Effect of rosiglitazone on spontaneous and clomiphene citrate-induced ovulation in women with polycystic ovary syndrome

Increased prevalence of insulin resistance in women with a history of recurrent pregnancy loss

Craig LB et al., 2002 · Fertil Steril

To determine whether insulin resistance is associated with recurrent pregnancy loss (RPL). Single center, case-controlled, prospective study. University-associated reproductive endocrinology clinical practice. PATIENT(S): Seventy-four nonpregnant, nondiabetic women with RPL. Controls were 74 fertile, nonpregnant, nondiabetic women without RPL who had at least one live infant, and were matched by age, race, and body mass index (BMI). INTERVENTION(S): Both groups consented to obtaining fasting insulin and glucose levels. MAIN OUTCOME MEASURE(S): Insulin resistance was defined as a fasting insulin level >20 microU/mL or a fasting glucose to insulin ratio of <4.5. RESULT(S): Among the 74 women with RPL, 20 (27.0%) demonstrated insulin resistance, whereas only 7 of 74 (9.5%) of the matched controls were insulin resistant (odds ratio 3.55; 95% confidence interval 1.40-9.01). The RPL and control groups were similar with respect to age, ethnicity, and BMI. The RPL and control groups had similar fasting glucose levels and glucose-to-insulin ratios. However, fasting insulin levels > or =20 microU/mL were statistically different between the two groups (odds ratio 3.92). CONCLUSION(S): Women with RPL have a significantly increased prevalence of insulin resistance when compared with matched fertile controls.

Etiologic Factors in Women with a History of Recurrent Pregnancy Loss

Kutteh W H et al., 1999 · Obstetrics & Gynecology

Recurrent Pregnancy Loss in Textbook of Reproductive Medicine, 2nd Edition

Kutteh WH, 1998

Improvement in insulin sensitivity followed by ovulation and pregnancy in a woman with polycystic ovary syndrome who was treated with rosiglitazone

Cataldo NA et al., 2001 · Fertil Steril

To determine the metabolic and reproductive effectiveness of rosiglitazone in polycystic ovary syndrome (PCOS). Case report. Academic clinical practice and General Clinical Research Center. PATIENT(S): A 25-year-old woman with PCOS. INTERVENTION(S): Rosiglitazone maleate, 4 mg daily for 5 months until conception. MAIN OUTCOME MEASURE(S): Insulin sensitivity by steady-state plasma glucose technique; serum androgens, progesterone, and hCG; and pelvic ultrasound images. RESULT(S): Rosiglitazone treatment for 5 months improved insulin sensitivity, lowered serum free testosterone, and resulted in spontaneous ovulation and conception. CONCLUSION(S): Rosiglitazone is a promising insulin sensitizer for treatment of PCOS. Clinical trials are warranted.

Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone

Vandermolen DT et al., 2001 · Fertil Steril · Free to read

To determine whether metformin treatment increases the ovulation and pregnancy rates in response to clomiphene citrate (CC) in women who are resistant to CC alone. Randomized, double-blind, placebo-controlled trial. Multicenter environment. PATIENT(S): Anovulatory women with the polycystic ovary syndrome (PCOS) who were resistant to CC. INTERVENTION(S): Participants received placebo or metformin, 500 mg three times daily, for 7 weeks. Information on reproductive steroids, gonadotropins, and oral glucose tolerance testing was obtained at baseline and after treatment. Metformin or placebo was continued and CC treatment was begun at 50 mg daily for 5 days. Serum P level > or =4 ng/mL was considered to indicate ovulation. With ovulation, the daily CC dose was not changed, but with anovulation it was increased by 50 mg for the next cycle. Patients completed the study when they had had six ovulatory cycles, became pregnant, or experienced anovulation while receiving 150 mg of CC. MAIN OUTCOME MEASURE(S): Ovulation and pregnancy rates. RESULT(S): In the metformin and placebo groups, 9 of 12 participants (75%) and 4 of 15 participants (27%) ovulated, and 6 of 11 participants (55%) and 1 of 14 participants (7%) conceived, respectively. Comparisons between the groups were significant. CONCLUSION(S): In anovulatory women with PCOS who are resistant to CC, metformin use significantly increased the ovulation rate and pregnancy rate from CC treatment.

Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome

Nestler JE et al., 1999 · N Engl J Med

Women with the polycystic ovary syndrome have insulin resistance and hyperinsulinemia, possibly because of a deficiency of a D-chiro-inositol-containing phosphoglycan that mediates the action of insulin. We hypothesized that the administration of D-chiro-inositol would replenish stores of the mediator and improve insulin sensitivity. We measured steroids in serum and performed oral glucose-tolerance tests before and after the oral administration of 1200 mg of D-chiro-inositol or placebo once daily for six to eight weeks in 44 obese women with the polycystic ovary syndrome. The serum progesterone concentration was measured weekly to monitor for ovulation. In the 22 women given D-chiro-inositol, the mean (+/-SD) area under the plasma insulin curve after the oral administration of glucose decreased from 13,417+/-11,572 to 5158+/-6714 microU per milliliter per minute (81+/-69 to 31+/-40 nmol per liter per minute) (P=0.007; P=0.07 for the comparison of this change with the change in the placebo group); glucose tolerance did not change significantly. The serum free testosterone concentration in these 22 women decreased from 1.1+/-0.8 to 0.5+/-0.5 ng per deciliter (38+/-7 to 17+/-3 pmol per liter) (P=0.006 for the comparison with the change in the placebo group). The women's diastolic and systolic blood pressure decreased by 4 mm Hg (P<0.001 and P=0.05, respectively, for the comparisons with the changes in the placebo group), and their plasma triglyceride concentrations decreased from 184+/-88 to 110+/-61 mg per deciliter (2.1+/-0.2 to 1.2+/-0.1 mmol per liter) (P=0.002 for the comparison with the change in the placebo group). None of these variables changed appreciably in the placebo group. Nineteen of the 22 women who received D-chiro-inositol ovulated, as compared with 6 of the 22 women in the placebo group (P<0.001). D-Chiro-inositol increases the action of insulin in patients with the polycystic ovary syndrome, thereby improving ovulatory function and decreasing serum androgen concentrations, blood pressure, and plasma triglyceride concentrations.

Extended clomiphene citrate (CC) and prednisone for the treatment of chronic anovulation resistant to CC alone

Isaacs JD Jr et al., 1997 · Fertil Steril

To evaluate effectiveness and safety of a regimen of extended clomiphene citrate (CC) and prednisone for patients who fail treatment with CC alone. Retrospective observational analysis. University-based tertiary infertility center. PATIENT(S): Twenty-four anovulatory patients who failed to ovulate after CC 150 mg administered for 5 days. INTERVENTION(S): Treatment consisted of CC given on cycle days 3 through 9 (extended) at a starting dose of 100 to 150 mg/d. Additionally, patients were given prednisone 5 mg orally each night throughout the cycle. MAIN OUTCOME MEASURE(S): Ovulation was confirmed by luteal serum P. Pregnancy was confirmed by rising hCG levels and transvaginal ultrasound. RESULT(S): A total of 60 cycles were available for review. Forty-four of these cycles were ovulatory (73%) and 11 patients (46%) conceived on this therapy. Logistic (two-parameter) pregnancy occurrence over time (cycles) revealed a maximum pregnancy probability of 0.66 and a cycle fecundity of 0.36. No complications of therapy were noted. CONCLUSION(S): Clomiphene citrate-resistant anovulatory patients have high rates of ovulation and pregnancy after treatment with extended CC and prednisone. This therapy offers a potential reduction in cost and risk and should be considered in this group of patients before gonadotropin stimulation or surgery.