Is a thin endometrial lining associated with a higher incidence of ectopic pregnancies in ovulation induction cycles?

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American Society for Reproductive Medicine 2018 Scientific Congress & Expo
October 6 to 10, 2018 Denver, Colorado, USA
Title:
IS A THIN ENDOMETRIAL LINING ASSOCIATED WITH A HIGHER INCIDENCE
OF ECTOPIC PREGNANCIES IN OVULATION INDUCTION CYCLES?
Authors:
S. Chang1, 2; T.G. Nazem 1, 2; D. Gounko1; J.A. Lee1; B. McAvey1, 2
Affiliations:
1. Reproductive Medicine Associates of New York, 635 Madison Avenue, 10th Floor New
York, NY, United States, 10022
2. Department of OBGYN and Reproductive Science, Mount Sinai School of Medicine,
Klingenstein Pavilion, 9th Floor 1176 Fifth Avenue, New York, NY, United States, 10029
Objective:
Clinicians continue to explore risk factors and apply clinical pathways to prevent the occurrence
of an ectopic pregnancy during assisted reproduction technologies treatment. Rombauts et al.
published a report that demonstrated a 4-fold increased risk of ectopic pregnancy in women who
underwent a fresh in vitro fertilization cycle with an endometrial thickness (EnT) of <9mm as
compared to >12mm.1 No studies to date have evaluated whether there is a similar association in
ovulation induction (OI) cycles. This study aimed to determine the value of EnT at time of surge
to predict ectopic pregnancies in OI cycles.
Design:
Retrospective, cohort study
Materials and Methods:

The study included patients who underwent an OI cycle from 2001-2018 using clomiphene
citrate (CC) or letrozole. Gonadotropin cycles were excluded. OI cycles were separated into
groups based on outcome (ectopic pregnancy (EP) and no EP). EnT was treated as a continuous
variable. A sub-analysis was performed treating EnT as a dichotomous variable, thin (<7mm) or
not thin (≥7mm). Age, body mass index (BMI), EnT and endometrial pattern (EnP) at time of
surge, gravidity, parity, and anti-mullerian hormone level (AMH) were collected. Data were
analyzed using t-tests, Chi square analysis, and binary logistic regressions with a general
estimate equation (GEE) model with an exchangeable working correlation structure to account
for repeated measures.
Results:
A total of 22,956 OI cycles from 11,043 patients were included. Baseline characteristics were
similar between cycle outcome groups (Table 1). There was a significant difference in the
number of CC cycles that resulted in a thin lining (<7mm) compared to letrozole (18.6% vs.
13.4%, p=0.0001). The overall rate of EP in the study was 1.13% (n=259). There was no
difference in the rate of EP between CC or letrozole cycles (1.15% vs. 1.07%, p=0.65).
Controlling for age, gravidity BMI, EnP, and type of cycle (CC vs. letrozole), there was no
significant increase in likelihood of patients experiencing an EP based on EnT at time of surge
(OR 0.96, [95% CI 0.96-1.05], p= 0.43). When EnT was treated as a dichotomous variable, there
was still no significant difference in incidence of EP with an EnT <7mm, compared to ≥7mm
(OR 0.75, [95% CI -1.00-0.42], p= 0.42). Similarly, a suboptimal EnP was not associated with
risk of EP (OR 1.30, [95% CI -0.18 - 0.71], p=0.25).

Conclusions:
In contrast to recent reports that EnT is an independent risk factor for EP in IVF cycles, this
study demonstrated that there is no association between EnT and EP in OI cycles. Although CC
predisposes a patient to having a thin endometrium, there was no increase in the risk of an EP, as
compared to patients exposed to letrozole. Clinicians can be reassured that patients do not have a
greater risk of experiencing an EP during OI, even in the presence of a thin endometrial lining.
References:
1. Rombauts L, McMaster R, Motteram C. Risk of ectopic pregnancy is linked to
endometrial thickness in a retrospective cohort study of 8120 assisted reproduction
technology cycles. Hum Reprod 2015; 30(12):2846-2852.
Table 1:
Patient demographics
Ectopic pregnancy
(N=259)
No ectopic pregnancy
(N=22,698)
P value
Age
34.89 ± 4.38
35.02 ± 5.05
0.66
BMI
24.92 ± 5.28
24.30 ± 5.06
0.10
EnT at surge
8.34 ± 1.89
8.12 ± 1.88
0.06
Endometrial type
1- 109 (42.9%)
2- 115 (45.3%)
3- 30 (11.8%)
1- 10501 (46.1%)
2- 9299 (40.8%)
3- 2720 (11.9%)
0.42
AMH
4.48 ± 7.68
4.18 ± 5.31
0.70
Gravidity
1.37 ± 1.53
0.81 ± 1.19
0.00
Parity
0.33 ± 0.59
0.26 ± 0.59
0.28
Cycle Type
Clomid: 73.0%
Letrozole: 27.0%
Clomid: 71.5%
Letrozole: 28.5%
0.60

Table 2:
Chi square analysis results comparing lining thickness and cycle type
Clompihene Citrate
Letorozole
P value
EnT <7 mm
3,057 (18.6%)
876 (13.4%)
0.0001
EnT ≥7 mm
13,356 (81.4%)
5,667 (86.6%)