Metformin With or Without Clomiphene Citrate Versus Laparoscopic Ovarian Drilling With or Without Clomiphene Citrate to Treat Patients With Clomiphene Citrate-Resistant Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

Abstract

Introduction: Which is optimal to treat clomiphene citrate-resistant polycystic ovary syndrome (CCR-PCOS) with LOD or metformin remains a problem. There are three inconsistent or even contradictory views.Objectives: The present meta-analysis aimed to evaluate the effectiveness and safety of Metformin with or without CC and to compare them with LOD with or without CC (Met/Met-CC vs. LOD/LOD-CC) in women with CCR-PCOS who also have anovulation.Data source: The PubMed, Cochrane, and Embase databases were searched to identify relevant studies reported between 1 Jan 1966 and 31 Aug 2019; the search was updated on 17 May 2022.Study eligibility criteria: We included randomized controlled trials (RCTs) of CCR-PCOS that had considered Met/Met-CC and LOD/LOD-CC as the exposure variables and fertility as the main outcome variable.Study appraisal and synthesis methods: We assessed study quality using the Cochrane risk-of-bias tool. The primary effectiveness outcome was live birth/ongoing pregnancy rate and the primary safety outcome was miscarriage rate. A fixed-effect meta-analysis was performed. The robustness of the results was assessed using sensitivity analyses. Meta-regression and subgroup analysis were performed to examine the reasons for heterogeneity. Publication bias was examined using the funnel plot, Egger linear regression, and Begg rank correlation tests. The quality of this meta-analysis was estimated according to the GRADE approach. This meta-analysis has been registered in PROSPERO (CRD42021240156).Results: Among 71 potentially relevant studies, we included five RCTs in our meta-analysis. We found no difference in effectiveness between Met-CC and LOD in terms of live birth/ongoing pregnancy (RR = 1.02, 95% CI: 0.87–1.21, z = 0.28; p = 0.780), and miscarriage rates (RR = 0.79, 95% CI: 0.46–1.36, z = 0.86; p = 0.390). I2 tests results revealed moderate or no heterogeneity (I2 = 51.4%, p = 0.083; I2= 0.0%; p = 0.952). Sensitivity analysis confirmed the robustness of the results. Funnel plot, Egger linear regression, and Begg rank correlation tests implied no publication bias (p > 0.05). LOD was more expensive than Met (€1050 vs. €50.16). The evidence quality was moderate.Conclusion: There is no evidence on the difference in the outcomes between the two interventions regarding ovulation, pregnancy, and live birth. As LOD is an invasive procedure and carries inherent risks, the use of Met/Met-CC should be the second-line treatment for women with CCR-PCOS.Systematic Review Registration: identifier CRD42021240156.

Clomiphene Supported Ovulation Induction in Subfertile Polycystic Ovary Syndrome Women: Role of Different Insulin Sensitizers

“…Nearly 5 to 15% of women of reproductive age have PCOS, including ovulation disorder, hyperandrogenism and infertility. 10,11 of insulin resistance is central and mainly based on daily routine, eating modifications and insulin-sensitising agents like metformin, as shown in studies of glucose intolerance and type -2 diabetes. 12,13 In the present study, subfertile PCOS women treated with metformin were more likely to ovulate than those treated with Myo-inositol (p-0.001).…”

Combined traditional Chinese medicine therapy for the treatment of infertility with polycystic ovary syndrome: A network meta-analysis of randomized controlled trials

“…[11][12][13] Alternative, non-pharmacological treatment options such as ultrasound-guided follicular puncture and laparoscopic ovarian drilling also entail certain risks and may lead to postoperative complications like periovarian adhesions and ovarian hypoplasia. [14] While assisted reproductive technologies are already in clinical use, such as intrauterine insemination and in vitro maturation culture of immature eggs are available, their efficacy remains a matter of debate; and often lead to high ovulation rate, low pregnancy rate, high miscarriage rate. [11,15] In addition, ovulation induction and in vitro fertilization may increase economic burden on patients, as well as adverse effects on their psychological status.…”

Bioequivalence and Safety Assessment of 2 Formulations of Low‐Dose Metformin Hydrochloride under Fasting Conditions in Healthy Chinese Participants: A Randomized Phase 1 Clinical Trial

“…1,2 The incidence and prevalence of type 2 diabetes mellitus are high, particularly in developing countries such as China, 3 therefore the development of generic metformin hydrochloride (MH) tablets is urgently needed to fill the market gap created by the high demand for original metformin sustained-release tablets for patients with type 2 diabetes. 4,5 Recently, a growing number of studies have suggested benefits of the off-label use of metformin in different conditions, 6 such as the promotion of successful pregnancy in patients with polycystic ovarian syndrome with infertility due to anovulation, 7 weight loss, [8][9][10] cardiovascular protection, 11,12 breast and colorectal cancer, 13,14 glioblastoma, 15,16 amelioration of inflammation, 17,18 as a potential geroprotective agent for dementia, 19,20 and stimulation of hair growth. 21,22 These additional benefits of the off-label use of metformin exacerbate the mismatch between the supply and demand for the original drug.…”