Letrozole /GnRH Antagonist Protocol in Women Over 40 Years Undergoing ICSI Cycle

NCT ID: NCT05166668

Last Updated: 2025-02-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-01
• Study Completion Date: 2025-02-10

Brief Summary

The aim of this study To compare the clinical and laboratory outcomes of two ovarian stimulation protocols (standard GnRH antagonist protocol and aromatase inhibitor/ antagonist protocol) in women (40-44) years undergoing ICSI cycle.

Detailed Description

Fertility is known to decline significantly in women after the age of 35 years, and fecundity is almost completely lost after the age of 45 . As age increases the natural fecundity and pregnancy rates after assisted reproduction decrease .This reduction in fecundity is thought to be due to ovarian aging mainly, which is defined as a decline in both the quantity and quality of the ovarian follicle pool .The increase in patient's age is associated with poor ovarian response, as represented by smaller ovarian volume, lower antral follicle count and poor stromal vascularity. In addition to the reduction in fecundity, there is an increase in spontaneous abortion rates in this group of women .It has been reported that about 19% of all women undergo ART are 40 years, and they could be considered as expected poor responders .Various protocols of ovarian stimulation have been proposed to optimize IVF results in this age group, however, satisfactory results remain a challenge . The lack of initial central down-regulation in early follicular phase and adequate prevention of premature luteinizing hormone (LH) surge in late follicular phase provide GnRH antagonist protocol as a potentially proper option .The use of aromatase inhibitors in a GnRH antagonist protocol was suggested by some studies [Mit. Yarali and colleagues demonstrated that adjuvant therapy with letrozole could improve the response [Yarali et al., 2009]. Meanwhile, in another study, adding letrozole to ovarian stimulation has no positive effect on the likelihood of pregnancy . Letrozole is a selective, non-steroidal third generation aromatase inhibitor. Letrozole causes a reduction in conversion of androstenedione and testosterone to estrone and estradiol by inhibiting the aromatase enzyme activity . According to some published studies, the decline in early follicular phase estrogen levels, and consequently decrease in negative feedback of estrogen on FSH release in hypothalamic-pituitary axis cause an increase in endogenous gonadotropin secretion and stimulation of ovarian follicular growth. In addition, an increase in intraovarian androgens secondary to aromatase inhibition, augments the follicular sensitivity to FSH stimulation and follicular growth . Letrozole has no antiestrogenic effect over the endometrium . These reports prompted us to hypothesize that use of letrozole as a co-treatment agent in GnRH antagonist protocol might enhance cycle outcomes.

I

Conditions

Ovarian Stimulation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

standard GnRH antagonist protocol

Gonadotropins (300-450 IU) IM start on cycle day 2 then the dose modulated according to response

Group Type: ACTIVE_COMPARATOR

Letrozole 2.5mg tablet

Intervention Type: DRUG

letrozole (femara, Novartis) orally in a dose of 2.5 mg daily, on day 2 of cycle for 5 days and gonadotropins (300-450 IU) IM start on cycle day 3. then the dose modulated according to response

Aromatase inhibitor/flexible antagonist protocol

letrozole orally in a dose of 2.5 mg daily, on day 2 of cycle for 5 days and gonadotropins (300-450 IU) IM start on cycle day 3. then the dose modulated according to response

Group Type: ACTIVE_COMPARATOR

Letrozole 2.5mg tablet

Intervention Type: DRUG

letrozole (femara, Novartis) orally in a dose of 2.5 mg daily, on day 2 of cycle for 5 days and gonadotropins (300-450 IU) IM start on cycle day 3. then the dose modulated according to response

Interventions

Letrozole 2.5mg tablet

letrozole (femara, Novartis) orally in a dose of 2.5 mg daily, on day 2 of cycle for 5 days and gonadotropins (300-450 IU) IM start on cycle day 3. then the dose modulated according to response

Intervention Type: DRUG

Other Intervention Names

Gonadotropins units

Eligibility Criteria

Inclusion Criteria

• Women between 40- 44-years undergoing ICSI cycle with FSH less than 15 and AMH more than 0.30.

Exclusion Criteria

• Azoospermia in male partner,
• Previous ovarian surgery,
• Severe endometriosis,
• Uterine cavity lesion
• Metabolic or endocrine disorders including hyperprolactinemia and ypo/hyperthyroidism.
• Previous failed ICSI cycle.
• BMI more than 30.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 44 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Menoufia University

OTHER

Sponsor Role: lead

Responsible Party

Mohamed Elsibai Anter

Assistant professor of obstetrics and gynecology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Menoufia University hospital

Shibīn al Kawm, Menoufia, Egypt

Countries

Egypt

Other Identifiers

12/2021OBSGN 1

Identifier Type: -

Identifier Source: org_study_id