Ovarian Hyperstimulation Syndrome (OHSS) requiring Intensive Care Unit (ICU) admission between 1996-2020 in England, Wales, and Northern Ireland

Abstract

Introduction: Ovarian Hyperstimulation Syndrome (OHSS) is a life-threatening iatrogenic complication of In vitro fertilisation (IVF). This study aimed to quantify rates of Ovarian Hyperstimulation Syndrome (OHSS) requiring intensive care unit (ICU) admission and assess whether trends have changed between 1996-2020 commensurate with the introduction of safer IVF practices.

Methods: Data regarding Intensive Care Unit (ICU) admission across England, Wales and Northern Ireland was gathered retrospectively from the Intensive Care National Audit and Research Centre (ICNARC) database. 38,957 female patients aged between 18-55 years were admitted to ICU for OHSS or related conditions between 1996-2020. The primary outcome was the rate of OHSS requiring ICU admission expressed as a proportion of the number of fresh IVF cycles conducted in that year according to Human Fertility and Embryology Authority (HFEA) records. Baseline characteristics (for example, age, ethnicity, BMI), biochemical parameters (such as renal function, serum electrolytes), length of ICU stay and duration and need for organ support, were also compared between ICU patients with 'confirmed OHSS' and those 'without OHSS'.

Results: There were 238 cases of 'confirmed OHSS' requiring ICU admission recorded between 1996-2020. Rates of OHSS requiring ICU admission declined over the study period (P=0.006); the annual rate of severe OHSS requiring intensive care admission halved when comparing those occurring between 1996-2007 and 2008-2020 (OR=0.37, 95% CI 0.37-0.45; P<0.0001). Patients spent a mean of 3.5 days in the ICU, with 86.3% of patients with 'confirmed OHSS' requiring at least 2 days of higher level (i.e., level 2 or 3) care. Patients with 'confirmed OHSS' required a shorter duration of renal, advanced cardiovascular, and advanced respiratory support than patients 'without OHSS' (P<0.0001 for all comparisons). There was no significant difference in BMI or ethnicity between those with 'confirmed OHSS' and those 'without OHSS', however women with 'confirmed OHSS' were younger (34 versus 41 years old, p<0.0001).

Discussion: Although absolute rates of OHSS requiring ICU admission recorded in this study are likely to represent a significant underestimate of all clinically significant OHSS, rates of OHSS requiring ICU admission have decreased since 1996 in concordance with the introduction of modern IVF practices.

Keywords: In Vitro Fertilization (IVF); Intensive Care Unit (ICU); Ovarian Hyperstimulation Syndrome (OHSS); rates; severe OHSS.

Figure 1

The absolute number of ‘confirmed’ and ‘potential’ OHSS cases from 1996-2020. The annual combined number of ‘confirmed’ and ‘potential’ OHSS cases between 1996 to September 2020. ‘Potential OHSS’ includes patients who presented to ICU with an OHSS-related condition and had a history of recent ART. All female patients were aged between 18-55 years presenting to an ICU in England, Wales, or Northern Ireland. OHSS cases for the year 2020 have been adjusted to account for the lack of data between October-December 2020. OHSS, Ovarian Hyperstimulation Syndrome; ICU, Intensive Care Unit; ART, Assisted Reproductive Technology.

Figure 2

The rate of ‘confirmed OHSS’ cases following normalization for the number of reporting centers from 1996-2018. (A) The total absolute number of ‘confirmed OHSS’ cases before normalization. (B) The prevalence (%) of ‘confirmed OHSS’ cases expected after normalization for the number of ICUs surveyed in 2020, expressed as a proportion of the number of fresh IVF cycles per year in England, Wales, and Northern Ireland. All female patients were aged between 18-55 years presenting to an ICU in England, Wales, or Northern Ireland. OHSS, Ovarian Hyperstimulation Syndrome; ICU, Intensive Care Unit; IVF, In Vitro Fertilization.

Figure 3

The ICU duration of stay for patients ‘without OHSS’ and ‘confirmed OHSS’ cases from 1996-2020. The ICU length of stay (up to 16 days) of female patients aged 18-55 years in England, Wales and Northern Ireland, 1996-Sept 2020, showing (A) patients ‘without OHSS’, and (B) patients with ‘confirmed OHSS’. Two outliers, ‘783’ and ‘2557’ days not included for two patients ‘without OHSS’. Data between 17-553 days spent in ICU (n=2,331 patients) for patients ‘without OHSS’ has not been presented in Figure 3A to allow its direct comparison with Figure 3B. Data is presented without normalization or adjustment. Coverage of ICUs in England, Wales and Northern Ireland has increased over time and therefore, relevant historical admissions for OHSS or potential OHSS are likely to be excluded. ICU, Intensive Care Unit; OHSS, Ovarian Hyperstimulation Syndrome.