Sperm Und Drang

The sud­den rise in male in­fer­til­ity is a scary na­tional cri­sis, and we can’t blame it on Trump—or can we?

Newsweek - - NEWS - by Bryan Walsh

HAGAI LEVINE DOESN’T SCARE EAS­ILY. THE HE­BREW UNIVER­SITY PUB­LIC HEALTH

re­searcher is the for­mer chief epi­demi­ol­o­gist for the Is­rael De­fense Forces, which means he’s ac­quainted with dan­ger and risk in a way most of his aca­demic coun­ter­parts aren’t. So when he raises doubts about the fu­ture of the hu­man race, it’s worth lis­ten­ing. To­gether with Shanna Swan, a pro­fes­sor of en­vi­ron­men­tal medicine and pub­lic health at the Ic­ahn School of Medicine at Mount Si­nai, Levine authored a ma­jor new anal­y­sis that tracked male sperm lev­els over the past few decades, and what he found fright­ened him. “Re­pro­duc­tion may be the most im­por­tant func­tion of any species,” says Levine. “Some­thing is very wrong with men.”

That's some­thing you may not be used to hear­ing. It takes a man and a woman—or at least a sperm and an egg—to cre­ate life, but women bear the med­i­cal and psy­cho­log­i­cal bur­den of try­ing to get—and stay—preg­nant. It is women whose life­style choices are end­lessly dis­sected for their sup­posed im­pact on fer­til­ity, and women who hear the omi­nous tick of the bi­o­log­i­cal clock. Women are bom­barded with fer­til­ity di­ets, spe­cial fer­til­ity-boost­ing yoga prac­tices and all the fer­til­ity apps they can fit on their phone. They are the tar­gets of a fer­til­ity in­dus­try ex­pected to be val­ued at more than $21 bil­lion glob­ally by 2020. Even the Cen­ters for Dis­ease Con­trol and Preven­tion fix­ates on women, track­ing in­fer­til­ity in the U.S. by tal­ly­ing the num­ber of sup­pos­edly in­fer­tile women. “It is as if the en­tire med­i­cal realm is shaped to cater to women’s in­fer­til­ity and women’s bod­ies,” says Lib­erty Barnes, a so­ci­ol­o­gist and the au­thor of Con­ceiv­ing Mas­culin­ity: Male In­fer­til­ity, Medicine, and Iden­tity. “For men, there’s just noth­ing there.”

That ab­sence might be un­der­stand­able if women were solely re­spon­si­ble for the suc­cess of a preg­nancy. But they’re not. Ac­cord­ing to the Amer­i­can So­ci­ety for Re­pro­duc­tive Medicine, the male part­ner is ei­ther the sole or con­tribut­ing cause in about 40 per­cent of in­fer­til­ity cases. Past in­fec­tions, med­i­cal con­di­tions, hor­monal im­bal­ances and more can cause what is known as male fac­tor in­fer­til­ity. Men even have their ver­sion of a bi­o­log­i­cal clock. Be­gin­ning around the mid-30s, fer­til­ity grad­u­ally de­grades, and while most men pro­duce sperm to their dy­ing day, those past 40 who help con­ceive have a greater risk of pass­ing on ge­netic ab­nor­mal­i­ties to their chil­dren, in­clud­ing autism. “Men are a huge part of this prob­lem,” says Bar­bara Col­lura, the pres­i­dent and CEO of Re­solve: the Na­tional In­fer­til­ity As­so­ci­a­tion.

Star­tling new ev­i­dence sug­gests male in­fer­til­ity may be much worse than it ap­pears. Ac­cord­ing to Levine and Swan’s work, sperm lev­els—the most im­por­tant mea­sure­ment of male fer­til­ity— are de­clin­ing through­out much of the world, in­clud­ing the U.S. The re­port, pub­lished in July, re­viewed thou­sands of stud­ies and con­cluded that sperm con­cen­tra­tion fell 59.3 per­cent in Western coun­tries be­tween 1973 and 2011. Four decades ago, the av­er­age Western man had a sperm con­cen­tra­tion of 99 mil­lion per mil­li­liter. By 2011, that had fallen to 47.1 mil­lion. The plum­met is alarm­ing be­cause sperm con­cen­tra­tions be­low 40 mil­lion per mil­li­liter are con­sid­ered be­low nor­mal and can im­pair fer­til­ity. (The re­searchers found no sig­nif­i­cant de­clines for non-western men, in part be­cause of a lack of qual­ity data, though other stud­ies have found ma­jor drops in coun­tries like China and Ja­pan.) And the de­cline has grown steeper in re­cent years, which means that the cri­sis is deep­en­ing. “This is pretty scary,” says Swan, who has long stud­ied re­pro­duc­tive health. “I think we should be very con­cerned about this trend.”

