P-395 Vaginal probiotics and vitamin D, as immunomodulatory approaches in improving the implantation and live birth in repeated implantation failure (RIF) women with imbalanced immune system
Authors: Abdolmohammadi-vahid S , Naser A , Chakari-Khiavi F , Darayee M , Berjis K , Aghebati-Maleki L , Najdi N , Ahmadian-Heris J , Yousefi M 
Published: July 2024

Abstract

Study question
Are vaginal probiotics and vitamin D (Vit.D) capable of improving implantation and live birth rate in RIF women with imbalanced immune system?

Summary answer
Vaginal probiotics and Vit.D are capable of improving the rate of implantation and live birth in RIF women with imbalanced immune system.

What is known already
RIF, determined as failure in achieving pregnancy after at least three in-vitro fertilization (IVF), is related to various factors including maternal and embryonic factors. Any abnormalities in maternal or embryonic part, such as maternal imbalanced immune profile, pose a risk for implantation. It has been estimated that endometrial microbiota and Vit.D would affect immune profile of endometrium and consequently, the process of implantation. Considering the effects of probiotics in normalizing the endometrium microbiota, it is likely that probiotics besides Vit.D regulate the imbalance of immune system in endometrium of RIF patients, to improve the rate of implantation and live birth.

Study design, size, duration
148 women with a history of at least 3 consecutive implantation failures (from Feb 2021- Sep 2023), who referred to infertility centers of Valiasr International Hospital of Tabriz, were enrolled. Blood samples were taken, T helper 1 (Th1)/Th2 ratio (CD4+ interferon-γ (IFNγ)+/CD4+ interleukin-4 (IL-4)+ ratio) was evaluated by flowcytometry. Pregnancy (by the positive β- human chorionic gonadotropin (HCG) test and ultrasound) and live birth rate were also determined.

Participants/materials, setting, methods
The group of RIF women with elevated Th1/Th2 ratio (n = 65) was divided into 2 subgroups. The study group (n = 41) received probiotics (two capsules vaginally, every day for 6 months) and Vit.D (50,000 international unit (IU) every week for 10 weeks prior to the transfer). The control group (n = 24) received no treatment. At the end of the treatment, the embryo transfer was conducted. Finally, the pregnancy and live birth rate was evaluated.

Main results and the role of chance
Evaluation of pregnancy rate among the groups indicated that RIF women who received probiotics and Vit.D had a significantly higher rate of pregnancy (20/41, 48%) in comparison with no-treatment group (5/24, 20%). Live birth rate was also significantly higher in probiotics- and Vit.D-receiving RIF women (18/41, 43%) than no treatment group (3/24, 12%).

Limitations, reasons for caution
Lack of evaluation of endometrium microbiota, Vit.D level and local immune system profile prior to the study are the limitations of the current study.

Wider implications of the findings
The crucial role of balanced immune profile and presence of normal microbiota in the endometrium is undeniable for a successful implantation and pregnancy. Providing an optimum microbial microenvironment by probiotics and a favorable immunologic balance with Vit.D, as an immunomodulator, improves the implantation and pregnancy outcome of RIF patients.

Trial registration number
not applicable