InfertilityPhase 3TALESNCT03011684
Fertility Preservation Using Tamoxifen and Letrozole in Estrogen Sensitive Tumors Trial
A Phase 3 study testing Tamoxifen and Letrozole in people with Infertility, run by University of California, San Francisco at 1 site in United States.
Trial summary
Latrogenic infertility as a result of cancer treatment has a profound effect on long-term quality of life in survivors of reproductive-age cancers. Oocyte cryopreservation prior to cancer treatment has been associated with improved quality of life, with a potential ability to reduce long-term decision-related regret… Read more about this study
- Who is it for?
- Ages 18 to 50 years, women only
- Conditions the study is for
- Infertility
- What is being tested?
- Tamoxifen and Letrozole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 309 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jul 2016to 31 Mar 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 50 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- New breast cancer diagnosis
- Has not yet begun chemotherapy
- Desires to undergo ovarian stimulation and oocyte retrieval prior to cancer treatment
- Age 18 years old or greater
Who cannot join
- Chemotherapy has already commenced or been completed
- History of recurrent breast cancer (with a prior history of chemotherapy)
- Stage IV breast cancer diagnosis (metastases remote from the breast)
- Patient's oncologist advises against the trial - in which case they can choose to receive stimulation with letrozole+gonadotropin
- Does not plan to undergo ovarian stimulation and oocyte retrieval prior to diagnosis
- Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow-up, or interpretation of study results
- Age less than 18 years old
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of California at San Francisco
San Francisco, California, 94143
Rebecca Wong, 415-353-4305, Rebecca.Wong@ucsf.edu
Mitchell Rosen, M.D.
About this study
Latrogenic infertility as a result of cancer treatment has a profound effect on long-term quality of life in survivors of reproductive-age cancers. Oocyte cryopreservation prior to cancer treatment has been associated with improved quality of life, with a potential ability to reduce long-term decision-related regret in cancer survivors. Though letrozole plus gonadotropin and and tamoxifen plus gonadotropin are currently routinely used worldwide in ovarian stimulation cycles for fertility preservation in patients with estrogen-receptor-positive breast cancer, it is not clear which of the two might lead to improved oocyte yield. Improved knowledge about the efficacy of these medications, with regard to oocyte yield, has the potential to significantly improve quality of life in reproductive-age breast cancer survivors.
Read the detailed description
Purpose:
Our primary objective is to determine whether concomitant administration of tamoxifen 20 mg oral with gonadotropins (tamoxifen-gonadotropin) versus a starting dose of letrozole 5 mg oral with gonadotropins (letrozole-gonadotropin) will result in a difference in mature oocyte yield during our routine ovarian stimulation protocol for fertility preservation for Estrogen-Receptor-Positive (ER+) breast cancer.
Specific Aims: Each of the following aims will include a primary comparison and secondary comparisons.
Primary aim: The primary aim will be to compare patients with ER+ breast cancer who are treated with letrozole-gonadotropin versus patients with ER+ breast cancer who are treated tamoxifen-gonadotropin with regard to ovarian stimulation outcomes.
- Primary comparison:
- To determine if the assigned stimulation regimen will result in a difference in mature (meiosis II) oocyte yield in patients with breast cancer who undergo ovarian stimulation for fertility preservation.
- Secondary comparison:
- To compare estrogen, progesterone, and androgen levels during the ovarian stimulation cycle.
- To compare estrogen, letrozole, and tamoxifen levels in follicular fluid.
- To compare duration of stimulation (days) and total gonadotropin dose (international units of FSH).
- To assess embryo quality, if applicable, on day 3 and day 5 of embryo culture, a measure of the developmental competence of the oocytes.
- Experimental comparison:
- To compare clinical pregnancy rates when cryopreserved tissue is eventually utilized among patients from the assigned stimulation regimens. This comparison is labeled experimental because of the remoteness of such an outcome from our present study.
Secondary Aim: We will repeat the above comparisons among patients with ER+ breast cancer who are treated with tamoxifen-gonadotropin versus a prospectively-obtained reference group of patients with Estrogen-Receptor-Negative (ER-) breast cancer who are treated gonadotropin alone. We will then again repeat the above comparisons among patients with ER+ breast cancer who are treated letrozole-gonadotropin versus patients with ER- breast cancer who are treated gonadotropin alone.