There have re­ports of de­clin­ing sperm counts be­fore, but they were easy to ig­nore. Re­search has been spotty, us­ing dif­fer­ent method­olo­gies and draw­ing from vary­ing groups, mak­ing it dif­fi­cult to know if de­clines some sci­en­tists ob­served were real, and not a func­tion of mis­count­ing. Skep­tics of the lat­est con­clu­sions coun­tered that the new re­port was a study of many stud­ies—it could only be as good as the work from which it drew. And even if the con­clu­sions of the meta-anal­y­sis are ac­cu­rate, the av­er­age sperm count still leaves most men on the nor­mal side of fer­tile. Just barely.

Yet fer­til­ity rates—live births per woman— have dras­ti­cally de­clined in the same coun­tries with fall­ing sperm counts. That in­cludes the U.S., where fer­til­ity rates hit a record low this year, and where women are no longer bear­ing enough chil­dren to re­place the ex­ist­ing pop­u­la­tion. Women need to av­er­age roughly 2.1 chil­dren—enough to re­place them­selves and their part­ner, with a spare bit to off­set kids who don’t sur­vive to re­pro­duc­tive age—to keep a coun­try’s pop­u­la­tion sta­ble through birth alone. The U.S. is at 1.8 and de­pen­dent on im­mi­gra­tion to keep the pop­u­la­tion grow­ing. So­ci­o­log­i­cal and eco­nomic fac­tors play a role in the chang­ing size of the Amer­i­can fam­ily. Fer­til­ity rates were above the re­place­ment level un­til the 2007 re­ces­sion, then plunged. And de­spite a years-long eco­nomic re­cov­ery, they’re still fall­ing. Pair that with stud­ies show­ing that nearly one in six cou­ples in the U.S. try­ing to get preg­nant can’t do so over the course of a year of un­pro­tected sex—the med­i­cal def­i­ni­tion of in­fer­til­ity—and it’s clear that some­thing be­yond eco­nomic in­se­cu­rity is pre­vent­ing Amer­i­cans from hav­ing as many ba­bies as they want. “When I see birth rates go­ing down, I worry as a fer­til­ity doc­tor that men’s sperm counts are de­clin­ing,” says Harry Fisch, a urol­o­gist at Weill Cor­nell Medicine in New York.

THE MALE PART­NER IS EI­THER THE SOLE OR CON­TRIBUT­ING CAUSE IN ABOUT 40% OF CASE OF IN­FER­TIL­ITY

This would seem to be the mo­ment for the med­i­cal world to throw ev­ery­thing at un­der­stand­ing what is hap­pen­ing, yet re­searchers are forced to rely on less-than-per­fect data be­cause com­pre­hen­sive, lon­gi­tu­di­nal stud­ies have never been done. The irony is that the med­i­cal es­tab­lish­ment has been ac­cused—with rea­son—of ig­nor­ing the needs of women over the years, yet in re­pro­duc­tion it is men whose prob­lems are poorly stud­ied and of­ten misun­der­stood. Some ex­perts even wonder whether an un­con­scious de­sire to ig­nore threats to male fer­til­ity may be tied up in fears over the fu­ture of mas­culin­ity. “Here is di­rect ev­i­dence that that func­tion of re­pro­duc­tion is fail­ing,” says Michael Eisen­berg, a urol­o­gist and an as­so­ci­ate pro­fes­sor at Stan­ford Univer­sity, re­fer­ring to the lat­est sperm-level re­search. “We should try to fig­ure out why that is.”

What we do know tells us a great deal about not only re­pro­duc­tion but also the health of men. Young men may think they're in­vin­ci­ble, but the male re­pro­duc­tive sys­tem is a tem­per­a­men­tal ma­chine. Obe­sity, in­ac­tiv­ity, smok­ing—your ba­sic poor mod­ern life­style—can dra­mat­i­cally re­duce sperm counts, as can ex­po­sure to some en­vi­ron­men­tal tox­ins. Low sperm counts may presage a pre­ma­ture death, even among men in their prime who might seem oth­er­wise healthy. “Sperm count de­cline is the ca­nary in the coal mine,” says Levine. “There is some­thing very wrong in the en­vi­ron­ment.” Which means there may be some­thing very wrong with men.

