Probiotic and Antibiotic Therapies in Women With Unexplained Infertility

NCT ID: NCT04955574

Last Updated: 2023-06-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2023-01-31

Study Completion Date

2024-12-31

Brief Summary

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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.

Detailed Description

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Previous research has demonstrated that the uterine microbiota can impact fertility and embryo implantation. This information leads to the hypothesis that prophylactic antibiotic and/or probiotic treatment may improve reproductive outcomes in women with unexplained infertility/endometriosis who are seeking In Vitro Fertilization (IVF). No therapeutic protocols to improve these outcomes currently exist. However, there are safe and easily accessible medications and supplements that may be able to optimally modify the uterine microbiota. Herein we are proposing a proof of concept pilot study of the feasibility, safety and tolerability of administering oral probiotics, or oral probiotics in combination with antibiotics, to women seeking IVF.

Conditions

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Unexplained Infertility Endometriosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Probiotic + Antibiotic Placebo

Group Type EXPERIMENTAL

SH-DS01 + Antibiotic Placebo

Intervention Type 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

Group Type EXPERIMENTAL

SH-DS01 + Metronidazole

Intervention Type 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 Placebo + Antibiotic Placebo

Group Type PLACEBO_COMPARATOR

Probiotic Placebo + Antibiotic Placebo

Intervention Type 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.

Interventions

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Probiotic Placebo + Antibiotic Placebo

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.

Intervention Type OTHER

SH-DS01 + Antibiotic Placebo

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.

Intervention Type OTHER

SH-DS01 + Metronidazole

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

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

1. Oral probiotics
2. Alcohol
3. Anticoagulant therapies (Warfarin type)
4. Drugs containing alcohol
5. Busulfan
6. Cyclosporin
7. Disulfiram
8. 5-Fluoruracil
9. Lithium
10. Phenytoin or Phenobarbital
11. Vecuronium
12. Proton pump inhibitors
13. Histamine H2-receptor antagonists
13. Currently experiencing nausea, fever, vomiting, bloody diarrhea or severe abdominal pain
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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One Fertility

OTHER

Sponsor Role collaborator

McMaster University

OTHER

Sponsor Role lead

Responsible Party

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Jocelyn Wessels

Postdoctoral Fellow

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jocelyn Wessels, PhD

Role: PRINCIPAL_INVESTIGATOR

McMaster University

References

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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.

Reference Type BACKGROUND
PMID: 12839628 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17636439 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27717732 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30013432 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9806568 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10466674 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11119737 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16832124 (View on PubMed)

Other Identifiers

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JW-001

Identifier Type: -

Identifier Source: org_study_id

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