Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Change in departmental research focus.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| One Fertility | OTHER |
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Probiotic + Antibiotic Placebo | Experimental |
| |
| Probiotic + Antibiotic | Experimental |
| |
| Probiotic Placebo + Antibiotic Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Difference in implantation rate | Evaluated by number of people with a positive beta hCG 2 weeks following frozen embryo transfer (FET), between intervention groups. | Endpoint of interventions to 4 weeks gestation (if applicable) |
| Difference in clinical pregnancy rate |
Not provided
Inclusion Criteria:
Exclusion Criteria:
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:
Currently experiencing nausea, fever, vomiting, bloody diarrhea or severe abdominal pain
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Jocelyn Wessels, PhD | McMaster University | Principal Investigator |
Not provided
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12839628 | Background | 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. | |
| 17636439 | 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. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D004715 | Endometriosis |
| ID | Term |
|---|---|
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D008795 | Metronidazole |
| ID | Term |
|---|---|
| D009593 | Nitroimidazoles |
| D009574 | Nitro Compounds |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| 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 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. |
|
Evaluated by number of people with a clinical pregnancy (gestational sac with fetal pole and cardiac activity seen on ultrasound at 6 weeks gestation), between intervention groups. |
| Endpoint of interventions to 6 weeks gestation (if applicable) |
| Difference in ongoing pregnancy rate | Evaluated by number of people with an ongoing pregnancy (gestational sac with fetal pole and cardiac activity seen on ultrasound at 12 weeks gestation), between intervention groups. | Endpoint of interventions to 12 weeks gestation (if applicable) |
| Change in uterine microbiota composition | Evaluated by 16S rRNA sequencing of the uterine microbiota at baseline versus on the day of FET, and compared between experimental groups. | Baseline, immediately after interventions |
| Change in serum LPS | Evaluated by changes in LPS-binding protein (LPS) at baseline versus on the day of FET, and compared between intervention groups. | Baseline, immediately after interventions |
| Change in intestinal permeability | Evaluated by changes in untargeted peripheral blood metabolites at baseline versus on the day of FET, and compared between intervention groups. | Baseline, immediately after interventions |
| Change in peripheral cytokines | Evaluated by changes in peripheral cytokines (TNF, IL-6, IL-8, IFNg - in pg/mL) at baseline versus on the day of FET, and compared between intervention groups. | Baseline, immediately after interventions |
| Change in urinary metabolites | Evaluated by changes untargeted urinary metabolites at baseline versus on the day of FET, and compared between intervention groups. Nontargeted metabolic phenotyping of >100 urinary metabolites will be performed by multisegment injection capillary electrophoresis-mass spectrometry (MSI-CE-MS) as a high throughput platform to analyze metabolites. The fold change for each metabolite will be calculated between baseline vs. after interventions, and the fold changes will be compared between intervention groups. | Baseline, immediately after interventions |
| 27717732 | 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. |
| 30013432 | 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. |
| 9806568 | 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. |
| 10466674 | 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. |
| 11119737 | 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. |
| 16832124 | 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. |
| D000091662 | Genital Diseases |
| D001393 |
| Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |