Abstract

Abstract Study question Does OHSS affect maternal and neonatal outcomes in perinatal life? Summary answer OHSS is associated with an increased risk of postpartum hemorrhage, large birth weight, neonatal respiratory distress syndrome, and intraventricular hemorrhage. What is known already Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic condition caused by ovulation induction. Golan et al.(1989)’s clinical staging system categorizes OHSS into mild, moderate, and severe based on the clinical characteristics. Among them, severe OHSS is considered potentially fatal and requires hospitalization. In 2021, a systematic review of 3,303 pregnant patients with OHSS and 89,720 pregnant patients without OHSS, drawn from 13 studies, revealed a notable impact of OHSS on preterm birth. However, owing to the characteristics of spontaneous resolution in the relatively early stages of pregnancy, no large-scale study has confirmed the OHSS and pregnancy outcomes. Study design, size, duration This retrospective study utilized a combined dataset from two primary sources: the Korea National Health Insurance (KNHI) claims database and the National Health Screening Program for Infants and Children (NHSP-IC) database. We identified all women who delivered between January 1, 2012, and December 31, 2020 from KNHI claims database. Pregnancy outcomes including preterm birth and PPH were identified from NHSP-IC database and KNHI claims database, respectively. Participants/materials, setting, methods We enrolled all women who delivered between January 1, 2012, and December 31, 2020 (N = 3,446,520). Women diagnosed with multiple pregnancy or had missing data were excluded (N = 2,565,461). The participants were divided into three groups according to the presence or absence of an ovarian hyperstimulation diagnosis code (ICD-10 code N981) and hospitalization within 3 months before pregnancy: non-OHSS group (N = 2,562,562), mild-to-moderate OHSS group (N = 2,293), severe OHSS group (N = 606). Main results and the role of chance In this study, mothers in the ovarian hyperstimulation group had a younger age and a higher rate incidence of primiparity and cesarean section. In the ovarian hyperstimulation group, a significantly high proportion of patients was diagnosed with pre-pregnancy hypertension or diabetes mellitus and gestational hypertension or gestational diabetes. The risk of postpartum hemorrhage was 38.2% higher in the mild-to-moderate OHSS group than in the non-OHSS group (adjusted odds ratio (aOR): 1.382, 95% confidence interval (CI): 1.223–1.562). No difference was found in the average birth weight of newborns according to the presence or absence of OHSS. However, the risk of macrosomia was elevated by 62.4% in the severe OHSS group (aOR: 1.624, 95% CI: 1.168–2.259) than the non-OHSS group. The mild-to-moderate OHSS group had a 36.8% higher risk of respiratory distress syndrome compared with the non-OHSS group (aOR: 1.368, 95% CI: 1.149–1.629). The mild-to-moderate OHSS group had a 2.697-fold increased risk of intraventricular hemorrhage compared with the non-OHSS group (aOR: 2.697, 95% CI: 1.338–5.437). Limitations, reasons for caution A limitation lies in the unknown details of the controlled ovarian stimulation protocol, type and dose of gonadotrophin used, hormone concentration, and embryo transfer method used due to the data structure. Despite the potential variations in the causes of hospitalization, hospitalized patients were classified into the severe OHSS group. Wider implications of the findings Although OHSS occurs during early pregnancy, further research is required to determine its long-term effects. Especially, if the incidence of IVH is significantly higher in the OHSS group, particularly among uncommon full-term neonates, further studies are warranted. Trial registration number Not Applicable

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