Comparison of clomiphene citrate, metformin, or the combination of both for first-line ovulation induction, achievement of pregnancy, and live birth in Asian women with polycystic ovary syndrome: a randomized controlled trial.

OBJECTIVE: To determine the first-line medication to be used in anovulatory patients with polycystic ovary syndrome (PCOS) for ovulation induction and pregnancy achievement. DESIGN: Randomized controlled trial. SETTING: Infertility unit of a public hospital. PATIENT(S): One hundred fifteen newly diagnosed patients with PCOS based on ESHRE/ASRM criteria. INTERVENTION(S): These patients were assigned to three groups: group 1 (38 patients) received 500 mg of metformin three times a day; group 2 (39 patients) received clomiphene citrate (CC) at an incremental dose; group 3 (38 patients) received both medications. MAIN OUTCOME MEASURE(S): Rates of ovulation, pregnancy (PR), and live birth. RESULT(S): The ovulation rate was 23.7% in the metformin group, 59% in the CC group, and 68.4% in the combination treatment group. This was translated into a similar PR and live birth rate, which were higher in the CC and combination groups compared to the metformin group (PR: 7.9%, 15.4%, and 21.1%; live birth rate: 7.9%, 15.4%, and 18.4% in metformin, CC, and combination treatment groups, respectively), although statistically the differences were not significant. There were no multiple pregnancies and the rate of spontaneous first trimester loss was similar to the general population. CONCLUSION(S): Clomiphene citrate should be the first-line treatment for ovulation induction in anovulatory patients with PCOS.

Follicle-stimulating hormone receptor polymorphism (Thr307Ala) is associated with variable ovarian response and ovarian hyperstimulation syndrome in Indian women.

OBJECTIVE: To evaluate the association of FSH receptor polymorphism and ovarian response. DESIGN: Retrospective study. SETTING: Academic research institute and private IVF clinic. PATIENT(S): Fifty women were recruited in an assisted reproductive technology program (ART) and 100 proven fertile women of Indian origin. INTERVENTION(S): Polymerase chain reaction, restriction fragment-length polymorphism for detecting polymorphisms at T(307)A and N(680)S. MAIN OUTCOME MEASURE(S): FSH receptor polymorphisms, serum FSH, and estradiol levels, amount of FSH administered, occurrence of ovarian hyperstimulation syndrome (OHSS). RESULT(S): Prevalence of polymorphism at 307 position was 24%, 53%, and 23% in controls and 24%, 62%, and 14% in ART subjects for TT, TA, and AA, respectively, whereas at position 680, it was 31%, 56%, and 13% in controls and 42%, 46%, and 12% in ART subjects for NN, NS, and SS, respectively. The amount of FSH required for ovulation induction was low in AA compared with TT and TA subjects; the estradiol levels before and on the day of hCG administration were significantly higher. Eighty-five percent of the subjects with AA genotype developed OHSS. CONCLUSION(S): In Indian women, the subjects with AA genotype require low amounts of FSH for ovarian stimulation and have an increased risk of developing OHSS.

Suppression of ovulation by a new subcutaneous depot medroxyprogesterone acetate (104 mg/0.65 mL) contraceptive formulation in Asian women.

BACKGROUND: A new progestin-only, nondaily depot medroxyprogesterone acetate (DMPA) SC injectable contraceptive suspension (104 mg/0.65 mL) has been developed. Clinical trials (including dose-ranging, pharmacokinetic/pharmacodynamic, and contraceptive efficacy studies) indicating the effectiveness of this new formulation were conducted primarily in white women. However, results of an early study by the World Health Organization suggested that in Thai women, medroxyprogesterone acetate (MPA) may be metabolized in <91 +/- 7 days (the range for effective suppression of ovulation established in clinical trials), resulting in a faster return to ovulation in this population. OBJECTIVES: This study was designed to determine the duration of ovulation suppression and investigate the pharmacokinetic profile of MPA after a single SC injection of DMPA 104 mg/0.65 mL in Asian women. It also assessed the effect of ethnicity and injection site on the duration of ovulation suppression. METHODS: : This was a single-center, single-dose, open-label outpatient trial conducted in Singapore in Asian women aged 18 to 40 years. After 1 control cycle, women with confirmed ovulation were randomized in a 1:1 ratio to receive an SC injection of DMPA 104 mg/0.65 mL in either the anterior thigh or the abdomen. Serum concentrations of MPA, progesterone, estradiol, luteinizing hormone, and follicle-stimulating hormone were measured during the 91-day dosing interval and for an additional 15 days thereafter. RESULTS: Twenty-four Asian women (mean [SD] age, 33.8 [43] years; range, 22.7-40.1 years; mean [SD] body mass index, 22.4 [3.0] kg/m(2)) belonging to 5 ethnic groups (Chinese, Filipino, Indian, Malaysian, and Thai) were included in the study Ovulation suppression was maintained throughout the 91-day dosing interval, regardless of ethnicity or injection site. Ovulation was suppressed for at least 112 days after injection in 23 (95.8%) women, as evidenced by maintenance of serum progesterone concentrations <4.7 ng/mL. The pharmacokinetic parameters for MPA in these Asian women were similar to those previously reported in white women. The most frequently reported adverse events were flulike symptoms and headache, all of mild to moderate intensity. No serious adverse events were reported. CONCLUSIONS: In this study, SC DMPA 104 mg/0.65 mL provided effective suppression of ovulation for at least 91 days in Asian women. Ethnicity and injection site had no effect on MPA profiles.