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

Pregnancy Related Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05969795
• Other study ID #: 2306-ABU-009-BL
• Status: Recruiting
• Phase: Phase 1
• Start date: September 5, 2023
• Est. completion date: September 30, 2024

Study information

• Verified date: November 2023
• Source: ART Fertility Clinics LLC
• Contact: Barbara Lawrenz, PhD
• Phone: +971 800 337845489
• Email: barbara.lawrenz[@]artfertilityclinics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 342
• Est. completion date: September 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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….)

Related Conditions & MeSH terms

• Infertility
• Infertility, Female
• Pregnancy Related

Intervention

Diagnostic Test:
• Transvaginal ultrasound
Intermittent transvaginal ultrasound throughout the cycle to monitor follicular growth
• 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
• 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)
• 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

Locations

Country	Name	City	State
United Arab Emirates	ART Fertility Clinics LLC	Abu Dhabi
United Arab Emirates	ART Fertility Clinics Al Ain	Al Ain
United Arab Emirates	ART Fertility Clinics Dubai	Dubai

Sponsors (1)

Lead Sponsor	Collaborator
ART Fertility Clinics LLC

Country where clinical trial is conducted

United Arab Emirates, 

References & Publications (10)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Practice Committee of the American Society for Reproductive Medicine. The clinical relevance of luteal phase deficiency: a committee opinion. Fertil Steril. 2012 Nov;98(5):1112-7. doi: 10.1016/j.fertnstert.2012.06.050. Epub 2012 Jul 20. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

von Versen-Hoynck F, Schaub AM, Chi YY, Chiu KH, Liu J, Lingis M, Stan Williams R, Rhoton-Vlasak A, Nichols WW, Fleischmann RR, Zhang W, Winn VD, Segal MS, Conrad KP, Baker VL. Increased Preeclampsia Risk and Reduced Aortic Compliance With In Vitro Fertilization Cycles in the Absence of a Corpus Luteum. Hypertension. 2019 Mar;73(3):640-649. doi: 10.1161/HYPERTENSIONAHA.118.12043. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Implantation rate	Number of embryos which have produced ultrasonographic evidence of an intrauterine gestational sac per the total number of embryos transferred into the uterine cavity (Zegers-Hochschild et al., 2009).	2 months
Primary	Clinical pregnancy rate	hCG > 15 Iu/ml and ultrasound confirmation of a gestational sac	2 months
Primary	Live birth rate	Number of deliveries that resulted in a live born neonate, expressed per 100 embryo transfers (Zegers-Hochschild et al., 2009)	41 weeks
Primary	Serum P4 levels on ET day	Progesterone level on the day of embryo transfer	1 day
Primary	Serum E2 and P4 levels on day 5 or 6 after ET procedure	Estradiol and Progesterone levels on day 5 or 6 after embryo transfer	6 days
Primary	Serum E2 and P4 levels on day 10 after ET procedure	Estradiol and Progesterone levels on day 10 after embryo transfer	10 days

External Links

•   Shapiro BS, Garner FC, Aguirre M. The Freeze-All Cycle: A New Paradigm Shift in ART. In Nagy ZP, Varghese AC, Agarwal A, editors. In Vitro Fertilization [Internet] 2019;, p. 765-778. Springer International Publishing