Clomiphene Resistant PCOS Research Articles

Statement of Retraction: L-Carnitine plus metformin in clomiphene-resistant obese PCOS women, reproductive and metabolic effects: a randomized clinical trial

Statement of Retraction: L-Carnitine plus metformin in clomiphene-resistant obese PCOS women, reproductive and metabolic effects: a randomized clinical trial

Efficacy of Progestin Primed Ovarian Stimulation versus GnRH Antagonist Protocols in Clomiphene Resistant PCOS Undergoing ICSI Cycles. Randomized Controlled Trial (RCT) aa

Efficacy of Progestin Primed Ovarian Stimulation versus GnRH Antagonist Protocols in Clomiphene Resistant PCOS Undergoing ICSI Cycles. Randomized Controlled Trial (RCT) aa

Statement of Retraction: Combined metformin and clomiphene citrate versus highly purified FSH for ovulation induction in clomiphene-resistant PCOS women: a randomised controlled trial

Statement of Retraction: Combined metformin and clomiphene citrate versus highly purified FSH for ovulation induction in clomiphene-resistant PCOS women: a randomised controlled trial

Retraction.

El Sharkwy, I.A. and Abd El Aziz, W.M. (2019), Randomized controlled trial of N-acetylcysteine versus l-carnitine among women with clomiphene-citrate-resistant polycystic ovary syndrome. Int J Gynecol Obstet, 147: 59-64. https://doi.org/10.1002/ijgo.12902 The above article, published online on 4 July 2019 on Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal's Editor-in-Chief, Professor Michael Geary, the International Federation of Gynecology and Obstetrics and John Wiley & Sons Ltd. The journal's Editor-in-Chief was contacted by a third party who raised concerns about the article. The concerns related to the plausibility of the data, recruitment rates, and evidence that a study1 published earlier in Gynecological Endocrinology (with the same corresponding author and carried out in the same institutions) presented very similar data. The corresponding author was contacted and asked to respond to the concerns raised, but was unable to provide the data file for review. Following further review by an independent Research Integrity consultant, it was found that the pattern of identical digits in tables across the two published papers was implausible. In addition, it was noted that the p-values in the baseline tables did not match the data in the tables-it was not possible to reproduce the results in these tables, or those corresponding to the outcomes in the study. As a result, the journal is issuing this retraction due to continued concerns regarding the integrity of the data, which questions the validity of the previously reported results. REFERENCE El Sharkwy I, Sharaf El-Din M. L-carnitine plus metformin in clomiphene-resistant obese PCOS women, reproductive and metabolic effects: a randomized clinical trial. Gynecol Endocrinol. 2019;35(8):701-705.

Retraction Note: Does laparoscopic ovarian diathermy change clomiphene-resistant PCOS into clomiphene-sensitive?

Retraction Note: Does laparoscopic ovarian diathermy change clomiphene-resistant PCOS into clomiphene-sensitive?

Bariatric Surgery versus Dieting Regimen and Lifestyle change as a modality to improve Ovarian Function in Clomiphene-resistant PCOS Women

Obesity is worldwide spreading epidemic and deleteriously affects the metabolic and reproductive functions of females. The results of therapeutic lines provided for obese citrate-resistant women with polycystic ovary syndrome (CCR-POCS) were variable and discrepant.

Peculiarities of carbohydrate and lipid metabolism in infertile patients with clomifen-resistant form of polycystic ovarian syndrome and obesity

