Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Polycystic ovary syndrome (PCOS) affects 5-10% of women in childbearing age. Hyperinsulinemia contributes to chronic anovulation commonly encountered in women with PCOS. The first choice therapy is clomiphene citrate (CC). In CC resistant cases, the American College of Obstetrics and Gynecology (ACOG) recommends the use of insulin sensitizer metformin. Other insulin sensitizing agents include rosiglitazone and pioglitazone. Pioglitazone is said to improve fertility and ovulation in patients with PCOS.CC may be associated with poor endometrial thickening due to its antiestrogenic effect. Letrozole may improve this condition. In this study we will compare the effect of combined letrozole-metformin-pioglitazone with that of combined CC-metformin-pioglitazone in ovulation induction in CC-resistant PCOS women.
Polycystic ovary syndrome (PCOS) affects 5-10% of women in childbearing age. Hyperinsulinemia contributes to chronic anovulation commonly encountered in women with PCOS. The first choice therapy is clomiphene citrate (CC). In CC resistant cases, the ACOG recommends the use of insulin sensitizer metformin. Other insulin sensitizing agents include rosiglitazone and pioglitazone. Pioglitazone is said to improve fertility and ovulation in patients with PCOS.CC has a long half-life (2 weeks), and this may have a negative effect on the cervical mucus and endometrium, leading to discrepancy between ovulation and conception rates. There has been a search for a compound capable of inducing ovulation but devoid of the adverse antiestrogenic effects of CC. recent studies have suggested that letrozole, an aromatase inhibitor, does not possess the adverse antiestrogenic effects of CC and is associated with higher pregnancy rates than CC treatment in patients with PCOS.
In this study we shall compare the effect of combined letrozole-metformin-pioglitazone with that of combined CC-metformin-pioglitazone in ovulation induction in CC-resistant PCOS women.This will be a prospective comparative clinical trial in which 2 groups of women will be generated (groups A and B) using the sealed envelopes randomization method.Group A (40 women) will receive: letrozole 2.5 mg/day from 3rd day of the cycle for 5 days and (pioglitazone 15 mg + metformin 850 mg) once daily from 1st day of the cycle for 10 days. Group B (40 women) will receive clomiphene citrate 100 mg/day from 3rd day of the cycle for 5 days and (pioglitazone 15 mg + metformin 850 mg) once daily from 1st day of the cycle for 10 days. Ovulation will be monitored by vaginal ultrasound and serum estrogen and progesterone.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| arm 1:letrozole-pioglitazone -metformin group | Active Comparator | Arm 1 will receive letrozole 2.5 mg/day starting from the 3rd day of the cycle and for 5 days and (combined pioglitazone 15 mg+ metformin 850 mg) once daily from the first day of the cycle for 10 days. |
|
| arm 2: clomiphene citrate-pioglitazone-metformin | Active Comparator | Arm 2 will receive clomiphene citrate 100 mg/day starting from the 3rd day of the cycle for 5 days and (combined pioglitazone 15 mg + metformin 850 mg) once daily from the first day of the cycle for 10 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| induction of ovulation using letrozole-pioglitazone-metformin | Drug | induction of ovulation will be done for arm 1 for 3 consecutive cycles unless pregnancy occured. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Ovulation Rate | 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Follicles>18mm. | 3 months | |
| Endometrial Thickness | 3 months | |
| Pregnancy Rate |
| Measure | Description | Time Frame |
|---|---|---|
| Safety of Pioglitazone as Regards Serum Creatinine | serum creatinine was measured at the end of the study period (after 3 months) in both groups. | 3 months |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Ghada Abdel Fattah Abdel Moety, lecturer | Cairo University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cairo University | Cairo | Egypt |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26613820 | Derived | El-khayat W, Abdel Moety G, Al Mohammady M, Hamed D. A randomized controlled trial of clomifene citrate, metformin, and pioglitazone versus letrozole, metformin, and pioglitazone for clomifene-citrate-resistant polycystic ovary syndrome. Int J Gynaecol Obstet. 2016 Feb;132(2):206-9. doi: 10.1016/j.ijgo.2015.06.063. Epub 2015 Nov 6. |
| Label | URL |
|---|---|
| Related Info | View source |
