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.     

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.     

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.     

Use of embryo culture supernatant to improve clinical outcomes in assisted reproductive technology: a systematic review and meta-analysis

We planned a systematic review and meta-analysis of randomized clinical trials (RCTs) to examine the best available evidence regarding the intrauterine instillation of embryo culture supernatant prior to embryo transfer in ART. The outcomes were: (i) live birth; (ii) clinical pregnancy; (iii) multiple pregnancy; and (iv) miscarriage rates. Five RCTs were considered eligible and available for qualitative synthesis. Due to clinical heterogeneity, results from only two trials were combined for the meta-analysis. The live birth rate (risk ratio [RR], 0.47; 95% confidence interval [CI] 0.22–0.98; one study, 60 participants, low-quality evidence) was found to be significantly lower with intrauterine instillation of embryo culture supernatant compared to no intervention. The clinical pregnancy rate was similar between the embryo culture supernatant group and the control group (RR 1.02 RR, 95% CI 0.77–1.36; two trials, 156 participants, I²?=?0%). To conclude, this review did not find any improvement in clinical pregnancy rate with the intrauterine instillation of embryo culture supernatant prior to embryo transfer compared to no intervention in women undergoing ART and we remain uncertain regarding its effect on live birth rate.     

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   

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.     

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.     

Effectiveness of mild ovarian stimulation versus GnRH agonist protocol in women undergoing assisted reproductive technology: a meta-analysis

Objective: our meta-analysis was conducted to evaluate the effectiveness of the mild ovulation induction protocol using CC/gonadotropin/GnRH antagonist compared to the conventional GnRH agonist protocol in women undergoing ART. Method: Six electronic databases were searched from their date of establishment until August 2016. Outcomes in our analysis were calculated in terms of relative risk (RR) and weighted mean differences (WMD) and standard mean differences (SMD) with 95% confidence intervals (CI) using random effect models or fixed effect models.

Results: Six prospective controlled clinical trials with 1543 women comparing the clinical impacts of the two protocols were included. The synthesized results suggested a significant reduction in the quantity of gonadotropins (SMD: ?1.96, 95% CI: ?2.28 to 1.64, I²?=?78.5%), the incidence of OHSS (RR: 0.16, 95% CI 0.03–0.86, I²?=?0%) and an increase in the cycle cancelation rate (RR: 1.46, 95% CI 1.05–2.03, I²?=?89.4%). While no evidence of statistically signi?cant differences between the groups existed in the other clinical outcomes.

Conclusion: This study suggested that the probable benefits of the mild protocol, including its less costs and safer process without reducing the overall IVF treatment success rates, seemed to make it a better treatment option. Larger sample prospective trials evaluating live birth, clinical pregnancy, OHSS, multiple pregnancy incidence and so on were desired to establish.     

Luteal support with vaginal dydrogesterone increases pregnancy rate in patients with clomifene resistant polycystic ovary syndrome receiving letrozole for ovulation induction

A prospective observational study was conducted on 186 patients with clomifene citrate (CC)-resistant polycytic ovary syndrome (PCOS) who were allocated into two treatment arms for three months; letrozole alone (n?=?92) and letrozole with luteal support using vaginal dydrogestrone (n?=?94). Patients received luteal support experienced significantly higher clinical pregnancy rate than those who received letrozole alone (48.9% vs. 23.9%, respectively). Luteal support in letrozole treated CC-resistant PCOS significantly improves pregnancy rate and should be implemented in ovulation induction regimens.     

Efficacy of luteal phase support with vaginal progesterone in intrauterine insemination: a systematic review and meta-analysis

Purpose

To evaluate the efficacy of luteal phase support with vaginal progesterone in women undergoing intrauterine insemination (IUI).

Methods

Systematic review and meta-analysis. Randomized controlled trials (RCT) comparing supplementation of luteal phase with vaginal progesterone among women undergoing IUI versus a control group were included. The main outcome assessed was live birth rate.

Results

Five RCT met the inclusion criteria. In all 1,271 patients were included (951 IUI cycles in the progesterone group, 935 in the control group). Women treated with vaginal progesterone achieved significantly higher live birth rate (risk ratio [RR] 1.94, 95 % confidence interval [CI] 1.36 to 2.77,), and clinical pregnancy rate (RR 1.41, 95 % CI 1.14 to 1.76) as compared with controls. In the subgroup analysis per stimulation protocol, this beneficial effect of receiving progesterone was only observed in the group stimulated with gonadotropins (RR 2.28, 95 % CI 1.49 to 3.51), compared to the group stimulated with clomiphene citrate (CC) (RR 1.30, 95 % CI 0.68 to 2.50). No differences were observed in the miscarriage and multiple pregnancy rates.

Conclusions

The supplementation of luteal phase with vaginal progesterone significantly increases live birth among women undergoing IUI when receiving gonadotropins for ovulation induction. Women receiving CC to induce ovulation do not seem to benefit from this treatment.     

Effect of metformin on ovulation and reproductive outcomes in women with polycystic ovary syndrome: a meta-analysis of randomized controlled trials

Purpose

To evaluate the effect of MET on ovulation and reproductive outcomes in patients with polycystic ovary syndrome.

Methods

Meta-analysis of available data from randomized controlled trials that examined the ovulation, pregnancy and live birth rate after the administration of clomiphene citrate (CC) or MET alone or combined.

Results

The ovulation rate was found to be higher in the group treated with MET combined with clomiphene citrate (CC) than only with CC, odds ratio (OR): 1.27, 95 % confidence interval (95 % CI) (1.03–1.56), while the pregnancy and live birth rate showed no significant difference between the two groups, OR: 1.19, 95 % CI (0.99–1.42) and OR: 0.99, 95 % CI (0.84–1.17), respectively. The MET + CC group produced a higher ovulation and pregnancy rate than MET group, OR: 2.10, 95 % CI (1.89–2.34) and OR: 2.08, 95 % CI (1.55–2.80), respectively, while between two groups the live birth rate showed no significant difference, OR: 1.50, 95 % CI (0.75–3.00). The ovulation rate was lower in MET than in CC group, OR: 0.65, 95 % CI (0.43–0.995), while between the two groups the pregnancy and live birth rate showed no significant difference, OR: 0.86, 95 % CI (0.42–1.74) and OR: 0.89, 95 % CI (0.71–1.13).

Conclusion

The current study indicated that combination of MET and CC could gain advantage over a single administration in the ovulation induction and pregnancy rate.     

Thicker endometrial linings are associated with better IVF outcomes: a cohort of 6331 women

Abstract

Our objective was to determine if a correlation exists between endometrial thickness measured on the day of ovulation trigger during an in vitro fertilization (IVF) cycle and pregnancy outcomes among non-cancelled cycles. We performed a retrospective cohort study looking at 6331 women undergoing their first, fresh autologous IVF cycle from 1 May 2004 to 31 December 2012 at Boston IVF (Waltham, MA). Our primary outcome was the risk ratio (RR) of live birth and positive β-hCG. We found that thicker endometrial linings were associated with positive β-hCG and live birth rates. For each additional millimetre of endometrial thickness, we found a statistically significant increased risk of positive β-hCG (adjusted RR: 1.14; 95% CI: 1.09–1.18) and live birth (RR: 1.08; 95% CI: 1.05–1.11). There was no association between endometrial thickness and miscarriage (RR: 0.99; 95% CI: 0.91–1.07). Similar results were seen when categorizing endometrial thickness. Compared with an endometrial thickness >7 to <11?mm, the likelihood of a live birth was significantly higher for an endometrial thickness ≥11?mm (adjusted RR: 1.23; 95% CI: 1.11–1.37) and significantly lower for the ≤7?mm group (adjusted RR: 0.64; 95% CI: 0.45–0.90). In conclusion, thicker endometrial linings were associated with increased pregnancy and live birth rates.     

Ovulation induction using sequential letrozole/gonadotrophin in infertile women with PCOS: a randomized controlled trial

Research questionIs sequential letrozole/human menopausal gonadotrophin (HMG) superior to letrozole alone in ovulation induction and pregnancy promotion among infertile women with polycystic ovary syndrome (PCOS)?DesignThis open-label randomized controlled trial comparing sequential letrozole/HMG and letrozole alone included 174 participants enrolled from August 2019 to January 2020 at the Union Hospital of Tongji Medical College, Huazhong University of Science and Technology. Infertile women aged between 18 and 40 years who met Rotterdam criteria for PCOS and without other known causes of infertility were selected for this study. Patients were randomly assigned at a 1:1 ratio to receive 2.5 mg letrozole on cycle days 3–7 (n = 87) or 2.5 mg letrozole on cycle days 3–7 with a sequential injection of 75 IU HMG on cycle days 8–10 for one treatment cycle (n = 87). The pregnancy outcome was recorded after one treatment cycle.ResultsWomen receiving sequential treatment achieved a significantly higher ovulation rate than those in the letrozole group (90.8% versus 70.1%, P = 0.001) and the live birth rate of the sequential group was significantly higher than that of the letrozole protocol (23.0% versus 10.3%, P = 0.025); there was no statistical variation with respect to adverse events.ConclusionsThe data suggest that the sequential letrozole/HMG protocol may be superior to the letrozole alone protocol in terms of ovulation induction and pregnancy promotion among infertile women with PCOS.     

