Cryopreservation and delayed

embryo transfer–assisted
reproductive technology registry
and reporting implications
Kevin J. Doody, M.D.
Center for Assisted Reproduction, Bedford, Texas

Clinics performing assisted reproductive technology (ART) procedures have collected data via registry and publicly reported pregnancy
outcomes for more than 25 years. During this time, the practice of ART has changed considerably with frozen embryo transfer (FET)
procedures contributing an increasing proportion of live births. Cycles initiated with the intent of embryo banking for the purpose
of fertility preservation have been excluded from these public reports, because pregnancy outcomes are not immediately available.
An unintended consequence of the common sense handling of fertility preservation has been that cycles performed with intentional
short-term cryopreservation of all embryos for other indications have also been excluded from the report. Over the last few years, cryo-
preservation with short-term delayed transfer increasingly has been performed for reasons other than fertility preservation. The preg-
nancy outcomes of these cycles are expected within a reasonable time frame and should be transparently reported. The Society for
Assisted Reproductive Technology has collaborated with the Centers for Disease Control and Prevention to ‘‘recapture’’ these cycles
for the public reports. This recapture is done by linking the FET cycles to the stimulation cycles from which the embryos were derived
and by changing the labels of the outcome success metrics. Stimulations using ART, initiated for the purpose of transferring embryos
within 1 year will be included in the report despite any prospective intent to freeze all eggs or embryos. A positive outcome will be
reported when a live birth results from the first embryo transfer following stimulation (‘‘primary
transfer’’). Linkage of ovarian stimulation and egg-retrieval procedures to FET will also allow
development of other success metrics to further benefit fertility patients. (Fertil SterilÒ Use your smartphone
2014;102:27–31. Ó2014 by American Society for Reproductive Medicine.) to scan this QR code
Key Words: Success rates, reporting, assisted reproduction and connect to the
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I
n the United States, efforts to record est group within the American Fertility highly structured system within a
and publicly report assisted repro- Society (now the American Society for decade. This transformation was a
ductive technology (ART) activity Reproductive Medicine [ASRM]) coor- consequence of the passage of the Fed-
began in 1987. This effort tabulated dinated this process with the first of eral Clinic Success Rate and Certifica-
retrospectively collected data forms many annual reports published begin- tion Act (FCSRCA) in 1992. Sponsored
used to record an overall summary of ning in 1988. This special interest group by then-Representative Ron Wyden
in vitro fertilization (IVF) clinic activ- soon became the Society for Assisted (Democrat from Oregon), the statute
ities from cycles performed in 1985 Reproductive Technology (SART) and set out to establish a national public
and 1986 (1). At that time, participation remains affiliated with the ASRM. reporting framework for the clinical
was entirely voluntary but is believed to This initial reporting system outcomes of ART programs offering
have been high (2). An IVF special inter- evolved into a legally required and IVF and egg-donation services (3).
Specifically, the FCSRCA required
Received March 25, 2014; revised April 27, 2014; accepted April 28, 2014; published online June 4, that by 1994, ‘‘each assisted reproduc-
2014.
K.J.D. is on the advisory board of Good Start Genetics, Merck Pharmaceuticals, Ferring Pharmaceuti-
tive technology program shall annually
cals, and Watson Pharmaceuticals; and is on the Speaker Bureau for Merck Pharmaceuticals, report. pregnancy success rates
Ferring Pharmaceuticals, and Watson Pharmaceuticals. achieved by such program’’ through
Reprint requests: Kevin J. Doody, M.D., Center for Assisted Reproduction, 1701 Park Place Ave.,
Bedford, Texas 76022 (E-mail: kevind@embryo.net). the Centers for Disease Control and Pre-
vention (CDC), and that effective in
Fertility and Sterility® Vol. 102, No. 1, July 2014 0015-0282/$36.00
Copyright ©2014 American Society for Reproductive Medicine, Published by Elsevier Inc.
