L-thyroxine and 4-pregnane-3,20‑dione preserves pregnancy in bitches with hypothyroidism and hypoluteoidism

Abstract

Hypoluteoidism is characterized by insufficient secretion of progesterone (P4) by the corpus luteum (CL) during pregnancy, resulting in embryonic resorption and miscarriage. In dogs, hypothyroidism can occur concurrently with hypoluteoidism, therefore, the aim of this study was to propose a combination therapy to treat these two conditions in bitches. The study included 30 bitches that were artificially inseminated and divided into three experimental groups. The control group (G1) included 10 bitches with a history of normal pregnancies, normal thyroid activity and P4 levels. This group received no clinical treatment. Treatment groups included 20 bitches diagnosed with reproductive hypothyroidism and hypoluteoidism: 10 dogs in the G2 group were treated with L-thyroxine (20 μg/kg/day) only and 10 dogs in the G3 group were treated with L-thyroxine and a long-acting synthetic P4 analogue (4-pregnane-3,20-dione, 1.0 mg/kg every 72 h until cesarean section on day 61). In all dogs, pregnancy and embryonic viability was monitored by ultrasound until term. G1 females had normal pregnancies (P4: day 24, 33.33 ± 2.95 ng/mL [106.00 ± 9.38 nmol/L]; day 38, 23.95 ± 1.21 ng/mL [76.16 ± 3.85 nmol/L]; day 50, 10.53 ± 0.82 ng/mL [33.49 ± 2.61 nmol/L]; day 63, 1.11 ± 0.22 ng/mL [3.53 ± 0.70 nmol/L]; p < 0.001). G2 females suffered embryonic death detected between day 31 and day 33 by ultrasound (P4: 4.67 ng/mL ± 0.41 ng/mL, [14.85 ± 1.30 nmol/L]; p < 0.001). In contrast, G3 females had similar plasma P4 levels to G1 dogs, and pregnancy was maintained until the scheduled cesarean section. These data suggest that combination therapy of L-thyroxine and 4-pregnane-3,20-dione maintains pregnancy to term in dogs with concomitant hypothyroidism and hypoluteoidism.