Letrozole cotreatment with progestin-primed ovarian stimulation in women with polycystic ovary syndrome undergoing IVF treatment

Abstract

Background: Progestin is an alternative to gonadotropin-releasing hormone (GnRH) analogues in the follicular phase to suppress the premature luteinizing hormone (LH) surge in women with polycystic ovary syndrome (PCOS). However, progestin-primed ovarian stimulation (PPOS) is always accompanied by increased pituitary suppression and gonadotropin consumption. Previous studies suggested that letrozole appeared to have the potential to reduce the total gonadotropin dose required for ovarian stimulation. A retrospective cohort study was performed to evaluate the efficacy of PPOS with or without letrozole in infertile women with PCOS.Methods: This retrospective cohort study included 448 women with PCOS who underwent controlled ovarian stimulation (COS) with human menopausal gonadotropin (hMG) and medroxyprogesterone acetate (MPA) (n = 224) or hMG and MPA cotreatment with LE (n = 224) from January 2018 to March 2021 after propensity-score matching. The primary outcome measure was the hMG dose. The secondary outcomes were the durations of ovarian stimulation, the implantation rate, the number of oocytes retrieved and viable embryos, oocyte maturity and fertilization rates, the percentage of women with profound pituitary suppression (luteinizing hormone [LH] <1.0 IU/L on the trigger day).Results: The hMG doses (1949.89 ± 725.03 IU vs 2017.41 ± 653.32 IU,p > 0.05) and durations of ovarian stimulation (9.03 ± 1.79 days vs 9.21 ± 2.18 days,p > 0.05) were similar between the two groups. The implantation rate was significantly higher in the study group (MPA + hMG + LE) than in the control group (MPA + hMG) (42.22 vs 34.69%, p < 0.05). The numbers of oocytes and embryos retrieved were similar between the two groups. Interestingly, letrozole cotreatment was associated with decreased oocyte maturity and fertilization rates in comparison with standard PPOS protocols even though mature and fertilized oocyte yields were comparable. Compared with those in the control group, the LH values on the trigger day were significantly higher in the study group, together with significantly reduced pituitary suppression.Conclusion: Letrozole combined with PPOS cannot reduce hMG consumption in PCOS patients undergoing IVF treatment and shows no beneficial effect on cycle characteristics of COS. However, letrozole supplementation manifests as a superior implantation rate to that of the standard PPOS protocol in women with PCOS.

Letrozole cotreatment progestin‐primed ovarian stimulation in women undergoing controlled ovarian stimulation for in vitro fertilization

“…The results suggested that the clinical pregnancy of patients with the Le PPOS protocol was significantly higher than with the traditional PPOS protocol. Those results are supported by a previous study that showed higher implantation rates with Le PPOS compared with PPOS in patients with PCOS 20 . This study is unique in that the PSM method was used; the advantages of Le PPOS can be better reflected when the characteristics of the two groups are similar.…”

“…MPA cotreatment starting on MC3 can block the premature LH surge, but this strategy will fail if MPA is started during the mid‐follicular phase, at least in women with multiple follicles and high E2 levels 6 . In the present study, MPA was used from MC6 in the Le PPOS group, and there were no premature LH surges, as previously observed in women with polycystic ovary syndrome (PCOS) 20 . The results suggest that letrozole might create an environment with low estrogen levels and allow a reduced time and dose of MPA.…”

“…6 In the present study, MPA was used from MC6 in the Le PPOS group, and there were no premature LH surges, as previously observed in women with polycystic ovary syndrome (PCOS). 20 The results suggest that letrozole might create an environment with low estrogen levels and allow a reduced time and dose of MPA. Therefore, pituitary inhibition largely caused by MPA accumulation was avoided.…”

“…Those results are supported by a previous study that showed higher implantation rates with Le PPOS compared with PPOS in patients with PCOS. 20 This study is unique in that the PSM method was used; the advantages of Le PPOS can be better reflected when the characteristics of the two groups are similar. In addition, the number of oocytes obtained, the number of fertilized oocytes, and the number of available embryos in the Le PPOS group were superior to the traditional PPOS.…”

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

“…Previous research has shown that 10 mg of MPA effectively inhibits spontaneous ovulation, whereas 5 mg does not yield the same results ( 11 ). However, conflicting findings have been reported regarding the appropriate MPA dosage for preventing untimely LH surges, with some studies suggesting that daily doses of 4 mg ( 12 , 13 ) or 6 mg ( 3 , 6 ) are sufficient. In our previous study, we demonstrated that coadministration of letrozole (LE) with MPA during ovarian stimulation for IVF achieved comparable embryo and pregnancy outcomes while reducing the required MPA dosage ( 14 ).…”