A comparison of the effects of clomiphene citrate and the aromatase inhibitor letrozole on superovulation in Asian women with normal ovulatory cycles

OBJECTIVE: To compare the effect of the aromatase inhibitor letrozole and clomiphene citrate (CC) on superovulation in women with normal ovulation. METHODS: A cross-over randomized study of 22 women with normal ovulation, divided randomly into two equal cohorts, was carried out. Each group of 11 women was randomly allocated to take letrozole or CC for one cycle. After washing out for one cycle, the alternative drug was administered in the subsequent cycle. The number and size of mature follicles, endometrial thickness, and estradiol and progesterone levels were monitored. RESULTS: The number of mature follicles and estradiol levels on ovulation day were significantly lower in the letrozole group than the CC group (p < 0.05 for both). However, no differences between the two groups in endometrial thickness and pattern were observed. Progesterone levels showed ovulation in all cycles. CONCLUSIONS: The administration of 50 mg CC on days 3-5 was superior to 2.5 mg letrozole for superovulation induction in women with normal ovulation.     

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.     

A randomized comparison of ovulation induction and hormone profile between the aromatase inhibitor anastrozole and clomiphene citrate in women with infertility

Background. In the present study we evaluated and compared the effects of ovulation and hormonal dynamics induced by anastrozole and clomiphene citrate in women with infertility.

Materials and methods. Thirty-three infertile patients, aged 25–41 years, were enrolled. Patients received either anastrozole 1 mg daily (AI group) or clomiphene citrate 100 mg daily (CC group) from cycle day 3 to day 7. Number of mature follicles (≥18 mm), endometrial thickness, pregnancy rate and serial hormone profiles (follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E₂), testosterone and progesterone) were measured on cycle day 3, day 8, day 10, the day of intrauterine insemination (IUI), day 7 after IUI and day 14 after IUI.

Results. Baseline parameters were similar in the two groups, including age, body mass index, infertility duration and day-3 serum hormones except FSH. The mean FSH value on day 3 was significantly different (4.3 mIU/ml in the AI group vs. 6.3 mIU/ml in the CC group; p < 0.05). The women receiving anastrozole had fewer ovulatory follicles (1.2 in the AI group vs. 1.8 in the CC group; p < 0.05) and a thicker endometrium (10.6 mm in the AI group vs. 7.8 mm in the CC group; p < 0.05). The levels of progesterone and testosterone were similar during ovulation stimulation cycles in both groups. On the other hand, the AI group had a significantly higher LH level but a significantly lower E₂ level in the stimulation cycle.

Conclusion. Anastrozole has a high pregnancy rate, although it induces fewer ovulatory follicles compared with clomiphene citrate. The two drugs gave different responses of FSH, LH and E₂ during stimulation cycles.     

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.     

来曲唑联合克罗米芬治疗多囊卵巢综合征患者的疗效及对排卵、妊娠情况的影响#br#

Objective?To investigate the clinical effect of letrozole (LE) combined with clomiphene (CC) in the treatment of polycystic ovary syndrome (PCOS). Methods?A total of 120 patients with PCOS were selected as the research objects, of which 60 patients who received single CC treatment were the control group, while the combined group (60 patients) was given LE+CC treatment. Menstrual conditions and sex hormone levels [luteinizing hormone (LH), estradiol (E2), and progesterone (P)] were compared between the two groups, and ovulation and pregnancy were recorded in the two groups. Results?The number of mature follicles, endometrial thickness, menstrual cycle, menstrual volume and early abortion rate in the combined group were lower than those in the control group (P<0.05). After treatment, E2, LH, P secretion levels, ovulation rate, pregnancy rate and twin rate in the combined group were higher than those in the control group (P<0.05). Conclusion? LE combined with CC in the treatment of PCOS patients can achieve better efficacy in ovulation induction and pregnancy.     

