Innovative New Treatment for OHSS Proposed

April 8, 2013

Recombinant pigment epithelium-derived factor (rPEDF) proposed as a novel physiological treatment for ovarian hyperstimulation syndrome (OHSS).

With the discovery of an injectable protein to reverse the symptoms of certain currently untreatable conditions, researchers have suggested replacement therapy with recombinant pigment epithelium-derived factor (rPEDF) as a novel physiological treatment for ovarian hyperstimulation syndrome (OHSS), according to new findings from studies in mice.1
Abnormal angionesis in the female reproductive system is associated with endometriosis and OHSS. Currently, both conditions are considered untreatable, and OHSS can be life-threatening. To date, pro-angiogenic factors, such as vascular endothelial growth factor (VEGF), and anti-angiogenic factors, such as PEDF, have been studied extensively, but the investigations typically have involved the eye and tumors. Researchers at Tel Aviv University, however, have hypothesized that the protein may have therapeutic potential in gynecological and reproductive diseases that involve blood vessel growth.1
The researchers found an inverse relationship between the production and secretion of PEDF and VEGF by granulosa cells. In mice with OHSS, who exhibited signs of edema and vascular leakage, this PEDF-VEGF counterbalance was impaired. When mice with OHSS were treated with low doses of rPEDF, there was a “perfect reversal” of all symptoms of OHSS, including abdominal swelling and vascular leakage; in addition, the level of ovarian VEGF mRNA was reduced.1 The VEGF mRNA levels in granulosa cells in vitro were also reduced by therapeutic low doses of rPEDF. When higher doses of rPEDF were administered, these therapeutic effects disappeared, suggesting that there is a hormetic mechanism of rPEDF action, explained the study authors. There was also no negative effect of therapeutic low dose administration of PEDF on ovulation and pregnancy rates in treated mice.
The observed high expression level of VEGF paired with a nearly undetectable level of PEDF offers a new perspective in the pathophysiology of OHSS, concluded the study authors. The ability to control the reciprocal relationship between PEDF and VEGF has the potential for creating new therapeutic advancements for other angiogenic-related pathologies that may affect fertility. In another related study, these authors studied the effect of PEDF in mice with endometriosis and found that the lesions in mice with endometriosis were eradicated and that fertility was unaffected.2 Interestingly, the number of ovulated eggs increased after treatment in mice with endometriosis.2

Pertinent Points:
- New study findings show that the anti-angiogenic protein PEDF is active in the reproductive system.
- In mice OHSS models, therapeutic low dose PEDF completely eliminates the symptoms of OHSS and had no negative effect on ovulation or pregnancy rates.


1. Chuderland D, Ben-Ami I, Kaplan-Kraicer R, et al. The role of pigment epithelium-derived factor in the pathophysiology and treatment of ovarian hyperstimulation syndrome in mice. J Clin Endocrinol Metab. 2013;98:E258-266.
2. Chuderland D, Hasky N, Ben-Ami I, et al. A physiological approach for treating endometriosis by recombinant pigment epithelium-derived factor (PEDF). Hum Reprod. March 6, 2013. [Epub ahead of print.]