Two Different Types of Luteal Phase Support in Natural Cycle Frozen Embryo Transfer and Its Effect on Pregnancy Rates

Luteal Phase Support Clinical Trial

Official title:

Prospective Randomized Control Study of Two Different Types of Luteal Phase Support in Natural Cycle Frozen Embryo Transfer and Its Effect on Pregnancy Rates

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05838105
• Other study ID #: LutealSupport
• Status: Recruiting
• Phase: N/A
• Start date: October 1, 2022
• Est. completion date: January 1, 2025

Study information

• Verified date: April 2023
• Source: Shaare Zedek Medical Center
• Contact: Heli Alexandroni, MD
• Phone: +972549900913
• Email: heli.alexandroni[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to compare the pregnancy rate between women treated with Gonadotropin Releasing Hormone (GnRH) agonist together with Human Chorionic Gonadotropin (HCG) and standard luteal support with progesterone following transfer of frozen embryos in in-vitro-fertilization (IVF) natural cycles.

Description:

The rate of frozen embryos transfer (FET) has increased in recent years due to a higher tendency of single embryo transfer, use of preimplantation genetic testing, and prevention of ovarian hyperstimulation.

There are different methods to prepare the endometrium for FET:

1. Natural cycle (NC) - natural preparation of the body for implantation without the need for medicinal intervention.

2. Modified natural cycle (mNC) - Inducing ovulation by administration of Human Chorionic Gonadotropin (HCG) trigger.

3. Medical - preparation of endometrium with hormones (estrogen and progesterone).

Following embryo transfer, luteal phase support should be considered. Administration of treatment depends on the type of cycle chosen (either natural or medicated). Treatment options include progesterone, HCG and Gonadotropin Releasing Hormone (GnRH) analog - either one of them or combined. Different protocols (dosages and duration of use) with different pregnancy outcomes were explore before with inconclusive results. We wish to investigate administration of GnRH agonist+HCG vs. progesterone.

Patients included in the study will be women undergoing natural cycle FET at the IVF center in Shaare Zedek, Jerusalem, Israel. All patients will be randomly divided into two groups, each will receive a different luteal treatment support as will be detailed later. Patients demographic data and pregnancy outcomes will be collected.

Based on the clinical pregnancy rate in the prospective study by Bjuresten, et al [Fertil Steril, 2011], where a clinical pregnancy rate of 32% was found among women treated with progesterone for luteal support, and given an alpha of 5% and a power of 80%, 144 women (72 women in each group) are required in order to demonstrate a clinical pregnancy rate of 55% in the study group.

Comparison of categorical variables will be carried out using the the chi-squared test. Comparison of continuous variables will be performed using the Students t-Test or Mann-Whitney U method depending on the variable distribution (normal vs. non-normal distribution, respectively). A multivariate regression will also be conducted in order to determine which variables are significantly and independently related. Statistical significance will be defined when P values are less than 0.05

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 144
• Est. completion date: January 1, 2025
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Normo-ovulatory women

• Women undergoing frozen embryos transfer in a natural cycle

• Age 18-45

• BMI 18-35

Exclusion Criteria:

• Women undergoing medicated frozen embryos transfer

• Women with a BMI over 35 or under 18.

• Women with hydrosalpinges

• Women with defects or uterine malformations (congenital) or acquired such as myomas

• Egg donation and surrogacy

• Use of preimplantation genetic testing

Related Conditions & MeSH terms

• Luteal Phase Support

Intervention

Drug:
• GnRH agonist
125 mcg once at the day mentioned
• hCG
dose as mentioned
• Progesterone 100Mg Vag Tab
dose as mentioned

Locations

Country	Name	City	State
Israel	Shaare Zedek medical center	Jerusalem

Sponsors (1)

Lead Sponsor	Collaborator
Shaare Zedek Medical Center

Country where clinical trial is conducted

Israel, 

References & Publications (8)

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(7):CD003414. doi: 10.1002/14651858.CD003414.pub3. — 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. Erratum In: Hum Reprod Update. 2017 Mar 1;23(2):255-261. — View Citation

Le Lannou D, Griveau JF, Laurent MC, Gueho A, Veron E, Morcel K. Contribution of embryo cryopreservation to elective single embryo transfer in IVF-ICSI. Reprod Biomed Online. 2006 Sep;13(3):368-75. doi: 10.1016/s1472-6483(10)61441-1. — View Citation

Loutradi KE, Kolibianakis EM, Venetis CA, Papanikolaou EG, Pados G, Bontis I, Tarlatzis BC. Cryopreservation of human embryos by vitrification or slow freezing: a systematic review and meta-analysis. Fertil Steril. 2008 Jul;90(1):186-93. doi: 10.1016/j.fertnstert.2007.06.010. Epub 2007 Nov 5. — View Citation

Mackens S, Stubbe A, Santos-Ribeiro S, Van Landuyt L, Racca A, Roelens C, Camus M, De Vos M, van de Vijver A, Tournaye H, Blockeel C. To trigger or not to trigger ovulation in a natural cycle for frozen embryo transfer: a randomized controlled trial. Hum Reprod. 2020 May 1;35(5):1073-1081. doi: 10.1093/humrep/deaa026. — View Citation

Montagut M, Santos-Ribeiro S, De Vos M, Polyzos NP, Drakopoulos P, Mackens S, van de Vijver A, van Landuyt L, Verheyen G, Tournaye H, Blockeel C. Frozen-thawed embryo transfers in natural cycles with spontaneous or induced ovulation: the search for the best protocol continues. Hum Reprod. 2016 Dec;31(12):2803-2810. doi: 10.1093/humrep/dew263. Epub 2016 Oct 25. — View Citation

Weissman A, Horowitz E, Ravhon A, Steinfeld Z, Mutzafi R, Golan A, Levran D. Spontaneous ovulation versus HCG triggering for timing natural-cycle frozen-thawed embryo transfer: a randomized study. Reprod Biomed Online. 2011 Oct;23(4):484-9. doi: 10.1016/j.rbmo.2011.06.004. Epub 2011 Jun 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical pregnancy rate	visualization of intrauterine gestational sac on ultrasound divided by number of transfers	up to two month after embryo transfer
Secondary	Overall pregnancy rate	number positive beta-hCG divided by total number of transfers	up to two month after embryo transfer
Secondary	Implantation rate	number of gestational sacs divided by number of embryos transferred	up to two month after embryo transfer
Secondary	Ectopic pregnancy rate	number of ectopic pregnancy divided by number of positive beta-hCG	up to two month after embryo transfer
Secondary	Miscarriage rate	number of non-viable before 24 weeks divided by total number of positive beta-hCG	up to 20 weeks after embryo transfer
Secondary	Live birth rate	number of live births after 24 weeks divided by number of transfers.	up to 42 weeks after embryo transfer