Why Johnny Can’t Breed

IN 167 7, THE DUTCH DRAPER AND AM­A­TEUR sci­en­tist Antony van Leeuwen­hoek col­lected his se­men im­me­di­ately af­ter hav­ing sex with his wife, ex­am­ined it un­der a mi­cro­scope of his own creation and saw mil­lions of wrig­gling, tiny “an­i­mal­cules” swim­ming in the sem­i­nal fluid. The Dutch­man was the first per­son to ob­serve hu­man sperm cells, though he in­sisted that the sperm alone made an em­bryo that was merely nour­ished by the fe­male egg and ovaries. Van Leeuwen­hoek was sim­ply fol­low­ing the ex­am­ple of clas­si­cal thinkers like Aris­to­tle, who be­lieved fe­male part­ners at most pro­vided a fer­tile bed of soil in which the seed pro­vided by a man could ger­mi­nate and flower into a child. It wouldn’t be un­til the 19th cen­tury that the true roles of

“SPERM COUNT DE­CLINE IS THE CA­NARY IN THE COAL MINE. THERE IS SOME­THING VERY WRONG IN THE EN­VI­RON­MENT."

the sperm and the egg were fi­nally sorted out.

All those wrig­gling “swim­mers” van Leeuwen­hoek saw are what you would see if you mag­ni­fied the sam­ple of a healthy fer­tile man. A sperm cell is built for one thing: mo­tion. Its tor­pedo-like head is a DNA nugget con­tain­ing the 23 chro­mo­somes the male part­ner con­trib­utes to his fu­ture child, con­nected to a long tail that pro­pels the sperm to the egg, run­ning on the cel­lu­lar rocket fuel of the fruc­tose in the se­men. Most sperm will never come close to an egg—while a fer­tile man ejac­u­lates 20 mil­lion to 300 mil­lion sperm per mil­li­liter of se­men, only a few dozen might reach their des­ti­na­tion, and only one can drill through the egg’s mem­brane and achieve con­cep­tion. The chem­i­cal makeup of the vagina is ac­tively hos­tile to sperm, which can only sur­vive be­cause se­men con­tains al­ka­line sub­stances that off­set the acidic en­vi­ron­ment. That’s the para­dox of sperm counts— although one healthy sperm is enough to make a baby, it takes tens of mil­lions of sperm to beat the odds, which means that sig­nif­i­cant de­clines in sperm counts will even­tu­ally de­grade over­all male fer­til­ity. Notes Swan: “Even a rel­a­tively small change in the mean sperm count has a big im­pact on the per­cent­age of men who will be clas­si­fied as in­fer­tile or sub­fer­tile”—mean­ing a re­duced level of fer­til­ity that makes it harder to con­ceive.

The fears about male in­fer­til­ity go be­yond the stuff of dry science. “It’s the viril­ity and fer­til­ity dilemma,” says Sharon Cov­ing­ton, an in­fer­til­ity ther­a­pist in Mary­land. “How a man sees him­self, and how the world sees him as a man, is of­ten tied to his abil­ity to im­preg­nate a woman.” So per­haps it’s not sur­pris­ing that the ar­gu­ment over how much sperm counts are de­clin­ing—if they are de­clin­ing—has been less a cour­te­ous sci­en­tific de­bate than a fe­ro­cious bat­tle that has gone on for more than two decades.

This war be­gan in Den­mark, in 1990, with Dan­ish pe­di­atric en­docri­nol­o­gist Niels Skakke­baek. For years, he had been trou­bled by the rise in tes­tic­u­lar can­cer, as well as an in­crease in the num­ber of boys with mal­formed testes. He thought as­sess­ing sperm qual­ity and quan­tity might give him a clue to what was hap­pen­ing to his pa­tients.

In 1992, Skakke­baek and col­leagues re­viewed all the pub­lished stud­ies of sperm counts from around the world. (Sperm counts are done by tal­ly­ing the num­ber of sperm cells in one mi­cro­liter of se­men and then mul­ti­ply­ing by 10,000 to es­ti­mate the to­tal sperm in a mil­li­liter—not dis­sim­i­lar from the way po­lice try to es­ti­mate the size of a large crowd from a geo­graphic sam­ple.) They cal­cu­lated that the av­er­age sperm count in 1940 was about 113 mil­lion per mil­li­liter of se­men, and that by 1990 it had fallen to 66 mil­lion. In ad­di­tion, they saw a three­fold in­crease in the num­ber of men with a sperm count be­low 20 mil­lion, the point at which in­fer­til­ity be­comes a se­ri­ous risk.

