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.     

卵泡期地塞米松应用对克罗米芬抵抗的多囊卵巢综合征促排卵作用研究

目的:探讨克罗米芬(CC)联合地塞米松(DEX)对CC抵抗的多囊卵巢综合征(PCOS)患者的促排卵效果。方法:将50名CC抵抗患者随机分为治疗组(A组)和对照组(B组)。A组患者在月经第3￣7日口服CC100mg/d,同时在月经周期的第3￣12日口服DEX1.0mg/d;B组CC的应用同A组,同时在月经周期的第3￣12日口服叶酸片0.5mg/d。月经第8日开始监测卵泡发育情况。当有1个卵泡直径≥18mm或2个卵泡直径≥17mm时,肌注hCG10000IU,36h后性生活。观察2组注射hCG日成熟卵泡数和子宫内膜厚度、促排卵天数、月经周期第22日孕酮水平、排卵率和妊娠率。结果:A组注射hCG日的成熟卵泡数、子宫内膜厚度、月经第22日血清中孕酮水平以及排卵率和妊娠率与B组相比差异均有显著性(P<0.05￣P<0.01);促排卵天数组间无统计学差异(P>0.05)。结论:对CC抵抗的PCOS患者,DEX可以促进排卵,改善CC对子宫内膜的抗雌激素效应,增加子宫内膜厚度,提高排卵率和妊娠率。     

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.     

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.     

自然及促排卵周期子宫内膜整合素α4β1的表达

目的 了解氯米芬（CC）、绝经期促性腺激素（hMG）对黄体中期子宫内膜整合素α4β1表达的影响。方法 应用单克隆抗体,采用免疫组织化学技术检测48例正常妇女自然周期以及48例正常妇女、30例多囊卵巢综合征患者应用CC／绒毛膜促性腺激素（hCG）及CC／hMG/hCG方案促卵治疗后黄体中期子宫内膜整合素α4β1的表达。结果 子宫内膜整合素α4β1在正常妇女自然周期着床窗口期呈现强阳性表达,而CC、hMG抑制整合率α4β1的表达,两者比较,差异有极显著性（P＜0．01）;妊娠者较妊娠者整合素α4β1表达强度高。结论 促排卵周期黄体中期整合素α4β1表达下降或缺失,子宫内膜容受性下降,妊娠率降低。     

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.     

Adding the phytoestrogen Cimicifugae Racemosae to clomiphene induction cycles with timed intercourse in polycystic ovary syndrome improves cycle outcomes and pregnancy rates – a randomized trial

Background: Owing to their potential to act as estrogen receptor modulators and interfere with aromatase enzyme in animal studies, phytoestrogens (PE) may be useful as part of ovulation induction for polycystic ovary syndrome (PCOS).

Patients and methods: Patients <35 years, presenting with infertility and PCOS, were included and randomly allocated to either group I (clomiphene citrate; CC) or group II (CC plus Cimicifugae racemosae; CR). Primary outcome was pregnancy rate. Secondary outcomes included ovulation, midcycle serum estradiol and luteinizing hormone (LH) as well as mid-luteal serum progesterone.

Results: Analysis included 98 patients in group I versus 96 patients in group II. Both groups were matched regarding demographics and basic data. Significant differences were elicited when comparing days until HCG injection (15.0?±?1.7 versus 12.0?±?1.9, p?=?0.91), endometrial thickness (mm) (8.5?±?1.9 versus 12.5?±?1.9, p?p?p?p?p?Conclusions: Adding CR to clomiphene-induction cycles with timed intercourse in polycystic ovarian syndrome improves cycle outcomes and pregnancy rates.     

Time of initiation of clomiphene citrate and pregnancy rate in polycystic ovarian syndrome.

