Natural Cycles With Spontaneous Versus Induced Ovulation in FET

Frozen-Thawed Embryo Transfers: a Comparison Between Natural Cycles With Spontaneous or Induced Ovulation

In recent years, frozen-thawed embryo transfer procedure (FET) has been widely used to increase the cumulative pregnancy rate per IVF-cycle: which is the best preparation protocol remains a matter of debate.

A retrospective analysis was conducted between 2012-2017. The aim was comparing clinical pregnancy rate (CPR) of pure natural cycle frozen-thawed embryo transfer (NC-FET) versus natural cycle frozen-thawed embryo transfer with hCG-triggered ovulation (mNC-FET).

Study Overview

• Status: Completed
• Conditions: Embryo Transfer
• Intervention / Treatment: Drug: hCG administration before embryo transfer

Detailed Description

Compared to repeated oocyte retrieval procedure, frozen-thawed embryo transfer (FET) has been widely used to increase the cumulative pregnancy rate per IVF-cycle, with demonstrated superiority in preventing ovarian hyperstimulation syndrome and improving cost-efficiency and time to pregnancy.

It is controversial whether triggering ovulation of the dominant follicle using human chorionic gonadotrophin (hCG) may benefit or reduce embryo implantation, when compared with a natural cycle environment. Unfavourable clinical outcomes of controlled ovarian stimulation have been reported by recently published studies, compared to the spontaneous LH surge.

This study aimed to compare the effectiveness in terms of better clinical pregnancy rates (CPR) of pure natural cycle frozen-thawed embryo transfer (NC-FET) versus natural cycle frozen-thawed embryo transfer modified by HCG administration\with hCG-triggered ovulation (mNC-FET).

A retrospective analysis was conducted between 2012-2017. In patients with regular ovulatory cycles, the timing of embryo thawing and transferring was based on spontaneous LH surge (NC-FET). Patients attended for ultrasound evaluation of the dominant follicle from Day 8 to 10 of their menstrual cycle (depending on cycle length), detecting luteinizing hormone (LH) surge in urine/ taking an ovulation test for urinary LH measurement. In selected cases, a serum assays of LH, progesterone and estradioI has been further obtained. When the endometrial thickness reached 8 mm and dominant follicle 16-20 mm in diameter, hCG was administered in absence of urinary LH surge. Embryo thawing and transfer was planned 7 days after LH surge or HCG administration, whether G5 or G6 blastocyst. Exogenous progesterone supplementation started 2 days after hCG administration versus the same day of embryo transfer procedure in NC- ET. To limit potential confounders, only single blastocyst transfer cycles were included, vitrified on Days 5 or 6, excluding PGT-a (Pre Gestational Test for aneuploydia) cycles and cleavage stage embryo transfers. A unilevel and multi level logistic regression analysis was conducted using Stata Software versione15.

• Study Type: Observational
• Enrollment (Actual): 2866

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

2866 cycles were included in the analysis. To limit potential confounders, only single blastocyst transfer cycles were included, vitrified on Days 5 or 6, excluding PGT-a cycles and cleavage stage embryo transfers.

Description

Inclusion Criteria:

• only single blastocyst transfer cycles were included

Exclusion Criteria:

• PGT-a cycles and cleavage stage embryo transfers

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
NC-FET; pure natural cycle frozen-thawed embryo transfer
mNC-FET; modified natural cycle frozen-thawed embryo transfer by hCG administration	Drug: hCG administration before embryo transfer; Thawed embryo transfer with ovulation triggered by hCG; Other Names: Gonasi HP 5000 UI or Ovitrelle 250mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CPR in NCFET vs mNCFET	compare the effectiveness in terms of better clinical pregnancy rates (CPR) of pure natural cycle frozen-thawed embryo transfer (NC-FET) versus natural cycle frozen-thawed embryo transfer modified by HCG administration	2012-2017

Collaborators and Investigators

• Sponsor: Istituto Clinico Humanitas

Publications and helpful links

General Publications

• Levi Setti PE, Cirillo F, De Cesare R, Morenghi E, Canevisio V, Ronchetti C, Baggiani A, Smeraldi A, Albani E, Patrizio P. Seven Years of Vitrified Blastocyst Transfers: Comparison of 3 Preparation Protocols at a Single ART Center. Front Endocrinol (Lausanne). 2020 May 29;11:346. doi: 10.3389/fendo.2020.00346. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2012
• Primary Completion (Actual): June 15, 2015
• Study Completion (Actual): December 31, 2017

Study Registration Dates

• First Submitted: June 26, 2018
• First Submitted That Met QC Criteria: June 26, 2018
• First Posted (Actual): July 10, 2018

Study Record Updates

• Last Update Posted (Actual): July 19, 2018
• Last Update Submitted That Met QC Criteria: July 17, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Reproductive Control Agents; Chorionic Gonadotropin
• Other Study ID Numbers: xxxx2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No