Louisville Medicine Volume 67, Issue 4 | Page 24

UNDERSTANDING INFERTILITY (continued from page 21) National IVF success rates, 2016 (from SART). ture applications involve uterine transplants, mitochondrial transfers and in vitro gametogenesis. Genome editing via CRISPR-Cas9 may soon be on the horizon, though each of these methods remains in early stages of research and development at this time. Over 263,000 IVF cycles were performed in the United States in 2016. Year after year, treatment success rates are steadily increasing but remain far from perfect. Our most significant recent clinical advances in IVF treatment relate to applications of genetic profiling of embryos and the endometrium in transfer planning. Blastocyst trophectoderm (the outer layer of the blastocyst) biopsy with next generation sequencing is the current standard for preimplantation genetic testing (PGT) of embryos. Essentially, we take a small sample of cells from the outer layer of the embryo, the part that will later develop into the placenta, and screen them for euploidy. Rates of euploidy vary by age, and are roughly estimated as follows (by age strata): <35, 55%; 35-37, 48%; 38-40, 35%; 41-42, 23%; >42, 15%. Multiple randomized controlled trials have demonstrated significant improvements in live birth rates in women transferring screened embryos compared to unscreened, but a number of important questions remain unanswered, including how to manage the new- ly-recognized phenomenon of mosaicism, where both euploid and aneuploid cells are detected from a single biopsy. PGT has also been instrumental in reducing the rate of multiple gestation from IVF, as current guidelines recommend eSET whenever genetic screening has been performed. Implantation rates of euploid embryos are generally reassuring, even among women of advanced reproductive age. When euploid (or otherwise highly-graded) embryos fail to implant, new research 22 LOUISVILLE MEDICINE has suggested that a subgroup of these patients may suffer from a unique type of endometrial dysfunction. We generally transfer blastocysts back to the uterus based on hormonal landmarks that mimic the natural physiology of conception, anticipating a window of receptivity after about five or six days of progesterone exposure when the endometrium should be most fa- vorable to implantation. However, genetic profiling of endometrial biopsies taken during the traditional window of receptivity has revealed that some women may have a displaced timeline for optimal transfer, and modification of treatment protocols to accommodate these variations in individual physiology may lead to improved rates of successful implantation. Stud- ies in women with recurrent implantation failure of high-quality embryos have shown subsequent pregnan- cy rates exceeding 60% when a personalized embryo transfer is performed based on individualized markers of endometrial receptivity, which has highlighted the importance of synchrony between the embryo and endometrium during IVF transfer procedures. The improved efficiencies of IVF treatment over recent years have made it an increasingly-valuable tool for the modern reproductive medicine physician, but many challenges still remain, including systematic issues. Notably, only 16 states currently have an insur- ance mandate for infertility coverage, and in others (like Kentucky), benefits are commonly limited or excluded with the resultant out- of-pocket costs commonly presenting a significant barrier to care. Physicians, patients and advocates are working within the health care system to improve access to care, but progress remains slow, particularly since many employers, insurers and policymakers are continuing to view IVF as a “luxury” or “elective” service. We have introduced several bills in the Kentucky legislature in attempts to expand insurance coverage for fertility services, but they have failed to gain traction thus far. Of note, HB-87 introduced in the 2019 session would have specifically excluded coverage for IVF treatment though included other treatments for infertility; it was not passed out of committee. Nevertheless, IVF remains distinguished as one of medicine’s greatest accomplishments, and it will certainly endure as an indispensable resource for patients struggling to safely and successfully achieve their reproductive goals. Dr. Hunter is the Practice Director of the Kentucky Fertility Institute.