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

Shaare Zedek Medical Center

Status: Enrolling

Conditions: Luteal Phase Support

Treatments: Drug: hCG; Drug: GnRH agonist; Drug: Progesterone 100Mg Vag Tab

Study type: Interventional

Funder types: Other

Identifiers

NCT05838105

LutealSupport

Details and patient eligibility

About

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.

Full 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

Enrollment: 144 estimated patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

144 participants in 2 patient groups

Study group

Active Comparator group

Description:

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

Treatment:

Drug: hCG

Drug: GnRH agonist

Control group

Active Comparator group

Description:

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

Treatment:

Drug: Progesterone 100Mg Vag Tab