Gonadotrophins or clomiphene citrate in women with normogonadotropic anovulation and CC failure: does the endometrium matter?
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ABSTRACT:
SUBMITTER: Bordewijk EM
PROVIDER: S-EPMC7316496 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
Publications
Gonadotrophins or clomiphene citrate in women with normogonadotropic anovulation and CC failure: does the endometrium matter?
Bordewijk E M EM Weiss N S NS Nahuis M J MJ Kwee J J Lambeek A F AF van Unnik G A GA Vrouenraets F P J FPJ Cohlen B J BJ van de Laar-van Asseldonk T A M TAM Lambalk C B CB Goddijn M M Hompes P G PG van der Veen F F Mol B W J BWJ van Wely M M
Human reproduction (Oxford, England) 20200601 6
<h4>Study question</h4>Is endometrial thickness (EMT) a biomarker to select between women who should switch to gonadotropins and those who could continue clomiphene citrate (CC) after six failed ovulatory cycles?<h4>Summary answer</h4>Using a cut-off of 7 mm for EMT, we can distinguish between women who are better off switching to gonadotropins and those who could continue CC after six earlier failed ovulatory CC cycles.<h4>What is already known</h4>For women with normogonadotropic anovulation, ...[more]
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Project description: Not available
| S-EPMC9977112 | biostudies-literature
Project description:We aimed to investigate the effect of adding sildenafil vaginal gel to clomiphene citrate (CC) in infertile women with prior CC failure.MethodsThis is a self- controlled clinical trial. Women with CC failure (in prior 5 cycles) and thin endometrium were recruited (N = 42). In their 6th (CC only) cycle, women continued on CC 100 mg/ day for 5 days, and had measurement of endometrial thickness and Doppler assessment of uterine arteries on day of HCG administration. In the 7th cycle, women (N = 36) were given usual dose of CC supplemented with sildenafil vaginal gel (5 gm, containing 50 mg sildenafil) twice daily from cycle day 8 to day of HCG administration. Endometrial thickness and uterine artery Doppler were measured on the day of HCG injection.ResultsIn the 7th (CC + sildenafil vaginal gel) cycle, endometrial thickness was significantly higher than in the 6th (CC only) cycle (9.3 mm +/- 3.1mm versus 6.6 mm +/- 1.4 mm, respectively, P = < 0.001). Uterine artery pulsatility index dropped from 2.4 +/- 0.8 in 6th cycle to 1.6 +/- 1.3 in 7th cycle (P = 0.002). Clinical pregnancy rate increased but numbers were too small (only 3 pregnancies).ConclusionSildenafil vaginal gel significantly increased endometrial thickness and uterine blood flow, and may improve pregnancy rate in patients with CC failure due to thin endometrium. Mucoadhesive vaginal gel formulation allowed shorter duration of sildenafil application, and less frequent daily dosing.
| S-EPMC5506766 | biostudies-literature
Project description:ObjectiveTo determine whether endometrial thickness (EMT) differs between i) clomiphene citrate (CC) and gonadotropin (Gn) utilizing patients as their own controls, and ii) patients who conceived with CC and those who did not. Furthermore, to investigate the association between late-follicular EMT and pregnancy outcomes, in CC and Gn cycles.MethodsRetrospective study. Three sets of analyses were conducted separately for the purpose of this study. In analysis 1, we included all cycles from women who initially underwent CC/IUI (CC1, n=1252), followed by Gn/IUI (Gn1, n=1307), to compare EMT differences between CC/IUI and Gn/IUI, utilizing women as their own controls. In analysis 2, we included all CC/IUI cycles (CC2, n=686) from women who eventually conceived with CC during the same study period, to evaluate EMT differences between patients who conceived with CC (CC2) and those who did not (CC1). In analysis 3, pregnancy outcomes among different EMT quartiles were evaluated in CC/IUI and Gn/IUI cycles, separately, to investigate the potential association between EMT and pregnancy outcomes.ResultsIn analysis 1, when CC1 was compared to Gn1 cycles, EMT was noted to be significantly thinner [Median (IQR): 6.8 (5.5-8.0) vs. 8.3 (7.0-10.0) mm, p<0.001]. Within-patient, CC1 compared to Gn1 EMT was on average 1.7mm thinner. Generalized linear mixed models, adjusted for confounders, revealed similar results (coefficient: 1.69, 95% CI: 1.52-1.85, CC1 as ref.). In analysis 2, CC1 was compared to CC2 EMT, the former being thinner both before [Median (IQR): 6.8 (5.5-8.0) vs. 7.2 (6.0-8.9) mm, p<0.001] and after adjustment (coefficient: 0.59, 95%CI: 0.34-0.85, CC1 as ref.). In analysis 3, clinical pregnancy rates (CPRs) and ongoing pregnancy rates (OPRs) improved as EMT quartiles increased (Q1 to Q4) among CC cycles (p<0.001, p<0.001, respectively), while no such trend was observed among Gn cycles (p=0.94, p=0.68, respectively). Generalized estimating equations models, adjusted for confounders, suggested that EMT was positively associated with CPR and OPR in CC cycles, but not in Gn cycles.ConclusionsWithin-patient, CC generally resulted in thinner EMT compared to Gn. Thinner endometrium was associated with decreased OPR in CC cycles, while no such association was detected in Gn cycles.