OBJECTIVE: To investigate whether the timing of clomiphene citrate (CC) administration affects hormonal levels, follicular growth, endometrial thickness, and ovulation and pregnancy rates in women with polycystic ovarian syndrome (PCOS). METHODS: Of the 78 infertile women with PCOS who participated in this prospective, double-blind, randomized clinical trial, 37 collectively underwent 71 cycles of CC (100 mg/day) on days 1 through 5 of the menstrual cycle (group 1) and 41 collectively underwent 73 cycles of CC at the same concentration on days 5 through 9 (group 2). Hormonal levels, follicular growth, endometrial thickness, and ovulation and pregnancy rates were compared. RESULTS: The mean number of follicles and the maximum follicular size were greater in group 2. However, ovulation rates were 72.8% in group 1 and 70.8% in group 2 (P=.78), and pregnancy rates were 40.5% in group 1 and 19.5% in group 2 (P=.04). CONCLUSION: Treatment with CC is associated with higher rates of pregnancy if started early (days 1-5) in the menstrual cycle.     

N-acetyl-cysteine is a novel adjuvant to clomiphene citrate in clomiphene citrate-resistant patients with polycystic ovary syndrome

OBJECTIVE: To evaluate the effect of N-acetyl-cysteine (NAC), a mucolytic drug with insulin sensitizing properties, as an adjuvant therapy in subjects with polycystic ovary syndrome (PCOS) resistant to clomiphene citrate (CC). DESIGN: Placebo-controlled, double-blind randomized trial. SETTING: University-based hospital and private infertility practice. PATIENT(S): One hundred fifty women diagnosed with CC-resistant PCOS, aged 18-39 years undergoing therapy for infertility were included. INTERVENTION(S): The patients were assigned randomly to receive either NAC 1.2 g/d (group I) or placebo (group II) with CC 100 mg/d for 5 days starting at day 3 of the cycle. MAIN OUTCOME MEASURE(S): Ovulation rate and pregnancy rate (PR). RESULT(S): Combination of CC and NAC significantly increased both ovulation rate and PR in women with CC-resistant PCOS (49.3% vs. 1.3% and 21.3% vs. 0%, respectively). No cases of ovarian hyperstimulation syndrome (OHSS) were reported in the NAC group; two cases of miscarriage (12.5%) were reported. CONCLUSION(S): The NAC as an adjuvant to CC was more effective than placebo for CC-resistant patients with PCOS. It is safe and well tolerated.     

促排卵周期PCOS妇女子宫内膜纤维粘连蛋白及层粘连蛋白的表达

目的:了解促排卵药物氯米酚(CC)、hMG及GnRH-a对黄体中期子宫内膜内膜纤维粘连 蛋白(FN)及层粘连蛋白(LN)表达的影响。方法:应用单克隆抗体,采用免疫组织化学技术检测50 例正常妇女自然周期以及50例正常妇女,45例多囊卵巢综合征妇女应用CC／hCG,CC／hMG／hCG 及GnRH-a／hMG／hCG方案促排卵治疗后黄体中期子宫内膜FN和LN的表达。结果:子宫内膜FN 和LN表达在正常妇女自然周期着床窗口时呈现强阳性;而CC、hMG抑制FN和LN的表达,使 其阳性强度减弱,有显著性统计学差异P<0．01;GnRH-a对FN和LN抑制不明显。同时妊娠者较 未妊娠者FN和LN表达强度高。结论:CC／hCG及CC／hMG／hCG方案促排卵后黄体中期子宫内膜 中FN和LN表达下降或缺失,内膜容受性下降,妊娠率降低。     

促排卵治疗对多囊卵巢综合征患者子宫内膜整合素αv,β3表？…

目的 了解促排卵药物对多囊卵巢综合征（ＰＣＯＳ）患者黄体中期子宫内膜整合素αｖ、β３表达的影响。方法 应用单克隆抗体,采用免疫组织化学技术对２２例正常妇女、４０例无排卵ＰＣＯＳ患者促排卵治疗后黄体中期的子宫内膜整合素αｖ、β３进行测定。结果正常妇女子宫内膜整合素αｖ、β３表达在“着床窗口期”呈现强阳性;而氯米芬（ＣＣ）及绝经期促性腺激素（ｈＭＧ）抑制αｖ、βｂ的表达,使其表达呈弱阳性;而促性腺素释     

Nitric oxide donors increase the pregnancy rate in patients with unexplained infertility undergoing clomiphene citrate stimulation and intrauterine insemination: a randomized controlled pilot study

