Addition of human chorionic gonadotropin to clomiphene citrate ovulation induction therapy does not improve pregnancy outcomes and luteal function. A prospective randomized trial comparing clomiphene citrate with tamoxifen citrate for ovulation induction. Clomiphene citrate and dexamethazone in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective placebo-controlled study. The efficacy of clomiphene citrate for induction of ovulation. A controlled study. A randomized clinical trial of treatment of clomiphene citrate-resistant anovulation with the use of oral contraceptive pill suppression and repeat clomiphene citrate treatment. Conception rates in clomiphene citrate cycles with and without hormone supplementation: a pilot study. Use of micro-dose human chorionic gonadotropin (hCG) after clomiphene citrate (CC) to complete folliculogenesis in previous CC-resistant anovulation. A clomiphene citrate and tamoxifen citrate combination therapy: a novel therapy for ovulation induction. A randomized study of dexamethasone in ovulation induction with clomiphene citrate. Improved responsiveness of PCOS patients to clomiphene after CYP17a inhibitor. Use of dexamethasone and clomiphene citrate in the treatment of clomiphene citrate-resistant patients with polycystic ovary syndrome and normal dehydroepiandrosterone sulfate levels: a prospective, double-blind, placebo-controlled trial. A prospective, double-blind, randomized, placebo-controlled clinical trial of bromocriptine in clomiphene-resistant patients with polycystic ovary syndrome and normal prolactin level. Induction of ovulation with clomiphene citrate. A double-blind study.
In a randomized prospective study, 125 women with World Health Organization class II anovulation received 50 mg of clomiphene citrate alone (group A, n = 65) or 50 mg of clomiphene citrate plus hCG (group B, n = 60) in a total of 125 cycles during natural intercourse-advised cycles. There were no statistically significant differences between groups regarding pregnancy outcomes and midluteal P levels, but luteal phase length was longer in group A. To compare the rates of ovulation and pregnancy after tamoxifen citrate (TMX) or clomiphene citrate (CC) among anovulatory women with infertility.
                Prospective randomized trial.
                Infertility clinic in a university teaching hospital.
                Eighty-six anovulatory women under 40 years of age undergoing ovulation induction.
                The women were assigned randomly to receive either TMX or CC on cycle days 5-9.
                Rates of ovulation and pregnancy for the two treatment modalities.
                The overall rate of ovulation in the TMX group was 50 of 113 (44.2%) and in the CC group, 41 of 91 (45.1%). There were 10 pregnancies in the TMX group and 6 pregnancies in the CC group. The cycle fecundity per ovulatory cycle was 20.0% in the TMX group and 14.6% in the CC group.
                The overall rate of ovulation and pregnancy were similar with TMX and CC. TMX is a suitable alternative agent to CC in the management of anovulatory infertility. The aim of this work was to evaluate the efficacy of adding dexamethazone (DEX) (high dose, short course) to clomiphene citrate (CC) in CC-resistant polycystic ovary syndrome (PCOS) with normal dehydroepiandrosterone sulphate (DHEAS) in induction of ovulation.
                Eighty infertile women with CC-resistant PCOS were randomly assigned into two groups. Group I: Clomiphene citrate 100 mg/day was given from day 3 to day 7 of the cycle and DEX 2 mg/day from day 3 to day 12 of the cycle. Group II: Same protocol of CC combined with placebo (folic acid tablets) was given from day 3 to day 12 of the cycle. The main outcome was ovulation. Secondary measures included number of follicles >18 mm endometrial thickness and pregnancy rate. Ovarian follicular response was monitored by transvaginal ultrasound. HCG 10,000 U was given when at least one follicle measured 18 mm, and timed intercourse was advised.
                There were no statistically significant differences between groups as regards age, duration of infertility, BMI, waist-hip ratio (WHR), menstrual pattern, hirsutism, serum DHEAS or day of HCG administration. The mean number of follicles>18 mm at the time of HCG administration and the mean endometrial thickness were significantly higher in the DEX group than in the placebo group (P<0.05). Similarly, there were significantly higher rates of ovulation (75 versus 15%) (P<0.001) and pregnancy (40 versus 5%) (P<0.05) in the DEX group. Dexamethazone was very well tolerated as no patients complained of any side effect. There was a significant difference between the responders and non-responders in the presence of oligomenorrhea, amenorrhea or hirsutism.