Coenzyme Q10 and male infertility: a meta-analysis

Objective

To evaluate the effect of coenzyme Q10 treatments in male infertility, specifically in these parameters: live birth and pregnancy rates, CoQ10 seminal concentration, sperm concentration, and sperm motility.

Materials and methods

Systematic review and meta-analysis in male infertility patients with CoQ10 oral treatments. Three trials were included: 149 males in CoQ10 group and 147 males in placebo group.

Results

None of the included trials provided any data regarding live births. The results of this meta-analysis show that supplementing infertile men with CoQ10 does not increase pregnancy rates. The analysis showed, among patients receiving CoQ10 treatment, a statistically significant increase in: CoQ10 seminal concentration (RR 49.55, 95 % CI 46.44 to 52.66, I² = 17 %), sperm concentration (RR 5.33, 95 % CI 4.18 to 6.47, I² = 58 %), and sperm motility (RR 4.50, 95 % CI 3.92 to 5.08, I² = 0 %)

Conclusion

There is no evidence in the literature that CoQ10 increases either live birth or pregnancy rates, but there is a global improvement in sperm parameters. Adequately powered, robust trials of individual and combination antioxidant therapies are required to guide clinical practice.     

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.     

The role of metformin in ovulation induction: Current status

To define the exact role of metformin in ovulation induction, it is crucial to distinguish three different indications: naïve PCOS, CC-resistant PCOS and ART. In naïve PCOS: metformin as compared to placebo has been shown to improve ovulation rates, but metformin did not exert significant advantage over CC with respect to cumulative ovulation, pregnancy or live-birth rates. The combined approach of metformin plus CC is not better than CC or metformin monotherapy in naïve PCOS. In CC-resistant patients: metformin has no benefit over placebo in ovulation, pregnancy, and live-birth rates as a single agent, but the combination of metformin and CC significantly improved ovulation and pregnancy rates when compared with CC alone. However, combined therapy did not improve the odds of live birth. Metformin pretreatment improves the efficacy of CC in PCOS patients with CC resistance. In PCOS patients scheduled for ART: metformin addition to gonadotropins reduces the duration of gonadotropins administration and the doses of gonadotropins required, and increases the rate of monoovulations, reducing the risk of cancelled cycles. Metformin co-administration to IVF treatment does not improve pregnancy or live-birth rates but reduces the risk of OHSS.     

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.     

Effect of luteal phase support after ovulation induction and intrauterine insemination

Objective: This study aimed to evaluate the effect of luteal phase support on clinical pregnancy and live birth rates after ovulation induction and intrauterine insemination (IUI).

Methods: 579 cycles from 2010 to 2013 were retrospectively evaluated. Ovarian stimulation was performed with gonadotropins, and rHCG was used for ovulation triggering. All patients received IUI. 451 cycles were supported by receiving vaginal micronized progesterone capsules (142 cycles) or vaginal progesterone gel (309 cycles) whereas 128 cycles were not supported.

Results: Clinical pregnancy (20.6 versus 9.4%; p?=?0.004) and live birth rates (14 versus 7%; p?=?0.036) were higher for supported group than for unsupported group. Progesterone gel and micronized progesterone subgroups achieved similar clinical pregnancy and live birth rates (21.4 versus 19%, p?=?0.567 and 14.2 versus 13.4%, p?=?0.807; respectively).

Conclusions: Luteal phase support improved the success of IUI cycles affecting both clinical pregnancy and live birth rates when gonadotropins were used for ovulation induction. The use of vaginal progesterone gel or micronized progesterone significantly improves clinical pregnancy rates. The live birth rates were higher in the progesterone gel group, but were similar in the micronized progesterone group compared to the unsupported group.     

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.     

Cost effectiveness of letrozole and purified urinary FSH in treating women with clomiphene citrate-resistant polycystic ovarian syndrome: a randomized controlled trial

We aimed to compare the cost effectiveness of letrozole versus purified urinary follicle stimulating hormone (FSH) in treating patients with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). This was a randomized trial conducted in Cairo University and Beni-Suef University Hospitals, Egypt. A cohort of 140 eligible women was randomized to receive either letrozole 2.5?mg twice daily for five days, or FSH using a graduated regimen starting with a dose of 75?IU. Treatment was repeated for three months if pregnancy did not occur. There were no significant differences between the two treatments in the cumulative clinical pregnancy rate (30% vs. 34%; p?=?0.578), cumulative ovulation rate (47% vs. 57%; p?=?0.236), miscarriage rate (9% vs. 4%, p?>?0.999) or multiple pregnancy rate (0% and 8%, p?=?0.491) but the FSH cycles were 4.8 times more expensive. Letrozole and FSH were both effective in treating women with CC-resistant PCOS but letrozole was more cost effective.Study registration number: NCT02304107.