人绝经期促性腺激素联合氯米芬或来曲唑用于多囊卵巢综合征患者促排卵疗效比较

的探讨人绝经期促性腺激素（HMG）＋氯米芬（CC）、HMG和来曲唑（LE）＋HMO对多囊卵巢综合征（PCOS）患者宫腔内供精人工授精的治疗效果。方法将2007年12月-2008年5月期间在我中心就诊的114例PCOS妇女的114个宫腔内人工授精（AID）周期分为3组：CC＋HMG周期组38个周期，HMG周期组38个周期，LE＋HMG周期组38个周期。分析比较3组的年龄、血清T水平、绒毛膜促性腺激素肌肉注射日（HCG日）平均卵泡直径（MFD）≥14mm的卵泡（成熟卵泡）个数、平均卵泡E2水平、子宫内膜厚度、HCG日单优势卵泡发育成熟百分率、HMG用量和周期妊娠率。结果CC＋HMG组、HMG组和LE＋HMG组患者年龄和血清T水平比较，差异无显著性（P〉0．05），CC＋HMG组HCG日成熟卵泡个数为（2．9±1．6）个，明显多于其他两组[HMG组为（1．6±1．0）个，LE＋HMG组为（1．9±1．2）个]，差异有显著性（P〈0．05），而内膜厚度较其他两组薄，差异有显著性（P〈0．05），HMG组与LE＋HMG组HCG日成熟卵泡个数和子宫内膜厚度比较，差异无显著性（P〉0．05）。3组HCG日单优势卵泡发育成熟百分率分别21．05％、78．95％和52．63％，差异有显著性（P〈0．05）。CC＋HMG组、HMG组和LE＋HMG组HMG用量分别为（4．89±1．59）支和（9．88±4．59）支、（9．68±4．67）支（75IU／支），CC＋HMG组与后两组比较，差异有显著性（P=0．00）。HMG组、LE＋HMG组HMG用量比较，差异无显著性（P〉0．05）。3组的周期妊娠率分别为36．84％、39．48％和31．57％，差异无显著性（P〉0．05）。结论HMG促排卵周期更易得到单优势卵泡发育成熟；CC＋HMG促排卵HMG用药量最少；CC＋HMG、HMG和LE＋HMG均可获得满意的周期妊娠率。     

The adjuvant effect of metformin and N-acetylcysteine to clomiphene citrate in induction of ovulation in patients with Polycystic Ovary Syndrome

Abstract

Objectives: To assess the adjuvant effect of metformin and N-acetylcysteine (NAC) to clomiphene citrate (CC) in induction of ovulation in Polycystic Ovary Syndrome (PCOS) patients.

Study design: 120 women with PCOS were randomly divided into three equal groups: group I received CC only, group II received CC plus NAC and group III received CC plus metformin.

Results: There was a significant difference between group II and other two groups regarding average number of ovulatory follicles >18?mm (2.25 versus 1.75 and 1.89, respectively), but no significant difference between the three study groups regarding number of intermediate follicles 14–18?mm (4, 10 and 4, respectively). There was no significant difference between the three study groups regarding occurrence and laterality of ovulation, pregnancy rate per cycle but a significant difference between group II and other two groups regarding pregnancy rate per patient (20% versus 10% and 10%, respectively, p value 0.05). There was a highly statistically significant difference between group II and other two groups regarding peak endometrial thickness (7.3?±?1.1 versus 5.4?±?0.6 and 5.3?±?0.6, respectively).

Conclusions: NAC as an adjuvant to CC for induction of ovulation improves ovulation and pregnancy rates in PCOS patients with beneficial impacts on endometrial thickness.     

Comparison of endometrial receptivity of clomiphene citrate versus letrozole in women with polycystic ovary syndrome: a randomized controlled study

Abstract

The aim of the study was to compare the effect of clomiphene citrate (CC) and letrozole on endometrial receptivity for ovulation induction in women with polycystic ovary syndrome (PCOS). A randomized controlled study included 160 patients diagnosed with PCOS, out of which 80 patients received 50?mg of CC and 80 patients received 2.5?mg of letrozole for successful ovulation induction. Endometrial thickness and pattern, the blood flow of uterine artery and subendometrial region, endometrial volume and vascularization index were measured. The ratio of multilayered endometrial pattern in letrozole group was significantly increased on the day of human chorionic gonadotropin (hCG) administration compared with CC group (77.5% vs. 55.0%). The volume, vascularization index (VI), flow index (FI), and vascularization flow index (VFI) of endometrium on the day of hCG administration and 7–9?days after ovulation in letrozole group were significantly increased. The biochemical pregnancy rate, clinical pregnancy rate, and ongoing pregnancy rate in letrozole group were significantly increased compared with CC group (36.3%, 30.0%, 22.5% vs. 21.3%, 13.8%, 10.0%, respectively). Letrozole increased pregnancy rates by improving endometrial receptivity compared with CC in patients with PCOS.     

