A unique view on male infertility around the globe

Global

Male infertility is a global population health concern. There are an estimated 48·5 million couples with infertility worldwide [3]. In the current study, we calculated rates of male infertility across the globe based on a review of the current literature (Figure 2). Since we do not know the actual rates of infertility, most of the numbers shown are based on self-report, thus cover a wide range. Overall, by examining the available literature and consolidating the information, our data indicates that global rates of male infertility range from 2.5% to 12%.

North America and Europe

North America, Europe and Australia are developed countries, which may explain why rates of infertility are reportedly believed to be more accurate when compared to less developed countries. In North America, 4·5%-6% of males are infertile (Table 1). This number is similar to that of Australia, where 8% of males are infertile and 9% of males over the age of 40 have visited an infertility clinic at some point (Table 1) and Europe, where 7.5% of males are infertile. These numbers are based upon data from the National Health Statistics Report (NHSR) from the CDC National Health Interview Survey, the Australian Institute for Health and Welfare (AIHW), and the European Association of Urology (EAU) guidelines for male infertility [4,10,11]. These three regions of the world were the only organizations with the most accurate reporting of data available. The estimation that 20-30% of infertility is due to a sole male factor helped calculate numbers in the developing world, providing the most conclusive report of male infertility around the world. Quantifying the available information gives us insight into where the greatest need is for further research into underlying etiology and treatment.

When comparing regions with another, Europe reports similar population estimates as the United States, with 15% of European couples and 7.5% of men reported infertile [11]. Olsen and colleagues found that infertility varied across Europe. After 12 months, 51.1%, 43.2%, 37.9%, 19.1%, and 43.2% of couples sought help for infertility in Denmark, Germany, Italy, Poland, and Spain, respectively, with approximately 40% seeking help across the sample [12]. A classical French study completed by Thonneau and colleagues in 1991 examined 1686 infertile couples and found that in a small region of France to find that abnormal infertility was present in males 20% of the time, and present in females 34% of the time, and in both males and females 38% of the time [13]. This region is different from the whole of Europe, and statistics are sparse. However, Sanocka and colleagues state that Poland’s population is considered representative of Eastern Europe [14]. That study stated that 20% of couples are infertile in Poland, and 40-60% of those couples’ cases are due to male factor alone, whereas a more recent study by Bablok and colleagues states that 56% of infertility cases are due to an involved male factor [6,14]. The most interesting part of our manuscript references the fact that all these numbers reported are so different. We conclude that the large varieties in these numbers are largely due to cultural differences. In the United States and Europe, infertility is a problem that men often feel comfortable addressing with their physician. This allows the problem to both get addressed and reported statistically.

Australia

We see that Australia’s rates are similar to those in North America and the United States, at 8-9%; additionally, 40% of infertility cases in Australia are due to male factor involvement (Tables 1 and 3; Figure 1) [10,15]. While the Australian Institute for Health and Welfares (AIHW) statistics data is on males aged 40 and older, the AIHW states that 8% of males have reported trying to have children unsuccessfully and 9% are being evaluated for infertility [10].

Africa and the infertility belt

The rates in North Africa, Sub-Saharan Africa, and Eastern Europe are close to some of the higher percentages of male infertility estimated worldwide (Table 2) [16]. Male factor involvement for Table 2 was calculated using the statistics found by Cates, Farley, and Rowe in 1985 [17]. With the discovery that male infertility is most prevalent throughout this region, this may be where marketing for assisted reproductive therapy, treatment for infection, and efforts for WHO research can be concentrated.

