Progestin primed ovarian stimulation using corifollitropin alfa in PCOS women effectively prevents LH surge and reduces injection burden compared to GnRH antagonist protocol

Abstract

Utilizing corifollitropin alfa in GnRH antagonist (GnRHant) protocol in conjunction with GnRH agonist trigger/freeze-all strategy (corifollitropin alfa/GnRHant protocol) was reported to have satisfactory outcomes in women with polycystic ovary syndrome (PCOS). Although lessening in gonadotropin injections, GnRHant were still needed. In addition to using corifollitropin alfa, GnRHant was replaced with an oral progestin as in progestin primed ovarian stimulation (PPOS) to further reduce the injection burden in this study. We try to investigate whether this regimen (corifollitropin alfa/PPOS protocol) could effectively reduce GnRHant injections and prevent premature LH surge in PCOS patients undergoing IVF/ICSI cycles. This is a retrospective cohort study recruiting 333 women with PCOS, with body weight between 50 and 70 kg, undergoing first IVF/ICSI cycle between August 2015 and July 2018. We used corifollitropin alfa/GnRHant protocol prior to Jan 2017 (n = 160), then changed to corifollitropin alfa/PPOS protocol (n = 173). All patients received corifollitropin alfa 100 μg on menstruation day 2/3 (S1). Additional rFSH was administered daily from S8. In corifollitropin alfa/GnRHant group, cetrorelix 0.25 mg/day was administered from S5 till the trigger day. In corifollitropin alfa/PPOS group, dydrogesterone 20 mg/day was given from S1 till the trigger day. GnRH agonist was used to trigger maturation of oocyte. All good quality day 5/6 embryos were frozen, and frozen-thawed embryo transfer (FET) was performed on subsequent cycle. A comparison of clinical outcomes was made between the two protocols. The primary endpoint was the incidence of premature LH surge and none of the patients occurred. Dydrogesterone successfully replace GnRHant to block LH surge while an average of 6.8 days of GnRHant injections were needed in the corifollitropin alfa/GnRHant group. No patients suffered from ovarian hyperstimulation syndrome (OHSS). The other clinical outcomes including additional duration/dose of daily gonadotropin administration, number of oocytes retrieved, and fertilization rate were similar between the two groups. The implantation rate, clinical pregnancy rate, and live birth rate in the first FET cycle were also similar between the two groups. In women with PCOS undergoing IVF/ICSI treatment, corifollitropin alfa/PPOS protocol could minimize the injections burden with comparable outcomes to corifollitropin alfa/GnRHant protocol.

Letrozole cotreatment improves the follicular output rate in high-body-mass-index women with polycystic ovary syndrome undergoing IVF treatment

“…The sums of follicles with diameters of 10-12 mm and 12-14 mm were comparable across the two groups. The study group had a substantial reduction in the sum of follicles with a diameter of 14-16 mm (2 [0, 6] vs. 3 [1,6], P <.05) but significantly higher number of follicles larger than 16 mm when compared with the control group (10.5 [7,18] vs. 8 [4,11], P <.05) (Table 2). Consistent with the above results, FORT was substantially elevated in the study group compared with the control group (61% [35%, 86%] vs. 40% [25%, 60%], P <.01).…”

“…As an alternative to standard GnRH analogues, progestinprimed ovarian stimulation (PPOS) by administering human menopausal gonadotropin (hMG) and medroxyprogesterone acetate (MPA) simultaneously from the early follicular phase successfully inhibits the oestradiol (E2)-induced LH surge (4). The PPOS protocol could achieve similar numbers of oocytes, viable embryos, and pregnancy outcomes (5); moreover, it is more patient-friendly, as it can further reduce the injection burden compare with the conventional GnRH analogue protocol (6).…”

Efficacy of progestin-primed ovarian stimulation in women with polycystic ovary syndrome undergoing in vitro fertilization: a systematic review and meta-analysis

“…We included three RCTs ( 15 , 16 , 33 ) and six retrospective cohort studies ( 11 , 17 , 29 – 32 ) involving 2289 women. Most included studies were conducted in China ( 11 , 15 , 17 , 30 – 33 ), and the others were in Japan ( 29 ) and Iran ( 16 ). The average age of women was 28-34 years old.…”

“…Four studies ( 15 , 17 , 31 , 32 ) applied medroxyprogesterone acetate (MPA) as the oral progestin in the PPOS group; two used GnRH-a short protocol in the control group, and the other two used GnRH antagonist protocol. Three studies ( 16 , 29 , 30 ) used dydrogesterone in the PPOS group, with GnRH antagonist protocol in all control groups. The remaining two studies ( 11 , 33 ) used Utrogestan as the oral progestin, either GnRH-a short protocol or GnRH antagonist protocol in the control group.…”

Corifollitropin Alfa for Controlled Ovarian Stimulation in Assisted Reproductive Technologies: State of the Art

“…In that way, progestin-primed protocols have been studied in the last years, including oral medroxyprogesterone acetate or dydrogesterone, with satisfactory outcomes, but limited to freeze-all cycles. 33 34 35 36 Women at risk for a hyper-response, such as those with a history of OHSS, with polycystic ovary syndrome (PCOS) or with a high antral follicle count (> 19), remain to compose the group for whom corifollitropin alfa should be avoided. 3 Nevertheless, small observational studies have been demonstrating the feasibility of corifollitropin alfa use in PCOS, if the GnRH antagonist protocol is combined with GnRH agonist triggering and total embryo cryopreservation.…”