Letrozole versus clomiphene citrate for superovulation in Egyptian women with unexplained infertility: a randomized controlled trial

Objectives

To compare the efficacy of letrozole with clomiphene citrate (CC) in Egyptian women with unexplained infertility.

Study design

This randomized controlled trial was conducted at Ain Shams University Hospital and Dar Al Hekma hospital between February 2010 and May 2011.

Patients and methods

Two hundreds and seventy women with unexplained infertility were randomized into two groups using computer-generated randomization plan, and were given letrozole 2.5?mg/day from cycle day 3 to 7 (Letrozole group, n?=?136) or CC 100?mg/day from cycle day 3 to 7 (CC group, n?=?134). On day 9, the participants underwent a transvaginal sonography (TVS) every other day to monitor their ovulation and measure both endometrial thickness and Doppler flow indices of uterine and subendometrial vessels. Single injection of 10,000?IU of human chorionic gonadotropin (hCG) was given when the mean diameter of at least one ovarian follicle was ≥18?mm, quantitative βhCG was done 2?weeks after hCG injection to diagnose chemical pregnancy. Clinical pregnancy was confirmed by observing a gestational sac with fetal echoes and pulsation 4?weeks after positive pregnancy test by TVS.

Results

Both groups were comparable with regard to the day of hCG administration (letrozole 13.4?±?5 vs CC 12.1?±?4.9, respectively, p?=?0.06). The mean number of mature follicles was significantly higher in CC group (2?±?0.9 vs 1?±?0.0, P?=?0.02). Serum estradiol was significantly greater in CC group (817?±?299 vs 364?±?149?pg/ml, P?<?0.001). The clinical pregnancy rate was significantly higher in letrozole group (23.07 vs 10.68?%, P?<?0.001). There was statistically significant increase in endometrial receptivity in letrozole group as assessed by endometrial thickness and Doppler flow indices of uterine and subendometrial vessels. No serious side effects were reported in either group.

Conclusion

Letrozole has beneficial effect on endometrium, an action that may improve the implantation and pregnancy rates in women with unexplained infertility.     

A randomized double-blind comparison of the effects of clomiphene citrate and the aromatase inhibitor letrozole on ovulatory function in normal women

OBJECTIVE: To evaluate the ovarian follicular dynamics of cycle modification with the aromatase inhibitor letrozole compared with clomiphene citrate in normal ovulatory women. DESIGN: Randomized double-blind controlled trial. SETTING: Tertiary care hospital. PATIENT(S): Nineteen ovulatory female volunteers, ages 18-35 years. INTERVENTION(S): Subjects were monitored in one control cycle. Subjects then received either letrozole 2.5 mg daily or clomiphene citrate 50 mg daily on days 5-9 after menses. MAIN OUTCOME MEASURE(S): Number of mature follicles, endometrial thickness and endometrial pattern at ovulation, and follicular profiles of LH, FSH, and E(2). RESULT(S): The number of mature follicles at the LH surge in natural cycles was 1.0 with an exaggerated response seen for treatment both with clomiphene and letrozole. There was no difference in the endometrial thickness at midcycle during either the natural cycles or the medicated cycles. LH surges and spontaneous ovulation were documented in all natural and medicated cycles. When measured daily, follicular profiles of LH and FSH are similar between the groups in both the natural and medicated cycles. In the medicated cycles, clomiphene results in a significant increase in E(2) levels, while E(2) levels in letrozole-stimulated cycles appeared lower than in natural cycles. CONCLUSION(S): Transient inhibition of aromatase activity in the early follicular phase with the aromatase inhibitor letrozole results in stimulation of ovarian folliculogenesis similar to that seen with clomiphene citrate with no apparent adverse effect on endometrial thickness or pattern at midcycle.     

Combined metformin and clomiphene citrate versus highly purified FSH for ovulation induction in clomiphene-resistant PCOS women: a randomised controlled trial

Aim.?To compare the effect of combined metformin–clomiphene citrate (CC) with highly purified urinary FSH (HP-uFSH) for ovulation induction in CC-resistant women with polycystic ovary syndrome (PCOS).

