Infertility, FemalePhase 3COMPROSETNCT06644794
Progesterone-modified Natural Cycle for FET
A Phase 3 study testing Progesterone-modified natural cycle preparation for frozen embryo transfer and Hormone replacement therapy cycle preparation for frozen embryo transfer in people with Infertility, Female, run by Shandong University of Traditional Chinese Medicine at 1 site in China.
Trial summary
Hormone replacement therapy (HRT) cycles, despite the ease of synchronizing embryo thawing and embryo transfer timing, increase the risk of pregnancies and obstetric complications compared to natural cycles (NC). Read more about this study
- Who is it for?
- Ages 21 to 44 years, women only
- Conditions the study is for
- Infertility, Female
- What is being tested?
- Progesterone-modified natural cycle preparation for frozen embryo transfer and Hormone replacement therapy cycle preparation for frozen embryo transfer
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 336 participants
- Where
- 1 siteChina
- Study dates
- 5 Mar 2025to 1 Dec 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 21 to 44 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Patients aged 21 to 44 years undergoing FBT
- Body mass index (BMI) 18-35 kg/m2
- Having regular ovulatory cycles
Who cannot join
- Untreated uterine adhesions
- Medical contraindications to estrogen and progesterone therapy
- Illnesses contraindicating assisted reproductive technology or pregnancy
- History of recurrent implantation failures (> 2 embryo transfer failures)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Affiliated Hospital of Shandong University of Traditional Chinese Medicine
Jinan, Shandong, 250014
Jing-Yan Song, MD, 18765800113, songjingyan@sdutcm.edu.cn
About this study
Official title: Comparison of Progesterone-modified Natural Cycle and Hormone Replacement Therapy Cycle for Endometrial Preparation in Single Frozen Blastocyst Transfer
Hormone replacement therapy (HRT) cycles, despite the ease of synchronizing embryo thawing and embryo transfer timing, increase the risk of pregnancies and obstetric complications compared to natural cycles (NC). By ensuring the presence of the corpus luteum while reducing the number of monitoring sessions, the progesterone modified natural cycle (P4mNC) offers more convenience for the patient than the normal NC. This study is designed to compare the effects of P4mNC and HRT cycles on FET outcomes.
- Conditions
- Infertility, Female
- Being tested
- Progesterone-modified natural cycle preparation for frozen embryo transfer, Hormone replacement therapy cycle preparation for frozen embryo transfer
- Keywords
- Progesterone-modified natural cycle, Hormone replacement therapy, Frozen-thawed embryo transfer
- Medical subject headings
- Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Progesterone-modified natural cycle preparation for frozen embryo transferDrug
A novel endometrial preparation protocol that optimizes the natural cycle, whereby as long as the thickness of the endometrium is suitable for embryo transfer, vaginal progesterone can be used to transform the endometrium before ovulation and subsequently FET.
Hormone replacement therapy cycle preparation for frozen embryo transferDrug
A traditional endometrial preparation protocol is used for FET, which involves using fixed or flexible exogenous estradiol for artificial cycles. This protocol typically involves starting exogenous estradiol on day 3 or 4 of the cycle, continuing for 7-10 days, and then discontinuing. Upon determining that the endometrial thickness meets the standard, progesterone conversion of the endometrium can be performed.
| Study group | Role | What they receive |
|---|---|---|
| P4mNC group | Experimental | On days 8-12 of the menstrual cycle (MC), depending on the length of the patient's MC, transvaginal ultrasound is used to monitor follicular development and endometrial growth. Vaginal micronized progesterone (Utrogestan, Besins, Belgium) is started at 200 mg in the afternoon and 200 mg in the evening when the dominant follicle reached ≥16 mm and the endometrial thickness is at least 7 mm. A blastocyst is transferred on day 5 after the addition of progesterone. On day 14 after blastocyst transfer, serum β-hCG levels are measured. Upon positive serum pregnancy testing, progesterone support will continue until 8-10 weeks of gestation. However, afternoon progesterone use is eliminated for 30 days after embryo transfer. Receives: Drug: Progesterone-modified natural cycle preparation for frozen embryo transfer |
| HRT group | Active comparator | Endometrial preparation will begin on the second day of the menstrual cycle with oral estradiol (E2) valerate at a dose of 2 mg twice daily. When the patient's endometrial thickness is ≥7 mm, vaginal progesterone administration will be initiated at a dose of 200 mg 3 times daily. On day 5 of the progesterone administration, blastocysts are thawed and transferred. For patients with endometrial thickness <7 mm, patients continued oral E2 until the endometrium is ≥7 mm. On day 14 after blastocyst transfer, serum β-hCG levels are measured. Upon positive serum pregnancy testing, E2 and progesterone supplementation is continued for 8-10 weeks of gestation. Receives: Drug: Hormone replacement therapy cycle preparation for frozen embryo transfer |
What is being measured
The primary outcome is the main question the study is designed to answer.