                Induction of ovulation by adding DEX (high dose, short course) to CC in CC-resistant PCOS with normal DHEAS is associated with no adverse anti-estrogenic effect on the endometrium and higher ovulation and pregnancy rates in a significant number of patients. Induction with DEX appears to be independent on age, period of infertility, BMI or WHR. nan The purpose of this study was to evaluate the effectiveness and endocrine response of oral contraceptive ovarian suppression followed by clomiphene citrate in patients who previously were clomiphene citrate resistant.
                Forty-eight patients from a private tertiary infertility clinic were assigned randomly prospectively to either group 1 (oral contraceptive/clomiphene citrate), which received continuous oral contraceptives followed by clomiphene citrate, or to group 2 (control) received no treatment in the cycle before clomiphene citrate treatment. On day 3, 17 beta-estradiol, follicle-stimulating hormone, luteinizing hormone, and androgens were assayed before and after treatment. Follicle growth, ovulation, and pregnancy were evaluated. The Student t test and analysis of variance were used for statistical significance.
                The oral contraceptive/clomiphene citrate group had a significantly higher percentage of patients who ovulated and of ovulatory cycles and pregnancies. Significantly lower levels of 17 beta-estradiol, luteinizing hormone, and androgen levels were seen in the oral contraceptive/clomiphene citrate group, with no significant changes in group 2.
                Suppression of the ovary with oral contraceptives results in excellent rates of ovulation and pregnancy in patients who previously were resistant to clomiphene citrate. The decreases in ovarian androgens, luteinizing hormone, and 17 beta-estradiol may be responsible for the improved response. A trial was conducted to examine the effects of a timed sequence of hormone supplementation (HS) with oral estradiol (E(2)) and vaginal progesterone (P) following clomiphene citrate (CC) therapy to determine if this regimen can increase pregnancy rates in CC cycles.
                This study was a randomized, open-label study. Seventy-one oligo-ovulatory women were randomized into one of two groups; those who received CC plus HS (n = 34) and those who received no HS (n = 37). All subjects received 100 mg CC orally from cycle days 3 to 7. Subjects randomized to HS started oral E(2) at a dose of 1.5 mg BID on cycle day 8. All subjects monitored urine luteinizing hormone (LH) levels starting on cycle day 10; additionally, intercourse was encouraged starting on cycle day 10. Subjects receiving HS discontinued E(2) with LH surge and started using vaginal progesterone gel (Prochieve 8%) daily for 2 weeks starting 3 days after LH surge. All subjects had a pregnancy test (Assure) 2 weeks after LH surge. If pregnancy occurred, the subject continued using vaginal progesterone gel daily for an additional 10 weeks.
                Sixty-five (65) subjects (31 CC plus HS and 34 no HS) completed the study. Fifty of the 65 subjects (77%) (23 [74%] CC plus HS, 27 [79%] no HS) who completed the study ovulated. The mean (range) progesterone (P) concentration for these 50 subjects was 1662.6 (340 to 5690) ng/dL, and mean and median P levels were slightly higher, but not statistically significant, in the HS group compared with the no HS group. Pregnancy rates were clinically, but not statistically, different between the treatment groups. Of the 50 responders, 12% became pregnant (17% CC plus HS, 7% no HS).
                These findings show a potential supportive effect on pregnancy rates in the CC plus oral estradiol and vaginal progesterone gel group compared to CC alone that needs to be confirmed in a larger study. The purpose of this study was to compare the effectiveness of low-dose human chorionic gonadotropin (hCG) in the late follicular phase to induce ovulation and its endocrine response in patients who had previously failed to ovulate on clomiphene citrate (CC) alone.
