SubfertilityPhase 3NCT02912988
Letrozole in Stimulated IVF Cycles
A Phase 3 study testing Letrozole in people with Subfertility, run by The University of Hong Kong at 2 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 42 years, women only
- Conditions the study is for
- Subfertility
- What is being tested?
- Letrozole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 900 participants
- Where
- 2 sitesChina
- Study dates
- 1 Mar 2018to 30 Apr 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 42 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- women under 42 years of age
- medical indication for IVF treatment
- antral follicle count prior to ovarian stimulation >=3
- informed consent
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
China2 sites
Peking University Third Hospital
Beijing, 100191
Department of Obstetrics and Gynaecology
Hong Kong, Hong Kong
About this study
Official title: A Randomized Trial of Letrozole as an Adjunct to Follicle Stimulating Hormone in Stimulated in Vitro Fertilization Cycles
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.
Read the 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
- Being tested
- Letrozole
- Keywords
- Subfertility, In-vitro fertilization, Letrozole
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LetrozoleDrug
Also called Letrozole-Teva
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.
| Study group | Role | What they receive |
|---|---|---|
| Letrozole group | Experimental | 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. Receives: Drug: Letrozole |
| Control group | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Live birth rate
A baby born alive after 20 weeks gestation
Measured: through study completion, an average of 1 year
Secondary outcomes (19)
Miscarriage rate
Miscarriage before 20 weeks gestation
Measured: up to 20 weeks of gestation
Clinical and ongoing pregnancy rates
Presence of at least one gestational sac on ultrasound at 6 weeks and 8-10 weeks
Measured: up to 20 weeks
Ovarian hyperstimulation rate
Ovarian hyperstimulation rate classified according to Royal College of Obstetrics and Gynaecology of the United Kingdom
Measured: about 1 month
Total IU of FSH used per cycle
Total IU of FSH used per cycle
Measured: about 2 weeks
Number of follicles > 12 mm on day of hCG (or the day before)
Transvaginal ultrasound performed to measure and the follicles on day of hcG or the day before.
Measured: about 2 weeks
Number of oocytes obtained
Number of oocyte obtained during the operation of transvaginal ultrasound guided oocyte retrieval
Measured: On the operation day of transvaginal ultrasound guided oocyte retrieval
Proportion of oocytes resulting in top quality day 2 (or day 3) embryos according to validated morphological criteria.
Proportion of oocytes resulting in top quality day 2 (or day 3) embryos according to validated morphological criteria.
Measured: 2-3 days after the transvaginal ultrasound guided oocyte retrieval operation
Oocyte fertilization rate
Oocyte fertilization rate
Measured: 2-3 days after the transvaginal ultrasound guided oocyte retrieval operation
Number and quality of embryos obtained
Number and quality of embryos obtained
Measured: 2-3 days after the transvaginal ultrasound guided oocyte retrieval operation
Endometrial thickness on day of hCG (or the day before)
Endometrial thickness on day of hCG (or the day before) measured by transvaginal ultrasound
Measured: on day of hCG (or the day before)
Serum E2 level on day of hCG administration (or the day before)
Hormonal profile on day of hCG administration (or the day before): serum E2 level
Measured: on day of hCG administration (or the day before)
Serum P levels on day of hCG administration (or the day before)
Hormonal profile on day of hCG administration (or the day before): sSerum P level
Measured: on day of hCG administration (or the day before)
Serum testosterone levels on day of hCG administration (or the day before)
Hormonal profile on day of hCG administration (or the day before):serum testosterone level
Measured: on day of hCG administration (or the day before)
Follicular fluid E2 level
Follicular fluid hormonal profile: E2 level
Measured: On the operation day of transvaginal ultrasound guided oocyte retrieval
Follicular fluid testosterone level
Follicular fluid hormonal profile: testosterone level
Measured: On the operation day of transvaginal ultrasound guided oocyte retrieval
Follicular fluid inhibin B level
Follicular fluid hormonal profile: inhibin B level
Measured: On the operation day of transvaginal ultrasound guided oocyte retrieval
Follicular fluid AMH level
Follicular fluid AMH level
Measured: On the operation day of transvaginal ultrasound guided oocyte retrieval
Reported side effects
Measured: through study completion, an average of 1 year
Complications of pregnancy
small for gestational age, low birth weight, preterm delivery, pre-eclampsia, antepartum haemorrhage, congenital anomaly, perinatal mortality, multiple pregnancy
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2016 (estimated)
- Study start1 Mar 2018
- Primary completion30 Apr 2022
- Study completion30 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SubfertilityStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 900 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Collaborators
- Peking University Third Hospital
- Responsible party
- Sponsor
- Investigators
- Ernest HY Ng, MD, Principal investigator, Department of Obstetrics and Gynaecology, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02912988
- Sponsor's protocol ID
- UW 16-014
- Status last verified
- Nov 2022
- First submitted
- 13 Sep 2016
- Last updated
- 10 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35365197
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial of Letrozole as an Adjunct to Follicle Stimulating Hormone in Stimulated in Vitro Fertilization Cycles
- ClinicalTrials.gov ID
- NCT02912988
- Acronym / sponsor ID
- UW 16-014
- Conditions
- Subfertility
- Keywords
- Subfertility, In-vitro fertilization, Letrozole
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 900 participants (actual)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Collaborators
- Peking University Third Hospital
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 30 Apr 2022 (actual)
- Study completion
- 30 Apr 2023 (actual)
- First posted
- 23 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Letrozole group | Experimental | Drug: LetrozoleLetrozole + 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. |
| Control group | No intervention | –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. |
Who may qualify
- Ages
- 18 to 42 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- women under 42 years of age
- medical indication for IVF treatment
- antral follicle count prior to ovarian stimulation >=3
- informed consent
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LetrozoleAlso: Letrozole-TevaDaily 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. | Drug | Letrozole group |
Primary outcome
Live birth rate
Time frame: through study completion, an average of 1 year
A baby born alive after 20 weeks gestation
19 secondary outcomes
Miscarriage rate
Time frame: up to 20 weeks of gestation
Clinical and ongoing pregnancy rates
Time frame: up to 20 weeks
Ovarian hyperstimulation rate
Time frame: about 1 month
Total IU of FSH used per cycle
Time frame: about 2 weeks
Number of follicles > 12 mm on day of hCG (or the day before)
Time frame: about 2 weeks
Number of oocytes obtained
Time frame: On the operation day of transvaginal ultrasound guided oocyte retrieval
Proportion of oocytes resulting in top quality day 2 (or day 3) embryos according to validated morphological criteria.
Time frame: 2-3 days after the transvaginal ultrasound guided oocyte retrieval operation
Oocyte fertilization rate
Time frame: 2-3 days after the transvaginal ultrasound guided oocyte retrieval operation
Number and quality of embryos obtained
Time frame: 2-3 days after the transvaginal ultrasound guided oocyte retrieval operation
Endometrial thickness on day of hCG (or the day before)
Time frame: on day of hCG (or the day before)
Serum E2 level on day of hCG administration (or the day before)
Time frame: on day of hCG administration (or the day before)
Serum P levels on day of hCG administration (or the day before)
Time frame: on day of hCG administration (or the day before)
Serum testosterone levels on day of hCG administration (or the day before)
Time frame: on day of hCG administration (or the day before)
Follicular fluid E2 level
Time frame: On the operation day of transvaginal ultrasound guided oocyte retrieval
Follicular fluid testosterone level
Time frame: On the operation day of transvaginal ultrasound guided oocyte retrieval
Follicular fluid inhibin B level
Time frame: On the operation day of transvaginal ultrasound guided oocyte retrieval
Follicular fluid AMH level
Time frame: On the operation day of transvaginal ultrasound guided oocyte retrieval
Reported side effects
Time frame: through study completion, an average of 1 year
Complications of pregnancy
Time frame: through study completion, an average of 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2023.
- Derived from this study: PubMed 35365197Guo 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ernest HY Ng, MD principal investigator
Department of Obstetrics and Gynaecology, The University of Hong Kong
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Letrozole in people with Subfertility, run by The University of Hong Kong at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Live birth rate (time frame: through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02912988, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2023.