Ovarian Rejuvenation
Due to various causative factors, Infertility is becoming one of the major global concerns. Among the various causes of infertility, premature ovarian insufficiency and premature ovarian failure are increasingly becoming common across the globe. In India, it is more, may be because of ethnic/racial differences.

In women with ovarian insufficiency or premature ovarian failure, the chance of natural conception varies widely. Only 4-5% of such women can conceive naturally due to unpredictable ovulation, but the majority of them, require medical help. Particularly when women wish to have their own genetic material, they are met with limited options. The only well accepted proven treatment is IVF using donor eggs. Recently, many studies have shown that couples who are treated with stem cells show better hormonal milieu and improved possibility of conception.
What are stem cells?
Stem cells are cells which have the capacity to develop into particular type of cells due to specific environment stimuli provided. They repair and rejuvenate the tissues and organs. There are five types of stems cells which can all be used in different infertility conditions.
- Embryonic stem cells
- Induced pluripotent stem cells
- Mesenchymal stem cells
- Hematopoietic stem cells
- Spermatogonial and oogonial stem cells
What are the various sources of stem cells?
Stems cells can be collected from various regions, some of them are listed below,
- Inner cell mass of blastocyst
- Cells derived from mesoderm layers such as bone marrow, adipose tissue, placenta, umbilical cord and blood
- Adipose derived stem cells

How can stem cell-based therapy help infertility?
Many studies done using mesenchymal stem cells and hematopoietic stem cells have reported positive results such as
- Improvement in ovarian function
- Increase in ovarian volume
- Increase in estradiol concentration
- Increased number of antral follicles
- Improved follicular development
- Resumption of menstruation and endometrial improvement.

How is ovarian rejuvenation done using stem cells?
It is generally attempted by injecting prepared autologous stem cells in to the ovaries. Mostly mesenchymal stem cells derived from the bone marrow and adipose tissue are used. Intraovarian injection can be carried out by laparoscopic or transvaginal sonography guided procedure. The expected results are usually seen after 2-3 months
How does stem cell therapy improve ovarian function?
The stem cells are differentiated into granulosa cells which in turn rescued the oocyte otherwise destined to undergo apoptosis and directs them into development. The process involves various molecular mechanisms such as
- Inhibition of autophagy of theca interstitial cells
- Improved ovarian metabolome
Usually, hormonal support with a combination of estradiol and dydrogesterone is considered after stem cell therapy.
What is the role of platelet rich plasma in ovarian rejuvenation?

Platelet rich plasma is rich in several growth factors that have a significant role in tissue rejuvenation. Autologous intraovarian PRP injection can possibly stimulate the germ cell line to develop into oocytes. This procedure can be done using transvaginal ultrasound guidance. Even though the effects on ovarian rejuvenation seem promising, large scale data on pregnancy outcomes will be required before a drawing conclusion.

What is in vitro activation of ovary?

This method aims at activating residual dormant follicles using methods such as in vitro activation and drug free in-vitro activation. It is done by removing one or both ovaries using laparoscopy followed by cutting the cortical tissue into small strips before culturing and auto grafting. In drug free IVA, cortical strips are auto- grafted without culturing.
Conclusion:
Women with premature ovarian insufficiency or premature ovarian failure form a segment of the infertility population who need newer approaches for treatment. One such approach is stem cells, where autologous stem cells usage is ethical, safe and nonimmune and has great potential in the future. However, more clinical studies are needed for in-vitro activation of ovary before drawing any conclusions
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