Trophectoderm biopsy—perhaps not such a benign intervention
Catherine E. Gordon, M.D.
,
Catherine Racowsky, Ph.D.
Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
Article Info
In this issue of Fertility and Sterility, Lu et al. (1) conducted a retrospective cohort study to investigate whether the removal of a few trophectoderm cells during biopsy for preimplantation genetic testing (PGT) was associated with a decrease in serum human chorionic gonadotropin (β-hCG) level 12 days after transfer and/or any adverse perinatal outcomes. Comparison of clinical pregnancies after cryoembryo transfer of biopsied versus nonbiopsied single embryos showed that the biopsy group had statistically significantly lower mean β-hCG levels (703.1 ± 569.6 vs. 809.2 ± 582.0 mIU/mL; P=.004). The authors also noted a lower threshold serum β-hCG level in the biopsy group as compared with the control group for prediction of live birth (368.6 mIU/mL [area under the curve 0.79] vs. 411.5 mIU/mL for the controls). There was no difference in miscarriage rates, live-birth rates, or perinatal outcomes between the two groups.
We applaud the authors for this contribution to the literature. With the ever-increasing use of trophectoderm biopsy for preimplantation genetic testing for aneuploidy (PGT-A), it is important to understand how this invasive manipulation might affect pregnancy outcomes. The questions the authors pose are logical in that we know that β-hCG is secreted by differential syncytiotrophoblasts at the site of implantation, and serum β-hCG levels after embryo transfer are correlated with pregnancy outcome. Although previous studies have shown that implantation and pregnancy rates are similar between biopsied and nonbiopsied embryos (2), the data remain sparse regarding any association between this technology and perinatal outcomes. Any adverse long-term associations to the children born from trophectoderm biopsied embryos are currently unknown.
Many studies have attempted to determine the optimal initial β-hCG levels and threshold values for prediction of successful outcomes after embryo transfer. However, the day of β-hCG measurement and type of assay used have varied greatly between studies. A strength of the study by Lu et al. (1) is that although the cycles were performed over a 2-year period, the same assay platform was used throughout, and all β-hCG measurements were taken on day 12 after embryo transfer. Together, these methodologies allowed an unbiased comparison of the β-hCG values to be made between the unbiopsied and biopsied groups.
Previous investigations have shown that a single β-hCG value for predicting pregnancy outcome may have less value than serial measurements. Therefore, it would have been informative if Lu et al. had compared the trends in β-hCG rise for each of the two groups, derived from at least two measurements. Additionally, despite the observed statistically significant differences in the mean β-hCG values for each group, the standard deviations were large and significantly overlapped, which raises questions regarding the relevance of the authors’ findings to the clinical management of the patient. A much reduced β-hCG value in the biopsy group compared with the control group, combined with similar pregnancy outcomes, would have provided greater assurance to providers that pregnancies with low β-hCG levels after trophectoderm biopsy are still capable of progressing to a live birth. Although the study included more than 800 pregnancies, a larger data set is required to determine whether a lower β-hCG cutoff value predicts a successful pregnancy after trophectoderm biopsy.
We note that there were more programmed embryo transfer cycles in the biopsy group as compared with the control group. Although the authors controlled for this (as well as for other variables) in their generalized linear regression analyses, it remains to be seen whether increased use of a programmed endometrial preparation in the biopsy group had any impact on β-hCG levels.
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