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

NCT ID: NCT05838105

Last Updated: 2023-05-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

144 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-01

Study Completion Date

2025-01-01

Brief Summary

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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.

Detailed Description

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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

Conditions

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Luteal Phase Support

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

All patients will be randomly divided into two groups, each will receive a different luteal treatment:

1. Study group - patients will receive luteal support with GNRH agonist and HCG according to departmental protocol (described later).
2. Control group - patients will receive luteal support with vaginal progesterone.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Study group

Patients will receive luteal support with GNRH agonist and HCG according to departmental protocol:

Cleavage stage embryo:

* ET day (embryo day 2-3) - Ovitrelle 125mcg
* Day 3 after ET - Ovitrelle 125mcg + Decapeptyl 0.1mg
* Day 6 after ET- Ovitrelle 125mcg
* Day 9 after ET - Ovitrelle 125mcg

Embryo blastocyst stage:

* ET day (embryo day 5-6) - Ovitrelle 125mcg + Decapeptyl 0.1mg
* Day 3 after ET - Ovitrelle 125mcg
* Day 6 after ET - Ovitrelle 125mcg

Group Type ACTIVE_COMPARATOR

GnRH agonist

Intervention Type DRUG

125 mcg once at the day mentioned

hCG

Intervention Type DRUG

dose as mentioned

Control group

Patients will receive luteal support with vaginal progesterone - 100 mg Endometrin twice daily until week 8 of pregnancy.

Group Type ACTIVE_COMPARATOR

Progesterone 100Mg Vag Tab

Intervention Type DRUG

dose as mentioned

Interventions

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GnRH agonist

125 mcg once at the day mentioned

Intervention Type DRUG

hCG

dose as mentioned

Intervention Type DRUG

Progesterone 100Mg Vag Tab

dose as mentioned

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Shaare Zedek Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Heli Alexandroni

Alexandroni Heli

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Keren Rotshenker Olshnika, MD

Role: PRINCIPAL_INVESTIGATOR

Sharee Zedek Medical Center, Israel

Locations

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Shaare Zedek medical center

Jerusalem, , Israel

Site Status RECRUITING

Countries

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Israel

Central Contacts

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Heli Alexandroni, MD

Role: CONTACT

+972549900913

Facility Contacts

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Heli Alexandroni, MD

Role: primary

+972549900913

References

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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.

Reference Type BACKGROUND
PMID: 23820515 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16984767 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17980870 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21840758 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32395750 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28675921 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27798046 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20097333 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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LutealSupport

Identifier Type: -

Identifier Source: org_study_id

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