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MATERIALS AND METHODS: The NASS database is comprised of data
reported to the CDC for approximately 98% of ART cycles performed in the
United States, including patient demographics, reproductive history, infer-
tility diagnosis, clinical parameters for ART procedure, and cycle outcome
data (e.g., number and weight of infants delivered). NASS data from years
2004-2018 were used to examine trends in use of FET and incidence of
LGA. Also, all FET cycles between 2016 and 2018 resulting in singleton
live births (N¼127,916) were further analyzed to identify factors associated
with LGA after FET. Clinical, demographic, and associated retrieval cycle
characteristics were compared between the LGA and non-LGA groups.
Modified Poisson regression was used to estimate adjusted relative risk
(aRR) of LGA and 95% confidence intervals (CI) to determine possible fac-
tors associated with LGA after FET.
RESULTS: While the percentage of IVF transfers using frozen embryos
steadily increased from 20% in 2004 to 74% in 2018, the rate of LGA infants
following FET decreased from 18% to 12% during the same timeframe. Fac-
tors most strongly associated with increased risk of LGA after FET were
higher than normal body mass index (BMI 25.0-29.9 kg/m
2
(aRR 1.31,
95% CI 1.26-1.36), BMI 30.0-34.9 kg/m
2
(aRR 1.48, 95% CI 1.41-1.55),
and BMI >35 kg/m
2
(aRR 1.67, 95% CI 1.58-1.76)) and parity (1 prior birth
(aRR 1.36, 95% CI 1.31-1.42) and >1 prior birth (aRR 1.39, 95% CI 1.31-
1.47), compared to nulliparous patients). Use of gestational carrier (aRR
1.29, 95% CI 1.14-1.46) and use of donor sperm (aRR 1.20, 95% CI 1.12-
1.29) were also positively associated with LGA after FET. In contrast, low
BMI (<18.5 versus 18.5-24.9 kg/m
2
), geographic region (NE and West
compared to Midwest), low number of oocytes retrieved (5-9 versus 10-19
oocytes) and two or more fetal heartbeats were protective factors. In addition,
compared to non-Hispanic (NH) White patients, NH Black, Hispanic, and
Asian/Pacific Islander patients were at significantly lower risk of LGA in-
fants born after FET.
CONCLUSIONS: BMI, parity, and race/ethnicity were the strongest inde-
pendent risk factors for LGA infants following FET cycles. The annual rate
of LGA after FET cycles decreased over the fifteen-year period studied.
IMPACT STATEMENT: Increased understanding of risk factors for LGA
after FET can improve patient counseling and medical care for patients un-
dergoing assisted reproductive technologies.
O-41 11:45 AM Monday, October 18, 2021
ENDOMETRIAL PREPARATION FOR FROZEN EM-
BRYO TRANSFER AND IMPACT ON BIRTH WEIGHT:
A SYSTEMATIC REVIEW AND META-
ANALYSIS. Kendal Frances Rosalik, Do,
1
Samantha Car-
son, MD,
2
Jacqueline Luizzi, MLIS, AHIP,
1
Justin Pilgrim, MD,
3
Gary
Levy, MD,
2
Ryan Heitmann, DO,
4
Bruce D. Pier, MD
51
Madigan Army
Medical Center;
2
Tripler Army Medical Center;
3
Tripler Army Medical Cen-
ter, Honolulu, HI;
4
West Virginia University Medical Center;
5
Division of
Reproductive Endocrinology and Infertility, Tacoma, WA.
OBJECTIVE: Frozen embryo transfer (FET) has advantages over fresh
embryo transfer IVF for certain patient populations and circumstances but
may also increase some perinatal and maternal risks such as macrosomia,
large for gestational age (LGA), cesarean section, hemorrhage, and hyperten-
sive disorders of pregnancy. Given the growing number of studies comparing
outcomes between natural (NFET) and programmed FET (PFET) cycles, we
conducted a meta-analysis looking at the risk of fetal weight abnormalities in
patients undergoing NFET and PFET cycles.
MATERIALS AND METHODS: A literature search using MEDLINE,
SCOPUS, EMBASE and clinicaltrials.gov was conducted for published
research comparing neonatal outcomes in NFET and PFET cycles. Primary
outcomes interest were fetal weight, macrosomia, and large for gestational
age. Studies were included if the following criteria were met: study contained
cohorts of NFET and PFET with outcome data regarding birth weight, large
for gestational data, and/or macrosomia data. Data are presented as average
weight and odds ratio (OR) with 95% confidence interval (CI) with fixed- or
random-effects meta-analysis between cohorts of NFET and PFET cycles.
Given heterogeneity in defining NFET patients, a subgroup meta-analysis
was performed using true natural cycle FET (TNFET) (no ovarian stimula-
tion) and PFET cycles.
