Prophylactic Antibiotics Prior to Embryo Transfer (PAPET): RCT

NCT03386227 | Terminated DMC

• 1 other identifier: WashingtonU_REI
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to determine the impact on clinical pregnancy rate of withholding routine prophylactic antibiotic therapy during IVF. The hypothesis is that withholding antibiotic prophylaxis will be non-inferior to routine administration. To test this hypothesis, the investigators will conduct a randomized controlled non inferiority trial. Additionally an exploratory study will be conducted among the first 30 patients undergoing their first cycle enrolled to evaluate the microbiome across the IVF cycle, in addition to the human virome

Conditions

Assisted Reproductive Technology; Antibiotic Prophylaxis; Embryo Transfer

Keywords

Assisted Reproductive Technology; Antibiotic Prophylaxis; Microbiome

Outcome Measures

Primary Outcomes (1)

• Clinical pregnancy rate

  Defined as a gestational sac, with fetal pole and cardiac activity, on ultrasound

  Our primary outcome measure will be obtained at 5-8 weeks gestational age following embryo transfer

Secondary Outcomes (5)

• Miscarriage rate

  Prior to 20 weeks gestation in a previously established clinical pregnancy

• Embryo development

  Intraoperative (This outcome measure will be assessed from the time of egg retrieval to embryo transfer or embryo cryopreservation)

• Live birth

  delivery

• Reproductive Tract Microbiome

  Approximately 30 days from start of IVF cycle

• Reproductive Tract Virome

  Intraoperative (At the time of embryo transfer)

Study Arms (2)

Prophylactic antibiotics

NO INTERVENTION

Current standard of care in our practice for a fresh in vitro fertilization cycle is to administer one dose of 1 gram oral azithromycin on day one of the IVF cycle start to both the male and female partner. In cases of same-sex couples, only the female undergoing the embryo transfer receives prophylaxis. This will serve as our control arm entitled: prophylactic antibiotics.

No antibiotic prophylaxis.

EXPERIMENTAL

Couples randomized to the no-antibiotic treatment group will not be prescribed oral antibiotic prophylaxis.

Other: Withholding antibiotic prophylaxis

Interventions

Withholding antibiotic prophylaxis OTHER

Our intervention will be a deviation from our current standard of care which is universal antibiotic prophylaxis, even in low risk populations. Our intervention will be withholding antibiotic prophylaxis in low risk populations.

No antibiotic prophylaxis.

Eligibility Criteria

• Age: 18 Years - 43 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The female partner must be aged 18-43 years and going through a fresh IVF cycle

You may not qualify if:

• Couples will be excluded from enrollment if they have any contraindication to antibiotic treatment, are not intending to undergo embryo transfer (fertility preservation patients and oocyte donors), require use of extended antibiotic coverage at time of egg retrieval, are already on antibiotics for any reason (e.g., upper respiratory infection), have a recent history of pelvic infection, or are planning on limited insemination (inseminating a limited number of the eggs retrieved) or are using donor sperm.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University Reproductive Endocrinology

St Louis, Missouri, 63108, United States

Location

Related Publications (9)

• Kroon B, Hart RJ, Wong BM, Ford E, Yazdani A. Antibiotics prior to embryo transfer in ART. Cochrane Database Syst Rev. 2012 Mar 14;(3):CD008995. doi: 10.1002/14651858.CD008995.pub2.

  PMID: 22419341 BACKGROUND

• Brook N, Khalaf Y, Coomarasamy A, Edgeworth J, Braude P. A randomized controlled trial of prophylactic antibiotics (co-amoxiclav) prior to embryo transfer. Hum Reprod. 2006 Nov;21(11):2911-5. doi: 10.1093/humrep/del263. Epub 2006 Jul 10.

  PMID: 16832124 BACKGROUND

• Kaye L, Bartels C, Bartolucci A, Engmann L, Nulsen J, Benadiva C. Old habits die hard: retrospective analysis of outcomes with use of corticosteroids and antibiotics before embryo transfer. Fertil Steril. 2017 Jun;107(6):1336-1340. doi: 10.1016/j.fertnstert.2017.04.003. Epub 2017 May 10.

  PMID: 28501367 BACKGROUND

• Practice Committee of the American Society for Reproductive Medicine. Electronic address: ASRM@asrm.org; Practice Committee of the American Society for Reproductive Medicine. Performing the embryo transfer: a guideline. Fertil Steril. 2017 Apr;107(4):882-896. doi: 10.1016/j.fertnstert.2017.01.025.

  PMID: 28366416 BACKGROUND

• Franasiak JM, Scott RT Jr. Reproductive tract microbiome in assisted reproductive technologies. Fertil Steril. 2015 Dec;104(6):1364-71. doi: 10.1016/j.fertnstert.2015.10.012. Epub 2015 Oct 24.

  PMID: 26597628 BACKGROUND

• Fox C, Eichelberger K. Maternal microbiome and pregnancy outcomes. Fertil Steril. 2015 Dec;104(6):1358-63. doi: 10.1016/j.fertnstert.2015.09.037. Epub 2015 Oct 19.

  PMID: 26493119 BACKGROUND

• Ledger WJ, Blaser MJ. Are we using too many antibiotics during pregnancy? BJOG. 2013 Nov;120(12):1450-2. doi: 10.1111/1471-0528.12371. No abstract available.

  PMID: 24118809 BACKGROUND

• Wylie TN, Wylie KM, Herter BN, Storch GA. Enhanced virome sequencing using targeted sequence capture. Genome Res. 2015 Dec;25(12):1910-20. doi: 10.1101/gr.191049.115. Epub 2015 Sep 22.

  PMID: 26395152 BACKGROUND

• Eskew AM, Stout MJ, Bedrick BS, Riley JK, Herter BN, Gula H, Jungheim ES, Wylie KM. Association of vaginal bacterial communities and reproductive outcomes with prophylactic antibiotic exposure in a subfertile population undergoing in vitro fertilization: a prospective exploratory study. F S Sci. 2021 Feb;2(1):71-79. doi: 10.1016/j.xfss.2021.01.002. Epub 2021 Jan 11.

  PMID: 34632426 DERIVED

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The embryologists who assess embryo outcomes (as noted in the secondary outcomes) will be blinded to randomization.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study will have patients randomized in a 1:1 fashion to antibiotic prophylaxis or withholding antibiotic prophylaxis.

Study Record Dates

• First Submitted: December 21, 2017
• First Posted: December 29, 2017
• Study Start: January 21, 2018
• Primary Completion: June 30, 2019
• Study Completion: July 31, 2019
• Last Updated: August 18, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)