E.J. Forman

High relative deoxyribonucleic acid content of trophectoderm biopsy adversely affects pregnancy outcomes

OBJECTIVEnTo evaluate the association between relative DNA content of the trophectoderm biopsy and pregnancy outcomes.nnnDESIGNnRetrospective cohort study.nnnSETTINGnAcademic-affiliated private practice.nnnPATIENT(S)nThis study included patients undergoing their first single embryo transfer after trophectoderm biopsy and comprehensive chromosome screening (CCS) at a single center between January 2010 and Februaryxa02014.nnnINTERVENTION(S)nIn phase 1 of the study, a standard curve was developed to estimate the relative DNA content of trophectoderm biopsies. Phase 2 of the study examined reproductive outcomes in patients undergoing single embryo transfer after trophectoderm biopsy and CCS. Samples were divided into quartiles according to their relative DNA content, and clinical outcomes were compared.nnnMAIN OUTCOME MEASURE(S)nChemical pregnancy rate, clinical implantation rate, ongoing pregnancy rate, live birth rate.nnnRESULT(S)nThe quartile of highest relative DNA content had a significantly lower live birth rate when compared with the other three quartiles (relative risk 0.84, 95% confidence interval 0.75-0.95). There was no difference between the quartiles regarding age, body mass index, ovarian response, or endometrial thickness. Among those patients who had a live birth, there was no difference in hCG levels, gestational age at delivery, or birth weight with respect to biopsy DNA content.nnnCONCLUSION(S)nTrophectoderm biopsies with the highest relative DNA content are associated with lower live birth rates after single embryo transfer. Possible explanations for this phenomenon include diminished accuracy of the euploid diagnosis vs. a mechanical impact of the biopsy. Regardless of the cause, the outcomes emphasize the importance of obtaining appropriately sized trophectoderm biopsies for CCS.

DHEA supplementation can result in assay changes which may impact clinical decisions in IVF

Dear Editor, We read with interest Tsui et al.’s letter to the editor regarding DHEA-S interference with progesterone assays in reference to our manuscript. In it, they pointed out that the units for DHEA-S should have been micrograms per deciliter as noted in Fig. 2 of the manuscript. The micrograms per deciliter units should have been used throughout the manuscript and the use of micrograms per milliliter was an error, both in the scientific abstract and in the manuscript. DHEA-S controls from the manufacturer were supplied in micrograms per deciliter units and yielded assay results in the reportable range in micrograms per deciliter. With the proper units of measurement, the DHEA-S levels measured in our patient population, both those taking DHEA supplementation and controls, were within physiological ranges. We appreciate their careful review of the manuscript and appreciate the opportunity to correct this error. The authors repeated the experiment on their Siemens ADVIA Centaur assay and showed an increase in measured progesterone from 0.4 to 1.0 ng/mL which was a similar, but less pronounced, change noted in our manuscript in Fig. 1. There was a greater change noted on the progesterone assay of other platforms. The interactions reported with the corrected units of micrograms per deciliter rather than micrograms per milliliter remain true. Tsui et al.’s experiment lends support to the theory that circulating DHEA-S in women on supplementation may alter serum progesterone levels. Although the interactions may be small in absolute units, when clinical decisions regarding whether to cryopreserve all embryos rather than perform a fresh embryo transfer due to premature progesterone rise are in the balance, slight changes may have a meaningful clinical impact.