We can reactivate the ovarian function by cutting follicles into fragments.
Infertility in women in reproductive age is caused primarily by polycystic ovarian syndrome (PCOS) and by primary ovarian insufficiency (POI). In these patients ovarian follicles, which contain oocytes do not function properly and ovulation cannot occur, thus precluding pregnancy.
In an article published in PNAS, Kawamura and colleagues describe a new method that can reactivate ovarian function in infertile women, leading to successful pregnancy.
The scientists first employed mice to test their technique. They removed the ovaries, cut them into small pieces, and then re-implanted the ovarian fragments into the animals. Interestingly, they observed increased follicle growth in the fragments compared to re-implanted intact ovaries, which was followed by egg maturation. The eggs were retrieved, fertilized in vitro, and transferred back into the mice, producing healthy pups.
The researchers demonstrated that fragmentation per se promotes in fact follicles growth in normal ovaries, and further identified some of the molecules involved in this process. In particular they showed that ovary fragmentation blocks Hippo signaling, thus stimulating specific growth factors (CCN growth factors) and apoptosis (cell death) inhibitors.
Can this technique be useful to treat women infertility?
The researchers set up a trial for infertile young women affected by POI. They removed the patients’ ovaries, and, after selecting those containing residual follicles, cut them into small fragments, and additionally treated them in vitro with drugs that stimulate the enzymes PI3-Kinase and AKT. These two molecules when active promote follicle growth as shown in other studies, and their effects combine with growth stimulation that is induced by fragmentation.
After two days the scientists transplanted the treated ovarian fragments back in the patients’ Fallopian tubes and followed follicles maturation. In 5 patients out of the 13 that underwent auto-transplantation, mature eggs were produced and could be retrieved for subsequent in vitro fertilization. After embryo transfer, 2 patients became pregnant and as of today one gave birth to a baby.
This treatment is still experimental and definitely requires refinement. In this respect further research could help identify additional molecules that regulate follicle maturation, as well as design new treatments to make this technique more successful.
In addition, even if the pregnancy reported in this study did not present problems and the baby is healthy, both mother and baby will have to be monitored to detect potential, late-appearing adverse health effects.
Despite these concerns, this therapy represents an important advancement and is in fact the only effective treatment available today for women affected by POI, provided that their ovaries still contain follicles.
Photo: Flickr, bettina n
Source: Kawamura K, Cheng Y, Suzuki N, Deguchi M, Sato Y, Takae S, Ho CH, Kawamura N, Tamura M, Hashimoto S, Sugishita Y, Morimoto Y, Hosoi Y, Yoshioka N, Ishizuka B, & Hsueh AJ (2013). Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. Proceedings of the National Academy of Sciences of the United States of America PMID: 24082083
pregnant, infertile, pregnancy, follicle, ovariate, polycystic ovarian syndrome, pcos, primary ovarian insufficiency, POI