Experimental Design and Methods:
Study population:
The target population is reproductive-age women who have been recently diagnosed with ER+ breast cancer and choose to undergo oocyte or embryo cryopreservation prior to chemotherapy treatment. All eligible women will be asked to join the study at their initial University of California, San Francisco (UCSF) fertility preservation consult. Study participants will be recruited from the Reproductive Endocrinology Clinic at University of California, San Francisco Center for Reproductive Health. A consecutive sample with ER- disease will also be recruited at the same type of visit. They will be asked to take part in the gonadotropin only stimulation group, which will be used for a secondary aim.
- Conditions
- Infertility
- Keywords
- Fertility Preservation, Breast Cancer
- Medical subject headings
- Infertility, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Randomized ER Positive Participants (Letrozole) | Experimental | Participants will receive 5 mg of letrozole with the first day of non-investigational gonadotropin (letrozole-gonadotropin) and stopped on the day of oocyte retrieval. Receives: Drug: Letrozole |
| Randomized ER Positive Participants (Tamoxifen) | Experimental | Participants will receive 20 mg of tamoxifen with the first day of non-investigational gonadotropin (tamoxifen-gonadotropin) and stopped on the day of oocyte retrieval Receives: Drug: Tamoxifen |
| ER Negative (ER-) Participants | No intervention | Participants whose disease is ER negative will be consented and used as a reference cohort and will receive no study related medication. The Gonadotropin received is non-investigational and part of usual care. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mature Oocyte Yield
To determine if the assigned stimulation regimen will result in a difference in mature (meiosis II) oocyte yield in patients with breast cancer who undergo ovarian stimulation for fertility preservation. An Effect Size of 3 mature oocytes, based on clinically significant difference of 2 embryos to transfer. An average of 2 embryos are transferred per freeze-thaw cycle. If ~75% of mature oocytes will become embryos that can be frozen, then 3 mature oocytes should yield ~2 embryos for transfer. This effect size would effectively mean an additional event of embryos transferred.
Measured: Up to 2 weeks
Secondary outcomes (9)
Compare change in estrogen levels during the ovarian stimulation cycle
Estrogen level data will be collected at baseline and after completion of the stimulation cycle
Measured: Up to 2 weeks
Compare change in progesterone levels during the ovarian stimulation cycle
Progesterone level data will be collected at baseline and after completion of the stimulation cycle
Measured: Up to 2 weeks
Compare change in androgen levels during the ovarian stimulation cycle
Androgen level data will be collected at baseline and after completion of the stimulation cycle
Measured: Up to 2 weeks
Compare change in estrogen in follicular fluid
Estrogen levels in follicular fluid will be collected at baseline and after completion of the stimulation cycle
Measured: Up to 2 weeks
Compare change in letrozole in follicular fluid
Letrozole levels in follicular fluid will be collected at baseline and after completion of the stimulation cycle
Measured: Up to 2 weeks
Compare change in tamoxifen in follicular fluid
Tamoxifen levels in follicular fluid will be collected at baseline and after completion of the stimulation cycle
Measured: Up to 2 weeks
Compare duration of stimulation (days) and total gonadotropin dose
The duration of stimulation in days will be compared to total gonadotropin dose across all groups.
Measured: Up to 2 weeks
Number if competent oocytes on day 3 of embryo culture
To assess embryo quality, if applicable, on day 3 of embryo culture, a measure of the developmental competence of the oocytes.
Measured: Up to 2 weeks
Number if competent oocytes on day 5 of embryo culture
To assess embryo quality, if applicable, on day 5 of embryo culture, a measure of the developmental competence of the oocytes.
Measured: Up to 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2017 (estimated)
- Study start21 Jul 2016
- Primary completion31 Mar 2028 (estimated)
- Study completion31 Mar 2028 (estimated)
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 InfertilityStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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
- Model description
- Participants will be randomized at the time of enrollment to 1 of 2 experimental arms.
