Every year, more than 2.5 million cycles of in vitro fertilization (IVF) are being performed, resulting in more than 500,000 successful births every year. Since its introduction in the field of medicine, IVF has been instrumental in the birth of over 8 million children worldwide.¹ For this reason, infertile couples around the world seek IVF treatments to achieve their dream of having their own family.

However, the sad truth is that IVF, along with other existing assisted reproductive techniques (ART), cannot address all causes of infertility. Women with premature ovarian failure and men with zero sperm count still find it difficult to conceive even after multiple cycles of IVF and ART. For these cases, fertility scientists and clinicians are exploring the potential of an emerging scientific technique – stem cell therapy.

What is stem cell therapy?

Stem cell therapy refers to the use of stem cells in treating human diseases. Stem cells are a special type of living cells that can develop into more advanced cell types. Stem cells can be used to generate cells for tissue repair, development, and regeneration. Stem cells, when introduced to a certain tissue, can activate the surrounding dormant cells, and induce them undergo cell division, resulting in proliferation and regeneration.²

How can stem cell therapy be used for infertility?

In recent years, fertility scientists have launched several experimental studies that show how stem cell therapy could be used to treat infertility-related health conditions. Both female and male infertility studies have been conducted in previous years, demonstrating the power of stem cell therapy for the treatment of infertility.²

Preliminary scientific studies show that stem cells could be used in treating conditions that cause infertility, such as premature ovarian failure, low ovarian reserve due to aging, Asherman’s syndrome, endometrial dysfunction, and very low sperm count.

• Premature ovarian failure

Premature ovarian failure (POF) is a condition in which menopause starts even before age 40. POF affects about 1% of women and is a severe cause of female infertility. Women with POF have ovaries that have ceased to function due to the depletion of the ovarian follicles that are available for ovulation. Since there is no ovulation, there are no egg cells that could be fertilized, resulting in serious infertility among reproductive-aged women.³ In addition, as there are no egg cells that can be obtained for fertilization, IVF procedures are not successful in patients with POF.²

Recent animal studies have shown that stem cell therapy can be used to produce new egg cells in women with premature ovarian failure, thereby treating infertility in these patients.⁴ For instance, a study conducted in 2017 reported that when bone marrow-derived stem cells were transplanted to mice, the stem cells restored hormone production in the ovaries and induced the production of new egg cells.⁵ A study conducted in 2014 showed when stem cells derived from amniotic fluid were transplanted to mice with premature ovarian failure, the stem cells prevented depletion of ovarian follicles and helped maintain the viability of healthy follicles.⁶ New studies have also descried the presence of germ-line stem cells in the ovary that could be the ultimate treatment for premature ovarian failure in the near future.⁷

• Low ovarian reserve due to aging

As women age, the ovaries undergo physiologic aging, which is described by the decline of both the number and quality of the egg cells in the ovaries. This results in decreased optimal fertility once the woman reaches 50 years old. Diminished ovarian reserve due to aging is the most common cause of female infertility.⁸

Due to the decreased number and quality of egg cells, women with low ovarian reserve due to aging may find it difficult to conceive even after multiple IVF cycles. In this case, the use of stem cell therapy could be a viable treatment for infertility. A recent study, published in 2017, showed that human umbilical cord stem cells can promote the activity of growth factors in the ovary of perimenopausal rats, resulting in the improvement of ovarian reserve.⁹

• Asherman syndrome

Structural abnormalities in the female reproductive tract can also cause infertility. One of such abnormalities is Asherman syndrome, which refers to the presence of adhesions in the uterus. Asherman syndrome occurs after dilatation and curettage that is performed to terminate a pregnancy, an incomplete miscarriage, remove a retained placenta after delivery, sample for endometrial cancer, or remove endometrial polyps.¹⁰

Because of the presence of adhesions in the uterus, women with Asherman syndrome find it difficult to conceive. Asherman syndrome is diagnosed in 1.5% of women evaluated for infertility.¹⁰ Even if an embryo is successfully produced after IVF, women diagnosed with Asherman syndrome who desire to carry their child through after IVF may not be able to continue the pregnancy.