The highest numbers relate to a region known as the “African Infertility Belt,” which stretches east to west across central Africa from Gabon to the United Republic of Tanzania [18]. This region of the world has very high rates of infertility in women, and as men are involved in up to 43% of the problem, the argument follows that male infertility is also high in this region [17,19,20]. Male factor contribution to infertility is also extremely high in the close geographical region of the Middle East [21]. We also noticed that primary infertility rates were much lower than secondary infertility. This may result from the high amount of child marriage and young pregnancy occurring in developing countries, and the later development of sexually transmitted diseases (STDs) and pelvic infections [22]. However, these numbers are of questionable significance due to the scant nature of their collection. Additionally, the population of sub-saharan Africa grows yearly. This does not imply that the rates of male infertility may not be high, but rather that the population may be growing in other ways. Typically, in regions of Africa and other societies, the male is seen as the dominant individual in both the community and the family structure. Therefore, men, especially in Africa and the Middle East do not report their infertility, as they believe it is emasculating to be unable to impregnate a woman. As a result of this, the men in these societies especially tend to blame females for the lack of child and do not get help.

Other diseases

The “African Infertility Belt” also has high rates of STDs such as N. gonnorrhoeae and C. trachomatis, which may have some correlation and relationship with the high rates of infertility in this region of the world [23]. Collet and co-workers discovered that a tubal factor was present in 82.8% of females presenting to infertility clinics and frequently positive endocervical cultures for N. gonorrhoeae and C. trachomatis [23].

Total absolute numbers calculated

We have drawn on the arguments that approximately 50% of cases are due to women, and 20-30% of cases are due to men. The remaining 20-30% of infertility cases is due to a combination of male and female factors. In Table 1, multiple reports state an infertility rate of anywhere from 2.5% to 12% [6,10,11,14,20,21]. Total numbers of infertile men worldwide may amount from 30,625,864 to 30,641,262 (Table 3). This number does not include estimates from Latin America or Asia (the most populous continent on the planet), due to underreporting there. These numbers indicate over 30 million more men and their female counterparts who could benefit from assisted reproductive technology (ART) and treatment for infertility. Additionally, regardless of the lower rates of infertility in North America, Europe, and Australia, these regions should not be neglected in the research for future treatment options. These regions also make up a part of the worldwide infertility phenomenon. While there may be regions of Africa and Asia attracting more urgent attention, this same consideration should be extended globally.

Updated WHO guidelines

In 2010, the WHO changed their guidelines for semen analysis for the diagnosis of the infertile male [24]. In doing so, they established reference values that were much lower than their previous ones, resulting in more men qualifying as “normal” [6]. Now, a man with reference values of greater than 15 million sperm, greater than 5% normal morphology, and 40% progressive motility would be considered normal. [25] With the new guidelines, more men would be considered fertile, while there may be an unnoticed rise in the number of infertile men. Therefore, a recent study involving our group advises caution when interpreting the new WHO reference values because they have not yet been accurately defined to discriminate fertile from infertile men [25].

Limitations of our study

One major limitation of our study is the number of infertile couples who have never participated in intercourse. Following this limitation, we therefore cannot estimate the number of infertile men who have never participated in unprotected sexual intercourse. Additional limitations of any epidemiological study regarding infertility and sexual activity include that the quality of data varies from very poor to very good. Reproductive information is private and couples may not be inclined to be truthful in surveys [26]. Many men may not be willing to participate in semen studies [26]. Another limitation included the difference between one-year infertility rates and the five-year infertility rates reported by Mascarenhas et al. [3]. This difference in rates over a five-year projection may be due to the fact that over five years, the cases of infertility may either resolve, these couples may have found an alternative to traditional conception, or the study could have suffered from attrition. A major limitation of this study is that much of our data are based on WHO studies from the 1900’s and that the definition of a male factor in these studies was not well defined. Male factor infertility was based on both abnormal semen analyses and on associated factors like varicoceles and urogenital infections, and STDs in men with normal semen analyses. In countries with an accurate registration of diseases, the prevalence of both male infertility and male factor leading to couples’ infertility is lower than that in developing countries. Rates from developing countries are more likely due to a problem with definition of male infertility and lack of accurate reporting rather than a true reflection of male infertility in those regions. Finally, the biggest limitation was that we based our calculations on Sharlip et al. and applied these numbers for female infertility to that of men.