Skakke­baek’s 1992 pa­per raised con­cern about the abil­ity of the hu­man species to con­tinue re­pro­duc­ing it­self, but skep­tics ques­tioned the re­li­a­bil­ity of the sperm stud­ies the anal­y­sis was based on. The stud­ies drew from very dif­fer­ent groups of men of vary­ing age and fer­til­ity. (Sperm count tends to de­cline with age, and men who gave a se­men sam­ple in a visit to a fer­til­ity clinic can rea­son­ably be ex­pected to have a lower count than, say, healthy men se­lected as donors for a sperm bank.) Some sci­en­tists be­lieve older and less pre­cise tech­niques for sperm count­ing may have ar­ti­fi­cially in­flated the sperm lev­els of our fa­thers and

grand­fa­thers, which would make the drop to cur­rent counts ap­pear steeper than it is.

That’s why the new meta-anal­y­sis is so im­por­tant. Swan, Levine and their col­leagues sorted through more than 7,500 peer-re­viewed pa­pers be­fore fo­cus­ing on 185 pa­pers in­volv­ing 43,000 men from around the world. By ex­clud­ing stud­ies be­fore 1973, they cut out some of the less re­li­able mea­sure­ments, and they dis­carded any stud­ies of men with known fer­til­ity com­pli­ca­tions or who were smok­ers, since smok­ing low­ers sperm count. It’s not per­fect, but this ev­i­dence is the best we have, and the con­clu­sions are dis­turb­ing. “The com­mu­nity is com­ing around on this,” says Eisen­berg. “There have been some good coun­ter­ar­gu­ments about sperm-level de­cline, but this pa­per re­ally puts a lot of those ar­gu­ments to bed.”

En­vi­ron­men­tal Cas­tra­tion

PROV­ING THAT SPERM LEV­ELS ARE DROP­PING HAS been dif­fi­cult enough, and teas­ing out the cause is even tougher. Obe­sity, which has risen dra­mat­i­cally in Western coun­tries while sperm counts have sup­pos­edly dropped, is linked to poor se­men qual­ity, as is phys­i­cal in­ac­tiv­ity. A 2013 study of Amer­i­can col­lege stu­dents found that men who ex­er­cised more than 15 hours a week had sperm counts 73 per­cent higher than men who ex­er­cised less than five hours a week. And men who watched 20 or more hours of TV a week had much lower sperm counts than those who watched lit­tle to no TV. Stress is also a risk fac­tor, as is al­co­hol use, which is on an up­swing in the U.S., and drug use, which is in­creas­ing thanks to the opi­oid epi­demic. Some sci­en­tists have the­o­rized that elec­tro­mag­netic fields from de­vices like cell­phones de­grade se­men, lead­ing to weak, im­mo­bile sperm. Even heat can play a role. We know that high tem­per­a­tures can kill sperm, which is why the tes­ti­cles are out­side the body, keep­ing them up to 5.4 de­grees cooler. Re­searchers know that birth rates de­cline nine months af­ter a heat wave, lead­ing some in­fer­til­ity ex­perts to be­lieve that cli­mate change may ac­tu­ally be a fac­tor in sperm count de­cline.

Age also mat­ters. In a re­cent study, Laura Dodge of Beth Is­rael Dea­coness Med­i­cal Cen­ter looked at thou­sands of at­tempts at in vitro fer­til­iza­tion (IVF) per­formed in the Bos­ton area and tried to gauge the im­pact of both male and fe­male age on suc­cess. Fe­male age re­mained the dom­i­nant fac­tor, but male age fac­tored in as well—women un­der the age of 30 with a male part­ner be­tween 40 and 42 were sig­nif­i­cantly less likely to give birth than those whose male part­ner was be­tween 30 and 35. That dove­tails with re­search show­ing that as men age, their sperm suf­fers in­creas­ing num­bers of mu­ta­tions, which can make it slightly more likely their chil­dren will be born with dis­or­ders like autism and schizophre­nia. Older moth­ers may get blamed for in­fer­til­ity, but a new study found that new fa­thers in the U.S. are on av­er­age nearly four years older than they were in 1972, while al­most 9 per­cent of new fa­thers are over 40, dou­ble the per­cent­age from 45 years ago. “We tell men that age is not an is­sue, but now we know that the male bi­o­log­i­cal clock is real,” says Fisch.

So is it sim­ply mod­ern life—obe­sity, in­ac­tiv­ity, stress, cell­phones, older par­ent­hood—that’s driv­ing down sperm lev­els? That’s only the be­gin­ning of an an­swer. To­bacco use def­i­nitely hurts sperm counts, yet smok­ing has fallen sig­nif­i­cantly in the U.S. That’s one rea­son a grow­ing band of re­searchers have come to sus­pect the in­flu­ence of tox­ins in the en­vi­ron­ment—specif­i­cally, en­docrine-dis­rupt­ing chem­i­cals found in com­pounds like bisphe­nol A (BPA) and phtha­lates.

