Luteal phase clomiphene citrate for ovulation induction in women with polycystic ovary syndrome

Purpose

The aim was to test a new protocol of luteal phase administration of clomiphene citrate (CC) for ovulation induction in women with polycystic ovary syndrome (PCOS).

Methods

This was a prospective, randomized, controlled trial. Two hundred and fifty-two women (cycles) with PCOS were utilized to create two groups. Patients in Group 1 (126 patients) received 100 mg of CC daily for 5 days starting on day 5 of menses, and patients in Group 2 (126 patients) received 100 mg of CC daily for 5 days starting the next day after finishing medroxyprogesterone acetate (MPA) (before withdrawal bleeding). The main outcome measures were the number of growing and mature follicles, serum E2 (in pg/mL), serum progesterone (in ng/mL) levels, endometrial thickness (in mm), pregnancy, and miscarriage rates.

Results

The total number of follicles and the number of follicles ≥14 mm during stimulation were significantly greater in Group 2. The endometrial thickness at the time of human chorionic gonadotrophin (hCG) administration was significantly greater in Group 2 as compared to Group 1 (7.84 ± 1.22 and 8.81 ± 0.9, respectively). Serum E2 levels were also significantly higher (p < 0.05) in Group 2 as compared to Group 1 (449.61 ± 243.45 vs. 666.09 ± 153.41 pg/mL). Pregnancy occurred in 13 patients (10.3 %) in Group 2 and in 11 patients (8.7 %) in Group 1. The difference was not statistically significant.

Conclusion

Luteal phase administration of CC in patients with PCOS leads to increased follicular growth and endometrial thickness, which might result in a higher pregnancy rate.     

Comparison between two clomiphene citrate protocols for induction of ovulation in clomiphene resistant polycystic ovary syndrome

ObjectiveTo compare two protocols of CC therapy for induction of ovulation in a group CC resistant PCOS women.Study designDouble blind randomized controlled trial.Subjects and methods260 nulliparous CC resistant PCOS women randomized between two groups; In the first group each patient received 200 mg/day for 5 days while the second group received 100 mg/day for 10 days, both starting on day 3 of progestin induced withdrawal bleeding.Main outcome measuresOvulation defined as at least one follicle reaching ⩾14 mm diameter, and confirmed by timed serum progesterone. Secondary outcome measures included; number of dominant follicles, endometrial thickness, clinical pregnancy rate, and live birth rate.ResultsThe extended protocol resulted in significantly higher ovulation, pregnancy, and live-birth rates than the high dose protocol (p 0.001). Serum FSH levels on day 6 of treatment were comparable between the two groups while the level on day 11 was significantly higher in the second group (p 0.02). Serum LH levels were comparable both on days 6 and 11. Patients on longer protocol (group II) required a longer time to ovulate (18 ± 4.4 versus 14 ± 3.6 days) but had a significantly higher endometrial thickness at the time of ovulation. (p 0.02) FSH and LH levels were comparable between responders and non-responders in both groups.ConclusionsThe current study reports significantly higher ovulation and pregnancy rates with the longer lower dose protocol probably because of prolonged FSH rise. Study web address: ACTRN12611000639921.     

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.     

Endometrial biopsy during induction of ovulation with clomiphene citrate in polycystic ovary syndrome

Background.?The dichotomy between ovulation rates and pregnancy rates for women with polycystic ovary syndrome (PCOS) treated with clomiphene citrate (CC) prompted the present study to determine the effect of CC on endometrial maturity.

Methods.?Retrospective case–control study of anovulatory women with PCOS (n = 119) on their third ovulatory cycle of CC and controls, 238 healthy regularly ovulating women whose partners had abnormal sperm, all of whom had an endometrial biopsy in the late luteal phase.

Results.?Endometrial histology classified according to the classical Noyes criteria revealed out-of-phase endometrium in 19/119 (16%) of the CC group compared with 7/238 (3%) in controls (p < 0.0001). Duration of the luteal phase was not influenced by histological age of the endometrium. Endometrial biopsy performed during 138 conception cycles extracted from the database did not increase the miscarriage rate significantly (23.9%).

