Natural Cycle vs Programmed Cycle Frozen Embryo Transfer

July 29, 2023 updated by: Indira IVF Hospital Pvt Ltd

Preeclampsia Following Natural vs. Artificial Cycle Frozen Embryo Transfer

The goal of this[ type of study: randomized controlled trial]is to compare Preeclampsia following Natural vs. Artificial Cycle in patients undergoing frozen embryo transfer.

The main question[s] it aims to answer is

• Does NC-FET decreases the incidence of preeclampsia in patients undergoing frozen embryo transfer as compared to AC-FET ?

The main objective is to compare the proportion of preeclampsia in women with a viable pregnancy with natural cycle protocol to artificial cycle protocol when practicing frozen embryo transfer. Participants recruited will be divided into two ARM(1513 per arm). ARM 1 will undergo the Natural Cycle procedure of Embryo transfer, and ARM 2 will undergo the Artificial Cycle procedure of Embryo transfer. The primary outcome will be the proportion of preeclampsia. The duration of the study is around 2 year.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The Research question(PICO) addressed is Does NC-FET decreases the incidence of preeclampsia in patients undergoing frozen embryo transfer as compared to AC-FET . The hypothesis taken is NC-FET will decrease the incidence of preeclampsia compared to AC-FET. The sample size is taken as 3026 (1513 per arm). The Primary Objective is to compare the proportion of preeclampsia in women with a viable pregnancy with natural cycle protocol to artificial cycle protocol when practicing frozen embryo transfer. The study outcome of the proportion of preeclampsia after 20 weeks of gestation or 6 weeks post-delivery. There are two arms-Arm 1 Active Comparator: Natural Cycle and Arm 2 control: Artificial Cycle FET. The Randomization is done through Random Allocation as per computer generated sequence. The Blinding/masking is done Open labeled. The Study Duration is from Feb 2023 to Jan 2025. Participation Duration is 10 months.

Study Type

Interventional

Enrollment (Estimated)

3026

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • India
    • Rajasthan
      • Udaipur, Rajasthan, India, 313001
        • Recruiting
        • Indira IVF Hospital Private Limited
        • Contact:
        • Contact:
        • Principal Investigator:
          • Nihar R Bhoi, MD
        • Sub-Investigator:
          • Anuja Singh, MD
        • Sub-Investigator:
          • Shyam Gupta, MD
        • Sub-Investigator:
          • Ritu Punhani, MD
        • Sub-Investigator:
          • Anjali Gahlan, MD
        • Sub-Investigator:
          • Amol Wankhede, MS
        • Sub-Investigator:
          • Amol Lukund, MD
        • Sub-Investigator:
          • Akanksha Jangid, MD
        • Sub-Investigator:
          • Amrita Singh, MS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Endometrial preparation with Hormone replacement therapy/ Natural cycle.
  • Age 21-45 years following an autologous IVF cycle (with or without preimplantation genetic testing for aneuploidy)
  • BMI > 18 and < 30 kg/m2
  • Endometrial thickness ≥ 7 mm after estrogen therapy or on the day of ovulation
  • Blastocyst embryo transfer

Exclusion Criteria:

  • Uterine diseases (e.g. submucosal fibroids, polyps, previously diagnosed Müllerian abnormalities)
  • Hydrosalpinx untreated.
  • Recurrent pregnancy loss (≥ 3 previous miscarriages)
  • Recurrent implantation failure (≥ 3 previously failed embryo transfers of good-quality blastocysts)
  • Allergy to study medication
  • Pregnancy or lactation at recruitment
  • Contraindications for hormonal treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Natural Cycle
In this,hCG trigger and Luteal Phase Support is monitored for the natural frozen embryo cycle procedure of IVF.
Procedure: Natural Cycle
The participant will be administered a S/C injection of 250mcg r-hCG to assist ovulation and timing of the embryo transfer, when the dominant follicle reaches ≥ 18mm and serum LH < 20 IU/L, the administration of r-hCG will be in the evening, and the embryo transfer will be scheduled seven days later (window of ± two days). The participant will begin transvaginal progesterone gel (8 %) twice daily starting 36 hrs after the trigger until ten weeks of gestation.
Other: Artificial Cycle
In this, endometrial preparation and Luteal Phase Support is monitored for the artificial frozen embryo cycle procedure of IVF.
Procedure: Artificial Cycle
Estrogen priming with oral estradiol valerate 6mg/day (2mg every 8 hours) starting from cycle D1-D5 after a first TVU. TVU will be performed 10-15 days after beginning estradiol until ET ≥ 7mm, maximum until 21 days. Patients will begin progesterone injection 100mg/day until blastocyst transfer. Frozen embryo transfer will be performed on day 6 +/- 2 days of progesterone administration. After embryo transfer, a supplementation with transvaginal progesterone gel (8 %) twice daily starting from the day of embryo transfer until ten weeks of gestation. Patients will continue Estradiol 2 mg thrice daily until 6 weeks of gestation; then dose tapering will be done to 2 mg twice daily until 9 wks of gestation. From 9th wk the estrogen dose will be tapered further to 2 mg once daily for 10 days before stopping.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
proportion of preeclampsia
Time Frame: after the 20th week of gestation up to six weeks postpartum
The primary efficacy endpoint is the proportion of preeclampsia in women assigned to a natural cycle protocol compared to the proportion of preeclampsia in women assigned to an artificial cycle protocol.
after the 20th week of gestation up to six weeks postpartum

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biochemical Pregnancy Rate
Time Frame: 6 weeks after Embryo Transfer
Pregnancies diagnosed only by β-human chorionic gonadotropin detection without a gestational sac visualized by vaginal ultrasound at the 6th gestational week.
6 weeks after Embryo Transfer
Implantation Rate
Time Frame: 4 weeks +2 weeks after ET
The number of gestational sacs observed by transvaginal ultrasound at the 6th gestational week per the number of embryos transferred.
4 weeks +2 weeks after ET
Ongoing Pregnancy Rate
Time Frame: 12 weeks after embryo Transfer
Presence of gestational sacs with a heartbeat at the 12th gestational week per embryo transfer cycle.
12 weeks after embryo Transfer
Live Birth Rate
Time Frame: 28 weeks(+12 weeks) after embryo transfer
The number of deliveries that resulted in at least one live birth per 100 Embryo transferred cycle.
28 weeks(+12 weeks) after embryo transfer
Miscarriage Rate
Time Frame: Within 20 weeks of gestation
Number of spontaneous pregnancy losses in which a gestational sac/s was previously observed (before 20th gestational weeks) per 100 clinical pregnancy.
Within 20 weeks of gestation
Preterm birth
Time Frame: < 37 weeks
Preterm is defined as babies born alive before 37 weeks of pregnancy are completed
< 37 weeks
Extreme preterm birth
Time Frame: 20-28 weeks
Extreme Preterm is defined as babies born alive before 28 weeks of pregnancy
20-28 weeks
Fetal growth restriction
Time Frame: 20-40 weeks of gestation
Fetal growth restriction (FGR) is most often defined as an estimated fetal weight less than the 10th percentile for gestational age by prenatal ultrasound evaluation
20-40 weeks of gestation
Premature detachment of normally inserted placenta
Time Frame: 12 weeks of GA till labor
It is defined as a premature separation of the placenta before delivery.
12 weeks of GA till labor
Maternal hypertension
Time Frame: After 20 weeks of GA till 6 weeks postpartum
It is defined as blood pressure more than 140/90 mm Hg detected first time after 20 weeks of gestation till 6 weeks of postpartum without proteinuria
After 20 weeks of GA till 6 weeks postpartum
Eclampsia
Time Frame: After 20 weeks of GA till 6 weeks postpartum
Eclampsia is defined as the new onset of generalized tonic-clonic seizures in a woman with preeclampsia.
After 20 weeks of GA till 6 weeks postpartum
HELLP Syndrome
Time Frame: After 20 weeks of GA till 6 weeks postpartum
It is defined as hemodialysis, elevated liver enzymes, and low platelet count
After 20 weeks of GA till 6 weeks postpartum
Maternal mortality
Time Frame: from start of pregnancy to 42 weeks of pregnancy
Maternal death is defined as pregnancy or its management (excluding accidental or incidental causes) during pregnancy and childbirth or within 42 days of termination of pregnancy, irrespective of the duration and site of the pregnancy
from start of pregnancy to 42 weeks of pregnancy
Fetal death
Time Frame: 20 weeks of GA before delivery
Fetal death refers to the spontaneous intrauterine death of a fetus after 20 weeks of GA before delivery
20 weeks of GA before delivery
Frequency of adverse events
Time Frame: through study completion, an average of 1 year
An adverse event (AE) is any untoward medical occurrence in a patient.
through study completion, an average of 1 year
Clinical Pregnancy Rate
Time Frame: 4 weeks +2 weeks after ET
Detection of a foetal heartbeat on transvaginal ultrasound at the 6th gestational week per embryo transfer cycle.
4 weeks +2 weeks after ET
Fetal birthweight
Time Frame: within 30 minutes of birth
Is defined as the weight of baby just after birth
within 30 minutes of birth

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Indira IVF Hospital Pvt Ltd

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 15, 2023

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

January 1, 2025

Study Registration Dates

First Submitted

January 21, 2023

First Submitted That Met QC Criteria

January 28, 2023

First Posted (Actual)

February 8, 2023

Study Record Updates

Last Update Posted (Actual)

August 1, 2023

Last Update Submitted That Met QC Criteria

July 29, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IIHPL-UDR/RCT/013_2022

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

IPD will be shared with other researchers after publication of primary results.

IPD Sharing Time Frame

After six months of publication of primary results statistical plan and ICF

IPD Sharing Access Criteria

IPD will be shared on request

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Infertility

Clinical Trials on Natural Cycle

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Türkiye

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe