Transcervical administration of polidocanol foam prevents pregnancy in female baboons

Jeffrey T Jensen,Carol Hanna,Shan Yao,Emily Thompson,Cassondra Bauer,Ov D Slayden

doi:10.1016/j.contraception.2016.07.008

Abstract

BackgroundOur objective was to conduct a pilot study to determine if transcervical administration of polidocanol foam (PF) with or without doxycycline or benzalkonium chloride (BZK) would prevent pregnancy in baboons. MethodsIn study phase 1, adult cycling baboons underwent a hysterosalpingogram to evaluate tubal patency prior to transcervical infusion of 20 mL of 5% PF followed by 1 mL of saline containing 100 mg doxycycline (5%/doxy; n=5), 3% PF plus doxycycline (3%/doxy; n=4), 3% PF with 0.01% BZK (3%/BZK; n=4) or no additional treatment (control; n=9). Immediately following treatment, animals received intramuscular depot medroxyprogesterone acetate (DMPA, 2 mg/kg) to suppress cyclicity during healing and were then socially housed with males of proven fertility. The primary outcome was pregnancy within six cycles of resumption of menses (efficacy phase 1). During study phase 2, PF-treated females from study phase 1 contributed additional cycles (6–8) of exposure (efficacy phase 2), and 5 control females who had recovered from medical abortion (after study phase 1 pregnancy) were subsequently treated with 5% PF (with DMPA) and exposed to breeding (efficacy phase 1; n=3 six cycles, n=2 five cycles). ResultsAll females resumed normal menstrual cycles and mating activity after DMPA. During efficacy phase 1, 7/9 (78%) control females became pregnant. In contrast, fewer pregnancies occurred in PF-treated females: 5% PF 0/5 (0%), 5%/doxy 1/5 (20%), 3%/doxy 1/4 (25%) and 3%/BZK 1/4 (25%). During efficacy phase 2, only one additional pregnancy occurred (3%/BZK). ConclusionsA single transcervical treatment with 5% PF prevented pregnancy in most baboons. Cotreatment with doxycycline or BZK did not improve results. ImplicationsTranscervical intrauterine administration of PF resulted in a high rate of tubal occlusion with prevention of pregnancy; refinements are needed to increase the contraceptive rate following a single treatment to near 100%.

Highlights

Our objective was to conduct a pilot study to determine if transcervical administration of polidocanol foam (PF) with or without doxycycline or benzalkonium chloride (BZK) would prevent pregnancy in baboons
We previously reported that the addition of dilute (0.01%) benzalkonium chloride (BZK) to polidocanol improves the stability of the resulting foam [9]
Bilateral patency was confirmed in all of the females treated with PF; five were treated with 5% PF/doxy, four received 3% PF/doxy, and four received 3% PF/BZK

Summary

Introduction

Our objective was to conduct a pilot study to determine if transcervical administration of polidocanol foam (PF) with or without doxycycline or benzalkonium chloride (BZK) would prevent pregnancy in baboons. Methods: In study phase 1, adult cycling baboons underwent a hysterosalpingogram to evaluate tubal patency prior to transcervical infusion of 20 mL of 5% PF followed by 1 mL of saline containing 100 mg doxycycline (5%/doxy; n=5), 3% PF plus doxycycline (3%/doxy; n=4), 3% PF with 0.01% BZK (3%/BZK; n=4) or no additional treatment (control; n=9). During efficacy phase 2, only one additional pregnancy occurred (3%/BZK). Implications: Transcervical intrauterine administration of PF resulted in a high rate of tubal occlusion with prevention of pregnancy; refinements are needed to increase the contraceptive rate following a single treatment to near 100%.

Objectives

Methods

Results