- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03954587
What is the Optimal Cycle Regimen for Frozen- Thawed Embryo Transfer Cycles
What is the Optimal Cycle Regimen for Frozen- Thawed Embryo Transfer Cycles: Spontaneous Natural Cycles Versus Hormonal Replacement Treatment (HRT) Cycles
Study Overview
Status
Conditions
Detailed Description
The most common treatment protocols for frozen embryo transfers include natural cycles with or without human chorionic gonadotrophin (HCG) trigger or endometrial preparation with hormonal treatment (artificial cycles), with or without Gonadotrophin - releasing hormone agonist suppression. Recent studies comparing artificial and natural cycles concluded that the optimal means of endometrial preparation for frozen- thawed cycle remains unclear and both options may be offered to women with regular ovulatory cycles.
Correctly identified spontaneous natural cycles are the preferred option for frozen-thawed embryo transfer in women with regular menstrual cycles.
Investigators will be comparing artificial (HRT) frozen-thawed embryo transfer cycles to correctly conducted spontaneous natural cycles after the transfer of a chromosomally normal embryo.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Abu Dhabi, United Arab Emirates, 60202
- IVI Middle East Fertility Clinic
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion criteria include the following:
- Women aged 18 years to 42 years with regular menses (26-34 days)
- Having 1 or 2 chromosomally normal cryopreserved blastocysts available for transfer.
- First frozen-thawed transfer cycle
- Progesterone level < 1.5 ng/mL day of trigger injection in stimulation cycle from which embryos to be transferred were created.
Exclusion criteria include the following:
- Polycystic ovarian syndrome
- Poor ovarian responder in accordance with Bologna criteria
- Uterine abnormality US / saline infusion sonohysterogram
- Previous dilatation & curettage (D&C)
- Hydrosalpinx
- Asherman syndrome
- History of endometriosis
- ICSI due to severe male factor with testicular sperm
- Any known contraindications or allergy to oral estradiol or progesterone.
- Discontinuation of HRT medication ( medication error in research HRT cycle )
- Failure to detect ovulation in the research natural cycle
- Duration of estradiol exposure ≥ 17 days and endometrium < 6mm
- Spontaneous ovulation in HRT artificial cycle
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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Artificial (HRT) Cycles
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Spontaneous natural cycles:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Ongoing pregnancy rate to 8 weeks gestation
Time Frame: 8 weeks
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viable pregnancy to 8 gestational weeks
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8 weeks
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Pregnancy rate beta human chorionic gonadotropin (ß-hCG) > 5 IU
Time Frame: 12 days
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Number of patients with a hCG > 5 IU out of the number of patients who underwent an embryo transfer with one or two euploid embryos
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12 days
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Biochemical pregnancy rate
Time Frame: 5 weeks
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Positive ß-hCG, but at 5 gestational weeks no ultrasonographic visible gestational sac seen
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5 weeks
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Clinical implantation rate
Time Frame: 6 weeks
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Number of gestational sacs observed by ultrasound at 6 weeks of gestation divided by the number of embryos transferred
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6 weeks
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Clinical pregnancy rate
Time Frame: 5 weeks
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Ultrasonographic visible sac at 5 gestational weeks
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5 weeks
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Carol Coughlan, PhD, IVI Middle East Fertility Clinic LLC
Publications and helpful links
General Publications
- Fatemi HM, Kyrou D, Bourgain C, Van den Abbeel E, Griesinger G, Devroey P. Cryopreserved-thawed human embryo transfer: spontaneous natural cycle is superior to human chorionic gonadotropin-induced natural cycle. Fertil Steril. 2010 Nov;94(6):2054-8. doi: 10.1016/j.fertnstert.2009.11.036. Epub 2010 Jan 25.
- Groenewoud ER, Cantineau AE, Kollen BJ, Macklon NS, Cohlen BJ. What is the optimal means of preparing the endometrium in frozen-thawed embryo transfer cycles? A systematic review and meta-analysis. Hum Reprod Update. 2013 Sep-Oct;19(5):458-70. doi: 10.1093/humupd/dmt030. Epub 2013 Jul 2. Erratum In: Hum Reprod Update. 2017 Mar 1;23(2):255-261.
- 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.
- Bourgain C, Devroey P. The endometrium in stimulated cycles for IVF. Hum Reprod Update. 2003 Nov-Dec;9(6):515-22. doi: 10.1093/humupd/dmg045.
- Irani M, Robles A, Gunnala V, Reichman D, Rosenwaks Z. Optimal parameters for determining the LH surge in natural cycle frozen-thawed embryo transfers. J Ovarian Res. 2017 Oct 16;10(1):70. doi: 10.1186/s13048-017-0367-7.
- Kolibianakis E, Bourgain C, Albano C, Osmanagaoglu K, Smitz J, Van Steirteghem A, Devroey P. Effect of ovarian stimulation with recombinant follicle-stimulating hormone, gonadotropin releasing hormone antagonists, and human chorionic gonadotropin on endometrial maturation on the day of oocyte pick-up. Fertil Steril. 2002 Nov;78(5):1025-9. doi: 10.1016/s0015-0282(02)03323-x.
