Journal Article

Prediction of Ovarian Hyperstimulation Syndrome in Patients Treated with Corifollitropin alfa or rFSH in a GnRH Antagonist Protocol

Gates, Davis, Tarlatzis, Basil C., Gordon, Keith, Devroey, Paul, Stegmann, Barbara J., Griesinger, Georg, Verweij, Pierre J. M.

2016

Overview

What is the threshold for the prediction of moderate to severe or severe ovarian hyperstimulation syndrome (OHSS) based on the number of growing follicles ≥ 11 mm and/or estradiol (E2) levels? The optimal threshold of follicles ≥11 mm on the day of hCG to identify those at risk was 19 for both moderate to severe OHSS and for severe OHSS. Estradiol (E2) levels were less prognostic of OHSS than the number of follicles ≥ 11 mm. In comparison to long gonadotropin-releasing hormone (GnRH) agonist protocols, the risk of severe OHSS is reduced by approximately 50% in a GnRH antagonist protocol for ovarian stimulation prior to in vitro fertilisation (IVF), while the two protocols provide equal chances of pregnancy per initiated cycle. Nevertheless, moderate to severe OHSS may still occur in GnRH antagonist protocols if human chorionic gonadotropin (hCG) is administered to trigger final oocyte maturation, especially in high responder patients. Severe OHSS following hCG trigger may occur with an incidence of 1-2% in a relatively young (aged 18 to 36 years) IVF population treated in a GnRH-antagonist protocol. From the Engage, Ensure and Trust trials, in total, 2,433 women who received hCG for oocyte maturation and for whom the number of follicles ≥ 11 mm and the level of E2 on the day of hCG administration were known were included in the analyses. The threshold for OHSS prediction of moderate and severe OHSS was assessed in women treated with corifollitropin alfa or daily recombinant follicle stimulation hormone (rFSH) in a gonadotropin-releasing hormone (GnRH)-antagonist protocol. Receiver operating characteristics curve analyses for moderate to severe OHSS and severe OHSS were performed on the combined dataset and the sensitivity and specificity for the optimal threshold of number of follicles ≥ 11 mm, E2 levels on the day of (hCG), and a combination of both, were determined. The optimal threshold of follicles ≥ 11 mm on the day of hCG to identify those at risk of moderate to severe OHSS was 19 (sensitivity and specificity 62.3% and 75.6%, respectively) and for severe OHSS was also 19 (sensitivity and specificity 74.3% and 75.3%, respectively). The positive and negative predictive values were 6.9% and 98.6%, respectively, for moderate to severe OHSS, and 4.2% and 99.5% for severe OHSS. This was a retrospective analysis of combined data from three trials following ovarian stimulation with two different gonadotropins. For patients with 19 follicles or more ≥11 mm on the day of hCG, measures to prevent the development of OHSS should be considered. Secondary preventive measures include cycle cancellation or coasting, use of a GnRH agonist to trigger final oocyte maturation in place of hCG and a freeze all strategy. ClinicalTrials.gov NCT00702845 NCT00696800 NCT00696878.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 17β-Estradiol / Adolescent / Adult / Analysis / Biology and Life Sciences / Body mass index / Chorionic gonadotropin / Chorionic Gonadotropin - adverse effects / Chorionic Gonadotropin - pharmacology / Chorionic gonadotropins / Clinical medicine / Clinical trials / Clinical Trials as Topic / Coasting / Data processing / Drug dosages / Estradiol / Estradiol - metabolism / Estrogens / Female / Fertilization / Follicle Stimulating Hormone, Human - adverse effects / Follicle Stimulating Hormone, Human - pharmacology / Follicles / Glycoproteins / Gonadotropin-releasing hormone / Gonadotropin-Releasing Hormone - antagonists & inhibitors / Gonadotropins / Hormone Antagonists - adverse effects / Hormone Antagonists - pharmacology / Hormones / Humans / In vitro fertilization / Maturation / Medicine and health sciences / Organ Size - drug effects / Ovarian Follicle - drug effects / Ovarian Follicle - growth & development / Ovarian hyperstimulation syndrome / Ovarian Hyperstimulation Syndrome - chemically induced / Ovarian Hyperstimulation Syndrome - diagnosis / Ovarian Hyperstimulation Syndrome - metabolism / Ovarian Hyperstimulation Syndrome - pathology / Ovulation Induction - adverse effects / Patients / Pituitary (anterior) / Polycystic ovary syndrome / Predictions / Pregnancy / Prognosis / Reproductive health / Research and analysis methods / Retrospective Studies / Risk / Sensitivity / Sex hormones / Stimulation / Systematic review / Young Adult