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Fixed Gonadotropin-Releasing Hormone Antagonist Protocol Versus Flexible Progestin-Primed Ovarian Stimulation Protocol in Patients With Asynchronous Follicular Development During Controlled Ovulation Stimulation: A Retrospective Study.

ABSTRACT: Protocols utilizing gonadotropin-releasing hormone (GnRH) antagonists have emerged as mainstream procedures for ovarian stimulation; however, GnRH increases the risk for periodic cancellation of embryos. Therefore, this study aimed to compare the pregnancy outcomes of a fixed GnRH antagonist protocol and a flexible progestin-primed ovarian stimulation (fPPOS) protocol in patients with asynchronous follicular development during controlled ovulation stimulation and to explore the feasibility of converting patients undergoing a fixed GnRH antagonist protocol to an fPPOS protocol. This was the first retrospective study exploring the fPPOS protocol in patients with asynchronous follicular development, and it was conducted in a public reproductive medicine center from January to December 2020. We included infertile women. All participants were scheduled to undergo administration of a GnRH antagonist on the fifth day of controlled ovulation stimulation. The study group included 129 women who were converted from the fixed GnRH antagonist protocol to the fPPOS protocol for their asynchronous follicular development, while the antagonist group consisted of 258 women (ratio 1:2) who proceeded with a fixed GnRH antagonist protocol. On the second or third day of the menstrual period, 100-300 IU/day gonadotropin injections were administered. For patients who were converted to the fPPOS protocol, medroxyprogesterone acetate tablets at 10 mg/day were started on the fifth day of stimulation or when only one leading follicle reached 14 mm and the other follicles were ≤10 mm in diameter, whichever came first. The rates of embryo implantation, clinical pregnancy, and early pregnancy loss were obtained. The number of oocytes retrieved and the number of high-quality embryos in the antagonist group were significantly higher than those in the fPPOS group (P = 0.039 and P = 0.025, respectively). No significant differences in the rates of embryo implantation, clinical pregnancy, and early pregnancy loss were observed between the two groups. Our study found that in patients who were scheduled for administration of GnRH antagonists but presented with asynchronous follicular development on the fifth stimulation day, it was feasible to switch to the fPPOS protocol.

SUBMITTER: Dong M

PROVIDER: S-EPMC8636937 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveTo explore the cycle characteristics and pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) using fixed versus degressive doses of medroxyprogesterone acetate (MPA) in conjunction with letrozole (LE) in infertile women by propensity score matching (PSM) analysis.DesignA retrospective cohort study.SettingTertiary-care academic medical center.PopulationA total of 3173 infertile women undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment within the period from January 2017 to December 2020.MethodsA total of 1068 and 783 patients who underwent a fixed dose of MPA combined with LE and a degressive dose of MPA combined with LE protocols, respectively, were enrolled in this study. The freeze-all approach and later frozen-thawed embryo transfer (FET) were performed in both groups. Propensity score matching (1:1) was performed.Main outcome measuresThe primary outcomes were the dosage of MPA and the incidence of premature luteinizing hormone (LH) surges. The secondary outcomes were the number of oocytes retrieved, the cumulative live birth rate (CLBR) and the fetal malformation rate.ResultsWe created a perfect match of 478 patients in each group. The dosage of MPA, the LH serum level on the eighth day of stimulation, progesterone (P) level and LH level on the hCG trigger day were significantly higher in the LE + fixed MPA group than in the LE + degressive MPA group (52.1 ± 13.1 mg vs. 44.9 ± 12.5 mg; 5.0 ± 2.7 IU/L vs. 3.7 ± 1.7 IU/L; 0.9 ± 0.5 ng/ml vs. 0.8 ± 0.5 ng/ml; 3.3 ± 2.4 IU/L vs. 2.8 ± 1.9 IU/L; P < 0.01). The duration of Gn, the number of follicles with diameter more than 16 mm on trigger day, the estradiol (E2) level on the hCG trigger day were lower in the LE + fixed MPA group than in the LE + degressive MPA group (9.7 ± 1.7 days vs. 10.3 ± 1.5 days; 5.6 ± 3.0 vs. 6.3 ± 3.0; 1752.5 ± 1120.8 pg/ml vs. 1997.2 ± 1108.5 pg/ml; P < 0.001). No significant difference was found in the incidence of premature LH surge, the number of oocytes retrieved, the number of top-quality embryos, clinical pregnancy rate (CPR), CLBR or fetal malformation rate between the two groups.ConclusionThe combination of a degressive MPA dose with LE proved effective in reducing the total MPA dosage with comparable premature LH surge and pregnancy outcomes in women undergoing the PPOS protocol.

