Enhanced Assisted Reproductive Technology Pregnancy Rate by Prostacyclin Analog (Iloprost)

Human fallopian tube secretes high concentration of prostacyclin. Fallopian tube is the site for early embryo development. The effect of prostacyclin on human early embryo development is waiting to be clarified. The study hypothesis is prostacyclin can enhance early embryo development.

Huang et al, found that human fallopian tube expresses prostacyclin synthetase and cyclooxygenase. These enzyme systems synthesize abundant prostacyclin (PGI2). In the fallopian tube PGI2 causes smooth muscle relaxation, possibly facilitating tubal transport of gametes and embryos. Huang et al reported that addition of the PGI2 analogue Iloprost to embryo culture media significantly enhanced mouse embryo development to the blastocyst and complete hatched stages. The implantation and live birth rates of Iloprost cultured embryos were significantly better than non-Iloprost embryos in the mouse model. The mean weights of fetal mice were not significant different from control group. There was no teratogenic effect observed.

In a previously presented study, the investigators cultured donated frozen human zygotes in culture media with and without the addition of Iloprost. The Iloprost treated embryos showed significantly better growth rate and morphology, as determined by the size, and grading of the trophectoderm and inner cell mass.

Iloprost is FDA approved for the treatment of pulmonary hypertension. It has a significantly longer half-life than native PGI2. Iloprost is a class C pregnancy drug and has not been associated with teratogenic effects. This study intends to expand the usage of Iloprost to culture embryos.

ART cases with age < 40 and without pre-implantation genetic diagnosis

• Drug: Iloprost
  supplement in culture medium during culture in the lab. The concentration is 1 uM.
  Other Name: Ilomedin
• Other: normal saline
  Supplement with vehicle only no Iloprost.

• Iloprost
  This is the study group with 1 uM Iloprost.
  Intervention: Drug: Iloprost
• Control
  This is the control group with vehicle (normal saline) only.
  Intervention: Other: normal saline

• Battenfeld R, Schuh W, Schöbel C. Studies on reproductive toxicity of iloprost in rats, rabbits and monkeys. Toxicol Lett. 1995 Aug;78(3):223-34.
• Huang JC, Arbab F, Tumbusch KJ, Goldsby JS, Matijevic-Aleksic N, Wu KK. Human fallopian tubes express prostacyclin (PGI) synthase and cyclooxygenases and synthesize abundant PGI. J Clin Endocrinol Metab. 2002 Sep;87(9):4361-8.
• Huang JC, Wun WS, Goldsby JS, Matijevic-Aleksic N, Wu KK. Cyclooxygenase-2-derived endogenous prostacyclin enhances mouse embryo hatching. Hum Reprod. 2004 Dec;19(12):2900-6. Epub 2004 Oct 15.
• Huang JC, Goldsby JS, Wun WS. Prostacyclin enhances the implantation and live birth potentials of mouse embryos. Hum Reprod. 2004 Aug;19(8):1856-60. Epub 2004 Jun 17.

Inclusion Criteria:

• ART case

Exclusion Criteria:

• age < 40
• no pre-implantation genetic diagnosis procedure