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Risk factors and clinical outcomes of late-onset severe ovarian hyperstimulation syndrome in advanced maternal age women undergoing fresh embryo transfer

Ying Huang,Jiangman Gao,T. Tian,Lixue Chen,Rong Li,Rui Yang

Published 2025 in Journal of Ovarian Research

ABSTRACT

Since young age is an established risk factor for ovarian hyperstimulation syndrome (OHSS), most research has consequently focused on early-onset OHSS in this patient population. With increasing fertility demands among advanced maternal age (AMA) populations, their reproductive health and assisted reproductive outcomes have garnered significant clinical attention. However, there are few reports on late-onset OHSS in AMA patients, and its risk factors and impact on pregnancy outcomes remain unknown. This retrospective study analyzed 13,040 fresh embryo transfer cycles with positive serum hCG results in women aged ≥ 35 years from January 2010 to December 2021. Patients were stratified based on the occurrence of late-onset severe OHSS. Pregnancy and neonatal outcomes were analyzed and multivariable regression analysis was used to identify risk factors of OHSS in advanced-age women. Within this cohort, 142 patients were diagnosed with late-onset severe OHSS. Both long and ultra-long COH protocols were associated with a significantly higher risk of OHSS compared to the antagonist protocol. Lower total Gn dosage, higher trigger-day E2 level and greater number of good quality embryos were also independent risk factors. Patients with OHSS had significantly lower biochemical pregnancy rate (1.4% vs. 6.7%, P < 0.05), ectopic pregnancy incidence (0 vs. 3.4%, P < 0.05) and early miscarriage rate (10.0% vs. 19.0%, P < 0.05), but higher clinical pregnancy rate (98.6% vs. 93.3%, P < 0.05), and live birth rate (84.3% vs. 73.0%, P < 0.05). The Neonatal and delivery outcomes in singleton live births were comparable between the two groups. The clinical severity of OHSS during hospitalization (manifested as hepatic dysfunction, hypoalbuminemia, ascites, or pleural effusion) showed no significant impact on live birth outcomes. Elevated trigger-day E2 levels and increased good-quality embryos independently predict late-onset severe OHSS risk in AMA women, without compromising pregnancy outcomes.

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