Letrozole-stimulated Cycle Strategy Versus Artificial Cycle Strategy (LETSACT)

NCT06372119 | Recruiting DMC

• 1 other identifier: 13/23/DD-BVMD
• Study Type: interventional
• Target: 790
• Locations: 1 country
• Sites: 2

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.

Conditions

Embryo Transfer; Irregular Menstruation; Letrozole; Hormone Replacement Therapy

Keywords

Blastocyst Transfer; Irregular Menstruation; Letrozole; Hormone Replacement Therapy

Outcome Measures

Primary Outcomes (1)

• Live birth rate after one cycle of endometrial preparation

  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.

  After 22 completed weeks of gestational age.

Secondary Outcomes (30)

• Positive pregnancy test after one cycle of endometrial preparation

  At 11 days after blastocyst transfer.

• Clinical pregnancy after one cycle of endometrial preparation

  First ultrasound before 6 weeks of gestational age.

• Ongoing pregnancy after one cycle of endometrial preparation

  After 12 weeks of gestational age.

• Multiple pregnancy after one cycle of endometrial preparation

  Ultrasound at 6-9 weeks of gestational age.

• Implantation rate after one cycle of endometrial preparation

  Ultrasound at 6-9 weeks of gestational age.

Study Arms (2)

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.

Procedure: Letrozole-stimulated cycle strategy

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.

Procedure: Artificial cycle strategy

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.

Also known as: LETS

Letrozole-stimulated cycle strategy (LETS)

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.

Also known as: AC

Artificial cycle strategy (AC)

Eligibility Criteria

• Age: 18 Years - 42 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mỹ Đức Hospital: lead

Study Sites (2)

My Duc Hospital

Ho Chi Minh City, Ho Chi Minh City, 70000, Vietnam

RECRUITING

My Duc Phu Nhuan Hospital

Ho Chi Minh City, Ho Chi Minh City, 70000, Vietnam

RECRUITING

Related Publications (53)

• ACOG Committee on Obstetric Practice. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 2002 Apr;77(1):67-75.

  PMID: 12094777 BACKGROUND

• Aleyasin A, Aghahosseini M, Safdarian L, Noorzadeh M, Fallahi P, Rezaeian Z, Hoseinimosa S. Can letrozole plus HMG protocol improve pregnancy outcomes in frozen-thawed embryo transfer? An RCT. Int J Reprod Biomed. 2017 Feb;15(2):83-86.

  PMID: 28462399 BACKGROUND

• Aslih N, Dorzia D, Atzmon Y, Estrada D, Ellenbogen A, Bilgory A, Shalom-Paz E. Ovulatory-Based FET Cycles May Achieve Higher Pregnancy Rates in the General Population and among Anovulatory Women. J Clin Med. 2021 Feb 11;10(4):703. doi: 10.3390/jcm10040703.

  PMID: 33670133 BACKGROUND

• Atkinson M, Crittenden J, Smith H, Sjoblom C. Retrospective cohort study on preparation regimens for frozen embryo transfer. Reprod Fertil. 2021 Nov 23;2(4):308-316. doi: 10.1530/RAF-21-0044. eCollection 2021 Dec.

  PMID: 35118408 BACKGROUND

• Bocca-Tjeertes IF, Kerstjens JM, Reijneveld SA, Veldman K, Bos AF, de Winter AF. Growth patterns of large for gestational age children up to age 4 years. Pediatrics. 2014 Mar;133(3):e643-9. doi: 10.1542/peds.2013-0985. Epub 2014 Feb 24.

  PMID: 24567020 BACKGROUND

• Braakhekke M, Kamphuis EI, Dancet EA, Mol F, van der Veen F, Mol BW. Ongoing pregnancy qualifies best as the primary outcome measure of choice in trials in reproductive medicine: an opinion paper. Fertil Steril. 2014 May;101(5):1203-4. doi: 10.1016/j.fertnstert.2014.03.047.