Medical ovulation induction with clomiphene citrate is currently the first line treatment for anovulatory women with PCOS. Clomiphene resistance (failure to ovulate after taking clomiphene) is common, occurring in approximately 15% to 40% of women with PCOS. Resistance is associated with an increased body mass index. The aim of the study was to elucidate the characteristics of carbohydrate and lipid metabolism in patients with clomiphene-resistant PCOS and obesity. Material and methods. A comprehensive examination of 97 infertile patients with PCOS with obesity and clomiphene-resistant PCOS and 46 conditionally healthy normoovulatory women of control group K with 18.5 ≤ body mass index (BMI) < 25 kg/m2, without clinical or biochemical signs of hyperandrogenism, with ovarian volume less than 9 cm3 and without previously known endocrine disease. Clinical-anamnestic, anthropometric, sonographic, immunochemical, enzyme-linked immunosorbent assay, colorimetric, statistical research methods are used. Results and discussion. It was found that the most characteristic features of carbohydrate metabolism disorders in clomiphene-resistant women with PCOS and obesity are increased levels of hypoglycemic index, C-peptide, glucose levels after 2 h in oral glucose tolerance test, HOMA index; and of lipid metabolism - an increase in atherogenic factor, triglycerides, total cholesterol on the background of increased production of leptin and vaspin and decreased secretion of adiponectin, omentin and visfatin.. Conclusions. Visceral obesity plays an important role in the development of insulin resistance and hyperinsulinemia in infertile patients with clomiphene-resistant PCOS and obesity. This category of women in preconception training, before carrying out ovarian drilling or controlled ovarian stimulation, it is necessary to correct disorders of carbohydrate and lipid metabolism.

Correlation between serum carnitine level and Soluble Receptors for Advance Glycation End Products(sRAGE) in Clomiphene Citrate Resistant- PCOS Women

The most frequently diagnosed condition in women at the age of reproduction is the polycystic ovarian syndrome (PCOS).it could be related to a complex endocrine condition, due to its heterogeneity and uncertainty about its etiology, as the clinical highlights of PCOS incorporate those related to reproductive signs such as decreased frequency of ovulation, irregular menstrual cycles, decreased fertility. Carnitine plays a substantial role in weight loss, glucose tolerance, insulin function and fatty acid metabolism. Thus carnitine plays a crucial role in controlling obesity, insulin resistance, oxidative stress that are associated with PCOS .While, AGEs are a diverse group of reactive molecules that are formed endogenously by non-enzymatic reactions of carbonyl group of carbohydrates with free amino groups of proteins, nucleic acids or lipids. The soluble form of receptors of AGE (sRAGE) could play an important role in management obesity, insulin resistance, hyperandrogenism, oxidative stress which could be related to PCOS. This study was aimed to investigate serum levels of carnitine & soluble receptors for advanced glycation end products (sRAGE) in clomiphene resistant PCOS .Besides assessing the correlation between serum levels of carnitine ,as well as, soluble receptors of AGE with hormonal ( LH, FSH& Testosterone) and metabolic ( serum glucose , serum insulin & HOMA-IR) markers in these patients .
 The study included thirty women with clomiphene resistant PCOS and thirty apparently healthy women, as a control .In order to measure serum total carnitine and serum soluble receptor of advance glycation end product (sRAGE in PCOS and control groups.
 The results of our study have shown a decreased serum levels of total carnitine in PCOS group in comparison with control group (48.05 and 59.73 nmol/ml, respectively), but there was no significant elevation in serum levels of sRAGE in patients group as compared with control group .In addition to a significant correlation between serum total carnitine and serum sRAGE levels (r=0.45, P-value=0.03). 
 In conclusion serum total carnitine level was low in Clomiphene resistant-PCOS patients in comparison with control group. Although, sRAGE levels in clomiphene resistant- PCOS patients were not significantly different from the age and BMI-matching controls, but a significant correlation between serum total carnitine and sRAGE was detected.
 Key words: Poly cystic ovarian syndrome, soluble receptor of advance glycation end products (sRAGE) , SerumTotal Carnitine

Rosiglitazon Meleat’ın Klomifen Sitrata Dirençli Polikistik Over Sendromlu İnfertil Olgularda Tek Başına veya Klomifen Sitratla Kombine Kullanımının Karşılaştırılması

