Normoprolactinemic anovulation nonresponsive to clomiphene citrate: ovulation induction with bromocriptine

Ovulation under bromocriptine was studied in 14 women with normoprolactinemic amenorrhea (5 primary, 9 secondary), unresponsive to clomiphene citrate (CC). On bromocriptine alone, ovulation occurred in 4 (28.6%). In the same subjects, bromocriptine was subsequently associated with CC. Seven patients ovulated (50.0%), including 3 that had responded to bromocriptine alone. Ovulation occurred once or twice in 6 of the 9 cases of secondary amenorrhea (66.6%). In several occasions, when ovulation induction failed, luteinized unruptured follicles were found under ultrasonographic monitoring. Four patients who had a negative response to progestin challenge did not ovulate with the treatment. Women with plasma prolactin in the upper normal range had a greater probability of achieving ovulation induction.     

Combined coenzyme Q10 and clomiphene citrate for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome

This prospective randomized controlled trial evaluated the effect of combined oral coenzyme Q10 (CoQ10) and clomiphene citrate for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome (PCOS). A total of 101 infertile women with PCOS resistant to clomiphene citrate were randomized either to combined CoQ10 and clomiphene citrate (51 patients, 82 cycles) or to clomiphene citrate alone (50 patients, 71 cycles). The outcome measures were number of follicles, serum oestradiol, serum progesterone, endometrial thickness and ovulation, clinical pregnancy and miscarriage rates. Numbers of follicles >14 mm and ⩾18 mm were significantly higher in the CoQ10 group. Endometrial thickness on the day of human chorionic gonadotrophin was significantly greater in the CoQ10 group (8.82 ± 0.27 mm versus 7.03 ± 0.74 mm). Ovulation occurred in 54/82 cycles (65.9%) in the CoQ10 group and 11/71 cycles (15.5%) in the control group. Clinical pregnancy rate was significantly higher in the CoQ10 group (19/51, 37.3%) versus the control group (3/50, 6.0%). Combination of CoQ10 and clomiphene citrate in the treatment of clomiphene-citrate-resistant PCOS patients improves ovulation and clinical pregnancy rates. It is an effective and safe option and can be considered before gonadotrophin therapy or laparoscopic ovarian drilling.     

Induction of monofollicular cycles

The therapy of anovulatory infertility is not meant to obtain a pregnancy at any cost, but to restore an ovulation as physiological as possible. This involves the use of drugs and therapeutical protocols to obtain monofollicular cycles. Monofollicularity reduces the two main risks of induction of ovulation: ovarian hyperstimulation syndrome and multiple pregnancy. The aim of this study is a review of the Literature on ovulation induction and a comparison with the data of our Sterility Service. The importance of the question will be examined together with the most used ovulation induction drugs: clomiphene citrate, gonadotrophins and pulsatile GnRH. The parameters considered are: the number of follicles, single or multiple pregnancies and ovarian hyperstimulation. After a review about ovarian stimulation, the results of our Sterility Service are presented: 364 cycles of ovulation induction with clomiphene citrate, low-dose gonadotrophins or pulsatile GnRH were monitored; monofollicularity was obtained in 58,48% of ovulatory cycles. Differences between drugs will be described in the text. The therapy of anovulatory infertility aims to restore a physiological ovulation and to obtain a single pregnancy, not a pregnancy at any cost.     

卵泡期经阴道小卵泡穿刺抽吸术治疗多囊卵巢综合征排卵障碍

目的 探讨对克罗米芬治疗无反应的多囊卵巢综合征患者在卵泡期经阴道小卵泡穿刺抽吸术后,使用促性腺激素诱发排卵时卵泡的发育及其结局。方法 选择17例对克罗米芬治疗无反应,或对促性腺激素治疗发生卵巢过度刺激或无反应,但输卵管通畅、男方精液正常的多囊卵巢综合征不孕患者,在月经(人工周期)第5天给予促性腺激素治疗,给药5d后,在B超指引下经阴道行小卵泡穿刺抽吸术,双侧卵巢仅留1—2个较大卵泡,术后继续给予促性腺激素,观察卵泡发育、排卵和妊娠情况及血中性激素水平变化。结果 17例中除2例(11．8％)对该治疗方法无反应外,15例出现优势卵泡发育和排卵,其中单卵泡发育9例(52．9％),双卵泡发育4例(23.5％),3卵泡发育2例(11．8％),发育的优势卵泡全部排卵。总共有7例妊娠,全部为单胎妊娠,单周期治疗妊娠率41．2％(7／17)。结论 卵泡期经阴道小卵泡穿刺抽吸术能使对克罗米芬治疗无反应的多囊卵巢综合征不孕患者,使用促性腺激素治疗获得良好的单卵泡发育和单胎妊娠率。     