  PMID: 24786739 BACKGROUND

• Casper RF, Mitwally MF. Use of the aromatase inhibitor letrozole for ovulation induction in women with polycystic ovarian syndrome. Clin Obstet Gynecol. 2011 Dec;54(4):685-95. doi: 10.1097/GRF.0b013e3182353d0f.

  PMID: 22031258 BACKGROUND

• Chung TW, Park MJ, Kim HS, Choi HJ, Ha KT. Integrin alphaVbeta3 and alphaVbeta5 are required for leukemia inhibitory factor-mediated the adhesion of trophoblast cells to the endometrial cells. Biochem Biophys Res Commun. 2016 Jan 22;469(4):936-40. doi: 10.1016/j.bbrc.2015.12.103. Epub 2015 Dec 24.

  PMID: 26723254 BACKGROUND

• Committee on Practice Bulletins-Obstetrics. Practice Bulletin No. 183: Postpartum Hemorrhage. Obstet Gynecol. 2017 Oct;130(4):e168-e186. doi: 10.1097/AOG.0000000000002351.

  PMID: 28937571 BACKGROUND

• Donderwinkel PF, Schoot DC, Pache TD, de Jong FH, Hop WC, Fauser BC. Luteal function following ovulation induction in polycystic ovary syndrome patients using exogenous gonadotrophins in combination with a gonadotrophin-releasing hormone agonist. Hum Reprod. 1993 Dec;8(12):2027-32. doi: 10.1093/oxfordjournals.humrep.a137976.

  PMID: 8150898 BACKGROUND

• Duffy JMN, Bhattacharya S, Bhattacharya S, Bofill M, Collura B, Curtis C, Evers JLH, Giudice LC, Farquharson RG, Franik S, Hickey M, Hull ML, Jordan V, Khalaf Y, Legro RS, Lensen S, Mavrelos D, Mol BW, Niederberger C, Ng EHY, Puscasiu L, Repping S, Sarris I, Showell M, Strandell A, Vail A, van Wely M, Vercoe M, Vuong NL, Wang AY, Wang R, Wilkinson J, Youssef MA, Farquhar CM; Core Outcome Measure for Infertility Trials (COMMIT) initiative. Standardizing definitions and reporting guidelines for the infertility core outcome set: an international consensus development study. Fertil Steril. 2021 Jan;115(1):201-212. doi: 10.1016/j.fertnstert.2020.11.013. Epub 2020 Nov 30.

  PMID: 33272619 BACKGROUND

• ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, Collins BS, Hilliard ME, Isaacs D, Johnson EL, Kahan S, Khunti K, Leon J, Lyons SK, Perry ML, Prahalad P, Pratley RE, Seley JJ, Stanton RC, Gabbay RA, on behalf of the American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Care in Diabetes-2023. Diabetes Care. 2023 Jan 1;46(Suppl 1):S19-S40. doi: 10.2337/dc23-S002.

  PMID: 36507649 BACKGROUND

• ESHRE Working Group on Recurrent Implantation Failure; Cimadomo D, de Los Santos MJ, Griesinger G, Lainas G, Le Clef N, McLernon DJ, Montjean D, Toth B, Vermeulen N, Macklon N. ESHRE good practice recommendations on recurrent implantation failure. Hum Reprod Open. 2023 Jun 15;2023(3):hoad023. doi: 10.1093/hropen/hoad023. eCollection 2023.

  PMID: 37332387 BACKGROUND

• Franik S, Eltrop SM, Kremer JA, Kiesel L, Farquhar C. Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2018 May 24;5(5):CD010287. doi: 10.1002/14651858.CD010287.pub3.

  PMID: 29797697 BACKGROUND

• Ganesh A, Chauhan N, Das S, Chakravarty B, Chaudhury K. Endometrial receptivity markers in infertile women stimulated with letrozole compared with clomiphene citrate and natural cycles. Syst Biol Reprod Med. 2014 Apr;60(2):105-11. doi: 10.3109/19396368.2013.862316. Epub 2013 Dec 5.