1995, the CDC ‘‘annually publish and
http://dx.doi.org/10.1016/j.fertnstert.2014.04.048 distribute’’ the same data (4). The

VOL. 102 NO. 1 / JULY 2014 27

VIEWS AND REVIEWS
FCSRCA defined two pregnancy success rate calculations to
be annually publicly reported. The first success rate is ob-
tained ‘‘by dividing the number of pregnancies which result
in live births by the number of ovarian stimulation proce-
dures.’’ The second defined success rate is calculated ‘‘by
dividing the number of pregnancies which result in live births
by the number of successful oocyte retrieval procedures.’’
Additionally, the FCSRCA specified that other success rate
definitions could be developed in consultation with appro-
priate consumer and professional organizations. Success
rate calculations for frozen embryo transfer (FET) and donor
egg procedures were developed under this third guideline.
The CDC collaborated with SART to collect this informa-
tion beginning in 1995. In 1997, the CDC submitted to
Congress the first federally mandated annual report (5). The
format of the clinic summary report (CSR) and national sum-
mary report of ART outcomes has remained fundamentally
unchanged since that time. The CDC and SART ART success
reports have since become easily available to the public
over the Internet.
CHANGING TRENDS/EMBRYO BANKING
Although the format of the published outcome report has not
been previously revised, the practice of ART in the United
States has evolved significantly. The first pregnancy after
cryopreservation, thawing, and transfer of a human embryo
was reported in 1983. When the first national results were
tabulated for the 1985/1986 report, seven clinical pregnancies
had resulted from FET (1). This number represented slightly
<1% of the 822 total pregnancies. In 1995 (the first year
that SART collaborated with the CDC to publish outcomes),
1,282 births from cryopreserved embryos were reported (6).
This number represented slightly >10% of the nearly
12,000 deliveries reported. In 2012, the proportion of births
resulting from FET continued to increase, with 15,408 re-
ported by SART. This number accounted for nearly one third
of ART births nationwide.
This increase in proportion of births resulting from em-
bryo cryopreservation has occurred as a result of dramatic im-
provements in laboratory technology (including quality
assurance and vitrification) and is additionally a consequence
of widespread adoption of a strategy to reduce multiple ges-
tations by decreasing the number of embryos that are trans-
ferred when fresh. Initially, cryopreservation with
subsequent FET was viewed merely as a supplement to fresh
transfer. Availability of supernumerary embryos suitable for
cryopreservation was considered a ‘‘bonus.’’ More recently,
however, it has been recognized that in some circumstances
cryopreservation of all fertilized eggs/embryos might be
desirable.
Embryo banking has been the primary strategy for
fertility preservation in women for whom gonadotoxic
chemotherapy is planned. Less commonly, embryo banking
for fertility preservation is also performed at the request of
women who are wishing to delay pregnancy for 1 or more
years, but are concerned regarding the possible impact of
the delay on ultimate fertility. Assisted reproductive technol-
ogy procedures done for the purpose of embryo banking tradi-
28
tionally have been excluded from the national and clinic
summary success reports because pregnancy outcomes are
not expected within the required reporting time frame.
Fertility preservation is not the only widely accepted indi-
cation for cryopreservation of all fertilized eggs/embryos. It has
been suggested that severe ovarian hyperstimulation syndrome
(OHSS) can be nearly eliminated by a strategy that includes
segmentation of the IVF process such that embryo replacement
is avoided during the cycle of ovarian stimulation and egg
retrieval (7). Although cryopreservation of all embryos and
avoidance of a fresh transfer is a well-accepted means of
reducing the risk of OHSS in a patient with an unexpectedly
high response to stimulation, the term ‘‘embryo banking’’
does not generally apply. Embryo banking cycles have been
defined more rigorously by the CDC since 2000 (8). Specifically,
to qualify as ‘‘embryo banking,’’ a cycle must be initiated with
the intent of cryopreserving all embryos for later use. The
designation ‘‘does not apply to cycles initiated with the intent
to transfer embryos but for which all embryos were subse-
quently cryopreserved regardless of the reason’’ (6). The time
frame for ‘‘later use’’ was not defined.
The annual SART Registry report first included a separate
tabulation of embryo banking cycles in 1996 (9). At that time,
only 311 of more than 65,000 cycles carried this designation.
