Recurrent miscarriages are devastating experiences for couples that have been trying to start a family. Miscarriage, also known as spontaneous abortion, is a premature termination of pregnancy before the 20th week.

Approximately 15-20% of all pregnancies end in miscarriage, and 1-2% of women experience recurrent miscarriages, defined as three or more miscarriages in a row. While there are various causes of recurrent miscarriages, studies have indicated that insufficient number and function of uterine stem cells may be one of the underlying factors.

What are Uterine Stem Cells?

Stem cells are unspecialized cells that can divide and differentiate into other cell types with specific functions.

Uterine stem cells (USCs) are a population of multipotent cells that are responsible for the regeneration of the endometrium, the inner lining of the uterus. The endometrium undergoes cyclic changes during the menstrual cycle in preparation for pregnancy. The proliferation and differentiation of USCs play crucial roles in the establishment and maintenance of a receptive endometrium for embryo implantation.

Therefore, any defects in the quality or quantity of USCs can lead to implantation failure, pregnancy loss, or recurrent miscarriages.

How Does Uterine Stem Cells Deficiency Contribute to Recurrent Miscarriages?

Research studies have shown that women with recurrent miscarriages have lower numbers and impaired functions of USCs compared to women with successful pregnancies.

USCs are essential for the regeneration of the endometrium after menstruation and the preparation of the uterus for embryo implantation. USCs are also involved in the remodeling of the endometrial blood vessels to ensure adequate blood supply for the developing embryo.

Therefore, deficiencies in USCs can lead to inadequate endometrial preparation, unfavorable microenvironment, and impaired blood supply, all of which can contribute to implantation failure and pregnancy loss.

Causes of Uterine Stem Cells Deficiency

The exact causes of uterine stem cell deficiency are not clear, but several factors have been suggested, including:.

Age

As women age, the number and quality of USCs decrease, leading to a decline in fertility and increased risk of miscarriage.

Older women also have higher rates of chromosomal abnormalities in their eggs, which can make a successful pregnancy more challenging.

Hormonal Imbalances

Hormonal imbalances, including those associated with polycystic ovary syndrome (PCOS), can disrupt the proliferation and differentiation of USCs, leading to suboptimal endometrial preparation and implantation.

Inflammation and Infection

Inflammation and infection of the reproductive tract can damage USCs and impair their functions.

Sexually transmitted infections (STIs) such as chlamydia and gonorrhea, as well as chronic endometritis, have been associated with recurrent miscarriages due to their effects on the uterine microenvironment.

Autoimmune Disorders

Autoimmune disorders, such as antiphospholipid syndrome and systemic lupus erythematosus, can cause autoimmune reactions against USCs, leading to recurrent miscarriages.

Diagnosis and Treatment of Uterine Stem Cells Deficiency

Diagnosing uterine stem cell deficiency can be challenging, as there is no clear biomarker or clinical test to evaluate the number and function of USCs.

However, the diagnosis of recurrent miscarriages, combined with the exclusion of other known causes such as chromosomal abnormalities and structural abnormalities of the uterus, can support the suspicion of uterine stem cell deficiency.

Treatment of uterine stem cell deficiency mainly focuses on optimizing the endometrial preparation and supporting embryo implantation. This can be achieved through various approaches, including:.

Assisted Reproductive Technologies (ART)

Assisted reproductive technologies, such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), can bypass the need for natural embryo selection and enable the transfer of high-quality embryos into the uterus.

This can increase the chances of implantation and mitigate the effects of uterine stem cell deficiency.

Hormonal Therapy

Hormonal therapy, such as progesterone supplementation and gonadotropins stimulation, can enhance the proliferation and differentiation of USCs and improve endometrial thickening and receptivity.

Stem Cell-Based Therapies

Stem cell-based therapies, such as autologous or allogeneic transplantation of USCs, have been investigated as potential treatments for uterine stem cell deficiency.

These therapies aim to replenish and repair the deficient uterine stem cell population and improve the endometrial microenvironment for embryo implantation. However, more research is needed to evaluate the safety, efficacy, and feasibility of these approaches.

Conclusion

Recurrent miscarriages are a complex and multifactorial condition that can be caused by various underlying factors, including uterine stem cell deficiency.

USCs play critical roles in the regeneration of the endometrium and the establishment of a favorable uterine microenvironment for embryo implantation. Deficiencies in USCs can lead to implantation failure and recurrent miscarriages. Further research is needed to better understand the pathophysiology of uterine stem cell deficiency and develop more effective diagnostic and therapeutic options.