The couple married when they were 23 years old. For the next 10 years, they devoted themselves to their careers, moving around the country and earning doctorates. When they both secured jobs at a university, they decided it was time to start a family.
Except they couldn't.
When the couple sought out medical advice, a doctor showed the husband test results: He was not producing any sperm.
The news sent him zigzagging across the country, searching for the right physician to help him with his infertility. In the meantime, he felt under a great deal of pressure and lost interest in sex.
Finally, the couple ended up at the office of Johns Hopkins University urologist Pravin Rao, who confirmed the problem: a case of mumps the man had contracted as a child in India had damaged his ability to produce sperm. Although he was infertile, a new technique might be able to help.
"For any man, it ultimately takes just one sperm to fertilize an egg," Rao said. "However, he didn't even have one sperm. He had azoospermia, meaning there were no sperm in the ejaculate. In this case, this was due to a factory or production problem, as opposed to a blockage."
Couples are considered infertile if they are unable to conceive after having unprotected sex for one year, or six months if the woman is older than 35. According to the American Society for Reproductive Medicine, about 12 percent of couples in the United States, or 7.3 million couples, fall into this category. In about 40 percent of those cases, the problem is with the man.
Male infertility can be caused by such general health conditions as obesity and cancer as well as by problems including an obstruction in the ejaculatory ducts, a hormonal imbalance and genetic abnormalities. Also, childhood diseases such as the mumps, and sexually transmitted infections such as chlamydia and gonorrhea can cause genital-tract scarring that obstructs the flow of sperm.
There is an ongoing debate over whether sperm counts are going down worldwide. Some studies suggest rates are declining, but others point to inconsistency in data collection and standards.
"Sperm counts do appear to be falling," said Paul Turek, a San Francisco urologist who writes a popular blog that addresses male infertility. "But we are fully the men our grandfathers were. Women may be getting pregnant as efficiently as they did, but with fewer sperm."
In the best of scenarios, a man deposits millions of sperm at the base of a woman's cervix during ejaculation, and the sperm swim their way through her cervix, uterus and fallopian tubes just in time for one of them to fertilize an egg.
The production of sperm and testosterone begins when a boy reaches puberty and continues well into his 80s. Women, on the other hand, release the highest-quality eggs when they are young and stop altogether at menopause.
"Men always are producing sperm unless something happens in life," said Stuart Moss, program director for male reproductive health at the Eunice Kennedy Shriver National Institute of Child Health and Human Development, part of the National Institutes of Health. "Sperm are constantly being produced, a thousand sperm per second."
When doctors examine semen samples under a microscope, they look at the shape and size of sperm, counting them and assessing how many are swimming and how well. Normal sperm have oval heads and long tails. Normal sperm concentration is about 20 million per milliliter of semen. A low count is fewer than 15 to 20 million sperm in a milliliter of semen.
Motility — the ability to move proficiently — is key for sperm to reach their destination, an egg. As for sperm shape, scientists aren't certain how that might affect fertility. "The scientific idea is that the sperm that look 'perfect' are the ones that contain the best genetic package and are best equipped to fertilize an egg and create an embryo," said Juddson Chason, a urologist in Annapolis who specializes in male infertility. But, he said, data don't consistently support that notion.
Sperm are temperature-sensitive, and scientists believe testicles reside outside the body's core to keep them cool, said Peter Schlegel, chair of the department of urology at the Weill Medical College of Cornell University in New York.
"Testicles move to adjust their temperature," meaning they shrink in toward the body when they are cold and move away from the body when they are warm, he said. "The type of underwear you wear is not important," he said.
Sitting in a sauna or exercising intensely for more than 90 minutes a day, on the other hand, may affect sperm production temporarily, though the disruption "may last months, as sperm production takes months," Schlegel said.
Eating fruit and vegetables and taking vitamins such as folic acid and Vitamin E every day may help boost sperm production, though studies have been contradictory, he said.
"Human males have relatively lousy sperm production compared to other mammals," he said, and they "are more sensitive to environmental influences." Among those influences are smoking, drug use, significant weight issues, extreme exposure to toxins and childhood illnesses such as mumps.
"I ask about reproductive history, prior relationships and a history of conceiving," said Robert Brannigan, an associate professor in urology at the Northwestern University Feinberg School of Medicine in Chicago. "If the man has had a fever or a systemic illness, that could lead to a sharp drop in sperm production. I want a good understanding of his medical background and any behaviors that could adversely affect sperm production, such as use of anabolic steroids or testosterone replacement therapy, both of which can suppress sperm production."
According to some studies, sperm analysis can be a snapshot of the man's overall health. "Men should have a biomarker of their health [in the way that] periods and cycles can be for women," Turek said. "The semen analysis suffices as that male biomarker."
For example, he said, a low sperm count might indicate testicular cancer or prostate cancer. "I diagnose these conditions daily in my practice as part of male fertility evaluations. Making sure that the man is healthy is paramount to being a doctor and, when a man is systemically ill, fertility is the first thing to go," Turek said.
Male infertility also can be caused by structural deficiencies such as missing or deformed vas deferens, the tubes that carry sperm from the testes to the urethra during ejaculations. These are the tubes that are tied off during a vasectomy.
If the vas deferens are missing, the testicles continue to produce sperm, which eventually die off and are absorbed by the body. These tubes cannot be replaced. "You can't make an artificial tube," said Chason, and "these patients need assisted reproduction" using sperm that has been surgically removed.
Diabetes can damage the nerves needed to produce an ejaculation. Sometimes, the ejaculatory ducts connecting to the vas deverens are blocked, though these sometimes can be opened surgically. If the testicles didn't properly descend into the scrotum during fetal development, a man may not ejaculate large numbers of high-quality sperm, Chason said.
Some infertility is caused by a dilated vein that forces blood to pool or flow backward into the scrotum, raising the temperature inside the testicles, which can impede sperm production. Surgery can help here as well.
Insufficient testosterone production can also reduce sperm production. The pituitary gland regulates how much testosterone the testicles make. Anabolic steroids and testosterone replacement therapy can interrupt the natural production of sperm. The infertility drug Clomid can be effective in recalibrating the male's testosterone level, Chason said.
For some men, genetics is the issue. A small percentage of men are born with an extra X chromosome. This is called Klinefelter syndrome, where a man "instead of XY, he is XXY," which may result in his producing sperm early in life but then not later, said Moss, who has been researching male reproductive health for 30 years.
As much as doctors and scientists now understand about the causes of male infertility, in as many as 50 to 60 percent of cases there is no obvious explanation, he said.
As for Rao's patient at Johns Hopkins, mumps was the likeliest explanation since it is a known risk factor for sterility and he had not been vaccinated against the disease when he fell ill at age 11 in India. (In the United States, infants are routinely vaccinated against mumps.) About 25 percent of men who have had mumps experience swollen testicles because of the disease, and in 10 to 15 percent of these cases there may be some effect on fertility, according to Rao.
"As a child I had the mumps and then basically my testicles failed," the man said, speaking on condition of anonymity to preserve his privacy. "It's not reversible."
But Roa told him surgery might help. "Men with azoospermia may still be producing small amounts of sperm," Rao said, and it is now possible to extract some sperm from their testicles.
The two-hour surgery, called micro TESE, or micro-dissection testicular sperm extraction, has been used for more than 10 years and is successful in an estimated 50 to 60 percent of cases, depending on the issues involved.
The extracted sperm are united with eggs through in vitro fertilization and any resulting embryos are implanted in a woman's womb.
"Once we had the first procedure done and the doctors found some sperm, that gave us hope," Rao's patient said. "Now we are a little stressed again with the IVF [which was performed in June]. There is limited amount of sperm, so if that doesn't work, we are back to square one. My wife is emotionally attached to kids and wants her own."
Rao was able to harvest four vials from the man, and each vial is usually enough for one IVF treatment. "Once we have obtained sperm . . . the success rate is largely related to the female partner's age and reproductive health," he said. "On average, most couples will have success after two to three cycles of IVF."