Ectopic pregnancy secondary to in vitro fertilisation-embryo transfer: pathogenic mechanisms and management strategies

Bassem Refaat, Elizabeth Dalton, William L Ledger

Ectopic pregnancy (EP) is the leading cause of maternal morbidity and mortality during the first trimester and the incidence increases dramatically with in vitro fertilisation and embryo transfer (IVF-ET). The co-existence of an EP with a viable intrauterine pregnancy (IUP) is known as heterotopic pregnancy (HP) affecting about 1% of patients during assisted conception. EP/HP can cause significant morbidity and occasional mortality and represent diagnostic and therapeutic challenges, particularly during fertility treatment. Many risk factors related to IVF-ET techniques and the cause of infertility have been documented. The combination of transvaginal ultrasound (TVS) and serum human chorionic gonadotrophin (hCG) is the most reliable diagnostic tool, with early diagnosis of EP/HP permitting conservative management. This review describes the risk factors, diagnostic modalities and treatment approaches of EP/HP during IVF-ET and also their impact on subsequent fertility treatment. The scientific literature was searched for studies investigating EP/HP during IVF-ET. Publications in English and within the past 6 years were mostly selected. A history of tubal infertility, pelvic inflammatory disease and specific aspects of embryo transfer technique are the most significant risk factors for later EP. Early measurement of serum hCG and performance of TVS by an expert operator as early as gestational week 5 can identify cases of possible EP. These women should be closely monitored with repeated ultrasound and hCG measurement until a diagnosis is reached. Treatment must be customised to the clinical condition and future fertility requirements of the patient. In cases of HP, the viable IUP can be preserved in the majority of cases but requires early detection of HP. No apparent negative impact of the different treatment approaches for EP/HP on subsequent IVF-ET, except for risk of recurrence. EP/HP are tragic events in a couple's reproductive life, and the earlier the diagnosis the better the prognosis. Due to the increase incidence following IVF-ET, there is a compelling need to develop a diagnostic biomarker/algorithm that can predict pregnancy outcome with high sensitivity and specificity before IVF-ET to prevent and/or properly manage those who are at higher risk of EP/HP.