UNDERSTANDING INFERTILITY
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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.