Cost Effectiveness Analysis for Induction of Ovulation in the Polycystic Ovary Syndrome by Letrozole Versus Clomiphene Citrate

Early Phase 1

• Conditions: Infertility
• Interventions: Drug: Clomiphine Citrate; Drug: Letrozole

• Registration Number: NCT04361175
• Lead Sponsor: Assiut University

Brief Summary

To evaluate cost effectiveness of Letrozole versus clomiphene citrate (CC) in induction of ovulation in patients with polycystic ovary syndrome.

Detailed Description

Polycystic ovary syndrome (PCOS) is a common cause of infertility that affects 4% - 8% of reproductive-age females (Priya,M.R,2019).

Diagnosis of PCOS is very important for proper management. In literature, Rotterdam criteria are widely used for diagnosis and focus on polycystic ovarian morphology on ultrasound,a history of ovulatory disorders (oligo-anovulation), and clinical/biochemical signs of hyperandrogenism requiring two of three features after exclusion of other endocrinopathies (Wang,R,2017).

Although the syndrome is a complex reproductive-metabolic disorder, the hypothalamic-pituitary axis has been the target of first-line ovulation-induction therapy. Clomiphene citrate, a selective estrogen-receptor modulator that antagonizes the negative feedback of estrogen at the hypothalamus with a consequent increase in ovarian stimulation by endogenous gonadotropin, has been used for this indication for decades (Legro RS,2007).

Clomiphene citrate (CC) is still holding its place for ovulation induction being simple, safe, cheap and effective (Garg, N,2019).

However, clomiphene-resistance, i.e., failure to ovulate after receiving 150 mg/day for at least three cycles for five days per cycle affects 15% - 40% of patients with PCOS (Salaheldin,A.M,2016).

Aromatase inhibitors, which block estrogen synthesis, directly affect hypothalamic- pituitary-ovarian function and theoretically might increase pregnancy rates (Casper RF,2006).

Many tissues including the ovary (in premenopausal women), fat, muscle, breast and liver contain aromatase enzyme which controls the final step in estrogen synthesis, It is responsible for aromatization of androstenedione and testosterone into estrone and estradiol, respectively. This process can be inhibited by administration of a third-generation aromatase inhibitor such as letrozole by \>99% (Haynesa,B.P,2003).

Letrozole has become the first line drug for induction of ovulation in PCOS patients (Teede, H.J,2018).

Study Timeline

• Study First Submitted: 2020-04-12
• Study First Submitted QC: 2020-04-23
• Study First Posted: 2020-04-24
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-18
• Last Update Posted: 2021-01-20
• Study Start: 2021-03
• Primary Completion: 2021-09
• Study Completion: 2021-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 212

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Clomiphene Citrate group	Clomiphine Citrate	Clomiphene Citrate group, Patients will receive 100 mg : Clomiphene Citrate daily starting on cycle day 2 for 5 days for three successive cycles
letrozole group	Letrozole	letrozole group, Patients will receive 5 mg of letrozole oral tablets daily from day 2 of the cycle for 5 days for three successive cycles

Primary Outcome Measures

Name	Time	Method
Ovulation detection by Trans-vaginal ultrasound in day 12 of menstrual cycle	Three months	ovulation monitoring by Trans-vaginal ultrasound (Medison SonoACEX6 Soul Korea 2012 ) for mature GF in each group.