Recurrent IVF failure can be devastating for patients and challenging for their doctors. Several tests have been proposed to help identify the causes of embryo implantation failure, and possibly increase the likelihood of achieving a successful pregnancy.
According to Dr. Michael A. Feinman, a fertility doctor with HRC Fertility, a uterine evaluation should be done prior to initiating an IVF cycle, and again after two failed IVF cycles. At the same time, other potential causes of implantation failure should be investigated.
Which Tests Can Help Identify the Cause of My IVF Implantation Failure?
IVF implantation failure can be really frustrating and disheartening, but there are several tests and screenings available that can help pinpoint what the issue may be. Dr. Feinman outlines and explains the various test options below.
Uterine Evaluation/Hysterosalpingogram (HSG)
“The evaluation of the uterus should be done before the first IVF cycle,” Dr. Feinman says. “I still feel the HSG is the test of choice because it’s the only one that adequately looks at the uterus and the fallopian tubes.” A hydrosalpinx (blocked fallopian tube filled with fluid) reduces implantation by 50 percent, so you do need to know the tubal status even when doing IVF, he explains.
Sperm DNA Fragmentation Test
Another test that has gained interest is the sperm DNA fragmentation assay, which looks at the integrity of DNA in the sperm. Some data suggest that if the assay is abnormally high (a high level of DNA fragmentation), lower fertilization rates, lower implantation rates, and higher miscarriage rates might result. Men with normal semen analysis results can have abnormal DNA fragmentation results. While using sperm DNA fragmentation testing to better understand male fertility is gaining significant interest among fertility specialists, its role is not yet clearly defined, and further data is needed to determine the utility of these tests.
Endometrial Receptivity Assay (ERA)
Since the 1990s, a series of tests have been performed on the cells that line the uterine cavity (endometrium) to determine if there are certain chemical or genetic markers that predict the receptivity of the endometrium to implantation. One of these tests is the Endometrial Receptivity Assay (ERA), a test in which a biopsy of the endometrium is performed (typically in a non-treatment cycle), and the expression of hundreds of genes is investigated to determine the receptivity of the uterus to implantation.
It has been suggested that if the gene expression pattern from the ERA test reveals that the endometrium is not receptive on a particular day, it might provide clues as to whether a future embryo transfer should be performed a day earlier or a day later than expected.
“The nice thing about this is the technology uses genetic markers rather than biochemical markers,” Dr. Feinman says, “And it gives a solution.” The gene expression technology can see if the endometrial “implantation window” is open on the correct day of the cycle. If it is not, you can freeze the embryos and transfer them in a protocol that adjusts the number of days of progesterone given prior to the transfer.
“One in five patients have an abnormal biopsy, so it’s certainly a reasonable thing to do if they’ve failed to conceive in a good situation with fresh eggs, before moving on to the frozen transfer,” he says. As the value of the ERA test for improving pregnancy rates has not been proven, please note that this test is not approved for use in all states and is not considered standard of care.
Preimplantation Genetic Testing for Aneuploidy (PGT-A)
*Formerly Preimplantation Genetic Screening—PGS
For many couples, many if not most embryos created in an IVF cycle have an abnormal number of chromosomes. Transfer of abnormal embryos results in failure to conceive, or increased rates of miscarriage and abnormal births. PGT-A is a procedure in which cells are removed from a developing embryo and are tested for chromosome content. Embryos that have a normal complement of chromosomes are selected for embryo transfer, resulting in improved pregnancy rates and reduced miscarriage rates.
“In the 21st century, for women under 40, I don’t think that a suitable solution to IVF failure is to put in more embryos. PGT-A is a lot more of a logical approach than multiple embryo transfer,” Dr. Feinman says. Furthermore, PGT-A improves the ability to achieve pregnancy with single embryos, which reduces the risks related to multiple pregnancy faced by mothers and babies.
Dr. Feinman usually incorporates PGT-A, along with some of the other tests, on an individualized basis. Couples do need to understand, however, that a small amount of error does exist in the technologies used for embryo biopsy and chromosome testing.
Tests for circulating immune cells or proteins are controversial, as data is lacking that the detection of these factors, and proposed treatments for immunologic “abnormalities,” improve clinical outcomes for patients with recurrent implantation failure. Furthermore, these tests are often expensive and not covered by insurance. Therefore, there is no consensus on whether these tests should be performed.
“They might have appropriate value after IVF failure, if everything else has been done and a patient is still not getting pregnant with good quality embryos — particularly with PGT-A tested embryos,” Dr. Feinman says. “I tend to not do immunological testing before a woman has done her first IVF cycle, because it sets up people for over-treatment.”
Dr. Feinman offers a limited battery of tests after two failed IVF cycles. In his opinion, “There’s enough experience and science behind what these tests do to warrant an individualized approach for each couple. I’ve helped people who seemed helpless with these tests and treatments.”
The value of immunologic testing and treatment remains, however, unproven and therefore not the standard of care.
Dr. Daniel E. Stein is the Director of RMA of New York’s Westside office and is Chief of Reproductive Endocrinology at Mount Sinai West Hospital. Dr. Stein has over twenty years of experience as a Reproductive Endocrinologist and fertility specialist and served for eight years as Medical Director of the In Vitro Fertilization program of the former Continuum Reproductive Center before joining RMA of New York. He is board-certified in both obstetrics and gynecology and reproductive endocrinology and infertility.