Progestin vs. Gonadotropin-Releasing Hormone Antagonist for the Prevention of Premature Luteinizing Hormone Surges in Poor Responders Undergoing in vitro Fertilization Treatment: A Randomized Controlled Trial

Abstract

Objective: Progestin was recently used as an alternative of gonadotropin-releasing hormone (GnRH) analog for preventing premature luteinizing hormone (LH) surge with the aid of vitrification techniques, however, limited data were available about the potential of progestin in poor responders undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment. We performed a randomized parallel controlled trial to investigate the difference of progestin and GnRH antagonist in poor responders.Methods: A total of 340 poor responders who met with Bologna criteria were randomly allocated into the progestin-primed ovarian stimulation (PPOS) group and GnRH antagonist group. Fresh embryo transfer was preferred in the GnRH antagonist group and freeze-all was performed in the PPOS group. The primary outcome was the incidence of premature LH surge, secondary outcomes were the number of retrieved oocytes, the number of viable embryos and the pregnancy outcomes.Results: The results showed that the incidence of premature LH surge in PPOS group was lower than that in antagonist group (0 vs. 5.88%, P < 0.05). In PPOS group, the average numbers of oocytes and viable embryos were comparable to those in GnRH antagonist group (3.7 ± 2.6 vs. 3.4 ± 2.4; 1.6 ± 1.7 vs. 1.4 ± 1.3, P > 0.05), the live birth rate was similar between the two groups (21.8 vs. 18.2%, RR 1.25 (95% confidence interval 0.73, 2.13), P > 0.05).Conclusions: The study demonstrated that PPOS had a more robust control for preventing premature LH rise than GnRH antagonist in poor responders, but PPOS in combination with freeze-all did not significantly increase the probability of pregnancy than GnRH antagonist protocol for poor responders.

The best execution of the DuoStim strategy (double stimulation in the follicular and luteal phase of the same ovarian cycle) in patients who are poor ovarian responders

“…However, the literature in recent years has all related to the safety and effectiveness of the PPOS scheme [38]. It is suggested that the numbers of blastocysts and euploid blastocysts per patient and the number of euploid embryos per injected oocyte are similar for patients undergoing the PPOS program and for those undergoing COS with GnRH antagonists [39]. Flexible progestin-primed ovarian stimulation (FPPOS) with MPA seems to be an effective choice for preventing premature ovulation in women undergoing ovarian stimulation without compromising oocyte quality [40].…”

Effectiveness of progesterone-primed ovarian stimulation in assisted reproductive technology: a systematic review and meta-analysis

“…Table 1 provides brief details of populations and interventions. Two RCTs [ 4 , 15 ] included PCOS participants, and the studies by Chen et al [ 7 ] and Huang et al [ 9 ] included participants with poor responders. Wen et al [ 12 ] and Begueria et al [ 8 ] included participants with a maximum age of 35 years.…”

“…PPOS can effectively prevent the activation and transmission phases of oestradiol (E2)-induced LH surges and thus serves as an alternative to conventional treatment with GnRH analogs. Prior studies have shown that the PPOS protocol with medroxyprogesterone acetate (MPA) produces competent oocytes/embryos and achieves comparable pregnancy outcomes to those of GnRH antagonist protocols [ 3 , 4 , 7 – 11 ], as well as short-term protocols [ 12 , 13 ] and mild stimulation protocols [ 5 ] (see Table 1 ). Coupled with the application of frozen-thawed embryo transfer (FET) and the dual trigger of GnRH agonist with low-dose hCG, the PPOS protocol also allows for nearly complete avoidance of OHSS occurrence [ 14 , 15 ], since all the embryo transfers after PPOS are frozen.…”

“…Coupled with the application of frozen-thawed embryo transfer (FET) and the dual trigger of GnRH agonist with low-dose hCG, the PPOS protocol also allows for nearly complete avoidance of OHSS occurrence [ 14 , 15 ], since all the embryo transfers after PPOS are frozen. There are many clinical studies on PPOS protocol use in infertile women, including women who have normal ovarian function, PCOS [ 4 , 15 ], poor ovarian response [ 7 , 9 ], who are of advanced maternal age [ 5 ], having endometriosis [ 11 ] and donated oocytes [ 10 ]. The reported findings are variable; some studies have shown better live birth outcomes, while others showed no difference.…”

Controlled ovarian hyperstimulation for poor ovarian responders undergoing in vitro fertilisation/intracytoplasmic sperm injection: a protocol for systematic review and Bayesian network meta-analysis

“…Currently, the most frequently proposed COH protocols include delayed start GnRH antagonist protocol, 14 short GnRH agonist protocol, 15 mild ovarian stimulation protocol, 16 GnRH antagonist protocol, 17 natural cycle protocol, 18 long GnRH agonist protocol, 19 stop GnRH agonist protocol, 20 flare up GnRH agonist protocol, 21 luteal phase ovarian stimulation protocol 22 and progestin-primed ovarian stimulation protocol. 23 …”