ReviewMeta-analysis of letrozole versus clomiphene citrate in polycystic ovary syndrome
Introduction
Polycystic ovary syndrome (PCOS) is an endocrinopathy in women of reproductive age, with morbidity ranging from 5% to 10% (Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, 2008). The primary clinical manifestation is irregular or absent menstrual cycles and infertility. Ovulation induction is recognized as an essential treatment procedure for PCOS. The traditional ovulation induction agent is clomiphene citrate which is highly effective in selected patients. However, it has some adverse effects, especially the anti-oestrogenic effects on the endometrium and cervix mucus that could prevent pregnancy. Although exogenous gonadotrophin is recommended as second-line intervention when clomiphene citrate fails, it is associated with increased chances of multiple pregnancy and ovarian hyperstimulation syndrome (OHSS), and intense monitoring of ovarian response is required. Therefore, a more effective and safe ovulatory agent is needed.
In 2001, an aromatase inhibitor – letrozole, which was used to treat and prevent breast cancer – was first reported to be effective for ovulation induction and appeared to avoid the unfavourable effects of clomiphene citrate and gonadotrophin (Mitwally and Casper, 2001). In recent years many randomized controlled trials (RCT) have been conducted to assess the efficiency and safety of letrozole in PCOS, but conclusions have not been completely consistent. Furthermore, there has been no meta-analysis to provide definite evidence as to whether letrozole is superior to clomiphene citrate. Therefore this meta-analysis was performed to systematically evaluate the difference in letrozole and clomiphene citrate for PCOS on the basis of the available evidence.
Section snippets
Search strategy
This study systematically searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2010), PubMed (January 1978–June 2010), Embase (January 1978–June 2010), CBMdisc (January 1970–June 2010) and CNKI (January 1979–June 2010) to identify studies without language restriction. The following keywords were used: letrozole, aromatase inhibitors, clomiphene citrate, polycystic ovary syndrome, hyperandrogenism, anovulation, ovulation induction and randomized controlled trial.
Results
Of 1530 articles screened, 27 RCT were identified as potentially eligible for inclusion. Only six RCT (Atay et al., 2006, Aygen et al., 2007, Badawy et al., 2009, Bayar et al., 2006, Dehbashi, 2009, Zeinalzadeh et al., 2010) fulfilled the criteria in the meta-analysis. A total of 21 RCT were excluded for the following reasons: the patients did not fulfill the diagnostic criteria of PCOS (three); trials did not compare letrozole with clomiphene citrate (10); use of improper randomization methods
Discussion
Ovulation induction is consistently regarded as an essential treatment procedure for PCOS patients. Although clomiphene citrate is still the traditional agent used for inducing ovulation in this condition, clomiphene resistance, which refers to persistence of anovulation after standard clomiphene citrate therapy, occurs in 20–25% of patients (Hughes et al., 2000). Aromatase inhibitors are agents that suppress the biosynthesis of oestrogen and, therefore, reduce the negative feedback effect on
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Ovulation induction using sequential letrozole/gonadotrophin in infertile women with PCOS: a randomized controlled trial
2023, Reproductive BioMedicine OnlineCitation Excerpt :At present, the mainstream drugs for promoting ovulation include clomiphene, letrozole and HMG, among which HMG is the most effective drug with a most frequent presence of OHSS and multiple pregnancy, but there are additional disadvantages such as injection-related pain and high cost (Diamond et al., 2015; Gleicher et al., 2000; Quaas and Legro, 2019). The ovulation induction of letrozole is stronger than (Banerjee Ray et al., 2012; Hu et al., 2018) or equal to (He and Jiang, 2011) clomiphene, without a statistical difference in side effects (Amer et al., 2017). In addition, the changes in endometrial function are noticeable in patients with PCOS, which is caused by dysregulated expression of oestrogen receptors, cell adhesion molecules and metabolic variables (Baracat et al., 2015; Giordano et al., 2022).
Use of Letrozole versus clomiphene-estradiol for treating infertile women with unexplained infertility not responding well to clomiphene alone, comparative study
2018, Middle East Fertility Society JournalCitation Excerpt :Kar in a study showed that Letrozole has excellent pregnancy rates compared to Clomiphene citrate [32]. Regarding abortion rate & multiple pregnancies, this study showed, there is no difference between both medications which was convenient with results of meta-analysis done by He D Jiang F, who concluded, there were no significant differences in pregnancy, abortion and multiple pregnancy rates between the Letrozole & CC in PCOS infertile patients [33]. For conclusion, no superiority of Letrozole or CC plus estradiol for inducing ovulation in women with unexplained infertility if respond inadequately to CC alone (thin endometrium).
Systematic review and meta-analysis of letrozole and clomiphene citrate in polycystic ovary syndrome
2018, Middle East Fertility Society JournalCitation Excerpt :Dehbashi et al. [26] detected one major congenital anomaly, meningomyelocele, in the CC group, while Legro et al. [28] identified five major congenital anomalies (4 with letrozole and 1 with CC) but found no significant difference (P = 0.65) between the groups. The overall results of this review are generally consistent with those of equivalent comprehensive reviews comparing the clinical efficacy and safety of letrozole with CC for ovulation induction in women with PCOS [17,32]. Evidently, some notable limitations were found in this review.
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Fengyan Jiang: Graduated from Guangxi Medical University and was awarded Master Degree in 1994. Now she is a tutor for master of Guangxi Medical University and a chief physician of Department of gynaecology, First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, PR China. Specific research interests is Gynecological Endocrinology.