Probiotic and Antibiotic Therapies in Women With Unexplained Infertility

McMaster University

Status and phase: Withdrawn; Phase 2

Conditions: Endometriosis; Unexplained Infertility

Treatments: Drug: SH-DS01 + Metronidazole; Other: Probiotic Placebo + Antibiotic Placebo; Other: SH-DS01 + Antibiotic Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT04955574

JW-001

Details and patient eligibility

About

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.

Full description

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.

Sex: Female

Ages: 18 to 40 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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0 participants in 3 patient groups, including a placebo group

Probiotic + Antibiotic Placebo

Experimental group

Treatment:

Other: SH-DS01 + Antibiotic Placebo

Probiotic + Antibiotic

Experimental group

Treatment:

Drug: SH-DS01 + Metronidazole

Probiotic Placebo + Antibiotic Placebo

Placebo Comparator group

Treatment:

Other: Probiotic Placebo + Antibiotic Placebo