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1:Letrozole-pioglitazone -Metformin Group | Arm 1 received letrozole 2.5 mg/day starting from the 3rd day of the cycle and for 5 days and (combined pioglitazone 15 mg+ metformin 850 mg) once daily from the first day of the cycle for 10 days. induction of ovulation using letrozole-pioglitazone-metformin: induction of ovulation was done for arm 1 for 3 consecutive cycles unless pregnancy occurred. transvaginal ultrasound: transvaginal ultrasound will be done starting from day 10 and every 48 hours until finding a follicle of > 18 mm or till day 20 of the cycle body mass index (BMI) calculation: BMI was calculated. day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone: baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) were done for all women. serum estradiol (E2) was done on day of hCG administration for all women. serum progesterone on day 21 was done for all women. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| induction of ovulation using clomiphene citrate-pioglitazone-metformin | Drug | induction of ovulation for arm 2 will be done in 3 consecutive cycles unless pregnancy occured. |
|
| transvaginal ultrasound | Radiation | transvaginal ultrasound will be done starting from day 10 and every 48 hours until finding a follicle of > 18 mm or till day 20 of the cycle |
|
| body mass index (BMI) calculation | Other | BMI will be calculated for all women by dividing the weight in kilograms by the height in meters squared |
|
| day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone | Other | baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) will be done for all women. |
|
| pretreatment blood urea and serum creatinine | Other | blood urea and serum creatinine will be assayed before stating induction of ovulation to have baseline levels. |
|
| serum estradiol (E2) on day 12 | Other | serum E2 will be assayed on day 12 of the cycle for all women. |
|
| serum progesterone on day 21 | Other | serum progesterone will be assayed on day 21 for all women to monitor ovulation. |
|
| blood urea and serum creatinine every month | Other | blood urea and serum creatinine will be assayed every month during the treatment period to find out any hazards on kidney functions |
|
| 3 months |
| FG001 | Arm 2: Clomiphene Citrate-pioglitazone-metformin | Arm 2 received clomiphene citrate 100 mg/day starting from the 3rd day of the cycle for 5 days and (combined pioglitazone 15 mg + metformin 850 mg) once daily from the first day of the cycle for 10 days. induction of ovulation using clomiphene citrate-pioglitazone-metformin: induction of ovulation for arm 2 was done in 3 consecutive cycles unless pregnancy occurred. transvaginal ultrasound: transvaginal ultrasound was done starting from day 10 and every 48 hours until finding a follicle of > 18 mm or till day 20 of the cycle body mass index (BMI) calculation: BMI was calculated. day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone: baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) were done for all women. serum estradiol (E2) was done on day of hCG administration for all women. serum progesterone on day 21 was done for all women. |
| COMPLETED |
|
| NOT COMPLETED |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Arm 1:Letrozole-pioglitazone -Metformin Group | Arm 1 received letrozole 2.5 mg/day starting from the 3rd day of the cycle and for 5 days and (combined pioglitazone 15 mg+ metformin 850 mg) once daily from the first day of the cycle for 10 days. induction of ovulation using letrozole-pioglitazone-metformin: induction of ovulation was done for arm 1 for 3 consecutive cycles unless pregnancy occurred. transvaginal ultrasound: transvaginal ultrasound was done starting from day 10 and every 48 hours until finding a follicle of > 18 mm or till day 20 of the cycle body mass index (BMI) calculation: BMI was calculated. day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone: baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) were done for all women. serum estradiol (E2) was done on day of hCG administration for all women. serum progesterone on day 21 was done for all women. |
| BG001 | Arm 2: Clomiphene Citrate-pioglitazone-metformin | Arm 2 will received clomiphene citrate 100 mg/day starting from the 3rd day of the cycle for 5 days and (combined pioglitazone 15 mg + metformin 850 mg) once daily from the first day of the cycle for 10 days. induction of ovulation using clomiphene citrate-pioglitazone-metformin: induction of ovulation for arm 2 was done in 3 consecutive cycles unless pregnancy occured. transvaginal ultrasound: transvaginal ultrasound was done starting from day 10 and every 48 hours until finding a follicle of > 18 mm or till day 20 of the cycle body mass index (BMI) calculation: BMI was calculated. day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone: baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) were done for all women. serum estradiol (E2) was done on day of hCG administration for all women. serum progesterone on day 21 was done for all women. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| infertility period | Mean | Standard Deviation | years |
| |||||||||||||||
| BMI | Mean | Standard Deviation | kg/m^2 |
| |||||||||||||||
| waist/hip ratio | Mean | Standard Deviation | ratio |
| |||||||||||||||
| systolic blood pressure | Mean | Standard Deviation | mmHg |
| |||||||||||||||
