Top‐quality embryo transfer is associated with lower odds of ectopic pregnancy

Abstract

Introduction The incidence of ectopic pregnancy is up to four times higher after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) than in spontaneous pregnancies, and the risk of ectopic pregnancy is increased by tubal factor infertility and the transfer of multiple embryos. However, the effect of embryo quality on the probability of ectopic pregnancy has not been investigated until now and it is not clear whether ovarian stimulation parameters affect the incidence of ectopic pregnancy. Material and Methods An historical cohort study of 15 006 clinical pregnancies (diagnosed by ultrasound at 6–8 gestational weeks) after non‐donor IVF/ICSI with fresh embryo transfer (n = 8952) or frozen–thawed embryo transfer (n = 6054). Treatments were performed during 2000–2017 in Finland. A total of 9207 (61.4%) single and 5799 (38.6%) double embryo transfers of no more than one top‐quality embryo were evaluated. We analyzed the effects of multiple factors on ectopic pregnancy by logistic regression, including type of cycle (fresh vs frozen embryo transfer), female age, number and quality of embryos transferred, tubal factor infertility and factors of ovarian response to gonadotropin stimulation. Results Ectopic pregnancy was observed in 2.3% of cycles. There was no significant difference in ectopic pregnancy rate after fresh embryo transfer and frozen embryo transfer (2.2% vs 2.4%, p = 0.3). The ectopic pregnancy rate was lower in cycles with top‐quality embryo transfer (1.9%) than of those where only non‐top quality embryos were transferred (2.7%, p < 0.0001). Tubal factor infertility was diagnosed more often in ectopic pregnancy than in intrauterine pregnancies (21.2% vs 11.0%, p < 0.0001). Logistic regression revealed lower odds for ectopic pregnancy after a top‐quality embryo transfer than after transfer of a non‐top quality embryo (odds ratio [OR] 0.72, 95% confidence interval [CI] 0.56–0.92, p = 0.007). Transfer of two vs one embryo (OR 1.35, 95% CI 1.05–1.70, p = 0.02) and tubal factor infertility (OR 2.21, 95% CI 1.68–2.91, p < 0.0001) significantly increased the risk of ectopic pregnancy. Conclusions Transfer of non‐top quality embryos is associated with a higher rate of ectopic pregnancy. This is particularly important to keep in mind in treatments with only non‐top embryos available even in the absence of tubal factor infertility. To minimize the risk of ectopic pregnancy, the number of embryos transferred should be as low as possible.

ESHRE guideline: number of embryos to transfer during IVF/ICSI

“…Apart from the counselling regarding the risks of pregnancy complications with the transfer of more than one embryo, and resulting multiple gestations, patients for whom DET is considered should be aware that the risk of ectopic pregnancy increases along with the number of embryos transferred, up to about 20-fold ( Li et al , 2015 ; Perkins et al , 2015 ; Bu et al , 2016 ; Santos-Ribeiro et al , 2016 ; Pi et al , 2020 ; Anzhel et al , 2022 ; Cirillo et al , 2022 ). The risk of extrauterine pregnancy is elevated after the transfer of two versus one embryo, regardless of development stage or freezing status ( Santos-Ribeiro et al , 2016 ; Anzhel et al , 2022 ). The rate of ectopic pregnancy is higher after the transfer of non-top-quality embryos ( Anzhel et al , 2022 ).…”

“…The risk of extrauterine pregnancy is elevated after the transfer of two versus one embryo, regardless of development stage or freezing status ( Santos-Ribeiro et al , 2016 ; Anzhel et al , 2022 ). The rate of ectopic pregnancy is higher after the transfer of non-top-quality embryos ( Anzhel et al , 2022 ). Furthermore, even if a singleton pregnancy develops after DET, it is associated with an overall higher risk of neonatal death and a higher risk of low birthweight in frozen embryo transfer, compared with singleton pregnancies after SET ( Rodriguez-Wallberg et al , 2023 ).…”

Body mass index impacts ectopic pregnancy during in vitro fertilization: an analysis of 42,362 clinical pregnancy cycles

“…To date, there has been numerous data identifying risk factors for EP during ART treatment [ 4 , 7 , 19 ]. Whether a correlation exists between female BMI and the risk of EP has been previously discussed.…”

“…In pregnancies after natural conception, the incidence of this early pregnancy complication varies from 1 to 2% [ 3 ]. However, the rate of EP in assisted reproduction techniques (ART), especially in in vitro fertilization (IVF) and embryo transfer (ET) treatment cycles, reaches 1.4-8.6% [ 4 ]. During spontaneous pregnancy, it is known that EP is highly associated with tubal surgery history, pelvic inflammatory disease.…”

Higher obstetric and perinatal risks for twins and the need for single embryo transfers in assisted reproduction

“…If single embryo transfers become the standard, several negative outcomes associated with prematurity that have an impact in the health of the children might be reduced 1 . Additional risks associated with multiple embryo transfers include also higher risks for ectopic pregnancy, which also increases with the number of embryos transferred 5 . Finally, singleton pregnancies that develop after double embryo transfers have been associated with a higher risk of neonatal death and low birthweight compared with singleton pregnancies resulting from single embryo transfers in a recent Nordic population‐based study 6 …”