Live birth
A live birth is defined as the delivery of any surviving newborn at 28 weeks or more of gestation.
Measured: Within 1 year after randomization
Secondary outcomes (4)
Biochemical pregnancy
Serum level of ß-hCG > 50 mIU/mL
Measured: Two weeks after embryo transfer
Clinical pregnancy
Fetal heartbeat observed by vaginal ultrasound
Measured: Five weeks after embryo transfer
Ongoing pregnancy
The presence of a gestational sac and fetal heartbeat after 12 weeks of gestation
Measured: Ten weeks after embryo transfer
Miscarriage
A condition in which the embryo or fetus does not survive and is not spontaneously absorbed or expelled from the uterus
Measured: Within 28 weeks of pregnancy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2024
- Study start5 Mar 2025
- Primary completion10 Sep 2027 (estimated)
- Study completion1 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Infertility, FemaleStudies of the same condition, open and under way.
- 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
- 336 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shandong University of Traditional Chinese Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jing-Yan Song, Shandong University of Traditional Chinese Medicine
- Investigators
- Zhen-Gao Sun, MD, Principal investigator, Affiliated Hospital of Shandong University of Traditional Chinese Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06644794
- Sponsor's protocol ID
- P4mNC@SDUTCM
- Acronym
- COMPROSET
- Status last verified
- Apr 2026
- First submitted
- 12 Oct 2024
- Last updated
- 29 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Inhorn MC, Patrizio P. Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update. 2015 Jul-Aug;21(4):411-26. doi: 10.1093/humupd/dmv016. Epub 2015 Mar 22.
PubMed 25801630Mascarenhas MN, Cheung H, Mathers CD, Stevens GA. Measuring infertility in populations: constructing a standard definition for use with demographic and reproductive health surveys. Popul Health Metr. 2012 Aug 31;10(1):17. doi: 10.1186/1478-7954-10-17.
PubMed 22938182Doody KJ. Cryopreservation and delayed embryo transfer-assisted reproductive technology registry and reporting implications. Fertil Steril. 2014 Jul;102(1):27-31. doi: 10.1016/j.fertnstert.2014.04.048. Epub 2014 Jun 4.
PubMed 24907917Zhang Y, Fu X, Gao S, Gao S, Gao S, Ma J, Chen ZJ. Preparation of the endometrium for frozen embryo transfer: an update on clinical practices. Reprod Biol Endocrinol. 2023 Jun 8;21(1):52. doi: 10.1186/s12958-023-01106-5.
PubMed 37291605Roelens C, Blockeel C. Impact of different endometrial preparation protocols before frozen embryo transfer on pregnancy outcomes: a review. Fertil Steril. 2022 Nov;118(5):820-827. doi: 10.1016/j.fertnstert.2022.09.003.
PubMed 36273850Gu F, Wu Y, Tan M, Hu R, Chen Y, Li X, Lin B, Duan Y, Zhou C, Li P, Ma W, Xu Y. Programmed frozen embryo transfer cycle increased risk of hypertensive disorders of pregnancy: a multicenter cohort study in ovulatory women. Am J Obstet Gynecol MFM. 2023 Jan;5(1):100752. doi: 10.1016/j.ajogmf.2022.100752. Epub 2022 Sep 15.
PubMed 36115572von Versen-Hoynck F, Schaub AM, Chi YY, Chiu KH, Liu J, Lingis M, Stan Williams R, Rhoton-Vlasak A, Nichols WW, Fleischmann RR, Zhang W, Winn VD, Segal MS, Conrad KP, Baker VL. Increased Preeclampsia Risk and Reduced Aortic Compliance With In Vitro Fertilization Cycles in the Absence of a Corpus Luteum. Hypertension. 2019 Mar;73(3):640-649. doi: 10.1161/HYPERTENSIONAHA.118.12043.
PubMed 30636552Kornilov N, Polyakov A, Mungalova A, Yakovleva L, Yakovlev P. Progesterone-modified natural cycle preparation for frozen embryo transfer. Reprod Biomed Online. 2024 Nov;49(5):104350. doi: 10.1016/j.rbmo.2024.104350. Epub 2024 Jul 2.
