Probiotic and Antibiotic Therapies in Women With Unexplained Infertility

NCT04955574 | Withdrawn Phase 2

• 1 other identifier: JW-001
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The study is designed as a proof of concept pilot study with 3 study arms to evaluate the safety and feasibility of the use of oral probiotics and/or antibiotics in women with unexplained infertility/endometriosis. Our secondary outcomes will assess In Vitro Fertilization outcomes, and changes in the uterine microbiota (bacteria), intestinal barrier integrity, and urinary metabolites in response to study interventions.

Conditions

Unexplained Infertility; Endometriosis

Keywords

Uterine microbiota; Endometrial microbiota

Outcome Measures

Primary Outcomes (4)

• Rate of study enrollment

  Evaluated by number of eligible participants consenting to enrollment in the study.

  Screening

• Rate of retention of study participants

  Evaluated by number of study participants who complete, drop out or withdraw from the study.

  Immediately after the intervention

• Proportion of participants adhering to study protocol

  Evaluated as the percentage of study participants reporting daily administration of study interventions throughout the intervention period.

  Immediately after the intervention

• Incidence of intervention-emergent adverse events

  Evaluated as the percentage of adverse events occurring in each intervention group.

  Immediately after the intervention

Secondary Outcomes (8)

• Difference in implantation rate

  Endpoint of interventions to 4 weeks gestation (if applicable)

• Difference in clinical pregnancy rate

  Endpoint of interventions to 6 weeks gestation (if applicable)

• Difference in ongoing pregnancy rate

  Endpoint of interventions to 12 weeks gestation (if applicable)

• Change in uterine microbiota composition

  Baseline, immediately after interventions

• Change in serum LPS

  Baseline, immediately after interventions

Study Arms (3)

Probiotic + Antibiotic Placebo

EXPERIMENTAL

Other: SH-DS01 + Antibiotic Placebo

Probiotic + Antibiotic

EXPERIMENTAL

Drug: SH-DS01 + Metronidazole

Probiotic Placebo + Antibiotic Placebo

PLACEBO COMPARATOR

Other: Probiotic Placebo + Antibiotic Placebo

Interventions

SH-DS01 + Antibiotic Placebo OTHER

Participants will be instructed to take 2 capsules of SH-DS01 probiotic once daily (at lunch) from cycle day 1 to the day of ovulation/day of luteal progesterone initiation, followed by 2 capsules of SH-DS01 probiotic once daily (at lunch) and 1 capsule of placebo for antibiotic twice daily (at breakfast and dinner) from the day of ovulation/day of luteal progesterone initiation to the day of frozen embryo transfer.

Probiotic + Antibiotic Placebo

SH-DS01 + Metronidazole DRUG

Participants will be instructed to take 2 capsules of SH-DS01 probiotic once daily (at lunch) from cycle day 1 to the day of ovulation/day of luteal progesterone initiation, followed by 2 capsules of SH-DS01 probiotic once daily (at lunch) and 1 capsule of 500mg metronidazole twice daily (at breakfast and dinner) from the day of ovulation/day of luteal progesterone initiation to the day of frozen embryo transfer.

Probiotic + Antibiotic

Probiotic Placebo + Antibiotic Placebo OTHER

Participants will be instructed to take 2 capsules of placebo for probiotic once daily (at lunch) from cycle day 1 to the day of ovulation/day of luteal progesterone initiation, followed by 2 capsules of placebo for probiotic once daily (at lunch) and 1 capsule of placebo for antibiotic twice daily (at breakfast and dinner) from the day of ovulation/day of luteal progesterone initiation to the day of frozen embryo transfer.

