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ANDROGEN EXCESS AND POLYCYSTIC OVARY SYNDROME
O-193 10:45 AM Wednesday, October 20, 2021
FEMALE 21-OH CONGENITAL ADRENAL HYPER-
PLASIA CARRIER STATUS IS NOT ASSOCIATED
WITH SUBOPTIMAL IMPLANTATION RATES
AFTER A SINGLE EUPLOID EMBRYO
TRANSFER. Carlos Hernandez-Nieto, MD,
1
Teresa A. Cacchione, MS,
CGC,
1
Deborah Cassis-Bendeck, MD,
1
Joseph A. Lee, BA,
1
Beth McAvey, MD,
2
Tanmoy Mukherjee, MD,
1
Benjamin Sandler, MD,
1
Alan B. Copperman, MD
11
Reproductive Medicine Associates of New
York, New York, NY;
2
Icahn School of Medicine at Mount Sinai, New
York, NY.
OBJECTIVE: Female carriers of 21-OH Deficient Congenital Adrenal Hy-
perplasia (21-OH CAH) might experience hormonal disturbances in androgen
biosynthesis.
1,2
Given the critical role played by steroid hormones in reproduc-
tive function and endometrial receptivity, it is plausible that individuals affected
by these steroidogenic disorders might face potential fertility challenges.
Limited research has been published about the relationship between patients
who are heterozygous carriers for this disorder, infertility, and implantation po-
tential after IVF. Our study aims to evaluate the reproductive potential of 21-OH
CAH carriers who undergo single euploid embryo transfer (SET).
MATERIALS AND METHODS: Patients who underwent SET on a syn-
thetic preparation cycle from 2018 to 2021. PGT-A with NGS was performed
for all cases. All couples underwent preconception expanded carrier
screening. Patients were segregated into 2 groups based on female
CYP21A12 carrier status (Heterozygote carriers; vs Non-carriers). Patients
with biallelic CYP21A2 mutations were excluded. Baseline characteristics,
hormonal profiles, and pregnancy outcomes were compared between cohorts.
Comparative statistics and an adsuted multivariate analysis with a GEE was
performed. A sample size of 100 patients per cohort was calculated to ensure
an 80% power to detect a difference of 15% on implantation rates (a¼0.05)
RESULTS: 3,337 SET cycles were included in the analysis. 187 21-OH
CAH carriers (5.6% prevalence) were compared against 3,150 non-carriers.
No differences were found in age at ET, oocyte age, BMI, baseline estradiol,
progesterone, FSH, LH, AMH among groups, also no differences were found
on serum estradiol and serum progesterone levels the day ofprogesterone start
betweencohorts. A significant difference was found in mean endometrial thick-
ness at ET (9.7 2.2 vs 9.42.0,p¼0.01) and 17 -OH progesteron e levels (91.8
612 vs 415 521,p¼0.02) between cohorts. Furthermore, embryo quality at
ET, implantation rate, ongoing pregnancy, clinical pregnancy and clinical preg-
nancy loss rates were comparable between cohorts. In a multivariate analysis
after adjusting for age, BMI, AMH, day of embryo biopsy, embryo quality
and endometrial thickness, no association was found between being a 21-OH
CAH carrier and lower odds of implantation (OR 0.8 CI95% 0.5-1.2), clinical
pregnancy (OR 0.7; 0.5-1.09),ongoing pregnancy rate (0.7;0.5-1.06), or higher
odds of clinical pregnancy loss (OR 1.12; 0.6-1.8)
CONCLUSIONS: It had been suggested that 21-OH CAH carriers might
experience some degree of disruption in 21-hydroxylase enzymatic activity,
raising concern about the potential impact on endometrial receptivity and
IVF outcomes. However, despite a mild hyper-androgenic profile, 21-OH
CAH carriers present similar implantation rates and IVF outcomes after a
SET compared to non-carriers.
IMPACT STATEMENT: This study is first to show patients who are het-
erozygous carriers for 21-OH CAH do not appear to experience suboptimal
implantation rates and/or pregnancy outcomes compared to non-carriers after
IVF with a single euploid embryo transfer.
References
1. Knochenhauer ES, et al. Carriers of 21-hydroxylase deficiency are not at
increased risk for hyperandrogenism. J Clin Endocrinol Metab. 1997
Feb;82(2):479-85.
2. Guarnotta V, et al. Clinical and hormonal characteristics in heterozygote
carriers of congenital adrenal hyperplasia. J Steroid Biochem Mol Biol. 2020
Apr;198:105554.
SUPPORT: No financial support.
O-194 11:00 AM Wednesday, October 20, 2021
POLYCYSTIC OVARY SYNDROME AND RISK OF
ADVERSE PREGNANCY OUTCOMES: A REGISTRY
LINKAGE STUDY FROM MASSACHUSETTS.