Methods.?One-hundred fifty-three anovulatory women with CC-resistant PCOS were selected in this randomised controlled trial. Patients received combined metformin–CC (n?=?75, 205 cycles) or HP-uFSH (n?=?78, 186 cycles) for three cycles. Outcome measures were; Ovulation rate, number of growing and mature follicles, serum E2, serum P, endometrial thickness, pregnancy and miscarriage rates.

Results.?The ovulation rate per cycle was significantly higher in the HP-uFSH group (83.8% vs. 62%, p?=?0.01). The number of follicles ≥12?mm ≥14?mm and ≥18?mm on the hCG day was significantly greater in the HP-uFSH group (p?=?0.01, p?=?0.02 and p?=?0.03, respectively). Pregnancy occurred in 23/205 cycles (11.2%) in combined metformin–CC group and 40/186 cycles (21.5%) in the HP-uFSH group; the difference was statistically significant (p?=?0.02). Two patients in the HP-uFSH group suffered mild OHSS.

Conclusions.?Combined metformin–CC resulted in modest ovulation and pregnancy rates without side effects. It is logical to offer this first for CC-resistant PCOS women before resorting to more expensive alternatives especially in developing communities where economic aspects of therapy are important.     

Endometrial and follicular development following letrozole intervention in unexplained infertile patients failed to get pregnant with clomiphene citrate

Purpose  This study is designed to evaluate and compare follicular phase parameters during ovarian stimulation with the clomiphene citrate (CC) and letrozole (LET) in unexplained infertile patients who failed to get pregnant following frequent CC-treated cycles. Methods  A total of 64 unexplained infertile women who failed to get pregnant following frequent CC-treated cycles were studied for one CC-treated cycle (100 mg/day), 2 washout cycles, and then 1 LET-treated cycle (5 mg/day). Number of follicles over 14 mm in diameter, diameter of the largest follicles, endometrial thickness, serum estradiol (E2) and LH levels were measured when one mature follicle over 18 mm in diameter detected during transvaginal ultrasonography. Results  The mean value of the largest follicle diameter, number of developed follicles >14 mm, endometrial thickness and LH in LET-treated cycle was significantly higher than CC-treated cycle (P values were 0.007, <0.001, <0.001, and 0.004, respectively), whereas mean level of E2 showed a significantly lower level during LET-treated cycle (P < 0.001). Conclusions  About 5 mg/day of LET is associated with better follicular phase parameters, endometrial development, serum E2 and LH levels in women with unexplained infertility who failed to get pregnant following frequent CC-treated cycles.     

Letrozole usage adjuvant to gonadotropins for ovulation induction for patients with clomiphene citrate failure

Aim

To compare cycle properties of ovulation induction (OI) with gonadotropin alone or combined with letrozole in the patients with previous clomiphene citrate (CC) failure.

Methods

In this prospective study, 40 patients with previous at least three times CC cycle failure were evaluated. Half of them received 2.5 mg letrozole on days 3–7 of the menstrual cycle and recombinant follicle stimulating hormone (rFSH) starting on day 5. The other half of the patients received only rFSH starting on day 3. Groups were compared according to the OI duration, gonadotropin dosage, endometrial thickness, estradiol (E2) levels on day of human chorionic gonadotropin (HCG) administration and follicle count.

Results

Total rFSH dose, the E2 levels on the day of HCG and >18 mm follicle count was significantly lower and OI duration was significantly shorter in rFSH + letrozole group. Mean endometrial thickness was not different between groups.

Conclusion

Adding letrozole to gonadotropin in OI cycles decreases total gonadotropin dose and induction duration without any adverse effects on endometrial thickness. Monoovulation is better achieved by adding letrozole to gonadotropin stimulation without decreasing pregnancy rates.     

Clomiphene citrate combined with metformin versus letrozole for induction of ovulation in clomiphene-resistant polycystic ovary syndrome: a randomized clinical trial

A total of 202 patients with clomiphene citrate (CC) -resistant polycystic ovary syndrome (PCOS) were randomly allocated into two arms of induction of ovulation; the first group (n?=?102) received CC 100?mg and metformin 500?mg while the second group (n?=?100) received letrozole 2.5?mg with ovulation rate, clinical pregnancy rate, adverse effects, and acceptability were assessed. Patients in the letrozole arm experienced higher rate of ovulation (82% versus 43.1%, p?p?p?p?p?p?p?相似文献   

Letrozole ovulation induction: an effective option in endometrial preparation for frozen–thawed embryo transfer

Purpose

To evaluate the clinical efficacy of letrozole on ovulation induction and hormone replacement therapy (HRT) during endometrial preparation for frozen–thawed embryo transfer (FET).

