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Failed IVF cycle: What’s next?

It’s frustrating to get the “negative beta” call from the IVF coordinator/doctor after taking injections for a few weeks, undergoing egg retrieval, and embryo transfer. Whereas most IVF failures are due to the abnormalities of the embryos transferred, other variables have to be carefully looked at prior to the next attempt.

Both the embryo and the uterine cavity/endometrium have to be in optimal condition, but not necessarily perfect every time for a successful outcome. The uterine cavity may have minor problems or the embryo not in perfect condition under the microscope, but a healthy pregnancy can still be expected. The other way around is also true when everything looks “perfect” and the outcome is negative, which is confusing to most patients and sometimes even to doctors.

The most common reason for a failed IVF cycle is the abnormality of the embryo(s) chromosomally and/or genetically. An embryo is made up of the sperm and the egg, both of which must be normal for a healthy embryo. Most eggs and sperm recovered during the collection process are actually abnormal genetically or chromosomally and interestingly enough this is a normal finding. When sperm are examined under the microscope using the strictest criteria in the IVF lab, only about 10-15% of the sperm are considered “normal looking”. When it comes to the health of the eggs, a maximum of 50% of the eggs are typically normal.

In cases of failed IVF cycles, the next step is to further evaluate egg quantity and quality along with sperm parameters and quality. The goal of the next round of IVF treatment should be to improve egg and sperm quality. This can be done by changing medications, exposure times and sometimes the entire IVF protocol.

Additional testing of egg reserve and sperm quality may be helpful in cases of “unexplained infertility”. A newly developed test called Anti-Mullerian Hormone (AMH) measurement can hint changes in ovarian reserve that may not have been diagnosed by FSH and estrogen levels. Although the best diagnostic test to examine the ovarian reserve is ovarian stimulation, AMH level can still be helpful in determining the next steps.

Sperm quantity can be assessed by a semen analysis, but the quality is typically challenging to measure. Sperm DNA tests (SCSA, Sperm DNA fragmentation index, etc.) may provide helpful information in some cases, although in most couples it does not make a difference in the management. If sperm DNA is severely damaged, then alternatives can be considered, although in most of these cases, sperm quantity is already affected.

The uterus may need further evaluation by hysteroscopy (camera to look inside uterus) to make sure that there are no lesions such as fibroids, polyps or scar tissue. Previous radiographic images may need to be reviewed for presence of small lesions in the cavity or blocked tubes. Lastly, one has to make sure that there are no inflammatory changes in the uterus or immunological challenges that might have prevented implantation of embryos. In conclusion, a comprehensive discussion with the fertility specialist is essential prior to starting another treatment cycle.

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