagnosis also reported male infertility evaluation. Overall, 14% and 5% of men who reported using infertility services also reported sperm problems and varicocele, respectively. Of those who reported male evaluation 31% also reported sperm problems and 10% reported varicocele. To help assess the respondent definition of male infertility evaluation, we examined men from couples that had last visited a clinic for infertility services within the last 12 months. We determined which of these men had reported infertility evaluation as well as testicular examination within the last 12 months. Of the men who reported a history of male evaluation 81% also reported testicular examination in the last 12 months. Female Sample In the cycle 7 female sample approximately 9.4% of respondents indicated that they had used infertility services, representing approximately 5 million women. When analyzing data on cycles 6 and 7, 56.5% of those women who had used infertility services indicated who in the relationship had undergone fertility testing, including 27% who indicated that only the female partner was evaluated and 10%
who reported that only the male was evaluated. There were no differences in the reported rate of male or female evaluation from 1995 to 2008 (p ⫽ 0.49). In cycle 7 approximately 350,000 women from infertile couples reported that they did not undergo infertility evaluation, while 860,000 of their partners did not (see table). Supplementary table 2 (jurology.com) lists socioeconomic characteristics of the women in the sample who provided data on infertility evaluation. Couples with a white female partner were more likely to undergo male evaluation. In addition, longer infertility duration for the couple increased the likelihood of male evaluation. On multivariable modeling after adjusting for age, income, education, Metropolitan Statistical Area status and infertility duration only infertility duration increased the odds of male evaluation. Compared to couples with less than 12 months of infertility, those with 12 to 23 months (OR 4.33, 95% CI 1.84 –10.21) and 24 months or greater (OR 8.08, 95% CI 2.87–22.78) of infertility had significantly higher odds of male evaluation. When examining infertility treatment, couples that used medication, intrauterine insemination or IVF were more likely to undergo male evaluation (supplementary table 2, jurology.com). Fewer men from couples that used donor sperm were evaluated than those that used male partner sperm. In all 5 couples that used donor sperm but did not undergo male evaluation the male partner had undergone prior vasectomy.
DISCUSSION The current study shows that infertile couples do not undergo male evaluation 18% to 27% of the time.
FREQUENCY OF MALE INFERTILITY EVALUATION
This corresponds to between 370,000 and 860,000 men from infertile couples who did not undergo male evaluation. Indeed, most studies estimate a 15% incidence of infertility and yet only 8% of couples undergo evaluation.17 Current American Society of Reproductive Medicine guidelines advocate the evaluation of each partner during infertility assessment.5,6 The current report indicates the low rate of a complete evaluation of both members of an infertile couple. Prior research indicated that sociodemographic indicators, such as income, education and race, are associated with the intensity and duration of infertility service use.18-21 While unadjusted analysis suggested possible relationships with age, race, income and education, our study shows that after multivariable adjustment only race was significantly associated with male evaluation. The reason for the association is uncertain but it may reflect cultural biases in regard to fertility, as is also seen in varied use of surgical sterilization among races.22 In addition, socioeconomic influences could also explain the etiology even if it is not captured adequately in the NSFG. In the female sample infertility duration was most associated with a couple undergoing male evaluation, suggesting that as unmet reproductive goals persist, the couple explores all possible explanations. In fact, other data support that male evaluation is often explored after other reproductive interventions have been attempted, which has hampered recruitment for trials aimed at male infertility.23 Any delay in male evaluation may lead to delayed treatment and resultant increased maternal age. Women who receive advice on fertility without knowledge of male fertility have incomplete data. Evaluation of and treatment for male infertility can improve fertility outcomes by lowering treatment costs and allowing some couples to avoid assisted reproductive technology. Indeed, studies show that vasectomy reversal represents a more cost-effective option than IVF.4 In addition, studies suggest that surgical varicocelectomy can lower treatment costs compared to those of primary assisted reproductive technologies.4,24 Cayan et al noted that varicocelectomy can lead to improved semen parameters, qualifying couples for a lower level of assisted reproductive technology.3 In addition to cost savings, growing evidence suggests that the reproductive and overall health of the offspring conceived using IVF may be compromised.25,26 It remains uncertain whether the etiology of adverse offspring health effects is related to the technology or to the inherent infertility of the parents. Nevertheless, a reasoned approach to the evaluation and treatment of male infertility is clearly warranted.
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Expanding research also suggests that aberrations in reproductive fitness may be a harbinger of disease in men. Indeed, 1% to 6% of men evaluated for infertility have significant medical pathology, including malignancy, even when they have a socalled normal semen analysis.13,14 Moreover, male infertility is often associated with depression and erectile dysfunction.27,28 Investigators also found that impaired semen production or male infertility is associated with testis cancer and high grade prostate cancer years after infertility evaluation.8,9 Importantly, recent studies linked semen quality and fatherhood with cardiovascular and overall mortality.11,12 With the growing understanding of the link between male infertility and male health, it is imperative that all men from infertile couples undergo complete evaluation. While the focus of our report is on men, notably 8% to 12% of women underwent no evaluation for infertility. Similar to their male counterparts, some causes of infertility may have serious health implications for women. For example, primary ovarian insufficiency is associated with early onset osteopenia, increased total mortality and increased mortality due to ischemic heart disease.29 Moreover, the pregnancy outcome may also be compromised if conditions that affect fertility as well as pregnancy outcome, eg uterine cavity abnormalities, are not treated before conception. Interestingly, male and female participants reported different rates of no male evaluation (18% vs 27%). While the reason for the discrepancy is not clear, it may be related to recall bias. Indeed, only 51% of men and 56.5% of women who used infertility services reported who was evaluated. Moreover, since only 1 member per household completed the survey, recollections may have been incomplete without the partner. In addition, the definition of a male evaluation in the NSFG is uncertain. While respondents were asked who underwent evaluation, no criteria were applied to define a proper male evaluation. Whether semen analysis alone or a complete history, or physical or laboratory evaluation was performed is not known. Indeed, 20% of the men who reported male evaluation in the last year had not had a testicular examination during that period, which would certainly represent a complete examination. Thus, we may underestimate the number of men who failed to receive male evaluation, defined as a complete medical history and physical examination, semen analysis and indicated blood tests. Other important limitations warrant mention. The NSFG is a cross-sectional study that surveys participants at a single time point, often several years after the use of infertility services. While race
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FREQUENCY OF MALE INFERTILITY EVALUATION
remains constant, other variables could conceivably change with time, such as educational level or income. Such misreporting would likely occur randomly, leading to regression to the mean and favoring the null hypothesis. Nevertheless, the current
report suggests that many men from infertile couples do not undergo male evaluation. In conclusion, given the potential implications to reproductive goals, and male and offspring health, further examination of this pattern is warranted.
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