Citrate-resistant Polycystic Ovary Syndrome Research Articles

Correlation of serum leptin and ghrelin levels with endocrine and reproductive parameters in women with clomiphene citrate resistant polycystic ovary syndrome.

Objective:To investigate the changes in serum ghrelin and leptin levels in patients with clomiphene-resistant polycystic ovary syndrome (PCOS).Materials and Methods:Thirty-five patients who could not achieve ovulation or pregnancy despite using 150 mg/day of clomiphene citrate (CC) participated in the study. Thirty-five patients who were compatible with the study group in terms of age and body mass index (BMI) but did not have clinical and laboratory findings of PCOS constituted the control group. On the third day of the cycle, in addition to the basal hormone profile, ghrelin and leptin levels were also measured. Patients in both groups went to IVF/ICSI. Basal hormone values, leptin, ghrelin, metabolic, demographic parameters, and clinical pregnancy rates were correlated.Results:Patients in both groups were recorded to be similar in terms of age (29.4±0.11 vs 28.5±7.30), BMI (24.3±3.07 vs 23.8±1.55), and infertility time (6.14±4.30 vs 6.03±1.28). Serum ghrelin levels of the PCOS group were significantly lower than the control group (0.48±2.21 vs 1.19±4.02) Serum leptin levels of the PCOS group were significantly higher than the control patients (45.6±304 vs 16.5±0.32). Serum leptin levels and BMI (r=0.65, p<0.01) A positive correlation was found between luteinizing hormone (LH) (r=0.53, p<0.02), and insulin resistance (r=0.74, p<0.03). There was a negative (r=-0.76, p<0.03) correlation between serum ghrelin and LH. A positive and significant correlation was found between serum ghrelin, testosterone, mature oocyte, and implantation rates.Conclusion:Serum ghrelin correlates with fertility outcomes in women with CC-resistant PCOS undergoing IVF/ICSI.

Unilateral versus Bilateral Laparoscopic Ovarian Drilling in Clomiphene Citrate Resistant Polycystic Ovarian Syndrome in Minia Governate: Randomized Clinical Trial

Unilateral versus Bilateral Laparoscopic Ovarian Drilling in Clomiphene Citrate Resistant Polycystic Ovarian Syndrome in Minia Governate: Randomized Clinical Trial

Controlled ovarian hyperstimulation with gonadotropins for Clomiphene Citrate resistant Polycystic ovary syndrome leads to a higher risk of ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) caused by controlled ovarian hyperstimulation ,although usually regressingspontaneously, may occasionally occur with clomiphene citrate, typically with gonadotropin, which sometimes results in seriouscomplications. 25-year-old patient was followed up in our hospital due to OHSS. Since our patient was Clomiphene Citrate (CC)resistant Polycystic ovary syndrome (PCOS), follitropin alpha was started. Firstly, treatment started from 75 IU rFSH. Increasedto 150 IU on day 15, if no improvement in the ovaries. Due to the development of two 18 mm follicles on the 21 st day and theE2 value being 773 pg/mL, human chorionic gonadotropin (hCG) was applied and insemination was performed. Patients with CCresistant PCOS represent a challenge for reproductive medicine. We propose a calculated low-dose stimulation strategy with step-up according to ovarian response in gonadotropins protocols. If the treatment period is extended and the dose is increased; Even ifthe follow-up values are normal, the patient should be closely monitored to avoid OHSS.

Increased oxidative stress is associated with thiol/disulphide homeostasis in clomiphene citrate resistant polycystic ovary syndrome