The low percentage remained stable over the next 4 reporting
years. After implementation of the more rigorous definition
requiring prospective intent, the number of embryo banking
cycles significantly declined, even as the overall number of
ART cycles increased. In 2001, only 85 embryo banking cycles
were reported out of a total of 108,130 ART procedures (10).
Over the next decade, embryo banking cycles became
increasingly common for reasons other than fertility preser-
vation. Accumulation of eggs/embryos over multiple cycles
has been suggested as a strategy for managing low responder
patients (11). Preimplantation genetic screening (PGS) with
trophectoderm biopsy is used increasingly by some clinics
despite a requirement for freezing/vitrification of embryos
to allow time for genetic analysis (12). Embryonic/endome-
trial asynchrony might also be handled by cryopreservation
and delayed ET (13, 14).
In contrast to fertility preservation, these embryo banking
cycles are accompanied by the expectation of an immediate or
near-immediate pregnancy outcome. However, because the
rules for reporting banking cycles adopted by SART and the
CDC were geared toward fertility preservation, the outcomes
of these ‘‘other’’ embryo banking cycles have also been
excluded from both the national and clinic summary reports.
In 2012, more than 13% of the 165,955 ART cycles were
excluded from the success reports (15). Although ART cycles
were excluded from the report for other reasons (egg banking,
egg thaw cycles, egg donor cycles without transfer and em-
bryo thaw cycles with no associated ET), embryo banking is
by far the most common reason for reporting exclusion. In
2012, nearly 14,000 excluded cycles were designated as em-
bryo banking, representing 8.2% of the total ART cycles
nationwide. A relatively small number of outlier clinics
have been reported to account for the majority of these
excluded cycles. It is for these outlier clinics that the current
reporting system is most problematic. The exclusion of these
VOL. 102 NO. 1 / JULY 2014

cycles has been criticized as leading to decreased transpar-
ency (16).
Public reporting of health care outcomes is premised on
the tenets of transparency and accountability, with con-
sumers of medical services in mind. The decision to perform
fresh transfer, or alternatively, to ‘‘freeze all,’’ should be
made according to what is ideal for the patient, her preg-
nancy, and her offspring and should not be significantly
influenced by the reporting concerns (17). The Society for As-
sisted Reproductive Technology has identified the need to
distinguish true fertility preservation from ‘‘short-term’’ em-
bryo banking and has collaborated with the CDC to make
changes to data collection to implement a solution that will
abide by both the letter and the spirit of the FCSRCA (18, 19).
The principles of the new report are that [1] Embryo
banking for fertility preservation will continue to be excluded
from the CSR, as there is no immediate expected cycle
outcome; and [2] Cryopreservation of all eggs or embryos
with intent for embryo transfer within 12 months of cycle
start will not be considered the same as embryo banking.
This treatment paradigm is more appropriately referred to
as ‘‘delayed transfer’’ because the intended outcome is
the same as a fresh transfer. It is anticipated that short-term
autologous delayed transfer will in some cases have prospec-
tive intent (e.g., PGS or planned multiple cycles for egg/
embryo accumulation), but additionally it will include
‘‘freeze-all’’ cycles initiated with intent to transfer fresh
(e.g., endometrial receptivity concerns, risk of OHSS, inability
to obtain sperm). Because outcomes from ‘‘delayed transfer’’
cycles are available in a short time frame, they will be
included in the CSR, independent of the intent at the initiation
of the cycle.
An important feature of the data collection is that it will
link all ETs to the cycle(s) from which the embryo(s) originate.
The report ‘‘labels/category titles’’ for autologous (nondonor
egg) cycles will change from ‘‘fresh’’ and ‘‘frozen’’ to ‘‘pri-
mary’’ and ‘‘subsequent’’ to allow linkage of delayed ETs to
cycle starts. Each individual embryo transferred and each
ET procedure will be linked/assigned to the egg-retrieval pro-
cedure(s) from which it was derived.
All cycle starts are included in the denominator of the
outcome report. The outcome of the first ET following stimu-
lation will be included in the numerator of the outcome statis-
tic. This transfer can occur within 1 year of the cycle start or
the following year, if within 12 months of cycle start. The
outcome will be reported in the year of cycle start if possible.
