What is the Optimal Cycle Regimen for Frozen- Thawed Embryo Transfer Cycles

Infertility Clinical Trial

Official title:

What is the Optimal Cycle Regimen for Frozen- Thawed Embryo Transfer Cycles: Spontaneous Natural Cycles Versus Hormonal Replacement Treatment (HRT) Cycles

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03954587
• Other study ID #: 1901-ABU-015-CC
• Status: Terminated
• Start date: June 10, 2019
• Est. completion date: July 30, 2020

Study information

• Verified date: March 2021
• Source: ART Fertility Clinics LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: July 30, 2020
• Est. primary completion date: July 15, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 42 Years

Eligibility

Inclusion criteria include the following:

1. Women aged 18 years to 42 years with regular menses (26-34 days)

2. Having 1 or 2 chromosomally normal cryopreserved blastocysts available for transfer.

3. First frozen-thawed transfer cycle

4. 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:

1. Polycystic ovarian syndrome

2. Poor ovarian responder in accordance with Bologna criteria

3. Uterine abnormality US / saline infusion sonohysterogram

4. Previous dilatation & curettage (D&C)

5. Hydrosalpinx

6. Asherman syndrome

7. History of endometriosis

8. ICSI due to severe male factor with testicular sperm

9. Any known contraindications or allergy to oral estradiol or progesterone.

10. Discontinuation of HRT medication ( medication error in research HRT cycle )

11. Failure to detect ovulation in the research natural cycle

12. Duration of estradiol exposure = 17 days and endometrium < 6mm

13. Spontaneous ovulation in HRT artificial cycle

Related Conditions & MeSH terms

• Female Infertility
• Infertility
• Infertility, Female
• Pregnancy Early

Locations

Country	Name	City	State
United Arab Emirates	IVI Middle East Fertility Clinic	Abu Dhabi

Sponsors (1)

Lead Sponsor	Collaborator
ART Fertility Clinics LLC

Country where clinical trial is conducted

United Arab Emirates, 

References & Publications (19)

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. — View Citation

Bourgain C, Devroey P. The endometrium in stimulated cycles for IVF. Hum Reprod Update. 2003 Nov-Dec;9(6):515-22. Review. — View Citation

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. Review. — View Citation

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. — View Citation

Ghobara T, Gelbaya TA, Ayeleke RO. Cycle regimens for frozen-thawed embryo transfer. Cochrane Database Syst Rev. 2017 Jul 5;7:CD003414. doi: 10.1002/14651858.CD003414.pub3. Review. — View Citation

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. Review. Erratum in: Hum Reprod Update. 2017 Mar 1;23(2):255-261. — View Citation

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. Review. — View Citation

Haouzi D, Assou S, Mahmoud K, Tondeur S, Rème 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2006 Jan 26. — View Citation

Roque M, Lattes K, Serra S, Solà 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. Review. — View Citation

Roque M, Valle M, Guimarães 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. — View Citation

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. — View Citation

Simón C, Garcia Velasco JJ, Valbuena D, Peinado JA, Moreno C, Remohí 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. — View Citation

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. Review. — View Citation

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. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ongoing pregnancy rate to 8 weeks gestation	viable pregnancy to 8 gestational weeks	8 weeks
Primary	Pregnancy rate beta human chorionic gonadotropin (ß-hCG) > 5 IU	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	12 days
Primary	Biochemical pregnancy rate	Positive ß-hCG, but at 5 gestational weeks no ultrasonographic visible gestational sac seen	5 weeks
Primary	Clinical implantation rate	Number of gestational sacs observed by ultrasound at 6 weeks of gestation divided by the number of embryos transferred	6 weeks
Primary	Clinical pregnancy rate	Ultrasonographic visible sac at 5 gestational weeks	5 weeks

External Links

•   Characteristics of the urinary luteinizing hormone surge in young ovulatory women
•   Endometrial transcriptome analysis indicates superiority of natural over artificial cycles in recurrent implantation failure patients undergoing frozen embryo transfer
•   INTERPRETATION OF PLASMA LUTEINIZING HORMONE ASSAY FOR THE COLLECTION OF MATURE OOCYTES FROM WOMEN: DEFINITION OF A LUTEINIZING HORMONE SURGE-INITIATING RISE
•   Leon Speroff & Marc A. Fritz. Clinical Gynecologic Endocrinology and Infertility. Part 1. Reproductive Physiology. Chapter 6: Regulation of the Menstrual Cycle. Ovulation : 212-216p.