Feline Ovarian Remnant Syndrome

(Estrus after Ovariohysterectomy in the Queen)

Questions:

• What could be happening?

• How it can be diagnosed?

• How it can be treated?

• How did it happen?

Normal Feline Estrous Cycle Review:

• Understanding the normal feline estrous cycle is important when investigating signs of estrus after ovariohysterectomy.
• Puberty in the cat usually occurs at 9 to 10 months of age.
  • Puberty may occur as early as 4 months or as late as 2 years, however because cats are seasonal breeders, the season in which the kitten was born influences the age at which puberty occurs.
• Seasonality
  • Cyclicity is dependent on the photoperiod with cats being “long-day breeders” requiring 12 hours or more of light to maintain normal cyclicity.
  • Cyclicity and folliculogenesis stops abruptly in queens exposed to less than 8 hours of light, but resume an average of 16 days after returning to a 14-hour photoperiod.
  • Seasonality is more pronounced in cats exposed to natural lighting, especially at higher latitudes. Long-haired breeds tend to he more seasonal than short-haired breeds.
• Phases of the feline estrous cycle
  • Proestrus, estrus, interestrus, diestrus or pseudopregnancy, and anestrus.
  • Proestrus precedes estrus and lasts 1 to 2 days.
    • Seen in only 16% of estrous cycles.
    • Female is attractive to, but not willing to accept the male.
    • The queen may rub against objects, vocalize, and assume a lordotic or “dragster posture” where she will place her front quarters on the ground, elevate her hind quarters and lift her tail to one side. When the dorsal caudal area is stroked, she will tread with her hind legs.
  • Estrus is the period of sexual receptivity that lasts an average of 7 days (3 to 16) and then subsides for an average of 9 days (3 to 14).
    • Behavioral changes are pronounced in estrus, however the external genitalia has no conspicuous changes in appearance or size.
    • Because of several factors, such as the relatively short length of proestrus, the ability to induce ovulation by mechanical stimulation of the vagina, and the less dramatic changes observed in the queen; vaginal cytology is not as useful as it is in the bitch.
    • The duration of estrus is unaffected by breeding or ovulation.
    • Inducing ovulation to abruptly terminate objectionable estrous behavior will not shorten the duration of estrus for that cycle, however the subsequent interestrus period following estrus will be longer.
  • Interestrus is the period between successive estrus periods if ovulation does not occur.
    • If the queen is not bred, estrus will occur every 2 to 3 weeks.
    • If the queen ovulates, corpora lutea are formed and secrete progesterone.
  • If the queen is not pregnant, diestrus (pseudopregnancy) results which lasts 35 to 40 days.
  • Anestrus is the seasonal period when the cat does not cycle.
• Ovulation induction
  • Queens are induced ovulators and ovulate in response to vaginal stimulation, however spontaneous ovulation may occur in the queen.
  • Ovulation is triggered by copulation or mechanical stimulation of the vagina that causes a reflex stimulation of the hypothalamus via pathways in the spinal cord.
  • The hypothalamus releases gonadotropin-releasing hormone (GnRH), which causes a release of luteinizing hormone (LH) from the anterior pituitary.
  • The LH then stimulates ovulation and the development of corpora lutea.
  • Other forms of stimulation, for example stroking, may occasionally be responsible for ovulation.
    • Active corpora lutea have been found in cats unexposed to males or artificial coital stimuli.
  • Ovulation depends on adequate LH release, with both the peak concentration and the duration of elevation being important.
  • The LH release occurs within minutes of coitus and peaks about 1 to 2 hours later.
  • Release of LH is partially dependent upon the duration of prior exposure to estrogen so the LH response vary depending on the day of estrus coitus occurs.
  • Multiple copulations result in higher concentrations of plasma LH and are more likely to result in ovulation than single matings.
  • The duration of elevated LH in plasma also determines whether ovulation occurs, with LH decreasing to baseline values within 12 to 24 hours after a single mating or after multiple matings at less than 2-hour intervals.
  • LH remained elevated up to 38 hours after multiple mating intervals every 3 hours.
  • To achieve sufficient LH release, repeated breeding at reasonable intervals should be encouraged.
  • The LH response to a single mating can vary substantially, and neither single nor multiple copulations can ensure ovulation. T
  • To increase the likelihood of ovulation, breeders should try to maximize the number of matings and breed on successive days of estrus.
  • Ovulation occurs 24 to 60 hours postcoitus and may vary depending on the mating pattern.
• Three alternatives following estrus are possible in the feline:
  • Ovulation does not occur and an average 9 day (4 to 22) interestrus occurs before the next proestrus
  • Ovulation occurs without fertilization, resulting in a 35 to 40 day pseudopregnancy and a 1 to 10 day insterestus
    • Pseudopregnancy is when ovulation and corpora lutea formation occurs but not pregnancy.
    • The corpora lutea produce progesterone that rises rapidly from basal concentrations to a peak of 16 to 17 ng/ml 18 to 25 days post ovulation.
    • Following the peak, progesterone concentrations decline to basal values at approximately 40 days post ovulation.
    • The normal duration of pseudopregnancy is 36.5 days (35 to 40).
    • The corpora lutea appear to have a preprogrammed finite lifespan in that they are not subject to regression from uterine sources of prostaglandins. They are also resistant to multiple luteolytic doses of prostaglandins through days 11 to 25 postovulation, indicating that it is clinically difficult to shorten the time interval from the onset of pseudopregnancy to the subsequent estrus.
    • Lactation (pseudogenetra) at the end of pseudopregnancy is rare in the queen.
  • Pregnancy.