The purpose of this study was to evaluate the relation CC resistant PCOS and the thiol/disulphide homeostasis, used as a marker of OS, by measuring that exchange using a novel technique. Sixty women patients admitted to the infertility clinic were evaluated. The patients were divided into two groups. Group 1 comprised 30 infertile PCOS patients with CC resistance; Group 2 was the control group comprising 30 infertile PCOS patients with CC sensitivity. Serum total thiol (p = .024), native thiol (p = .0052), disulphide (p = .003), index 1 (p = .001), index 2 (p = .001) and index 3 (p = .001), HOMA-IR (p < .001) and free testosterone (p < .001) were statistically significant. The independent variables BMI and age effects were adjusted according to the logistic regression method with groups. Significant differences were observed between the two groups in the levels of native thiol (p* = .0042), total thiol (p* = .024), disulphide (p* = .0003), index 1 (p* = .0001) index 2 (p*= .0001), index 3 (p* = .0001), HOMA-IR (p* = .0044), insulin (p*= .032) and free testosterone (p* = .0001) values. The thiol/disulphide homeostasis viewed in favour of OS. Like a reflection of OS in the follicular endocrine microenvironment may be linked with increased thiol/disulphide homeostasis, free testosterone, insulin and HOMA-IR levels. Impact statement What is already known about this subject? In previous studies, thiol/disulphide homeostasis was compared between PCOS and control groups. In this study, serum thiol/disulphide homeostasis was measured in infertile PCOS patients resistant to CC for the first time. What do the results of this study add? Disulphide concentrations were significantly higher in patients with CC resistant patients thanthe control group. This shows us that more OS occurs in the CC-resistant group. What are the implications of these findings for clinical practice and further research? Thiol/disulphide homeostasis will be a guide for PCOS management in patients with CC-resistant PCOS.

Step-up protocol gonadotrophin versus laparoscopic ovarian drilling in clomiphene citrate resistant PCOS infertile women in two Iraqi hospitals

Background: Polycystic ovarian syndrome is a common endocrine disorder affecting 6-10% of women of reproductive age and the most common cause of anovulatory infertility.&#x0D; Objective: The aim of the study was to compare the effectiveness, side effects and outcomes of step-up gonadotrophin protocol versus laparoscopic ovarian diathermy (LOD) in infertile patients with clomiphene citrate resistant polycystic ovary syndrome.&#x0D; Methods: The sample included women who attended our infertility clinic at Al-Elwiya Maternity Teaching Hospital and Kamal Al-Samarraee for Infertility and IVF Hospital in Baghdad/ Iraq from November 2013 to November 2014. Eighty cases of infertile women with polycystic ovarian syndrome who failed to ovulate with clomiphene citrate for six months where collected, forty women treated with step-up protocol with low dose recombinant FSH gonadotrophin which increased gradually according to ovulation response, another forty women treated with LOD. Ovulation monitoring in each group was done with transvaginal ultrasound to exclude monofollicullar, bifollicular ovulation, ovarian hyperstimulation syndrome, multiple pregnancy and pregnancy rate in each cycle for 6 cycles.&#x0D; Results: Higher unifollicular ovulation and pregnancy rate in LOD than step-up protocol (91.4% &amp; 25% versus 75% &amp; 10%) respectively, while multifollicular and hyperstimulation rate were higher in gonadotrophin group (24.3% &amp; 0.1% versus 8.50% &amp; nil) respectively.&#x0D; Conclusion: Ovulation induction and pregnancy rate per cycle was higher with LOD group, not time consuming, also there was no risk of hyperstimulation of the ovary or twin pregnancy as compared to the step-up protocol with gonadotrophin

Clomiphene Citrate Combined with Tamoxifen Citrate versus Letrozole for Inducing Ovulation in Patients with Clomiphene Citrate -Resistant Polycystic Ovary Syndrome

This prospective observational study was conducted on 242 patients with clomiphene citrate (CC) resistant polycystic ovary syndrome (PCOS) who were allocated into two regimens of induction of ovulation, the first group(n=128) received both CC and tamoxifen and the second (n=114) received letrozole. The ovulation rate, endometrial thickness, number of dominant follicles, pregnancy rate, miscarriage rate and live birth rate were found comparable between the two groups. Combined therapy with CC and tamoxifen is beneficial in patients with PCOS who failed to respond to CC alone.

