Clinical parameters of ovarian hyperstimulation syndrome following different hormonal triggers of oocyte maturation in IVF treatment

A Abbara, R Islam, S A Clarke, L Jeffers, G Christopoulos, A N Comninos, R Salim, S A Lavery, T N L Vuong, P Humaidan, T W Kelsey, G H Trew, W S Dhillo, A Abbara, R Islam, S A Clarke, L Jeffers, G Christopoulos, A N Comninos, R Salim, S A Lavery, T N L Vuong, P Humaidan, T W Kelsey, G H Trew, W S Dhillo

Abstract

Objective: Ovarian hyperstimulation syndrome (OHSS) is a serious iatrogenic condition, predominantly related to the hormone used to induce oocyte maturation during IVF treatment. Kisspeptin is a hypothalamic neuropeptide that has recently been demonstrated to safely trigger final oocyte maturation during IVF treatment even in women at high risk of OHSS. However, to date, the safety of kisspeptin has not been compared to current hormonal triggers of oocyte maturation.

Design: We conducted a retrospective single-centre cohort study investigating symptoms and clinical parameters of early OHSS in women at high risk of OHSS (antral follicle count or total number of follicles on day of trigger ≥23) triggered with human chorionic gonadotrophin (hCG) (n = 40), GnRH agonist (GnRHa; n = 99) or kisspeptin (n = 122) at Hammersmith Hospital IVF unit, London, UK (2013-2016).

Results: Clinical Parameters of OHSS: Median ovarian volume was larger following hCG (138 ml) than GnRHa (73 ml; P < .0001), and in turn kisspeptin (44 ml; P < .0001). Median ovarian volume remained enlarged 20-fold following hCG, 8-fold following GnRHa and 5-fold following kisspeptin compared to prestimulation ovarian volumes. Mean (±SD) ascitic volumes were lesser following GnRHa (9 ± 44 ml) and kisspeptin (5 ± 8 ml) than hCG (62 ± 84 ml; P < .0001). Symptoms of OHSS were most frequent following hCG and least frequent following kisspeptin. Diagnosis of OHSS: The odds ratio for OHSS diagnosis was 33.6 (CI 12.6-89.5) following hCG and 3.6 (CI 1.8-7.1) following GnRHa, when compared to kisspeptin.

Conclusion: Triggering oocyte maturation by inducing endogenous gonadotrophin release is preferable to the use of exogenous hCG in women at high risk of OHSS.

Trial registration: ClinicalTrials.gov NCT01667406.

Keywords: GnRH agonist; IVF; hCG; kisspeptin; ovarian hyperstimulation syndrome.

© 2018 The Authors. Clinical Endocrinology Published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Clinical parameters of early ovarian hyperstimulation syndrome (OHSS) by trigger of oocyte maturation administered. A, Scattergram (median ± IQR) of mean ovarian volume at 2‐6 d following oocyte retrieval during IVF treatment in patients triggered with either human chorionic gonadotrophin (hCG) (n = 40), GnRH agonist (GnRHa; n = 99), or kisspeptin (n = 122). Baseline prestimulation median ovarian volume before stimulation with any of the 3 triggers is also presented. The three trigger groups were compared by the Kruskal‐Wallis test with post hoc Dunn's correction for multiple comparisons. ****P < .0001. B, Scattergram (median ± IQR) of maximal ovarian volume (largest ovarian volume of either ovary) at 2‐6 d following oocyte retrieval during IVF treatment in patients triggered with either hCG (n = 40), GnRH agonist (GnRHa; n = 99), or kisspeptin (n = 122). Groups were compared by the Kruskal‐Wallis test with post hoc Dunn's correction for multiple comparisons. ***P < .001, ****P < .0001. C, Scattergram (median ± IQR) of percentage increase in mean ovarian volume at 2‐6 d following oocyte retrieval when compared to prestimulation baseline values before IVF treatment in patients triggered with either hCG (n = 30), GnRH agonist (GnRHa; n = 90), or kisspeptin (n = 122). Groups were compared by the Kruskal‐Wallis test with post hoc Dunn's correction for multiple comparisons. ****P < .0001. D, Scattergram of total ascitic volume (median ± IQR) (free fluid in pouch of Douglas, adnexae and abdomen) at 2‐6 d following oocyte retrieval during IVF treatment in patients triggered with either hCG (n = 40), GnRH agonist (GnRHa; n = 99), or kisspeptin (n = 122). Groups were compared by Kruskal‐Wallis test with post hoc Dunn's correction for multiple comparisons. ****P < .0001
Figure 2
Figure 2
Symptoms of early ovarian hyperstimulation syndrome (OHSS) by trigger of oocyte maturation administered. The frequency of symptoms of OHSS by trigger of oocyte maturation is presented for patients receiving either human chorionic gonadotrophin (hCG) (n = 40), GnRH agonist (GnRHa; n = 99), or kisspeptin (n = 122). The frequency of symptoms consistent with OHSS including abdominal pain (A), abdominal bloating (B), diarrhoea (C), nausea (D), vomiting (E) and self‐reported reduction in urine output (F) are presented. The odds ratio of experiencing each symptom by trigger of oocyte maturation is presented in Table 1

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