However, if the transfer is significantly delayed, the cycle
start and outcome will in some cases be reported in the year
following. Lack of embryos (or lack of genetically normal em-
bryos following PGS/PGD) available for transfer will result in
a negative outcome for the cycle. Lack of ET within 12 months
of cycle start will result in a negative outcome reported for the
cycle.
The definition of ART delineated in the FCSRCA encom-
passes egg freezing (4); thus, data must be collected, and preg-
nancy outcomes following oocyte cryopreservation must be
appropriately reported. Short-term cryopreservation of eggs
will be handled in exactly the same fashion as short-term
cryopreservation of embryos. The outcome of the first transfer
VOL. 102 NO. 1 / JULY 2014
Fertility and Sterility®
resulting from thawing of eggs, embryos, or a combination of
both will be the reported primary transfer outcome.
It is foreseen that, infrequently, more than one stimula-
tion cycle could be conducted in the same patient with
different designations prior to a primary transfer. A cycle in-
tended to achieve a pregnancy in the short term may be pre-
ceded or followed by a cycle intended for fertility
preservation. Rules have been devised in anticipation of this
occurrence. Any cycle designated as intended for fertility
preservation will be reclassified if the retrieved eggs result
in an ET within the reporting time frame (within 12 months
of cycle start). It is the intention of the SART validation com-
mittee to audit clinics that are outliers. Clinics with a high per-
centage of fertility preservation cycles will have on-site visits
with review of medical records to confirm the prospective
intent of these cycles. Disingenuous designation of fertility
preservation will result in clinic sanction.
REPORTING VIA A ‘‘PATIENT-ANCHORED
APPROACH’’ VS. ‘‘CYCLE-CENTERED’’ METRICS
The emphasis on public reporting of ART cycle outcomes has
numerous negative unintended consequences. The current
cycle-centered approach encourages clinics to maximize the
pregnancy rate per cycle. One of the most effective ways to
do this is through the transfer of multiple embryos. The
many disadvantages and risks of the resulting twin pregnan-
cies and higher-order multiple gestations are well known. It
has been suggested that a cumulative performance metric,
termed ‘‘total reproductive potential’’ (TRP), might result in
increased use of single ET and hence better obstetrical and
neonatal outcomes (20). Although the term has been used in
varying ways, the general concept is that this statistic would
reflect the cumulative live-birth rate per initiated cycle.
Indeed, it can be argued that this statistic fully satisfies the
wording of the FCSRCA primary definition of success (live
births per stimulation procedure), as the initial definition
did not consider separately the outcome of the subsequent
FETs.
This metric would be calculated by counting in the
numerator as a success the first live birth following ovarian
stimulation. Thus, it makes no difference whether the success
is achieved in the first ET after stimulation or any subsequent
frozen transfer. No single success metric is perfect. Even FET
cycles carry associated burdens of expense and effort. Addi-
tionally, an unintended consequence of this TRP metric could
be more-aggressive ovarian stimulation (with attendant risk
of OHSS) for the purpose of maximizing egg numbers. The
SART Registry Committee believes the benefits of reporting
a TRP statistic outweigh the potential disadvantages. Fortu-
nately, the above reporting paradigm shift, whereby data
collection allows linkage of FETs to stimulation cycles will
greatly facilitate the implementation of reporting of a TRP
outcome measure.
The precise definition and calculation of TRP needs care-
ful consideration. One concern is that the primary ET and sub-
sequent transfer(s) can occur in different calendar/reporting
years. As a result, the reported TRP will consistently change
(increase) after the initial publication of outcomes for a given
29
VIEWS AND REVIEWS
reporting year. One possible option for handling this concern
is to publish a preliminary TRP initially, with a secondary
‘‘finalization’’ the following year. Very few additional preg-
nancies are anticipated to occur later than 12 months after
the primary transfer. Another issue to be addressed through
registry rules is the recognition that FETs can involve eggs/
embryos collected via various retrieval procedures (and
different calendar years). Although SART believes that the
consumer of fertility services would benefit from inclusion
of a TRP statistic in the report, specific details with regard
to implementation have not yet been finalized.
