Background It was been agreed that significantly elevated progesterone level on the hCG trigger day have detrimental effect on clinical outcomes in IVF/ICSI cycles. However, few studies explored whether slightly elevated progesterone level also same impact on clinical outcomes. Methods We retrospectively studies the effect of slightly elevated progesterone level on outcomes of IVF/ICSI in GnRH-ant cycles. Propensity score matching was used to confounding variables. The women were divided into two groups according to the progesterone level: Group 1: < 1.0 ng/ml; Group 2: 1.0 ng/ml–1.5 ng/ml. Then compare the clinical pregnancy rate (CPR) between the two groups. Result A total of 847 IVF/ICSI cycles were included in the present study. The average CPR per transfer cycle was 51.7%. CPR of group 1 was 55.22%, significantly higher than that of group 2 (40.66%, P = 0.013). Progesterone level on the day of hCG injection was further evaluated at threshold increments of 0.1 ng/ml, and the CPR was decreased dramatically once the progesterone level higher than 1.4 ng/ml. Conclusion The slight elevation progesterone level on the hCG trigger day may have a negative effect on the clinical pregnancy in GnRH-ant cycles. In the case of progesterone > 1.4 ng/ml on the hCG injection day, freeze-all strategy was recommended. Summary The present retrospective study aimed to evaluate the effect of slightly elevated progesterone (1.0 ng/ml ~ 1.5 ng/ml) on outcomes of IVF/ICSI in GnRH-ant cycles. Slightly elevated progesterone level leaded to significant lower clinical pregnancy rate (CPR) that that of group with normal progesterone level (40.66% vs. 55.22%, P = 0.013). The CPR was decreased dramatically once the progesterone level higher than 1.4 ng/ml. So slightly elevated progesterone level on the trigger day may have a negative effect on the clinical pregnancy in GnRH-ant cycles. In the case of progesterone > 1.4 ng/ml on the hCG injection day, freeze-all strategy was recommended.
Background We have previously shown that hsa-miR-423-5p expression in ovarian granulosa cells is decreased in high ovarian response populations. The objective of the present study was to find the target gene and mechanism for miR-423-5p involved in ovarian response regulation. Methods (a) TargetScan was used to predict the target gene of hsa-miR-423-5p. (b) A model for hsa-miR-423-5p overexpression or inhibition was constructed by transfecting KGN cells with lentivirus. CSF1 mRNA and protein expression and luciferase activity were measured. (c) The cell cycles of control and lentivirus treated KGN cells were analyzed. Western blot was used to measure the expression of CDKN1A in KGN cells. (d) The concentration of estradiol in KGN cell culture medium were measured. Results (a) TargetScan revealed that the 3′ un-translated region of CSF1 matched 11 bases at the 5′ end of miR-423-5p, making it a likely target gene. (b) Overexpression or inhibition of miR-423-5p were associated with respective decreases or increases in CSF1 expression (both mRNA and protein) (p < 0.05) and luciferase activity (p < 0.05). (c) When miR-423-5p expression increased, the number of G0/G1 phase cells and the expression of CDKN1A protein increased while estradiol concentrations in the cell culture solution decreased (p<0.05). However, when miR-423-5p expression decreased, the number of S phase cells increased and estradiol concentrations increased while the expression of CDKN1A protein decreased (p < 0.05). Conclusions Colony stimulating factor 1 is a target gene of miR-423-5p and that it may regulate ovarian response to ovulation induction by affecting granulosa cells proliferation and estrogen secretion.
