Corifollitropin Alfa in Participants Undergoing Repeated Controlled Ovarian Stimulation (COS) Cycles Using a Multiple Dose Gonadatropin Releasing Hormone (GnRH) Antagonist Protocol (Study 38825)(P05714)

Serum samples obtained pre-dose and at 2 weeks after embryo transfer (ET), or at cycle discontinuation and 2-3 weeks after cycle discontinuation if cycle was stopped before ET was performed, were analyzed for presence of anti-corifollitropin alfa antibodies using screening and confirmatory tests. If a participant was confirmed to have anti-corifollitropin alfa antibody present in a post dose sample according to these tests, review of adverse events (AEs) in the participant was performed. The sample was also tested to evaluate whether the antibody appeared to have neutralizing activity that would interfere with the study drug biological effect. A participant was determined to have clinically relevant immunogenicity if the participant had a confirmed post dose anti-corifollitropin alfa antibody test result accompanied by clinical signs of immunogenicity (e.g., hypersensitivity reaction), considering also the results of the test for neutralizing activity of any antibody present.

At 30 minutes after dosing in each treatment cycle, the corifollitropin alfa injection site was assessed for the presence of itching, pain, redness and swelling, each of which was scored as none (no event), mild, moderate or severe. This measure reports results for the assessment of itching. A participant with an event was counted once in this analysis.

At 30 minutes after dosing in each treatment cycle, the corifollitropin alfa injection site was assessed for the presence of itching, pain, redness and swelling, each of which was scored as none (no event), mild, moderate or severe. This measure reports results for the assessment of pain. A participant with an event was counted once in this analysis.

At 30 minutes after dosing in each treatment cycle, the corifollitropin alfa injection site was assessed for the presence of itching, pain, redness and swelling, each of which was scored as none (no event), mild, moderate or severe. This measure reports results for the assessment of redness. A participant with an event was counted once in this analysis.

At 30 minutes after dosing in each treatment cycle, the corifollitropin alfa injection site was assessed for the presence of itching, pain, redness and swelling, each of which was scored as none (no event), mild, moderate or severe. This measure reports results for the assessment of swelling. A participant with an event was counted once in this analysis.

At 30 minutes after dosing in each treatment cycle, the corifollitropin alfa injection site was assessed for the presence of itching, pain, redness and swelling, each of which was scored as none (no event), mild, moderate or severe. This measure reports results considering the occurrence of any of the defined local tolerance events. A participant with an event was counted once in this analysis.

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. SAEs that occurred in fetuses or infants during the study period are included in this summary of SAEs, and are allocated to the associated study participant who was administered corifollitropin alfa.

OHSS was classified on study based on a slightly modified WHO Scientific Group (1973) classification: Grade I (mild) = characterized by excessive steroid secretion and ovarian enlargement (5-7 cm). Abdominal discomfort, including abdominal pain, is present. Grade II (moderate) = characterized by distinct ovarian cysts (ovary size 8-10 cm), accompanied by abdominal pain and tension, nausea, vomiting, diarrhea. Grade III (severe) = characterized by enlarged cystic ovaries (ovary size >10 cm), accompanied by ascites and occasionally hydrothorax. Abdominal tension and pain may be severe. Pronounced hydrothorax together with an abdominal cavity filled with cysts and fluid elevating the diaphragm may cause severe breathing difficulties. Large quantities of fluid inside the cysts and in the peritoneal and pleural cavities cause haemoconcentration and increased blood viscosity. In rare cases, the syndrome may further be complicated by the occurrence of thromboembolic phenomena.

Beginning on Stimulation Day 8 of each treatment cycle, (rec)FSH was administered daily until the criteria for administration of (rec)hCG (presence of 3 follicles ≥17 mm documented by ultrasonography) was reached. The total amount of (rec)FSH administered in each participant to reach the criteria for (rec)hCG administration was calculated.

For each participant, the number of follicles ≥11 mm, ≥15 mm and ≥17 mm documented by ultrasonography on defined days during the treatment cycle was calculated.

For each participant, the number of follicles ≥11 mm, ≥15 mm and ≥17 mm documented by ultrasonography on defined days during the treatment cycle was calculated.

For each participant, the number of follicles ≥11 mm, ≥15 mm and ≥17 mm documented by ultrasonography on defined days during the treatment cycle was calculated.

For each participant, the number of follicles ≥11 mm, ≥15 mm and ≥17 mm documented by ultrasonography on defined days during the treatment cycle was calculated.

For each participant, the number of follicles ≥11 mm, ≥15 mm and ≥17 mm documented by ultrasonography on defined days during the treatment cycle was calculated.

For each participant, the number of follicles ≥11 mm, ≥15 mm and ≥17 mm documented by ultrasonography on defined days during the treatment cycle was calculated.