Failure of human oocyte release at ovulation

Among 150 patients admitted for ovum aspiration, in vitro fertilization, and embryo transfer in Perth, Western Australia, 14 were found to have had at least one ovulated follicle at the time of laparoscopy. Based upon ultrasound estimation of follicle diameter 24 hours previously, ovulation occurred in 6 of 22 follicles less than 1.7 cm in mean diameter and in 16 of 19 follicles greater than 1.7 cm in mean diameter. When the ruptured follicles were flushed with heparinized fertilization medium, oocytes were collected in 13 of the 22 dispersed follicles. Twelve oocytes developed pronuclei 16 hours after the addition of spermatozoa, and 11 cleaved to the 4-cell stage within 44 hours of insemination. Oocytes were recovered from 6 of 11 patients stimulated with clomiphene alone and from all 3 patients stimulated with clomiphene supplemented with human menopausal gonadotropin. These observations suggest that oocyte release and follicle rupture are not necessarily synonymous events and that the incidence of retained oocytes in ovulated follicles following stimulation with clomiphene or clomiphene plus human menopausal gonadotropin could be on the order of 60%.     

Octreotide is not useful for clomiphene citrate resistance in patients with polycystic ovary syndrome but may reduce the likelihood of ovarian hyperstimulation syndrome

OBJECTIVE: To determine whether octreotide is effective for ovulation induction in patients with polycystic ovary syndrome (PCOS) and clomiphene citrate resistance or for reduction of the risk of ovarian hyperstimulation syndrome (OHSS) with gonadotropin therapy. DESIGN: Prospective, double-blind, placebo-controlled, crossover trial. SETTING: Private infertility practice. PATIENT(S): Twelve patients with PCOS undergoing therapy for infertility. INTERVENTION(S): The patients were assigned randomly to receive either octreotide or placebo. Those with clomiphene citrate-resistant PCOS received clomiphene citrate, 150 mg. Patients at risk for the development of OHSS received urinary FSH for ovulation induction. MAIN OUTCOME MEASURE(S): Ovulation, pregnancy, the development of OHSS, and levels of fasting insulin, insulin-like growth factor 1, insulin-like growth factor binding proteins 1 and 3, testosterone, androstenedione, DHEAS, E2, LH, and FSH. RESULT(S): Octreotide significantly reduced levels of fasting insulin, insulin-like growth factor 1, and LH in both clomiphene citrate- and urinary FSH-stimulated cycles. Levels of insulin-like growth factor binding protein 3 were increased. Two of six clomiphene citrate-stimulated cycles reached ovulation with the use of either octreotide or placebo. In urinary FSH-stimulated cycles, patients who received octreotide had significantly lower E2 levels at the time of hCG administration and fewer mature follicles. No cases of OHSS occurred in either group. One pregnancy occurred in each group. CONCLUSION(S): Octreotide was no more effective than placebo for clomiphene citrate resistance in patients with PCOS, but it did reduce E2 levels and follicle numbers when combined with urinary FSH. Thus, octreotide may reduce the incidence of OHSS in patients with PCOS.     

Measurement of the ovarian follicle by ultrasound in ovulation induction.

Ultrasonic monitoring of ovarian follicles and estimation of serum estradiol were carried out in 12 patients with clomiphene therapy, in 5 patients with gonadotropin therapy, and in 7 normal controls. The average diameter of preovulatory follicles in normal controls was 12,8 mm; in ovulation induction groups it was 2 to 4 mm greater. The level of serum estradiol was also higher in ovulation induction groups than in normal controls. The combined use of these two methods is recommended: ultrasonic monitoring to minimize the risk of multiple pregnancies and estrogen level monitoring to minimize the risk of hyperstimulation. Ultrasound is also safe and practical in following the size of hyperstimulated ovaries.     

