Effect of L. crispatus M247 Administration on Pregnancy Outcomes in Women Undergoing IVF: A Controlled, Retrospective, Observational, and Open-Label Study

Abstract

The aim of our study was to retrospectively evaluate whether the oral administration of L. crispatus (M247) could increase pregnancy and live birth rates in women undergoing assisted reproductive technology procedures. Enrolled women (N = 160) were divided into two groups: treated (N = 80) or untreated (N = 80) with the probiotic strain. The odds ratio (OR) for a treated woman to have a clinical pregnancy (CP) was 1.56. In women aged 30-40 years, M247 increased the probability of a CP in correlation with the progressive rise in BMI, reaching 47% (35% in controls) with a BMI of 35 (OR: 2.00). The CAID statistics showed that in a woman of the blastocyst subgroup, below 43 years, with a BMI over 18.6, treatment with M247 increased the chance of a CP from 28.4% to 44.5% (OR: 2.08; p < 0.05). Considering live births, the rate of the probiotic group was 12.5% versus 7.5% (OR: 1.76). Considering only the blastocyst subgroup, the treatment increased the number of live births by 200% (OR: 3.64; p = 0.05). As confirmed also by statistical indices NNT, NNH, and LHH, the use of M247 demonstrated a risk-benefit ratio to the full advantage of the benefits.

Keywords: ART; D3 embryos; D5 blastocysts; FIVET; ICSI; vaginal microbiota.

Figure 1

Representative diagram of the various groups and subgroups retrospectively analyzed in the study. V/W: vitrified/warmed; IVF: in vitro fertilization; ICSI (intracytoplasmic sperm injection); D3: day 3; D5: day 5.

Figure 2

Multiple logistic model approach to evaluate the effects of probiotic treatment, age, and BMI on clinical pregnancy rate. Setting the age and BMI values respectively as 20–30 and 22, the pregnancy rate of the control group was 9.9%.

Figure 3

Multiple logistic model approach to evaluate the effects of probiotic treatment, age, and BMI on clinical pregnancy rate. Setting the age and BMI values respectively as 20–30 and 22, the pregnancy rate of the probiotic group was 14.7%.

Figure 4

Multiple logistic model approach to evaluate the effects of probiotic treatment, age, and BMI on clinical pregnancy rate. In the 30–40-year age range, the impact of probiotic treatment increased and determined a pregnancy rate of 34.8%.

Figure 5

Multiple logistic model approach to evaluate the effects of probiotic treatment, age, and BMI on pregnancy rate. In the 30–40-year age range, the impact of the treatment became even more evident when considering women with a BMI progressively increasing to a value of 35. With these parameters, the clinical pregnancy rate increased to 46.6%. * Odds ratio: 2.00 (lower 95%: 0.789284; upper 95%: 5.451833).

Figure 6

NNT (number needed to treat), NNH (number needed to harm) and LHH (likelihood to be helped or harmed). The indices are respectively 20 (calculated as 100/5.0, where 5.0 corresponds to the difference between the LB ratio of the probiotic group and the one of the control group); 80 (calculated as 1/11.25–12.50, where 11.25 and 12.50 are the incidences of side effects occurring respectively in the probiotic and in the control groups); and 4 (calculated as 1/20:1/80).