- Masking
- None (open label)
- Enrolment
- 309 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mitchell Rosen, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03011684
- Sponsor's protocol ID
- TALES Trial
- Other IDs
- NCI-2017-01809, 16751
- Acronym
- TALES
- Status last verified
- Jun 2026
- First submitted
- 4 Jan 2017
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Letourneau J, Juarez-Hernandez F, Wald K, Ribeiro S, Wang A, McCulloch CE, Mok-Lin E, Dolezal M, Chien AJ, Cedars MI, Rosen M. Concomitant tamoxifen or letrozole for optimal oocyte yield during fertility preservation for breast cancer: the TAmoxifen or Letrozole in Estrogen Sensitive tumors (TALES) randomized clinical trial. J Assist Reprod Genet. 2021 Sep;38(9):2455-2463. doi: 10.1007/s10815-021-02273-3. Epub 2021 Jul 26.
PubMed 34312774
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fertility Preservation Using Tamoxifen and Letrozole in Estrogen Sensitive Tumors Trial
- ClinicalTrials.gov ID
- NCT03011684
- Acronym / sponsor ID
- TALES / TALES Trial
- Conditions
- Infertility
- Keywords
- Fertility Preservation, Breast Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 309 participants (estimated)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- 21 Jul 2016 (actual)
- Primary completion
- 31 Mar 2028 (estimated)
- Study completion
- 31 Mar 2028 (estimated)
- First posted
- 5 Jan 2017 (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.
Latrogenic infertility as a result of cancer treatment has a profound effect on long-term quality of life in survivors of reproductive-age cancers. Oocyte cryopreservation prior to cancer treatment has been associated with improved quality of life, with a potential ability to reduce long-term decision-related regret in cancer survivors. Though letrozole plus gonadotropin and and tamoxifen plus gonadotropin are currently routinely used worldwide in ovarian stimulation cycles for fertility preservation in patients with estrogen-receptor-positive breast cancer, it is not clear which of the two might lead to improved oocyte yield. Improved knowledge about the efficacy of these medications, with regard to oocyte yield, has the potential to significantly improve quality of life in reproductive-age breast cancer survivors.
Detailed description
Purpose:
Our primary objective is to determine whether concomitant administration of tamoxifen 20 mg oral with gonadotropins (tamoxifen-gonadotropin) versus a starting dose of letrozole 5 mg oral with gonadotropins (letrozole-gonadotropin) will result in a difference in mature oocyte yield during our routine ovarian stimulation protocol for fertility preservation for Estrogen-Receptor-Positive (ER+) breast cancer.
Specific Aims: Each of the following aims will include a primary comparison and secondary comparisons.
Primary aim: The primary aim will be to compare patients with ER+ breast cancer who are treated with letrozole-gonadotropin versus patients with ER+ breast cancer who are treated tamoxifen-gonadotropin with regard to ovarian stimulation outcomes.
- Primary comparison:
- To determine if the assigned stimulation regimen will result in a difference in mature (meiosis II) oocyte yield in patients with breast cancer who undergo ovarian stimulation for fertility preservation.
- Secondary comparison:
- To compare estrogen, progesterone, and androgen levels during the ovarian stimulation cycle.
- To compare estrogen, letrozole, and tamoxifen levels in follicular fluid.
- To compare duration of stimulation (days) and total gonadotropin dose (international units of FSH).
- To assess embryo quality, if applicable, on day 3 and day 5 of embryo culture, a measure of the developmental competence of the oocytes.
- Experimental comparison:
- To compare clinical pregnancy rates when cryopreserved tissue is eventually utilized among patients from the assigned stimulation regimens. This comparison is labeled experimental because of the remoteness of such an outcome from our present study.
Secondary Aim: We will repeat the above comparisons among patients with ER+ breast cancer who are treated with tamoxifen-gonadotropin versus a prospectively-obtained reference group of patients with Estrogen-Receptor-Negative (ER-) breast cancer who are treated gonadotropin alone. We will then again repeat the above comparisons among patients with ER+ breast cancer who are treated letrozole-gonadotropin versus patients with ER- breast cancer who are treated gonadotropin alone.