                A total of 67 patients from a private tertiary infertility clinic, who had produced a dominant follicle 12 mm or larger but 20 mm or smaller on a prior CC cycle at 100 mg but had failed to ovulate, were prospectively randomly assigned to groups. Group 1 repeated the 100 mg dose of CC but started a 200 IU hCG intramuscular injection daily when the largest follicle was 12 mm or larger mean diameter. Group 2 received a 150 mg dose of CC and both groups were monitored with transvaginal ultrasound and serum levels of E 2 , P 4 , and testosterone. Ultrasound measurements of follicle number and growth, ovulation, pregnancy rates, and serum hormonal levels were recorded and compared between the 2 groups. Analysis of variance and Student t test were used for statistical significance.
                The low-dose hCG group had significantly higher percentage of ovulatory cycles (57% vs 7% P < .001), peak E 2 levels (378 pg/mL vs 125 pg/mL P < .01), and pregnancy rates (18% vs 0% P < .001). This group showed no evidence of premature leutinization from the hCG with preovulatory P 4 levels less than 1.0 ng/mL and a slight increase in androgen levels.
                The use of micro-dose hCG after CC in the late follicular phase results in continued follicle growth, increased E 2 levels, ovulation, and pregnancies. This treatment offers an efficient and cost-effective alternative before gonadotropin therapy for this type of patient. To assess the efficacy of a clomiphene citrate (CC) and tamoxifen citrate (CC/tamoxifen) combination therapy in ovulation induction by comparing with a CC alone therapy.
                A randomized cross-over study with CC alone and CC/tamoxifen combination therapies for 20 normoprolactinemic anovulatory women. Randomly selected 10 of the 20 women (group A) underwent a CC alone therapy (100 mg CC during cycle days 5 to 9) for the initial three consecutive treatment cycles and a CC/tamoxifen combination therapy (50 mg CC and 20 mg tamoxifen during cycle days 5 to 9) for the subsequent three consecutive treatment cycles. The remaining 10 (group B) were treated similarly but with the inverse sequence. Ovulation was documented when a high BBT phase persisted for 11 days or more, when midluteal serum P levels exceeded 7 ng/mL (22.3 nmol/L), or when pregnancy ensued.
                The rates of ovulatory/treated, pregnant/treated, and pregnant/ovulatory cycles were 42 of 56 (75.0%), 3 of 47 (6.4%), and 3 of 35 (8.6%) for CC/tamoxifen, respectively. Those were 25 of 57 (43.9%), 1 of 48 (2.1%), and 1 of 21 (4.8%) for CC, respectively. Clomiphene citrate/tamoxifen was more effective in ovulation induction than CC. All the pregnancies were normal and single. None of the treatments was accompanied by any remarkable side effects.
                Clomiphene citrate/tamoxifen is a novel treatment modality of ovulation induction with high efficacy. Improved understanding of follicular dynamics has led to a reevaluation of suppression of adrenal androgens in ovulation induction. To test whether adrenal suppression during clomiphene citrate (CC) therapy would improve ovulation/pregnancy rates, 64 anovulatory patients who had not previously received CC were randomly assigned to receive either 50 mg CC on days 5 to 9 alone or with 0.5 mg dexamethasone (CC + DEX). Patients were then screened for dehydroepiandrosterone sulfate (DHEA-S) (normal range, 80 to 320 micrograms/dl), prolactin, testosterone, and semen analysis of the partner. Nine patients discontinued participation prior to completing the first treatment cycle, and ten patients were found to have either elevated prolactin (4), severe male factors (3), or tubal disease (3) and were discontinued. CC was increased 50 mg/day per cycle through 150 mg/day until ovulation occurred. Once the patient was ovulatory on therapy, a properly timed postcoital test and endometrial biopsy for luteal phase defect were performed. If anovulatory at 150 mg/day of CC or demonstrating abnormal postcoital test or endometrial biopsy at 150 mg/day of CC, patients were crossed to the other arm of the treatment protocol. The results revealed a significantly higher rate of ovulation (P less than 0.01) and conception (P less than 0.05) in the CC + DEX-treated group. When correlated with DHEA-S levels, this improvement occurred in patients with DHEA-S greater than 200 micrograms/dl (P less than 0.05). To study the effect of CYP17a inhibitor, "ketoconazole," on clomiphene responsiveness in PCOS patients.
                Prospective analysis was employed with the setup at Alexandria IVF/ICSI center. Ninety-seven insulin-resistant PCOS patients undergoing ovulation induction using clomiphene citrate were randomly divided, by random number table, into two groups. The first group (n = 49) received ketoconazole (400 mg daily) till correction of metabolic syndrome followed by clomiphene (100 mg/day); the second group (n = 48) receiving clomiphene without ketoconazole pretreatment. Main outcome measures were incidence of clomiphene resistance, monofollicular response, fasting insulin/glucose ratio, serum testosterone, and pregnancy rates.
                The ketoconazole group showed significantly (p < 0.05) higher incidence of monofollicular response (38%), higher pregnancy rates, and significantly less marked antiestrogenic manifestations than did the control group. They also had significantly lower incidence of clomiphene resistance (11.6%), lower serum testosterone levels, less hyperinsulinaemia, than did the control group.
                Ketoconazole improved clomiphene responsivenss in PCOS patients and attenuated its untoward biological effects. To evaluate the effects of short-course administration of dexamethasone (DEX) combined with clomiphene citrate (CC) in CC-resistant patients with polycystic ovary syndrome (PCOS) and normal DHEAS levels.
                Prospective, double-blind, placebo-controlled, randomized study.
                Referral university hospitals.
                Two hundred thirty women with PCOS and normal DHEAS who failed to ovulate after a routine protocol of CC.
                The treatment group received 200 mg of CC from day 5 to day 9 and 2 mg of DEX from day 5 to day 14 of the menstrual cycle. The control group received the same protocol of CC combined with placebo.
                Follicular development, hormonal status, ovulation rate, pregnancy rate.
                Mean follicular diameters were 18.4124 +/- 2.4314 mm and 13.8585 +/- 2.0722 mm for the treatment and control groups, respectively. Eighty-eight percent of the treatment group and 20% of the control group had evidence of ovulation. The difference in the cumulative pregnancy rate in the treatment and control groups was statistically significant.
                Hormonal levels, follicular development, and cumulative pregnancy rates improved with the addition of DEX to CC in CC-resistant patients with PCOS and normal DHEAS. This regimen is recommended before any gonadotropin therapy or surgical intervention. To evaluate the effects of administration of bromocriptine combined with clomiphene citrate (CC) in CC-resistant patients with polycystic ovary syndrome (PCOS) and normal prolactin (PRL) level.
                Prospective double-blind, placebo-controlled, randomized.
                Referral university hospitals.
                One hundred women with PCOS and normal PRL who failed to ovulate with a routine protocol of CC.
                Treatment group received 150 mg of CC from day 5 to 9 and 7.5 mg bromocriptine continuously, with hCG 10,000 units on day 16 or 17. Control group received the same protocol of CC combined with placebo.
                Follicular development, hormonal changes, ovulation rate, pregnancy rate.
                Follicular development (follicular size greater than 15 mm) was observed in 12 (25.5%) and 8 (15.1%) women in the treatment and placebo group, respectively (p = 0.29). The serum prolactin level was within normal limits in all patients before treatment. After 3 and 6 months of treatment with bromocriptine, there was a significant decrease in serum level of prolactin (p = 0.000001). No significant differences were seen in ovulation, pregnancy rate, or serum levels of FSH, LH, DHEAS, and progesterone between treatment and placebo groups after treatment.
                The only significant effect of long-term bromocriptine therapy in CC-resistant women with PCOS was to lower the serum PRL concentration. It is also concluded that 10%-15% of patients with PCOS experienced occasional ovulatory cycles and pregnancy whether or not they were on treatment. nan
This review shows evidence supporting the effectiveness of clomiphene citrate and clomiphene in combination with dexamethasone for pregnancy rate only. There is limited evidence on the effects of these drugs on outcomes such as miscarriage. Evidence in favour of these interventions is flawed due to the lack of evidence on live births.