--- title: Letrozole-stimulated Cycle Strategy Versus Artificial Cycle Strategy (LETSACT) nct_id: NCT06372119 overall_status: RECRUITING phase: NA sponsor: Mỹ Đức Hospital study_type: INTERVENTIONAL primary_condition: Embryo Transfer countries: Vietnam canonical_url: "https://parkinsonspathways.com/agent/trials/NCT06372119.md" clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT06372119" ct_last_update_post_date: 2025-09-25 last_seen_at: "2026-05-12T06:30:23.985Z" source: ClinicalTrials.gov (mirrored, no enrichment) --- # Letrozole-stimulated Cycle Strategy Versus Artificial Cycle Strategy (LETSACT) **Official Title:** Letrozole-stimulated Cycle Strategy Versus Artificial Cycle Strategy for Endometrial Preparation in Women With Irregular Menstrual Cycles: A Randomized Controlled Trial **NCT ID:** [NCT06372119](https://clinicaltrials.gov/study/NCT06372119) ## Key Facts - **Status:** RECRUITING - **Phase:** NA - **Study Type:** INTERVENTIONAL - **Target Enrollment:** 790 - **Lead Sponsor:** Mỹ Đức Hospital - **Conditions:** Embryo Transfer, Irregular Menstruation, Letrozole, Hormone Replacement Therapy - **Start Date:** 2024-04-22 - **Completion Date:** 2026-04 - **CT.gov Last Update:** 2025-09-25 ## Brief Summary The goal of this randomized clinical trial is to evaluate the effectiveness of the letrozole-stimulated cycle strategy versus the artificial cycle strategy for endometrial preparation in women with irregular menstrual cycles after one cycle of endometrial preparation. The primary question it aims to answer is: • Does the letrozole-stimulated cycle strategy for endometrial preparation result in a higher live birth rate compared to the artificial cycle strategy in women with irregular menstrual cycles after one cycle of endometrial preparation? Participants will undergo screening before endometrial preparation for frozen embryo transfer, following which they will be randomly assigned to one of two groups: LETS or AC. In the LETS group, investigators will prescribe letrozole 5 milligrams/day for 5 days to stimulate follicular development and micronized progesterone 800 milligrams/day for luteal phase support. In contrast, the AC group will receive oral estradiol valerate 6-12 milligrams/day and micronized progesterone 800 milligrams/day. Researchers will compare the LETS and AC groups to determine if there are differences in live birth rates. ## Detailed Description Freeze-all and later frozen embryo transfer (FET) to reduce the risk of ovarian hyperstimulation syndrome (OHSS) is a common strategy in modern assisted reproduction technology (ART). Preparing the endometrium for FET in women with irregular menstrual cycles poses a challenge due to limited protocol options. There are two basic endometrial preparation regimens before FET: artificial cycle (AC) or natural cycle (NC). NC is often only considered if the woman has regular ovulation. In women with irregular menstrual cycles, the most popular conventional technique of endometrial preparation is AC. The advantages of AC include its convenience (meaning that the window of implantation can be determined actively and correctly) and its adaptability (meaning that the duration and the dose of exposure to estradiol and progesterone hormones can be flexibly scheduled). On the other hand, artificial exogenous estradiol levels may diminish endometrial receptivity, increase the risk of thrombosis and cancer, and negatively impact the baby's outcomes. Furthermore, the absence of the corpus luteum and its products in early pregnancy may be associated with an increased risk of placentation deficiency and an increased risk of (pre)eclampsia, which is already common in this population. The current modern approach in endometrial preparation is to create the endometrial proliferative phase that mimics the NC's physiology and to attempt to produce the corpus luteum. Previous studies showed that in the general population, ovulation-based cycles resulted in considerably greater pregnancy rates than AC, regardless of whether ovulation was natural or