| S-EPMC11228293 | biostudies-literature
Project description:BackgroundThe aim of this study was to compare the efficacy of the combination of clomiphene citrate (CC) and letrozole to that of CC alone in inducing ovulation in infertile women with ovulatory dysfunction.MethodsA randomized controlled trial was conducted at a single academic medical center between November 2020 and December 2021. Anovulatory infertility females, aged 18 to 40, were evenly distributed by a computer-generated block of four into two treatment groups. A "combination group" received a daily dose of CC (50 mg) and letrozole (2.5 mg), while a "CC-alone group" received a daily dose of CC alone (50 mg). The study medications were administered on days 3 through 7 of menstrual cycle. The primary outcome was the ovulation rate, defined by serum progesterone levels exceeding 3 ng/mL at the mid-luteal phase. The secondary outcomes were ovulation induction cycle characteristics, endometrial thickness, conception rate, and adverse events.ResultsOne hundred women (50 per group) were enrolled in the study. The mean age was not significantly different in both groups: 31.8 years in the combination group and 32.4 years in the CC-alone groups (P = 0.54). The prevalence of polycystic ovary syndrome in the combination and CC-alone groups was 48% and 44%, respectively (P = 0.841). According to intention-to-treat analysis, the ovulation rates were 78% and 70% in the combination and CC-alone groups, respectively (P > 0.05). There was no significant difference in the mean endometrial thickness or the number of dominant follicles of the groups. No serious adverse events were observed in either group.ConclusionsOur study found no significant difference between the combination of CC and letrozole and CC alone in inducing ovulation in infertile women with ovulatory dysfunction in one cycle. The small number of live births precluded any meaningful statistical analysis. Further studies are needed to validate and extend our findings beyond the scope of the current study.Trial registrationThe study was registered at https://www.thaiclinicaltrials.org with the following number: TCTR20201108004 and was approved on 08/11/2020.
| S-EPMC10647029 | biostudies-literature
Project description:ContextPolycystic ovary syndrome (PCOS), the most common endocrinopathy of reproductive-aged women, is characterized by ovulatory dysfunction and hyperandrogenism.ObjectiveThe aim was to compare gene expression between endometrial samples of normal fertile controls and women with PCOS.Design and settingWe conducted a case control study at university teaching hospitals.PatientsNormal fertile controls and women with PCOS participated in the study.InterventionsEndometrial samples were obtained from normal fertile controls and from women with PCOS, either induced to ovulate with clomiphene citrate or from a modeled secretory phase using daily administration of progesterone.Main outcome measureTotal RNA was isolated from samples and processed for array hybridization with Affymetrix HG U133 Plus 2 arrays. Data were analyzed using GeneSpring GX11 and Ingenuity Pathways Analysis. Selected gene expression differences were validated using RT-PCR and/or immunohistochemistry in separately obtained PCOS and normal endometrium.ResultsANOVA analysis revealed 5160 significantly different genes among the three conditions. Of these, 466 were differentially regulated between fertile controls and PCOS. Progesterone-regulated genes, including mitogen-inducible gene 6 (MIG6), leukemia inhibitory factor (LIF), GRB2-associated binding protein 1 (GAB1), S100P, and claudin-4 were significantly lower in PCOS endometrium; whereas cell proliferation genes, such as Anillin and cyclin B1, were up-regulated.ConclusionsDifferences in gene expression provide evidence of progesterone resistance in midsecretory PCOS endometrium, independent of clomiphene citrate and corresponding to the observed phenotypes of hyperplasia, cancer, and poor reproductive outcomes in this group of women.
| S-EPMC3100753 | biostudies-literature
Project description:PurposeThe aim of the study was to evaluate the effect of clomiphene citrate on uterine artery blood flow using pulsed Doppler and endometrial and subendometrial micro vascularization using 3D power Doppler in unexplained infertility.Patients and methodsIn a prospective observational study at a university teaching hospital, the mid-luteal (peri-implantation) endometrial thickness and volume, uterine artery pulsatility index (PI) and resistance index (RI), endometrial and subendometrial vascularization index (VI), flow index (FI), and vascularization flow index (VFI), and serum estradiol and progesterone levels were compared between natural and clomiphene citrate stimulated cycles in the same group of 50 patients with unexplained infertility. Statistical analysis was done using paired t-test to compare different study variables.ResultsThe primary outcome, which was the endometrial flow index, was significantly lower in the stimulated cycles (mean ± SD: 23.89±7.96 vs 27.49±8.73, mean difference (95% CI): -3.6 (-2, -5.9); P=0.03). The mean ± SD of endometrial thickness (10.92±3.04 vs 12.46±3.08 mm; P=0.01), volume (4.57±1.28 vs 5.26±1.32 cm3; P=0.009), endometrial VI (0.86±0.15 vs 0.95%±0.21%; P=0.02), VFI (0.25±0.08 vs 0.31±0.12; P=0.004), subendometrial VI (1.93±0.68 vs 2.26%±0.75%; P=0.02), FI (26.81±9.16 vs 30.73±9.87; P=0.04), and VFI (0.68±0.18 vs 0.79±0.21; P=0.006) were significantly lower in the stimulated cycles. However, there were no significant differences in the uterine artery PI (P=0.12) and RI (P=0.08) or serum estradiol (P=0.54) and progesterone (P=0.37) levels between natural and stimulated cycles.ConclusionPeri-implantation endometrial perfusion is significantly lower in clomiphene citrate stimulated cycles when compared to natural ones in patients with unexplained infertility.
| S-EPMC5894743 | biostudies-literature
Project description:Introduction: Which is optimal to treat clomiphene citrate-resistant polycystic ovary syndrome (CCR-PCOS) with LOD or metformin remains a problem. There are three inconsistent or even contradictory views. Objectives: The present meta-analysis aimed to evaluate the effectiveness and safety of Metformin with or without CC and to compare them with LOD with or without CC (Met/Met-CC vs. LOD/LOD-CC) in women with CCR-PCOS who also have anovulation. Data source: The PubMed, Cochrane, and Embase databases were searched to identify relevant studies reported between 1 Jan 1966 and 31 Aug 2019; the search was updated on 17 May 2022. Study eligibility criteria: We included randomized controlled trials (RCTs) of CCR-PCOS that had considered Met/Met-CC and LOD/LOD-CC as the exposure variables and fertility as the main outcome variable. Study appraisal and synthesis methods: We assessed study quality using the Cochrane risk-of-bias tool. The primary effectiveness outcome was live birth/ongoing pregnancy rate and the primary safety outcome was miscarriage rate. A fixed-effect meta-analysis was performed. The robustness of the results was assessed using sensitivity analyses. Meta-regression and subgroup analysis were performed to examine the reasons for heterogeneity. Publication bias was examined using the funnel plot, Egger linear regression, and Begg rank correlation tests. The quality of this meta-analysis was estimated according to the GRADE approach. This meta-analysis has been registered in PROSPERO (CRD42021240156). Results: Among 71 potentially relevant studies, we included five RCTs in our meta-analysis. We found no difference in effectiveness between Met-CC and LOD in terms of live birth/ongoing pregnancy (RR = 1.02, 95% CI: 0.87–1.21, z = 0.28; p = 0.780), and miscarriage rates (RR = 0.79, 95% CI: 0.46–1.36, z = 0.86; p = 0.390). I2 tests results revealed moderate or no heterogeneity (I2 = 51.4%, p = 0.083; I2= 0.0%; p = 0.952). Sensitivity analysis confirmed the robustness of the results. Funnel plot, Egger linear regression, and Begg rank correlation tests implied no publication bias (p > 0.05). LOD was more expensive than Met (€1050 vs. €50.16). The evidence quality was moderate. Conclusion: There is no evidence on the difference in the outcomes between the two interventions regarding ovulation, pregnancy, and live birth. As LOD is an invasive procedure and carries inherent risks, the use of Met/Met-CC should be the second-line treatment for women with CCR-PCOS. Systematic Review Registration: identifier CRD42021240156.
