Letrozole /GnRH Antagonist Protocol in Women Over 40 Years Undergoing ICSI Cycle
- Registration Number
- NCT05166668
- Lead Sponsor
- Menoufia University
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 200
- Women between 40- 44-years undergoing ICSI cycle with FSH less than 15 and AMH more than 0.30.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Aromatase inhibitor/flexible antagonist protocol Letrozole 2.5mg tablet 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 standard GnRH antagonist protocol Letrozole 2.5mg tablet Gonadotropins (300-450 IU) IM start on cycle day 2 then the dose modulated according to response
- Primary Outcome Measures
Name Time Method live birth rate 1 year after embryo transfer deliveries ≥22 weeks gestation with heartbeat and breath
- Secondary Outcome Measures
Name Time Method positive hCG 2 weeks after FET serum β-hCG ≥10 mIU/mL
clinical pregnancy 5 weeks' gestation presence of intrauterine gestational sac by trans-vaginal ultrasound at gestational weeks.
Total gonadotropin /cycle (IU), two weeks number of gonadotropin units needed per cycle
serum E2 levels two weeks measuring E2 level during stimulation
Duration of stimulation (Day), two weeks number of days needed for stimulation
Endometrial thickness (mm) two weeks measure endometrial thickness
Follicles number two weeks number of follicles during stimulation
Trial Locations
- Locations (1)
Menoufia University hospital
🇪🇬Shibīn Al Kawm, Menoufia, Egypt