The Essure system is one type of effective, permanent birth control for women that relies on the insertion of a polymer-coated metal or fiber coil into the Fallopian tube to cause inflammation and through it their irreversible blockage with scar tissue. Advantages over tubal ligation are that the insertion of the device through the vagina, the cervix and the uterus into the Fallopian tube with a hysteroscope (a flexible tube equipped with a camera) is an effective (<1% women pregnant during first year after implantation), permanent, low-cost, non-surgical procedure which typically takes less than 30 min. Disadvantages are that Essure takes 3 months to become effective, that allergies to the contrast-agent used in hysterosalpingography to confirm tubal blockage is a contraindication, that electrosurgical procedures (e.g. endometrial ablation) may no longer be possible, and that complications, when they occur, can be very serious, such as ectopic pregnancies, miscarriages and the perforation of the uterus or fallopian tubes by the metal coils and their migration into other organs. Increasing concerns surrounding Essure highlight the need for a new, improved device that offers Essure's advantages without its risks. We propose a novel device that uses precisely dosed, site-specifically delivered magnetic nanoparticles (MNP) and their temporary immobilization in the Fallopian tubes for heating with an externally applied alternating magnetic field (AMF) to cause initial physical blockage, localized heating and inflammation, followed by scar formation and permanent tube blockage. Such a MNP-based device has never been demonstrated. Our preliminary results illustrate the great promise of this approach through: i) the homogeneous distribution of a well-defined concentration of MNPs in a non-penetrating, flexible device for ii) targeted placement and uniform heating during treatment that iii) allows fo the delivery of a well-controlled heat dose and, after treatment, iv) removes itself by controlled degradation v) whose components have been proven not to be toxic, vi) has shown tubal occlusion in only thirty days in an animal model, and vii) which will not preclude in vitro fertilization by the presence of a foreign body in the uterus. For the study of the proposed MNP-enabled device, we will use NT-01 particles (Micromod GmbH, Rostock, Germany) that have been manufactured by the Good Manufacturing Process (GMP) are currently under review for approval by the U.S. Food and Drug Administration for human use. We will determine the optimal material composition and consistency (e.g. gel, paste) for MNP delivery, device heating and degradation. While we propose the use of a specific type of MNP for this study, because of considerable experience with them, the device will be particle independent; in fact, we anticipate that further studies beyond the scope of this one will show that the combination of several different MNP types with different heating and diffusion properties may be advantageous. Key to the proposed approach is the hypothesis that MNP can be carefully dosed and site-specifically placed for sterilization and then safely be removed by device degradation. The hypotheses will be addressed in three interrelated aims.
In Aim 1, we will develop a MNP-based device with well-defined heating properties for placement into the Fallopian tube with a hysteroscope.
In Aim 2, we will in in vitro studies systematically determine the heating performance of different device options developed in Aim 1. Finally, in Aim 3 we will systematically test in vivo in cats th efficacy of the device. The successful completion of the project will be transformative to the field, offering new, low cost sterilization options, with all of Essure's advantages and significanly reduced risks.
The only non-surgical permanent birth control option currently available for women is a hysteroscopically implanted metal or fiber coil, which causes inflammation into the Fallopian tube and through it its irreversible blockage with scar tissue. We propose a novel device that can be inserted in the same way, but uses precisely dosed, site-specifically delivered magnetic nanoparticles (MNP) for heating with an externally applied alternating magnetic field (AMF) to cause localized heating and inflammation, followed by scar formation and permanent tube blockage in only thirty days, and the device' removal from the tube by safe and non-toxic decomposition. This approach offers all advantages of the currently available commercial device, but at significantly reduced risks and with greater speed.
|Divakar, Prajan; Caruso, Isabella; Moodie, Karen L et al. (2018) Design, Manufacture, and In vivo Testing of a Tissue Scaffold for Permanent Female Sterilization by Tubal Occlusion. MRS Adv 3:1685-1690|