OVARIAN REMNANT SYNDROME (ORS) IN DOGS AND CATS

Introduction

Ovarian remnant syndrome (ORS) is characterized by clinical signs related to the functional residual ovarian tissue in a previously spayed bitch or queen (Wallace, 1991). This complication is mainly attributed to improper surgical techniques during ovariohysterectomy (OHE). Suggested reasons include failure to remove whole or a portion of ovary during the spay, failure to remove ectopic extraovarian tissue or accessory ovary at the time of spay (Miller, 1995) and revascularization of the ovarian tissue in the abdominal cavity (DeNardo et al. 2001). The residual ovarian tissue causes clinical sings of estrus and the behavioral changes associated with it (Johnston, 1991). The diagnosis can be made using vaginal cytology, abdominal ultrasound, hormonal testing, and exploratory laparotomy (Feldman and Nelson, 2004). Surgical removal of residual ovarian tissue is the recommended treatment of choice (Ball et al. 2010).

Clinical Presentation

The animals with remnant ovarian tissue show the clinical signs of proestrus and estrus, such as swelling of the vulva, serosanguineous vaginal discharge and behavioral changes such as flagging and standing, and attraction of the male dogs. Queens with this syndrome show estrus associated behavioral signs such as vocalization, rolling, lordosis, and attraction of the toms (Wallace, 1991). The estrus cycles usually show the normal periodicity for that species.

Diagnosis

Diagnosis is based on history, clinical signs, vaginal cytology, abdominal ultrasound, hormonal analysis and exploratory laparotomy (Adin, 2011).

1.                                                                                     Physical examination and vaginal cytology

Physical examination reveals vulvar swelling and serosanguinous vaginal discharge. Vaginal exfoliative cytology (VEC) reveals superficial cells with their nuclei becoming pyknotic/absent and intermediate cells (Fig.1) indicating elevated estrogen concentration (Davidson, 2015). The sample swabs are rolled on the slides and are stained with Diff Quik.

1.                                                                                                             Abdominal ultrasound

Abdominal sonography is useful in assessing remnant ovarian tissue (Fig 2). The effectiveness of the procedure depends on the expertise of the examiner and stage of the estrus cycle.

1.                                                                                                                                 Hormonal assay

a)     Anti-Müllerian Hormone (AMH). Complete removal of ovaries should result in the absence of AMH in the circulation. A single serum AMH determination is a useful diagnostic tool to diagnose dogs and cats with ORS (Turna et al. 2015) (Flock et al. 2022).

b)    Luteinizing Hormone (LH) is negative (<1ng/mL) in intact females or those with ovarian remnant syndrome. LH is negative in bitches exposed to endogenous and exogenous estrogen. LH assay will be positive during the transient pre-ovulatory LH peak; therefore, it is not performed if the animal is showing signs of estrogen stimulation (Alm and Holst, 2018).

c)     Progesterone (P4). It is produced by post-ovulatory corpus luteum. Confirmation of ovarian tissue by serum P4 requires the bitch or queen to be in diestrus or pregnant. There won’t be a significant difference in serum P4 levels between spayed and intact anestrus queens and bitches. If the random serum P4 levels are <2ng/mL, GnRH stimulation tests can be used to induce ovulation and P4 production, according to the following protocols:

Queen: Two 0.5 ml IM doses of GnRH at 24 hours interval. Three days later, take serum sample and submit for P4 analysis, there will be a five-fold increase in P4 concentration in ORS cases.

Bitches: Inject GnRH at 2 ug/kg IM. Take serum samples at 7 and 14 days later and submit for P4 analysis. P4 concentration >2ng/mL confirms ORS.

