Transcervical administration of polidocanol foam prevents pregnancy in female baboons

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%.

Effect of menstrual cycle phase and hormonal treatments on evaluation of tubal patency in baboons

“…Sinha found that secretory phase timing reduced the success of placement of Essure ™ microinserts . In support of research evaluating non‐surgical approaches to PC, we performed HSGs in female baboons prior to other transcervical procedures . During the course of these studies, we noted differences in the success of our tubal imaging based on cycle timing and hormonal treatment.…”

“…Between October 2012 and November 2016, we completed several studies investigating approaches to non‐surgical permanent contraception in women at SNPRC and ONPRC using the baboon model. Results from some of these studies have previously been reported and others are ongoing . We performed one or more baseline hysterosalpingogram procedures and serum sampling for estradiol and progesterone prior to the investigational treatment in 110 healthy adult (ages 5—16 years) female baboons (Papio anubis n = 62, [SNPRC]; Papio hamadryas n = 48, [ONPRC]).…”

Large conductance voltage- and calcium-gated potassium channels (BK) in cerebral artery myocytes of perinatal fetal primates share several major characteristics with the adult phenotype

“…Cesarean sections were performed at 165±3 days of gestation, as confirmed by a Doppler sonography evaluation. This gestational age is near-term in baboons [ 20 ], and results in viable neonates [ 21 ]. Cesarean section surgery was performed using standard methodology that included maternal anesthesia (induction with ketamine hydrochloride, 10 mg/kg of body weight, and maintenance with 1.5–2% isoflurane).…”

Contraception in Canada: A Nod to the Past and Look Into the Future

“…Recently, primate studies have found that a single intrauterine dose of polidocanol foam administered transcervically has high rates of tubal occlusion. 9 Other methods in early development include the intrauterine injection of a degradable polymer to induce tubal blockage (FemBloc).…”