Optimal Planning of a Day 3 Cryopreserved(Frozen)-Thawed Embryo Transfer in a Natural Cycle With hCG Administration or After Spontaneous LH Peak? (PLUS)

The aim of the study is to determine whether spontaneous LH peak is superior to human chorionic gonadotropin before a transfer of a day 3 frozen embryo.

Study Overview

• Status: Completed
• Conditions: Supervision of Pregnancy Resulting From In-vitro Fertilization
• Intervention / Treatment: Other: LH peak; Drug: hCG

Detailed Description

For surplus embryos after fresh IVF-cycles, cryopreservation has become common medical practice. These frozen embryos are mostly replaced in an artificial cycle with exogenous estrogen and progesterone or in a natural cycle. Often, hCG is administered as an ovulation induction agent for scheduling purposes.

Successful implantation requires a co-ordinated series of events allowing a timely dialogue between a receptive endometrium and the intrusive blastocyst . The period of receptivity is thought to be 3 days in human. It is suggested that blastocyst apposition begins about day LH+6 and is completed by day LH+10

In general, the aim is to transfer the embryo during the 'window of implantation', what is defined as the period during which the uterus is receptive for implantation of the free-lying blastocyst. This has been a subject of debate since many years.

A prospective study by Fatemi et al. (2010) revealed a significantly higher ongoing pregnancy rate after transferring frozen-thawed embryos in natural cycles with a spontaneous LH peak compared with natural cycles controlled by hCG for final oocyte maturation and ovulation (31.1% vs. 14.3%, respectively). In this trial, FrET (frozen embryo transfer) was planned 5 days after the LH surge or 5 days after the administration of 5000IU of hCG.

In order to optimize the synchronization in the hCG group, and therefore enhance the pregnancy rates, the aim is to plan a FrET 6 days after hCG administration instead of 5 days. The rationale behind is that day 3 frozen embryos are thawed the day before embryo transfer, which means they are already at day 4 of the embryonic development.

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Brussels
    • Jette, Brussels, Belgium, 1090
      • Centre of Reproductive Medicine CRG

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 39 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Natural cycles, in which a frozen-thawed day 3 embryo is replaced.
• Signed informed consent.
• Regular cycle (i.e. between 26 and 35 days)
• Normal transvaginal ultrasound at screening, without evidence of clinically significant abnormality consistent with finding adequate for ART with respect to uterus and adnexa.
• Embryos frozen by vitrification.
• Single or dual embryo transfer.

Exclusion Criteria:

• Known allergic reactions to progesterone products.
• Intake of experimental drug within 30 days prior to study start.
• Contraindication for pregnancy.
• Embryos of women above 39 years of age at the time of embryo freezing.
• Recipients of oocyte donation cycles

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: A: spontaneous LH peak; In group A, embryos are thawed 4 days after LH surge, with a re-evaluation and transfer 5 days after LH surge.	Other: LH peak
Active Comparator: B: hCG; In group B, embryos are thawed 5 days after hCG administration, with a re-evaluation and transfer 6 days after hCG.	Drug: hCG; Other Names: spontaneous LH peak

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinical pregnancy rate	We evaluate the pregnancy, at 7 weeks amenorrhoea. Outcome is clinical pregnancy rate	7 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
number of monitoring visits at the clinic per cycle	7 weeks

Collaborators and Investigators

• Sponsor: Universitair Ziekenhuis Brussel

Publications and helpful links

General Publications

• Mackens S, Stubbe A, Santos-Ribeiro S, Van Landuyt L, Racca A, Roelens C, Camus M, De Vos M, van de Vijver A, Tournaye H, Blockeel C. To trigger or not to trigger ovulation in a natural cycle for frozen embryo transfer: a randomized controlled trial. Hum Reprod. 2020 May 1;35(5):1073-1081. doi: 10.1093/humrep/deaa026.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): September 1, 2019
• Study Completion (Actual): September 1, 2019

Study Registration Dates

• First Submitted: January 8, 2014
• First Submitted That Met QC Criteria: May 20, 2014
• First Posted (Estimate): May 23, 2014

Study Record Updates

• Last Update Posted (Actual): September 27, 2019
• Last Update Submitted That Met QC Criteria: September 25, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: PLUS