1.                                                                             Exploratory laparotomy - Surgical procedure

Exploratory laparotomy is performed for all the cases under general anaesthesia. The bitch/queen is placed in dorsal recumbency, the surgical site is clipped and scrubbed with chlorhexidine followed by isopropyl alcohol spray. A ventral midline celiotomy incision is performed and ovarian remnant is identified in the abdominal cavity (Fig 3), caudal to the kidney. The incision site is cranial to that of routine OHE (Sontas et al. 2007). The pedicle ligation is done using 2-0 or 3-0 PDS (Polydioxanone), great care must be taken to identifying ureter prior to resecting the ovarian remnant, to avoid inadvertent ureteral damage (Adin, 2011). The muscle and subcutaneous tissue are closed in simple continuous pattern and the skin is closed with intradermal pattern with PDS 2-0/3-0 in queen and PDS 1-0 in bitches. A course of post operative analgesics is prescribed for the animals undergoing ORS surgery. The resected ovarian tissue is fixed in 10% formalin and sent for histopathological examination (Fig 4).

                                                                         Discussion

Ovarian remnant syndrome (ORS) is one of the complications of the OHE in companion animals. The other complications include hemorrhage, wound healing complications, retained surgical sponges or foreign bodies (gossypibomas), inadvertent ureteral ligation and hormonal changes (Tobias, 2020). Right ovary and uterine horn are located more cranially than the left ovary and uterine horn, it predisposes the right ovary to be the remnant in most cases (Wallace, 1991) (Ball et al. 2010). Remnant ovary may promote the development of granulosa cell tumour, mammary neoplasia and stump pyometra (Pluhar et al. 1995, Sangster 2005). The duration between OHE and the onset of estrus in bitches had a range from three months to five years (Miller, 1995). Ball et al. 2010 reported that there is higher incidence of ORS in dogs compared to cats, because of deeper abdominal cavity and abundant periovarian adipose tissue. On the contrary, an earlier report by Wallace, 1991 states that ORS is more common in cats compared to dogs. Surgical inexperience of the surgeon is not considered a factor in increasing the likelihood of incomplete removal of ovaries at the time of OHE (Miller 1995, Ball et al. 2010). The recommended time for exploratory laparotomy is post-ovulation, 2 to 4 weeks after the bitch/queen goes out of heat, this is when the remnant is easily located (Hess, 2015). Since, no reports describe the sufficient production of estrogens from adrenal glands to induce estrous signs in companion animals, any bitch displaying proestrus or estrous signs following OHE should be evaluated for an ovarian residue (Prats, 2001). According to Turna et al. 2015, the measurement of serum Anti Müllerian Hormone (AMH) is a useful tool for diagnosis of ORS in bitches and Flock et al. 2022 concluded that single serum AMH determination is a useful diagnostic tool to identify cats with an ORS independent of the hormonal activity of the remnant ovarian tissue. Whereas Place et al. 2019 states that AMH expression is limited to granulosa cells of ovarian follicle and corpus lutea do not appear to express AMH. Therefore, an ovarian remnant that is largely occupied by luteal tissue might not secrete a sufficient amount of AMH to be detected in the circulation. So, they concluded that combined determination of AMH and P4 concentrations in a single serum sample can be an efficient diagnostic test for dogs suspected of ORS. Differential diagnosis are the conditions that cause hemorrhagic vulvar discharge including vaginitis, trauma, stump pyometra, vaginal neoplasia and coagulopathy (Sontas et al. 2007). One differential diagnosis for false positive identification of remnant ovarian tissue by the abdominal sonography is the suture granuloma at the site of ligation at ovarian pedicle (Ball et al. 2010). The use of megestrol acetate or mibolerone has been suggested in the medical management of ORS (Romagnoli 2004, Feldman and Nelson 2004). The side effects of progestogens include increase in the incidence of mammary gland neoplasia (Van Os et al. 1981), and acromegaly (Scott and Concannon, 1983). The only recommended treatment is the surgical removal of the remnant ovarian tissue (Prats 2001, Feldman and Nelson 2004). Van et al. 2018 reports that laparoscopic approach to the surgery of ORS in companion animals is effective as it has short convalescence and minimum complications compared to the conventional, invasive, open surgical procedure. Although identified as a syndrome, ORS is an iatrogenic condition that can be prevented through proper surgical techniques such as sufficient surgical incision and proper clamp placement. The prognosis is good if the remnant ovarian tissue is completely removed. There is no published data about the reoccurrence of ORS in companion animals. 

                                                             References

1.     Adin, C.A., 2011. Complications of ovariohysterectomy and orchiectomy in companion animals. Veterinary Clinics: Small Animal Practice, 41(5), pp.1023-1039.