Effects of clomiphene treatment on infertile women with normal menstrual rhythm

Summary. Fourteen infertile women with normal menstrual rhythm were investigated; each provided daily blood samples throughout two menstrual cycles: one control cycle and another on therapy with clomiphene (50 mg/day) given either from days 1 to 5 ( n =7; group I) or from days 5 to 9 ( n =7; group II) of the cycle. The effects of this empirical clomiphene therapy on the menstrual cycles were assessed by reference to the delay from termination of clomiphene therapy to ovulation (day after the LH peak) and by comparing pre-ovulatory oestradiol levels and luteal phase progesterone indices (total progesterone levels from days 4 to 8 post LH peak) in patients' control and treated cycles. No differences were observed in the effects of the treatment on the two groups of women except that the clomiphene to ovulation delay was greater in those treated earlier in the cycle (group I). Clomiphene caused increased follicular development as indicated by elevated pre-ovulatory oestradiol levels but this was not followed by improved progesterone indices. Ovarian ultrasonography indicated that the increased follicular development was in terms of numbers of follicles and not in maturity or oestrogen biosynthetic capacity of individual follicles. The lack of increased luteal progesterone levels thereafter indicated that mean luteal progesterone production per luteinized follicle was reduced. Clomiphene therapy as given in this study was therefore not successful in stimulating increased follicular/luteal hormone production from the dominant follicle/corpus luteum in such patients.     

N-Acetyl cysteine and clomiphene citrate for induction of ovulation in polycystic ovary syndrome: a cross-over trial

OBJECTIVE: To compare clomiphene citrate plus N-acetyl cysteine versus clomiphene citrate for inducing ovulation in patients with polycystic ovary syndrome. DESIGN: Prospective cross-over trial. SETTING: University teaching hospital and a private practice setting. PATIENTS: Five hundred and seventy-three patients were treated with clomiphene citrate for one menstrual cycle among which 470 patients were treated with clomiphene citrate plus N-acetyl cysteine for another cycle. All women suffered from polycystic ovary syndrome. INTERVENTIONS: Patients had clomiphene citrate 50-mg tablets twice daily alone or with N-acetyl cysteine 1,200 mg/day orally for 5 days starting on day 3 of the menstrual cycle. OUTCOME MEASURES: Primary outcomes were number of mature follicles, serum E2, serum progesterone, and endometrial thickness. Secondary outcome was the occurrence of pregnancy. RESULTS: Ovulation rate improved significantly after the addition of N-acetyl cysteine (17.9% versus 52.1%). Although the number of mature follicles was more in the N-acetyl cysteine group (2.1+/-0.88 versus 3.2+/-0.93), the difference was not statistically significant. The mean E2 levels (pg/ml) at the time of human chorionic gonadotropine injection, serum progesterone levels (ng/ml) on days 21-23 of the cycle, and the endometrial thickness were significantly improved in the N-acetyl cysteine group. The overall pregnancy rate was 11.5% in the N-acetyl cysteine group. Insulin resistance occurred in 260 patients (55.4%). There was no significant difference between the insulin resistance group (n = 260) and non-insulin resistance group (n = 210) as regards ovulation rate, number of follicles, serum E2 (pg/ml), serum progesterone (ng/ml), endometrial thickness (mm), or pregnancy rate. CONCLUSION: N-Acetyl cysteine is proved effective in inducing or augmenting ovulation in polycystic ovary patients.     

Extending clomiphene treatment in clomiphene-resistant women with PCOS: a randomized controlled trial

The purpose of this study was to test the effect of extended clomiphene citrate treatment compared with gonadotrophin therapy for the management of clomiphene-resistant women with polycystic ovary syndrome (PCOS). The study comprised 318 women (802 cycles) with clomiphene-resistant PCOS randomized to two treatment groups. Patients in the clomiphene citrate group were given 100 mg of clomiphene citrate daily starting on day 2 of menses for 9 days (160 patients, 405 cycles) while patients in the gonadotrophin group were given human menopausal gonadotrophin 75 IU intramuscularly daily for 5 days starting on day 3 of menses (158 patients, 397 cycles). The number of ovulating patients was significantly higher (P = 0.001) in the gonadotrophin group (57.6 versus 28.1%). The total number of follicles during stimulation was significantly greater (P = 0.01) in the gonadotrophin group (6.7 +/- 0.3 versus 4.1 +/- 0.4). Pregnancy occurred in 46/405 cycles in the clomiphene citrate group (11.4%) and in 80/397 cycles (20.2%) in the gonadotrophin group; the difference was statistically significant (P = 0.03). The extended clomiphene citrate regimen resulted in modest ovulation and pregnancy rates with no side effects. This therapy seems to offer economic, efficacy and safety advantages and it is worth undergoing before starting more expensive or sophisticated alternatives.     

