Infertility in the queen

1. Infertility in the queen • Alain Fontbonne, DVM , PhD, Ass. Pr., Dipl. ECAR • Past-President of EVSSAR • Alfort Veterinary College, Paris, France • Elise Malandain, DVM, MSc • R&D , ROYAL CANIN France

2. Infertility in the queen • Introduction • Anestrus • Hyperestrus • Mating failure • Ovulation failure • Lack of fertilization • Early embryonic death

3. Introduction • Nowadays • Pure bred cats become more and more popular • People are more professional: • They ask veterinarians to provide more technical help • It is necessary to have an accurate diagnosis procedure • Begin with the most frequent causes • Follow a chronological order

4. Infertility in the queen • Introduction • Anestrus • Hyperestrus • Mating failure • Ovulation failure • Lack of fertilization • Early embryonic death

5. Anestrus • Usual in northern hemisphere during the short days period • Physiological anestrus is longer in long haired breeds • False anestrus • Silent heat: • Normal hormonal events without obvious estrus behaviour • Timid queens; low on social scale; crowding • Differentiate from pseudopregnancy: vaginal cytology, serum progesterone • Perform vaginal smears and hormonal assays • More difficult to appreciate than in the bitch: • Generally progesterone blood level does not increase except if a spontaneous ovulation occurs .

6. Anestrus • Primary anestrus • Check eventual drugs administration: • Progestagens (given when the queen suffers from prurit) • Antifungic drugs (ketoconazole) • Congenital problem • Clinical examination • Ultrasound examination • Check that ovaries are present • Beware of neutered queens

7. Anestrus • Primary anestrus • Environmental problems • Frequent travel, exhibition • Overcrowding, temperature/ventilation • Antagonistic social interactions • Social life (stress) • Lack of light • Stress • Transport • Delayed puberty! • Persians may reach puberty near 12-14 months.

8. Anestrus • Secondary anestrus • Racial variations • Some persian queens may exhibit only one or two heat periods per year • Changes in the living environment • Light period • Below 10 hours of light per day  anoestrus • Persistant corpus luteum • Continuous progesterone secretion • Normally <1ng/L

9. Estrus induction • Indications • Medical indications • Prolonged anestrus • Zootechnical indications • Try to breed queens at the non-breeding period • Long-haired queens • Problem due to the « group effect » • Methods • Light stimulation • Hormonal treatments: • gonadotropins: eCG=PMSC

10. Light stimulation • Interest • Is a « physiological » method • No adverse reactions • Methods • A 14 hours day light helps to get two monthly estrous periods • Needs 3 weeks before the beginning of heats • Avoid continuous light

11. Light stimulation • In practice • Hurni makes the proposal of • one month of 9 hours of day light • followed by one month of 14 hours of day light. • Programs using dis-continuous lighting programs 12 h-1h-1h-9h seem to give better results. • In all cases, the best results are obtained when light stimulation is associated with a social stimulus (other queens + males).

12. Infertility in the queen • Introduction • Anestrus • Hyperestrus • Mating failure • Ovulation failure • Lack of fertilization • Early embryonic death

13. Hyper-estrus • Siamese cats • Social factors • Queens that are not in heat may accept a mating • Aetiology : • Successive phases of follicular growth • Hormonal secreting follicular cysts: • GnRH, hCG, follicular puncture, unilateral ovariectomy • Granulosa Cells Tumor • Drugs

14. Infertility in the queen • Introduction • Anestrus • Hyperestrus • Mating failure • Ovulation failure • Lack of fertilization • Early embryonic death

15. Mating failure • Before doing any complementory investigation, check that the mating has occured • In practice, mating failure is THE big cause of infertility in the queen

16. Mating failure • Environnemental causes • Transport of the queen leading to interruption of estrous behavior • Time necessary for adaptation • Non-experimented or scared male cat... • …or agressive queen! • Organise transport • Help....

17. Mating failure • Physical causes in the male • Gingivitis or pain of the jaws • Penis stricture due to hair • Anatomical abnormalities of the genital tract • Infection • Retrograde ejaculation • Urinari calculi • Pain during ejaculation

18. Mating failure • Lack of libido of the male • Hypothyroidism • Hormonal treatments • Age • Lack of A vitamine, iodide, poly insaturated fatty acids • Weight excess • Low efficiency of usual treatments(testosterone IM) • Try with another male cat • AI

19. Infertility in the queen • Introduction • Anestrus • Hyperestrus • Mating failure • Ovulation failure • Lack of fertilization • Early embryonic death

20. Ovulation failure • Mounting • Not repeated enough • Too long period between two successive mountings • 1 coitus leads to ovulation in only 50% of the cases • Before going through many complementary investigations,the breeder has to know the frequency and intensity of mountings, and to check if the queen exhibits a normal post-coital reaction.