For each participant, the number of follicles ≥11 mm, ≥15 mm and ≥17 mm documented by ultrasonography on defined days during the treatment cycle was calculated.

For each participant, the number of follicles ≥11 mm, ≥15 mm and ≥17 mm documented by ultrasonography on defined days during the treatment cycle was calculated.

For each participant, the number of follicles ≥11 mm, ≥15 mm and ≥17 mm documented by ultrasonography on defined days during the treatment cycle was calculated.

For each participant, the number of follicles ≥11 mm, ≥15 mm and ≥17 mm documented by ultrasonography on the day of (rec)hCG administration during the treatment cycle was recorded.

For each participant, the number of follicles ≥11 mm, ≥15 mm and ≥17 mm documented by ultrasonography on the day of (rec)hCG administration during the treatment cycle was recorded.

For each participant, the number of follicles ≥11 mm, ≥15 mm and ≥17 mm documented by ultrasonography on the day of (rec)hCG administration during the treatment cycle was recorded.

Oocyte retrieval, also known as oocyte pick-up, is a technique used in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in order to remove oocytes from the ovary of the female, enabling fertilization outside the body. The number of oocytes retrieved, per participant, is summarized.

This measure summarizes results of assessment of the quality of oocytes performed following oocyte retrieval, among participants scheduled for ICSI in Treatment Cycle 1. For oocytes obtained from each participant, the number in each of 3 stages of oocyte development were determined. The earliest phase is the germinal vesicles stage, during which the immature oocyte appears as a large vesicular nucleus. Metaphase I is an intermediate stage during which the vesicles have broken down and the polar body has not yet formed; the oocyte is still immature. Metaphase II is the mature oocyte and is indicated by the presence of the polar body. Rating of quality for usefulness in ICSI follows the order metaphase II (best quality), metaphase I (lesser quality) and germinal vesicles stage (poorest quality). Only metaphase II oocytes can be fertilized. Metaphase I oocytes can develop in vitro to metaphase II oocytes. Germinal vesicles stage oocytes are the least useful for ICSI procedures.

This measure summarizes results of assessment of the quality of oocytes performed following oocyte retrieval, among participants scheduled for ICSI in Treatment Cycle 2. For oocytes obtained from each participant, the number in each of 3 stages of oocyte development were determined. The earliest phase is the germinal vesicles stage, during which the immature oocyte appears as a large vesicular nucleus. Metaphase I is an intermediate stage during which the vesicles have broken down and the polar body has not yet formed; the oocyte is still immature. Metaphase II is the mature oocyte and is indicated by the presence of the polar body. Rating of quality for usefulness in ICSI follows the order metaphase II (best quality), metaphase I (lesser quality) and germinal vesicles stage (poorest quality). Only metaphase II oocytes can be fertilized. Metaphase I oocytes can develop in vitro to metaphase II oocytes. Germinal vesicles stage oocytes are the least useful for ICSI procedures.

This measure summarizes results of assessment of the quality of oocytes performed following oocyte retrieval, among participants scheduled for ICSI in Treatment Cycle 3. For oocytes obtained from each participant, the number in each of 3 stages of oocyte development were determined. The earliest phase is the germinal vesicles stage, during which the immature oocyte appears as a large vesicular nucleus. Metaphase I is an intermediate stage during which the vesicles have broken down and the polar body has not yet formed; the oocyte is still immature. Metaphase II is the mature oocyte and is indicated by the presence of the polar body. Rating of quality for usefulness in ICSI follows the order metaphase II (best quality), metaphase I (lesser quality) and germinal vesicles stage (poorest quality). Only metaphase II oocytes can be fertilized. Metaphase I oocytes can develop in vitro to metaphase II oocytes. Germinal vesicles stage oocytes are the least useful for ICSI procedures.

This measure presents the number of fertilized oocytes obtained per participant from the IVF or ISCI procedure, by category of number of pronuclei (PN) present: 0 PN, 1 PN, 2 PN, ≥3 PN, other (fertilized oocyte that was not placed in PN category). Normal fertilized ooctyes have 2 pronuclei (2 PN).

This measure presents the number of fertilized oocytes obtained per participant from the IVF or ISCI procedure, by category of number of PN present: 0 PN, 1 PN, 2 PN, ≥3 PN, other (fertilized oocyte that was not placed in PN category). Normal fertilized ooctyes have 2 pronuclei (2 PN).

This measure presents the number of fertilized oocytes obtained per participant from the IVF or ISCI procedure, by category of number of PN present: 0 PN, 1 PN, 2 PN, ≥3 PN, other (fertilized oocyte that was not placed in PN category). Normal fertilized ooctyes have 2 pronuclei (2 PN).

This measure presents the number of fertilized oocytes obtained per participant from the IVF or ICSI procedure that were cryopreserved (frozen) for possible later use, by category of number of PN present: 0 PN, 1 PN, 2 PN, ≥3 PN, other (fertilized oocyte that was not placed in PN category). Normal fertilized ooctyes have 2 pronuclei (2 PN).

