Following recruitment and growth of follicles to the mature stage resulting from ovarian stimulation, the next step is maturation of oocytes facilitated by ovulation trigger in COS regimens. The LH surge that induces germinal vesicle breakdown and ovulation in a natural menstrual cycle is not reliable in stimulated multi-follicular cycles necessitating artificial triggering of ovulation. hCG which is naturally produced by the human placenta and excreted in large quantities in the urine of pregnant women bears a close molecular resemblance to LH and has a similar effect on the LH receptor. hCG can be used because of its longer serum half-life (36 h) compared to the short serum half-life of LH (108–148 min) [36], thus avoiding the inconvenience of repeated administration. Administration of hCG results in luteinisation of the granulosa cells, progesterone biosynthesis, resumption of meiosis, oocyte maturation, and subsequent follicular rupture 36–40 h later. It is administered after the stimulated development of mature preovulatory follicles in order to induce maturation, but oocyte retrieval is undertaken before ovulation. The usual criteria for the administration of hCG is the presence of ≥3 follicles of ≥18 mm in diameter. The preparations of hCG that are available for clinical use are the urinary and recombinant forms and are comparable for IVF outcomes [37]. The usual dose of hCG for final ovulation triggering is between 5,000 IU and 10,000 IU as a single dose.

The GnRH agonist trigger has been proposed as an alternative to the hCG trigger by virtue of inducing an endogenous rise in LH and FSH due to its initial flare effect [38, 39]. The GnRH agonist trigger can only be used with COS regimens where prior pituitary suppression has not been achieved with a GnRH agonist, as the mechanism of action of the GnRH agonist for downregulation and desensitisation of the pituitary receptors precludes the use of the agonist trigger. Due to the specific mode of action of the antagonist by competitive blockade of the pituitary receptors and a shorter half-life, the pituitary remains responsive to the GnRH agonist, thus enabling its use for triggering ovulation. The Cochrane review comparing the GnRH agonist versus the hCG trigger in IVF demonstrated a significantly lower incidence of OHSS and a lower live birth rate with the GnRH agonist trigger [40]. It demonstrated significantly reduced live birth rates in fresh autologous cycles with the use of the GnRH agonist trigger, but there was no reduction in live birth rates in oocyte donor/recipient cycles. Following initial use of the GnRH agonist trigger, it was soon recognised of the need to modify the standard luteal support to obtain reliable reproductive outcomes [41]. Study groups have since endeavoured to fine-tune the luteal phase support in IVF cycles using the GnRH agonist trigger to optimise clinical outcomes [42, 43]. Recent suggestions and developments in overcoming the luteal insufficiency with the GnRH agonist trigger are use of (1) a “dual trigger” [44], (2) low-dose hCG supplementation [41, 43], (3) intensive luteal oestradiol and progesterone supplementation [42], (4) rec-LH supplementation [45], and (5) luteal GnRH agonist administration [46]. A recent RCT demonstrated that an individualised luteal support based on the number of follicles following the GnRH agonist trigger optimised the pregnancy rates [47]. This study proposed ovulation triggering with 0.5 mg buserelin subcutaneously followed by a bolus of 1,500 IU of hCG after oocyte retrieval when the total number of follicles ≥11 mm was between 15 and 25 on the day of trigger and an additional 1,500 IU hCG bolus when the total number of follicles was ≤14 mm. All women received micro-ionised progesterone vaginally, 90 mg twice daily, and 4 mg of oestradiol orally commencing on the day of oocyte retrieval and continuing until 7 weeks of gestation.

The ultimate aim of IVF is to obtain a healthy singleton live birth with minimal adverse effects. Multiple pregnancies are recognised as a major avoidable complication of IVF. Planning of effective COS regimens is important as it leads to good quality embryos enabling selection of the best single embryo for transfer. After decades of IVF practice, it is now recognised that individualisation in IVF is the way forward. The long GnRH agonist and antagonist regimens are effective in normal responders and the ideal gonadotrophin dose is 225 IU daily. The GnRH antagonist regimen is ideal for women with PCOS and women categorised as hyper-responders. Whilst the pregnancy rates are comparable to the GnRH agonist regimen, the antagonist regimen significantly lowers the risk of OHSS in addition to enabling the use of the GnRH agonist trigger which potentially eliminates OHSS. A lower gonadotrophin dose ≤150 IU daily is recommended in these women. The long GnRH agonist and antagonist regimens are ideal for poor responders. Higher gonadotrophin doses >300 IU daily are unlikely to be beneficial in poor responders apart from higher costs and hence the maximal gonadotrophin dose should not exceed 300 IU daily.