21. Ovulation failure • Progesterone secretion (ovarian tumors, luteal cysts) • Some queens may have follicular maturation under progesterone secretion. • This level can be sufficient to prevent ovulation, without preventing estrus: • It is useful to assay progesteronemia before a mating: <1ng/L • May induce false interpretation of the ovulation detection after mating

22. To confirm ovulation: progesterone testing !!

23. Ovulation failure • Sedatives/anesthesic drugs • Used in agressive queens • May prevent the LH peak • Stress • A stressed queen may not ovulate, even when exhibiting a normal post-coital reaction • Try eventually to bring the male and to allow him to mate the queen , after a period of adaptation

24. Infertility in the queen • Introduction • Anestrus • Hyperestrus • Mating failure • Ovulation failure • Lack of fertilization • Early embryonic death

25. Lack of fertilization • Diagnosis • Ovulation has to be confirmed • Mating has to be confirmed • Negative early pregnancy diagnosis using ultrasonography • Impossible to differenciate from early embryonic death • Cause • Spontaneous ovulation, before presenting the queen to the male • Relatively rare  MALE INFERTILITY

26. Male infertility • Genetical problems • « 3 colors » male cat (tortoise shell) • Infertility: • Abnormalities of semen (Cf. AI) • Treatments are of low efficiency (GnRH) • Presence of spicles on the penis • Under the control of androgens

27. Male infertility • Miscellaneous problems • Urinary calculi, • Increased temperature of the testis, • Testicular tumors • Inflammatory diseases ( check testis and prepucial cavity). • Back pain • Gingivitis!!!

28. Male infertility • Drugs • Cortico-steroids, anabolic steroids, antifungic compounds, progestagens • Age • Too young or too old !

29. Male infertility: procedure • History • Previous treatments (ketoconazole, progesterone, anti-androgens) • Previous matings • Clinical examination • External genitalia • Check the urine • Semen evaluation • See AI

30. Infertility in the queen • Introduction • Anestrus • Hyperestrus • Mating failure • Ovulation failure • Lack of fertilization • Early embryonic death

31. Cystic endometrial hyperplasia • First stage of pyometra • Due to hormonal disorders • Repeated pseudo pregnancies • Drugs (pills, injection) • Secondary, infection and accumulation of fluid = pyometra • Particularly frequent in Siamese queens • Leads to infertility • Ovulation occurs, without implantation • No other clinical signs….

32. Infertility in the queen • Introduction • Anestrus • Hyperestrus • Mating failure • Ovulation failure • Lack of fertilization • Early embryonic death

33. Abortion/Pregnancy arrest • Early embryonic resorption and further abortion most often unnoticed in the queen: •  infertility is the main sign • Scientific knowledge on this topic is very limited (Schlafer 2003)

34. Early embryonic death • In practice • Try to diagnose pregnancy as early as possible D 10 D 11 D 13 D 15

36. Hormonal problems

37. Hormonal problems • Hypoluteoidism: • Very rare in queens • Progesterone therapy may be used •  be careful not to counteract with normal parturition Pregnancy

38. Infectious diseases

39. Infectious diseases • Viruses: • FelV the most common cause: • Testing and housing procedures • FIV: • Outdoors catteries • Feline Herpes virus • Feline calicivirus: • Many different strains - Cases in vaccinated animals ? • Rarely suspected (Van Vuuren et al. 1999) • Feline panleucopenia virus: • Beware of attenuated live vaccines injected in pregnant queens • Feline coronavirus: • Uncommon cause of abortion in cats (Ström-Holst 2002)

40. Infectious diseases • Bacteria: • Probably under-diagnosed • E.coli, Staphylococcus sp., Streptococcus sp.: • potential causes of abortion(Root-Kustritz 2006) • Chlamydophila felis ? • Its role is unclear : experimentally: suppurative placentitis may occur (Schlafer 2003) • Treatment: Doxyxyclin 28 days (Dean et al. 2005) • Diagnosis is difficult • Vaccination does not protect against infection • Salmonella sp. • Bartonella henselae (Guptill et al. 1998) • Parasites: • Toxoplama gondii (Root-Kustritz 2006) • Cytauxzoon felis ? (Weismann et al. 2007)

41. Infectious causes of « abortion » • In practice • Test the queen for FelV-FIV • Serology-PCR for Chlamydiosis, FHV • Vaginal smear: many neutrophils ? • Bacterial identification: vaginal culture • with a urinary catheter : infuse a few drops of sterile fluid in the vagina, and aspirate them again

45. Chromosomal problems

46. Chromosomal defects • May cause abortion or fetal death (Romagnoli 2003) • 37, X0 • Trisomies • If repeated abortions: • karyotype the aborted fetuses

47. Nutritional causes

48. Proteins and Taurine • Proteins • Higher level diet recommended for reproduction • Taurine • During gestation • Essential amino acid selectively transported through the placenta • A deficiency may induce early embryonic resorption (before 25 days) (Sturman 1991, Dieter 1993,Champion et al. 2005) • with or without an increase in relaxine plasma level

49. Arachidonic acid • Essential in cats • Can not be synthesized in quantity (limiting action of desaturase δ 6) • Not enough to cover high needs • But adults cat can survive with a deficiency • During pregnancy • A deficiency IMPAIRS reproduction in queens • Essential for gestation and viability of kittens! (Pawlosky1996) • No effect on males reproduction ,

50. Copper (Fascetti 1998, 2000) • Role on reproduction: • Has been particularly studied in cats • Direct link between Copper and reproductive performances • Some chemical forms are not assimilated • Copper oxide for example • Under 10 mg/kg, progressive decrease of fertility, prolificity and vitality of kittens • To ensure the best assimilation • Some authors recommend to use chelated forms • Trace element link with an amino acid • Less competition for absorption