Effect of Metformin Only versus Effect of Metformin and Corticosteroids after Laparoscopic Ovarian Drilling on Ovulation in Women with Clomiphene Citrate Resistant Polycystic Ovary Syndrome

Background: the syndrome of polycystic ovary syndrome (PCOS) is clinically and biochemically heterogeneous. Medical treatment of PCOS is tailored to the patient's goals. Broadly, these may be considered fewer than four categories: lowering of insulin levels, restoration of fertility, treatment of hirsutism acne and restoration of regular menstruation. Objective: this study aimed to study the effect of Metformin alone after laparoscopic ovarian drilling on ovulation in women with clomiphene citrate resistant polycystic ovary syndrome in comparison with studying the effect of Metformin with Dexamethasone after laparoscopic ovarian drilling on ovulation in women with clomiphene citrate resistant polycystic ovary syndrome. Methodology: in the present study, 60 patients with PCO were resistant to clomiphene citrate therapy had undergone ovarian drilling. Those patients had been classified into 2 groups according to the selected therapy. Two trails had been compared; group A received metformin (850 mg twice daily) plus dexamethasone (2mg daily from day 5 to day 14 monthly) for 3 months while group B had received metformin only (850 mg twice daily). Results: our study showed no significant correlation between serum progesterone level after therapy and different parameters in both study groups. Conclusion: we concluded that there was a good value of administration of Dexamethasone with Metformin after laparoscopic ovarian drilling in patients with clomiphene resistant polycystic ovarian disease especially those patients with normal DHEAS levels.

Effect of Metformin Only versus Effect of Metformin and Corticosteroids after Laparoscopic Ovarian Drilling on Ovulation in Women with Clomiphene Citrate Resistant Polycystic Ovary Syndrome

Background: the syndrome of polycystic ovary syndrome (PCOS) is clinically and biochemically heterogeneous. Medical treatment of PCOS is tailored to the patient's goals. Broadly, these may be considered fewer than four categories: lowering of insulin levels, restoration of fertility, treatment of hirsutism acne and restoration of regular menstruation. Objective: this study aimed to study the effect of Metformin alone after laparoscopic ovarian drilling on ovulation in women with clomiphene citrate resistant polycystic ovary syndrome in comparison with studying the effect of Metformin with Dexamethasone after laparoscopic ovarian drilling on ovulation in women with clomiphene citrate resistant polycystic ovary syndrome. Methodology: in the present study, 60 patients with PCO were resistant to clomiphene citrate therapy had undergone ovarian drilling. Those patients had been classified into 2 groups according to the selected therapy. Two trails had been compared; group A received metformin (850 mg twice daily) plus dexamethasone (2mg daily from day 5 to day 14 monthly) for 3 months while group B had received metformin only (850 mg twice daily). Results: our study showed no significant correlation between serum progesterone level after therapy and different parameters in both study groups. Conclusion: we concluded that there was a good value of administration of Dexamethasone with Metformin after laparoscopic ovarian drilling in patients with clomiphene resistant polycystic ovarian disease especially those patients with normal DHEAS levels.

Adding Prednisolone During Ovulation Induction with Clomiphene Citrate in Lean Women with Clomiphene Citrate Resistant Polycystic Ovarian Syndrome

