Reproductive outcome after letrozole versus laparoscopic ovarian drilling for clomiphene-resistant polycystic ovary syndrome

Objective

To compare the clinical outcomes of letrozole and laparoscopic ovarian drilling (LOD) in patients with clomiphene-citrate-resistant polycystic ovary syndrome (PCOS).

Methods

In the present prospective randomized trial, 140 women with clomiphene-citrate-resistant PCOS were randomly allocated to receive 5 mg letrozole from day 3 to day 7 of menses for 6 consecutive cycles, or to undergo LOD. When a leading follicle of at least 18 mm was present, ovulation was triggered with human chorionic gonadotropin (hCG). The 6-month rates of ovulation, pregnancy, abortion, and live births were evaluated.

Results

The groups were similar with regard to baseline clinical characteristics and hormonal profiles. The ovulation rate was significantly higher in the letrozole group than in the LOD group (59.0% versus 47.5%). On the days of the hCG injection, women in the letrozole group had a significantly thicker endometrium than those in the LOD group (P < 0.0001). Women receiving letrozole had a higher pregnancy rate (35.7% versus 28.6%) and a lower rate of spontaneous abortion (8.0% versus 20.0%, respectively), but these differences were not statistically significant.

Conclusion

Letrozole seems to be a suitable second-line ovulation-inducing alternative to LOD in women with PCOS who do not conceive with clomiphene citrate.     

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.     

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.     

Letrozole versus clomiphene citrate in polycystic ovary syndrome: systematic review and meta-analysis

Abstract

The objective of the present systematic review and meta-analysis was to examine the literature and to identify the results of randomized controlled trials (RCTs) comparing the use of letrozole to clomiphene citrate (CC) for ovulation induction in patients with polycystic ovary syndrome (PCOS). An exhaustive electronic literature search was performed using the MEDLINE and EMBASE databases until October 2014. Seven prospective RCTs comparing the use of letrozole to CC in PCOS patients met the inclusion criteria. Overall, the seven included studies accounted for 1833 patients (906 in the letrozole group and 927 in the CC group) and for 4999 ovulation induction cycles (2455 in the letrozole group and 2544 in the CC group). Five of the included studies reported data on live birth rates. There was a statistically significant increase in the live birth and pregnancy rates in the letrozole group when compared to the CC group, with a relative risk (RR)?=?1.55 (95% confidence interval (CI): 1.26–1.90; I^2?=?0%) and RR?=?1.38 (95% CI: 1.05–1.83; I^2?=?61%), respectively. There were no differences in the multiple pregnancy, miscarriage and ovulation rates between the two groups. Our study found that letrozole is superior to CC when considering the live birth and pregnancy rates in patients with PCOS.     

Endometrial effects of letrozole and clomiphene citrate in women with polycystic ovary syndrome using spiral artery Doppler

Objectives  To compare the effects of letrozole and clomiphene citrate (CC) on endometrial response in PCOS using subendometrial spiral artery Doppler. Methods  Fifty consecutive patients of anovulatory PCOS were recruited. Twenty-five patients (58 cycles) received 2.5–5 mg of letrozole; 25 patients (56 cycles) received 50–100 mg of CC (both orally on days 5–9 of menses). Main outcome measures: number of dominant follicles, endometrial thickness (ET), spiral artery resistance index (RI) and pulsatility index (PI) and pregnancy rate. Results  The mean number of dominant follicles in letrozole group and CC groups was 1.63 ± 1.02 and 1.62 ± 0.96, respectively (P > 0.05). The mean mid cycle ET was 6.9 ± 0.74 mm in letrozole group and 5.9 ± 0.53 mm in CC group (P < 0.05). In letrozole and CC groups, the mean RI of spiral artery were 0.63 ± 0.05 and 0.79 ± 0.09, respectively, and the mean PI of spiral artery were 1.19 ± 0.06 and 1.55 ± 0.13, respectively. Both RI and PI in the letrozole group showed significant lower impedance compared to CC group (P < 0.05). Pregnancy rate per cycle was 19% (11/58) in the letrozole group and 12.5% (7/56) in the CC group (P > 0.05). Conclusion  The effect of letrozole showed a significantly better endometrial response compared to CC.     

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.     

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.     