PubMed 39244908Yuan HN, Song JY, Sun ZG. Comparison of progesterone-modified natural cycle and hormone replacement therapy cycle for endometrial preparation in single frozen blastocyst transfer (COMPROSET): protocol for an open-label randomized controlled trial. Front Med (Lausanne). 2025 Apr 28;12:1522004. doi: 10.3389/fmed.2025.1522004. eCollection 2025.
PubMed 40357273
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Progesterone-modified Natural Cycle and Hormone Replacement Therapy Cycle for Endometrial Preparation in Single Frozen Blastocyst Transfer
- ClinicalTrials.gov ID
- NCT06644794
- Acronym / sponsor ID
- COMPROSET / P4mNC@SDUTCM
- Conditions
- Infertility, Female
- Keywords
- Progesterone-modified natural cycle, Hormone replacement therapy, Frozen-thawed embryo transfer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 336 participants (estimated)
- Lead sponsor
- Shandong University of Traditional Chinese MedicineUniversity, hospital or other
- Study start
- 5 Mar 2025 (actual)
- Primary completion
- 10 Sep 2027 (estimated)
- Study completion
- 1 Dec 2028 (estimated)
- First posted
- 16 Oct 2024 (actual)
- 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.
Hormone replacement therapy (HRT) cycles, despite the ease of synchronizing embryo thawing and embryo transfer timing, increase the risk of pregnancies and obstetric complications compared to natural cycles (NC). By ensuring the presence of the corpus luteum while reducing the number of monitoring sessions, the progesterone modified natural cycle (P4mNC) offers more convenience for the patient than the normal NC. This study is designed to compare the effects of P4mNC and HRT cycles on FET outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| P4mNC group | Experimental | Drug: Progesterone-modified natural cycle preparation for frozen embryo transferOn days 8-12 of the menstrual cycle (MC), depending on the length of the patient's MC, transvaginal ultrasound is used to monitor follicular development and endometrial growth. Vaginal micronized progesterone (Utrogestan, Besins, Belgium) is started at 200 mg in the afternoon and 200 mg in the evening when the dominant follicle reached ≥16 mm and the endometrial thickness is at least 7 mm. A blastocyst is transferred on day 5 after the addition of progesterone. On day 14 after blastocyst transfer, serum β-hCG levels are measured. Upon positive serum pregnancy testing, progesterone support will continue until 8-10 weeks of gestation. However, afternoon progesterone use is eliminated for 30 days after embryo transfer. |
| HRT group | Active comparator | Drug: Hormone replacement therapy cycle preparation for frozen embryo transferEndometrial preparation will begin on the second day of the menstrual cycle with oral estradiol (E2) valerate at a dose of 2 mg twice daily. When the patient's endometrial thickness is ≥7 mm, vaginal progesterone administration will be initiated at a dose of 200 mg 3 times daily. On day 5 of the progesterone administration, blastocysts are thawed and transferred. For patients with endometrial thickness <7 mm, patients continued oral E2 until the endometrium is ≥7 mm. On day 14 after blastocyst transfer, serum β-hCG levels are measured. Upon positive serum pregnancy testing, E2 and progesterone supplementation is continued for 8-10 weeks of gestation. |
Who may qualify
- Ages
- 21 to 44 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Patients aged 21 to 44 years undergoing FBT
- Body mass index (BMI) 18-35 kg/m2
- Having regular ovulatory cycles
Key exclusion criteria (4 listed)
- Untreated uterine adhesions
- Medical contraindications to estrogen and progesterone therapy
- Illnesses contraindicating assisted reproductive technology or pregnancy
- History of recurrent implantation failures (> 2 embryo transfer failures)
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 |
|---|---|---|
| Progesterone-modified natural cycle preparation for frozen embryo transferA novel endometrial preparation protocol that optimizes the natural cycle, whereby as long as the thickness of the endometrium is suitable for embryo transfer, vaginal progesterone can be used to transform the endometrium before ovulation and subsequently FET. | Drug | P4mNC group |
| Hormone replacement therapy cycle preparation for frozen embryo transferA traditional endometrial preparation protocol is used for FET, which involves using fixed or flexible exogenous estradiol for artificial cycles. This protocol typically involves starting exogenous estradiol on day 3 or 4 of the cycle, continuing for 7-10 days, and then discontinuing. Upon determining that the endometrial thickness meets the standard, progesterone conversion of the endometrium can be performed. | Drug | HRT group |
Primary outcome
Live birth
Time frame: Within 1 year after randomization
A live birth is defined as the delivery of any surviving newborn at 28 weeks or more of gestation.
