Introduction
Late miscarriage, also known as second-trimester or mid-trimester pregnancy loss, has different definitions across countries(1, 2). In China, LM refers to a complete pregnancy loss between 12 weeks and 28 weeks of gestational age. The main reasons for LM include cervical incompetence, fetal anomaly, maternal infection as well as premature rupture of membranes according to a previous retrospective study(3). LM is a heavy blow to pregnancy women at the second trimester who are almost preparing for delivery and brings about substantial physical harms (4). There is no doubt that LM is more devastating for infertile women who have spent plenty of time and money on in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) treatments.
The pregnancy loss rate among IVF population is reported to be approximately 15% (2, 5, 6), which is slightly higher than that after natural conception (7). The vast majority of pregnancy loss occurs before 12 weeks of gestational age, called early miscarriage (EM), and only 1-2% of pregnancies are spontaneously terminated after 12 weeks (8). It has already been known that a history of EMs significantly increased the risk of recurrent pregnancy loss and has an adverse influence on live birth (9, 10). Thus, the focus has always been on EM by clinicians in IVF cycles and the impact of LM is greatly underestimated(2, 5, 11).
It’s documented in a retrospective cohort study that women with a history of previous LM or stillbirth had a high recurrence risk during the subsequent pregnancy in general population(12). Further, both two studies have found that there was a significant association between a previous LM and subsequent adverse pregnancy outcomes, including an elevated EM rate and a reduced live-birth rate, after conventional IVF (13) or preimplantation genetic testing for aneuploidy (14). However, some studies drew a contradictory conclusion that one LM did not correlate with pregnancy prognosis (15). More importantly, they all failed to further investigate the separate impact of LM with different causes on subsequent pregnancy outcomes. Therefore, it remains unclear whether and how previous LM might impact future outcomes.
In the present study, the main objective was to explore whether a previous LM after first embryo transfer has a prognostic impact on the subsequent pregnancy outcomes during IVF.