The SART plans also include the reporting of outcomes
‘‘per patient.’’ This metric would reflect success per individual
patient cumulatively over all stimulation cycles/fresh and
frozen transfers within a clinic. This metric is useful to the
patient that might desire estimation of the ultimate chance
of live birth with ART treatment. Reporting of this statistic
would encourage adoption of strategies to reduce patient
‘‘drop-out.’’ These strategies might include less-intensive
stimulation/monitoring and lower patient cost. Although
this outcome metric is likely to be greatly appreciated by
patients, the handling of treatment cycles occurring over
multiple calendar years needs to be considered and carefully
addressed to avoid underestimation of the likelihood of suc-
cess. Additionally, reporting of outcomes per patient may
enhance access to care for those patients with a low chance
of pregnancy per cycle that are willing to undergo multiple
ART attempts.
In conclusion, the federal government and SART have
decided that public report cards should complement
nonpublic efforts to improve patient safety and the quality
of care. This noble goal is more likely to be achieved if reports
are accurate, meaningful, and current. Information should be
verified and selectively audited to correct mistakes. External
data review and on-site validation is required to prevent
‘‘gaming the system.’’ Public report cards are not going
away. Indeed, they are likely to become more common and
will cover individual physicians as well as institutions/clinics
(21). The FCSRCA was intended to allow patients to estimate
the chance of success with ART treatment within a specific
clinic. This law will likely remain unchanged, but administra-
tive rules will be added/modified to more appropriately apply
the legislated intent.
The above considerations notwithstanding, well-
intentioned public reporting of ART clinical outcomes is
accompanied by error and unintended consequences.
Although the ART reporting system was not intended to be
used by the public to directly compare outcomes among cen-
ters, it is widely used that way. Commercial attempts have
even been made to ‘‘rank’’ ART programs using publicly re-
ported data. Such ranking is inappropriate given that reports
have made no effort to stratify the ‘‘severity’’ of infertility by
criteria other than age (3). Variation in clinic-specific case
mix is well recognized. Furthermore, until now, some ART cy-
cles involving very short-term cryopreservation of eggs and
or embryos have been excluded from the public clinic-
specific reports. Lag in appropriate handling of these ‘‘delayed
transfer’’ cycles has resulted in decreased transparency for
consumers of fertility services.
30
A minority of clinics have high numbers of ART stimula-
tions that are not included in the current public report because
they are categorized as ‘‘embryo banking.’’ Most of these cycles
should be included in the clinic summary report because preg-
nancy outcomes are expected within a short time frame. In
recognition of that fact, plans are in place to improve the public
reporting system. Increased transparency will be achieved by
reporting the outcome of all stimulations conducted with the
intent of achieving pregnancy in the short term.
The most common reasons for cryopreservation and de-
layed transfer are PGD/PGS, egg/embryo accumulation for
poor responders and embryo/endometrial asynchrony. Other
possible benefits of delayed transfer may also be considered.
Cryopreservation of all embryos retrieved should be per-
formed if indicated without concern of public reporting of
outcomes. This will be achieved by linking the outcome of
the first (primary) transfer to the prior stimulation(s)/retrieval.
The annual SART and CDC reports will continue to strive
to improve the clinic and national summary reports to make
the rates more transparent and meaningful to consumers of
fertility services. The current cycle-centered report will be sup-
plemented with patient-centered data. A patient-anchored
approach will better approximate the ‘‘true’’ live-birth rate
per cycle by including potential future births due to the subse-
quent transfer of frozen embryos. Moreover, by ordering and
linking the outcomes of sequential cycles in a given patient,
the cumulative live-birth rate of consecutive cycles could
also be established (live birth per patient). In that the ‘‘true’’
live-birth rate of a single cycle and the cumulative live-birth
rate of consecutive cycles are of intense interest to consumers,
the development of such metrics for public report deserves
further effort. The level of difficulty and complexity involved
in such a shift in reporting cannot be underestimated.
The most important aspect of the report is that the format
take into consideration the needs of the patient. An average
patient has difficulty understanding the multiple numerators
and denominators inherent in a detailed report (22). We must
do our best to make the report patient friendly. At present,
these reports are best understood by the patient in consulta-
tion with her physician.
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