Immediate Versus Delayed Natural Cycle Frozen Embryo Transfers

NCT05215119 | Completed

• 1 other identifier: timetoFETJan2022
• Study Type: observational
• Target: 818
• Locations: 1 country
• Sites: 1

Brief Summary

Introduction: Based on recent studies the suggestion is that natural cycle frozen embryo transfers (NC FET) should preferably be used, with evidence suggesting that artificial cycle FET (AC FET) is subject to increased risks of adverse obstetric and perinatal outcomes and possibly lower live birth rates. There, however, is limited evidence on the most efficient and effective timing of NC FET following oocyte retrieval. Objective: In this non-inferiority randomised controlled trial, the effect on reproductive outcomes of NC FET performed immediately following the oocyte retrieval cycle (i.e., after one menstruation) will be investigated. Materials and Methods: At a single IVF centre, patients will be recruited from infertile patients presenting for freeze-all-IVF treatments. Patients aged 18 to 30 years will be enrolled, if they had ≤2 previous embryo transfers and had ≥1 blastocyst cryopreserved in their freeze-all cycles. Enrolled patients (N = 800) will be randomised (1:1) to either the immediate group (i.e., FET performed in the menstrual cycle immediately following the oocyte retrieval cycle) or the delayed group (i.e., FET performed in the menstrual cycle following two menstruations). All FET will be performed in NC. The primary outcome measure will be clinical pregnancy, defined as the visual confirmation by transvaginal ultrasound scan of a gestational sac with normal heartbeat at \>5 weeks of gestation. The analyses will be performed according to per-procedure principles. Results: The ovarian, endometrial and time to transfer outcomes of the immediate group will be compared with those of the delayed group. The clinical pregnancy rate of the immediate group will be compared with that of the delayed group.

Conditions

Clinical Pregnancy

Keywords

frozen embryo transfer; time-to-transfer; natural cycle; endometrial preparation

Outcome Measures

Primary Outcomes (1)

• Clinical pregnancy from frozen embryo transfers

  Clinical pregnancy rate will be defined as a pregnancy cycle with a normal gestational sac and fetal heartbeat confirmed by ultrasound at \>5.5 weeks of gestation.

  Transvaginal ultrasound examination will be performed after 5 weeks of gestation (>5.5 weeks)

Secondary Outcomes (3)

• Pregnancy from frozen embryo transfers

  Blood serum pregnancy tests will be performed 9 days after blastocyst transfer

• Early pregnancy loss of frozen embryo transfer pregnancies

  Serial transvaginal ultrasound scans will be performed to 12 weeks of gestation

• Ongoing pregnancy from frozen embryo transfers

  Transvaginal ultrasound scan will be performed after 12 weeks of gestation

Study Arms (2)

Immediate

NC endometrial preparation will start immediately after blastocyst cryopreservation confirmation.

Procedure: natural cycle endometrial preparation

Delayed

NC endometrial preparation will start on day 1 of the patient's 2nd menstruation after the oocyte retrieval cycle menstruation or in a subsequent cycle.

Procedure: natural cycle endometrial preparation

Interventions

natural cycle endometrial preparation PROCEDURE

Cycles will be monitored from either day-10 or-12, according to patient's menstrual cycle length, with serial analysis of blood serum LH and progesterone levels and assessment of dominant follicle growth. In a spontaneous cycle, ovulation will be determined by a LH surge (\>20 IU/L) and a corresponding rise in progesterone (\>0.8 ng/ml). In a triggered cycle, ovulation will be determined by the administration of an hCG trigger when the dominate follicle reached \>16 mm (and LH was \<20 IU/L).

Delayed; Immediate

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Study participants will be recruited from (unselected) infertile patients presenting for freeze-all-IVF treatment at the IVF centre from the start date of enrollment.

You may qualify if:

• Patients with female age 18≤40 years.
• Patients who provide written informed consent to participate in the trial and for the use of their anonymized data in research.
• Patients with \<2 previous IVF treatments.
• Patients with ≥1 blastocyst cryopreserved.

