Natural Versus Programmed Frozen Embryo Transfer (NatPro)

Last updated: May 15, 2025
Sponsor: JHSPH Center for Clinical Trials
Overall Status: Active - Not Recruiting

Phase

3

Condition

Pregnancy Complications

Treatment

Programmed cycle

Modified natural cycle

Clinical Study ID

NCT04551807
IRB00214688
  • Ages 18-41
  • Female
  • Accepts Healthy Volunteers

Study Summary

NatPro is a two-arm, parallel-group, multi-center, randomized trial in which women undergoing frozen embryo transfer (FET) will be randomized to receive either a modified natural cycle (corpus luteum present) or a programmed cycle (corpus luteum absent).

Eligibility Criteria

Inclusion

Inclusion criteria

To be eligible, subjects must meet all these criteria:

  • Age 18-39 years at the time that embryos were created if no PGT testing was performed. If PGT testing was performed and indicates that an embryo is euploid, the patient can be included if she was age 18-41 years at the time that the embryo was created.

  • Age 18-41 years at the time of randomization as advancing age itself becomes a significant risk for preeclampsia

  • Normal uterine cavity as assessed by saline infusion sonohysterogram, hysterosalpingogram, or hysteroscopy within one year of the enrollment visit, and repeated at the discretion of the investigator

  • Regular menstrual cycle length (approximately 24-35 days) indicative of ovulatory cycles.

  • Willing to undergo elective single embryo transfer

  • Body Mass Index <=40

  • If Body Mass Index is over 30 or individual has other risk factors for diabetes, normal hemoglobin A1C

  • Prior to enrollment, participant will have at least one vitrified blastocyst with euploid result by pre-implantation genetic testing (PGT-A) or at least one vitrified blastocyst of fair or better morphologic quality if no PGT-A results are available.

  • Willingness to be randomized to either a modified natural or programmed cycle, with a willingness to administer intramuscular progesterone in oil if assigned to the programmed cycle.

  • Normal thyroid stimulating hormone (TSH), according to local laboratory standards (or TSH level with a clinically insignificant abnormality per the site director), within one year of study enrollment and repeated at the discretion of the investigator. Use of thyroid medication is permitted.

Exclusion criteria

To be eligible, subjects must not meet any one of these criteria:

  • Medical contraindication to pregnancy

  • Embryos created using donor oocytes

  • Embryo donation

  • Gestational carrier

  • Reciprocal IVF (one female partner carrying pregnancy, other female partner as source of eggs)

  • Fresh embryos created from frozen oocytes. Patients with frozen embryos created from frozen oocytes can be included.

  • Recurrent implantation failure defined as no clinical pregnancy with ≥ 2 prior consecutive embryo transfers unless patient also had successful live birth between or after the failed embryo transfers

  • Anti-phospholipid antibody syndrome or rheumatologic disease requiring chronic systemic medications

  • Uncontrolled diabetes mellitus

  • History of >1 pregnancy loss in the second or third trimester

  • Uncontrolled hypertension

  • Untreated hydrosalpinx (i.e., hydrosalpinx in situ which has not been ligated or removed)

  • Mullerian uterine anomaly, if not correctable

  • Physician recommendation to perform the embryo transfer outside of the timing specified by the protocol

  • Contraindication to any medication which must be used in preparation for the frozen embryo transfer (i.e., estradiol, progesterone, hCG)

Study Design

Total Participants: 788
Treatment Group(s): 2
Primary Treatment: Programmed cycle
Phase: 3
Study Start date:
September 16, 2020
Estimated Completion Date:
April 01, 2026

Study Description

NatPro is a two-arm, parallel-group, multi-center, randomized trial in which women undergoing FET will be randomized to receive either a modified natural cycle (corpus luteum present) or a programmed cycle (corpus luteum absent). The study will implement a stratified randomization design to balance the use of pre-implantation genetic testing (PGT) across the two treatment arms. Each participant will have up to 3 FET cycles until live birth occurs, or the participant has no embryos available for transfer. Primary endpoints will be the proportion of women experiencing preeclampsia comparing modified natural to programmed FET among women with viable pregnancy (defined as pregnancy lasting at least 20 weeks) and the cumulative proportion of women having live births in the two arms.

Connect with a study center

  • University of California San Francisco

    San Francisco, California 94158
    United States

    Site Not Available

  • Stanford University

    Sunnyvale, California 94087
    United States

    Site Not Available

  • Yale

    Orange, Connecticut 06477
    United States

    Site Not Available

  • Fertility Institute of Hawaii

    Honolulu, Hawaii 96814
    United States

    Site Not Available

  • Northwestern University

    Chicago, Illinois 60611
    United States

    Site Not Available

  • Johns Hopkins

    Baltimore, Maryland 21093
    United States

    Site Not Available

  • Shady Grove Fertility

    Rockville, Maryland 20850
    United States

    Site Not Available

  • Boston IVF

    Waltham, Massachusetts 02451
    United States

    Site Not Available

  • University of Rochester

    Rochester, New York 14642
    United States

    Site Not Available

  • Atrium Health

    Charlotte, North Carolina 28203
    United States

    Site Not Available

  • Cleveland Clinic Foundation

    Beachwood, Ohio 44122
    United States

    Site Not Available

  • University of Oklahoma

    Oklahoma City, Oklahoma 73104
    United States

    Site Not Available

  • University of Pennsylvania

    Philadelphia, Pennsylvania 19104
    United States

    Site Not Available

  • CARE Fertility

    Bedford, Texas 76022
    United States

    Site Not Available

  • West Virginia University Center for Reproductive Medicine

    Morgantown, West Virginia 26505
    United States

    Site Not Available

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