Letrozole in Stimulated IVF Cycles

NCT ID: NCT02912988

Last Updated: 2023-05-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 900 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-01
• Study Completion Date: 2023-04-30

Brief Summary

In-vitro fertilization (IVF) is the treatment of choice for couples with prolonged infertility. The treatment usually involves hormonal stimulation of the ovaries by follicle stimulating hormone (FSH), followed by surgical removal of eggs which are then mixed with sperm in the laboratory to create embryos. The success rates of IVF treatment remain unsatisfactory and are no longer increasing. One of the reasons is an adverse effect of high serum estradiol levels following FSH stimulation on the lining of the uterus.

Letrozole is a drug used in the prevention of recurrence of breast cancer because of its action to reduce the intra-ovarian aromatization of androgens to estrogens. It is now increasingly used for ovulation induction and is as safe as clomiphene citrate. Use of letrozole during standard ovarian stimulation for IVF producing adequate numbers of oocytes with physiological levels of estradiol may increase the present success rate of standard IVF treatment.

The aim of this randomized study is to compare the live birth rate of FSH alone versus combined FSH and letrozole used for ovarian stimulation in IVF treatment.

Detailed Description

Trial design:

Infertile women undergoing IVF treatment will be randomized into one of the following two groups by an online randomization program:

Letrozole group: letrozole 2.5mg daily will be given at the start of the antagonist during ovarian stimulation i.e. day 5 of stimulation.

Control group: standard care with FSH alone during ovarian stimulation.

Intervention:

Subjects can be put on oral contraceptive pill in the preceding cycle for scheduling stimulation. On day 2-3, a pelvic ultrasound will be performed for antral follicle count.

Letrozole group:

Daily 150-225 IU human menopausal gonadotrophin (HMG) / Follicle stimulating hormone (FSH) from cycle day 2-4 (at least 5 days after stopping the oral contraceptive pill) and co-treatment with letrozole 2.5 mg daily from stimulation day 5 until the day before hCG administration. GnRH antagonist (cetrotide or orgalutran) 0.25 mg daily from stimulation day 5 until the day of hCG administration.

Control group:

Daily 150-225 IU HMG/FSH cycle day 2-4 (at least 5 days after stopping the oral contraceptive pill) until the day before hCG administration. GnRH antagonist 0.25 mg daily from stimulation day 5 until the day of hCG administration.

A blood sample will be taken and analyzed in the local laboratory for serum E2, P and testosterone levels on cycle day 2 or 3 (baseline) and day of hCG (or the day before). The remaining serum will be frozen and stored for later analysis.

A sample of follicular fluid (FF) will be collected from the first blood free follicle. The FF will be frozen and stored for later analysis: Estradiol, testosterone, inhibin B and AMH levels.

All techniques of IVF including harvesting of oocytes, insemination with specially prepared sperm, embryo culture in the laboratory, embryo transfer and luteal phase support will be according to local protocols. One or two embryos or blastocysts will be replaced.

A pregnancy test will be carried out 2 weeks after embryo transfer in both arms. All women who have a positive pregnancy test 2 weeks after embryo transfer will undergo a transvaginal ultrasound scan to identify the presence and number of gestation sac with a fetal heart signifying an ongoing pregnancy. Pelvic scan will be repeated at 8 weeks, 12 weeks, 24 weeks and 36 weeks of gestation for fetal growth.

Conditions

Subfertility

Study Design

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

Study Groups

Letrozole group

Letrozole + standard treatment:

Daily 150-300 IU human menopausal gonadotrophin (HMG) / Follicle stimulating hormone (FSH) from cycle day 2-4 (at least 5 days after stopping the oral contraceptive pill) and co-treatment with letrozole 2.5 mg daily from stimulation day 5 until the day before hCG administration. GnRH antagonist (cetrotide or orgalutran) 0.25 mg daily from stimulation day 5 until the day of hCG administration.

Group Type: EXPERIMENTAL

Letrozole

Intervention Type: DRUG

Daily 150-300 IU human menopausal gonadotrophin (HMG) / Follicle stimulating hormone (FSH) from cycle day 2-4 (at least 5 days after stopping the oral contraceptive pill) and co-treatment with letrozole 2.5 mg daily from stimulation day 5 until the day before hCG administration. GnRH antagonist (cetrotide or orgalutran) 0.25 mg daily from stimulation day 5 until the day of hCG administration.

Control group

Standard treatment:

Daily 150-300 IU HMG/FSH cycle day 2-4 (at least 5 days after stopping the oral contraceptive pill) until the day before hCG administration. GnRH antagonist 0.25 mg daily from stimulation day 5 until the day of hCG administration.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Letrozole

Daily 150-300 IU human menopausal gonadotrophin (HMG) / Follicle stimulating hormone (FSH) from cycle day 2-4 (at least 5 days after stopping the oral contraceptive pill) and co-treatment with letrozole 2.5 mg daily from stimulation day 5 until the day before hCG administration. GnRH antagonist (cetrotide or orgalutran) 0.25 mg daily from stimulation day 5 until the day of hCG administration.

Intervention Type: DRUG

Other Intervention Names

Letrozole-Teva

Eligibility Criteria

Inclusion Criteria

• women under 42 years of age
• medical indication for IVF treatment
• antral follicle count prior to ovarian stimulation >=3
• informed consent

Exclusion Criteria

• women using donor oocytes
• women undergoing preimplantation genetic diagnosis
• women with abnormal uterine cavity shown on hysterosalpingogram or saline infusion sonogram
• women with hydrosalpinges shown on scanning and not corrected
• previous documented poor response (<=3 oocytes) to ovarian stimulation using at least FSH 225 IU daily

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 42 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Peking University Third Hospital

OTHER

Sponsor Role: collaborator

The University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ernest HY Ng, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Obstetrics and Gynaecology, The University of Hong Kong

Locations

Department of Obstetrics and Gynaecology

Hong Kong, Hong Kong, China

Peking University Third Hospital

Beijing, , China

Countries

China

References

Guo W, Li HWR, Yang Z, Zeng L, Yang R, Qiao J, Li R, Ng EHY. Live birth after letrozole as an adjunct to follicle-stimulating hormone versus follicle-stimulating hormone alone for ovarian stimulation in in vitro fertilisation cycles-study protocol for a randomised controlled trial. Trials. 2022 Apr 1;23(1):247. doi: 10.1186/s13063-022-06185-0.

Reference Type: DERIVED

PMID: 35365197 (View on PubMed)

Other Identifiers

UW 16-014

Identifier Type: -

Identifier Source: org_study_id