Treatment with Suprelorin in a pregnant cat

Abstract

Suppression of oestrus is of major interest in feral cat populations, but also in breeding queens temporarily not intended for breeding. Slow release gonadotropin-releasing hormone (GnRH) agonist implants are a new off-label approach for reproduction control in cats. However, initially, oestrus induction may occur and no data exist regarding what happens if previously mated queens are treated. This case report presents a queen mismated 9 and 8 days before treatment with a 4.7 mg deslorelin implant. The queen delivered four healthy kittens 66 days after mismating, but showed no interest in the kittens and lactation was not adequate. Progesterone and oestradiol concentrations were monitored and the queen was followed until the return of oestrus and subsequent breeding. The next oestrus was observed 498 days after treatment and the queen was mated in the second oestrus afterwards, became pregnant and delivered two healthy kittens, both of which were raised successfully by the queen. This case report clearly shows that pregnancy following a GnRH-agonist implant may go to term, but maternal care might be influenced owing to hormonal changes induced by treatment. In addition, this is the first report demonstrating reversibility of effects induced by long-term treatment with a deslorelin implant (return to oestrus, fertility and normal maternal care).

Case Report

Suppression of oestrus is essential to control reproduction in stray cat populations, but also in breeding cats temporarily not intended for breeding, ¹ and slow release gonadotropin-releasing hormone (GnRH)-agonist implants are a promising new, reversible approach.^2–5 Oestrus induction is observed following treatment in some cases in queens^2–5 and, as a consequence, (mis-)mating may occur. In the dog it has been reported that (mis-)mating may result in pregnancy and parturition, in resorption or abortion.^6–8 However, data in the cat regarding fertility after oestrus induction or after mating in an oestrus during treatment do not exist, and it is not known what happens if a cat is treated accidentally in early pregnancy. Toydemir et al ⁵ reported recently that 2/14 queens allowed mating after oestrus induction following treatment with a 9.5 mg deslorelin implant; however, pregnancy was not established in either of these queens. As Toydemir et al did not measure progesterone (P4) concentrations, it remained unclear whether the cats ovulated or not. It is important to understand the effects of GnRH-agonist implants on pregnancy and subsequent fertility, both for treatment of pet cats and for control of stray cat populations.

This report describes a queen that was treated with a 4.7 mg deslorelin implant (Suprelorin; Virbac) for oestrus suppression 7 days after the end of oestrus. The queen was mated accidentally 1 and 2 days before the end of oestrus while being tested for sexual receptivity (Figure 1). As the cat was part of a large study, mating was not intended and normally not allowed. Following contact with the tom, no typical ‘after-reaction’ was displayed, so the queen was not considered to be pregnant when treated. The queen was a proven breeder and had given birth to healthy kittens before treatment. Blood samples were taken to monitor changes in P4 and oestradiol-17ß (E2) at 48-h intervals from day 0 (treatment) to day 6, then twice weekly until week 6 and thereafter once weekly (Table 1, Figure 2a, b). P4 and E2 concentrations were determined by in-house radioimmunoassays.^9,10 Ultrasound examination was performed on day 32 after treatment owing to swelling and reddening of the nipples, and abdominal enlargement, which confirmed pregnancy. Parturition occurred 66 days after mating (57 days after treatment with the GnRH-agonist implant) and four healthy kittens were delivered. However, maternal care and milk production were inadequate so that — although an attempt was made to hand-raise the kittens — three of the four kittens died. The duration of oestrus suppression after treatment with the GnRH-agonist implant was 498 days. A second oestrus occured 12 days after the first oestrus (day 510) and the queen was mated in this respective oestrus. It became pregnant and delivered a healthy litter of two kittens 66 days after the first mating (day 576). Nursing and maternal care were adequate and both kittens survived.