When does estrus occur after surgery?

•  17 days to 9 years was interval from surgery to estrus (mean of 2 years). Wallace, MS. Veterinary Clinics of North America Small Animal Practice. 21:501-507 (1991)

• 3 weeks to 6 months - Miller, D. J. Diagnostic Investigation 7: 572-574 (1995) - GA Diagnostic Lab

  • Looked at 29 cats over 5 years. 

  • No purebred cats.

  • OHE < 4 months of age did not have any ovarian remnants.

  • The prolonged interestrus - time cannot be fully answered, possibly spontaneous ovulation kept queens out of estrus. 
    

The following table shows the results of one study that investigated queens returning to estrus after ovariohysterectomy. The study documents 29 cats over 5 years that had ovarian remnants submitted to the Georgia Diagnostic Laboratory in Athens, Georgia. No purebred cats had any ovarian remnants. Queens that had surgery under 4 months of age did not have any ovarian remnants.

Table 1. Ovarian remnant location, time form surgery to estrus, and interestrus intervals in queens showing estrus after ovariohysterectomy.

Remnant Location

OHE to Estrus = time from initial surgery until signs of estrus seen
Interestrus Interval = Time from one estrus period to next estrus period.
NA = Unknown
From - Miller, D. J. Diagnostic Investigation 7: 572-574 (1995)

Diagnostics:
 

• Estrual signs are enough to confirm that the queen is in estrus and has ovarian tissue present.

• Estrogen samples > 70 pmol/L are an indication that the queen has estrogen production from follicular activity on the ovary.

  • Estrogens are not really reliable

  • Hard to measure accurately,

  • Concentrations may fluctuate during estrus

  • Estrogen concentration falls before the queen ends behavioral estrus.

• Induce ovulation and then measure the plasma concentration of progesterone 2 to 4 weeks later.

  • If progesterone is high (>6 nmol/ml), the queen ovulated and produced corpora lutea.

  • Ovulation can be induced by vaginal stimulation with a glass rod, thermometer

    • You must give multiple stimulations at least 2 hours apart to induce a sufficient LH peak.

    • Listen for the 'aftercry' to ensure complete stimulation.

  • Exogenous hormones

    • GnRH or LH after mating can be used to increase the likelihood of ovulation.

    • Both stimulate ovulation by bypassing the vaginal/hypothalamic neural pathway.

    • According to one report, administration of 25 ug of GnRH on the second day of estrus resulted in all mature follicles present ovulating in all queens treated.

    • The results of two reports suggest that a dose of 500 IU hCG on day 1 or days 1 and 2 of estrus achieved maximal ovulation rates.

      • With lower doses, all queens ovulated, but ovulation rates per queen were less than 100%.

      • hCG, administered at a dose of 250 IU on days 2 and 3 of estrus, and coupled with mating three times per day at three hour intervals for the first three days of estrus resulted in a doubling of the number of corpora lutea formed.

• LH testing

  • Using a commercially available canine LH assay (ICG Status-LH™ canine ovulation timing test; Synbiotics, San Diego, California, USA)
  • 92% positive predictive value and a 100% negative predictive value for a sexually intact queen (or an ovarian remnant), if its measured LH was less than 1 ng/mL (low test). In the intact queen, LH is maintained at basal concentrations through the negative feedback influence of ovarian estradiol secretion,
  •  Following ovariectomy, this control is lost and LH concentrations increase resulting in a positive test.

    Scebra LR, Griffin B. Evaluation of a commercially available luteinizing hormone test to distinguish between ovariectomized and sexually intact queens. Proc Am Coll Vet Intern Med Forum 2003. Available from: http://www.vin.com/Members/Proceedings/Proceedings.plx?CID=acvim2003&PID=pr04197&O=VIN L

Treatment:

• Surgery is the treatment of choice.

  • It is recommend that surgery be done during the time of estrual behavior or during diestrus.

  • During estrus follicles will be present, and during diestrus corpora lutea will be present.

  • In either case, the ovaries will be much larger than during anestrus.

  • The ovarian remnant(s) may be bilateral, so it is important to complete in the exploratory.

  • In all cases in one study, experienced surgeons found ovarian remnants in those animals that presented for signs of estrus after ovariohysterectomy.

    • This even applies to animals that had previous exploratory surgeries performed by more inexperienced surgeons that not find any ovarian tissue.

  • The ovarian tissue is usually at the ovarian pedicle, but has been reported in the mesentery, or even in the linea alba.

Why did it happen?

• It is more common in the queen than the bitch.

• It is not associated with difficult surgeries.

• It is not associated with new graduates or inexperienced surgeons.

• Dropping a piece of the ovary can result in revascularization of the remnant and return to estrus, but the ovaries are relatively easy to remove in the queen.

• Accessory ovarian tissue that extends into the ovarian ligament has been reported.

• Accessory ovarian tissue has also been documented in the proper ligament of the ovary, but separate from the ovary.

  • When the normal ovaries are removed, accessory tissue can become functional.

• The prolonged interestrus time cannot be fully answered, however it has been shown that some queens do spontaneously ovulate. Spontaneous ovulation may result in a diestrus and anestrus periods that approximate many of the interestrus times seen in one study.

Summary:
 

• Some queens show signs of estrus after ovariohysterectomy.

• It may be months between the surgery and return to estrus.

• The condition can be diagnosed by the estrual signs of the queen, or by inducing ovulation and measuring progesterone.

• Surgery is the treatment of choice, but the surgeon must be thorough.

• It probably was not the veterinarians fault that a remnant is there!
   

Other references: