Natural Cycle vs. Modified Natural Cycle vs. Artificial Cycle Protocol for Endometrial Preparation.

NCT04804020 | Completed DMC

• 1 other identifier: 187/HĐĐĐ-ĐHYD
• Study Type: interventional
• Target: 1,428
• Locations: 1 country
• Sites: 1

Brief Summary

Fresh embryo transfer is a routine procedure in vitro fertilization (IVF) treatment. Since the first live birth after an IVF-FET (frozen embryo transfer), recent years have seen a dramatic rise in the number of FET cycles. Three endometrial preparation protocols for frozen-thawed embryo transfer, including artificial, natural, modified natural protocol, have been studied and applied to maximize treatment outcomes. However, those methods are being applied empirically as their efficacy and safety are yet to be determined. The objective of this study is to compare the effectiveness and safety of those protocols.

Conditions

IVF; Frozen Embryo Transfer

Outcome Measures

Primary Outcomes (1)

• Live birth rate after one frozen embryo transfer cycle

  Live birth is defined as the complete expulsion or extraction from a woman of a product of fertilisation, after 24 completed weeks of gestational age; which, after such separation, breathes or shows any other evidence of life, such as heart beat, umbilical cord pulsation or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is attached. A birth weight of 350 grams or more can be used if gestational age is unknown (twins are a single count).

  At 24 weeks of gestation

Secondary Outcomes (22)

• Positive pregnancy test

  At 2 weeks after embryo placement

• Clinical pregnancy

  At 5 weeks after embryo placement

• Ongoing pregnancy

  At 10 weeks after embryo placement

• Implantation

  At 3 weeks after embryo placement

• Ectopic pregnancy

  At 12 weeks of gestation

Study Arms (3)

NC (Natural cycle)

ACTIVE COMPARATOR

Performing the first ultrasound scan will be performed on the second to the fourth day of the menstrual cycle to identify any problem related to the patients' uterus or adnexa. The second ultrasound will be performed on the sixth day of the cycle. Daily ultrasound and serum estradiol and LH level evaluation will be performed when the mean diameter of the dominant follicle of ≥14 mm. LH surge initiation is defined as a concentration of 180% above the latest serum value available in that patient with a continued rise thereafter to a level of 20 IU/l or more detected by the ECLIA method (Roche Cobas® E 801, Roche Diagnostics, Germany). Embryo transfer will be scheduled by the time of the initiation of LH and embryo stages.

Procedure: NC

mMC (modified Natural cycle)

ACTIVE COMPARATOR

Performing the first ultrasound scan on the second to the fourth day of the menstrual cycle to identify any problem related to patients' uterus or adnexa. A second ultrasound scan will be performed on the sixth day of the cycle; if there is at least one follicle with a diameter of ≥12 mm, an ultrasound scan will be performed daily. When the dominant follicle's mean diameter is ≥16 mm, human chorionic gonadotropin (Ovitrelle® 250 μg; Merck, Kenilworth, NJ, USA) will be injected to trigger ovulation. Embryo transfer will be scheduled by the time of the hCG injection and embryo stages.

Procedure: mNC

AC (Artificial cycle)

ACTIVE COMPARATOR

Preparing the endometrium by using oral estradiol valerate (Valiera®; Laboratories Recalcine) 8 mg/day, ranging from the second or fourth menstruation day. The endometrial thickness will be monitored from day six onwards, and vaginal progesterone (Utrogestan®; Besins) 800 mg/day will be initiated when endometrial thickness reaches ≥7 mm. Estradiol exposure must be lasting for ≥9 days before progesterone administration. Embryo transfer will be scheduled by the time of the initiation of progesterone and embryo stages.

Procedure: AC

Interventions

NC PROCEDURE

The first ultrasound scan will be performed on the second to the fourth day of the menstrual cycle to identify any problem related to the patients' uterus or adnexa. The second ultrasound will be performed on the sixth day of the cycle. Daily ultrasound and serum estradiol and LH level evaluation will be performed when the mean diameter of the dominant follicle of ≥14 mm. LH surge initiation is defined as a concentration of 180% above the latest serum value available in that patient with a continued rise thereafter9 to a level of 20 IU/l or more10 detected by the ECLIA method (Roche Cobas® E 801, Roche Diagnostics, Germany). Embryo transfer will be scheduled by the time of the initiation of LH and embryo stages.

NC (Natural cycle)

mNC PROCEDURE

The first ultrasound scan will be performed on the second to the fourth day of the menstrual cycle to identify any problem related to patients' uterus or adnexa. A second ultrasound scan will be performed on the sixth day of the cycle; if there is at least one follicle with a diameter of ≥12 mm, an ultrasound scan will be performed daily. When the dominant follicle's mean diameter is ≥16 mm, human chorionic gonadotropin (Ovitrelle® 250 μg; Merck, Kenilworth, NJ, USA) will be injected to trigger ovulation. Embryo transfer will be scheduled by the time of the hCG injection and embryo stages.

mMC (modified Natural cycle)

AC PROCEDURE

The endometrium is prepared using oral estradiol valerate (Valiera®; Laboratories Recalcine) 8 mg/day, ranging from the second or fourth menstruation day. The endometrial thickness will be monitored from day six onwards, and vaginal progesterone (Utrogestan®; Besins) 800 mg/day will be initiated when endometrial thickness reaches ≥7 mm. Estradiol exposure must be lasting for ≥9 days before progesterone administration. Embryo transfer will be scheduled by the time of the initiation of progesterone and embryo stages.

AC (Artificial cycle)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Aged of 18 to 45
• Having menstrual cycle duration of 24 to 38 days
• Undergoing no more than 3 previous IVF/ICSI - FET cycles
• Planning a frozen-thawed embryo transfer
• Agreeing to have no more than 2 day 3 and 1 day 5 embryos transferred
• Not participating in another IVF study at the same time

You may not qualify if:

• Menopausal/ Anovulatory women
• Having contraindication for exogenous hormones administration: breast cancer, risks of venous thromboembolism
• Having embryos from in vitro Maturation or oocyte donation or PGT (pre-implantation genetics testings) cycles
• Having uterine abnormalities (e.g., adenomyosis, intrauterine adhesions, unicornuate/ bicornuate/ arcuate uterus; unremoved hydrosalpinx, endometrial polyp)

Sponsors & Collaborators

• Mỹ Đức Hospital: lead
• University of Medicine and Pharmacy at Ho Chi Minh City: collaborator

Study Sites (1)

My Duc Hospital

Ho Chi Minh City, Vietnam

Location

Related Publications (1)

• Ho VNA, Pham TD, Nguyen NT, Wang R, Norman RJ, Mol BW, Ho TM, Vuong LN. Livebirth rate after one frozen embryo transfer in ovulatory women starting with natural, modified natural, or artificial endometrial preparation in Viet Nam: an open-label randomised controlled trial. Lancet. 2024 Jul 20;404(10449):266-275. doi: 10.1016/S0140-6736(24)00756-6. Epub 2024 Jun 26.

  PMID: 38944045 DERIVED

Study Officials

• Lan N Vuong, MD, PhD

  University of Medicine and Pharmacy at Ho Chi Minh City

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2021
• First Posted: March 18, 2021
• Study Start: March 22, 2021
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: July 29, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

VN (1)