INTRODUCTION: Most of the obese PCOS patients are resistant to clomiphene citrate standard doses. In these cases metabolic syndromes are treated by using insulin sensitizing drugs so that ovulation can be achieved.In this study rosiglitazine maleat was used in order to induce ovulation in obese clomiphene resistant PCOS patients. METHODS: 30 women(18-40 year old) with clomiphene resistant polycystic ovary syndrome that were obese (BMI>25 kg/m2) and hyperinsulinemic were seperated in two groups. In the first group (n=15) oral antidiabetic Rosiglitazone maleate( 4mg bid) which belongs to thiazolidinediones were used.In the second group(n=15) in addition to clomiphen citrate(50 bid)and Rosiglitazone maleate(4 mg bid) were used, ovulation and pregnancy rates were compared. In both groups ovulation and pregnancy were recorded, in the second group ovulation and pregnancy rates were higher than the first group but these rates were not significant. RESULTS: In group 1, ovulation was achieved in 5 patients (%33) and pregnancy was achieved in 1 patient (%7). In group 2, ovulation was achieved in 9 patients (%60) and pregnancy was achieved in 3 patients (%20).There was no statistical significance between two groups. DISCUSSION AND CONCLUSION: In our study in obese and hyperinsulinemic patients rosiglitazone maleat can induce ovulation and in addition to clomiphene citrate also ovulation can be achieved although it is statistical insignificant. As a result Rosiglitazone maleate can be used alternatively as an insulin sensitizer and ovulation induction agent.

Comparative study between L-carnitine versus co-enzyme Q10 as an adjuvant therapy to clomiphene resistant pcos women on improving pregnancy rate and prevention of early pregnancy loss

Aim of the work: Compare the effectiveness of L-carnitine versus Co-enzyme Q10 on improving pregnancy rates and decraese the rate of early pregnancy loss in patients with PCO resistant to clomiphene citrate.Setting and Design: A prospective randomized controlled study conducted in infertility clinic of a tertiary care center from June 2017 to June 2019.Patients and Methods: A total of 225 subjects presenting with infertility and diagnosed with PCOS (based on Rotterdam criteria 2003) and resistant to clomiphene citrate were enrolled in the study. Subjects were randomly allocated into three groups. Group A: received clomiphene citrate (CC) only, Group B: received clomiphene citrate plus L-carnitine (2gm). Group C: received clomiphene citrate plus co- enzyme Q10 (200 mg). Main outcome measures include the ovulation rate, cumulative clinical pregnancy rate (CPR) are the primary outcome measures.Results: The ovulation rate was significantly higher among the groups B,C compared to group A (62.5%, 66.6% vs 18.3% respectively). Total number of cases who get pregnant were higher in Group B 35(47.3%), Group C 33(44.6%) compared to Group A 6(8.1%). Cumulative Clinical pregnancy rate was 3%, 49.3%, and 47.8% for Group A, Group B, and Group C, respectively. The abortion rate was low in Group B 4 % and significantly lower in Group C 2.7% compared to Group A 6.7%. Conclusion: Adding either L-carnitine or Co-enzyme Q10 to clomiphene citrate in patients with clomiphene-resistant PCOS were beneficial in increasing the quality of ovulation, the clinical pregnancy rate ،also in decreasing the rate of early pregnancy loss.

Impact of laparoscopic ovarian drilling on the pregnancy rate in clomiphene-resistant polycystic ovarian syndrome patients undergoing in vitro fertilization: randomized controlled trial

BackgroundThe main objective of this randomized controlled trial was to study the impact of LOD on the pregnancy rate after ICSI-ET in PCOS.ResultsThe study was conducted in Egypt in the period 2015–2017 and included 212 clomiphene-resistant PCOS patients, with at least 1-year infertility. The study group was the drilling group who underwent LOD and then ICSI-ET, while the control group did not undergo LOD but directly proceeded to ICSI-ET. The primary outcome was the clinical pregnancy rate per ET cycle. The baseline characteristics and hormonal profiles were comparable (p > 0.05) between the two groups. Ovarian stimulation days were (p < 0.001) higher in the drilling group. Endometrial thickness, estradiol at triggering day, and the number of oocytes retrieved were (p < 0.001) lower in the drilling group. The numbers of embryos transferred were not different (p > 0.05). The clinical pregnancy rate per ET cycle was higher in the drilling group (51%) than in the control group (37%) (p = 0.046). Multiple pregnancies were not significantly (p = 0.265) different between groups. The rate of OHSS was (p = 0.046) higher in the control group. Coasting was (p < 0.001) higher in the control group (18%) compared to the drilling group (2%).ConclusionLaparoscopic ovarian drilling for PCOS patients before ICSI-ET improves the clinical pregnancy rate with a reduction of OHSS.Trial registrationClinical Trial Registration: Pan African Clinical Trials Registry (PACTR), PACTR201604001567272, 5 April 2016.

Coenzyme q 10 and Fertility Outcome in Women With Clomiphene Resistant PCOS

Coenzyme q 10 and Fertility Outcome in Women With Clomiphene Resistant PCOS

Laparoscopic Ovarian Drilling Improves Endometrial Homeobox Gene Expression in PCOS.

The study was designed to investigate whether laparoscopic ovarian drilling (LOD) of ovaries alters the expression levels of HOXA-10 and HOXA-11 mRNA in the endometrium of infertile women with clomiphene-resistant PCOS. Expression of HOXA-10 and HOXA-11 mRNA in the endometrium obtained before and after LOD during the midsecretory phase was measured. Expression of each gene was evaluated using real-time reverse transcriptase polymerase chain reaction (RT-PCR). Expression levels of HOXA-10 and HOXA-11 mRNA were lower in endometrium of patients with PCOS before LOD compared with fertile controls. But the differences failed to show statistical significance. Compared with fertile subjects, LOD of PCOS ovaries up-regulated endometrial HOXA-10 and HOXA-11 mRNA expression. Fold changes of HOXA-10 and HOXA-11 mRNA after LOD were found to be 4.46 and 4.19, respectively. Fold change increase in HOXA-10 and HOXA-11 mRNA was found to be statistically significant (P < .01, P < .02). There is a receptivity defect in the endometrium of women with PCOS that affects fertility regardless of other causes of infertility. LOD increases endometrial HOXA-10 and HOXA-11 mRNA expressions and improves receptivity in patients with clomiphene-resistant PCOS.

Effect of Adding L-Carnitine to Clomiphene Resistant PCOs Women on the Ovulation and the Pregnancy Rate

Background: polycystic ovary (PCO) syndrome is an endocrionologic disorder that affecting about 6-10% of women in their reproductive age. Conception rate with clomiphene citrate treated cycles is about 40% only and the number of ovulated oocyte decrease significantly with repeated cycles of ovulation. Objective: evaluation of the effectiveness of usage of clomiphene citrate with L-carnitine (LC) in induction of ovulation in clomiphene citrate resistant patients. Patients and Methods: Randomized controlled study included a total number of 50 women with clomiphene-resistant PCOs. They were divided into 2 groups, group (A) where patients received 100 to 150 mg clomiphene citrate from day three until day seven of the cycle and L-carnitine (LC) 3g daily till positive pregnancy test and group (B) received 100 to 150 mg clomiphene citrate with placebo. Results: There was statistically significant difference (p-value 17 mm and E2 on day of HCG injection. Conclusion: Adding L-carnitine to clomiphene from the follicular phase and extending through the luteal phase in patients with clomiphene-resistant PCOS, at the given dose and duration, may be of beneficial to the quality of ovulation and the clinical pregnancy rate.

Drospirenone Containing Combined Oral Contraceptive Premedication before Letrozole Ovulation Induction in Clomiphene Resistant PCOS, Is it Worth the Wait?

Drospirenone Containing Combined Oral Contraceptive Premedication before Letrozole Ovulation Induction in Clomiphene Resistant PCOS, Is it Worth the Wait?

RETRACTED ARTICLE: l-Carnitine plus metformin in clomiphene-resistant obese PCOS women, reproductive and metabolic effects: a randomized clinical trial

We, the Editor and Publisher of Gynecological Endocrinology, have retracted the following article: Ibrahim El Sharkwy & Mostafa Sharaf El-Din (2019) L-Carnitine plus metformin in clomiphene-resistant obese PCOS women, reproductive and metabolic effects: a randomized clinical trial, Gynecological Endocrinology, 35:8, 701–705, DOI: 10.1080/09513590.2019.1576622 Since publication, significant concerns have been raised about the integrity of the data and reported results in the article. When approached for an explanation, the authors have not adequately addressed the concerns raised, and they have not provided their original data to verify that the research and published article comply with the journal’s Editorial Policies. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The authors have been informed, and they do not agree with the retraction. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted.’