  PMID: 24304327 BACKGROUND

• Godiwala P, Makhijani R, Bartolucci A, Grow D, Nulsen J, Benadiva C, Grady J, Engmann L. Pregnancy outcomes after frozen-thawed embryo transfer using letrozole ovulation induction, natural, or programmed cycles. Fertil Steril. 2022 Oct;118(4):690-698. doi: 10.1016/j.fertnstert.2022.06.013. Epub 2022 Jul 19.

  PMID: 35863997 BACKGROUND

• Haouzi D, Assou S, Mahmoud K, Tondeur S, Reme T, Hedon B, De Vos J, Hamamah S. Gene expression profile of human endometrial receptivity: comparison between natural and stimulated cycles for the same patients. Hum Reprod. 2009 Jun;24(6):1436-45. doi: 10.1093/humrep/dep039. Epub 2009 Feb 26.

  PMID: 19246470 BACKGROUND

• Harmsen MJ, Van den Bosch T, de Leeuw RA, Dueholm M, Exacoustos C, Valentin L, Hehenkamp WJK, Groenman F, De Bruyn C, Rasmussen C, Lazzeri L, Jokubkiene L, Jurkovic D, Naftalin J, Tellum T, Bourne T, Timmerman D, Huirne JAF. Consensus on revised definitions of Morphological Uterus Sonographic Assessment (MUSA) features of adenomyosis: results of modified Delphi procedure. Ultrasound Obstet Gynecol. 2022 Jul;60(1):118-131. doi: 10.1002/uog.24786.

  PMID: 34587658 BACKGROUND

• Healey S, Tan SL, Tulandi T, Biljan MM. Effects of letrozole on superovulation with gonadotropins in women undergoing intrauterine insemination. Fertil Steril. 2003 Dec;80(6):1325-9. doi: 10.1016/j.fertnstert.2003.03.001.

  PMID: 14667860 BACKGROUND

• Hecher K, Diehl W. Chapter 13 - Multiple pregnancies. In Wladimiroff JW, Eik-Nes SH, editors. Ultrasound Obstet Gynaecol 2009. p. 247-258. Elsevier: Edinburgh. Available from: https://www.sciencedirect.com/science/article/pii/B9780444518293000131.

  BACKGROUND

• Herskovits AZ, Chen Y, Latifi N, Ta RM, Kriegel G. False-Negative Urine Human Chorionic Gonadotropin Testing in the Clinical Laboratory. Lab Med. 2020 Jan 2;51(1):86-93. doi: 10.1093/labmed/lmz039.

  PMID: 31245816 BACKGROUND

• Hosseini-Najarkolaei A, Moini A, Kashani L, Farid Mojtahedi M, Hosseini-Najarkolaee E, Salehi E. The effect of letrozole versus artificial hormonal endometrial preparation on pregnancy outcome after frozen-thawed embryos transfer cycles: a randomized clinical trial. Reprod Biol Endocrinol. 2020 Nov 20;18(1):115. doi: 10.1186/s12958-020-00675-z.

  PMID: 33218350 BACKGROUND

• Hu YJ, Chen YZ, Zhu YM, Huang HF. Letrozole stimulation in endometrial preparation for cryopreserved-thawed embryo transfer in women with polycystic ovarian syndrome: a pilot study. Clin Endocrinol (Oxf). 2014 Feb;80(2):283-9. doi: 10.1111/cen.12280. Epub 2013 Jul 24.

  PMID: 23808904 BACKGROUND

• Khadem Ghaebi N, Mahmoudiniya M, Najaf Najafi M, Zohdi E, Attaran M. Comparison of letrozole with gonadotropin-releasing hormone agonist in frozen embryo transfer after recurrent implantation failure: An RCT. Int J Reprod Biomed. 2020 Feb 27;18(2):105-112. doi: 10.18502/ijrm.v18i2.6417. eCollection 2020 Feb.

  PMID: 32259004 BACKGROUND

• Li SJ, Zhang YJ, Chai XS, Nie MF, Zhou YY, Chen JL, Tao GS. Letrozole ovulation induction: an effective option in endometrial preparation for frozen-thawed embryo transfer. Arch Gynecol Obstet. 2014 Mar;289(3):687-93. doi: 10.1007/s00404-013-3044-0. Epub 2013 Oct 10.

  PMID: 24121690 BACKGROUND

• Lin J, Wang N, Huang J, Cai R, Fan Y, Kuang Y, Wang Y. Pregnancy And Neonatal Outcomes Of hMG Stimulation With Or Without Letrozole In Endometrial Preparation For Frozen-Thawed Embryo Transfer In Ovulatory Women: A Large Retrospective Cohort Study. Drug Des Devel Ther. 2019 Nov 14;13:3867-3877. doi: 10.2147/DDDT.S212235. eCollection 2019.

  PMID: 31814708 BACKGROUND

• Lou L, Xu Y, Lv M, Yu J, Xiao Q, Chen P, Bai M, Zhang Z. Comparison of different endometrial preparation protocols on frozen embryo transfer pregnancy outcome in patients with normal ovulation. Reprod Biomed Online. 2022 Dec;45(6):1182-1187. doi: 10.1016/j.rbmo.2022.06.026. Epub 2022 Jul 4.

  PMID: 36085270 BACKGROUND

• Macrosomia: ACOG Practice Bulletin, Number 216. Obstet Gynecol. 2020 Jan;135(1):e18-e35. doi: 10.1097/AOG.0000000000003606.

  PMID: 31856124 BACKGROUND

• Miller PB, Parnell BA, Bushnell G, Tallman N, Forstein DA, Higdon HL 3rd, Kitawaki J, Lessey BA. Endometrial receptivity defects during IVF cycles with and without letrozole. Hum Reprod. 2012 Mar;27(3):881-8. doi: 10.1093/humrep/der452. Epub 2012 Jan 13.

  PMID: 22246449 BACKGROUND

• Montville CP, Khabbaz M, Aubuchon M, Williams DB, Thomas MA. Luteal support with intravaginal progesterone increases clinical pregnancy rates in women with polycystic ovary syndrome using letrozole for ovulation induction. Fertil Steril. 2010 Jul;94(2):678-83. doi: 10.1016/j.fertnstert.2009.03.088. Epub 2009 Jun 9.

  PMID: 19515366 BACKGROUND

• Munro MG, Critchley HO, Broder MS, Fraser IS; FIGO Working Group on Menstrual Disorders. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet. 2011 Apr;113(1):3-13. doi: 10.1016/j.ijgo.2010.11.011. Epub 2011 Feb 22.

  PMID: 21345435 BACKGROUND

• Niu Y, Zhao D, Wang Y, Suo L, Zou J, Wei D. Ovulation induction regimens are associated with a higher rate of livebirth after frozen single-blastocyst transfer among women with polycystic ovary syndrome. Front Endocrinol (Lausanne). 2022 Aug 15;13:987813. doi: 10.3389/fendo.2022.987813. eCollection 2022.

  PMID: 36046783 BACKGROUND

• de Onis M, Habicht JP. Anthropometric reference data for international use: recommendations from a World Health Organization Expert Committee. Am J Clin Nutr. 1996 Oct;64(4):650-8. doi: 10.1093/ajcn/64.4.650.

  PMID: 8839517 BACKGROUND

• Oxford Textbook of Obstetrics and Gynaecology 2020; Oxford University Press Available from: https://academic.oup.com/book/29679.

  BACKGROUND

• Pathirana J, Munoz FM, Abbing-Karahagopian V, Bhat N, Harris T, Kapoor A, Keene DL, Mangili A, Padula MA, Pande SL, Pool V, Pourmalek F, Varricchio F, Kochhar S, Cutland CL; Brighton Collaboration Neonatal Death Working Group. Neonatal death: Case definition & guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine. 2016 Dec 1;34(49):6027-6037. doi: 10.1016/j.vaccine.2016.03.040. Epub 2016 Jul 19.

  PMID: 27449077 BACKGROUND

• Pfeifer SM, Attaran M, Goldstein J, Lindheim SR, Petrozza JC, Rackow BW, Siegelman E, Troiano R, Winter T, Zuckerman A, Ramaiah SD. ASRM mullerian anomalies classification 2021. Fertil Steril. 2021 Nov;116(5):1238-1252. doi: 10.1016/j.fertnstert.2021.09.025.

  PMID: 34756327 BACKGROUND

• Rezk M, Hamza H, El-Shamy ES. Luteal support with vaginal dydrogesterone increases pregnancy rate in patients with clomifene resistant polycystic ovary syndrome receiving letrozole for ovulation induction. Gynecol Endocrinol. 2019 Mar;35(3):217-219. doi: 10.1080/09513590.2018.1512571. Epub 2018 Oct 16.

  PMID: 30324834 BACKGROUND

• Royal College of Obstetricians and Gynaecologists. Antepartum Haemorrhage (Green-top Guideline No. 63). 2011; Available from: https://www.rcog.org.uk/guidance/browse-all-guidance/green-top-guidelines/antepartum-haemorrhage-green-top-guideline-no-63/.

  BACKGROUND

• Samsami A, Ghasmpour L, Davoodi S, Moradi Alamdarloo S, Rahmati J, Karimian A, Homayoon H. Frozen embryo transfer: Endometrial preparation by letrozole versus hormone replacement cycle: A randomized clinical trial. Int J Reprod Biomed. 2019 Dec 30;17(12):915-922. doi: 10.18502/ijrm.v17i12.5793. eCollection 2019 Dec.

  PMID: 31970313 BACKGROUND

• Simon C, Cano F, Valbuena D, Remohi J, Pellicer A. Clinical evidence for a detrimental effect on uterine receptivity of high serum oestradiol concentrations in high and normal responder patients. Hum Reprod. 1995 Sep;10(9):2432-7. doi: 10.1093/oxfordjournals.humrep.a136313.

  PMID: 8530680 BACKGROUND

• Sotiriadis A, Papatheodorou S, Makrydimas G. Threatened miscarriage: evaluation and management. BMJ. 2004 Jul 17;329(7458):152-5. doi: 10.1136/bmj.329.7458.152. No abstract available.

  PMID: 15258071 BACKGROUND

• Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, Piltonen T, Norman RJ; International PCOS Network. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil Steril. 2018 Aug;110(3):364-379. doi: 10.1016/j.fertnstert.2018.05.004. Epub 2018 Jul 19.

  PMID: 30033227 BACKGROUND

• Teede HJ, Tay CT, Laven JJE, Dokras A, Moran LJ, Piltonen TT, Costello MF, Boivin J, Redman LM, Boyle JA, Norman RJ, Mousa A, Joham AE. Recommendations From the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2023 Sep 18;108(10):2447-2469. doi: 10.1210/clinem/dgad463.

  PMID: 37580314 BACKGROUND

• Wang X, Chen C, Wang L, Chen D, Guang W, French J. Conception, early pregnancy loss, and time to clinical pregnancy: a population-based prospective study. Fertil Steril. 2003 Mar;79(3):577-84. doi: 10.1016/s0015-0282(02)04694-0.

  PMID: 12620443 BACKGROUND

• Webster K, Fishburn S, Maresh M, Findlay SC, Chappell LC; Guideline Committee. Diagnosis and management of hypertension in pregnancy: summary of updated NICE guidance. BMJ. 2019 Sep 9;366:l5119. doi: 10.1136/bmj.l5119. No abstract available.

  PMID: 31501137 BACKGROUND

• Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, Rienzi L, Sunde A, Schmidt L, Cooke ID, Simpson JL, van der Poel S. The International Glossary on Infertility and Fertility Care, 2017. Hum Reprod. 2017 Sep 1;32(9):1786-1801. doi: 10.1093/humrep/dex234.

  PMID: 29117321 BACKGROUND

• Zeng MF, Zhou X, Duan JL. Stimulated cycle versus artificial cycle for frozen embryo transfer in patients with polycystic ovary syndrome: a Meta-analysis. Gynecol Endocrinol. 2021 Apr;37(4):294-299. doi: 10.1080/09513590.2020.1867976. Epub 2021 Jan 10.

  PMID: 33426930 BACKGROUND

• Zhang J, Li Z, Sun L, Guan Y, Du M. Comparison of Pregnancy and Neonatal Outcomes of Single Frozen Blastocyst Transfer Between Letrozole-Induction and HRT Cycles in Patients With Abnormal Ovulation. Front Endocrinol (Lausanne). 2021 Apr 16;12:664072. doi: 10.3389/fendo.2021.664072. eCollection 2021.

  PMID: 33935972 BACKGROUND

• Zhang J, Wang L, Li C, Zhang H, Li R, Li M. Letrozole promotes the expression of integrin alphavbeta3 and HOXA10 in endometrium of endometriosis. Syst Biol Reprod Med. 2022 Apr;68(2):121-128. doi: 10.1080/19396368.2021.2013577. Epub 2021 Dec 28.

  PMID: 34962452 BACKGROUND

• Zhang J, Wei M, Bian X, Wu L, Zhang S, Mao X, Wang B. Letrozole-induced frozen embryo transfer cycles are associated with a lower risk of hypertensive disorders of pregnancy among women with polycystic ovary syndrome. Am J Obstet Gynecol. 2021 Jul;225(1):59.e1-59.e9. doi: 10.1016/j.ajog.2021.01.024. Epub 2021 Jan 30.

  PMID: 33529574 BACKGROUND

• Zhang W, Liu Z, Zhang J, Ren B, Liu M, Li J, Zhang W, Guan Y. Comparison of Perinatal Outcomes of Letrozole-Induced Ovulation and Hormone Replacement Therapy Protocols in Patients With Abnormal Ovulation Undergoing Frozen-Thawed Embryo Transfer: A Propensity Score Matching Analysis. Front Endocrinol (Lausanne). 2022 Mar 16;13:837731. doi: 10.3389/fendo.2022.837731. eCollection 2022.

  PMID: 35370976 BACKGROUND

• Zhang 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.

  PMID: 37291605 BACKGROUND

• Zhang Y, Wu L, Li TC, Wang CC, Zhang T, Chung JPW. Systematic review update and meta-analysis of randomized and non-randomized controlled trials of ovarian stimulation versus artificial cycle for endometrial preparation prior to frozen embryo transfer in women with polycystic ovary syndrome. Reprod Biol Endocrinol. 2022 Apr 2;20(1):62. doi: 10.1186/s12958-022-00931-4.

  PMID: 35366912 BACKGROUND

MeSH Terms

Conditions

Menstruation Disturbances

Interventions

enkephalinamide-Leu, Tyr sulfate(1)-

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Lan TN Vuong, Assoc. Prof.

  University of Medicine and Pharmacy at Ho Chi Minh City

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nam T Nguyen, MD.

CONTACT

+84354120209; bsnam.nt@myduchospital.vn

Vu NA Ho, MD.

CONTACT

+84935843336; bsvu.hna@myduchospital.vn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2023
• First Posted: April 17, 2024
• Study Start: April 22, 2024
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

VN (2)