Role of aromatase inhibitor in ovulation induction in patients with poor response to clomiphene citrate

AIM: To examine the efficacy of aromatase inhibitor in the induction of ovulation. METHODS: This prospective clinical trial in patients with infertility and poor response to clomiphene citrate (CC) was undertaken in a tertiary referral infertility clinic. Thirty-five infertile patients, who were treated by clomiphene citrate for several cycles and referred to the infertility clinic, were the target population. Initially, the response of CC was assessed by same dose of CC that the patient had in her last cycle. The patients who did not respond adequately were treated by aromatase inhibitor 2.5-5 mg/day from day 3-7 of the menstrual cycle. The main outcome measures were the number of mature follicles, ovulation rate, endometrial thickness and pregnancy rate. RESULTS: Twenty-seven (90%) patients developed mature follicles by day 12. The majority (77.77%) developed single follicle. Except for one cycle of one patient, the follicles of all patients were ruptured in all cycles and seven (25.94%) got pregnant. CONCLUSION: The aromatase inhibitor letrozole is effective for ovulation induction in anovulatory infertility in patients that failed to ovulate by CC.     

Avoidance of multiple pregnancies after ovulation induction by supernumerary preovulatory follicular reduction

OBJECTIVE: To evaluate the effect of supernumerary preovulatory follicular reduction as an approach to avoid multiple pregnancies in ovulation induction or superovulation cycles. DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENT(S): In 26 cycles, 24 patients underwent ovulation induction or superovulation with either clomiphene citrate or hMG. INTERVENTION(S): Selective follicle aspiration was performed before hCG administration. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate and numbers of multiple pregnancies. RESULT(S): A mean number of 4.5 follicles with a diameter > or =15 mm and a mean number of 4.5 follicles with a diameter < or =14 mm were observed before hCG administration. A mean number of 2.3 follicles with a diameter > or =15 mm and a mean number of 1.8 follicles with a diameter < or =14 mm were aspirated before the hCG administration. Seven singleton pregnancies (26.9% per cycle) ensued from the treatment. CONCLUSION(S): Aspiration of supernumerary follicles after ovulation induction or superovulation seems to be a valid approach to avoid multiple pregnancies without affecting pregnancy rate.     

Meta-analysis of letrozole versus clomiphene citrate in polycystic ovary syndrome

The aim of this study was to systematically compare the clinical efficacy and safety of letrozole with clomiphene citrate for ovulation induction in women with polycystic ovary syndrome (PCOS). The Cochrane Central Register of Controlled Trials, PubMed, EMbase, CBMdisc and CNKI were searched for eligible randomized controlled trials (RCT) comparing letrozole with clomiphene citrate in PCOS patients. Two reviewers independently extracted information and evaluated methodological quality according to the Cochrane Handbook 5.0. Meta-analysis was performed with the fixed-effects model or random-effects model according to the heterogeneity. Six eligible RCT involving 841 patients were included. Letrozole was associated with a number of lower mature follicles per cycle (standardized mean difference (SMD) -1.41; 95% confidence intervales (CI) -1.54 to -1.28; P<0.00001) compared with clomiphene citrate. There were no significant differences in pregnancy rate (relative risk (RR) 0.97; 95% CI 0.79 to 1.18), abortion rate (RR 1.38; 95% CI 0.48 to -3.96) and multiple pregnancy rate (RR 0.34; 95% CI 0.07 to -1.72) between the two groups. The evidence from ovulation rates was not enough to support either letrozole or clomiphene citrate. In conclusion, letrozole is as effective as clomiphene citrate for ovulation induction in patients with PCOS.     

A short course of menotropin after clomiphene failure in infertile women with luteal phase defects

