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

January 18, 2021 updated by: Nora Fayek Zaki, Assiut University

Cost Effectiveness Analysis for Induction of Ovulation in the Polycystic Ovary Syndrome by Letrozole Versus Clomiphene Citrate: A Randomised Controlled Trial

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

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

212

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: fayek

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 31 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion criteria:

  • Women with infertility secondary to PCOS according to ESHRE/ASRM (Rotterdam criteria) 2004. Patients have at least two of the following; clinical and/or biochemical hyperandrogenism, oligo-ovulation or anovulation, polycystic ovaries by sonography (Diagnosis of oligo-/anovulation will be based on a menstrual pattern of oligo-/amenorrhoea (cycle >35 days) and/or a low mid-luteal serum progesterone concentration. Hyperandrogenaemia will be diagnosed either clinically (acne/hirsutism) or biochemically (testosterone ≥2.5 nmol/l or free androgen index [FAI] ≥5). Ultrasound criteria will include ≥12 follicles (2-9 mm) and/or an ovarian volume of >10 ml).
  • Age between 18 to 35 years with Body Mass Index (BMI) not more than 35 kg/m2, free of any medical disease and not receiving medications in the last 3 months.

Exclusion criteria:

  • Patients with other causes of infertility, gross ovarian pathology diagnosed by ultrasound, previous tubal or ovarian surgery or laparoscopic ovarian drilling will be excluded from the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: letrozole group
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
Drug: Letrozole
Each group will be followed up for ovulation by day 12 ovulation monitoring by Transvaginal ultrasound for mature griffian follicle and measure endometrial thickness and volume then day 21 test serum progesterone level to confirm ovulation and if pregnancy occurred confirm by serum pregnancy test at day 35 of the cycle and follow pregnancy till confirmed by fetal pulsation by ultrasound.
Experimental: Clomiphene Citrate group
Clomiphene Citrate group, Patients will receive 100 mg : Clomiphene Citrate daily starting on cycle day 2 for 5 days for three successive cycles
Drug: Clomiphine Citrate
Clomiphine Citrate

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

March 1, 2021

Primary Completion (Anticipated)

September 1, 2021

Study Completion (Anticipated)

December 1, 2021

Study Registration Dates

First Submitted

April 12, 2020

First Submitted That Met QC Criteria

April 23, 2020

First Posted (Actual)

April 24, 2020

Study Record Updates

Last Update Posted (Actual)

January 20, 2021

Last Update Submitted That Met QC Criteria

January 18, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Induction of ovulation

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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