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As this year marks the 26th birthday of the first test-tube baby, the fight against infertility continues. Approximately 10 percent of Americans in their reproductive years are affected by infertility, according to the American Society for Reproductive Medicine, Birmingham, AL.
However, like most other medical fields, advancements can be charted on nearly a daily basis.
When it comes to trying to determine the source of reproduction problems, clinical laboratory tests like semen analysis and a test of FSH (follicle-stimulating hormone) levels, are considered standbys.
Semen analysis, says Michael Tucker, PhD, director, embryology lab, Fertility Center of Illinois, in Glenview, has become the foundation for testing men after other sperm testing methods were left by the wayside, "because there either is or there is not."
The WHO established the parameters for "normal" semen. According to the standards, sperm density should be >20 million sperm/ml, motility should be >60 percent and morphology should be >60 percent normal forms.
FSH, a blood test, looks at the hormone levels in women. Normal values range from 4-30 U/L or 5-20 micro-international units per milliliter. "If FSH levels are abnormal, that is a very poor prognosis," says Randy Morris, MD, board certified reproductive endocrinologist and associate clinical professor, division of reproductive endocrinology, University of Illinois School of Medicine, Chicago.
While tests like these help in diagnosing fertility problems, it's the advancements in the testing arena that are causing reserved excitement among many in the field.
SCSA Testing
Dr. Tucker said he is perhaps most excited by the prospects the sperm chromatin structure assay (SCSA®) holds for the future. "This is a whole new area of [fertility] testing," he said of the assay that uses a flow cytometer to examine the DNA fragmentation of sperm.
"The clinical data," says Dr. Tucker, "is correlating higher levels of fragmentation with lower rates of implantation."
Currently, SCSA Diagnostics, Brookings, SD, is the only lab approved by CLIA for the SCSA. The lab was founded and is operated by Donald P. Evenson, PhD, HCLD.
Saying he is confident in the results he has found after 15 years of research, Dr. Evenson explained that the SCSA test "looks at the integrity of the DNA, something a sight microscope can't pick up."
In the SCSA test, the cells are stained with a fluorescent dye and then forced through a glass channel suspended in liquid. As the cells pass the laser beam, the dye emits a green color if the sperm have very low levels of fragmented DNA. Sperm that show up as red have moderate to high DNA fragmentation levels. In the SCSA test, 5,000 sperm are measured to determine the extent of DNA fragmentation and the percent of sperm nuclear immaturity.
The DNA Fragmentation Index (DFI) has been developed using SCSA test data and is expressed as the percentage of sperm in a sample with elevated levels of DNA fragmentation. The statistically significant threshold for infertility has been established at >30 percent DFI.
Both SCSA Diagnostics and fertility experts, such as Alan R. Thornhill, PhD, reproductive endocrinology, Mayo Clinic, Rochester, MN, say two tests several months apart are often advised if a high percentage of fragmentation is found, as DNA fragmentation in sperm may be the result of many factors, including, but not limited to, diet, drug use, high fever, smoking and pollution. These exterior influences won't show up for 3-4 months in the sperm and, if addressed, can sometimes reduce the fragmentation levels.
However, Dr. Thornhill cautions, more studies on SCSA must be done before he is convinced of its efficacy. "It can still be argued whether it works," he says.
Generally, tests conducted with a flow cytometer bring to the fertility testing table objective results, he adds. "Many of the other tests are subjective and results vary depending on the technician and the lab. With flow cytometry, you are using an instrument that is calibrated every day. You get much less interassay variation."
The method also allows the number of sperm examined to be increased from 100, as examined in a typical semen analysis, to several thousand. "But that's still a small percentage of the 100 million or so sperm contained in the ejaculate," Dr. Thornhill says.
Because of this, Dr. Thornhill says he is hoping to do a study with Dr. Evenson on SCSA. He is proposing using a homogeneous population of women who have a good chance of getting pregnant, allowing the SCSA score to be fully examined as it relates to the resulting pregnancies.
"I do believe that maybe there is a future," he says, of the testing method.
Other Tests
While SCSA is creating a buzz among the male fertility testing circles, preimplantation genetic diagnosis (PGD) is stirring up its own talk when it comes to testing used during in vitro fertilization procedures.
PGD allows the screening of embryos 3 days after fertilization in an attempt to eliminate the "problematic" embryos and only implant the healthy ones, says Dr. Tucker. The test requires a single cell to be removed from an embryo, which is then analyzed for the proper number of chromosomes. If it is found to be normal, the embryo it was taken from is then placed in the uterus.
PGD was first performed in 1989, but it's been only recently that the testing has become more mainstream. While examination of the testing process continues, Dr. Morris says he is confident that PGD will make its mark. "This is one test where 20 years from now, we'll probably look back and say this really changed the industry," he says.
When it comes to testing women, Dr. Morris says the endometrial function test (EFT®) has shown promising results, "but more studies need to be done."
The EFT was developed by Harvey J. Kliman, MD, a research scientist in the Department of Obstetrics, Gynecology and Reproductive Sciences at the Yale School of Medicine, New Haven, CT. It is designed to determine whether a woman's endometrium is healthy and ready for embryo implantation.
The EFT looks for the biochemical markers cyclin E and p27. According to Dr. Kliman, fertile women express cyclin E in their glands only up to about cycle day 19, while infertile women frequently express cyclin E well after day 19.
Changes in Patients
A shift in testing methods isn't the only change in the industry. "Patients seem to be getting older," says Joni Stehlik, BS, technical supervisor for daily laboratory operations at The Fertility Center of Illinois' embryology lab, Glenview.
Dr. Morris says he, too, has seen that trend. He says when he started in the fertility field 14 years ago, the average age of his female patients was in the early 30s. Today, on average, his female patients are about 38.
"It's not surprising," he says. "As women get more rights, they are attempting pregnancy later in life."
This trend, says Charles H. Koh, MD, obstetrics and gynecology, Columbia St. Mary's, Milwaukee, WI, is creating the impression that more and more people are facing infertility. Instead, he says, the constant business he and his partner, Grace M. Janik, MD, have seen over the last 5 years is due to "more people deferring pregnancy."
The Future of Infertility
While the infertility business remains steady, there is no doubt that advances in testing will continue to make huge impacts on the industry. In fact, at a conference last summer in London, several fertility doctors went so far as to say infertility eventually could be wiped out. But the experts ADVANCE interviewed had mixed reactions to that notion.
Dr. Morris says he strongly disagrees with the idea that infertility will be eliminated. "We always think we are smarter than we are," he says. "The more you learn, the more you realize the less you know."
Others, like Dr. Koh, believe elimination is possible, depending on one's definition. "I believe probably in 10 years time there will be ovarian egg banks like there are sperm banks," he says. "Everyone may be able to one day have a baby; it just won't necessarily be their own genetically."
Fred Licciardi, MD, of New York University's Obstetrics and Gynecology Department, New York, NY, believes the elimination of infertility is near. "Most women who come in now can have a baby. It just happens in different ways," he says. There has been a trend toward greater acceptance of donor eggs used, he added, and eventually technology will be able to take a woman who does not produce eggs and insert her DNA in donor eggs so she can produce her own child.
"That will probably happen," he says. "But it is a slow process with the political situation as it is." If the way is made for a full-scale research effort, Dr. Licciardi says the ability to do such a procedure could be available within 5 years.
Stehlik, however, counters that while "better technologies are being invented every day," there will always be people who feel uncomfortable with infertility treatments. "These people would most likely remain infertile," he says.
Bajeerah Lowe is a former assistant editor of ADVANCE. Assistant editor Pamela Kropf contributed to this article.
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