Objective: To investigate whether circulating LH levels could be used as an indicator for the timing of antagonist addition in GnRH antagonist protocol. Design: Retrospective cohort study. Setting: University-based hospital. Patients: A total of 567 women stimulated with recombinant FSH monotherapy in a GnRH antagonist protocol were studied. Among them, 256 patients showed relatively low LH levels [highest LH level (LHmax) < 4 IU/L] during the entire ovarian stimulation process; 88 (Group A) and 168 patients (Group B) were stimulated without and with antagonist co-treatment, respectively. The remaining 311 patients had LHmax≥4 IU/L and were stimulated with a modified flexible antagonist protocol based on LH levels (Group C). Intervention(s): Patients in Group B and C received antagonist during ovarian stimulation, whereas patients in Group A did not. Main outcome measure: Clinical pregnancy rate and ongoing pregnancy rate. Results: The clinical and ongoing pregnancy rates were significantly higher in group A than group B (69.3 vs. 54.7%, P = 0.03 and 62.5 vs. 48.2%, P = 0.04, respectively), but the primary outcome measures did not differ between groups B and C. There were no significant differences in terms of patient demographics, LH levels, total dosage of gonadotrophin, duration of stimulation, follicular output rate between groups A and B, and between groups B and C. Also, there were no significant differences in laboratory and clinical outcomes in pairwise group comparisons. No canceled cycles due to premature ovulation was reported among the treated patients. Conclusion: LH levels may be used as an indicator for the time of antagonist addition. Patients with sustained low LH levels (LHmax<4 IU/L) during controlled ovarian stimulation (COS) might not require antagonist administration. Although further well-designed randomized controlled trials (RCTs) are needed to confirm our results, a novel treatment regimen based on LH measurements during COS might provide clinicians new insights about when to start antagonist administration in the GnRH antagonist protocol.

Research question Using RNA-sequencing analysis, we investigated the relationship between ovarian stimulation and endometrial transcriptome profiles during the window of implantation (WOI) to identify candidate predictive factors for the WOI and to optimize timing for embryo transfer. Methods Twelve women with normal basal hormone levels and regular ovulation were randomly assigned into three groups based on sampling time: late-proliferate phase (P group), and receptive phase in natural cycles (LH+7, N group) and stimulated cycles (hCG+7, S group). Transcriptome profiles of mRNAs and long non-coding RNAs (lncRNAs) were then compared among the three groups. Validation was performed using real-time qPCR. Results Comparison of transcriptome profiles between the natural and stimulated endometrium revealed 173 differentially expressed genes (DEGs), with a > 2-fold change (FC) and p < 0.05, under the influence of supraphysiological estradiol (E 2 ) induced by ovarian stimulation. By clustering and KEGG pathway analysis, molecules and pathways associated with endometrial receptivity were identified. Of the 39 DEGs common to the three groups, eight genes were validated using real-time PCR. ESR1, MMP10, and HPSE were previously reported to be associated with endometrial receptivity. In addition, three novel genes (IL13RA2, ZCCHC12, SRARP) and two lncRNAs (LINC01060, LINC01104) were new potential endometrial receptivity-related markers. Conclusion Using mRNA and lncRNA sequencing, we found that supraphysiological E 2 levels from ovarian stimulation had a marked impact upon endometrial transcriptome profiles and may result in a shift of the WOI. The precise mechanisms underlying the supraphysiological hormone-induced shift of the WOI require further research. Registration number ChiCTR180001453

ObjectiveTo verify if patients with deep ovarian suppression following gonadotropin releasing hormone (GnRH) agonist long protocol may benefit from a modified GnRH antagonist protocol based on luteinizing hormone (LH) levels.DesignRetrospective cohort study.SettingUniversity-based hospital.Patients110 patients exhibited ultra-low LH levels during ovarian stimulation using GnRH agonist long protocol.Intervention(s)As all the embryos in the first cycle were exhausted without being pregnant, these patients proposed to undergo a second cycle of ovarian stimulation. 74 of them were treated with a modified GnRH antagonist protocol based on LH levels. Other 36 patients were still stimulated following GnRH agonist long protocol.Main Outcome MeasureThe primary outcome was live birth rate (LBR). The second outcomes were biochemical pregnancy rate, clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR) and cancellation rate.ResultsReproductive outcomes were much better in the modified GnRH antagonist protocol. The OPR and LBR were much higher in the GnRH antagonist protocol group than in the GnRH agonist long protocol group [odds ratio (OR) 3.82, 95% confidence interval (CI) 1.47, 10.61, P=0.018; OR 4.33, 95% CI 1.38, 13.60, P=0.008; respectively]. Meanwhile, the cancellation rate was much lower in the GnRH antagonist protocol group (OR 0.13, 95% CI 0.02, 0.72; P=0.014). Mean LH level during stimulation did not have a predictive value on live birth. However, it was independently associated with the occurrence of ongoing pregnancy (OR 2.70, 95% CI 1.25, 5.85; P=0.01). The results of sensitivity analyses were consistent with the data mentioned above. The patients got completely different and excellent clinical outcomes in their second cycles stimulated with the modified GnRH antagonist protocol.ConclusionPatients with deep ovarian suppression following GnRH agonist long protocol may benefit from a modified GnRH antagonist protocol based on LH levels.