Comparison of Cumulative Live Birth Rates Between Progestin and GnRH Analogues in Preimplantation Genetic Testing Cycles

Abstract

Context Progestins have recently been used as an alternative for GnRH analogues to prevent premature LH surge due to the application of vitrification technology. However, the long-term efficacy and safety of progestin-primed ovarian stimulation (PPOS) regimen, including oocyte competence, cumulative live birth rate (LBR), and offspring outcomes, remain to be investigated. Objective To compare cumulative LBR of preimplantation genetic testing (PGT) cycles between PPOS regimen and GnRH analogues. Design Retrospective cohort study. Setting Tertiary academic medical center. Patients A total of 967 patients with good prognosis were categorized into three groups, of which 478 patients received a long GnRH agonist, 248 patients received a GnRH antagonist and 250 received a PPOS regimen. Medroxyprogesterone 17-acetate (MPA) was the only progestin used in PPOS regimen. Intervention None. Main Outcome Measures The primary outcome was cumulative LBR. Secondary outcomes included time to live birth, cumulative rates of biochemical and clinical pregnancy and pregnancy loss, and perinatal outcomes. Results The PPOS regimen was negatively associated with cumulative LBR compared to GnRH antagonists and GnRH agonists (28.4% versus 40.7% and 42.7%). The average time to live birth was significantly shorter with GnRH antagonists than with PPOS regimen. The cumulative biochemical and clinical pregnancy rates were also lower in PPOS regimen than GnRH analogues, while cumulative pregnancy loss rates were similar across groups. Furthermore, the number and ratio of good-quality blastocysts were significantly reduced in PPOS regimen compared to GnRH analogues. In addition, perinatal outcomes were comparable across three groups. Conclusions PPOS regimen may be adversely affect cumulative LBR and blastocyst quality in women with good prognosis compared to GnRH analogues in PGT cycles.

Progestin-primed ovarian stimulation

“…In addition to the usual limitations associated with retrospective studies, data regarding GnRH agonist triggers and cancelled embryo biopsied were not included. Likewise, in this study and another by the authors, the same normorresponder population was assessed [25,26]. On the other hand, a lower CLBR was observed in the PPOS-treated patients compared to the GnRH analogue group, despite a similar OS response and number of euploid blastocysts obtained.…”

“…The study did not refer to the euploidy rate, but highlighted that blastocyst morphologic classification and number were inferior in the PPOS group, which would have justified the lower cumulative LBR. The study was limited by its retrospective nature, discrepant population size in each branch, and the fact that the largest group (478) to undergo the GnRH agonist protocol produced significantly more oocytes, which may have affected the cumulative LBR, the primary outcome [26] (Table 2).…”

Progestin-primed ovarian stimulation

“…Zhou et al [16,17] published 2 retrospective studies claiming sig nificantly lower CLBR with PPOS. In addition to errors in design, ie, exclusion of patients who received a GnRH agonist trigger or had the embryo biopsy canceled, both of which can be related to ovarian response and choice of stimulation protocol, the nor moresponders in the GnRH antagonist and PPOS groups were the same patients in the 2 studies, as evidenced by patient num bers, baseline characteristics, and treatment outcomes reported in the 2 papers [16,17] . This duplicate publication of the same group of patients with erroneous design features undermines the credibility of the results.…”