Discussion
This matched cohort study of pregnant Chinese women provided a comprehensive assessment of the associations between a history of HA-treated IUAs and obstetric outcomes in subsequent pregnancies. We observed that women with a history of HA-treated IUAs were at higher risk of PE, placenta accreta spectrum and previa, PPH and PTB. Those women were also more likely to receive cervical cerclage during pregnancy and hemostatic therapies after delivery. Moreover, we observed that the RRs of adverse obstetric outcomes increased with the increasing number of hysteroscopic surgeries. To our knowledge, this is one of the largest studies to report such associations.
PE, characterized by a multiorgan disorder, occurs in pregnancy with a clinical syndrome of hypertension and multiorgan hypoperfusion. In this study, we observed a significantly higher incidence of PE among women with a history of HA-treated IUAs than among women with no such exposure. PE are rarely mentioned in previous literature. Two previous studies compared the incidence of pregnancy-induced hypertension (GH, PE, eclampsia and HELLP syndrome) between women with a history of HA-treated IUAs and women with no such exposure. However, neither of these studies reported any significant difference in the incidence of pregnancy-induced hypertension between the two groups23,24. The development of PE is thought to be associated with abnormal placentation and placental hypoxia and/or ischemia34. Patients with previous IUAs usually experience endometrial trauma damaging the decidua basalis, insufficient or defective maturation of the endometrium and decidualization35. Impaired endometrial function and the abnormal adherence of the blastocyst to the decidualized endometrium have been shown to be involved in the pathogenesis of PE 36-38. Additionally, patients with IUAs often have a prior history of recurrent spontaneous abortions (RSA), which may have shared risk factors and etiology with PE.
The placenta accreta spectrum, which refers to abnormal adherence of the placental trophoblast to the uterine myometrium or morbidly adherent placenta, is a major cause of PPH. It includes placenta accreta (directly implanted onto the uterine myometrium), placenta increta (invasion of the trophoblast into the myometrium) and placenta percreta (invasion through the myometrium into the surrounding organs)39. Cases of women who developed placenta accreta spectrum and PPH after IUA surgery have been frequently reported5,40,41. Additionally, some small studies also reported higher incidences of placenta accreta spectrum and PPH among women with a history of IUAs or a history of HA-treated IUAs13,17,22,24, which were consistent with our findings. The placenta accreta spectrum results from the absence of the normal decidua basalis and endometrial re-epithelialization in the scar area, so the trophoblast and villous tissue can invade deeply within the myometrium 39,42. Women with a history of HA endometrial scar repair and loss of the endometrial basal layer may have higher incidences of placenta accreta spectrum. In addition to the placenta accreta spectrum, we also observed a higher incidence of placenta previa. To our knowledge, placenta previa has rarely been reported. Consistent with our study, two retrospective cohort studies conducted in Changsha and Beijing also reported a higher incidence of placenta previa among women with a history of HA-treated IUAs22,24.
The placenta plays a crucial role in fetal growth and development, and placental abnormalities may impair fetal growth and result in adverse birth outcomes 43,44. We further examined the impacts of HA-treated IUAs on birth outcomes. Although previous studies did not report any difference in newborn gestational weeks22,24, we observed a significantly higher incidence of PPROM and iatrogenic PTB among women with a history of HA-treated IUAs, and those women were also more likely to receive cervical cerclage to prevent spontaneous abortion or PTB. Various risk factors have been consistently associated with PTB. Recent studies suggest that bacterial vaginosis and vaginal microbiota disorder also play an important role in the development of PTB, especially PPROM 31, 45-48. The pathological changes in IUAs are bound to influence the physiology and metabolites in the uterus, which may influence vaginal microbial diversity 49. Additionally, after the first HA surgery, a copper intrauterine device (Cu-IUD) was often inserted into the uterus to prevent the recurrence of adhesion. However, the use of Cu-IUDs may increase the risk of bacterial vaginosis50,51, which may explain the higher risk of PPROM among those women. A history of cervical dilation has been associated with an increased risk of PTB, which may explain why women with more HA surgeries have a higher risk of PTB. Iatrogenic PTB may be attributed to the higher incidence of the placental accreta spectrum, placenta previa and PE in women with a history of HA-treated IUAs, as they are common cause of iatrogenic PTB 52.
Previous studies on newborn birth weight also yielded inconsistent results. In a case‒control study, Saeed et al. reported that newborns of women with IUAs had significantly lower birth weights (2.23 ± 0.28 kg) than newborns of women without IUAs (3.13 ± 0.383 kg)25. Two other studies did not find any difference in newborn birth weight between women with a history of HA-treated IUAs and women with no such exposure 22,24. Considering birth weight was highly dependent on gestational age, we compared the differences in SGA rate between the two groups. In our study, we found no significant association between history of HA-treated IUAs and risk of SGA.