Comparative effectiveness of 9 ovulation-induction therapies in patients with clomiphene citrate-resistant polycystic ovary syndrome: a network meta-analysis

Abstract

The comparative efficacies of ovulation-induction treatments in patients with clomiphene citrate-resistant (CCR) polycystic ovary syndrome (PCOS) are not well known. Therefore, we conducted a network meta-analysis to rank the reproductive efficacies of these treatments. We ultimately included 26 randomized clinical trials with 2722 participants and 9 types of therapies: clomiphene citrate (CC), metformin, letrozole, follicle stimulating hormone (FSH), human menopausal gonadotropin (hMG), unilateral laparoscopic ovarian drilling (ULOD), bilateral laparoscopic ovarian drilling (BLOD), the combination of metformin with letrozole (metformin+letrozole), and the combination of metformin with CC (metformin+CC). The network meta-analysis demonstrates that hMG therapy result in higher pregnancy rates than BLOD, ULOD and CC therapies. Pregnancy, live birth and ovulation rates are significantly higher in metformin+letrozole and FSH groups than CC group. The abortion rate in the metformin+letrozole group is significantly lower than that in the metformin+CC group. Ranking probabilities show that, apart from gonadotropin (FSH and hMG), metformin+letrozole is also potentially more effective in improving reproductive outcomes than other therapies. In conclusion, owing to the low quality of evidence and the wide confidence intervals, no recommendation could be made for the treatment of ovulation-induction in patients with CCR PCOS.

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

“…The RCT published by Hashim HA (2011), which included the largest number of patients and cited by two reviews ( Yu et al, 2017 ; Bordewijk et al, 2020a ) and Guidelines ( Teede et al, 2018 ) are essential and had recently been suspected by rationalization on the study and data integrity ( Bordewijk et al, 2020b ; Bordewijk et al, 2020c ; Bordewijk et al, 2020d ). Although Hashim HA.…”

“…The results of Yu et al (2017) showed no difference in live birth, pregnancy, ovulation induction, or miscarriage rates between Met/Met-CC and LOD (Yu et al, 2017). The same authors concluded that no recommendation could be made regarding ovulation induction in patients with CCR-PCOS because the quality of evidence was low and the confidence intervals wide.…”

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

“…The RCT published by Hashim HA (2011), which included the largest number of patients and cited by two reviews ( Yu et al, 2017 ; Bordewijk et al, 2020a ) and Guidelines ( Teede et al, 2018 ) are essential and had recently been suspected by rationalization on the study and data integrity ( Bordewijk et al, 2020b ; Bordewijk et al, 2020c ; Bordewijk et al, 2020d ). Although Hashim HA.…”

“…The results of Yu et al (2017) showed no difference in live birth, pregnancy, ovulation induction, or miscarriage rates between Met/Met-CC and LOD (Yu et al, 2017). The same authors concluded that no recommendation could be made regarding ovulation induction in patients with CCR-PCOS because the quality of evidence was low and the confidence intervals wide.…”

Comparative study between the effect of letrozole versus letrozole with Metformin in treatment of anovulation in overweight women.

“…Eventually, combination treatments, like metformin plus CC (metformin+CC) and metformin plus letrozole (metformin+letrozole), were developed and are now frequently employed to stimulate ovulation in CCR-PCOS women. The comparative efficacy of such therapies, on the other hand, is unknown 13 .…”

Variation of Laparoscopic Ovarian Drilling for Clomiphene Citrate-resistant Patients with Polycystic Ovary Syndrome and Infertility: A Meta-analysis

“…Reproductive outcomes of unilateral LOD were compared with bilateral LOD in 2 previous reviews, both of which included 5 RCTs [32,33].…”

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

“…The RCT published by Hashim HA (2011), which included the largest number of patients and cited by two reviews ( Yu et al, 2017 ; Bordewijk et al, 2020a ) and Guidelines ( Teede et al, 2018 ) are essential and had recently been suspected by rationalization on the study and data integrity ( Bordewijk et al, 2020b ; Bordewijk et al, 2020c ; Bordewijk et al, 2020d ). Although Hashim HA.…”

“…The results of Yu et al (2017) showed no difference in live birth, pregnancy, ovulation induction, or miscarriage rates between Met/Met-CC and LOD (Yu et al, 2017). The same authors concluded that no recommendation could be made regarding ovulation induction in patients with CCR-PCOS because the quality of evidence was low and the confidence intervals wide.…”

Comparative study between the effect of letrozole versus letrozole with Metformin in treatment of anovulation in overweight women.

“…Eventually, combination treatments, like metformin plus CC (metformin+CC) and metformin plus letrozole (metformin+letrozole), were developed and are now frequently employed to stimulate ovulation in CCR-PCOS women. The comparative efficacy of such therapies, on the other hand, is unknown 13 .…”

Variation of Laparoscopic Ovarian Drilling for Clomiphene Citrate-resistant Patients with Polycystic Ovary Syndrome and Infertility: A Meta-analysis

“…Reproductive outcomes of unilateral LOD were compared with bilateral LOD in 2 previous reviews, both of which included 5 RCTs [32,33].…”

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

“…The RCT published by Hashim HA (2011), which included the largest number of patients and cited by two reviews ( Yu et al, 2017 ; Bordewijk et al, 2020a ) and Guidelines ( Teede et al, 2018 ) are essential and had recently been suspected by rationalization on the study and data integrity ( Bordewijk et al, 2020b ; Bordewijk et al, 2020c ; Bordewijk et al, 2020d ). Although Hashim HA.…”

“…The results of Yu et al (2017) showed no difference in live birth, pregnancy, ovulation induction, or miscarriage rates between Met/Met-CC and LOD (Yu et al, 2017). The same authors concluded that no recommendation could be made regarding ovulation induction in patients with CCR-PCOS because the quality of evidence was low and the confidence intervals wide.…”

Comparative study between the effect of letrozole versus letrozole with Metformin in treatment of anovulation in overweight women.

“…Eventually, combination treatments, like metformin plus CC (metformin+CC) and metformin plus letrozole (metformin+letrozole), were developed and are now frequently employed to stimulate ovulation in CCR-PCOS women. The comparative efficacy of such therapies, on the other hand, is unknown 13 .…”

Variation of Laparoscopic Ovarian Drilling for Clomiphene Citrate-resistant Patients with Polycystic Ovary Syndrome and Infertility: A Meta-analysis

“…Reproductive outcomes of unilateral LOD were compared with bilateral LOD in 2 previous reviews, both of which included 5 RCTs [32,33].…”