RESULTS: A total of 798 studies were identified, with 13 meeting inclu-
sion criteria. Studies varied with respect to country of origin, definition of
natural cycle FET, and type of progesterone supplementation used. Studies
included had similar gestational age at time of birth. PFET cycles had a
higher fetal weight (14.6gm, p ¼0.03) compared to NFET cycles. PFET cy-
cles were at higher risk for macrosomia (OR 1.16, 95% CI 1.09-1.23) and
LGA (OR 1.13, 95% CI 1.07-1.19). In a subgroup meta-analysis, PFET cy-
cles had a higher fetal weight (62.2gm, p ¼0.0001) compared to TNFET cy-
cles. PFET cycles were also at higher risk for macrosomia compared to
TNFET cycles (OR 1.35, 95% CI 1.14-1.60).
CONCLUSIONS: Data demonstrates that programmed endometrial prep-
aration for FET cycles has a small, yet significant increase effect on fetal birth
weight, and increased risks of LGA and macrosomia. These effects appear to
be more significant when comparing TNFET and PFET cycles.
IMPACT STATEMENT: Frozen embryo transfer is being used increas-
ingly in the United States. Accurate and specific patient counseling as to risks
associated with this specific procedure are important to discuss.
SUPPORT: None.
O-42 12:00 PM Monday, October 18, 2021
IVF OUTCOMES IN BRCA CARRIERS WITH AND
WITHOUT ADDITION OF LETROZOLE TO
STIMULATION. Chelsea M. Canon, MD,
1
Matthew A. Le-
derman, MD,
2
Carlos Hernandez-Nieto, MD,
2
Dmitry
Gounko, MA,
2
Joseph A. Lee, BA,
2
Jeffrey Klein, MD,
2
Beth McAvey,
MD,
2
Daniel E. Stein, MD,
2
Alan B. Copperman, MD
21
Icahn School of
Medicine at Mount Sinai, New York;
2
Reproductive Medicine Associates
of New York, New York, NY.
OBJECTIVE: Women with BRCA 1/2 mutations are commonly referred
to reproductive endocrinologists to discuss fertility preservation options
prior to ovarian and breast cancer risk reducing surgery. Researchers
remain divided about whether BRCA carriers might be predisposed to
decreased ovarian reserve and accelerated ovarian aging compared to non-
carriers, and debate optimal stimulation dosage and protocols.
1
The aro-
matase inhibitor letrozole is commonly used during controlled ovarian
stimulation (COH) of breast cancer patients to minimize circulating Estra-
diol levels, but it is unclear whether its use negatively affects stimulation
response, fertilization, and embryo quality. Our study aims to evaluate
IVF outcomes in BRCA carriers who include or do not include Letrozole
during stimulation.
MATERIALS AND METHODS: The study included BRCA mutation car-
riers without a diagnosis of cancer who underwent COH from March 2009 to
April 2021. Study groups were segregated by stimulation type (Group A: IVF
cycles with Letrozole; Group B: IVF cycles without Letrozole). Basic demo-
graphic and cycle characteristics were compared between the groups. Both
cohorts included cycles in which preimplantation genetic testing for aneu-
ploidy (PGT-A) and/or monogenic/single gene defects (PGT-M) via Next
Generation Sequencing for both BRCA and aneuploidy screening was per-
formed. Data was analyzed using student’s t-test, chi-square and logistic
regression.
RESULTS: A total of 72 IVF cycles for embryo cryopreservation (n¼59)
and egg freezing (n ¼13) were included. Patients in which Letrozole was
included during stimulation (n¼22) were similar to group B (n¼50) in base-
line characteristics. Study groups were stimulated with an equivalent cumu-
lative gonadotropin dose and had similar oocyte yield, number of mature
oocytes, fertilization rate and number of embryos biopsied. 78 embryos
from Group A and 219 embryos from Group B underwent PGT-A, which
demonstrated equivalent rates of embryonic aneuploidy. 46 embryos from
Group A and 47 embryos from Group B underwent PGT-M for BRCA, which
demonstrated equivalent number of BRCA-free embryos. On multivariate lo-
gistic regression, after adjusting for age, BMI, D3 FSH, D3 E2, Gravidy, Par-
ity, Gonadotropin Cumulative Dose, BAFC, and AMH, there was no
association with use of Letrozole and lower number of oocytes retrieved
(OR 1.41 (95% CI 0.47-4.19), lower number of mature oocytes (OR 0.951
95% CI 0.31-2.90), and lower number of usable euploid, BRCA embryos
(1.76 95% CI 0.25-12.66).
e18 ASRM Abstracts Vol. 116, No. 3, Supplement, September 2021
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