Production of exogenous gonadotrophin-neutralizing immunoglobulins in cats after repeated eCG-hCG treatment and relevance for assisted reproduction in felids

Abstract

Combination regimens of equine chorionic gonadotrophin (eCG) and human chorionic gonadotrophin (hCG) are used in ovarian stimulation protocols for assisted reproduction of felids. In the present study, domestic cats exhibited decreased ovarian responsiveness after repeated administration of eCG-hCG and a possible immunological mechanism for this ovarian refractoriness was investigated. An ELISA was used to analyse sera from male, naive female and previously eCG-hCG-stimulated (1x, 3x and 4x) female cats for the presence of immunoglobulins binding to eCG, hCG and pig FSH (pFSH). The sera of cats receiving multiple eCG-hCG injections, at intervals of 44-50 days, displayed greater eCG and hCG-binding than did the sera of male, naive female or female cats stimulated once, and demonstrated variable affinity for pFSH. In preovulatory and postovulatory ovarian stimulation assays, mice injected with an eCG-antisera mixture had lower ovary masses than did mice injected with eCG-saline and fewer ovulated oocytes compared with mice treated with eCG-naive sera. Treatment of queens that were refractory to eCG-hCG with a pFSH-hCG regimen caused a rebound in development of ovarian follicles but not in oocyte maturity. These studies indicated that repeated treatment of domestic cats with eCG and hCG may cause an immunologically mediated refractoriness to ovarian stimulation. Although alternative gonadotrophin regimens may alleviate this refractoriness, a preferable strategy might be the avoidance of potential immunological complications through the cautious use of eCG and hCG in domestic and endangered nondomestic felids.

Approaches and efficacy of artificial insemination in felids and mustelids

“…pregnancies (%) [34,50] can disturb endocrine profiles causing an aberrant follicular, oviductal or uterine environment and disruptions in oocyte maturation, embryo development, or implantation [78][79][80]. Safety also can be an issue with eCG and hCG as these are large, foreign glycoproteins that persist for days in circulation and can induce gonadotropin-neutralizing antibodies after subsequent eCG/hCG treatments [74,81,82]. Too frequent administration results in refractoriness, which can be avoided by giving eCG or hCG treatments no more than once every 6-12 mo [81,82].…”

“…Safety also can be an issue with eCG and hCG as these are large, foreign glycoproteins that persist for days in circulation and can induce gonadotropin-neutralizing antibodies after subsequent eCG/hCG treatments [74,81,82]. Too frequent administration results in refractoriness, which can be avoided by giving eCG or hCG treatments no more than once every 6-12 mo [81,82]. Currently, the most common means of stimulating ovum release from ovarian follicles prior to AI is to give two im injections, the first eCG, followed by hCG 80-84 h later.…”

The potential for gamete recovery from non-domestic canids and felids

“…Moreover, repeated treatment of domestic cats with eCG and hCG may cause an immune mediated refractoriness to ovarian stimulation, dictating that the suitability of these hormonal combinations should be further investigated (Swanson et al, 1995). Similarly, protocols using porcine FSH and LH resulted in reduced numbers of follicles at the second treatment as compared with the first (Morato et al, in press), possibly due to a humoral immune response.…”

Induction of ovarian activity and ovulation in an induced ovulator, the maned wolf (Chrysocyon brachyurus), using GnRH agonist and recombinant LH

“…However, evidence suggests that these protocols can cause hyperstimulation of follicles [16] and estrogen production [17], which can ultimately be detrimental to fertilization, embryogenesis, and implantation [6]. Continued use of eCG with hCG can also result in refractoriness [18,19] and can trigger an immune response [20]. Recently, a recombinant form of equine LH (reLH) that is purified and free of other pituitary hormones has been shown to effectively induce ovulation within 48 hours of administration in domestic mares (Equus ferus caballus) [21]; however, reLH has not been tested in domestic or wild carnivores.…”