Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis:  Recurrent pregnancy loss (RPL).
Issue under review:  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 G2 P0 Ab2 female with a history of recurrent pregnancy loss.  One pregnancy was found to be Trisomy 15, while the other was of unknown ploidy.  The patient consulted a reproductive endocrinologist who has recommended preimplantation genetic testing for aneuploidy (PGT-A) as a treatment.

Since 24 chromosome techniques have become available, there have been few well-designed studies providing Level-I evidence regarding IVF pregnancy outcomes in select populations with these techniques.  Several opinion pieces have discussed advantages and disadvantages of PGT-A.  Other potential advantages and disadvantages exist with PGT-A, though there are limited data to support or refute these.  For example, PGT-A testing may lower the risk of aneuploidy detected during pregnancy or after birth.  Another consideration is that identification and discard of aneuploid embryos could potentially lessen the burden of excess embryos cryopreserved.  Also, identifying euploid embryos may decrease the time to pregnancy by focusing embryo transfer cycles only using euploid embryos to select populations; this may be helpful in older women. 

One RCT in patients aged 38-41 demonstrated improved live-birth rates per cycle with a day 3 single-blastomere biopsy and PGT-A.  Large, prospective, well-controlled studies evaluating the combination of multiple approaches (genomics, time-lapse imaging, transcriptomics, proteomics, metabolomics, etc.) for enhanced embryo selection applicable in a more inclusive IVF population are needed to determine not only the effectiveness, but also the safety and potential risks of these technologies.  

PGT-A will likely be part of a future multidimensional approach to embryo screening and selection.  At present however, there is insufficient evidence to recommend the routine use of blastocyst biopsy with aneuploidy testing in all infertile patients.  Therefore, at this time PGT-A is considered experimental/investigational. 

The ASRM, in its Practice Committee Opinion, states: "The mechanism of first-trimester pregnancy loss is largely due to aneuploidy, providing biologic plausibility for PGT-A.  An analysis of a retrospective cohort study (118 PGT-A vs 188 expectant management) demonstrated similar clinical pregnancy rates and miscarriage rates between the two groups, though time to successful pregnancy was statistically shorter in the expectant-management group (3.0 vs 6.5 months, respectively).  Of the PGT-A cohort, 77% were able to create embryos that were tested, and, of those, 74% had at least one euploid embryo to transfer.  This study is limited by its retrospective design, which makes it difficult to interpret potentially different clinical prognoses for those who did or did not pursue PGT-A.  A prospective study explored the relationship between ovarian reserve in RPL patients and found that in women younger than 38 years, decreased ovarian reserve (defined as a cycle day-3 follicle-stimulating hormone level >10 IU/mL and/or anti-Mullerian hormone <1 ng/mL) resulted in a significantly lower likelihood of having a euploid embryo to transfer compared with women with normal ovarian reserve testing.  These studies can assist in personalizing the counseling for patients considering PGT-A, regarding one's likelihood of successfully obtaining a euploid embryo from the technology.  It is worth noting that the increased rate of aneuploidy with decreased ovarian reserve is likely not unique to the RPL population.  However, to date, the literature has not suggested an improved live-birthrate using PGT-A in RPL patients." 

Therefore, the above services are not medically appropriate.