Premature ovarian failure (POF) is also referred to as primary ovarian insufficiency which involves abnormal functioning of ovaries before age 40. Basically, POF is defined by the association of amenorrhea, sex steroid insufficiency and increased (menopausal) levels of serum gonadotropins before age 40. Infertility is a common outcome of premature ovarian failure. The main symptoms of POF includes Irregular or skipped periods (amenorrhea), Difficulty conceiving, vaginal dryness, night sweats, Irritability or difficulty concentrating, Decreased sexual desire. POF is occasionally also known as premature menopause, although these two conditions are different. Women with POF can have occasional or irregular periods for years and might even become pregnant while in case of premature menopause, periods stop before age 40 and can’t become pregnant. It is not a rare condition; its occurrence is approximately 1 in 100 between the age of 30 and 39 and 1 in 1000 between the age of 15 and 29. The average age of early onset is 27 years . Concern has been expressed that rates of premature menopause (before age 40) are elevated in India and may be increasing in certain sections of the population. For example, National Family Health Survey (NFHS-2) indicated that 3.1 % of women between the age of 30-34 and 8.0 % among 35-39 were in menopause. It further demonstrated that 22.1 % of the women between the ages of 35-39 in Andhra Pradesh were in menopause, a potentially remarkable observation as this State has a high incidence level of female sterilization at a young age .
Management of premature ovarian failure :-
- Hormone replacement therapy (HRT)
- Calcium and vitamin D supplements
- In vitro fertilization (IVF)
- Regular physical activity and a healthy body weight
- Treatments for associated conditions
Usage of stem cells on premature ovarian failure
Bone marrow mesenchymal stem cells (BM-MSCs) are a type of adult stem cell with a low immunogenicity. These cells are majorly present in bone marrow microenvironment, which can further differentiate in most cell types of mesodermal, ectodermal and endodermal which includes adipocytes, osteocytes, epithelial cells, neurons, chondrocytes, myocytes, fibroblast and myofibroblasts. Furthermore, MSCs are easy to derived and proliferate in vitro and, as a consequences of paracrine and immunomodulation functions, MSCS migrate to the site of injured tissue and also differentiate into specific cell types in the tissue under the induction of particular factors to restore the local microenvironment. These cells repair the damaged tissue via regulating the immune response and enhancing the function of endogenous cell, which makes BM-MSCs an ideal seed cell for transplantation. Autologous stem cell transplantation for the clinical treatment of premature ovarian failure is a significant step [7, 8]. BM-MSCs ameliorate the ovarian reserve of POF, which is related to the following aspects. BM-MSCs are induced via cytokines and migrate to the site of damaged tissue but do not differentiate into oocytes, as per the present study . They secret specific cytokines which are further helpful for antiapoptosis and antifibrosis, including insulin-like growth factor (IGF), hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) to help ovarian restoration. They also protect ovarian function via supressing the inflammatory response and reducing oxidative stress. As per the study conducted by Hala et al, 3-5 million of BM-MSCs in the ovarian tissue via laparoscope and 3-5 million in the ovarian artery via catheter. 26 out of the 30 patients included (86.7%) indicated drop down in follicle-stimulating hormone (FSH) levels and increase in estrogen and Anti-Mullerian hormone (AMH) levels after 4 weeks of injection and this change was maintained for the duration of 48 week follow-up period. 18 patients (60%) indicated ovulation along with ovum sizes ranging from 12-20 mm. This study demonstrated that autologous MSC may ameliorate the conditions in patients with premature ovarian failure and Optimization of the cell dose and route of administration requires further experimentation. In conclusion, number of studies demonstrated the potential of mesenchymal stem cell for premature ovarian failure, although this approach needs more clinical results to emerge as therapeutic treatment for premature ovarian failure.
- Ebrahimi M, Akbari AF. Pathogenesis and causes of premature ovarian failure: an update. Int J Fertil Steril. 2011;5(2):54-65.
- Mayo clinic. Premature ovarian failure, 2018. https://www.mayoclinic.org/diseases-conditions/premature-ovarian-failure/symptoms-causes/syc-20354683
- Resolve (National infertility association). Premature ovarian failure (POF), https://resolve.org/infertility-101/medical-conditions/premature-ovarian-failure/
- Pallikadavath S, Ogollah R, Singh A, et al. Natural menopause among women below 50 years in India: A population-based study. Indian J Med Res. 2016;144(3):366-377.
- Primary Ovarian Insufficiency, 2018.
- Raeth S, et al. A mouse bone marrow stromal cell line with skeletal stem cell characteristics to study osteogenesis in vitro and in vivo. Stem Cells Dev. 2014;23(10):1097–108.
- Edessy M, et al. Autologous stem cells therapy, the first baby of idiopathic premature ovarian failure. Acta Medica International. 2016;3(1):19–23.
- Elkheir EAH. Autologous stem cell transplantation in patients with idiopathic premature ovarian failure. J Tissue Sci Eng. https://doi.org/10.4172/2157-7552.C1.030.
- Tsai S-C, Lu C-C. Stem cells prevent radiation exposure-induced ovarian follicular depletion. Biol Reprod. 2010;83(1):699.
- Hala G, Wael AE, Ahmed EG. Autologous stem cell transplantation in patients with idiopathic premature ovarian failure. J Tissue Sci Eng. 2016;7:3(Suppl).