Objective To systematically review the effectiveness of letrozole combined with GnRH antagonist for in vitro fertilization-embryo transfer (IVF-ET) in poor responders. Methods Such databases as VIP, CNKI, PubMed, EMbase and FMJS were electronically searched for randomized controlled trials (RCTs) or quasi-RCTs on the effectiveness of letrozole combined with GnRH antagonist for IVF-ET. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality. Then, meta-analysis was performed using RevMan 5.0 software. Results Six studies involving 977 patients were finally included. The results of meta-analysis showed that, for IVF-ET poor responders, compared with the control group, the letrozole combined with GnRH antagonist group had less dosage of Gn (MD=–8.05, 95%CI –13.67 to –2.43, P=0.005), and lower serum E2 value on the day of HCG administration (MD= –1 026.41, 95%CI –1 949.61 to –103.20, P=0.03). However, no significant difference was found in the number of ocytes obtained (MD= –0.61, 95%CI –2.41 to –1.19, P=0.51) and clinical pregnancy rates (OR=1.03, 95%CI 0.53 to 2.02, P=0.92) between the two groups. Conclusion As for the effectiveness of impelling-ovulation treatment for IVF-ET in poor responders, letrozole combined with GnRH antagonist is similar to the control scheme in clinical outcomes, but it reduces the dosage of Gn and treatment costs of IVF-ET, which provides another clinical option for poor responders. Due to the limited quantity and quality of the included studies as well as the difference in methodology, we suggest this above conclusion could be taken as a reference for clinical analysis which needs to be further evaluated in its effects.
Objective To assess the effectiveness of letrozole in ovulation induction treatment. Methods We searched CBMdisc (1979 to 2009), Wanfang (1994 to 2009), CNKI (1994 to 2009), VIP(1989 to 2009), PubMed (1997 to 2009), PML (1997 to 2009), FMJS(2000 to 2009) and 9 relevant journals to identify randomized controlled trails (RCTs) comparing letrozole with clomiphene citrate in ovulation induction treatment. The quality of the included trials was critically appraised. RevMan 4.2.7 software was used for statistical analyses. Results Ten RCTs involving 3100 patients were included, among which 5 RCTs were graded A, 4 were graded B, and 1 was graded C. Five RCTs showed that endometrial thickness at the time of human chorionic gonadotrophin (HCG) administration in the letrozole group was significantly higher than that in the clomiphene group. One RCT showed that endometrial thickness at the time of HCG administration in the letrozole group was significantly lower than that in the clomiphene group. Three RCTs showed no significant differences between the two groups. Four RCTs showed that the number of dominant follicle at the time of HCG administration in the letrozole group was signficantly lower than that in the clomiphene group. One RCT showed that the number of dominant follicle at the time of HCG administration in the letrozole group was significantly higher than that in the clomiphene group. Two RCTs showed no significant differences between the two groups. Compared with clomiphene citrate, the pregnancy rate in the letrozole monotherapy group was slightly lower at the RR 1.03 and 95%CI 0.82 to 1.29, pregnancy rate in the combination group was higher at RR 1.73 and 95%CI 1.37 to 2.18. The ovulation rate in the letrozole group was higher and no significant differences were found between the two groups at RR 1.23 and 95%CI 0.97 to 1.57. Conclusions There may be differences between letrozole and clomiphene citrate in ovulation induction treatment in terms of endometrial thickness, number of dominant follicle, ovulation rate, and pregnancy rate, but no significant differences. Letrozole can make up for the shortcomings of clinical clomiphene in ovulation induction and serve as an alternative. This conclusion needs to be further confirmed through more well-designed, multi-centered, large-sample RCTs.