inducted. Exogenous gonadotropins, clomiphene citrate (CC), and aromatase inhibitors (AI) are the three types of ovulation-inducing agents widely utilized for women with irregular menstrual periods. Gonadotropin is not patient-friendly due to the route of administration and increases the risk of OHSS. CC is well-known for its antagonistic effect on estrogen receptors and its negative impact on endometrial receptivity. Letrozole, a preferred drug in the AI group, has been explored for almost two decades to avoid the drawbacks of other methods. First, letrozole can stimulate mono-follicular growth and minimize the incidence of OHSS at a low cost and in a more patient-friendly manner. Second, letrozole decreases intraovarian and serum estrogen levels, thereby upregulating endometrial estrogen receptors, increasing endometrial sensitivity to estrogen increase, and preventing premature progesterone action, which results in increased endometrial proliferation. Thirdly, there was evidence that letrozole may improve endometrial receptivity by modulating the formation of αvβ3 and HOXA10 integrin, leukemia inhibitory factor (LIF), L-selectin, and pinopode formation. The findings of some previous studies showed that the letrozole-stimulated cycle was superior to AC in terms of improving clinical pregnancy rate, live birth rate, and lower risk of miscarriage, preterm birth, pre-ecclampisa and also decreasing the risk of ectopic pregnancy. However, there was also evidence that shows no consistent advantage of letrozole as compared to AC. Notably, prior research on the effectiveness of letrozole in endometrial preparation for FET was predominantly retrospective. There were few randomized controlled trials (RCT) comparing the letrozole-stimulated cycle versus AC. However, these studies found similar treatment outcomes with two endometrial preparation methods. The sample size was also limited (N \< 150), and letrozole was often used in combination with hMG concurrently. This study will be undertaken at IVFMD, a reproductive center of My Duc Hospital in Ho Chi Minh City, Vietnam, to provide evidence on how effective letrozole is compared to conventional AC. ## Eligibility - **Minimum age:** 18 Years - **Maximum age:** 42 Years - **Sex:** FEMALE - **Healthy Volunteers:** Yes ``` Inclusion Criteria: * Aged between 18 - 42. * Irregular menstrual cycle (\< 21 days or \> 35 days or \< 8 cycles/years). * Indicated for endometrial preparation. * Transfer of only one blastocyst. * Not participating in any other trials. Exclusion Criteria: * Allergy to letrozole or Ovitrelle or oral estradiol valerate or micronized progesterone * Having embryos from either oocyte donation or PGT (pre-implantation genetics testings) cycles. * Ovarian cysts that are unrelated to the oocyte pick-up. * Confirmed diagnosis with recurrent pregnancy loss (RPL) according to ESHRE guideline 2023, recurrent implantation failure (RIF) according to ESHRE 2023 good practice recommendations. * Endometrial abnormalities include endometrial hyperplasia, intrauterine adhesions, endometrial polyp, and chronic endometritis. * Uterine abnormalities include leiomyomas L0, L1, or L2 (according to FIGO 2011); adenomyosis (according to MUSA 2022); congenital uterine abnormalities, include didelphus, arcuate, unicornuate, bicornuate, septate (according to ASRM 2021). * Untreated hydrosalpinx. ``` ## Arms - **Letrozole-stimulated cycle strategy (LETS)** (ACTIVE_COMPARATOR) — to fourth day of the menstrual cycle. Post-letrozole, ultrasound checks follicle growth. If ≥18mm, Ovitrelle® 250 mcg (Merck, Kenilworth, New Jersey, USA) induces ovulation. Luteal phase support with vaginal micronized progesterone (Cyclogest® 400 milligrams, Actavis, UK or Utrogestan® 200 milligrams, Besins, Belgium) 800 milligrams/day starting two days post-hCG. Embryo transfer, 5 days post-progesterone. Ultrasounds use Samsung HS-30, vaginal probe, and ≥7.5MHz frequency. Hormonal support until the 12th gestational week with vaginal micronized progesterone 800 milligrams/day. Cycle cancellation