| diastolic blood pressure | Mean | Standard Deviation | mmHg |
| |||||||||||||||
| hirsutism | Number | participants |
| ||||||||||||||||
| acne | Number | participants |
| ||||||||||||||||
| ovarian volume | Mean | Standard Deviation | ml |
| |||||||||||||||
| FSH | Mean | Standard Deviation | mIU/L |
| |||||||||||||||
| LH | Mean | Standard Deviation | mIU/L |
| |||||||||||||||
| E2 | Mean | Standard Deviation | Pmol/dL |
| |||||||||||||||
| prolactin | Mean | Standard Deviation | ng/ml |
| |||||||||||||||
| total testosterone | Mean | Standard Deviation | nmol/L |
| |||||||||||||||
| free testosterone | Mean | Standard Deviation | Pmol/dL |
| |||||||||||||||
| TSH | Mean | Standard Deviation | mIU/L |
| |||||||||||||||
| free T4 | Mean | Standard Deviation | nmol/L |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Ovulation Rate | Posted | Number | percentage of all cycles | 3 months |
|
|
| |||||||||||||||||||||||||||||||
| Secondary | Number of Follicles>18mm. | Posted | Mean | Standard Deviation | follicles | 3 months |
| ||||||||||||||||||||||||||||||||
| Secondary | Endometrial Thickness | Posted | Mean | Standard Deviation | mm | 3 months |
| ||||||||||||||||||||||||||||||||
| Secondary | Pregnancy Rate | Posted | Number | participants | 3 months |
| |||||||||||||||||||||||||||||||||
| Other Pre-specified | Safety of Pioglitazone as Regards Serum Creatinine | serum creatinine was measured at the end of the study period (after 3 months) in both groups. | Posted | Mean | Standard Deviation | mg/dL | 3 months |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm 1:Letrozole-pioglitazone -Metformin Group | Arm 1 received letrozole 2.5 mg/day starting from the 3rd day of the cycle and for 5 days and (combined pioglitazone 15 mg+ metformin 850 mg) once daily from the first day of the cycle for 10 days. induction of ovulation using letrozole-pioglitazone-metformin: induction of ovulation was done for arm 1 for 3 consecutive cycles unless pregnancy occurred. transvaginal ultrasound: transvaginal ultrasound will be done starting from day 10 and every 48 hours until finding a follicle of > 18 mm or till day 20 of the cycle body mass index (BMI) calculation: BMI was calculated. day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone: baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) were done for all women. serum estradiol (E2) was done on day of hCG administration for all women. serum progesterone on day 21 was done for all women. | 0 | 50 | 0 | 50 | ||
| EG001 | Arm 2: Clomiphene Citrate-pioglitazone-metformin | Arm 2 received clomiphene citrate 100 mg/day starting from the 3rd day of the cycle for 5 days and (combined pioglitazone 15 mg + metformin 850 mg) once daily from the first day of the cycle for 10 days. induction of ovulation using clomiphene citrate-pioglitazone-metformin: induction of ovulation for arm 2 was done in 3 consecutive cycles unless pregnancy occurred. transvaginal ultrasound: transvaginal ultrasound was done starting from day 10 and every 48 hours until finding a follicle of > 18 mm or till day 20 of the cycle body mass index (BMI) calculation: BMI was calculated. day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone: baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) were done for all women. serum estradiol (E2) was done on day of hCG administration for all women. serum progesterone on day 21 was done for all women. | 0 | 50 | 0 | 50 |
Not provided
Not provided
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ghada Abdel Fattah | Cairo University | 00201006513305 | ghadaabdelfatah2007@yahoo.com |
| ID | Term |
|---|---|
| D011085 | Polycystic Ovary Syndrome |
| D007246 | Infertility |
| ID | Term |
|---|---|
| D010048 | Ovarian Cysts |
| D003560 | Cysts |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D015992 | Body Mass Index |
| D007986 | Luteinizing Hormone |
| D013972 | Thyrotropin |
| D013739 | Testosterone |
| D001806 | Blood Urea Nitrogen |
| ID | Term |
|---|---|
| D001837 | Body Weights and Measures |
| D001824 | Body Constitution |
| D010808 | Physical Examination |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D000886 | Anthropometry |
| D008919 | Investigative Techniques |
| D010829 | Physiological Phenomena |
| D001699 | Biometry |
| D015991 | Epidemiologic Measurements |
| D011634 | Public Health |
| D004778 | Environment and Public Health |
| D006065 | Gonadotropins, Pituitary |
| D006062 | Gonadotropins |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010908 | Pituitary Hormones, Anterior |
| D010907 | Pituitary Hormones |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000737 | Androstenols |
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D045165 | Testosterone Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D001774 | Blood Chemical Analysis |
| D019963 | Clinical Chemistry Tests |
| D019411 | Clinical Laboratory Techniques |
| D007677 | Kidney Function Tests |
| D003950 | Diagnostic Techniques, Urological |
Not provided
Not provided
| Male |
|
|
|
|
|
|
|
|
|