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

Assiut University

Status and phase: Unknown; Early Phase 1

Conditions: Infertility

Treatments: Drug: Clomiphine Citrate; Drug: Letrozole

Study type: Interventional

Funder types: Other

Identifiers

NCT04361175

Induction of ovulation

Details and patient eligibility

About

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

Full 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).

Enrollment: 212 estimated patients

Sex: Female

Ages: 18 to 35 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Screening

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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212 participants in 2 patient groups

letrozole group

Experimental group

Description:

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

Treatment:

Drug: Letrozole

Clomiphene Citrate group

Experimental group

Description:

Clomiphene Citrate group, Patients will receive 100 mg : Clomiphene Citrate daily starting on cycle day 2 for 5 days for three successive cycles

Treatment:

Drug: Clomiphine Citrate