METHODS FOR DIAGNOSING AND/OR TREATING STERILITY

1 . A polypeptide comprising N-terminal fragment of a cystatin, and/or a cystatin expression inducer for use for the treatment of sterility and/or infertility.

2 . The polypeptide comprising N-terminal fragment of a cystatin and/or cystatin expression inducer for its use according to claim 1 , wherein said cystatin is cystatin 3.

3 . The polypeptide comprising N-terminal fragment of a cystatin and/or cystatin expression inducer for its use according to claim 1 , wherein the polypeptide comprising N-terminal fragment of a cystatin is administered in combination with at least one N-terminal fragment of another cystatin.

4 . The polypeptide comprising N-terminal fragment of a cystatin and/or cystatin expression inducer for its use according to claim 1 , for treating male and/or female sterility and/or infertility.

5 . The polypeptide comprising N-terminal fragment of a cystatin and/or cystatin expression inducer for its use according to claim 1 , for treating sterility and/or infertility of a couple of subjects.

6 . The polypeptide comprising N-terminal fragment of a cystatin and/or cystatin expression inducer for its use according to claim 1 , wherein said polypeptide or cystatin expression inducer is administered locally.

7 . A polypeptide comprising N-terminal fragment of a cystatin, and/or cystatin expression inducer, for use as a fertilization promoting or improving drug.

8 . A polypeptide comprising N-terminal fragment of a cystatin and/or cystatin expression inducer for use for promoting or improving the step of migration of a zygote from the fallopian tubes to the uterus in a female mammal.

9 . The polypeptide comprising N-terminal fragment of a cystatin and/or cystatin expression inducer for its use according to claim 8 , wherein said female mammal is a mammal undergoing gamete intrafallopian transfer procedure (GIFT) or therapeutic donor insemination (TDI), or is a mammal turning to in vitro fertilization (IVF), during assisted reproductive technologies (ART).

10 . A method of in vitro fertilization and/or artificial insemination comprising the steps of contacting an ovum obtained from a female mammal and a spermatozoon obtained from a male mammal in a fluid medium comprising a polypeptide comprising N-terminal fragment of a cystatin.

11 . The method according to claim 10 , wherein said cystatin is cystatin 3.

12 . An in vitro method of diagnosing and/or predicting sterility and/or infertility of a subject and/or of a couple of subjects comprising the steps of:

(a1) measuring the level of at least one cystatin in a biological sample of a male subject, wherein said sample is selected from the group consisting of blood, plasma, serum, semen, sperm and seminal plasma and/or

(a2) measuring the level of at least one cystatin in a biological sample of a female subject, wherein said sample is selected from the group consisting of blood, plasma, serum, cervical mucus, vaginal mucus, and any other kind of female reproductive tract sample; and

(b) comparing the level of the at least one cystatin measured in step (a1) and/or (a2) with a male control level of said at least one cystatin or female control level of said at least one cystatin, as appropriate;

and optionally further the steps of

(c1) measuring the level of at least one cathepsin in a biological sample of a male subject, wherein said sample is selected from the group consisting of blood, plasma, serum, semen, sperm and seminal plasma, and/or

(c2) measuring the level of at least one cathepsin in a biological sample of a female subject, wherein said sample is selected from the group consisting of blood, plasma, serum, cervical mucus, vaginal mucus and any other kind of female reproductive tract sample;

(d) calculating at least one cystatin/cathepsin ratio [(a1+a2)/(c1+c2)] based on the measures of steps (a1) and (c1) and/or (a2) and (c2), as appropriate, and comparing the calculated cystatin/cathepsin ratio with a control threshold level of cystatin/cathepsin ratio;

wherein

i) a decreased level of the at least one cystatin measured in step (a1) and/or (a2) compared to said male control level of said at least one cystatin or female control level of said at least one cystatin, or

ii) a decreased cystatin/cathepsin ratio calculated in step (d) compared with said control threshold level of cystatin/cathepsin ratio

is indicative of sterility and/or infertility of said subject and/or couple of subjects, or is indicative of a higher risk of sterility and/or infertility of said subject and/or couple of subjects.

13 . The method according to claim 12 , comprising the steps of:

(a1) measuring the level of at least one cystatin in the biological sample of the male subject as defined in claim 12 ,

(a2) measuring the level of at least one cystatin in the biological sample of the female subject as defined in claim 12 ;

(a3) adding the level of said at least one cystatin measured in step (a1) and the level of said at least one cystatin measured in step (a2); and

(b) comparing the level of said at least one cystatin obtained in step (a3) with a control level of said at least one cystatin;

and optionally further the steps of

(c1) measuring the level of at least one cathepsin in a biological sample of a male subject, wherein said sample is selected from the group consisting of blood, plasma, serum, semen, sperm and seminal plasma, and/or

(c2) measuring the level of at least one cathepsin in a biological sample of a female subject, wherein said sample is selected from the group consisting of blood, plasma, serum, cervical mucus, vaginal mucus and any other kind of female reproductive tract sample;

(d) calculating at least one cystatin/cathepsin ratio [(a1+a2)/(c1+c2)] based on the measures of steps (a1) and (c1) and/or (a2) and (c2), as appropriate, and comparing the calculated cystatin/cathepsin ratio with a control threshold level of cystatin/cathepsin ratio; wherein

i) a decreased level of the at least one cystatin obtained in step (a3) compared to the control level of said at least one cystatin is indicative of sterility and/or infertility of said couple of subjects, or

ii) a decreased cystatin/cathepsin ratio calculated in step (d) compared with said control threshold level of cystatin/cathepsin ratio

is indicative of a higher risk of sterility and/or infertility of said couple of subjects.

14 . The method according to claim 12 , wherein steps (c1), (c2) and (d) are carried out.

15 . A kit intended for diagnosing and/or predicting sterility and/or infertility of a subject and/or of a couple of subjects comprising:

(i) means for detecting at least one cystatin in a biological sample of a male subject, wherein said sample is selected from the group consisting of blood, plasma, serum, semen, sperm and seminal plasma and/or

(ii) means for detecting at least one cystatin in a biological sample of a female subject, wherein said sample is selected from the group consisting of blood, plasma, serum, cervical mucus and vaginal mucus.

16 . A method of determining whether a subject and/or a couple of subjects suffering from sterility and/or infertility is likely to benefit from a treatment regimen that includes treatment with a ipolypeptide comprising N-terminal fragment of a cystatin and/or with a cystatin expression inducer comprising:

(a1) measuring the level of a cystatin in a biological sample of a male subject, wherein said sample is selected from the group consisting of blood, plasma, serum, semen, sperm and seminal plasma and/or

(a2) measuring the level of a cystatin in a biological sample of a female subject, wherein said sample is selected from the group consisting of blood, plasma, serum, cervical mucus and vaginal mucus.

17 . The polypeptide comprising N-terminal fragment of a cystatin and/or cystatin expression inducer for its use according to claim 2 , wherein the polypeptide comprising N-terminal fragment of a cystatin is administered in combination with at least one N-terminal fragment of another cystatin.

18 . The polypeptide comprising N-terminal fragment of a cystatin and/or cystatin expression inducer for its use according to claim 3 , for treating male and/or female sterility and/or infertility.

19 . The polypeptide comprising N-terminal fragment of a cystatin and/or cystatin expression inducer for its use according to claim 4 , for treating sterility and/or infertility of a couple of subjects.

20 . The polypeptide comprising N-terminal fragment of a cystatin and/or cystatin expression inducer for its use according to claim 5 , wherein said polypeptide or cystatin expression inducer is administered locally.