Leslie V. Farland, ScD,
1
Judy E. Stern, PhD,
2
Chia-Ling Liu,
RN, MPH, ScD,
3
Howard J. Cabral, PhD, MPH,
4
Charles C. Coddington,
MD,
5
Dmitry Dukhovny, MD MPH,
6
Hafsatou Diop, MD, MPH,
3
Sunah S. Hwang, MD MPH,
7
Stacey A. Missmer, ScD
81
Mel and Enid Zuck-
erman College of Public Health, Tucson, AZ;
2
Dartmouth-Hitchcock,
Lebanon, NH;
3
MPDH, Boston, MA;
4
Boston University, Boston, MA;
5
Atrium Health Reproductive Medicine, Charlotte, NC;
6
Oregon Health &
Science University, Portalnd, OR;
7
University of Colorado School of Medi-
cine, Aurora, CO;
8
College of Human Medicine, Michigan State University,
Grand Rapids, MI.
OBJECTIVE: To investigate whether women with polycystic ovary syn-
drome (PCOS) had greater risk of pregnancy complications (gestational dia-
betes, preeclampsia, placental abnormalities), or adverse pregnancy
outcomes (preterm birth, small for gestational age, cesarean section, prolonged
neonatal hospitalization) compared to women with no history of PCOS; and to
determine if risk varied by subfertility and fertility treatment utilization.
MATERIALS AND METHODS: Deliveries among women >18 years old
during 2013-2017 from Massachusetts state vital records were linked to the
Society for Assisted Reproductive Technology Clinic Outcome Reporting
System (SART CORS), to case data that encompasses hospital discharge,
observational stays and emergency room visits, and to the All-Payers Claims
Database (APCD) for the state of Massachusetts. PCOS was identified by
ICD 9 and 10 codes in APCD prior to index delivery. Relative risks (RR)
and 95% confidence intervals (CI) for pregnancy and delivery complications
were modeled using generalized estimating equations with a log link and a
Poisson distribution and were adjusted a priori for maternal age, body
mass index, race, education, plurality, birth year, chronic hypertension, and
chronic diabetes. Tests for heterogeneity investigated differences between
deliveries that used ARTor had a history of subfertility (defined by birth cer-
tificates, SART CORS records, APCD, or hospital records) and fertile deliv-
eries (no documentation of ART or subfertility).
RESULTS: Among 91,825 deliveries, 3.9% had a history of PCOS, 8.4%
used ART, and 14.6% had a history of subfertility or prior fertility treatment.
Women with a history of PCOS had a 51% greater risk of gestational diabetes
(CI: 1.38-1.65) and a 25% greater risk of preeclampsia (CI: 1.15-1.35)
compared to women without a diagnosis of PCOS. Neonates born to women
with a history of PCOS were more likely to be born preterm (RR:1.17,
CI:1.06-1.29) and more likely to have a prolonged delivery hospitalization
after additionally adjusting for gestational age (RR:1.23, CI: 1.09-1.40)
compared to those of women without a diagnosis of PCOS. The risks of
adverse pregnancy outcomes for women with PCOS were elevated similarly
among deliveries to women who utilized ART/experienced subfertility and
among fertile deliveries.
CONCLUSIONS: Deliveries to women with a history of PCOS were at
greater risk of pregnancy complications associated with cardiometabolic
function, including gestational diabetes and preeclampsia, as well as preterm
birth and prolonged length of delivery hospitalization. This elevated risk of
adverse pregnancy outcomes did not vary by ART/subfertility history.
IMPACT STATEMENT: In this large general population study, regardless
of past subfertility or ART, women with a history of PCOS were at greater
risk of pregnancy complications associated with cardiometabolic function
and preterm birth. Obstetricians need to be aware of patient’s PCOS status
and closely monitor for onset signs of these pregnancy complications to
improve outcomes for mother and infant.
SUPPORT: R01HD067270
O-195 11:15 AM Wednesday, October 20, 2021
ADIPOSE CLC-3 DEFICIENCY PROTECTS AGAINST
DIET-INDUCED OBESITYAND INSULIN RESISTANCE
BY REGULATING GLUT4 THROUGH THE PI3K/AKT
PATHWAY. Sushi Jiang, MD,
1
Xiaojia Li, M.D.,
2
Xiaomiao Zhao, MD, Ph.D
11
Sun Yat-sen Memorial Hospital, Sun Yat-sen
University, Guangzhou, China;
2
Center for Reproductive Medicine, Depart-
ment of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun
Yat-sen University.
OBJECTIVE: Obesity is a worldwide medical condition with excess body
fat and has negative effects on personal health. Adipocyte hyperplasiaor hyper-
trophy are considered tobe accountable for excessive accumulation of adipose
tissue. One of the main reasons thatinduce obesity is high-fat diet (HFD),HFD
can also lead to a series of complications such as insulin resistance and type 2
diabetes.GLUT4 is an important glucose transporter regulating blood glucose,
it is supervised by a complicated cascade known as PI3K/Akt pathway for
sensing the high concentration of glucose in the blood. Upregulation of
PI3K/Akt pathway can stimulate GLUT4 to be activated to transport glucose
into adipose cells. Here, we identify voltage-gated chloride ion channel family
e82 ASRM Abstracts Vol. 116, No. 3, Supplement, September 2021