criteria: no follicle development on day 21 from the day of starting letrozole, spontaneous ovulation, letrozole intolerance, fluid retention. Cycle cancellation will be noted as a study's outcome. - **Artificial cycle strategy (AC)** (ACTIVE_COMPARATOR) — Oral estradiol valerate (Progynova® 2 milligrams, Bayer Pharma AG, Germany or Valiera® 2 milligrams, Laboratories Recalcine, Chile) 6 milligrams/day for 10 days, starting on the second to fourth day of the menstrual cycle. Post-estradiol, ultrasound checks endometrial thickness. If ≥7mm, start vaginal micronized progesterone (Cyclogest® 400 milligrams, Actavis, UK or Utrogestan® 200 milligrams, Besins, Belgium) 800 milligrams/day. If \<7mm, increase the dose of oral estradiol valerate to 8 milligrams/day (5-6 days) and 12 milligrams/day (5-6 days). Embryo transfer, 5 days post-progesterone. Ultrasounds use Samsung HS-30, vaginal probe, and ≥7.5MHz frequency. Hormonal support until the 12th gestational week with vaginal micronized progesterone 800 milligrams/day. Cycle cancellation criteria: endometrial thickness \<7mm on day 21 of using estradiol, spontaneous ovulation, oral estradiol valerate intolerance, fluid retention. Cycle cancellation will be noted as a study's outcome. ## Interventions - **Letrozole-stimulated cycle strategy** (PROCEDURE) — Letrozole (Femara® 2.5 milligrams, Novartis, Switzerland or Lezra® 2.5 milligrams, Actavis, Rumani) 5 milligrams/day for 5 days, starting on the second to fourth day of the menstrual cycle. Post-letrozole, ultrasound checks follicle growth. If ≥18mm, Ovitrelle® 250 mcg (Merck, Kenilworth, New Jersey, USA) induces ovulation. Luteal phase support with vaginal micronized progesterone (Cyclogest® 400 milligrams, Actavis, UK or Utrogestan® 200 milligrams, Besins, Belgium) 800 milligrams/day starting two days post-hCG. Embryo transfer, 5 days post-progesterone. Ultrasounds use Samsung HS-30, vaginal probe, and ≥7.5MHz frequency. Hormonal support until the 12th gestational week with vaginal micronized progesterone 800 milligrams/day. Cycle cancellation criteria: no follicle development on day 21 from the day of starting letrozole, spontaneous ovulation, letrozole intolerance, fluid retention. Cycle cancellation will be noted as a study's outcome. - **Artificial cycle strategy** (PROCEDURE) — Oral estradiol valerate (Progynova® 2 milligrams, Bayer Pharma AG, Germany or Valiera® 2 milligrams, Laboratories Recalcine, Chile) 6 milligrams/day for 10 days, starting on the second to fourth day of the menstrual cycle. Post-estradiol, ultrasound checks endometrial thickness. If ≥7mm, start vaginal micronized progesterone (Cyclogest® 400 milligrams, Actavis, UK or Utrogestan® 200 milligrams, Besins, Belgium) 800 milligrams/day. If \<7mm, increase the dose of oral estradiol valerate to 8 milligrams/day (5-6 days) and 12 milligrams/day (5-6 days). Embryo transfer, 5 days post-progesterone. Ultrasounds use Samsung HS-30, vaginal probe, and ≥7.5MHz frequency. Hormonal support until the 12th gestational week with vaginal micronized progesterone 800 milligrams/day. Cycle cancellation criteria: endometrial thickness \<7mm on day 21 of using estradiol, spontaneous ovulation, oral estradiol valerate intolerance, fluid retention. Cycle cancellation will be noted as a study's outcome. ## Primary Outcomes - **Live birth rate after one cycle of endometrial preparation** _(time frame: After 22 completed weeks of gestational age.)_ — Live birth will be defined as the complete expulsion or extraction from a woman of a product of fertilization, after 22 completed weeks of gestational age; which, after such separation, breathes or shows any other evidence of life, such as heart beat, umbilical cord pulsation or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is atached. A birth weight of 500 grams or more can be used if gestational age is unknown. Twin and higher multiple births will be reported as a single live birth event. ## Secondary Outcomes - **Positive pregnancy test after one cycle of endometrial preparation** _(time frame: At 11 days after blastocyst transfer.)