Risk Factors for Different Types of Pregnancy Losses: Analysis of 15,210 Pregnancies After Embryo Transfer

Abstract

Objective: To evaluate the risk factors for different types of pregnancy losses after embryo transfer (ET).

Design: Retrospective cohort study.

Setting: Reproductive medicine center.

Participants: A total of 15,210 pregnancies after fresh and frozen-thawed embryo transfer between January 2014 and June 2019.

Main outcome measures: The primary outcome was pregnancy loss (PL) throughout the entire pregnancy. Secondary outcomes were non-visualized PL, early miscarriage, late miscarriage, and stillbirth.

Methods: The effect of patients' baseline characteristics and IVF/ICSI cycle-specific factors on the risk of PL after fresh and frozen-thawed ET was determined by multivariate logistic regression analysis.

Results: Compared to women under 35 years old, those between 35 and 40 had an increased risk of early miscarriage [odds ratio (OR) 1.49, 95% confidence interval (CI) 1.22-1.83], while those after 40 appeared to have an increased risk of both early miscarriage (OR 3.82, 95% CI 2.65-5.51) and late miscarriage (OR 2.79, 95% CI 1.64-4.77). Overweight patients were observed to have a higher risk of late miscarriage (OR 1.38, 95% CI 1.16-1.65), while obese patients showed a higher risk of both early miscarriage (OR 1.47, 95% CI 1.14-1.91) and late miscarriage (OR 1.80, 95% CI 1.33-2.44). Polycystic ovary syndrome (PCOS) was an independent risk factor for late miscarriage (OR 1.58, 95% CI 1.28-1.96), and the detrimental effect of PCOS was independent of obesity status. Women with uterine factors had a higher risk of early miscarriage (OR 1.77 (95% CI 1.32-2.38) than women without uterine factors. A negative correlation was observed between the thickness of the endometrium and PL (OR 0.95 95% CI 0.92-0.97). There was an increased risk of PL after frozen-thawed ET versus fresh ET (OR 1.12, 95% CI 1.01-1.24). Women who transferred ≥2 embryos showed lower risk of overall PL than women who transferred a single embryo, with adjusted ORs ranged from 0.57~0.94. However, women who transferred three embryos demonstrated a higher risk of late miscarriage than women who transferred a single embryo (OR 2.23, 95% CI 1.36-3.66).

Conclusions: Patients with uterine factors demonstrated higher risk of early miscarriage and stillbirth. Being overweight, PCOS, and transferring three embryos was associated with late miscarriage. Being aged 40 and over, obese, and using frozen embryo transfer was associated with early and late miscarriage.

Keywords: frozen-thawed embryo transfer; obesity; polycystic ovary syndrome; pregnancy loss; thickness of endometrium.

Figure 1

Flow chart for selection of patients from January 2014 to June 2019.

Figure 2

The proportion of live birth, pregnancy loss, induced abortion, ectopic pregnancy of all pregnancies. Percentage of non-visualized PL, early miscarriage, late miscarriage, and stillbirth of all pregnancy losses.

Figure 3

(A) Multivariate adjusted smoothing spline plots of pregnancy loss rate by maternal age. (B) Multivariate adjusted smoothing spline plots of pregnancy loss rate by maternal body mass index. (C) Multivariate adjusted smoothing spline plots of pregnancy loss rate by maternal thickness of endometrium. Solid red lines demonstrate the relationship between continues variables and pregnancy loss rate. Gray dotted curves represent the 95% of confidence intervals. Analyses were adjusted for number and stage of embryos transferred, duration of infertility, cycle type, maternal age, maternal body mass index, male age, indication for IVF treatment.