This study evaluated the effects of nitric oxide donor’s treatment on the pregnancy rate and uterine blood flow in patients with unexplained infertility undergoing clomiphene citrate stimulation and intrauterine insemination. A total of 120 patients were randomly allocated to a control group who received 100?mg clomiphene citrate daily from day 5 to 9 of cycle plus placebo vaginal tablets, and a study group received clomiphene citrate plus isosorbide mononitrate 10?mg vaginal tablets. Vaginal ultrasound was done before treatment and every other day starting from day 12 of cycle to count mature follicles and ovulation was triggered by IM injection of 10 000?IU hCG when one follicle measured 18?≥?mm followed by intrauterine insemination after 36?h. The endometrial thickness, uterine arteries resistance and pulsation indices, and endometrial vascular flow and vascular flow indices were measured before treatment and at day of hCG injection. Results were analyzed after one cycle treatment using the Mean?±?SD, the Student t test and the Fisher Exact test. Significant result was considered at p values?<0.05. The study group had significant higher pregnancy rate/cycle, higher endometrial and lower uterine artery blood flow indices (p?相似文献   

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.     

不同促排卵方案来源胚胎冻融胚胎移植妊娠结局分析北大核心CSCD

目的探讨不同促排卵方案来源胚胎冻融胚胎移植(FET)的妊娠结局。方法回顾性分析2016年1月至2021年5月在南通大学附属医院生殖医学中心接受体外受精或卵泡浆内单精子注射-胚胎移植(IVF/ICSI-ET)治疗,因鲜胚移植失败或全胚冷冻而要求FET的252个周期,根据刺激周期方案的不同将其分为5组:高孕激素促排卵(PPOS)组(n=26)、枸橼酸氯米芬+人绝经期促性腺激素(CC+hMG)组(n=50)、超短方案组(n=57)、拮抗剂组(n=78)及长方案组(n=41),分析各组的临床结局。结果 252个FET周期中,各组体重指数(BMI)、不孕年限、不孕类型、刺激周期时扳机日E2水平/扳机日直径≥14mm卵泡数、移植周期时转化日内膜厚度、转化日E2水平、移植D3胚胎或囊胚比例,差别均无统计学意义(P>0.05)。各组间患者年龄、基础FSH、获卵数、刺激周期Gn总量及平均移植胚胎数,差异有统计学意义(P<0.05)。各组间hCG阳性率、临床妊娠率、流产率及继续妊娠率差异无统计学意义(P>0.05)。但CC+hMG组hCG阳性率、临床妊娠率及继续妊娠率数值上最低,长方案组hCG阳性率、临床妊娠率及继续妊娠率数值上均最高。多因素logistic回归分析发现CC+hMG组FET临床妊娠率低于长方案组,差别有统计学意义(P<0.05),但与其他各组比较差异无统计学意义。其他4组间比较妊娠结局无明显差异(P>0.05)。结论 PPOS、超短方案、长方案、拮抗剂促排卵方案来源胚胎FET妊娠结局在数值上优于CC+hMG促排卵方案,其中长方案显著优于CC+hMG促排卵方案。     

来曲唑联合促性腺激素用于行宫腔内人工授精的排卵障碍者的促排卵研究

目的:探讨来曲唑在促排卵过程中的功效。方法:100例不孕症常规检查确诊为女性排卵障碍并接受超促排卵及IUI的不孕患者,随机分为A组(50例):口服来曲唑(LE)+hMG,B组(50例):口服氯米芬(CC)+hMG,分别监测hCG注射日子宫内膜的厚度、形态、血E2、P水平,分别统计排卵率及妊娠率。结果:A组血清中雌激素水平明显较低,hCG注射日子宫内膜较厚。直径>17mm卵泡数组间无明显差异,临床妊娠率也无明显差异。结论:对因女性排卵障碍引起的不孕,用LE或CC促排卵,其获卵数和临床妊娠率无差异,但用LE促排卵,可以减少CC抗雌激素样作用对子宫内膜的不良影响,使子宫内膜有较好的容受性,有利于妊娠。     

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   

Management of women with polycystic ovary syndrome who experienced premature luteinization during clomiphene citrate treatment