- Roque M, Lattes K, Serra S, Sola I, Geber S, Carreras R, Checa MA. Fresh embryo transfer versus frozen embryo transfer in in vitro fertilization cycles: a systematic review and meta-analysis. Fertil Steril. 2013 Jan;99(1):156-162. doi: 10.1016/j.fertnstert.2012.09.003. Epub 2012 Oct 3.
- Roque M, Valle M, Guimaraes F, Sampaio M, Geber S. Freeze-all policy: fresh vs. frozen-thawed embryo transfer. Fertil Steril. 2015 May;103(5):1190-3. doi: 10.1016/j.fertnstert.2015.01.045. Epub 2015 Mar 4.
- Devroey P, Bourgain C, Macklon NS, Fauser BC. Reproductive biology and IVF: ovarian stimulation and endometrial receptivity. Trends Endocrinol Metab. 2004 Mar;15(2):84-90. doi: 10.1016/j.tem.2004.01.009.
- Nikas G, Develioglu OH, Toner JP, Jones HW Jr. Endometrial pinopodes indicate a shift in the window of receptivity in IVF cycles. Hum Reprod. 1999 Mar;14(3):787-92. doi: 10.1093/humrep/14.3.787.
- Simon C, Garcia Velasco JJ, Valbuena D, Peinado JA, Moreno C, Remohi J, Pellicer A. Increasing uterine receptivity by decreasing estradiol levels during the preimplantation period in high responders with the use of a follicle-stimulating hormone step-down regimen. Fertil Steril. 1998 Aug;70(2):234-9. doi: 10.1016/s0015-0282(98)00140-x.
- Weinerman R, Mainigi M. Why we should transfer frozen instead of fresh embryos: the translational rationale. Fertil Steril. 2014 Jul;102(1):10-8. doi: 10.1016/j.fertnstert.2014.05.019. Epub 2014 Jun 2.
- Liu Y, Lee KF, Ng EH, Yeung WS, Ho PC. Gene expression profiling of human peri-implantation endometria between natural and stimulated cycles. Fertil Steril. 2008 Dec;90(6):2152-64. doi: 10.1016/j.fertnstert.2007.10.020. Epub 2008 Jan 14.
- Ghobara T, Gelbaya TA, Ayeleke RO. Cycle regimens for frozen-thawed embryo transfer. Cochrane Database Syst Rev. 2017 Jul 5;7(7):CD003414. doi: 10.1002/14651858.CD003414.pub3.
- Groenewoud ER, Cohlen BJ, Macklon NS. Programming the endometrium for deferred transfer of cryopreserved embryos: hormone replacement versus modified natural cycles. Fertil Steril. 2018 May;109(5):768-774. doi: 10.1016/j.fertnstert.2018.02.135.
- Agha-Hosseini M, Hashemi L, Aleyasin A, Ghasemi M, Sarvi F, Shabani Nashtaei M, Khodarahmian M. Natural cycle versus artificial cycle in frozen-thawed embryo transfer: A randomized prospective trial. Turk J Obstet Gynecol. 2018 Mar;15(1):12-17. doi: 10.4274/tjod.47855. Epub 2018 Mar 29.
- Zimmermann G, Ackermann W, Alexander H. Epithelial human chorionic gonadotropin is expressed and produced in human secretory endometrium during the normal menstrual cycle. Biol Reprod. 2009 May;80(5):1053-65. doi: 10.1095/biolreprod.108.069575. Epub 2009 Jan 21.
- Shi Y, Sun Y, Hao C, Zhang H, Wei D, Zhang Y, Zhu Y, Deng X, Qi X, Li H, Ma X, Ren H, Wang Y, Zhang D, Wang B, Liu F, Wu Q, Wang Z, Bai H, Li Y, Zhou Y, Sun M, Liu H, Li J, Zhang L, Chen X, Zhang S, Sun X, Legro RS, Chen ZJ. Transfer of Fresh versus Frozen Embryos in Ovulatory Women. N Engl J Med. 2018 Jan 11;378(2):126-136. doi: 10.1056/NEJMoa1705334. Erratum In: N Engl J Med. 2021 Nov 4;385(19):1824.
- O'Connor KA, Brindle E, Miller RC, Shofer JB, Ferrell RJ, Klein NA, Soules MR, Holman DJ, Mansfield PK, Wood JW. Ovulation detection methods for urinary hormones: precision, daily and intermittent sampling and a combined hierarchical method. Hum Reprod. 2006 Jun;21(6):1442-52. doi: 10.1093/humrep/dei497. Epub 2006 Jan 26.
Helpful Links
- Characteristics of the urinary luteinizing hormone surge in young ovulatory women
- INTERPRETATION OF PLASMA LUTEINIZING HORMONE ASSAY FOR THE COLLECTION OF MATURE OOCYTES FROM WOMEN: DEFINITION OF A LUTEINIZING HORMONE SURGE-INITIATING RISE
- Endometrial transcriptome analysis indicates superiority of natural over artificial cycles in recurrent implantation failure patients undergoing frozen embryo transfer
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1901-ABU-015-CC
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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