The Comparison of Fixed and Flexible Progestin Primed Ovarian Stimulation on Mature Oocyte Yield in Women at Risk of Premature Ovarian Insufficiency

Abstract

While gonadotrophin releasing hormone (GnRH) antagonists have been the standard of pituitary suppression during ovarian stimulation for ART, progestin primed ovarian stimulation (PPOS) has emerged as an alternative. Progestins can be started simultaneously with gonadotrophins (fixed PPOS) or later in the cycle depending on follicle growth (flexible PPOS). However, the flexible and fixed PPOS regimens have not been directly compared as of yet. This was a retrospective cohort study including women with diminished ovarian reserve who underwent oocyte cryopreservation. All women underwent ovarian stimulation with a fixed 300 IU daily dose of FSH. The primary outcome was the number of MII oocyte retrieved per cycle. Secondary outcome measures included the incidence of premature LH surge (>10ng/mL) and number of follicles larger than 14mm on the day of maturation trigger. During the screening period 2 out of 97 cycles were cancelled before oocyte retrieval, one in each group yielding an overall cancelation rate of 2%. Among women who had oocyte retrieval, 65 underwent flexible and 30 fixed PPOS. At baseline women on fixed and flexible PPOS had similar age (mean difference: -2.17 years, 95% CI: -4.46 to 0.11) and serum AMH levels (mean difference: 0.10 ng/mL, 95% CI: -0.24 to 0.47). Slight imbalances between the groups were rectified with propensity score matching using age and AMH levels. The incidence of premature LH surge (RR: 1.47, 95% CI: 0.51 – 5.27, p = 0.50), follicle count larger than 14mm on hCG day (RR: 1.14, 95% CI: 0.93 – 1.42, p = 0.22), number of MII oocytes retrieved (RR: 0.95, 95% CI: 0.79 – 1.15, p = 0.61) were similar between flexible and fixed PPOS. The rate of no oocyte retrieval was same between the groups (0.0% both) but no formal estimation was possible. Flexible and fixed PPOS regimens had no appreciable differences regarding MII oocyte yield and the incidence of premature LH surges. Cycles without oocyte retrieval were rare in both groups and ultrasonographic parameters of gonadotropin response were similar. Our study suggests the performances of either progestin regimen are comparable in this group of women.

Progestin-primed ovarian stimulation

“…As mentioned previously, cPPOS and fPPSO render comparable results in patients with poor ovarian response according to POSEIDON Criteria [6].…”

“…Two retrospective studies compare the efficacy of fPPOS versus cPPOS in preventing a premature LH surge in patients with diminished ovarian reserve. Kalafat et al administered 10 mg-a-day of medroxyprogesterone acetate (MPA) to patients who had undergone OS for FP and found no differences between the two protocols in terms of number of cycles without oocyte retrieval, MII obtained or incidence of premature LH surge [6]. Similarly, Doğan Durdağ et al reported similar numbers of MII and incidence of premature luteinization and no differences in the number of two pronuclear zygotes and clinical pregnancy rate per transfer [7].…”

The comparison between fixed versus degressive doses of medroxyprogesterone acetate combined with letrozole in patients of progestin-primed ovarian stimulation protocol: a propensity score-matched study

“…To achieve optimal results, MPA should be applied before the LH surge induced by E 2 (10). As a flexible-start MPA protocol, the initiation of MPA usage could occur on stimulation day 7 or when the leading follicle reaches ≥ 12-14 mm or serum E 2 levels reach > 200 ng/mL (5,(28)(29)(30)(31)(32)(33). Notably, the peak plasma MPA concentration is typically reached 1-3 hours after oral administration (34), and the pituitary LH levels decrease after 5 days of MPA administration (10).…”

“…Most importantly, it significantly reduces the occurrence of ovarian hyperstimulation syndrome (OHSS), a severe complication associated with other COH protocols. Due to these benefits, the PPOS protocol is considered suitable for women with various ovarian responses, including those with poor ovarian response (3)(4)(5)(6), normal responders (7,8), and even high responders (7,9) in IVF/ICSI cycles.…”

Comparison of Cumulative Live Birth Rates between Flexible and Conventional Progestin-Primed Ovarian Stimulation Protocol in Poor Ovarian Response Patients According to POSEIDON Criteria: A Cohort Study

“…GnRH-ant and GnRH-a [ 25 ] are equally recommended for predicted poor responders according to ESHER guidelines [ 26 ]. Recently, progestins have been used as an alternative to GnRH analogs for preventing ovulation during ovarian stimulation [ 27 ]. High progesterone can inhibit LH peaks when multiple follicles are recruited with exogenous gonadotropin.…”