The Impact of Past Coronavirus Disease 19 (COVID-19) Infection on the Live Birth Rates of Frozen Embryo Transfer Cycles

A Prospective Observational Study of the Impact of a Recent Past COVID-19 Infection on the Live Birth Rates of Frozen Embryo Transfer Cycles

This is a prospective observational study. In this study, we aim to investigate the effect of a recent past Covid-19 infection on the live birth rate in the frozen embryo transfer cycles

Study Overview

• Status: Completed
• Conditions: COVID-19; Frozen Embryo Transfer
• Intervention / Treatment: Other: frozen embryo transfer

• Study Type: Observational
• Enrollment (Actual): 820

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • ShangHai JIAI Genetics&IVF Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 42 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Infertile women for frozen embryo transfer will be recruited for study after explanation and counseling if they fulfil the inclusion criteria and do not have the exclusion criteria.

Description

Inclusion Criteria:

1. Women aged 20-42 years at the time of ovarian stimulation for in vitro fertilization
2. Women have embryos frozen prior to COVID infection.

Exclusion Criteria:

1. Previous COVID infection before oocyte retrieval
2. Recipient of oocyte donation
3. Undergoing preimplantation genetic testing
4. Presence of hydrosalpinx or endometrial polyp which is not surgically treated

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
COVID-19 infection group; Infertile women attending for frozen embryo transfer with a recent past COVID-19 infection	Other: frozen embryo transfer; transfer one or two embryos in frozen embryo transfer cycles
Control group; Infertile women attending for frozen embryo transfer without a recent past COVID-19 infection	Other: frozen embryo transfer; transfer one or two embryos in frozen embryo transfer cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
live birth rate	live birth rate of the frozen embryo transfer cycle (>22 weeks of gestation)	a live birth after 22 weeks gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
multiple pregnancy	more than one intrauterine sacs on scanning	multiple pregnancy beyond gestation 12 weeks
ectopic pregnancy	pregnancy outside the uterine cavity	ectopic pregnancy during 12 weeks gestation
serum hCG level	serum hCG level	a blood pregnancy test is performed 14 days after the embryo transfer
clinical pregnancy	presence of intrauterine gestational sac on ultrasound	presence of intrauterine gestational sac on ultrasound at 6 weeks of pregnancy
ongoing pregnancy	viable pregnancy beyond gestation 12 weeks	viable pregnancy beyond gestation 12 weeks
biochemical pregnancy	positive blood pregnancy test not followed by clinical pregnancy	positive blood pregnancy test not followed by clinical pregnancy during 12 weeks gestation
implantation rate	number of gestational sacs per embryo transferred	number of gestational sacs per embryo transferred during 4 weeks of pregnancy
miscarriage	the loss of a pregnancy before 22 weeks gestation	the loss of a pregnancy before 22 weeks gestation
birth weight	birth weight of the baby delivered	a live birth after 22 weeks gestation
serum COVID-19 antibody level	serum COVID-19 antibody level immunoglobulin G and immunoglobulin M	7 days before embryo transfer

Collaborators and Investigators

• Sponsor: ShangHai Ji Ai Genetics & IVF Institute
• Investigators: Study Director: Xiaoxi Sun, Phd, Shanghai JiAi Genetics & IVF Institute

Publications and helpful links

General Publications

• Zou X, Chen K, Zou J, Han P, Hao J, Han Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med. 2020 Apr;14(2):185-192. doi: 10.1007/s11684-020-0754-0. Epub 2020 Mar 12.
• Henarejos-Castillo I, Sebastian-Leon P, Devesa-Peiro A, Pellicer A, Diaz-Gimeno P. SARS-CoV-2 infection risk assessment in the endometrium: viral infection-related gene expression across the menstrual cycle. Fertil Steril. 2020 Aug;114(2):223-232. doi: 10.1016/j.fertnstert.2020.06.026. Epub 2020 Jun 17.
• Lukassen S, Chua RL, Trefzer T, Kahn NC, Schneider MA, Muley T, Winter H, Meister M, Veith C, Boots AW, Hennig BP, Kreuter M, Conrad C, Eils R. SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. EMBO J. 2020 May 18;39(10):e105114. doi: 10.15252/embj.20105114. Epub 2020 Apr 14.
• Vaz-Silva J, Carneiro MM, Ferreira MC, Pinheiro SV, Silva DA, Silva-Filho AL, Witz CA, Reis AM, Santos RA, Reis FM. The vasoactive peptide angiotensin-(1-7), its receptor Mas and the angiotensin-converting enzyme type 2 are expressed in the human endometrium. Reprod Sci. 2009 Mar;16(3):247-56. doi: 10.1177/1933719108327593. Epub 2009 Jan 22.
• Aizer A, Noach-Hirsh M, Dratviman-Storobinsky O, Nahum R, Machtinger R, Yung Y, Haas J, Orvieto R. The effect of coronavirus disease 2019 immunity on frozen-thawed embryo transfer cycles outcome. Fertil Steril. 2022 May;117(5):974-979. doi: 10.1016/j.fertnstert.2022.01.009. Epub 2022 Jan 10.
• Youngster M, Avraham S, Yaakov O, Landau Rabbi M, Gat I, Yerushalmi G, Baum M, Maman E, Hourvitz A, Kedem A. The impact of past COVID-19 infection on pregnancy rates in frozen embryo transfer cycles. J Assist Reprod Genet. 2022 Jul;39(7):1565-1570. doi: 10.1007/s10815-022-02517-w. Epub 2022 May 7.

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2023
• Primary Completion (Actual): January 1, 2025
• Study Completion (Actual): February 1, 2025

Study Registration Dates

• First Submitted: February 21, 2023
• First Submitted That Met QC Criteria: February 21, 2023
• First Posted (Actual): February 22, 2023

Study Record Updates

• Last Update Posted (Actual): May 28, 2025
• Last Update Submitted That Met QC Criteria: May 27, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19
• Other Study ID Numbers: JIAI 2023-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results after deidentification (text, tables, figures, and appendices) and study protocol will be shared. Data will be available when beginning 3 months and ending 5 years following article publication. To achieve aims in the approved proposal, researchers who provide a methodologically sound proposal will be shared with.Data will be made available by the following way. Proposals should be directed to lihe198900@163.com. And data are available for 5 years at a third party website (link to be included after the article publication
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No