You may not qualify if:

• Patients with female age \>40 years
• Patients with female BMI ≥30 kg/m2.
• Female patients with insulin dependent diabetes or non-insulin dependent diabetes mellitus and female patients with gastrointestinal, cardiovascular, pulmonary, liver or kidney disease.
• Female patients with any contraindications or allergies to the drugs used in routine freeze-all-IVF.
• Patients with untreated intrauterine anomalies and tubal pathology.
• Patients undergoing PGT-A (aneuploidy) or PGT-M (monogenic disorders)
• Patients with no blastocysts cryopreserved.

Sponsors & Collaborators

• Antalya IVF: lead

Study Sites (1)

Antalya IVF

Antalya, Antalya, 07080, Turkey (Türkiye)

Location

Related Publications (8)

• Mackens S, Santos-Ribeiro S, van de Vijver A, Racca A, Van Landuyt L, Tournaye H, Blockeel C. Frozen embryo transfer: a review on the optimal endometrial preparation and timing. Hum Reprod. 2017 Nov 1;32(11):2234-2242. doi: 10.1093/humrep/dex285.

  PMID: 29025055 BACKGROUND

• 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.

  PMID: 23820515 BACKGROUND

• von Versen-Hoynck F, Narasimhan P, Selamet Tierney ES, Martinez N, Conrad KP, Baker VL, Winn VD. Absent or Excessive Corpus Luteum Number Is Associated With Altered Maternal Vascular Health in Early Pregnancy. Hypertension. 2019 Mar;73(3):680-690. doi: 10.1161/HYPERTENSIONAHA.118.12046.

  PMID: 30636549 BACKGROUND

• Singh B, Reschke L, Segars J, Baker VL. Frozen-thawed embryo transfer: the potential importance of the corpus luteum in preventing obstetrical complications. Fertil Steril. 2020 Feb;113(2):252-257. doi: 10.1016/j.fertnstert.2019.12.007.

  PMID: 32106972 BACKGROUND

• Makhijani R, Bartels C, Godiwala P, Bartolucci A, Nulsen J, Grow D, Benadiva C, Engmann L. Maternal and perinatal outcomes in programmed versus natural vitrified-warmed blastocyst transfer cycles. Reprod Biomed Online. 2020 Aug;41(2):300-308. doi: 10.1016/j.rbmo.2020.03.009. Epub 2020 Mar 21.

  PMID: 32505542 BACKGROUND

• Pier BD, Havemann LM, Quaas AM, Heitmann RJ. Frozen-thawed embryo transfers: time to adopt a more "natural" approach? J Assist Reprod Genet. 2021 Aug;38(8):1909-1911. doi: 10.1007/s10815-021-02151-y. Epub 2021 Mar 19.

  PMID: 33738681 BACKGROUND

• Wu H, Zhou P, Lin X, Wang S, Zhang S. Endometrial preparation for frozen-thawed embryo transfer cycles: a systematic review and network meta-analysis. J Assist Reprod Genet. 2021 Aug;38(8):1913-1926. doi: 10.1007/s10815-021-02125-0. Epub 2021 Apr 7.

  PMID: 33829375 BACKGROUND

• Matorras R, Pijoan JI, Perez-Ruiz I, Lainz L, Malaina I, Borjaba S. Meta-analysis of the embryo freezing transfer interval. Reprod Med Biol. 2021 Jan 5;20(2):144-158. doi: 10.1002/rmb2.12363. eCollection 2021 Apr.

  PMID: 33850447 BACKGROUND

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2022
• First Posted: January 31, 2022
• Study Start: March 4, 2022
• Primary Completion: February 8, 2025
• Study Completion: February 8, 2025
• Last Updated: February 11, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: To be published immediately after publication acceptance
• Access Criteria: Open access at the Mendeley Data registry at the URLs provided

Locations

TU (1)