4 secondary outcomes
Biochemical pregnancy
Time frame: Two weeks after embryo transfer
Clinical pregnancy
Time frame: Five weeks after embryo transfer
Ongoing pregnancy
Time frame: Ten weeks after embryo transfer
Miscarriage
Time frame: Within 28 weeks of pregnancy
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 29 Apr 2026.
- Background: PubMed 25801630Inhorn MC, Patrizio P. Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update. 2015 Jul-Aug;21(4):411-26. doi: 10.1093/humupd/dmv016. Epub 2015 Mar 22.
- Background: PubMed 22938182Mascarenhas MN, Cheung H, Mathers CD, Stevens GA. Measuring infertility in populations: constructing a standard definition for use with demographic and reproductive health surveys. Popul Health Metr. 2012 Aug 31;10(1):17. doi: 10.1186/1478-7954-10-17.
- Background: PubMed 24907917Doody KJ. Cryopreservation and delayed embryo transfer-assisted reproductive technology registry and reporting implications. Fertil Steril. 2014 Jul;102(1):27-31. doi: 10.1016/j.fertnstert.2014.04.048. Epub 2014 Jun 4.
- Background: PubMed 37291605Zhang Y, Fu X, Gao S, Gao S, Gao S, Ma J, Chen ZJ. Preparation of the endometrium for frozen embryo transfer: an update on clinical practices. Reprod Biol Endocrinol. 2023 Jun 8;21(1):52. doi: 10.1186/s12958-023-01106-5.
- Background: PubMed 36273850Roelens C, Blockeel C. Impact of different endometrial preparation protocols before frozen embryo transfer on pregnancy outcomes: a review. Fertil Steril. 2022 Nov;118(5):820-827. doi: 10.1016/j.fertnstert.2022.09.003.
- Background: PubMed 36115572Gu F, Wu Y, Tan M, Hu R, Chen Y, Li X, Lin B, Duan Y, Zhou C, Li P, Ma W, Xu Y. Programmed frozen embryo transfer cycle increased risk of hypertensive disorders of pregnancy: a multicenter cohort study in ovulatory women. Am J Obstet Gynecol MFM. 2023 Jan;5(1):100752. doi: 10.1016/j.ajogmf.2022.100752. Epub 2022 Sep 15.
- Background: PubMed 30636552von Versen-Hoynck F, Schaub AM, Chi YY, Chiu KH, Liu J, Lingis M, Stan Williams R, Rhoton-Vlasak A, Nichols WW, Fleischmann RR, Zhang W, Winn VD, Segal MS, Conrad KP, Baker VL. Increased Preeclampsia Risk and Reduced Aortic Compliance With In Vitro Fertilization Cycles in the Absence of a Corpus Luteum. Hypertension. 2019 Mar;73(3):640-649. doi: 10.1161/HYPERTENSIONAHA.118.12043.
- Background: PubMed 39244908Kornilov N, Polyakov A, Mungalova A, Yakovleva L, Yakovlev P. Progesterone-modified natural cycle preparation for frozen embryo transfer. Reprod Biomed Online. 2024 Nov;49(5):104350. doi: 10.1016/j.rbmo.2024.104350. Epub 2024 Jul 2.
- Derived from this study: PubMed 40357273Yuan HN, Song JY, Sun ZG. Comparison of progesterone-modified natural cycle and hormone replacement therapy cycle for endometrial preparation in single frozen blastocyst transfer (COMPROSET): protocol for an open-label randomized controlled trial. Front Med (Lausanne). 2025 Apr 28;12:1522004. doi: 10.3389/fmed.2025.1522004. eCollection 2025.
- Individual participant dataSharing planned: Undecided
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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.
Zhen-Gao Sun, MD principal investigator
Affiliated Hospital of Shandong University of Traditional Chinese Medicine
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 Progesterone-modified natural cycle preparation for frozen embryo transfer and Hormone replacement therapy cycle preparation for frozen embryo transfer in people with Infertility, Female, run by Shandong University of Traditional Chinese Medicine at 1 site 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 3 inclusion and 4 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 29 Apr 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 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?
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 Xian-Ling Cao, MD (0531-68901236, caoxianlingling@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Live birth (time frame: Within 1 year after randomization). 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 NCT06644794, which also lists 9 linked publications.
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 29 Apr 2026.