Twenty-four women with luteal phase defects who were ovulatory on clomiphene therapy with or without human chorionic gonadotropin (hCG) at midcycle for three to eight cycles yet failed to produce a live birth were treated with a short course of menotropin (hMG-S), one to two ampules for five days in the early follicular phase followed or not followed by hCG at midcycle for three to eight cycles. The luteal phase defect was diagnosed with repeat endometrial biopsies with a lag time of three or more days prior to clomiphene therapy. A complete infertility workup revealed only eight patients (33%) with a purely endocrine factor (luteal phase defect). The rest (16 patients, or 67%) had one or two additional infertility factors. Two abortions occurred in this group during clomiphene therapy, while five pregnancies (four live births and one spontaneous abortion) occurred during hMG-S therapy. The ovulation rates were similar for hMG-S (89%) and clomiphene (91%) therapy, but the frequency of a normal ovulatory cycle was significantly greater (P = .026) for hMG-S therapy (71%) than for clomiphene therapy (57%). The midluteal mean serum progesterone level was lower and the mean luteal length shorter in the cycles with less than 130 ng/mL/d of total integrated luteal progesterone. The postcoital test results showed better cervical mucus, with increased mucus volume and better fluidity and spinnbarkeit, in hMG-S cycles than in clomiphene cycles. It appears that hMG-S treatment can improve ovarian function and achieve successful pregnancy in patients with luteal phase defects who fail to produce a live birth during clomiphene treatment.     

促性腺激素释放激素激动剂触发排卵的临床观察

目的:探讨促性腺激素释放激素激动剂(GnRH-a)触发排卵的疗效。方法:对应用氯米芬(CC)、来曲唑(LE)和/或人绝经期促性腺激素(hMG)促排卵治疗的不孕患者,卵泡成熟时给与GnRH-a(A组)或人绒毛膜促性腺激素(hCG)(B组)触发排卵,卵巢过度刺激综合征(OHSS)高危周期则给予GnRH-a,观察比较其临床结局。结果:共分析了81例患者132个促排卵周期,A、B组周期数分别为75和57,组间周期排卵率、多胎率、流产率相似(P>0.05)。周期临床妊娠率、OHSS发生率A组高于B组(P<0.05),无重度OHSS发生。结论:GnRH-a触发排卵临床妊娠率高,可有效预防重度OHSS的发生。     

Clomiphene and dexamethasone in women unresponsive to clomiphene alone

Twelve oligomenorrhic women with polycystic ovary syndrome (PCO) in whom clomiphene (250 mg daily for 5 days) and 10,000 IU human chorionic gonadotropin had failed to induce ovulation were treated with clomiphene and dexamethasone. Eight of the 12 women underwent complete hormonal assessment during treatment. Six of the 12 ovulated and 1 conceived. Serum total and unbound estradiol and testosterone (T), serum dehydroepiandrosterone sulfate (DHEA-S), sex hormone binding-globulin binding capacity (SHBG-BC), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL) were measured during clomiphene and dexamethasone therapy. SHBG-BC increased in response to clomiphene whether or not ovulation occurred. After treatment with clomiphene and dexamethasone there was a significant decrease in serum T, unbound T, and DHEA-S 2 weeks after dexamethasone administration, but there were no change in LH, FSH, or PRL. In patients who ovulated after clomiphene and dexamethasone, T and unbound T increased again after clomiphene was begun despite the continuation of dexamethasone. The women who ovulated after clomiphene and dexamethasone treatment had significantly higher pretreatment levels of DHEA-S than those who did not ovulate. Clomiphene and dexamethasone treatment may be beneficial to women who have elevated levels of DHEAS and who fail to ovulate with maximum doses of clomiphene.     

Clomiphene citrate and ovulation induction

Clomiphene can be used to treat anovulation due to hypothalamus or pituitary gland dysfunction, and it normalizes the luteal phase in stimulated patients. It can be used to estimate ovarian follicle reserve, and may be predictive of ovulation in women aged >/=35 years or with failed IVF. Contraindications include risk of congenital anomalies, chronic liver disease and visual disorders. Clomiphene may impair fertility through its effects on cervical mucus and in causing various endometrial dysfunctions. However, if clomiphene is administered in 50 mg doses, side-effects are avoided and efficacy is similar to that of a 100 mg dose, although daily dosages of 200 mg/day over 5 days can induce ovulation in approximately 70% of treated patients. Gonadotrophin concentrations increase up to days 5-9 when follicles are selected, and clomiphene is effective in patients with polycystic ovary syndrome (PCOS). Fifty percent of normal patients conceive, a value perhaps biased by the antagonistic effects of clomiphene on cervical mucus in some women. Clomiphene is valuable for IVF, and is used by some clinics in combination with HMG or recombinant FSH. Resistance to clomiphene can develop, and human chorionic gonadotrophin may be needed to induce ovulation in clomiphene cycles. Corticosteroids and human menopausal gonadotrophin (HMG) can be combined with clomiphene for stimulation, its combination with HMG long having been a standard protocol in assisted reproduction. PCOS patients may become insulin resistant, a condition improved by the administration of metformin. Other adverse effects include multiple pregnancies, an increase in the rate of multiple births, ovarian hyperstimulation and unsubstantiated claims of ovarian cancer.     

