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

NCT ID: NCT04361175

Last Updated: 2021-01-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 212 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-31
• Study Completion Date: 2021-12-31

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).

Conditions

Infertility

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SCREENING
• Blinding Strategy: SINGLE

Study Groups

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

Group Type: EXPERIMENTAL

Letrozole

Intervention Type: DRUG

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.

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

Group Type: EXPERIMENTAL

Clomiphine Citrate

Intervention Type: DRUG

Clomiphine Citrate

Interventions

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.

Intervention Type: DRUG

Clomiphine Citrate

Clomiphine Citrate

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Assiut University

OTHER

Sponsor Role: lead

Responsible Party

Nora Fayek Zaki

Residant doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

fayek

Role: CONTACT

References

Casper RF, Mitwally MF. Review: aromatase inhibitors for ovulation induction. J Clin Endocrinol Metab. 2006 Mar;91(3):760-71. doi: 10.1210/jc.2005-1923. Epub 2005 Dec 29.

Reference Type: RESULT

PMID: 16384846 (View on PubMed)

Other Identifiers

Induction of ovulation

Identifier Type: -

Identifier Source: org_study_id