Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis:  Recurrent pregnancy loss (RPL).
Treatment:  Biopsy, oocyte polar body or embryo blastomere, microtechnique (for pre-implantation genetic screening).

The health plan denied the Biopsy, oocyte polar body or embryo blastomere, microtechnique (for pre-implantation genetic screening).  The determination was upheld.

The patient is an adult female with two miscarriages, one from trisomy 15, the other unknown. She is undergoing IVF, and the plan is for preimplantation genetic screening for aneuploidy (PGT-A).

There is no scientific evidence to support that this technology will improve outcomes and the take-home baby rate.

According to the ACOG, PGS differs from preimplantation genetic diagnosis for single gene disorders and was introduced for the detection of chromosomal aneuploidy. 

Nonrandomized studies of preimplantation genetic screening in women with advanced maternal age suggested improved implantation rates and decreased spontaneous abortion rates but did not document an improvement in live birth rates.  A study of women with recurrent miscarriages found no evidence of benefit of preimplantation genetic screening in women of any age.  There have now been two randomized trials for women older than 35 years comparing IVF with and without preimplantation genetic screening for aneuploidy.  Neither study provides support for preimplantation genetic screening in women older than 35 years, and one study suggests lowered live birth rates, possibly due to the impact of the biopsy on the embryo's ability to implant.

PGT-A was formerly called PGS. The goal of PGT-A is to identify embryos with de novo aneuploidy, including subchromosomal deletions and additions (duplications), in embryos of couples presumed to be chromosomally normal.  Theoretically, avoiding transfer of these embryos will reduce the risk of miscarriage and complications related to pregnancy failure and improve the probability of conceiving a viable pregnancy.

Older women are at higher risk of having an aneuploid embryo, so PGT-A in this population can help select a euploid embryo for single-embryo transfer (eSET) and increase the efficiency of IVF.  Since aneuploid embryos that have little chance of implanting or developing are discarded with PGT-A, the delivery rate per transfer is higher than with transfer of untested embryos.

Randomized trials using contemporary IVF and PGT techniques in patients with recurrent aneuploid pregnancy losses have not been performed.  Although some observational studies have reported that RPL patients who underwent PGT-A had pregnancy rates comparable to those in control populations without RPL, the probability of subsequent live birth in patients with RPL without intervention is already high, approaching 70 percent; thus, these studies do not prove the benefit of PGT-A in management of RPL.  It is theoretically possible that PGT-A may reduce the probability of miscarriage in patients with RPL due to aneuploidy and reduce the potential sequelae of recurrent miscarriage; however, there is no evidence that PGT-A will increase the eventual take-home baby rate.

According to the ASRM and the SART, the value of PGT-A as a screening test for IVF patients has yet to be determined.  Many studies demonstrate higher birth rates after aneuploidy testing and eSET, suggesting the potential for this testing to decrease the risk of multiple gestations, though these studies have important limitations.

In review of the current literature and the medical record, the patient is planning to undergo IVF with PGT-A due to recurrent pregnancy loss and a known loss with trisomy 15.  The literature reports that there is no data to support the use of preimplantation genetic testing for aneuploidy for recurrent pregnancy loss, as there is not any evidence that this technology will increase the take-home baby rate.  Therefore, this technology would be considered under investigation and not medically appropriate.