Objective To systematically evaluate the efficacy and safety of letrozole combined with metformin in the treatment of polycystic ovarian syndrome (PCOS) infertility. Methods PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, Chongqing VIP, Wanfang, and SinoMed were searched from establishment to December 31, 2022. The literature on randomized controlled trials of letrozole combined with metformin in the treatment of PCOS infertility were included. RevMan 5.4 software was used for meta-analysis. Results A total of 29 articles including 3226 subjects were included, with trial group of 1614 treated with letrozole combined with metformin, and control group of 1612 treated with letrozole alone. The meta-analysis results showed that the clinical pregnancy rate [relative risk (RR)=1.76, 95% confidence interval (CI) (1.61, 1.92)], induced ovulation rate [RR=1.22, 95%CI (1.17, 1.28)], and number of dominant follicles [mean difference (MD)=1.15, 95%CI (0.86, 1.43)] in the trial group were higher than those in the control group (P<0.05). The follicle growth time [MD=−5.41 d, 95%CI (−6.03, −4.80) d], estradiol level [MD=−7.57 pmol/L, 95%CI (−10.59, −4.56) pmol/L], luteinizing hormone level [MD=−2.27 U/L, 95%CI (−2.59, −1.95) U/L], testosterone level [MD=−1.29 nmol/L, 95%CI (−1.74, −0.85) nmol/L], fasting blood glucose level [MD=−0.91 mmol/L, 95%CI (−1.71, −0.65) mmol/L], fasting insulin level [MD=−25.93 pmol/L, 95%CI (−29.06, −22.80) pmol/L], insulin resistance index [MD=−1.40, 95%CI (−1.61, −1.19)], and the incidence of ovarian hyperstimulation syndrome [RR=0.44, 95%CI (0.22, 0.88)] in the trial group were lower than those in the control group (P<0.05). There was no statistically significant difference in follicle stimulating hormone level, incidence of adverse reactions, and spontaneous abortion rates between the two groups (P>0.05). Conclusion Existing evidence suggests that compared to using trazole alone, the combination of letrozole and metformin can improve ovulation induction and pregnancy outcomes in patients with PCOS infertility. The combination of the two drugs can reduce levels of estradiol, testosterone, and luteinizing hormone in patients, while effectively reducing the incidence of ovarian hyperstimulation syndrome.
ObjectiveThe growth potential of children with short stature in middle and late adolescence may be limited by the effect of estrogen on epiphyseal closure. In recent years, the third generation of non-steroidal aromatase inhibitors (AIs) have been used in the treatment of short stature but with off-label. This study aimed to systematically review the efficacy and safety of the third-generation non-steroidal AIs in the treatment of children with short stature, and to provide evidences for rational drug use in clinical practice. MethodsWe searched PubMed, Embase, Cochrane Library, CNKI, WanFang Data, VIP and CBM from inception to December 28, 2022. Relevant studies on the treatment for children with short stature using the recombinant human growth hormone (rhGH) combined with or without the third-generation non-steroidal AIs were collected. Two reviewers independently screened the literature, extracted data, and evaluated the risk of bias of the included studies. Meta-analysis was performed using RevMan 5.3 software. ResultsA total of 18 articles were finally included, involving 9 randomized controlled trials and 9 cohort studies, with a total of 1 053 patients. The Meta-analysis showed that: (1) in terms of efficacy, the final adult height (MD=2.48, 95%CI 2.02 to 2.94, P<0.01), predicted adult height (MD=4.27, 95%CI 2.71 to 5.83, P<0.01), predicted adult height difference (MD=4.26, 95%CI 3.23 to 5.28, P<0.01), bone age (MD=−0.62, 95%CI −0.89 to −0.36, P<0.01), bone age difference/actual age difference (MD=−0.47, 95%CI −0.56 to −0.37, P<0.01), and growth velocity (MD=1.34, 95%CI 0.89 to 1.78, P<0.01) at the end of treatment in the experimental group were better than those in the control group, but there was no statistical difference in the height at the end of treatment between the two groups (MD=4.03, 95%CI −0.01 to 8.06, P=0.05). (2) in terms of safety, the total incidence of adverse events in the experimental group (RR=2.10, 95%CI 1.48 to 2.99, P<0.01) was higher than that in the control group, among which the incidence of adverse events in the endocrine system and skin and subcutaneous tissue system was statistically different between the two groups (P<0.05), and the incidence of adverse events in the hepatobiliary system, kidney and urinary system, metabolism and nutrition, gastrointestinal system, musculoskeletal system, blood and lymph system, vascular and lymphatic system, and neuropsychiatric system was not statistically different between the two groups (P>0.05). ConclusionCurrent evidence shows that the third-generation non-steroidal AIs combined with rhGH can effectively improve the final height of children with short stature, but it may increase the incidence of adverse drug events. Limited by the quality and the follow-up period of the included studies, high-quality studies are still needed to demonstrate the above conclusions and further evaluate the long-term safety of AIs in children with short stature.