Long-term use of clomiphene citrate in induction of ovulation in PCO patients with clomiphene citrate resistance

ObjectiveThe aim of our study to evaluate the effect of extended clomiphene citrate treatment on the ovulation rate, pregnancy rate, and hormonal profile of clomiphene resistant PCOS. MethodologyThis a prospective study conducted in Maternity Hospital Minia University, 200 patients with PCOS recruited in the study during the period from September 2015 till February 2016 (6 months was duration of the study), they were diagnosed as PCO with clomiphene resistance before being recruited in the study. They received 150mg clomiphene citrate for 10 days start in 2nd day of cycle for three consecutive cycles, and followed up for another three months without treatment, last follow-up cycle was on February. We studied the effect of extended treatment with CC in ovulation rate, pregnancy rate and hormonal profile in patients before and after treatment. ResultsThere was significant improvement in ovulation rate in the patients after extended CC treatment for 3 months and 3 months follow-up (as 12 cases in the first cycle and 32 cases in the second cycle and increased to 76 cases in the third cycle) while no ovulation documented before treatment pregnancy rate was 17% itis generally low but it highly significant when compared with was zero preceding treatment. ConclusionExtended CC treatment is good method to improve ovulation and pregnancy rate in CC resistant PCOS but further multi-center studies are needed to provide more powerful evidence.

Tamoxifen versus letrozole in combination with clomiphene citrate to stimulate ovulation in clomiphene-resistant PCOS women

Tamoxifen versus letrozole in combination with clomiphene citrate to stimulate ovulation in clomiphene-resistant PCOS women

Serum Leptin, Ghrelin and Insulin Resistance in Iraqi Women with Clomiphene Resistance Polycystic Ovary Syndrome

Background: Polycystic ovary syndrome is the most common endocrine disorder in women with reproductive age. it has a multifactorial etiology characterized by menstrual irregularities, manifesting as oligomenorrhea or amenorrhea, a part of abnormalities of hyperandrogenism and polycystic ovaries. Recent evidence has demonstrated the complex function of adipose tissue and stomach as endocrine organs through release of hormones into the blood stream involved in physiological activities of the body with potential implication in PCOS development. One of the most important of these hormones are ghrelin, leptin and insulin that have role in process of PCOS development. Aims of the study: The aim of present study to evaluate serum ghrelin, leptin and insulin resistance in clomiphene resistance PCOS women and to find correlation between these parameters. Methodology: During Sep 2013 to May 2014, already diagnosed infertile Iraqi women with PCOS they are recruited in the private medical clinic of Dr. Ahlam ali naser during their periodic visit. There were 23 girls at mean age 21.3±1.2 on clomiphene therapy as clomiphene resistant PCOS group (CR-PCOS), 25 PCOS girls at mean age 23.5±1.4 consumed drugs other than clomiphene for PCOS treatment consider as (OT-PCOS) and 20 girls at mean age 22±2.4 as control group included in the present study. Blood samples were taken after at least 8 hours of fasting in all PCOS girls and control, serum glucose, ghrelin and leptin were measure, insulin resistance value were calculated using HOMA-IR model. Results: The highest Ghrelin, leptin and IR levels were observed in CR-PCOS group and this level considered significantly high when compared with control and OT-PCOS groups. The only significant positive correlation between IR and ghrelin was observed in CR-PCOS group with no significant correlation in all study groups were observed. In other hand when we make correlation between ghrelin and study parameters, significant negative correlations that observed with leptin in control group not observed in CR-PCOS and OT-PCOS, meanwhile no significant correlation between ghrelin and leptin or IR in OT-PCOS group. Conclusions: Women with clomiphene resistance PCOS exhibit significantly increased serum ghrelin, leptin and insulin resistance levels than control subjects and PCOS women taking therapy other than clomiphene indicating good biochemical markers in detection clomiphene resistance status in PCOS women. Furthermore we speculate significant positive correlation between ghrelin and IR in CR-PCOS group. Recommendation: Assessment of ghrelin and leptin levels in women taking metformin and clomiphene combination therapy for PCOS treatment

Ovarian reserve after fixed versus adjusted laparoscopic ovarian drilling in clomiphene resistant PCOS patients

To evaluate the impact of fixed versus adjusted laparoscopic ovarian drilling (LOD) on ovarian reserve assessed by serum anti-Mullerian hormone (AMH), basal follicle stimulating hormone (FSH ), antral follicle count (AFC) and ovarian volume in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS).