Treatment of chronic anovulation resistant to clomiphene citrate (CC) by using oral contraceptive ovarian suppression followed by repeat CC treatment

OBJECTIVE: To evaluate the effectiveness of a 2-month oral contraceptive (OC) ovarian suppression followed by clomiphene citrate (CC) in patients who had failed to ovulate on maximum doses of CC alone. DESIGN: Prospective, nonrandomized observational study. SETTING: Private tertiary infertility center. PATIENT(S): Thirty-eight patients with documented anovulation by transvaginal ultrasound follicular monitoring while receiving CC in doses of 150 mg or higher. INTERVENTION(S): Two-month ovarian-hypothalamic-pituitary axis suppression with OCs followed by repeat CC 100 mg for 5 days. MAIN OUTCOME MEASURE(S): Follicle growth, endometrial development, and ovulation were confirmed by transvaginal ultrasound. Pregnancy was confirmed by serum hCG levels and 7-week gestation ultrasound. RESULT(S): Thirty-eight patients completed 95 treatment cycles. Twenty-nine patients became ovulatory (76%), and 69 of the 95 cycles were ovulatory (72.6%), resulting in 22 pregnancies in the 38 patients for a cumulative pregnancy rate of 58%. CONCLUSION(S): Suppression of the hypothalamic-pituitary-ovarian axis for 2 months with OCs followed by CC treatment results in excellent rates of ovulation and pregnancy in women who had previously failed to ovulate on CC alone. This treatment offers an effective, reasonable, inexpensive, and low-risk alternative before gonadotropin therapy.     

Minimal stimulation IVF using clomiphene citrate and oral contraceptive pill pretreatment for LH suppression

OBJECTIVE: To determine if oral contraceptive pill (OC) pre-treatment prior to minimal stimulation IVF using clomiphene citrate (CC) would make the procedure easier to perform by preventing the LH surge and result in pregnancy rates (PRs) comparable to stimulated IVF. DESIGN: Prospective cohort study. SETTING: Private tertiary infertility center. PATIENT(s): Thirty-two women with tubal or pelvic adhesive disease as the cause of their infertility, ovulatory cycles, under the age of 40, and no male factor. INTERVENTION(s): Two-month ovarian-hypothalamic-pituitary axis suppression with OC followed by CC 100 mg on day 3 of the cycle for 8 days, hCG administration midcycle, follicle aspiration, IVF, and embryo transfer. MAIN OUTCOME MEASURE(s): Oocytes retrieved, serum LH and estradiol levels, maturity of oocytes, fertilization rates, embryo number and quality, and PRs. RESULT(s): Thirty-six patients completed 71 stimulation cycles and 64 follicle aspirations. No LH surges occurred with a mean mature oocytes retrieved of 3.2, 90% fertilization rate, and mean 2.5 embryos transferred. Twenty-one of the 64 cycles resulted in a clinical pregnancy (32.8% PR per retrieval) with 2 other biochemical pregnancies and 3 twin gestations. This was not significantly different from the matched cohort stimulated IVF. CONCLUSION(s): Minimal stimulation IVF is a simple, low-cost, and low-risk alternative to stimulated IVF with comparable PRs.     

A prospective randomized trial comparing clomiphene citrate with tamoxifen citrate for ovulation induction

OBJECTIVE: To compare the rates of ovulation and pregnancy after tamoxifen citrate (TMX) or clomiphene citrate (CC) among anovulatory women with infertility. DESIGN: Prospective randomized trial. SETTING: Infertility clinic in a university teaching hospital. PATIENT(S): Eighty-six anovulatory women under 40 years of age undergoing ovulation induction. INTERVENTION(S): The women were assigned randomly to receive either TMX or CC on cycle days 5-9. MAIN OUTCOME MEASURE(S): Rates of ovulation and pregnancy for the two treatment modalities. RESULTS(S): 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. CONCLUSION(S): 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.     

Lipid and lipoprotein changes associated with oral contraceptive use: a randomized clinical trial

To determine the effects of oral contraceptives on lipids and lipoproteins over a six-month period, we randomized 266 women into four oral contraceptive groups: ethinyl estradiol 35 micrograms plus ethynodiol diacetate 1 mg, ethinyl estradiol 30 micrograms plus levonorgestrel 0.15 mg, ethinyl estradiol 35 micrograms plus norethindrone 1 mg, and ethinyl estradiol 35 micrograms plus norethindrone 0.5 and 1 mg (biphasic). For all groups, total cholesterol increased 5.9-9.1% from baseline values over the six months. Triglycerides increased with all preparations, with the ethynodiol diacetate group (37.6%) and the biphasic norethindrone group (45.3%) showing the greatest increase. Low-density lipoprotein cholesterol increased 10-15.6% among the groups; low-density lipoprotein-apolipoprotein B changed proportional to the low-density lipoprotein cholesterol increases. All groups except the ethynodiol diacetate group showed a decrease of high-density lipoprotein cholesterol, with the levonorgestrel group (8.7%) and biphasic norethindrone group (4.5%) showing the largest declines. Apolipoprotein A-1 increased in all groups, with the ethynodiol diacetate preparation (19.3%) showing the greatest increase and the levonorgestrel preparation (3.2%) showing the smallest increase from baseline values. The changes in apolipoprotein A-1 were out of proportion to the changes in high-density lipoprotein cholesterol, suggesting that the high-density lipoprotein particle may be undergoing some type of metabolic alteration.     

The combined effect of bromocriptine and clomiphene citrate on normoprolactinemic anovulation; the lack of effectiveness of clomiphene citrate treatment alone

The purpose of this study is to investigate the combined effect of bromocriptine and clomiphene citrate (Cl) treatment on 35 patients with normoprolactinemic amenorrhea who failed to respond to Cl alone. Ovulation was restored by this treatment in 20 of these patients (57.1%), and the pregnancy rate was 26.7%. This treatment was effective in 11 of 15 women with polycystic ovary like syndrome (73.3%). Resting levels of prolactin, estradiol and testosterone in the effective group were significantly higher than those in the non-effective group. As a result of the treatment, the prolactin and LH levels were significantly decreased, and estradiol and progesterone levels were significantly increased in the effective group. Before the treatment, the responsiveness of LH to LHRH in the effective group was significantly higher, but the responsiveness of prolactin to TRH in this group was not significantly higher than that in the non-effective group. After the treatment, the LH-releasing response following a premarin injection in the effective group was significantly higher than that in the non-effective group. The present results indicate that the therapeutic effect of this treatment may be primarily due to the restoration and improvement of the impaired hypothalamo-pituitary system without the suppression of pituitary prolactin secretion.     

Comparative trial of clomiphene citrate/human menopausal gonadotropin and the contraceptive pill,followed by clomiphene citrate/human menopausal gonadotropin,in a gamete intrafallopian transfer program

Purpose It may sometimes be necessary to regulate cycles in assisted reproduction. Cycles can be regulated with gonadotropin releasing hormone (GnRHa) agonist but other methods can also be used. The aim of this study was to compare the pregnancy rate in a gamete intrafallopian transfer (GIFT) program in patients receiving a contraceptive pill/Clomid/human menopausal gonadotropin (hMG) regimen (study group), with the standard Clomid/hMG regime (control group). Fifty one patients in the study group were carefully matched for patient age, infertility diagnosis (female), semen parameters, number of follicles, and number of oocytes transferred into consideration with a control group.Results The overall pregnancy rate was 21.6% (11/51) in the study group and 47% (24/51) in the control group (P =0.01). However, the ongoing pregnancy rate in the two groups did not differ significantly, 11.8% (6/51) vs 27.5% (14/51) (P =0.08). In the study group, 7.8% of patients had to be seen over a weekend, compared to 13.7% in the control group (not significant). Conclusion From the findings we conclude that, although this method of controlling cycles can be useful in selected patients, it is not the ultimate method.     

Prediction of ovulation with the use of oral and vaginal electrical measurements during treatment with clomiphene citrate

This study was undertaken to evaluate the usefulness of measuring salivary and vaginal electrical resistance in monitoring ovulation induced by clomiphene citrate (CC). Data from 28 cycles of 12 women treated with CC were compared with those of 18 cycles of 13 women who were ovulating spontaneously. Patterns of salivary readings in CC and spontaneous cycles were similar and showed a preovulatory peak 6.2 (mean) days before the luteinizing hormone peak. The trend in vaginal readings for CC cycles differed from that of spontaneous ovulations in that the values were depressed during and shortly after CC therapy. Occurrence of the periovulatory nadir and subsequent rise was common to both groups. The rise in vaginal readings CC cycles occurred within 24 hours of the luteinizing hormone peak in 88% of cases. Retrospective analysis showed that, based on this method, artificial insemination would have been timed appropriately in 25 of 27 cycles or in every cycle, depending on the protocol used. The results indicate that the method is equally useful for predicting and confirming ovulation in cycles in which CC was used to induce ovulation as it is in spontaneous cycles.     

A randomized trial of letrozole versus clomiphene citrate in women undergoing superovulation

OBJECTIVE: To compare the effects of the aromatase inhibitor letrozole (7.5 mg) and clomiphene citrate (CC; 100 mg) in women undergoing superovulation and IUI. DESIGN: Prospective randomized trial. SETTING: University teaching hospital. PATIENT(S): We studied a total of 238 cycles of superovulation and IUI in women with idiopathic infertility. INTERVENTIONS: Patients were randomized into treatment with 7.5 mg of letrozole daily (74 patients, 115 cycles) or 100 mg of CC daily (80 patients, 123 cycles). MAIN OUTCOME MEASURE(S): Number of follicles, endometrial thickness, pregnancy rate, and miscarriage rate. RESULT(S): The mean age, parity, and duration of infertility in both groups of patients were similar. There was no significant difference between the total number of developing follicles in the letrozole (5.7 +/- 3.7) and in the CC groups (4.8 +/- 2.5). The number of follicles of > or =14 mm and of >18 mm were 2.1 +/- 1.2 and 1.4 +/- 0.7 in the letrozole group, and 1.7 +/- 0.9 and 1.1 +/- 0.5 in the CC group, respectively. No difference was found in the endometrial thickness between the two groups (7.1 +/- 0.2 mm in the letrozole group, 8.2 +/- 5.9 mm in the CC group). The pregnancy rate per cycle was 11.5% in the letrozole group and 8.9% in the CC group. Four of the 11 pregnancies in the CC group resulted in a miscarriage (36.6%). CONCLUSION(S): Superovulation and IUI with letrozole and CC are associated with similar pregnancy rates, but the miscarriage rate is higher with CC. The ideal dose of letrozole remains unknown and further study is needed.     

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

OBJECTIVE: 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. DESIGN: Prospective, double-blind, placebo-controlled, randomized study. SETTING: Referral university hospitals. PATIENT(S): Two hundred thirty women with PCOS and normal DHEAS who failed to ovulate after a routine protocol of CC. INTERVENTION(S): 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. MAIN OUTCOME MEASURE(S): Follicular development, hormonal status, ovulation rate, pregnancy rate. RESULT(S): 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. CONCLUSION(S): 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.     

A randomized controlled trial of laparoscopic ovarian diathermy versus gonadotropin therapy for women with clomiphene citrate-resistant polycystic ovary syndrome

OBJECTIVE: To compare the effectiveness of laparoscopic ovarian diathermy with gonadotropin ovulation induction for women with clomiphene citrate-resistant polycystic ovary syndrome. DESIGN: Randomized controlled trial. SETTING: A tertiary referral fertility clinic. PATIENT(S): Women with anovulatory infertility secondary to clomiphene-resistant polycystic ovary syndrome. Inclusion criteria were age of <39 years, body mass index of <35 kg/m(2), failure to ovulate with 150 mg of clomiphene citrate for 5 days in the early follicular phase, >12 months of infertility, and no other causes of infertility. INTERVENTION(S): Laparoscopic ovarian diathermy versus three cycles of urinary or recombinant gonadotropins. MAIN OUTCOME MEASURE(S): Cumulative pregnancy and miscarriage rates. RESULT(S): Cumulative pregnancy rates were 28% at 6 months for laparoscopic ovarian diathermy and 33% for three cycles of ovulation induction with gonadotropins. There were three miscarriages in each group. Women in the laparoscopic ovarian diathermy arm of the study had four additional spontaneous pregnancies 6 to 12 months after surgery. CONCLUSION(S): There was no statistically significant difference in pregnancy or miscarriage rates during the 6-month follow-up period or the three cycles. Laparoscopic ovarian diathermy is a safe and effective alternative to ovulation induction with gonadotropins.     

Clomiphene citrate plus cabergoline versus clomiphene citrate for induction of ovulation in infertile euprolactinemic patients with polycystic ovary syndrome: A randomized clinical trial

Objective

To compare the effect of adjunctive use of cabergoline with clomiphene citrate (CC) in infertile polycystic ovarian syndrome (PCOS) patients with normal prolactin level.