_ - **Clinical pregnancy after one cycle of endometrial preparation** _(time frame: First ultrasound before 6 weeks of gestational age.)_ - **Ongoing pregnancy after one cycle of endometrial preparation** _(time frame: After 12 weeks of gestational age.)_ - **Multiple pregnancy after one cycle of endometrial preparation** _(time frame: Ultrasound at 6-9 weeks of gestational age.)_ - **Implantation rate after one cycle of endometrial preparation** _(time frame: Ultrasound at 6-9 weeks of gestational age.)_ - **Cycle cancellation rate** _(time frame: During the intervention (on day 21 from the day of starting to use letrozole or valiera).)_ - **Ectopic pregnancy rate after one cycle of endometrial preparation** _(time frame: Ultrasound at 6-9 weeks of gestational age.)_ - **Threatened miscarriage rate before 12 weeks of gestation after one cycle of endometrial preparation** _(time frame: At 12 weeks of gestational age.)_ - **Early miscarriage rate after one cycle of endometrial preparation** _(time frame: At 12 weeks of gestational age.)_ - **Late miscarriage rate after one cycle of endometrial preparation** _(time frame: At 22 weeks of gestational age.)_ - **Gestational age at birth** _(time frame: On the day of delivery.)_ - **Onset of labor** _(time frame: On the day of delivery.)_ - **Mode of delivery** _(time frame: On the day of delivery.)_ - **Very low birth weight** _(time frame: On the day of delivery.)_ - **Low birth weight** _(time frame: On the day of delivery.)_ - **High birth weight (macrosomia)** _(time frame: On the day of delivery.)_ - **Very high birth weight (macrosomia)** _(time frame: On the day of delivery.)_ - **Gestational diabetes (GDM)** _(time frame: At 24-28 weeks of gestational age.)_ - **Hypertensive disorders of pregnancy** _(time frame: On the day of delivery.)_ - **Preterm birth** _(time frame: On the day of delivery.)_ - **Stillbirth** _(time frame: On the day of delivery.)_ - **Antepartum hemorrhage** _(time frame: On the day of delivery.)_ - **Postpartum hemorrhage** _(time frame: On the day of delivery.)_ - **Small for gestational age (singleton/twins)** _(time frame: On the day of delivery.)_ - **Large for gestational age (singleton/twins)** _(time frame: On the day of delivery.)_ - **Birth weight** _(time frame: On the day of delivery.)_ - **Congenital anomalies** _(time frame: Within 28 days of birth.)_ - **NICU admission** _(time frame: Within 28 days of birth.)_ - **Reason for NICU admission** _(time frame: Within 28 days of birth.)_ - **Neonatal mortality rate** _(time frame: Within 28 days of birth.)_ ## Locations (2) - My Duc Hospital, Ho Chi Minh City, Ho Chi Minh City, Vietnam — _RECRUITING_ - My Duc Phu Nhuan Hospital, Ho Chi Minh City, Ho Chi Minh City, Vietnam — _RECRUITING_ ## Recent Field Changes (last 30 days) - `status.overallStatus` — added _(2026-05-12)_ - `status.primaryCompletionDate` — added _(2026-05-12)_ - `status.completionDate` — added _(2026-05-12)_ - `status.lastUpdatePostDate` — added _(2026-05-12)_ - `design.phases` — added _(2026-05-12)_ - `design.enrollmentCount` — added _(2026-05-12)_ - `eligibility.criteria` — added _(2026-05-12)_ - `eligibility.minAge` — added _(2026-05-12)_ - `eligibility.maxAge` — added _(2026-05-12)_ - `eligibility.sex` — added _(2026-05-12)_ - `outcomes.primary` — added _(2026-05-12)_ - `outcomes.secondary` — added _(2026-05-12)_ - `armsInterventions.arms` — added _(2026-05-12)_ - `armsInterventions.interventions` — added _(2026-05-12)_ - `sponsor.lead` — added _(2026-05-12)_ - `results.hasResults` — added _(2026-05-12)_ - `locations.my duc hospital|ho chi minh city|ho chi minh city|vietnam` — added _(2026-05-12)_ - `locations.my duc phu nhuan hospital|ho chi minh city|ho chi minh city|vietnam` — added _(2026-05-12)_ --- *Canonical: https://parkinsonspathways.com/agent/trials/NCT06372119.md* *Source data (authoritative): https://clinicaltrials.gov/study/NCT06372119* *This page is a raw mirror with no AI summary, no editorial enrichment, and no Parkinson's-specific filtering.*