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.