Conclusions.?CC treatment significantly increases the prevalence of out-of-phase endometrium and this could explain, in part, the large difference between ovulation and pregnancy rates. There was no correlation between the results of the endometrial biopsy and the duration of the luteal phase. Performing an endometrial biopsy during a conception cycle does not seem to have a significant negative effect on the outcome of pregnancy.     

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.     

Endometrial biopsy during induction of ovulation with clomiphene citrate in polycystic ovary syndrome.

BACKGROUND: The dichotomy between ovulation rates and pregnancy rates for women with polycystic ovary syndrome (PCOS) treated with clomiphene citrate (CC) prompted the present study to determine the effect of CC on endometrial maturity. METHODS: Retrospective case-control study of anovulatory women with PCOS (n = 119) on their third ovulatory cycle of CC and controls, 238 healthy regularly ovulating women whose partners had abnormal sperm, all of whom had an endometrial biopsy in the late luteal phase. RESULTS: Endometrial histology classified according to the classical Noyes criteria revealed out-of-phase endometrium in 19/119 (16%) of the CC group compared with 7/238 (3%) in controls (p < 0.0001). Duration of the luteal phase was not influenced by histological age of the endometrium. Endometrial biopsy performed during 138 conception cycles extracted from the database did not increase the miscarriage rate significantly (23.9%). CONCLUSIONS: CC treatment significantly increases the prevalence of out-of-phase endometrium and this could explain, in part, the large difference between ovulation and pregnancy rates. There was no correlation between the results of the endometrial biopsy and the duration of the luteal phase. Performing an endometrial biopsy during a conception cycle does not seem to have a significant negative effect on the outcome of pregnancy.     

Comparison of metformin and clomiphene citrate therapy for induction of ovulation in the polycystic ovary syndrome

Objective  

To compare the efficacy of metformin and clomiphene citrate (CC) therapies for ovulation induction in anovulatory infertile women with polycystic ovary syndrome (PCOS).     

Luteal phase clomiphene citrate for ovulation induction in women with polycystic ovary syndrome: a systematic review and meta-analysis

Objective: To assess the efficacy of late luteal phase clomiphene citrate (CC) administration relative to early follicular phase CC for ovulation induction for polycystic ovary syndrome (PCOS).

Study design: Review.

Materials and methods: A complete electronic databases including PubMed, Embase, The Cochrane Library, Web of Science, and CBM were searched for relevant randomized controlled trials (RCTs). The search was not restricted by language and publication time. Two reviewers selected trials and assessed trial quality by the Cochrane Handbook 5.1.0 independently.

Results: Four eligible RCT studies involving 708 women (934 cycles) were included. The results of the Meta-analysis: Late luteal phase group was associated with a number of higher total follicles (MD 1.82; 95% CI 0.86–2.78, p?p?p?=?0.26), ovulation rate (RR 0.99; 95% CI 0.86–1.14, p?=?0.87), and abortion rate (RR 1.12; 95% CI 0.38 to 3.29, p?=?0.84) between the two groups.

Conclusion: It appeared that late luteal phase CC for ovulation induction might be an effective method for ovulation induction in women with PCOS compared to conventional CC administration. Further intensive randomized-controlled studies should be warranted to define the efficacy of CC used in late luteal phase.     

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.

N-acetylcysteine as an adjuvant to clomiphene citrate for successful induction of ovulation in infertile patients with polycystic ovary syndrome

Aim: The aim of this study was to evaluate the effect of oral N-acetylcysteine (NAC) administration as an adjuvant to clomiphene citrate (CC) on induction of ovulation outcomes in patients with polycystic ovary syndrome (PCOS). Material and Methods: In this placebo-controlled double-blind randomized clinical trial, 180 PCOS infertile patients were randomly divided into two groups for induction of ovulation. Patients in group 1 received CC 100?mg/d plus NAC 1.2?g/d and patients in group 2 received CC plus placebo for 5?days starting at day 3 of the cycle. On the 12th day of the menstrual cycle in the presence of at least one follicle with an 18-20-mm diameter in ultrasound evaluation, 10?000?U hCG was injected intramuscularly and timed intercourse was advised 36?h after hCG injection. Serum β-hCG level was measured on the 16th day after hCG injection. Results: The number of follicles >18?mm and the mean endometrial thickness on the day of hCG administration were significantly higher among the CC+NAC group (P-value?=?0.001). The ovulation and pregnancy rates were also significantly higher in the CC+NAC group (P-value?=?0.02 and 0.04, respectively). No adverse side-effects and no cases of ovarian hyperstimulation syndrome were observed in the group receiving NAC. Conclusion: NAC as a safe and well-tolerated adjuvant to CC for induction of ovulation can improve the ovulation and pregnancy rates in PCOS patients. It may also have some beneficial impacts on endometrial thickness.     

克罗米芬联合促卵泡素治疗多囊卵巢综合征的疗效观察

目的:比较单用克罗米芬(CC)及其联合不同促卵泡素(FSH)治疗多囊卵巢综合征(PCOS)患者的效果,以指导PCOS患者选择合适的促排卵方案.方法:选取2009年1月至2012年7月就诊于我院生殖门诊的81例PCOS患者(共92周期),患者均以CC促排卵,根据月经第8天的卵泡生长情况,决定是否联合应用基因重组促卵泡素(rFSH)或尿促卵泡素(uFSH).按促排卵方案不同将患者分为3组:CC+ HCG组(A组,26例,32周期);CC+rFSH+HMG+HCG组(B组,23例,26周期);CC+uFSH+HMG+HCG组(C组,32例,34周期).患者排卵后均用黄体酮胶丸或地屈孕酮黄体支持12 ～ 14天.比较3组患者促排卵治疗的效果.结果:A组中2例患者发生黄素化综合征(LUFS);B组中4例发生轻度卵巢过度刺激综合征(OHSS);C组中1例发生重度OHSS,1例LUFS.3组患者的HCG日最大卵泡直径、内膜厚度、排卵率及妊娠率均无显著差异(P＞0.05).A组D8优势卵泡直径大于B、C组(P＜0.05);至HCG日平均时间少于B、C组(P＜0.05);B组直径≥1.5cm卵泡数和排卵数均显著高于A、C组(P＜0.05).B组与C组的至HCG注射日时间和FSH用量均无显著差异(P＞0.05).结论:CC促排周期D8优势卵泡直径大小对决定联合FSH治疗PCOS患者有一定的参考意义.单用CC促排卵可能抵抗周期,联合uFSH是经济有效的促排卵方案.     

来曲唑、他莫昔芬和氯米芬治疗多囊卵巢综合征不孕疗效比较

目的比较多囊卵巢综合征(PCOS)不孕患者经纠正内分泌代谢紊乱后应用3种不同促排卵药物的效果及对子宫内膜的影响。方法选择2009年3月至2010年1月中山大学孙逸仙纪念医院妇产科生殖中心128例PCOS不孕患者,于本院行第1次促排卵,有高雄激素或胰岛素抵抗者经预处理至少3个月。随机分为3组,来曲唑44个周期、他莫昔芬40个周期和氯米芬44个周期。结果月经第10天的子宫内膜厚度,他莫昔芬组[(6.4±1.2)mm]高于来曲唑组[(5.4±1.7)mm]和氯米芬组[(5.4±1.3)mm](P=0.01);HCG日血雌二醇(E2)水平,来曲唑组[(838.6±678.2)pmol/L]低于他莫昔芬组[(2629.2±1931.5)pmol/L]和氯米芬组[(1971.2±1222.8)pmol/L](P<0.001);3组间加用尿促性腺激素(HMG)周期数,HCG日子宫内膜厚度、血黄体生成素及孕酮、直径≥18mm成熟卵泡数,妊娠率和早期流产率,差异无统计学意义(P>0.05);HCG日子宫内膜的厚度与注射HCG的月经周期日及月经第10天的子宫内膜厚度呈正相关(P<0.05),与药物的种类及HCG日血E2水平等无显...     

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