Novel Approaches in Addressing Ovarian Insufficiency in 2019: Are We There Yet?

Abstract

Ovarian insufficiency is described as a multifaceted issue typically encountered in the field of assisted reproduction. The three main identified diagnoses of ovarian insufficiency include premature ovarian failure (POF), poor ovarian response (POR), and advanced maternal age (AMA). Patient heterogeneity in the era of individualized medicine drives research forward leading to the emergence of novel approaches. This plethora of innovative treatments in the service of adequately managing ovarian insufficiency is called to undertake the challenge of addressing infertile patients exploring their reproductive options. This review provides an all-inclusive presentation and critical analysis on novel treatments that have not achieved routine clinical practice status yet, but have recently emerged as promising. In light of the lack of randomized controlled trials conveying safety and efficiency, clinicians are left puzzled in addressing the “how” and “for whom” these approaches may be beneficial. From ovarian injection employing platelet-rich plasma (PRP) or stem cells to artificial gametes and ovaries, ovarian transplantation, and mitochondrial replacement therapy, this descriptive review provides insight toward assisting the practitioner in decision making regarding these cutting-edge treatments. Biological mechanisms, invasiveness levels, efficiency, as well as possible complications, the current status along with bioethical concerns are discussed in the context of identifying future optimal treatment.

Intraovarian injection of platelet-rich plasma in assisted reproduction: too much too soon?

“…The prospective pilot study by Sfakianoudis et al (2020b ) determined that perimenopausal women and women deemed to be POR benefitted the most from the treatment, more so than POI and menopausal patients. In an article by Sfakianoudis et al (2020a ), they describe how novel techniques (such as PRP, ovarian stem cells transplant and ovarian tissue transplant) may effectively treat ovarian insufficiency by reactivating follicular growth through restoring the microenvironment of the ovary. Therefore, it should be acknowledged that PRP infusion may only be an appropriate treatment for select ovarian disorders.…”

G-CSF-mobilized Peripheral Blood Mononuclear Cells Combined with Platelet-rich Plasma Restored the Ovarian Function of aged rats via angiogenesis and glycolysis modulation

“…The arti cial ovary is also a promising alternative that will be used in in vitro growth and maturation approaches or to improve ovarian transplant in the future. Although it has been applied successfully in animal models, its e cacy and safety have to be proven before it is clinically used for patients [55].…”

Stem Cell Paracrine Signaling for Treatment of Premature Ovarian Insufficiency

“…Artificial ovary is also a promising alternative that will be used to in vitro growth and maturation approaches or to improve ovarian transplant in the future. Although it has been applied successfully in animal models, its efficacy and safety have to be proved before it becomes a reality for patients ( 45 ).…”

“…Another strategy, closely related to the previous one, is the generation of artificial gametes in patients who are not able to produce functional gametes. Artificial gametes could be generated from induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs) derived from blastocysts inner cell mass, or the putative germline stem cells (GSCs) ( 45 ). In animals, artificial gametes have been generated from GSCs ( 46 ), ESCs ( 47 ), and iPSCs ( 48 , 49 ).…”