An emerging treatment for patients with Asherman syndrome and other endometrial and uterine structural abnormalities is stem cell therapy. A study reported in 2011 the successful use of adult stem cells to induce the regeneration of the endometrium (inner lining of the uterus) followed by conception in a patient with severe Asherman syndrome. The stem cells were isolated from the patient’s own bone marrow and were then injected into the uterus. The stem cells induced the proliferation of new cells in the endometrium, resulting in an 8 mm endometrial layer with viable blood vessels. Embryo transfer was then performed, and this resulted in a viable intrauterine pregnancy. The pregnancy was confirmed with the detection of the gestational sac, yolk sac, and good cardiac activity on ultrasound.¹¹

• Azoospermia (absence of sperm in the ejaculate)

Male infertility constitutes almost 50% of all cases of infertility. The most severe form of male infertility is non-obstructive azoospermia, a condition in which no sperm are produced in the testes due to failure of spermatogenesis.¹²

As there are no viable sperm cells that can be used for IVF, couples dealing with azoospermia would require the use of donor sperm for IVF. This poses a serious challenge to assisted reproduction, especially when we consider the fact that most couples want their child to be genetically related to them.¹³

A promising therapeutic strategy for males with azoospermia is the use of human induced pluripotent stem cells which can be produced from the patient’s existing adult cells. While preliminary studies have already been published about how stem cells could be generated from existing adult cells, the use of stem cells clinically in humans are yet to be done. Still, scientists acknowledge that stem cells have a huge potential in treating male infertility by inducing sperm production in the testes.¹³

If you are interested in learning more about stem cell therapy, other advanced technologies for assisted reproduction, and clinics that offer such technologies, it is best that you consult a fertility consultant today. Your fertility consultant will provide online courses to help you learn more about IVF and the most affordable and accessible IVF clinics in Northern Cyprus. Contact a fertility consultant today and start your journey towards having the baby of you’ve always dreamed of.

References

• Fauser, B. (2019). Towards the global coverage of a unified registry of IVF outcomes. Reproductive BioMedicine Online, 38(2).
• Wang, J. et al. (2019). Stem cells as a resource for treatment of infertility-related diseases. Current Molecular Medicine. 19, 539-546.
• Jankowska, K. (2017). Premature ovarian failure. Prz Menopauzalny, 16(2): 51-56.
• Sheikhansari, G. et al. (2018). Current approaches for the treatment of premature ovarian failure with stem cell therapy. Biomedicine & Pharmacotherapy, 102: 254-262.
• Mohamed, S. et al. (2018). Human mesenchymal stem cells partially reverse infertility in chemotherapy-induced ovarian failure. Reprod. Sci., 25(1): 51-63.
• Xiao, G. et al. (2014). Amniotic fluid stem cells prevent follicle atresia and rescue fertility of mice with premature ovarian failure induced by chemotherapy. PLoS One, 9(9): e106538.
• Liu, J. et al. (2017). Isolation and characterization of string-forming female germline stem cells from ovaries of neonatal mice. J. Biol. Chem., 799403.
• Amanvermez, R. and Tosun, M. (2016). An update on ovarian aging and ovarian reserve test. Int J Fertil Steril. 9(4): 411-415.
• Li, J. et al. (2017). Human umbilical cord mesenchymal stem cells improve the reserve function of perimenopausal ovary via a paracrine mechanism. Stem Cell Research & Therapy, 8(55).
• Smikle, C., Yarrarapu, S., and Khetarpal, S. (2022). Asherman syndrome. In: StatPearls.
• Nagori, C., Panchal, S., and Patel, H. (2011). Endometrial regeneration using autologous adult stem cells followed by conception by in vitro fertilization in a patient of severe Asherman’s syndrome. Journal of Human Reproductive Sciences, 4(1): 43-48.
• Chiba, L., Enatsu, N., and Fujisawa, M. (2016). Management of non-obstructive azoospermia. Reprod Med Biol. 15(3): 165-173.
• Fang, F. et al. (2018). Human induced pluripotent stem cells and male infertility: an overview of current progress and perspectives. Human Reproduction, 33(2): 188-195.