Background: polycystic ovarian syndrome (PCOS) is a common cause of chronic anovulation; insulin resistance is considered an accepted mechanism for anovulation in PCOS especially in obese patients. Excess adrenal androgens are observed in patients with PCOS. An inverse relationship exists betweenDehydroepiandroste- rone sulfate (DHEAS) the body mass index (BMI). The use of cor- ticosteroids could improve ovulation in PCOS by decreasing serum androgen level. Objective: Evaluation of the efficacy of concomitant administra- tionof prednisolone and clomiphene citrate (CC) for the ovulation inductionin infertile lean women having CC-resistant polycystic ovarian syndrome(PCOS). Methods: Three hundred infertile lean women with clomiphene ci- trate (CC) resistant PCOS were randomly divided into two groups. Group 1:150 patient received clomiphene citrate (5 consecutive days of 150mg daily starting from the second day of the cycle) and pred- nisolone tablet (10 consecutive days of 10mg daily starting from the second day of the cycle). Group 2:150 patientreceived the same pro- tocol of CC plus placebo (10 consecutive days of 0.5mg folic acid daily starting from the second day of the cycle). All patientsshowed clinical manifestations of Hyperandrogenism (variable degree of hir- sutism and/or acne) where 18 patients were dropped out, and data on all relevant outcomes were available for 282 women and data were analyzed from 143 women in the CC-Prednisolone group and 139 in the CC-placebo group. The main outcome was the ovulation rate. Secondary measures included a number of follicles 18 mm or more, endometrial thickness on day of HCG administration and clinical pregnancy rate. Ovarian follicular response was monitored by trans- vaginal ultrasound and mid-luteal phase serum progesterone. HCG 10000 IU was given when at least one follicle measured 18 mm, and timed intercoursewas advised. Results: There were no statistically significant differences between groups as regards age, duration of infertility, BMI,the serum level of FSH, LH, TSH,and prolactin. The mediannumber offollicles ≥18 mm) at the time of HCG administration and the mean endometri- al thickness wassignificantly higher in the prednisolone group than in the placebo group (P < 0.001).Similarly, there were significantly higher rates of ovulation (58.7% versus 23%) (P < 0.001) in the pred- nisolone group. The clinical pregnancy rate was significantly higher in the prednisolone group (p =0.006). Conclusion: The addition of prednisolone to CC in CC-resistant PCOS infertilelean patients was significantlyassociated with a higher ovulation rate, number of ovarian follicles ≥18 mm and en- dometrial thicknesson day of HCG administration, and number of patients becameclinical pregnant

Simultaneous Letrozole and Clomiphene Citrate versus Letrozole Alone in Clomiphene Citrate Resistant Polycystic Ovary Syndrome: A Randomised Controlled Trial

Background: Polycystic ovary syndrome (PCOS) is a common cause of anovulatory infertility. The therapeutic strategies for clomiphene citrate (CC)- resistant patients include the addition of corticosteroids, extended duration of clomiphene, gonadotrophin therapy, laparoscopic ovarian drilling, in vitro fertilization or the use of aromatase inhibitors recently. Letrozole decreases estrogen levels in the body, so it releases the hypothalamus and/or pituitary gland from the negative feedback of estrogen. This increases levels of gonadotrophins, which stimulates follicular growth. Objectives: To evaluate the role of letrozole alone and simultaneous use of letrozole and clomiphene citrate (CC) for ovulation induction in patients with clomiphene citrate-resistant PCOS (CCR-PCOS). Patients and Methods: This open-label randomised controlled study was conducted in the Department of Obstetrics and Gynecology, Faculty of Medicine, Zagazig University, Egypt during the period from February 2018 to June 2019. The study included 60 CCR-PCOS patients who were randomly allocated by independent personnel into two arms: group A (letrozole alone) or B (letrozole + CC). In either group, monitoring the mean follicular diameter and endometrial thickness in the days 10, 12, and 14 of the cycle by transvaginal ultrasound and Measurement of serum Progesterone (ng/ml) 7 days after the expected time of ovulation. Results: We investigated various clinical and sonographic factors that may predict the outcome of the method of induction of ovulation in CCR-PCOS with no significant affection for the results. There was a non-significant difference between the studied groups regarding ovulation and pregnancy per cycle or per patient. Conclusion: Letrozole alone or simultaneous use of letrozole and CC offers a good second-line option for induction of ovulation in CCR-PCOS patients. However, the combination of CC and letrozole did not add any benefit over the use of letrozole alone regards ovulation rate, follicular volume, endometrial thickness, pregnancy rate and live birth rate.

