Does Letrozole Improve Pregnancy Outcome in Fresh Embryo Transfer IVF/ICSI Cycle?

NCT03901170 | Unknown Phase 4

• 1 other identifier: 201810102MINC
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Letrozole (Femara), is an aromatase inhibitor which is used in the treatment of hormonally-responsive breast cancer after surgery. It is a good target for selective inhibition because estrogen production is a terminal step in the biosynthetic sequence. Aromatase inhibitors are widely used as adjuvant endocrine therapy for postmenopausal women with breast cancer. They have been used off-label in the treatment of patients for increasing the number of ovarian follicles recruited in ovulatory women undergoing controlled ovarian hyperstimulation (COH). A shorter half-life (48 hours) which would predict a lower risk of teratogenicity. No direct antiestrogenic adverse effects on the endometrium, due to an absence of peripheral estrogen receptor blockade and the shorter half-life. For ovarian normal responders, instead of hCG (human chorionic gonadotropin), luteal support with exogenous progesterone supplementation is the standard protocol for patients who received fresh embryo transfer for avoiding the risk of OHSS. In other normal responders who have increasing risk of OHSS, the strategy of freezing all embryos are more favored. In previous studies, high estrogen-induced endometrial gland cells apoptosis might account for the defective endometrial receptivity in women with excessively high estrogen concentrations after ovarian hyperstimulation in IVF cycles. Since letrozole can reduce the serum level of estrogen due to its pharmacological properties, which in turn reduces the adverse effects of high estrogen on the endometrium and improve the endometrial receptivity for embryo implantation. The investigators anticipate that infertility patients will receive short-term oral administration of letrozole (2.5 mg/tab) once a day when estrogen is elevated in the late stage of ovulation stimulation when receiving ovulation stimulation for two to three days. And transvaginal ultrasound was performed every two to three days for growth of ovarian follicles until two days before oocyte retrieval. Observing whether taking the drug can improve the maturity of the oocyte, pregnancy rate, implantation rate, miscarriage rate, ongoing pregnancy rate and live birth rate of the fresh embryo transfer cycle.

Conditions

Investigative Techniques; Reproductive Techniques; Reproductive Techniques, Assisted

Keywords

In Vitro Fertilization; letrozole; endometrial receptivity

Outcome Measures

Primary Outcomes (3)

• pregnancy rate

  16 days after oocyte retrieval

• implantation rate

  intra-uterine gestational sac/total transfer embryo number

  23 days after oocyte retrieval

• miscarriage rate

  pregnancy loss before gestational weeks 12

  gestational weeks 12

Secondary Outcomes (1)

• live birth rate

  from gestational weeks 24 to 42

Other Outcomes (1)

• cumulative pregnancy rate

  within three months after failure to achieve pregnancy in fresh embryo transfer cycle

Study Arms (2)

letrozole

EXPERIMENTAL

patients with letrozole

Drug: Letrozole 2.5mg

control

NO INTERVENTION

patients without letrozole

Interventions

Letrozole 2.5mg DRUG

oral administration of letrozole 2.5mg/tab, 1tab once per day from stimulation Day 7 to hCG Day.

letrozole

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women aged from 20 to 45 years old
• Receive IVF treatment due to infertility
• Plan to have fresh embryo transfer
• Total ovarian follicle number from 8 to 15 before oocyte retrieval
• Plan to have letrozole in IVF treatment routine

You may not qualify if:

• Systemic disease, such as diabetes mellitus, hypertension, heart disease, hypothyroidism, liver or renal disease, cancer, autoimmune disease, etc.
• Treatment cycle with pre-implantation genetic screening (PGS)/ pre-implantation genetic diagnosis(PGD)
• Oocyte recipient
• Poor ovarian responders according to Bologna criteria
• Patients who have risk of Ovarian Hyperstimulation Syndrome (OHSS)

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Related Publications (3)

• Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S. Evidence of impaired endometrial receptivity after ovarian stimulation for in vitro fertilization: a prospective randomized trial comparing fresh and frozen-thawed embryo transfer in normal responders. Fertil Steril. 2011 Aug;96(2):344-8. doi: 10.1016/j.fertnstert.2011.05.050. Epub 2011 Jul 6.

  PMID: 21737072 RESULT

• Kyrou D, Popovic-Todorovic B, Fatemi HM, Bourgain C, Haentjens P, Van Landuyt L, Devroey P. Does the estradiol level on the day of human chorionic gonadotrophin administration have an impact on pregnancy rates in patients treated with rec-FSH/GnRH antagonist? Hum Reprod. 2009 Nov;24(11):2902-9. doi: 10.1093/humrep/dep290. Epub 2009 Aug 11.

  PMID: 19671625 RESULT

• Chen SU, Chou CH, Chen MJ, Chen TH, Yang YS, Yang JH. Apoptotic effects of high estradiol concentrations on endometrial glandular cells. J Clin Endocrinol Metab. 2014 Jun;99(6):E971-80. doi: 10.1210/jc.2013-3794. Epub 2014 Feb 19.

  PMID: 24552218 RESULT

MeSH Terms

Conditions

Helping Behavior

Interventions

Letrozole

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Compare with others who did not usage of letrozole

Study Record Dates

• First Submitted: April 2, 2019
• First Posted: April 3, 2019
• Study Start: April 25, 2019
• Primary Completion: June 30, 2020
• Study Completion: April 8, 2021
• Last Updated: April 29, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)