Experimental Design and Methods:
Study population:
The target population is reproductive-age women who have been recently diagnosed with ER+ breast cancer and choose to undergo oocyte or embryo cryopreservation prior to chemotherapy treatment. All eligible women will be asked to join the study at their initial University of California, San Francisco (UCSF) fertility preservation consult. Study participants will be recruited from the Reproductive Endocrinology Clinic at University of California, San Francisco Center for Reproductive Health. A consecutive sample with ER- disease will also be recruited at the same type of visit. They will be asked to take part in the gonadotropin only stimulation group, which will be used for a secondary aim.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Participants will be randomized at the time of enrollment to 1 of 2 experimental arms.
| Arm | Type | Receives |
|---|---|---|
| Randomized ER Positive Participants (Letrozole) | Experimental | Drug: LetrozoleParticipants will receive 5 mg of letrozole with the first day of non-investigational gonadotropin (letrozole-gonadotropin) and stopped on the day of oocyte retrieval. |
| Randomized ER Positive Participants (Tamoxifen) | Experimental | Drug: TamoxifenParticipants will receive 20 mg of tamoxifen with the first day of non-investigational gonadotropin (tamoxifen-gonadotropin) and stopped on the day of oocyte retrieval |
| ER Negative (ER-) Participants | No intervention | –Participants whose disease is ER negative will be consented and used as a reference cohort and will receive no study related medication. The Gonadotropin received is non-investigational and part of usual care. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- New breast cancer diagnosis
- Has not yet begun chemotherapy
- Desires to undergo ovarian stimulation and oocyte retrieval prior to cancer treatment
- Age 18 years old or greater
Key exclusion criteria (7 listed)
- Chemotherapy has already commenced or been completed
- History of recurrent breast cancer (with a prior history of chemotherapy)
- Stage IV breast cancer diagnosis (metastases remote from the breast)
- Patient's oncologist advises against the trial - in which case they can choose to receive stimulation with letrozole+gonadotropin
- Does not plan to undergo ovarian stimulation and oocyte retrieval prior to diagnosis
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 |
|---|---|---|
| TamoxifenAlso: Nolvadex, SoltamoxGiven orally | Drug | Randomized ER Positive Participants (Tamoxifen) |
| LetrozoleAlso: FemaraGiven orally | Drug | Randomized ER Positive Participants (Letrozole) |
Primary outcome
Mature Oocyte Yield
Time frame: Up to 2 weeks
To determine if the assigned stimulation regimen will result in a difference in mature (meiosis II) oocyte yield in patients with breast cancer who undergo ovarian stimulation for fertility preservation. An Effect Size of 3 mature oocytes, based on clinically significant difference of 2 embryos to transfer. An average of 2 embryos are transferred per freeze-thaw cycle. If ~75% of mature oocytes will become embryos that can be frozen, then 3 mature oocytes should yield ~2 embryos for transfer. This effect size would effectively mean an additional event of embryos transferred.
9 secondary outcomes
Compare change in estrogen levels during the ovarian stimulation cycle
Time frame: Up to 2 weeks
Compare change in progesterone levels during the ovarian stimulation cycle
Time frame: Up to 2 weeks
Compare change in androgen levels during the ovarian stimulation cycle
Time frame: Up to 2 weeks
Compare change in estrogen in follicular fluid
Time frame: Up to 2 weeks
Compare change in letrozole in follicular fluid
Time frame: Up to 2 weeks
Compare change in tamoxifen in follicular fluid
Time frame: Up to 2 weeks
Compare duration of stimulation (days) and total gonadotropin dose
Time frame: Up to 2 weeks
Number if competent oocytes on day 3 of embryo culture
Time frame: Up to 2 weeks
Number if competent oocytes on day 5 of embryo culture
Time frame: Up to 2 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
- Derived from this study: PubMed 34312774Letourneau J, Juarez-Hernandez F, Wald K, Ribeiro S, Wang A, McCulloch CE, Mok-Lin E, Dolezal M, Chien AJ, Cedars MI, Rosen M. Concomitant tamoxifen or letrozole for optimal oocyte yield during fertility preservation for breast cancer: the TAmoxifen or Letrozole in Estrogen Sensitive tumors (TALES) randomized clinical trial. J Assist Reprod Genet. 2021 Sep;38(9):2455-2463. doi: 10.1007/s10815-021-02273-3. Epub 2021 Jul 26.
- 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.
Mitchell Rosen, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tamoxifen and Letrozole in people with Infertility, run by University of California, San Francisco at 1 site in United States.
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 7 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: looking for participants now, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rebecca Wong (415-353-4305, Rebecca.Wong@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mature Oocyte Yield (time frame: Up to 2 weeks). 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 NCT03011684, 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 4 Jun 2026.