Melatonin (MT) regulates a variety of important actions related to reproduction. Many studies have investigated the effect of MT application on the outcome after assisted reproductive technology (ART), with controversial results. The aim of this systematic review was to synthesize evidence from clinical studies that examine the effect of MT on the main outcomes of ART. PubMed, Embase, Web of Science, and Google scholar were searched. Clinical trials, which studied the effect of MT supplementation on outcome after ART and published in English from inception to April 2020, were included. One author assessed the risk of bias in the studies using the Cochrane Collaboration checklist. Dichotomous outcomes were analyzed as risk ratios (RR) using the Mantel-Haenszel statistical method and a random/fixed effect model. Continuous outcomes were analyzed as Mean Difference (MD) using the Inverse Variance statistical method. Eleven studies performed between 2008 and 2019 were included in this meta-analysis. Clinical pregnancy rate (CPR), live birth rate (LBR), Miscarriage rate (MR), fertilization rate (FR), Number of oocyte retrieved, MII oocyte, top-quality embryo were reported in 10, 3, 6, 7, 9, 8, and 6 studies, respectively. MT supplementation significantly increased the CPR (RR, 1.24; 95% confidence interval [CI], 1.04, 1.47), the No. of MII oocyte (MD, 1.39; 95% CI, 0.74, 2.04), the No. of top-quality embryo (MD, 0.56; 95% CI, 0.24, 0.88), and the FR (4 studies with RR, 1.10; 95% CI, 1.03, 1.17; 3 studies with MD, 0.13; 95% CI, 0.01, 0.24). However, there was no significant difference in LBR (RR, 1.23; 95% CI, 0.85, 1.80), No. of oocyte retrieved (MD, 0.58; 95% CI, -0.12, 1.27), and the MR (RR, 0.96; 95% CI, 0.50, 1.82). When studies were sub-grouped by the interventions, no matter the control group is MI+FA or placebo/none, MT supplementation increased No. of MII oocyte (MT+MI+FA vs. MI+FA MD, 0.91; 95% CI, 0.40, 1.41; MT vs. Placebo/none MD, 2.06; 95% CI, 0.73, 3.39) and No. of top embryo (MT+MI+FA vs. MI+FA MD, 0.70; 95% CI, 0.24, 1.16; MT vs. Placebo/none MD, 0.33; 95% CI, 0.11, 0.54), whereas showed similar CPR (MT+MI+FA vs. MI+FA RR, 1.22; 95% CI, 0.96, 1.54; MT vs. Placebo/None RR, 1.26; 95% CI, 0.97, 1.62). When studies were sub-grouped according to women’s characteristic, MT supplementation showed no significant beneficial effect on CPR in women with PCOS (RR, 1.18; 95% CI, 0.92, 1.52), with normal ovary function (RR, 1.15; 95% CI, 0.87, 1.53), and women with previous low fertilization or poor-quality embryo (RR, 1.71; 95% CI, 0.95, 3.07). However, MT supplementation increased the No of MII in women with PCOS (MD, 0.97; 95% CI, 0.22, 1.73), but did not show such benefit in women with normal ovary function (MD, 1.49; 95% CI, -0.33, 3.31). In conclusion, MT supplementation may not improve the clinical pregnancy and live birth of ART. But MT seems to be beneficial to the quality of oocyte and embryo, especially for women with PCOS and DOR, at least to some extent. Further well-designed studies are needed before recommendation of its use in clinical practice.
Background We have previously shown that hsa-miR-423-5p expression in ovarian granulosa cells is decreased in high ovarian response populations. The objective of the present study was to find the target gene and mechanism for miR-423-5p involved in ovarian response regulation. Methods (a) TargetScan was used to predict the target gene of hsa-miR-423-5p. (b) A model for hsa-miR-423-5p overexpression or inhibition was constructed by transfecting KGN cells with lentivirus. CSF1 mRNA and protein expression and luciferase activity were measured. (c) The cell cycles of control and lentivirus treated KGN cells were analyzed. Western blot was used to measure the expression of CDKN1A in KGN cells. (d) The concentration of estradiol in KGN cell culture medium were measured. Results (a) TargetScan revealed that the 3′ un-translated region of CSF1 matched 11 bases at the 5′ end of miR-423-5p, making it a likely target gene. (b) Overexpression or inhibition of miR-423-5p were associated with respective decreases or increases in CSF1 expression (both mRNA and protein) (p < 0.05) and luciferase activity (p < 0.05). (c) When miR-423-5p expression increased, the number of G0/G1 phase cells and the expression of CDKN1A protein increased while estradiol concentrations in the cell culture solution decreased (p<0.05). However, when miR-423-5p expression decreased, the number of S phase cells increased and estradiol concentrations increased while the expression of CDKN1A protein decreased (p < 0.05). Conclusions Colony stimulating factor 1 is a target gene of miR-423-5p and that it may regulate ovarian response to ovulation induction by affecting granulosa cells proliferation and estrogen secretion.
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