Ovulation Induction in Women With Clomiphene Citrate Resistant PCOS

Infertility Clinical Trial

Official title:

Combined Letrozole-metformin-pioglitazone Versus Combined Clomiphene Citrate-metformin-pioglitazone in Clomiphene Citrate-resistant Women With Polycystic Ovary Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01909141
• Other study ID #: fem2013
• Status: Completed
• Phase: Phase 0
• First received: July 15, 2013
• Last updated: September 30, 2015
• Start date: August 2013
• Est. completion date: April 2014

Study information

• Verified date: September 2015
• Source: Cairo University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Egypt: Cairo University-Faculty of Medicine
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: April 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 40 Years

Eligibility

Inclusion Criteria:

• 20-40 years old

• PCOS infertile women resistant to CC for3 cycles

Exclusion Criteria:

• presence of medical disorders as diabetes, hypertension, cardiac problems, liver or kidney diseases, hyperprolactinemia or thyroid dysfunction.

• use of gonadotropins before

• previous ovarian drilling

• presence of urinary symptoms especially bloody urine

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infertility
• Polycystic Ovary Syndrome

Intervention

Drug:
• induction of ovulation using letrozole-pioglitazone-metformin
induction of ovulation will be done for arm 1 for 3 consecutive cycles unless pregnancy occured.
• induction of ovulation using clomiphene citrate-pioglitazone-metformin
induction of ovulation for arm 2 will be done in 3 consecutive cycles unless pregnancy occured.

Radiation:
• 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

Other:
• body mass index (BMI) calculation
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
baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) will be done for all women.
• pretreatment blood urea and serum creatinine
blood urea and serum creatinine will be assayed before stating induction of ovulation to have baseline levels.
• serum estradiol (E2) on day 12
serum E2 will be assayed on day 12 of the cycle for all women.
• serum progesterone on day 21
serum progesterone will be assayed on day 21 for all women to monitor ovulation.
• blood urea and serum creatinine every month
blood urea and serum creatinine will be assayed every month during the treatment period to find out any hazards on kidney functions

Locations

Country	Name	City	State
Egypt	Cairo University	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Cairo University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	Yes
Primary	Ovulation Rate		3 months	No
Secondary	Number of Follicles>18mm.		3 months	No
Secondary	Endometrial Thickness		3 months	No
Secondary	Pregnancy Rate		3 months	No