Introduction
Ovarian stimulation is a crucial step in assisted reproduction and the aim is to produce multiple follicles with the use of gonadotropins. The rapid rise of oestrogen can induce a positive feedback that gives rise to LH surge1. However, premature LH surge can cause early ovulation and affect oocyte quality and embryo development resulting in a low pregnancy rate. Therefore, how to inhibit the early onset LH surge becomes the core issue in the process of ovulation stimulation2,3. Efforts to minimize the occurrence of a premature LH surge have mainly relied on the use of GnRH agonist (GnRHa) and antagonist 3. Down-regulation of GnRHa promotes follicle synchronization, with the consequences being increased procedure complexity, higher cost, and greater risk of ovarian hyperstimulation syndrome (OHSS)4,5. GnRH antagonists produce rapid LH suppression with no initial flare effect 6. A Cochrane meta-analysis showed similar pregnancy outcomes in both protocols (Al-Inany, et al. 2011). Moreover, the use of the GnRH agonist trigger in the antagonist regimen can reduce the incidence of OHSS 7, 8. Up to now, GnRH antagonist protocol has become the most popular regimen in the great majority of assisted reproduction centers worldwide.
In 2015, progestin-primed ovarian stimulation (PPOS) was proposed9. In this new protocol, progestin is used as an alternative to GnRH analog or antagonist to suppress a premature LH surge during the follicular phase. Moreover, progestin has the advantage of being administered orally and is more patient friendly. Furthermore, to avoid a low response of the hypothalamic pituitary ovarian (HPO) axis, a double trigger with GnRHa and a low dose of hCG (1000 IU) was used to induce final oocyte maturation without increasing the risk of moderate or severe OHSS10. This new regimen of ovarian stimulation has been proven to effectively prevent a premature LH surge and does not compromise oocyte competence in cycles followed by embryo cryopreservation9, 11
However, in most trials, the efficacy and reproductive outcomes of PPOS regimen were compared to short GnRH agonist protocol, which is now rarely used in many assisted reproduction programs. One randomized trial12 compared use of medroxyprogesterone versus a GnRH antagonist on the number of mature oocytes retrieved in oocyte donation cycles. Though no differences were found in the number of mature oocytes between the two groups, the clinical pregnancy rate was 31% versus 46% (P = 0.006) and the ongoing pregnancy rate 27% versus 40% (P = 0.015) for medroxyprogesterone and GnRH antagonists, respectively. This suggests a possible impairment of oocyte quality when medroxyprogesterone is used in ovarian stimulation. However, the oocyte recipients were not randomized. There is scarcity of information comparing the pregnancy outcomes between PPOS and antagonist protocol.
The aim of this retrospective study is to compare the efficacy of PPOS regimen and GnRH antagonist protocol in terms of pregnancy outcomes in first frozen embryo transfer (FET) cycles.