Probiotic Placebo + Antibiotic Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female aged 18-40 at the time of egg retrieval
• Generally in good health (at physician's discretion)
• Diagnosed with Unexplained Infertility
• Diagnosed with or suspected of having endometriosis (at ONE Fertility physician's discretion)
• Normal uterine cavity as assessed by prior sonohysterogram
• Planning to undergo Frozen Embryo Transfer with ≥1 frozen blastocyst ≥3BB (grade Gardner) to transfer
• Able to understand, comply and consent to protocol requirements and instructions
• Able to attend scheduled study visits and complete required investigations

You may not qualify if:

• Any known endometrial pathologies other than endometriosis
• Polycystic ovary syndrome
• Ovulatory dysfunction
• Male factor infertility (Total Motile Sperm Count \<5M/mL)
• Poorly controlled auto-immune disease and/or diabetes (at physician's discretion)
• Is immune-compromised
• Cockayne syndrome
• Allergy to Metronidazole
• Allergy to rice (bran and hull), pomegranate, Acacia gum, hypromellose, fermented gellan gum, chlorophyllin, or sunflower oil
• Known intolerance of Lactobacillus and/or Bifidobacterium-containing probiotics
• Antibiotic use in the past month
• Use of any of the following:
• Oral probiotics
• Alcohol
• Anticoagulant therapies (Warfarin type)

Sponsors & Collaborators

• McMaster University: lead
• One Fertility: collaborator

Related Publications (8)

• Eckert LO, Moore DE, Patton DL, Agnew KJ, Eschenbach DA. Relationship of vaginal bacteria and inflammation with conception and early pregnancy loss following in-vitro fertilization. Infect Dis Obstet Gynecol. 2003;11(1):11-7. doi: 10.1155/S1064744903000024.

  PMID: 12839628 BACKGROUND

• Selman H, Mariani M, Barnocchi N, Mencacci A, Bistoni F, Arena S, Pizzasegale S, Brusco GF, Angelini A. Examination of bacterial contamination at the time of embryo transfer, and its impact on the IVF/pregnancy outcome. J Assist Reprod Genet. 2007 Sep;24(9):395-9. doi: 10.1007/s10815-007-9146-5. Epub 2007 Jul 17.

  PMID: 17636439 BACKGROUND

• Moreno I, Codoner FM, Vilella F, Valbuena D, Martinez-Blanch JF, Jimenez-Almazan J, Alonso R, Alama P, Remohi J, Pellicer A, Ramon D, Simon C. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am J Obstet Gynecol. 2016 Dec;215(6):684-703. doi: 10.1016/j.ajog.2016.09.075. Epub 2016 Oct 4.

  PMID: 27717732 BACKGROUND

• Kyono K, Hashimoto T, Nagai Y, Sakuraba Y. Analysis of endometrial microbiota by 16S ribosomal RNA gene sequencing among infertile patients: a single-center pilot study. Reprod Med Biol. 2018 May 6;17(3):297-306. doi: 10.1002/rmb2.12105. eCollection 2018 Jul.

  PMID: 30013432 BACKGROUND

• Fanchin R, Harmas A, Benaoudia F, Lundkvist U, Olivennes F, Frydman R. Microbial flora of the cervix assessed at the time of embryo transfer adversely affects in vitro fertilization outcome. Fertil Steril. 1998 Nov;70(5):866-70. doi: 10.1016/s0015-0282(98)00277-5.

  PMID: 9806568 BACKGROUND

• Egbase PE, Udo EE, Al-Sharhan M, Grudzinskas JG. Prophylactic antibiotics and endocervical microbial inoculation of the endometrium at embryo transfer. Lancet. 1999 Aug 21;354(9179):651-2. doi: 10.1016/s0140-6736(99)02415-0.

  PMID: 10466674 BACKGROUND

• Moore DE, Soules MR, Klein NA, Fujimoto VY, Agnew KJ, Eschenbach DA. Bacteria in the transfer catheter tip influence the live-birth rate after in vitro fertilization. Fertil Steril. 2000 Dec;74(6):1118-24. doi: 10.1016/s0015-0282(00)01624-1.

  PMID: 11119737 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

MeSH Terms

Conditions

Endometriosis

Interventions

Metronidazole

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jocelyn Wessels, PhD

  McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Postdoctoral Fellow

Study Record Dates

• First Submitted: June 11, 2021
• First Posted: July 9, 2021
• Study Start: January 1, 2023
• Primary Completion: January 1, 2024
• Study Completion: December 1, 2024
• Last Updated: June 28, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share