Clomiphene, Metformin, or Both for Infertility in the Polycystic Ovary Syndrome

Legro, Richard S.; Barnhart, Huiman X.; Schlaff, William D.; Carr, Bruce R.; Diamond, Michael P.; Carson, Sandra Ann; Steinkampf, Michael P.; Coutifaris, Christos; McGovern, Peter G.; Cataldo, Nicholas A.; Gosman, Gabriella G.; Nestler, John E.; Giudice, Linda C.; Leppert, Phyllis C.; Myers, Evan R.

doi:10.1056/nejmoa063971

Cited by 897 publications

(548 citation statements)

References 33 publications

Supporting

Mentioning

486

Contrasting

Unclassified

Order By: Relevance

“…This result contrasts with data observed in hyperandrogenic patients without T1D, who experience increases in ovulation, menstrual cyclicity and pregnancy rates upon treatment with metformin [32,33,34,35]. We hypothesize that ovulatory function in adolescents with T1D does not change upon metformin treatment because the ovulatory function was similar to healthy control girls at a basal level.…”

Section: Discussioncontrasting

confidence: 55%

Metformin for the Treatment of Hyperandrogenism in Adolescents with Type 1 Diabetes Mellitus

et al. 2013

View full text Add to dashboard Cite

Background: A high prevalence of hyperandrogenism has been reported in women with type 1 diabetes (T1D). Metformin has been used as a therapeutic agent in patients with polycystic ovarian syndrome and in T1D patients without hyperandrogenism. This study sought to determine the effect of metformin on hyperandrogenism and ovarian function in adolescents with T1D. Methods: We recruited 24 girls with T1D. The participants had hyperandrogenism and displayed suboptimal metabolic control. The patients were enrolled in a randomized, double-blind, placebo-controlled trial. One group received metformin (850 mg bid) and the other group received a placebo. Treatment was administered for 9 months. Ovulation, steroids and gonadotropin levels were evaluated. Results: Metformin treatment was associated with decreases in testosterone, free androgen index, androstenedione, 17-OH progesterone and estradiol levels. The girls who were treated with placebo showed stable steroid, gonadotropin and sex hormone-binding globulin levels during the analysis. No differences were observed in the Ferriman-Gallwey scores, ovulation rates, HbA_1c levels or daily insulin doses of the girls treated with metformin compared with the placebo group. Conclusion: Treating hyperandrogenic T1D adolescents with metformin significantly decreased the serum androgens compared to the placebo, but metformin therapy did not significantly affect clinical parameters, such as hirsutism, ovulation and metabolic control.

show abstract

Section: Discussioncontrasting

confidence: 55%

Metformin for the Treatment of Hyperandrogenism in Adolescents with Type 1 Diabetes Mellitus

et al. 2013

View full text Add to dashboard Cite

show abstract

“…From the remaining 106 articles, 60 were excluded on the basis of the abstract. For the remaining 46, we obtained full manuscripts and following scrutiny of these, we identified 32 potentially relevant studies; 6 publications were duplicated [19,20,21,22,23,24]. From these 32, another 4 were excluded because they included women with PCOS who were CC resistant.…”

Section: Resultsmentioning

confidence: 99%

Is Metformin Indicated as Primary Ovulation Induction Agent in Women with PCOS? A Systematic Review and Meta-Analysis

Siebert¹,

Viola²,

Steyn³

et al. 2012

Gynecol Obstet Invest

View full text Add to dashboard Cite

Background: A recent meta-analysis has proven that metformin (M) is highly effective for ovulation induction in the clomiphene citrate (CC)-resistant patient. There is uncertainty whether M should be introduced as a primary ovulation induction agent in polycystic ovarian syndrome (PCOS). Methods: We conducted a systematic review and meta-analysis to establish if M is better when given alone or in combination with CC (CC+M) when compared with CC alone. This systematic review studied live birth delivery rate as the primary outcome. Results: We identified 14 prospective trials. Analysis of these results showed a reduction in the live birth rate in the group of patients treated only with M when compared with CC alone (OR = 0.48, 95% CI 0.31–0.73, p = 0.0006). An increase in ovulation (OR = 1.6, 95% CI 1.2–2.1, p = 0.0009) and pregnancy rate (OR = 1.3, 95% CI 1.0–1.6, p = 0.05) with CC+M when compared with CC alone was reported, but no difference was found when live birth rate was analyzed (OR = 1.1, 95% CI 0.8–1.5, p = 0.61). Conclusion: CC alone is superior to M alone regarding live birth rate and ovulation. The combination (CC+M) is superior to CC alone as a primary method for ovulation induction and to achieve pregnancy in PCOS. However, when addressing live birth rate, no statistically significant difference could be demonstrated. Because of the side effects profile and contraindications of M, we believe M should not be indicated as a primary ovulation induction agent in women with PCOS.

show abstract

“…Another randomized controlled trial involving 626 infertile women with PCOS demonstrated the rates of miscarriage in the first trimester did not differ significantly among the group that received metformin only, the group that received clomiphene only, and the combination therapy group. The live-birth rate of the metformin group was however lower than that of the clomiphene citrate and combination groups (7.2, 22.5, and 26.8%, respectively) [20]. Two meta-analyses conducted by Palomba et al [21,22] to evaluate the effect of ovulatory rate of metformin only and metformin + clomiphene citrate found out that neither metformin nor metformin + clomiphene citrate could reduce the rate of miscarriage.…”

Section: Discussionmentioning

confidence: 99%

Relationship between Recurrent Miscarriage and Insulin Resistance

Wang¹,

Zhao²,

Li³

et al. 2011

Gynecol Obstet Invest

View full text Add to dashboard Cite

Aims: To investigate the differences in insulin resistance between women with recurrent miscarriage and those with normal pregnancy. Methods: Pregnant women with a history of recurrent miscarriage were included in the patient group (n = 97), while those with no history of abnormal pregnancy were included in the control group (n = 52). Both groups consented to undertake an oral glucose tolerance test and insulin-releasing test between the 5th and 13th weeks of pregnancy. Results: (1) Levels of fasting plasma glucose, fasting plasma insulin, homeostasis model assessment of insulin resistance index, and homeostasis model assessment β function were not statistically significantly different (p < 0.05) between the two groups. (2) The area under the curve of glucose and area under the curve of insulin were higher in the patient group than in the control group. The composite insulin sensitivity index of the patient group was lower than that of the control group. The differences in these three parameters between the groups were statistically significant (p < 0.05). Conclusion: Women with a history of recurrent miscarriage are at an increased risk for insulin resistance during the first trimester of a new pregnancy.

show abstract

Clomiphene, Metformin, or Both for Infertility in the Polycystic Ovary Syndrome

Abstract: Clomiphene is superior to metformin in achieving live birth in infertile women with the polycystic ovary syndrome, although multiple birth is a complication. (ClinicalTrials.gov number, NCT00068861 [ClinicalTrials.gov].).

Cited by 897 publications

References 33 publications

Metformin for the Treatment of Hyperandrogenism in Adolescents with Type 1 Diabetes Mellitus

Metformin for the Treatment of Hyperandrogenism in Adolescents with Type 1 Diabetes Mellitus

Is Metformin Indicated as Primary Ovulation Induction Agent in Women with PCOS? A Systematic Review and Meta-Analysis

Relationship between Recurrent Miscarriage and Insulin Resistance

Contact Info

Product

Resources

About