2.     Alm, H. and Holst, B.S., 2018. Identifying ovarian tissue in the bitch using anti-Müllerian hormone (AMH) or luteinizing hormone (LH). Theriogenology, 106, pp.15-20.

3.     Ball, R.L., Birchard, S.J., May, L.R., Threlfall, W.R. and Young, G.S., 2010. Ovarian remnant syndrome in dogs and cats: 21 cases (2000–2007). Journal of the American veterinary medical association, 236(5), pp.548-553.

4.     Davidson, P.A., 2015. Determining canine estrus stage via vaginal cytology. Clinician’s Brief, 13, pp.19-21.

5.     DeNardo, G.A., Becker, K., Brown, N.O. and Dobbins, S., 2001. Ovarian remnant syndrome: revascularization of free-floating ovarian tissue in the feline abdominal cavity. Journal of the American Animal Hospital Association, 37(3), pp.290-296.

6.     Feldman, E.C. and Nelson, R.W., 2004. Infertility, associated breeding disorders, and disorders of sexual development. Canine and feline endocrinology and reproduction, 3, pp.893-898.

7.     Flock, U., Fischer, S., Weeger, J., Reese, S. and Walter, B., 2022. Anti-Müllerian hormone as a diagnostic tool to identify queens with ovarian remnant syndrome. Journal of Feline Medicine and Surgery, 24(8), pp.e168-e174.

8.     Hess, M., 2015. Determining whether a dog is spayed. Clinician’s Brief, pp.35-37.

9.     Johnston, S.D., 1991. Questions and answers on the effects of surgically neutering dogs and cats. Journal of the American Veterinary Medical Association, 198(7), pp.1206-1214.

10.  Miller, D.M., 1995. Ovarian remnant syndrome in dogs and cats: 46 cases (1988–1992). Journal of veterinary diagnostic investigation, 7(4), pp.572-574.

11.  Place, N.J., Cheraskin, J.L. and Hansen, B.S., 2019. Evaluation of combined assessments of serum anti-Müllerian hormone and progesterone concentrations for the diagnosis of ovarian remnant syndrome in dogs. Journal of the American Veterinary Medical Association, 254(9), pp.1067-1072.

12.  Pluhar, G.E., Memon, M.A. and Wheaton, L.G., 1995. Granulosa cell tumor in an ovariohysterectomized dog. Journal of the American Veterinary Medical Association, 207(8), pp.1063-1065.

13.  Prats, A.E., 2001. Ovarian remnant syndrome in the queen. EVSSAR newsletter, 4(1), pp.5-8.

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15.  Sangster, C., 2005. Ovarian remnant syndrome in a 5-year-old bitch. The Canadian Veterinary Journal, 46(1), pp.62-64.

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17.  Sontas, B.H., Gürbulak, K. and Ekici, H., 2007. Ovarian remnant syndrome in the bitch: a literature review. Archivos de Medicina Veterinaria, 39(2), pp.99-104.

18.  Turna Yilmaz, Ö., Toydemir, T.S.F., Kirsan, I., Gunay Ucmak, Z. and Caliskan Karacam, E., 2015. Anti-Müllerian hormone as a diagnostic tool for ovarian remnant syndrome in bitches. Veterinary Research Communications, 39, pp.159-162.

19.  Tobias, K.M., 2020. Top 5 Complications of Gonadectomy. Clinician’s Brief, pp.10-16.

20.  Van Os, J.L., Van Laar, P.H., Oldenkamp, E.P. and Verschoor, J.S.C., 1981. Oestrus control and the incidence of mammary nodules in bitches, a clinical study with two progestogens. Veterinary Quarterly, 3(1), pp.46-56.

21.  Van Nimwegen, S.A., Van Goethem, B., de Gier, J. and Kirpensteijn, J., 2018. A laparoscopic approach for removal of ovarian remnant tissue in 32 dogs. BMC veterinary research, 14(1), pp.1-13.

Wallace, M.S., 1991. The ovarian remnant syndrome in the bitch and queen. Veterinary Clinics of North America: Small Animal Practice, 21(3), pp.501-507.