Composition comprising HP-hMG for use in treating infertility

1 . A method of treating infertility in a patient having a serum anti-Müllerian hormone (AMH) level≥35.7±0.5 pmol/L (≥5.0±0.2 ng/ml) prior to treatment/stimulation, comprising:

selecting a patient identified as having a serum anti-Müllerian hormone (AMH) level≥35.7±0.5 pmol/L (≥5.0±0.2 ng/ml) prior to treatment/stimulation;

conducting controlled ovarian stimulation by administering a daily dose of 75-450 IU highly purified human menopausal gonadotropin (HP-hMG) to the selected patient from day one of treatment;

at stimulation day 5 or 6 or 7 of controlled ovarian stimulation, determining whether the patient's serum level of human chorionic gonadotrophin (hCG) is at a target mid-follicular threshold level of ≥1.5 mIU/mL; and

maintaining or increasing the daily dose of highly purified human menopausal gonadotropin (HP-hMG) based on whether the patient's serum level of human chorionic gonadotrophin (hCG) is at or below the target mid-follicular threshold level.

2 . The method according to claim 1 , further comprising triggering final follicular maturation when the level of hCG in the patient's serum is at or above a specified threshold level for final follicular maturation of from 1.5-2.0 mIU/mL.

3 . The method according to claim 1 , further comprising, prior to stimulation, identifying the patient as having a serum anti-Müllerian hormone (AMH) level≥35.7±0.5 pmol/L (≥5.0±0.2 ng/ml).

4 . The method according to claim 1 , wherein the patient is not anovulatory.

5 . The method according to claim 1 , wherein the controlled ovarian stimulation comprises administering HP-hMG at a starting dose of 150 IU/day from day 1 to at least day 5 of stimulation.

6 . The method according to claim 1 , wherein the treatment of infertility increases the probability of live birth compared to treatment with CHO cell-derived recombinant FSH.

7 . The method according to claim 1 , further comprising triggering final follicular maturation by administering hCG or by administering a GnRH agonist, optionally supplemented with hCG.

8 . The method according to claim 1 , further comprising administering a GnRH antagonist starting on day 6 of stimulation.

9 . The method according to claim 1 , further comprising:

retrieving oocyte(s), fertilizing the oocyte(s), allowing the fertilized oocyte(s) to develop to the blastocyst stage, optionally assessing the quality/morphology of the blastocyst(s), and implanting a fresh blastocyst in a uterus; or

retrieving oocyte(s), fertilizing the oocyte(s), allowing the fertilized oocyte(s) to develop to the blastocyst stage, optionally assessing chromosomal quality of the blastocyst(s), freezing one or more or all blastocyst(s), and implanting a thawed-frozen blastocyst in a uterus; or

retrieving oocyte(s), freezing unfertilized oocytes(s), subsequently thawing one or more oocyte(s), fertilizing one or more or all thawed oocyte(s), allowing fertilized oocyte(s) to develop to the blastocyst stage, optionally assessing the quality/morphology of the blastocyst(s), and implanting a blastocyst in a uterus; or

retrieving oocyte(s), freezing unfertilized oocytes(s), subsequently thawing one or more frozen oocytes, fertilizing one or more or all thawed oocyte(s), allowing fertilized oocyte(s) to develop to the blastocyst stage, optionally assessing chromosomal quality of the blastocyst(s), freezing one or more or all blastocyst(s), and implanting a thawed-frozen blastocyst in a uterus.

10 . The method according to claim 1 , wherein the patient is 21-35 years old and has a BMI of 18-30 kg/m 2 at the start of treatment.

11 . The method according to claim 1 , wherein the method comprises increasing the daily dose of HP-hMG by 75 IU/day when the patient's serum level of hCG is below the target mid-follicular threshold level.

12 . The method according to claim 1 , wherein the method comprises maintaining the daily dose of HP-hMG when the patient's serum level of hCG is at the target mid-follicular threshold level.

13 . A method of treating infertility in a patient having a serum anti-Müllerian hormone (AMH) level≥35.7±0.5 pmol/L (≥5.0±0.2 ng/ml) prior to treatment/stimulation, comprising:

selecting a patient identified as having a serum anti-Müllerian hormone (AMH) level≥35.7±0.5 pmol/L (≥5.0±0.2 ng/ml) prior to treatment/stimulation;

conducting controlled ovarian stimulation by administering a daily dose of 75-450 IU highly purified human menopausal gonadotropin (HP-hMG) to the patient from day one of treatment;

at stimulation day 5 or 6 or 7, determining if the patient's serum level of human chorionic gonadotrophin (hCG) is at a target mid-follicular threshold level of ≥1.5 mIU/mL; and

triggering final follicular maturation when the level of human chorionic gonadotrophin (hCG) in the patient's serum is at or above a specified threshold level of serum human chorionic gonadotrophin (hCG) for final follicular maturation selected from 1.5-2.0 mIU/mL which leads to an increased probability of live birth.

14 . The method according to claim 13 , further comprising, prior to triggering final follicular maturation, increasing the daily dose of HP-hMG by 75 IU/day when the patient's serum level of hCG is below the target mid-follicular threshold level.

15 . The method according to claim 13 , further comprising, prior to triggering final follicular maturation, maintaining the daily dose of HP-hMG when the patient's serum level of hCG is at the target mid-follicular threshold level.

16 . A method of treating infertility in a patient having a serum anti-Müllerian hormone (AMH) level≥35.7±0.5 pmol/L (≥5.0±0.2 ng/ml) prior to treatment/stimulation, comprising:

selecting a patient identified as having a serum anti-Müllerian hormone (AMH) level≥35.7±0.5 pmol/L (>5.0±0.2 ng/ml) prior to treatment/stimulation;

conducting controlled ovarian stimulation by administering a daily dose of 75-450 IU highly purified human menopausal gonadotropin (HP-hMG) to the patient from day one of treatment;

at stimulation day 5 or 6 or 7, determining if the patient's serum level of human chorionic gonadotrophin (hCG) is at a target mid-follicular threshold level of ≥1.5 mIU/mL; and

triggering final follicular maturation when the level of human chorionic gonadotrophin (hCG) in the patient's serum is at or above 1.8 mIU/mL which leads to an increased probability of live birth.

17 . A method for increasing a probability of live birth following fresh or frozen embryo transfer in the treatment of infertility in a patient having a serum anti-Müllerian hormone (AMH) level≥35.7±0.5 pmol/L (≥5.0±0.2 ng/ml) prior to treatment/stimulation, comprising:

selecting a patient identified as having a serum anti-Müllerian hormone (AMH) level≥35.7±0.5 pmol/L (≥5.0±0.2 ng/ml) prior to treatment/stimulation;

conducting controlled ovarian stimulation by administering a daily dose of 75-450 IU highly purified human menopausal gonadotropin (HP-hMG) to the patient from day one of treatment;

at stimulation day 5 or 6 or 7, determining if the patient's serum level of human chorionic gonadotrophin (hCG) is at a target mid-follicular threshold level of ≥1.5 mIU/mL; and

triggering final follicular maturation when the level of human chorionic gonadotrophin (hCG) in the patient's serum is at or above a specified threshold level of serum human chorionic gonadotrophin (hCG) for final follicular maturation selected from 1.5-2.0 mIU/mL which leads to an increased probability of live birth.

18 . A method for increasing a probability of live birth following fresh or frozen embryo transfer in the treatment of infertility in a patient having a serum anti-Müllerian hormone (AMH) level≥35.7±0.5 pmol/L (≥5.0±0.2 ng/ml) prior to treatment/stimulation, comprising:

selecting a patient identified as having a serum anti-Müllerian hormone (AMH) level≥35.7±0.5 pmol/L (≥5.0±0.2 ng/ml) prior to treatment/stimulation;

conducting controlled ovarian stimulation by administering a daily dose of 75-450 IU/day highly purified human menopausal gonadotropin (HP-hMG) to the selected patient from day one of treatment;

at stimulation day 5 or 6 or 7, determining whether the patient's serum level of human chorionic gonadotrophin (hCG) is at a target mid-follicular threshold level≥1.5 mIU/mL; and

maintaining or increasing the daily dose of highly purified human menopausal gonadotropin (HP-hMG) based on whether the patient's serum level of hCG is at or below the target mid-follicular threshold level.

19 . A method of treating infertility in a patient having a serum anti-Müllerian hormone (AMH) level≥35.7±0.5 pmol/L (≥5.0±0.2 ng/ml) prior to treatment/stimulation, comprising:

selecting a patient identified as having a serum anti-Müllerian hormone (AMH) level≥35.7±0.5 pmol/L (≥5.0±0.2 ng/ml) prior to treatment/stimulation;

conducting controlled ovarian stimulation by administering a daily dose of 75-450 IU highly purified human menopausal gonadotropin (HP-hMG) to the selected patient from day one of treatment;

at stimulation day 5 or 6 or 7 of controlled ovarian stimulation, determining whether the patient's serum level of human chorionic gonadotrophin (hCG) is at a target mid-follicular threshold level of ≥1.5 mIU/mL;

maintaining or increasing the daily dose of highly purified human menopausal gonadotropin (HP-hMG) based on whether the patient's serum level of human chorionic gonadotrophin (hCG) is at or below the target mid-follicular threshold level; and

triggering final follicular maturation when the level of human chorionic gonadotrophin (hCG) in the patient's serum is at or above 1.8 mIU/mL.