Methods

We analyzed totally 1,230 cycles of patients that underwent FET from October 2010 to September 2012. Seven hundred and thirteen cycles of patients with ovulation disorders that underwent FET were randomly assigned to two groups by case control study. 359 cycles received letrozole ovulation induction and 354 cycles received HRT during endometrial preparation for FET, respectively. In the corresponding period, 517 cycles of patients with normal ovulation in the natural cycle group for FET endometrial preparation served as controls. Reproduction-related clinical outcomes of patients in the three groups were compared.

Results

The embryo implantation rate of patients in letrozole group (30.4 %) was significantly higher than the HRT group (22.8 %, P < 0.05). The clinical pregnancy rate of patients in the letrozole group (53.2 %) was significantly higher than the HRT group (44.4 %, P < 0.05), while no significant difference was observed between the letrozole and natural cycle groups (51.3 %, P > 0.05). Estradiol levels on the day of human chorionic gonadotropin administration in the letrozole group were significantly lower than those in the natural cycle group (280.32 ± 125.39 pg/ml and 351.06 ± 123.03 pg/ml, respectively; P < 0.05). The live birth rate of patients in letrozole group (44.6 %) was significantly higher than the HRT group (32.5 %, P < 0.05), while abortion rate (12.0 %) was significantly lower than the HRT group (21.0 %, P < 0.05). There were no significant differences in number of mature follicles, endometrial thickness, duration of follicle growth between the letrozole and the natural cycle groups, and there were no significant differences in twin birth rate and ectopic pregnancy rate among the three groups (all P values >0.05).

Conclusions

Ovulation induction with letrozole during endometrial preparation for FET has a higher rate of pregnancy success and a lower abortion rate than HRT. Letrozole treatment exhibits clinical progression and outcomes similar to those patients undergoing a natural cycle or normal ovulation cycle. Therefore, letrozole treatment may be an effective option in endometrial preparation for FET in patients with ovulation disorders or irregular menstruation.     

Sequential clomiphene citrate/hMG versus hMG for ovulation induction in clomiphene citrate-resistant women

Objective

This study was designed to compare sequential clomiphene citrate/hMG regimen to hMG regimen for ovulation induction in clomiphene citrate-resistant women.

Study design

A comparative prospective study.

Patients and methods

Ninety infertile women were randomized to receive either sequential CC/hMG regimen (45 women) or low-dose step-up protocol of hMG (45 women). All participants had received at least six consecutive cycles of clomiphene citrate for ovulation induction within the last year before inclusion in this study, but they did not conceive. The CC/hMG regimen group received clomiphene citrate 100 mg/day for 5 days, followed by hMG 75 IU for 4 days. The hMG group received low-dose step-up protocol for 10–14 days. To detect the number and size of the follicles, TVS was done on cycle day 8 and repeated daily or every other day according to follicular development. When one to three follicles reached a diameter ≥18 mm, hCG injection was scheduled. Before hCG injection, the E2 level and endometrial thickness were evaluated. β-hCG levels were measured on cycle day 22.

Results

There was no significant difference between the two studied groups regarding the demographic data, sperm parameters, and day 3 FSH, LH and estradiol. Also, there was no significant difference between the two studied groups regarding endometrial thickness, number of mature follicles, peak of E2 before hCG injection and number of cases that developed ovarian cyst or OHSS. The dose of gonadotropins used was significantly low in the CC/hMG group compared to the hMG group (295.2 ± 75.5 vs. 625.3 ± 65.0, respectively), and the pregnancy rate was significantly high in the CC/hMG group compared to the hMG group [12 (26.7 %) vs. 3 (6.7 %), respectively, p < 0.05].

Conclusion

The sequential CC/hMG regimen is as effective as hMG regimen for ovulation induction, produces satisfactory pregnancy results and reduces the treatment cost.     

