Gonadotropin-releasing hormone (GnRH) agonists and
antagonists have been traditionally used in ovarian stimulation cycles to
suppress luteinizing hormone surges and ovulation. In 2015, the
progestin-primed ovarian stimulation (PPOS) protocol was proposed as an
alternative to cycles with GnRH analogues. This cycle type has several
advantages for patients, including lower costs, fewer injections, and
flexibility in trigger medication choice. Studies comparing GnRH antagonist and
PPOS protocols show no difference in the number of oocytes and the pregnancy
rate per transfer. In addition, live birth rates and ongoing pregnancy rates
are similar; however, the quality of evidence is low.
Recently, Zhang et al. published a retrospective
observational study that investigated cumulative live birth rates (CLBRs) in
patients with poor prognosis and a low body mass index undergoing ovarian stimulation
with GnRH antagonist regimens vs. PPOS regimens. The investigators showed that
in this subset of patients, GnRH antagonist protocols were superior. Patients
in the PPOS group had significantly lower CLBRs per oocyte retrieval cycle
(25.2% vs. 35.3%; P.001).
This effect was even greater in patients aged ≥35 years.
As the long-term outcome data are currently very limited on
the PPOS protocol, Chen et al. offered valuable insight into the utility of
PPOS. This was a retrospective cohort study that compared infertility patients
undergoing GnRH antagonist protocol ovarian stimulation with PPOS protocol
ovarian stimulation. It is the first study to describe CLBR and time to live
birth (TTLB) in the general population with infertility. This study
demonstrated that GnRH antagonist protocols are superior to PPOS regimens. The
number of oocytes obtained, number of oocytes fertilized, number of cleaving
embryos, number of transferable embryos, total implantation rate, and pregnancy
rate per transfer between the groups were comparable but the CLBRs were not.
After one complete in vitro fertilization cycle and within 22 months of
follow-up, those in the GnRH antagonist group had a CLBR of 36% vs. 32% in the
PPOS group that was statistically significant.
Similarly, in the study by Zhang et al., CLBR outcomes were
even more disparate in women with antral follicle counts of %5 and aged >35
years. Furthermore, TTLB was significantly longer in the PPOS group. However,
the PPOS protocol requires a freeze-all cycle that may have contributed to this
difference (5). Overall, this study illustrates that PPOS protocols, although
perhaps more patient-friendly, do not offer the same results as GnRH antagonist
cycles when it comes to CLBR.
The study by Chen et al. was the first study to investigate
CLBR and TTLB in patients with infertility with a variety of diagnoses. The
thorough analyses performed in this study show that despite both protocols
resulting in similar numbers of oocytes and transferable embryos, GnRH
antagonist protocols have improved CLBRs and shorter TTLB. Thus, previous
studies have considered the protocols to have similar efficacy because they
lacked the long-term follow-up performed by Chen et al. In addition, this study
controlled for its retrospective nature by using propensity score matching to
reduce the difference between the two groups. The propensity score matching
reduces bias by accounting for confounding variables that may affect outcomes.
After propensity score matching based on nine variables, the study groups were
highly comparable and allowed for a direct comparison between the two
protocols.
This study offers a detailed statistical analysis and
investigation of CLBR and TTLB after PPOS but is also limited by its
retrospective nature. In the future, a freeze-all randomized control study with
a diverse population with infertility and a long-term follow-up should be
conducted to improve understanding of the use of PPOS regimens for ovarian
stimulation and the effect on CLBRs compared with GnRH antagonist protocols.
This would allow for a better comparison of the two regimens by removing the
variability of fresh and frozen transfers. In the meantime, this study
illustrates that the PPOS protocol, although more patient-friendly and
economical, may come at the cost of lower CLBRs and longer TTLB.
Source: https://doi.org/10.1016/j.fertnstert.2022.08.847