The Effect of Vitamin D3 and Co-enzyme Q10 Supplementation on Metabolic Biomarkers in Women with Clomiphene Citrate Resistant Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) one of the most common endocrine disorders in women of reproductive age, the pathogenesis of PCOS imitated to be as a vicious cycle involving both hyperandrogenaemia and insulin resistance/hyperinsulinemia. Vitamin D deficiency (VDD) is common among women with PCOS (approximately 67%–85% women with PCOS have VDD). Vitamin D3 and CoQ10 could affect glucose metabolism and insulin sensitivity and improve metabolic abnormalities in PCOS. The study was designed to evaluate the effect of combining oral vitamin D3 tablet or CoQ10 capsule with clomiphene citrate on metabolic biomarkers in women with clomiphene citrate resistance PCOS patients. A prospective interventional randomized-controlled, open-label study include 41 PCOS patients aged range (18-34)years who are clomiphene citrate resistant divided into two groups, group 1 (n=24) whose endogenous vitamin D status less than 20ng/ml receive clomiphene citrate 100mg daily(for 5 days monthly induction) plus vitamin D 10000IU daily (2 months) and group 2 (n=17) whose endogenous vitamin D status equal or more than 20ng/ml receive clomiphene citrate 100mg daily(for 5 days monthly induction) plus CoQ10 200mg daily (2 months). Fasting blood samples were taken at baseline and 2 months after intervention to measure metabolic biomarkers [fasting serum insulin (FSI), fasting blood glucose (FBG), homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI)]. After 2 months both interventions result in non-significant change in FSI and FBG while HOMA-IR and QUICKI decreased by both interventions, but the decrease is significant only with CoQ10 supplementations. In conclusion, Vitamin D and CoQ10 supplementation result in improvement in HOMA-IR and QUICKI but the improvement was more obvious in CoQ10 group.

The Effect of Vitamin D3 and Co-enzyme Q10 Supplementation on Metabolic Biomarkers in Women with Clomiphene Citrate Resistant Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) one of the most common endocrine disorders in women of reproductive age, the pathogenesis of PCOS imitated to be as a vicious cycle involving both hyperandrogenaemia and insulin resistance/hyperinsulinemia. Vitamin D deficiency (VDD) is common among women with PCOS (approximately 67%–85% women with PCOS have VDD). Vitamin D3 and CoQ10 could affect glucose metabolism and insulin sensitivity and improve metabolic abnormalities in PCOS. The study was designed to evaluate the effect of combining oral vitamin D3 tablet or CoQ10 capsule with clomiphene citrate on metabolic biomarkers in women with clomiphene citrate resistance PCOS patients. A prospective interventional randomized-controlled, open-label study include 41 PCOS patients aged range (18-34)years who are clomiphene citrate resistant divided into two groups, group 1 (n=24) whose endogenous vitamin D status less than 20ng/ml receive clomiphene citrate 100mg daily(for 5 days monthly induction) plus vitamin D 10000IU daily (2 months) and group 2 (n=17) whose endogenous vitamin D status equal or more than 20ng/ml receive clomiphene citrate 100mg daily(for 5 days monthly induction) plus CoQ10 200mg daily (2 months). Fasting blood samples were taken at baseline and 2 months after intervention to measure metabolic biomarkers [fasting serum insulin (FSI), fasting blood glucose (FBG), homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI)]. After 2 months both interventions result in non-significant change in FSI and FBG while HOMA-IR and QUICKI decreased by both interventions, but the decrease is significant only with CoQ10 supplementations. In conclusion, Vitamin D and CoQ10 supplementation result in improvement in HOMA-IR and QUICKI but the improvement was more obvious in CoQ10 group.

Efficacy of combined metformin- letrozole in comparison with metformin-laparoscopic ovarian diathermy in ovulation induction and reproductive outcome for women with clomiphene citrate resistant polycystic ovary syndrome

Background and objective: polycystic ovary syndrome(PCOS) is a common cause of infertility and is associated with chronic anovulation and hyperandrogenism.The aim of current study is to compare the effect of combined letrozole metformine to that of metformin-laparoscopic ovarian drilling (LOD) for ovulation induction in patients with PCOS.Materials and Methods: on the whole 138 ovarian cycles were studied in 60 patients with clomiphene citrate resistant PCOS in AL-Diwaniyah Maternity and Pediatrics Teaching Hospital during the period of June 2112-June 2114. All patients (n=60) received metformin 500mg /3times per day ,group A(n=30)received letrozole 5mg daily for 5 days repeated for 6 cycles, group B(n=30) underwent LOD and followed for six cycles. Outcome measures were ovulation rates, endometrialthickness, pregnancyrates, live birth rates and miscarriage rate.Results: ovulation rate was higher in group A than group B(63.33% versus 30.0%),a significant increase in endometrial thickness in group A than group B(9.9mm versus 9.03 mm).Live birth rate was higher in group A 83.33% compared to 33.33% in group B. There were no significant differences regarding miscarriage rates between both groups. No multiple pregnancy or ovarian hyper stimulation syndrome or congenital abnormality among live births were reported.Conclusions: Combinedletrozolemetformin seems to be a suitable second line ovulation inducing alternative to LOD in women with PCOS who do not respondwith clomiphene citrate.