Nitric oxide donors increases pregnancy rate in clomiphene citrate treated polycystic ovary infertile patients

ObjectivesTo test if treatment of polycystic ovary (PCO) infertile patients with clomiphene citrate (CC) and the nitric oxide (NO) donors isosobid mononitrate (ISMN) might improve the ovulation and pregnancy rates compared to treatment with CC alone.Study designProspective, randomized, controlled study.SettingBenha university hospital. January 2008 to January 2009.Subjects and methodsThe study included thirty PCO infertile patients divided randomly into a control and a study groups each fifteen cases. Patients in the control group were treated with 100mg CC for five days starting from the fifth day of the cycle. The study group received in addition to CC, 20mg ISMN tablet applied vaginally till the diagnosis of ovulation and pregnancy.Primary outcome measuresOvulation and pregnancy rate in the CC+ISMN group compared to the CC alone group.Secondary outcome measuresNumber of mature follicles (?18mm), cervical mucus score and endometrial thickness in both groups.ResultsThere was a significant increase in the ovulation and pregnancy rates in the CC+ISMN group. The number of mature follicles, the cervical mucus score and the endometrial thickness were significantly higher in this group.ConclusionsThis novel treatment of infertile PCO patients with combination of CC and NO donors is simple and promising. The ovulation and pregnancy rates are increased due to improvement of follicular maturation, cervical mucus quality and endometrial receptivity.     

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.     

A randomized comparison of ovulation induction and hormone profile between the aromatase inhibitor anastrozole and clomiphene citrate in women with infertility.

BACKGROUND: IN the present study we evaluated and compared the effects of ovulation and hormonal dynamics induced by anastrozole and clomiphene citrate in women with infertility. MATERIALS AND METHODS: Thirty-three infertile patients, aged 25-41 years, were enrolled. Patients received either anastrozole 1 mg daily (AI group) or clomiphene citrate 100 mg daily (CC group) from cycle day 3 to day 7. Number of mature follicles (> or =18 mm), endometrial thickness, pregnancy rate and serial hormone profiles (follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E(2)), testosterone and progesterone) were measured on cycle day 3, day 8, day 10, the day of intrauterine insemination (IUI), day 7 after IUI and day 14 after IUI. RESULTS: Baseline parameters were similar in the two groups, including age, body mass index, infertility duration and day-3 serum hormones except FSH. The mean FSH value on day 3 was significantly different (4.3 mIU/ml in the AI group vs. 6.3 mIU/ml in the CC group; p < 0.05). The women receiving anastrozole had fewer ovulatory follicles (1.2 in the AI group vs. 1.8 in the CC group; p < 0.05) and a thicker endometrium (10.6 mm in the AI group vs. 7.8 mm in the CC group; p < 0.05). The levels of progesterone and testosterone were similar during ovulation stimulation cycles in both groups. On the other hand, the AI group had a significantly higher LH level but a significantly lower E(2) level in the stimulation cycle. CONCLUSION: Anastrozole has a high pregnancy rate, although it induces fewer ovulatory follicles compared with clomiphene citrate. The two drugs gave different responses of FSH, LH and E2 during stimulation cycles.     

Systematic review and meta-analysis of letrozole and clomiphene citrate in polycystic ovary syndrome

This study aims to systematically evaluate the clinical efficacy and safety of both clomiphene citrate (CC) and letrozole, and to examine if the efficacy of letrozole is superior to CC in women with polycystic ovary syndrome (PCOS).Major databases were searched for eligible randomised controlled trials (RCTs). The methodological quality of the included studies was assessed by two independent reviewers. Meta-analysis was performed using random-effect model to account for the high levels of heterogeneity. Overall, ten eligible RCTs involving 1905 women were included. Letrozole was associated with significantly higher ovulation rate (relative risk (RR) 1.20; 95% CI 1.03–1.40; P?=?0.02); clinical pregnancy rate (RR 1.48; 95% Cl 1.12–1.94; P?=?0.005) and endometrial thickness (standardized mean difference (SMD) 2.31; 95% Cl 0.85–3.76; P?=?0.002). There was no evidence of a difference between the treatment groups in the rate of miscarriage, number of mature follicles and multiple pregnancy rates. The result suggests that letrozole is a superior ovulation induction agent for women with PCOS as it is associated with higher ovulation and clinical pregnancy rates with no obvious increased side effects. However, this conclusion should be considered with a slight caution in that the quality of the evidence could have improved if more recent studies on the subject were available to be included in the review.