The initial experience with the use of a portable infusion pump in the delivery of human menopausal gonadotropins

The initial experience with the use of a portable infusion pump for the delivery of human menopausal gonadotropins (hMG) in the therapy of ovulation dysfunction of women who failed to conceive following (1) either clomiphene citrate (five patients with polycystic ovary syndrome) or danazol (three patients with mild endometriosis) and (2) standard intramuscular hMG-human chorionic gonadotropin therapy is reported. In six of these patients this approach was used because of suboptimal response of serum estradiol levels to standard hMG therapy, and all six patients had an increase in estradiol response with infusion therapy; therapy duration and total dosage of hMG were similar in both treatment modalities. Sonography suggested stimulation of several follicles with infusion therapy. Advantages and disadvantages of the use of the infusion pump for hMG therapy are discussed. In conclusion, hMG therapy via the infusion pump is feasible. This mode of administration appears to lead to more satisfactory follicular development in selected patients. Multiple follicular stimulation is to be expected. Self-administration of medication is readily achieved by the educated patient. Further consideration and exploration of hMG infusion therapy is suggested.     

New advances in ovulation induction

PURPOSE OF REVIEW: To review recent advances in ovulation induction. RECENT FINDINGS: Aromatase inhibitors can replace clomiphene citrate as ovulation-inducing substances. The most widely used aromatase inhibitor for this purpose is letrozole and the optimal dose is 5 mg daily for 5 days. Compared to clomiphene citrate, it is associated with a thicker endometrium and a better pregnancy rate. It is as effective as gonadotropin but yet less expensive. The overall rates of congenital malformation among newborns conceived after infertility treatment with letrozole or clomiphene citrate are similar. When letrozole is combined with gonadotropin, it leads to lower gonadotropin requirements with pregnancy rates comparable to gonadotropin treatment alone. Another promising aromatase inhibitor is anastrazole. Recent evidence suggests that luteinizing hormone activity in human menopausal gonadotropin modifies follicular development so that fewer intermediate-sized follicles develop. Compared to the use of follicular stimulating hormone only, human menopausal gonadotropin is associated with less ovarian hyperstimulation. SUMMARY: Aromatase inhibitors are alternative drugs to clomiphene or gonadotropin for ovulation induction or superovulation.     

Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate

OBJECTIVE: To use aromatase inhibition for induction of ovulation in women in whom clomiphene citrate (CC) treatment was unsuccessful. DESIGN: Prospective trial in infertility patients treated with CC. SETTING: Two tertiary-referral infertility clinics associated with the Division of Reproductive Sciences, University of Toronto. PATIENT(S): Twelve patients with anovulatory polycystic ovary syndrome (PCOS) and 10 patients with ovulatory infertility, all of whom had previously received CC with an inadequate outcome (no ovulation and/or endometrial thickness of < or =0.5 cm). INTERVENTION(S): The aromatase inhibitor letrozole was given orally in a dose of 2.5 mg on days 3-7 after menses. MAIN OUTCOME MEASURE(S): Occurrence of ovulation, endometrial thickness, and pregnancy rates. RESULT(S): With CC treatment in patients with PCOS, ovulation occurred in 8 of 18 cycles (44.4%), and all ovulatory cycles for the women included in this study had endometrial thickness of < or =0.5 cm. In 10 ovulatory patients, 15 CC cycles resulted in a mean number of 2.5 mature follicles, but all cycles had endometrial thickness of < or =0.5 cm on the day of hCG administration. With letrozole treatment in the same patients with PCOS, ovulation occurred in 9 of 12 cycles (75%) and pregnancy was achieved in 3 patients (25%). In the 10 patients with ovulatory infertility, letrozole treatment resulted in a mean number of 2.3 mature follicles and mean endometrial thickness of 0.8 cm. Pregnancy was achieved in 1 patient (10%). CONCLUSION(S): Oral administration of the aromatase inhibitor letrozole is effective for ovulation induction in anovulatory infertility and for increased follicle recruitment in ovulatory infertility. Letrozole appears to avoid the unfavorable effects on the endometrium frequently seen with antiestrogen use for ovulation induction.