The progestin-primed ovarian stimulation protocol: more economical, but at what cost?

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 R35 years (4).>.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