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

NCT03954587 | Terminated

• 1 other identifier: 1901-ABU-015-CC
• Study Type: observational
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Infertility; Female Infertility; Pregnancy Early

Keywords

Hormone replacement therapy; Frozen thawed embryos; Frozen embryo cycle

Outcome Measures

Primary Outcomes (5)

• Ongoing pregnancy rate to 8 weeks gestation

  viable pregnancy to 8 gestational weeks

  8 weeks

• 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

• Biochemical pregnancy rate

  Positive ß-hCG, but at 5 gestational weeks no ultrasonographic visible gestational sac seen

  5 weeks

• Clinical implantation rate

  Number of gestational sacs observed by ultrasound at 6 weeks of gestation divided by the number of embryos transferred

  6 weeks

• Clinical pregnancy rate

  Ultrasonographic visible sac at 5 gestational weeks

  5 weeks

Study Arms (2)

Artificial (HRT) Cycles

1. Commence estradiol valerate (E2) 4mg from day 2 or 3 of period for 3 days 2. Increase E2 to 6mg on day 4 of E2 treatment, according to clinician discretion based on endometrial thickness. 3. Transvaginal scan throughout the HRT cycle to not only monitor endometrial development but to also exclude the presence of a dominant follicle on the ovaries. 4. Serial measurements of serum LH (luteinizing hormone), estradiol and progesterone levels. 5. Initial progesterone dose of 100mg at 22hrs (vaginal suppository) after ≥ 7 days and ≤ 16 days of estradiol administration when the minimal endometrial thickness achieved is 6mm with a trilaminar appearance. 6. Subsequently increase progesterone administration to 100mg vaginally three times daily. Continue E2 administration 6mg (3 tablets daily). 7. Embryo transfer is scheduled on the 5th full day of progesterone administration.

Spontaneous natural cycles:

1. Day 2 of menses and throughout patients' natural cycle scans to monitor follicular growth. 2. Measurements of serum LH, estradiol and progesterone levels to determine ovulation. 3. The LH surge will be considered to have begun when the concentration rises by 180% above the most recent serum value and continues to rise thereafter (Irani et al. 2017, Fatemi et al., 2010). 4. Day 1 after the LH rise, a decrease in estradiol concentration is identified. Twenty four hours later progesterone concentrations rise with a level of greater than or equal to 1.5ng/mL confirming ovulation (day 0) (Irani et al., 2017; Speroff et al.). This is considered as day 0 with initiation of vaginal progesterone 100mg at 22hrs that night. The following day (day 1) the patient increases progesterone administration to 100mg vaginally 8 hourly and continues until 7 weeks gestation as per clinic protocol. Embryo transfer is scheduled 5 days (day 5) following confirmation of ovulation (day 0).

Eligibility Criteria

• Age: 18 Years - 42 Years
• Gender Eligibility Details: Female under infertility treatment
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Female who underwent a previous ovarian stimulation for In Vitro Fertilisation/Intracytoplasmic Sperm Injection with pre-implantation genetic screening and embryo vitrification, who are planned for their first frozen thaw embryo transfer cycle

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• ART Fertility Clinics LLC: lead

Study Sites (1)

IVI Middle East Fertility Clinic

Abu Dhabi, 60202, United Arab Emirates

Location

Related Publications (19)

• 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.

  PMID: 23040524 BACKGROUND

• 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.

  PMID: 25747130 BACKGROUND

• 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.

  PMID: 14714588 BACKGROUND

• 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.

  PMID: 15036255 BACKGROUND

• 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.

  PMID: 12413988 BACKGROUND

• 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.

  PMID: 10221715 BACKGROUND

• 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.

  PMID: 9696213 BACKGROUND

• 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.

  PMID: 24890274 BACKGROUND

• 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.

  PMID: 18191855 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

• 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.

  PMID: 28675921 BACKGROUND

• 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.

  PMID: 23820515 BACKGROUND

• 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.

  PMID: 29778369 BACKGROUND

• 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.

  PMID: 29662710 BACKGROUND

• 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.

  PMID: 20097333 BACKGROUND

• 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.

  PMID: 19164178 BACKGROUND

• 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.

  PMID: 29320646 BACKGROUND

• 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.

  PMID: 16439502 BACKGROUND

• 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.

  PMID: 29037231 BACKGROUND

MeSH Terms

Conditions

Infertility; Infertility, Female

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications

Study Officials

• Carol Coughlan, PhD

  IVI Middle East Fertility Clinic LLC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director

Study Record Dates

• First Submitted: May 15, 2019
• First Posted: May 17, 2019
• Study Start: June 10, 2019
• Primary Completion: July 15, 2020
• Study Completion: July 30, 2020
• Last Updated: March 8, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

AE (1)