The the­ory is straight­for­ward: These chemi- cals mimic the ef­fect of the fem­i­niz­ing hor­mone es­tro­gen and can in­ter­fere with mas­culin­iz­ing hor­mones like testos­terone. The chem­i­cals, found in many plas­tics through­out the en­vi­ron­ment, may be rewiring the sen­si­tive male re­pro­duc­tive sys­tem, erod­ing sperm qual­ity and quan­tity and even con­tribut­ing to the sort of tes­tic­u­lar dis­or­ders that first alarmed Skakke­baek years ago. The pro­duc­tion of sperm is tightly reg­u­lated by the body’s hor­mones, and so any in­ter­fer­ence with those hor­mones—say, through ex­po­sure to en­docrine-dis­rupt­ing chem­i­cals—could make it­self felt first through dam­age to sperm quan­tity or qual­ity. “You could still have sperm, but [lev­els] might be sig­nif­i­cantly lower than your fa­ther’s,” says Ger­maine Louis, the di­rec­tor and se­nior in­ves­ti­ga­tor at the Eu­nice Kennedy Shriver Na­tional In­sti­tute of Child Health and Hu­man De­vel­op­ment.

Most ev­i­dence for how these chem­i­cals af­fect sperm comes from an­i­mal stud­ies. One in 2011 found that mice who got daily BPA in­jec­tions had lower sperm counts and testos­terone lev­els than mice who got saline in­jec­tions. A star­tling study

MEN WHO EX­ER­CISED MORE THAN 15 HOURS A WEEK HAD SPERM COUNTS 73% HIGHER THAN MEN WHO EX­ER­CISED LESS THAN 5 PER WEEK.

from 2016 of fish in U.S. wildlife refuges in the North­east found that 60 to 100 per­cent of all the male small­mouth bass stud­ied had eggs grow­ing in their testes—a star­tling fem­i­niza­tion—which re­searchers linked to en­docrine dis­rupters in the wa­ters. Other stud­ies have shown that phtha­lates ap­pear to dis­rupt the mas­culin­iza­tion of young lab rats. An­i­mal mod­els aren’t per­fect, but as Univer­sity of Texas tox­i­col­o­gist An­drea Gore notes, “the bi­ol­ogy of re­pro­duc­tion is in­cred­i­bly sim­i­lar in all mam­mals. We are all ver­te­brates, and we have the same re­pro­duc­tive or­gans and pro­cesses that de­velop sim­i­larly with the same hor­mones.”

Sci­en­tists can’t ex­pose hu­mans to en­docrine dis­rupters in an ex­per­i­ment, but re­cent re­search has found as­so­ci­a­tions be­tween ex­po­sure to BPA and phtha­lates in the world, and de­clin­ing sperm counts and male in­fer­til­ity in adults. A 2010 study of Chi­nese fac­tory work­ers by De-kun Li at Kaiser Per­ma­nente found that in­creas­ing lev­els of BPA in urine were sig­nif­i­cantly linked with de­creased sperm count and qual­ity, even among men who were ex­posed to lev­els of BPA com­pa­ra­ble to men in the gen­eral Amer­i­can pop­u­la­tion. An­other study from 2014 fol­lowed about 500 cou­ples try­ing to con­ceive and found that ph­tha­late ex­po­sure among men was tied to re­duced fer­til­ity. These find­ings are all as­so­ci­a­tions, which means that while ex­po­sure to en­docrine dis­rupters is more likely to be found in men suf­fer­ing from re­duced fer­til­ity, it doesn’t mean that the chem­i­cals them­selves are defini­tively the cause. But the stud­ies are stack­ing up. “For some of the en­docrine dis­rupters like phtha­lates, the ba­sic ev­i­dence is strong that they af­fect re­pro­duc­tive health,” says Louis, who car­ried out the phtha­lates study.

Even more con­cern­ing, but harder to prove, is the dam­age en­docrine dis­rupters may be do­ing in utero. As a fe­tus de­vel­ops in a mother’s uterus, it is bar­raged by hor­mones and other chem­i­cals that sculpt de­vel­op­ment. That in­cludes the male re­pro­duc­tive sys­tem—tes­ti­cles are formed in the womb, and although sperm lev­els can be al­tered in adult­hood, they seem to be largely set be­fore a boy is born. That means we could see sperm lev­els con­tinue to de­cline for years, as boys who were ex­posed to en­docrine dis­rupters be­fore birth reach re­pro­duc­tive age and run into prob­lems try­ing to have chil­dren of their own. “This trend hasn’t turned around, and it’s not go­ing

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