Figure 1

Timeline of the case

Table 1

Changes in progesterone (P4) and oestradiol-17ß (E2) concentrations during pregnancy until parturition

Day	P4 (ng/ml)	E2 (pg/ml)
0	10.9	11.0
2	11.5	22.5
4	15.2	53.0
6	24.0	32.5
7	26.8	7.5
11	31.0	17.0
15	33.3	16.5
18	33.9	17.0
22	43.9	18.0
25	37.2	19.5
29	43.9	6.5
32	42.7	29.5
36	41.7	23.5
39	33.9	21.0
43	25.2	18.5
50	19.7	22.0
56	1.3	2.0

Figure 2

Hormonal changes, (a) progesterone, ng/ml and (b) oestradiol-17ß, pg/ml, in the queen mismated 8 and/or 9 days before treatment with a 4.7 mg deslorelin implant from day 0 (treatment) to day 560

In the present case, the queen was considered not to be pregnant at the time of treatment with a 4.7 mg deslorelin implant for oestrus suppression, as mating was not observed. To date, no data have been published on the treatment of pregnant cats with a GnRH-agonist implant and data are also lacking on whether the induced oestrus following injection of a GnRH-agonist implant is fertile. In the bitch, it has been reported that the induced oestrus might be fertile, and that mating in this oestrus might result in pregnancy with successful parturition or in reabsorption/abortion due to luteal insufficiency.^6–8 It has been speculated that the loss of pregnancy and the luteal dysfunction may be associated with the effect of the GnRH-agonist on plasma luteinising hormone (LH) related to down-regulation and negative feedback. In contrast, this queen remained pregnant, although it was treated in early pregnancy before embryo implantation, which is usually on day 13. ¹ It is known that the fetoplacental unit produces relaxin from day 20 of pregnancy and that prolactin is synthesised from day 35. In physiological pregnancy, P4 concentrations increase steadily until days 25–35 and then decrease slowly until parturition. The same was observed in this queen, with increasing P4 concentrations until day 28 followed by decreasing P4 concentrations until parturition. ¹¹ Consequently, it is very unlikely that deslorelin had a progesterone-mediated influence on placental function and thus fetal development. Placental P4 is generally assumed to be necessary to maintain pregnancy after days 40–45. However, its role is still controversial,^12,13 although a recent study proved the ability of progesterone production by the feline placenta via extra-placental steroid precursors. ¹³ As only 6/12 queens showed a typical E2 increase before parturition ¹¹ the absence of an E2 peak is also not unusual. In the dog, prolactin and LH are known to be essential for the maintenance of pregnancy.^{14 –17} It is quite likely that these factors are also important luteotrophic factors in queens, as demonstrated by the well-known capacity of cabergoline to cause abortion in queens during the second half of pregnancy.^18,19 Furthermore, no data exist in queens and bitches about the concentrations of LH and follicle stimulating hormone following treatment with a GnRH-agonist implant. P4 concentrations following treatment in the first pregnancy in this queen were as expected during normal pregnancy^11,20 and the duration of pregnancy was 66 days, which is in agreement with the published mean of 65–66.9 days.^21,22

No abnormalities or malformations were detected in the kittens born, but milk production, nursing and maternal care were not adequate in this queen. This queen was a proven breeder before treatment with the deslorelin implant and subsequently gave birth to a healthy litter and exhibited normal maternal care. It is possible that the lack of maternal care and poor milk production is related to a lack of prolactin, as it is reported after late application of cabergoline (from day 48.5 onwards over a period of 9 or more days) that litters could not be nursed and perished quickly. ²³ But as P4 concentrations drop, as reported previously, ¹¹ it seems unlikely that the prolactin peak is prevented (thus limiting lactation and maternal instinct) or that the changes in P4 are responsible for prevention of the final stages of mammary growth (thus limiting lactation). Unfortunately, prolactin concentrations were not measured to verify this hypothesis. Lack of maternal care and poor milk production might also be related to other hormonal differences, which were not investigated.

No further oestrus was observed until day 498 after injection of the 4.7 mg deslorelin implant (although E2 is increased slightly from day 364 on), indicating that suppression of oestrous cycles was achieved.

Conclusions

This is the first reported case of a queen where the reversibility of the effects induced by long-term treatment with slow release GnRH-agonists (suppression of oestrus, infertility) is proven.