Follicular phase dexamethazone administration in polycystic ovarian syndrome patients who are clomiphene citrate resistant

Aim of the workTo compare the effect of adding short course follicular phase dexamethazone to clomiphene citrate versus increasing clomiphene citrate dose in cases of resistance. Materials and methodsThe study was conducted on 85 with polycystic ovary syndrome who were resistant to 150mg clomiphene citrate daily for 5 days for 3 months and were attending El Shatby Maternity University Hospital in the period between September 2011 and May 2013. These patients were randomly allocated by closed envelope method into one of the two groups: Group I: 44 patients received 200mg daily of clomiphene citrate from day 3 and for 5 days together with 2mg dexamethazone daily from day 3 and for 10 days. Group II: 41 patients received 200mg daily of clomiphene from day 3 and for 5 days. ResultsWe found that a significant higher rate of ovulation was reported in the dexamethazone group compared to clomphine citrate only group, endometrial thickness was more favorable in dexamethazone group than the other group, mid luteal serum progesterone was a higher level in dexamesathone group compared to the other group and serum pregnancy rate was higher in dexamethazone group than the other group. ConclusionAlthough the mechanism underlying the beneficial effects of dexamesathone is not exactly understood, it is apparent from our data that dexamesathone therapy during the follicular phase can enhance follicular development and ovulation. Dexamethazone (corticosteroids) therapy combined with clomphine citrate can improve folliculogenesis, ovulation, and pregnancy rate in clomphine citrate resistant polycystic ovary syndrome.

Effects of Letrozole in Prevention of Premature Luteinizing Hormone (LH) Surge in Infertile Women with Clomiphene Citrate Resistant Polycystic Ovary Syndrome (PCOS) Undergoing Intrauterine Insemination

Background: Polycystic ovarian syndrome (PCOS) is among the important causes of infertility in young women. Premature luteinizing hormone (LH) surge (PLS) is one of its complications. PLS can reduce the quality of oocytes and therefore decrease the success of intrauterine insemination (IUI). Letrozole, a non-steroidal aromatase inhibitor, prevents LH surge. In this study, we aim to evaluate the effects of letrozole on preventing premature LH surge in clomiphene-resistant patients with PCOS undergoing IUI. Materials and Methods: In this randomized clinical trial, 131 patients who were developed with PCOS were selected for IUI cycle, divided into two groups randomly: control group (n=67) and letrozole group (n=64). Incidence of premature LH surge, pregnancy, abortion and ongoing pregnancy rate, endometrial thickness and number of follicles were measured in both groups. Results: No significant difference was seen between mean ages in the two groups; 11.9% of the control group and 21.9% of the letrozole group became pregnant (P =0.005); furthermore, premature LH surge was seen in 4.7% of the letrozole group and 8.9% of the control group (P =0.003). E2 and Endometrial thickness was higher in letrozole group; however, LH was significantly higher in the control group (P =0.026). Conclusion: Administration of letrozole in clomiphene-resistant patients with PCO undergoing IUI cycle can decrease the incidence of PLS. In addition, it can increase pregnancy rate significantly. Therefore, using letrozole is more reasonable in patients who have not responded to clomiphene or are hypersensitive. [GMJ.2015;4(3):104-11]

Insulin sensitizing agent (metformin) improves clinical pregnancy rate in clomiphene citrate resistant polycystic ovarian syndrome patients with acanthosis nigricans

