Comparison of Live Birth Rate in Natural Cycle Single Euploid FET Versus Without Luteal Phase Support

Official title

Comparison of Live Birth Rate (> 24 Weeks) in Natural Cycle (NC) Single Euploid Frozen Embryo Transfers (FET) With Versus Without Luteal Phase Support (LPS)

Overview

To evaluate whether single euploid embryo transfer in NC without routinely administered LPS is non-inferior to NC with routinely administered LPS.

Detailed description

In case the study will show that the live birth rate in single euploid NC frozen embryo transfer cycles without LPS is not inferior to NC cycles with LPS, treatment can be simplified, and participants comfort can be increased.

Interventions

• Diagnostic test Transvaginal ultrasound
  Intermittent transvaginal ultrasound throughout the cycle to monitor follicular growth
• Diagnostic test Serial serum LH, E2, P4
  Serial measurements of serum Luteinizing Hormone (LH), Estradiol (E2) and Progesterone (P4 )levels throughout the cycle to determine ovulation. LH-surge is identified when a rise of 180% above the previous level occurred and ovulation is confirmed with a decrease in E2 concentration, and a rise of progesterone level to ≥ 1.0 ng/ml (Irani et al., 2017).
• Drug Progesterone 100 Mg Vaginal Insert
  On day of ET procedure, to administer 200 mg of vaginal progesterone and increase to 300 mg/day from the day after the ET onwards until the pregnancy test. In case of an implantation, vaginal P4 will be continued until 7 weeks of pregnancy
• Diagnostic test Serum P4 day of ET - Control Group
  Serum P4 will be drawn before starting LPS in form of vaginal progesterone on the day of ET procedure
• Diagnostic test Serum P4 day of ET - Study Group
  Serum P4 will be drawn when study group participants are admitted to the clinic for the ET procedure.
• Procedure Embryo transfer
  The procedure in which embryo is placed in the uterus.
• Diagnostic test Serum hCG 10 days after ET
  Pregnancy will be confirmed / excluded by measurement of serum hCG 10 days after ET procedure and a level of \> 15 IU will be regarded as positive result. The definitions of biochemical, ectopic, clinical and ongoing pregnancy follow the ICMART criteria (Zegers-Hochschild, 2006)
• Diagnostic test Serum P4 10 days after ET
  Serum P4 will be drawn on day 5 or day 6 after the ET procedure and together with the hCG 10 days after ET procedure

Primary outcome measures

• Implantation rate [Time frame: 2 months]
• Clinical pregnancy rate [Time frame: 2 months]
• Live birth rate [Time frame: 41 weeks]
• Serum P4 levels on ET day [Time frame: 1 day]
• Serum E2 and P4 levels on day 5 or 6 after ET procedure [Time frame: 6 days]
• Serum E2 and P4 levels on day 10 after ET procedure [Time frame: 10 days]

Eligibility criteria

Inclusion criteria

• Age: 18 to 40 years
• Regular ovulatory cycles
• Availability of at least one euploid embryo after Trophectoderm biopsy for PGT-A on day 5 or day 6
• Detection of ovulation by P4 rise > 1.0 ng/ml after LH surge
• P4 value of at least 5 ng/ml on day 4 after ovulation

Exclusion criteria

• History of repeated pre-menstrual spotting
• Factors affecting the implantation through anatomical changes of the uterus / ovaries or the tubes (adenomyosis, Asherman syndrome, endometriosis, uterine fibroids / polyps, isthmocele with intracavitary fluid presence, hydrosalpinx….)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Basic science

Study locations

United Arab Emirates · 3 centers

• ART Fertility Clinics LLC — Abu Dhabi
• ART Fertility Clinics Al Ain — Al Ain City
• ART Fertility Clinics Dubai — Dubai

Publications

• Bortoletto P, Prabhu M, Baker VL. Association between programmed frozen embryo transfer and hypertensive disorders of pregnancy. Fertil Steril. 2022 Nov;118(5):839-848. doi: 10.1016/j.fertnstert.2022.07.025. Epub 2022 Sep 25. PMID 36171152
• Csapo AI, Pulkkinen M. Indispensability of the human corpus luteum in the maintenance of early pregnancy. Luteectomy evidence. Obstet Gynecol Surv. 1978 Feb;33(2):69-81. doi: 10.1097/00006254-197802000-00001. No abstract available. PMID 341008
• Filicori M, Butler JP, Crowley WF Jr. Neuroendocrine regulation of the corpus luteum in the human. Evidence for pulsatile progesterone secretion. J Clin Invest. 1984 Jun;73(6):1638-47. doi: 10.1172/JCI111370. PMID 6427277
• Ginstrom Ernstad E, Wennerholm UB, Khatibi A, Petzold M, Bergh C. Neonatal and maternal outcome after frozen embryo transfer: Increased risks in programmed cycles. Am J Obstet Gynecol. 2019 Aug;221(2):126.e1-126.e18. doi: 10.1016/j.ajog.2019.03.010. Epub 2019 Mar 22. PMID 30910545
• Pape J, Levy J, von Wolff M. Early pregnancy complications after frozen-thawed embryo transfer in different cycle regimens: A retrospective cohort study. Eur J Obstet Gynecol Reprod Biol. 2022 Dec;279:102-106. doi: 10.1016/j.ejogrb.2022.10.015. Epub 2022 Oct 21. PMID 36308939
• Roelens C, Blockeel C. Impact of different endometrial preparation protocols before frozen embryo transfer on pregnancy outcomes: a review. Fertil Steril. 2022 Nov;118(5):820-827. doi: 10.1016/j.fertnstert.2022.09.003. PMID 36273850
• Soules MR, Clifton DK, Steiner RA, Cohen NL, Bremner WJ. The corpus luteum: determinants of progesterone secretion in the normal menstrual cycle. Obstet Gynecol. 1988 May;71(5):659-66. PMID 3357651
• Su S, Zeng M, Duan J. Luteal phase support for natural cycle frozen embryo transfer: a meta-analysis. Gynecol Endocrinol. 2022 Feb;38(2):116-123. doi: 10.1080/09513590.2021.1998438. Epub 2021 Nov 3. PMID 34730071

Identifiers

NCT: NCT05969795 · 2306-ABU-009-BL

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