Project description:Background: The ability of anti-Müllerian hormone (AMH) to predict ovarian response has been studied extensively in gonadotropin-releasing hormone agonist and antagonist treatments, but no information is available regarding its value in progestin-primed ovarian stimulation (PPOS) protocol. Methods: This retrospective data analysis included 523 patients without polycystic ovary syndrome who underwent their first in vitro fertilization/intracytoplasmic sperm injection cycle with PPOS protocol at our center between Jan. 2015 and Jul. 2018. Serum AMH measurements were acquired within 12 months prior to ovarian stimulation using the automated Access AMH assay. Results: AMH exhibited a significantly positive correlation with the number of retrieved oocytes (r = 0.744, P < 0.001). For the prediction of poor (<4 oocytes) and high (>15 oocytes) response, AMH had an area under the receiver operating characteristic curve (AUC) of 0.861 and 0.773, corresponding with an optimal cutoff point of 1.26 and 4.34 ng/mL, respectively. When stratified according to the dose of medroxyprogesterone acetate (MPA) (4 mg vs. 10 mg per day), AMH retained its similarly high predictive value for poor (AUC = 0.829 and 0.886, respectively) and high response (AUC = 0.770 and 0.814, respectively) in both groups. Amongst the 314 women who received their first frozen embryo transfer (FET) following PPOS protocol, no significant differences were observed on the rates of biochemical pregnancy, clinical pregnancy, implantation, early miscarriage, multiple pregnancy and ectopic pregnancy (all P > 0.05) across AMH quartiles (≤1.43, 1.44-2.55, 2.56-4.35, >4.35 ng/mL). In a multivariable logistic regression model, age was suggested to be the only independent risk factor for clinical pregnancy (P = 0.011). Conclusions: Our data demonstrated that AMH is an adequate predictor of both high and poor ovarian response in PPOS protocol regardless of MPA dose, but it does not associate with pregnancy outcomes in the first FET cycles in a freeze-all strategy.

Project description:ObjectivesProgestin-primed ovarian stimulation (PPOS) is a new ovarian stimulation protocol that can block the luteinizing hormone (LH) surge through progesterone instead of traditional down regulating or gonadotropin-releasing hormone (GnRH) antagonist, and in order to achieve multi-follicle recruitment. This paper aims to investigate the effectiveness of PPOS and its suitability for infertile patients with different ovarian reserve functions.MethodsWe searched published randomized controlled trials (RCTs) about PPOS on Cochrane Library, PubMed, Embase, and Web of Science. The search period spanned from January 1, 2015 to November 16, 2020. The data were extracted, and the meta-analysis was performed on ovarian stimulation as well as embryological and clinical outcomes. The outcomes were pooled by a random effects model, and the risk of heterogeneity was evaluated. Subgroup analysis was performed for different ovarian reserve patients.ResultsThe clinical pregnancy rates and live birth or ongoing pregnancy rates with the PPOS protocol were not different from those with the control group. In the diminished ovarian reserve (DOR) subgroup, the PPOS protocol had a lower rate of premature LH surge [RR = 0.03, 95% CI = 0.01 to 0.13, p < 0.001]. The PPOS protocol had a lower rate of ovarian hyperstimulation syndrome (OHSS) [RR = 0.52, 95% CI = 0.36 to 0.76, p < 0.001, I 2 = 0.00%]. The secondary outcomes showed that the number of oocytes retrieved, MII oocytes, and viable embryos was higher than that of the control protocol in DOR patients [(MD = 0.33, 95% CI = 0.30 to 0.36, p < 0.001), (MD = 0.30, 95% CI = 0.27 to 0.33, p < 0.001), (MD = 0.21, 95% CI = 0.18 to 0.24, p < 0.001)] and normal ovarian reserve (NOR) patients [(MD = 1.41, 95% CI = 0.03 to 2.78, p < 0.001), (MD = 1.19, 95% CI = 0.04 to 2.35, p < 0.001), (MD = 1.01, 95% CI = 0.21 to 1.81, p = 0.01)].ConclusionThe findings suggest that PPOS is an effective ovarian stimulation protocol and is beneficial for patients with different ovarian reserve functions, which needs to be validated in more RCTs with larger samples.

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Fixed Gonadotropin-Releasing Hormone Antagonist Protocol Versus Flexible Progestin-Primed Ovarian Stimulation Protocol in Patients With Asynchronous Follicular Development During Controlled Ovulation Stimulation: A Retrospective Study.

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