ObjectiveThere are several studies that showed a positive correlation between acanthosis nigricans (AN) with hyperinsulinemia and increased insulin resistance. The present study evaluated the effect of adding insulin sensitizing agent (metformin) to clomiphene citrate (CC) on improving insulin resistance parameters and pregnancy rate (PR) in clomiphene-resistant polycystic ovary (PCOS) patients with AN.DesignA double blinded randomized control trialed.Materials and MethodsSixty six CC resistant PCO patients (unsatisfactory ovulation after at least 3 month of CC induction) with AN had been recruited in the study. All study participants had proper clinical evaluation to ensure the diagnosis of AN. Additionally, day 3 follicle stimulating hormone level, fasting insulin, fasting glucose and homeostatic model assessment used to quantify insulin resistance (HOMA–IR) were done. Randomization was done using serial number closed opaque envelopes. Blinding was done using two identical packages for induction (group I) two 50 mg CC tablets taken from day 3 to day 7 of the cycle + placebo tablets taken twice daily all through the cycle (Group II) received the above CC dose + metformin 500 mg twice daily continuously for three cycles. Insulin resistance parameters as well as clinical pregnancy rate had been evaluated in both groups. The statistical analysis was done using Chi-square and Fischer exact tests.ResultsTable 1GI(CC)GII (CC + metformin)P. valueMeanSDMeanSDFasting glucose96.856.8489.766.220.001Fasting insulin12.063.127.832.950.005HOMA_IR2.900.711.720.670.001 Open table in a new tab ConclusionAddition of metformin to CC in PCOS patients with AN, decreases insulin resistance and improve clinical pregnancy rate in patients with previous unsatisfactory response to CC alone. ObjectiveThere are several studies that showed a positive correlation between acanthosis nigricans (AN) with hyperinsulinemia and increased insulin resistance. The present study evaluated the effect of adding insulin sensitizing agent (metformin) to clomiphene citrate (CC) on improving insulin resistance parameters and pregnancy rate (PR) in clomiphene-resistant polycystic ovary (PCOS) patients with AN. There are several studies that showed a positive correlation between acanthosis nigricans (AN) with hyperinsulinemia and increased insulin resistance. The present study evaluated the effect of adding insulin sensitizing agent (metformin) to clomiphene citrate (CC) on improving insulin resistance parameters and pregnancy rate (PR) in clomiphene-resistant polycystic ovary (PCOS) patients with AN. DesignA double blinded randomized control trialed. A double blinded randomized control trialed. Materials and MethodsSixty six CC resistant PCO patients (unsatisfactory ovulation after at least 3 month of CC induction) with AN had been recruited in the study. All study participants had proper clinical evaluation to ensure the diagnosis of AN. Additionally, day 3 follicle stimulating hormone level, fasting insulin, fasting glucose and homeostatic model assessment used to quantify insulin resistance (HOMA–IR) were done. Randomization was done using serial number closed opaque envelopes. Blinding was done using two identical packages for induction (group I) two 50 mg CC tablets taken from day 3 to day 7 of the cycle + placebo tablets taken twice daily all through the cycle (Group II) received the above CC dose + metformin 500 mg twice daily continuously for three cycles. Insulin resistance parameters as well as clinical pregnancy rate had been evaluated in both groups. The statistical analysis was done using Chi-square and Fischer exact tests. Sixty six CC resistant PCO patients (unsatisfactory ovulation after at least 3 month of CC induction) with AN had been recruited in the study. All study participants had proper clinical evaluation to ensure the diagnosis of AN. Additionally, day 3 follicle stimulating hormone level, fasting insulin, fasting glucose and homeostatic model assessment used to quantify insulin resistance (HOMA–IR) were done. Randomization was done using serial number closed opaque envelopes. Blinding was done using two identical packages for induction (group I) two 50 mg CC tablets taken from day 3 to day 7 of the cycle + placebo tablets taken twice daily all through the cycle (Group II) received the above CC dose + metformin 500 mg twice daily continuously for three cycles. Insulin resistance parameters as well as clinical pregnancy rate had been evaluated in both groups. The statistical analysis was done using Chi-square and Fischer exact tests. ResultsTable 1GI(CC)GII (CC + metformin)P. valueMeanSDMeanSDFasting glucose96.856.8489.766.220.001Fasting insulin12.063.127.832.950.005HOMA_IR2.900.711.720.670.001 Open table in a new tab ConclusionAddition of metformin to CC in PCOS patients with AN, decreases insulin resistance and improve clinical pregnancy rate in patients with previous unsatisfactory response to CC alone. Addition of metformin to CC in PCOS patients with AN, decreases insulin resistance and improve clinical pregnancy rate in patients with previous unsatisfactory response to CC alone.

The impact of preoperative FSH on the long-term outcomes of laparoscopic ovarian drilling in women with clomiphene citrate resistant polycystic ovary syndrome

Laparoscopic ovarian drilling (LOD) is currently recommended as a second-line treatment for clomiphene citrate (CC)-resistant infertile women with polycystic ovary syndrome (PCOS). Many authors have reported high ovulation and pregnancy rates following LOD. However, the duration of the positive effect of LOD on ovulation is unknown and some anovulatory PCOS women fail to respond to LOD. The purpose of this study was to identify the factors that may predict the long-term outcome of LOD.

Letrozole versus Tamoxifen in Treatment of Clomiphene Citrate Resistant Polycystic Ovarian Syndrome

Objective The objective of this prospective randomized study was to make a comparison between Letrozole and Tamoxifen (TMX) effects in ovulation induction in clomiphene (CC)-resistant women with polycystic ovarian syndrome (PCOS).

N -acetyl cysteine in clomiphene citrate resistant polycystic ovary syndrome: A review of reported outcomes

Clomiphene citrate (CC) has been the gold-standard drug for ovulation induction in polycystic ovary syndrome (PCOS), but still CC resistance is seen in approximately 15-40% in women with PCOS. N-acetyl cysteine (NAC), a safe and cheap drug available in the market many years ago as mucolytic agent, was found to have a role in infertility management. Recently, some reports discussed the possible beneficial effects of NAC on ovulation. The biological properties of the NAC make this drug a potential candidate for its use in the infertility treatment, especially in the PCOS in inducing or augmenting ovulation. An updated electronic search was performed through PUBMED, MEDLINE, and COCHRANE and focused on peer-reviewed, full text, randomized controlled trials, and observational cohort or case-control studies for role of NAC in CC-resistant PCOS. Thorough search through all the clinical studies showed mixed results. Studies with positive results showed improvement in induction of ovulation as compared to negative studies showing contrary results. More randomized clinical trials are still needed to establish its definitive role in CC-resistant PCOS.

The prevalence of metabolic syndrome in clomiphene citrate resistant polycystic ovary syndrome

Objective: To investigate the prevalence of metabolic syndrome in clomiphene citrate (CC) resistant polycystic ovary syndrome (PCOS) patients. Methods: 58 CC resistant PCOS patients, 52 CC responders, 53 fertile PCOS and 53 age and body mass index-matched normoandrogenic ovulatory fertile women were evaluated for metabolic syndrome. Results: Metabolic syndrome prevalence was 41.4% in CC resistants, in 23.1% of CC responders, in 11.3% of PCOS fertiles and 0% of controls (p < 0.0001). Waist circumference (WC) > 88 cm was 44.8%, systolic blood pressure (BP) ≥ 130 mmHg and diastolic BP ≥85 mmHg were 27.6%, TG (triglyceride) ≥150 mg/dL was 36.2%, HDL(high density lipoprotein) < 50 mg/dL was 63.8%, fasting glucose levels ≥ 100 mg/dL was 20.7% in CC resistant PCOS women. There were positive associations between CC resistance and WC >88 cm, BP ≥ 130 ≥ 85 mmHg, TG ≥ 150 mg/dL, HDL < 50 mg/dL, fasting glucose ≥ 100 mg/dL, and presence of metabolic syndrome (p < 0.05, for all). Moreover, WC > 88 cm, and HDL < 50 mg/dL were independent variables that were associated by CC resistance by multivariate regression analysis. Conclusions: CC resistant PCOS patients have high prevalence of metabolic syndrome. These women have an increased risk of future cardiovascular disease.