| S-EPMC9256960 | biostudies-literature
Project description:ObjectiveTo compare the efficacy of letrozole vs Clomiphene citrate for ovulation induction in PCOS women.MethodsThis double blind randomized controlled trial was conducted at Services Hospital, Lahore, from January 2016 to December 2020. Total 220 patients, diagnosed with PCOS according to Rotterdam criteria were randomly assigned into two groups after taking informed consent. The women were followed for ovulation, pregnancy and live birth rates in the next five consecutive menstrual cycles with either clomiphene citrate or letrozole.ResultsLetrozole had significantly better pregnancy rate (29.0% vs 15.4% p-value 0.015), monofollicular development (77.2% vs 52.7% p-value 0.000) and live birth rate (25.4% vs 10.9% p-value 0.005) as compared to clomiphene citrate. There was no difference between the two groups in ovulation rate (68.1% vs 63.6%, p-value 0.477), early pregnancy loss (3.6% vs 4.5% p-value 0.734), and twin pregnancy (0.0% vs 1.81% p-value 0.155). There was no ectopic pregnancy and no congenital anomalies in both groups. Hot flushes were higher in clomiphene group (31.8% vs 12.7% p-value 0.001) while fatigue (30.9% vs 8.1% p-value 0.000) and dizziness (21.8% vs 10.0% p-value 0.029) was higher with letrozole but these were well tolerated.ConclusionLetrozole is better treatment choice than clomiphene citrate in PCOS women with infertility in terms of pregnancy and live birth rate.ClinicalTrials.gov Identifier: NCT05702957.
| S-EPMC10772410 | biostudies-literature
Project description: Not available
| S-EPMC5850470 | biostudies-literature
Project description:BackgroundThe purpose of this study was to assess the effect of combining low dose of Coenzyme Q10 with clomiphene citrate on ovulation induction in polycystic ovary syndrome (PCOS) women with clomiphene resistance.MethodsA total of 149 women with clomiphene resistant PCOS who needed ovulation induction were randomly allocated to oral clomiphene citrate and Coenzyme Q10 group and oral clomiphene citrate only group using a computer generated allocation sequence. The study was conducted at Aziz Medical Center, Karachi, Pakistan from 1st July 2020 to 1st October 2020. Polycystic ovary syndrome was diagnosed according to Rotterdam criteria. The primary outcome was ovulation and conception rate per cycle. Chi square test and Fischer's exact test were used to compare these variables at p<0.05 level of significance.ResultsOf the 133 women assessed, the proportion of women who ovulated with combination (70% vs., 19%, p=0.001) was greater and the combination group had greater conception rate per cycle than those who received only clomiphene (48.6% vs. 6.3%, p<0.001). When stratified according to obesity, 85.3% of non-obese women who received combination ovulated whereas only 55.6% of obese women ovulated (p=0.002). Moreover, 48.6% of non-obese women conceived in the combination group as compared to 6.3% of obese women (p=0.007). Women who received combination were six times more likely to conceive than women who only received clomiphene citrate (AOR=6.344, 95% CI: 1.452-27.71, p=0.014).ConclusionCoenzyme Q10 is a valuable adjunct in women with PCOS undergoing ovulation induction. It improves ovulation and conception in women with clomiphene resistance.
| S-EPMC9666598 | biostudies-literature