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Five Tests to Identify the Cause of IVF Implantation Failure

Written in Partnership with HRC Fertility, July 23, 2015

Recurrent IVF failure is a real challenge for patients and their doctors. However, there are several tests that can help explain the nature of embryo implantation failure and lead to a successful pregnancy. According to Dr. Michael A. Feinman, a fertility doctor with HRC Fertility, a uterine evaluation should be done prior to an IVF cycle, and it’s important to look into the other potential causes of implantation failure after two failed IVF cycles.

Uterine Evaluation/Hysterosalpingogram (HSG)
“The evaluation of the uterus clearly should be done before the first IVF cycle,” 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, Feinman explains.

Sperm DNA Fragmentation Test
Another test that has gained interest is the DNA fragmentation assay, which looks at the integrity of DNA in the sperm, Feinman says. If the assay is abnormally high ( a high level of DNA fragmentation), it will result in lower implantation rates -- as well as lower fertilization rates and higher miscarriage rates. Men with normal semen analysis results can have abnormal DNA results.

Endometrial Biopsy Test for Implantation Markers
Since the 1990s there have been a series of endometrial biopsy tests that look at implantation markers to determine if the lining of the uterus (endometrium) is receptive to implantation. The newest generation is the Endometrial Receptivity Assay (ERA) biopsy. “The nice thing about this is the technology uses genetic markers rather than biochemical markers,” 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 it’s 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.

Preimplantation Genetic Diagnosis (PGD)
Because the vast majority of embryos are abnormal, PGD is helpful in addressing the cause of implantation failure. With PGD, embryos are biopsied to determine whether they are chromosomally normal. Only normal embryos are transferred back into the uterus.

“I don’t think in the 21st century for women under 40 that a suitable solution to IVF failure is put in more embryos. PGD is a lot more logical approach than multiple embryo transfer,” Feinman says.

He usually incorporates PGD along with some of the other tests on an individualized basis.

Immunologic Tests
Immunologic tests are controversial and there is a lack of consensus on whether they should be used, Feinman explains. It has been hard to prove that testing and subsequent treatments affect outcomes.

The theory behind these tests is that the immune system causes implantation failure. “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 PGD tested embryos,” he 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.” But when appropriate, Feinman offers a limited battery of tests to address this possible problem.

In summary, Feinman says that the above tests should be considered after two failed IVF cycles. “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.”


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