Effect of GnRHa ovulation trigger dose on follicular fluid characteristics and granulosa cell gene expression profiles

Abstract

Purpose: A recent dose-finding study showed no significant differences in number of mature oocytes, embryos and top-quality embryos when triptorelin doses of 0.2, 0.3 or 0.4 mg were used to trigger final oocyte maturation in oocyte donors co-treated with a gonadotropin-releasing hormone (GnRH) antagonist. This analysis investigated whether triptorelin dosing for triggering final oocyte maturation in oocyte donors induced differences in follicular fluid (FF) hormone levels and granulosa cell gene expression.

Methods: This single-centre, randomised, parallel, investigator-blinded trial was conducted in oocyte donors undergoing a single stimulation cycle at IVFMD, My Duc Hospital, Ho Chi Minh City, Vietnam, from August 2014 to March 2015. A total of 165 women aged 18-35 years with body mass index <28 kg/m2, anti-Müllerian hormone >1.25 ng/mL, and antral follicle count ≥6 were randomised to three different triptorelin doses for trigger. The main outcome was concentration of steroid hormones in FF collected from the first punctured follicle on each side. Moreover, luteinising hormone receptor (LHR), 3β-hydroxy-steroid-dehydrogenase (3ßHSD) and inhibin-Ba (INHB-A) gene expression in cumulus and mural granulosa cells were investigated in a subset of women from each group.

Results: Progesterone and oestradiol levels in FF did not differ significantly by trigger doses; findings were similar for 3βHSD, LHR and INHB-A gene expression in both cumulus and mural granulosa cells.

Conclusions: In women co-treated with a GnRH antagonist, no significant differences in FF steroid levels and granulosa cell gene expression were seen when different triptorelin doses were used to trigger final oocyte maturation.

Keywords: Follicular fluid; Gonadotropin-releasing hormone agonist trigger; In vitro fertilisation; LHR gene expression; Triptorelin.

Conflict of interest statement

Funding

The study was supported by Merck Sharp and Dohme.

Competing interests

The authors state that they have no competing interests.

Ethics approval and informed consent

All patients provided written informed consent. The study protocol was approved by the Institutional Review Board (IRB) and Ethics Committee on 21 July 2014 (IRB reference number: NCKH/CGRH_01_2014).

Figures

Fig. 1

CONSORT flow diagram. AMH anti-Müllerian hormone, COS controlled ovarian stimulation, GnRH gonadotropin-releasing hormone, OPU oocyte pick-up, PCOS polycystic ovary syndrome

Fig. 2

Hormone levels (a progesterone and b oestradiol) in follicular fluid after trigger using triptorelin 0.2, 0.3 and 0.4 mg

Fig. 3

Gene expression in cumulus cells, normalised to glyceraldehyde 3-phosphate dehydrogenase (GAPDH), after trigger using triptorelin 0.2, 0.3 and 0.4 mg. a 36-Hydroxysteroid dehydrogenase (HSD). b Luteinising hormone receptor (LHR). c Inhibin beta A (IHNB-A)

Fig. 4

Gene expression in mural granulosa cells, normalised to glyceraldehyde 3-phosphate dehydrogenase (GAPDH), after trigger using triptorelin 0.2, 0.3 and 0.4 mg. a 36-Hydroxysteroid dehydrogenase (HSD). b Luteinising hormone receptor (LHR). c Inhibin beta A (IHNB-A)