Prognostic factors for ovulatory response with clomiphene citrate in polycystic ovary syndrome

OBJECTIVE: To evaluate prospectively the prognostic factors for ovulatory responses following clomiphene citrate (CC) administration in polycystic ovary syndrome (PCOS). STUDY DESIGN: Fifty-nine infertile patients with a diagnosis of PCOS were recruited. Ovulation was induced using 100 mg/day CC administered daily from days 5 to 9 of the cycle. Endocrine and metabolic parameters between responder and non-responder groups were analyzed. RESULTS: For a 75-g fasting glucose load (75-g OGTT), blood glucose levels at 60 and 120 min, the area under the curve (AUC) and blood insulin levels at 120 min in the non-responder group (n=25) were significantly higher than those in the responder group (n=34), although the measurements of fasting blood glucose and insulin were not significantly different between the two groups. In the receiver operating characteristic curves, the most appropriate cutoff point was 120 mg/dl for the blood glucose level at 120 min and 9000 for the blood glucose x insulin level at 120 min. There were no significant differences in the clinical characteristics or in the endocrine and metabolic parameters between conceived (n=9) and non-conceived groups (n=21). CONCLUSION: The levels of blood glucose and blood glucose x insulin at 120 min after 75-g OGTT could be good biochemical markers of CC resistance in PCOS. No predictors of conception following CC therapy were identified by this study.     

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.     

Short-term metformin treatment for clomiphene citrate-resistant women with polycystic ovary syndrome

Objective

To evaluate the effect of a short-course pretreatment with metformin on hyperandrogenism, insulin resistance, cervical scores, and pregnancy rates in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS).

Methods

Thirty-seven women with CC-resistant PCOS were randomly assigned to be pretreated with 500 mg of metformin or placebo 3 times per day for 2 cycles, and 100 mg of CC was given on days 5 through 9 of the second cycle in both groups. Luteinizing hormone (LH), follicle stimulating hormone (FSH), dehydroepiandrostendione sulfate (DHEAS), total testosterone (T), glucose, and insulin levels were measured at baseline and after the first cycle, as well as body mass index (BMI), cervical score, and pregnancy rate.

Results

After 1 cycle, BMI, total T level, and percentage of participants with insulin resistance were significantly decreased in the metformin group, without any significant decrease in LH, FSH, and DHEAS levels; and in the second cycle, CC treatment resulted in a higher ovulation rate and a thicker endometrium in the metformin group. The pregnancy rate and cervical scores were also higher in that group.

Conclusion

The short-course pretreatment with metformin decreased hyperandrogenism and insulin resistance and improved cervical sores, ovulation rate, and pregnancy rate among women with CC-resistant PCOS.     

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.

Clomiphene citrate plus tamoxifen versus laparoscopic ovarian drilling in women with clomiphene-resistant polycystic ovary syndrome

Objective

To compare the efficacy of clomiphene citrate (CC) plus tamoxifen with that of laparoscopic ovarian drilling in clomiphene-resistant women with polycystic ovary syndrome (PCOS).

Method

We randomly allocated 150 women with CC-resistant PCOS to a combined medication group (group 1) or a laparoscopic surgery group (group 2). The primary outcome was the live birth rate in each group; secondary outcomes were the rates of ovulation, clinical pregnancy and miscarriage.

Results

There were no significant differences between the groups regarding rates of ovulation (81.3% vs 85.3%), pregnancy (53.3% vs 50.7%), or live births (49.3% vs 44.0%), but the mean endometrium thickness was significantly greater on the day of human chorionic gonadotropin administration in group 1 (P < 0.001).

Conclusion

Clomiphene citrate plus tamoxifen was as effective as laparoscopic ovarian drilling in promoting ovulation and pregnancy.     

Comparison of letrozole with continuous gonadotropins and clomiphene-gonadotropin combination for ovulation induction in 1387 PCOS women after clomiphene citrate failure: a randomized prospective clinical trial

Purpose  Letrozole, though reported to be an effective ovulation inducing agent, warrants larger randomized trials. The purpose of this study is to compare the efficacy of letrozole with that of rFSH and clomiphene citrate(CC)/rFSH for ovarian stimulation in IUI cycles. Methods  Randomized, prospective, single-blinded clinical trial. 1387 PCOS women after CC failure were randomized into three groups: Group A received letrozole, Group B received CC with two doses rFSH and Group C received continuous rFSH day 2 onwards until hCG injection. Results  Group A, B and C had an ovulation rate of 79.30%, 56.95% and 89.89% and cycle cancellation rate of 20.70%, 43.05% and 10.11%, respectively. Pregnancy rates in Group A, B and C were 23.39%, 14.35% and 17.92%, while the miscarriage rates were 13.80%, 16.67% and 14.52%, respectively. Conclusion  Letrozole appears to be a suitable ovulation inducing agent in PCOS women with CC failure and is found to be most effective when baseline estradiol level >60 pg/ml. Capsule Letrozole appears to be an effective ovulation inducing agent as compared to clomiphene-rFSH and continuous rFSH protocols in PCOS women after clomiphene citrate failure.     

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.     

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.     

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