Abstract

Persistent infertility is a complex condition influenced by numerous factors, including potential imbalances in the vaginal microbiome. Emerging evidence suggests that probiotics, particularly those targeting Lactobacillus species, may play a critical role in restoring reproductive health by addressing microbiome dysbiosis. This case study examines the fertility outcomes of a 36-year-old woman with a four-year history of primary infertility, endometriosis, and a failed IVF cycle. Following microbiome testing, which revealed severely depleted vaginal Lactobacillus levels (<1%), the patient was administered Daye’s ProViotics both orally and vaginally. Remarkably, within four weeks of treatment, the patient conceived naturally for the first time. This outcome suggests a potential link between microbiome restoration and improved fertility. However, while promising, these findings are based on a single case and underscore the need for further research involving larger patient populations to validate the effectiveness of probiotics in treating subfertility.

Introduction

The microbiome, a complex collection of bacteria, fungi, viruses, and other microorganisms living in and on our bodies, has gained significant attention for its broad influence on health. Initially focused on the gut, research has expanded to include the reproductive system, revealing that the uterus, once thought to be sterile, also hosts its own microbiome. This uterine microbiome, distinct from that of the vagina, plays a crucial role in women’s health, potentially affecting fertility, pregnancy outcomes, and risks for conditions like endometriosis and endometrial cancer [1]. Maintaining a healthy balance of “good” bacteria, known as eubiosis, is vital, as an imbalance, or dysbiosis, can lead to various health issues.

Dysbiosis in the reproductive tract, unlike the gut, often lacks noticeable symptoms, making it harder to detect without specific investigation, despite its potential link to serious reproductive complications. For instance, bacterial vaginosis (BV) is a well-known form of dysbiosis characterised by an overgrowth of harmful bacteria such as Gardnerella vaginalis, which can lead to issues like recurrent miscarriage and preterm labour. Current research suggests that Lactobacilli, a genus of bacteria producing lactic acid, are crucial in maintaining a healthy vaginal environment by lowering the pH and preventing the growth of pathogenic bacteria and fungi [2]. However, the exact strains and quantities of Lactobacilli required for optimal health are still being studied [3]. There is growing evidence that Lactobacilli in the vagina may protect from sexually transmitted diseases such as Chlamydia and HPV [4].

Methods

Our patient was a 36-year-old woman who was unable to achieve a pregnancy for over four years. She also suffered from endometriosis and had undergone a laparoscopy in 2021. She had also undergone two hysteroscopies: the first in 2023, which showed polypoid endometrium, and the second in early 2024, which was normal. Her AMH was low at 3.6 pmol/L. The husband’s sperm was slightly suboptimal, with mild teratoasthenospermia.

Due to the mild male factor and prolonged primary infertility, they consulted with their local fertility clinic, which advised them to proceed try IVF with ICSI. This treatment cycle was done in January 2023, during which she was on an antagonist protocol with 300 units of HMG. This resulted in three eggs, all of which fertilised with ICSI. One embryo was transferred on Day 5 at the morula stage; no embryos were available for freezing, and no pregnancy resulted.

After consulting with us with a view to setting up another IVF with ICSI cycle, she was advised to consider microbiome testing. Her Daye vaginal microbiome test in May showed a severely depleted Lactobacillus count at <1%, with all other parameters being normal. She was advised to start taking Daye ProViotics orally daily and to use them vaginally daily for seven days, then twice weekly thereafter.

Results

After using the ProViotics for around four weeks, she was surprised to find that she had conceived naturally for the first time ever. Her early pregnancy course was uneventful, and a singleton viable pregnancy was confirmed on ultrasound at six weeks’ gestation. Her 12-week dating scan was reassuring, and her pregnancy is still ongoing.

Discussion

This patient, who had four years of primary infertility and a failed IVF cycle, conceived very quickly after starting to take Daye ProViotics orally and vaginally for severely depleted Lactobacillus levels. This may suggest that the replenishment of Lactobacillus was the missing key to her achievement. However, this is only a single case, and it is difficult to obtain conclusive answers without studying more cases.

Conclusion

This case report is promising for the use of microbiome testing and treatment with probiotics in patients with subfertility. Ideally, further studies with larger numbers should be performed to investigate the treatment of low Lactobacillus levels with probiotics in fertility patients.

References

1. Lewis, F. M., et al. “Vaginal Microbiome and Its Relationship to Behaviour, Sexual Health, and Sexually Transmitted Diseases.” Obstetrics & Gynecology, vol. 129, no. 4, 2017, pp. 643-654. doi:10.1097/aog.0000000000001932.

2. Petricevic, Leopold, and Gudrun Domig. “The Association between Vaginal Microbiota and Female Infertility: A Systematic Review and Meta-Analysis.” Archives of Gynecology and Obstetrics, vol. 307, no. 4, 2023, pp. 1015-1030.

doi:10.1007/s00404-023-06973-1.

3. Morre, S.A., et al. “The Vaginal Microbiota: What Have We Learned after the First Decade of the Human Microbiome Project?” Journal of Reproductive Immunology, vol. 145, 2021, pp. 1-10. doi:10.1016/j.jri.2020.103246.

4. Tamarelle, Jade, et al. “The Vaginal Microbiota and Its Association with Human Papillomavirus, Chlamydia Trachomatis, Neisseria Gonorrhoeae, and Mycoplasma Genitalium Infections: A Systematic Review and Meta-Analysis.” Clinical Microbiologyand Infection, vol. 25, no. 1, 2019, pp. 35-47. doi:10.1016/j.cmi.2018.04.019