OBJECTIVE: To determine the preferred treatment modality in patients with PCOS who experienced premature luteinization during CC treatment. DESIGN: Prospective randomized study. SETTING: Tertiary medical center. PATIENTS: Twenty-two infertile women with PCOS demonstrating premature luteinization during at least two consecutive CC cycles. INTERVENTIONS: Randomized induction of ovulation either with FSH alone or with GnRH agonist combined with FSH for a single treatment cycle. MAIN OUTCOME MEASURES: Premature luteinization was defined as serum progesterone >1.5 ng/mL before hCG administration. RESULTS: Premature luteinization occurred in eight of the 10 patients (80%) in group A and in two of the 12 patients in group B (16.6%). This result corresponds to the higher mean (+/-SD) progesterone level present in group A patients as compared to those in group B (2.0 +/- 1.2 ng/mL vs. 1.2 +/- 0.6 ng/mL, P=0.03). No pregnancies were achieved in group A, whereas the pregnancy rate per cycle observed in group B was 33.3% (4/12). On the day of hCG administration, the maximum mean (+/-SD) estradiol level was significantly lower (P<0.0001) in group A (210.6 +/- 37.9 pg/mL) than in group B (600.3 +/- 253.8 pg/mL). The treatment duration and the number of FSH ampules used did not differ between the groups.Conclusions: Pituitary desensitization with GnRH analog in combination with FSH is superior to FSH-only treatment in PCOS patients who demonstrate premature luteinization during CC treatment.     

Is it possible to run a successful ovulation induction program based solely on ultrasound monitoring? The importance of endometrial measurements

OBJECTIVE: To attempt the monitoring of ovulation induction solely with ultrasound (US). DESIGN: Using serial US measurements to monitor ovulation induction using human menopausal gonadotropin and human chorionic gonadotropin (hCG), in comparison with estradiol (E2) concentrations that became available at the end of each cycle. SETTING: Specialist Reproductive Endocrine Unit. PATIENTS, PARTICIPANTS: Twenty hypogonadotropic and 29 ultrasonically diagnosed polycystic ovary patients. MAIN OUTCOME MEASURE: Follicular growth, uterine measurements, endometrial thickness, and serum E2 concentrations. RESULTS: Follicular growth, uterine measurements, and endometrial thickness correlated strongly with E2 concentrations (P less than 0.0001). The endometrium on the day of hCG administration was significantly thicker (P less than 0.01) in the conception (n = 27) compared with the nonconception cycles (n = 87), whereas no significant difference were observed in serum E2 concentrations. No pregnancy was observed when hCG had been administered when the endometrial thickness was less than or equal to 7 mm. Midluteal endometrial thickness of greater than or equal to 11 mm was found to be a good prognostic factor for detecting early pregnancy (P less than 0.008). CONCLUSIONS: Serial US examinations used alone have proven to be safe and highly efficient. It also has a unique ability to detect pregnancy in the midluteal phase.     

Comparison of clomiphene citrate and letrozole for ovulation induction in women with polycystic ovary syndrome: a prospective randomized trial

To compare the therapeutic efficacy of clomiphene citrate (CC) and letrozole (LE) on ovulation, pregnancy, and live birth in women with polycystic ovary syndrome (PCOS); and to ensure if LE can replace CC as the first-line therapy for ovulation induction in these women. This is a prospectively, randomized, controlled trial in the tertiary hospital. Two-hundred and sixty-eight anovulatory PCOS patients were treated by CC or CC plus metformin and LE or LE plus metformin for three continuous cycles or conception; their ovulation rates, pregnancy rates, and live birth rates were calculated and compared. No significant difference was noted among the four groups regarding to the baseline data of clinical manifestations, serum sex hormone levels, and serum insulin levels. A total of 240 patients completed the therapies. The ovulation rate was significantly higher in the group LE than the group CC; however, no significant difference was noted between the groups LE and CC, CC, and CC?+?MET, or LE and LE?+?MET in the pregnancy rate, abortion rate, and live birth rate. No birth defect was found in the total of 63 newborns. CC regimen was still recommended to be the first-line therapy of ovulation induction for PCOS.