This measure presents the number of fertilized oocytes obtained per participant from the IVF or ICSI procedure that were cryopreserved (frozen) for possible later use, by category of number of PN present: 0 PN, 1 PN, 2 PN, ≥3 PN, other (fertilized oocyte that was not placed in PN category). Normal fertilized ooctyes have 2 pronuclei (2 PN).

This measure presents the number of fertilized oocytes obtained per participant from the IVF or ICSI procedure that were cryopreserved (frozen) for possible later use, by category of number of PN present: 0 PN, 1 PN, 2 PN, ≥3 PN, other (fertilized oocyte that was not placed in PN category). Normal fertilized ooctyes have 2 pronuclei (2 PN).

This measure presents the number of fertilized oocytes obtained per participant from the IVF or ISCI procedure that were used for embryo development, by category of number of PN present: 0 PN, 1 PN, 2 PN, ≥3 PN, other (fertilized oocyte that was not placed in PN category). Normal fertilized ooctyes have 2 pronuclei (2 PN).

This measure presents the number of fertilized oocytes obtained per participant from the IVF or ISCI procedure that were used for embryo development, by category of number of PN present: 0 PN, 1 PN, 2 PN, ≥3 PN, other (fertilized oocyte that was not placed in PN category). Normal fertilized ooctyes have 2 pronuclei (2 PN).

This measure presents the number of fertilized oocytes obtained per participant from the IVF or ISCI procedure that were used for embryo development, by category of number of PN present: 0 PN, 1 PN, 2 PN, ≥3 PN, other (fertilized oocyte that was not placed in PN category). Normal fertilized ooctyes have 2 pronuclei (2 PN).

The fertilization rate (in percent) is defined as 100 times the ratio of the number of fertilized 2 PN oocytes obtained and the number of oocytes that was used for fertilization, per participant.

At Day 3 after oocyte pick-up, embryos obtained from IVF or ISCI process for each participant were counted and quality was assessed. Quality was rated as Grade 1, 2 or 3, or "other grade", with Grade 1 representing the best quality. The 2 highest quality grades (Grade 1 + 2) were combined into a summary category of "good quality."

At Day 3 after oocyte pick-up, embryos obtained from IVF or ISCI process for each participant were counted and quality was assessed. Quality was rated as Grade 1, 2 or 3, or "other grade", with Grade 1 representing the best quality. The 2 highest quality grades (Grade 1 + 2) were combined into a summary category of "good quality."

At Day 3 after oocyte pick-up, embryos obtained from IVF or ISCI process for each participant were counted and quality was assessed. Quality was rated as Grade 1, 2 or 3, or "other grade", with Grade 1 representing the best quality. The 2 highest quality grades (Grade 1 + 2) were combined into a summary category of "good quality."

ET is the procedure in which one or more embryos are placed in the uterus. The number of embryos transferred, per participant, is summarized.

The number of embryos transferred, for each participant, by category of number of "good quality" embryos transferred, is summarized. Quality was rated as Grade 1, 2 or 3, or "other grade", with Grade 1 representing the best quality. The 2 highest quality grades (Grade 1 + 2) were combined into a summary category of "good quality."

The number of embryos transferred, for each participant, by category of number of "good quality" embryos transferred, is summarized. Quality was rated as Grade 1, 2 or 3, or "other grade", with Grade 1 representing the best quality. The 2 highest quality grades (Grade 1 + 2) were combined into a summary category of "good quality."

The number of embryos transferred, for each participant, by category of number of "good quality" embryos transferred, is summarized. Quality was rated as Grade 1, 2 or 3, or "other grade", with Grade 1 representing the best quality. The 2 highest quality grades (Grade 1 + 2) were combined into a summary category of "good quality."

The number of embryos that were cryopreserved (frozen) for possible later use, for each participant, overall and by embryo quality categories, is summarized. Quality was rated as Grade 1, 2 or 3, or "other grade", with Grade 1 representing the best quality. The 2 highest quality grades (Grade 1 + 2) were combined into a summary category of "good quality."

The number of embryos that were cryopreserved (frozen) for possible later use, for each participant, overall and by embryo quality categories, is summarized. Quality was rated as Grade 1, 2 or 3, or "other grade", with Grade 1 representing the best quality. The 2 highest quality grades (Grade 1 + 2) were combined into a summary category of "good quality."

The number of embryos that were cryopreserved (frozen) for possible later use, for each participant, overall and by embryo quality categories, is summarized. Quality was rated as Grade 1, 2 or 3, or "other grade", with Grade 1 representing the best quality. The 2 highest quality grades (Grade 1 + 2) were combined into a summary category of "good quality."

The implantation rate (in percent) is defined as 100 times the maximum number of gestational sacs as assessed by any ultrasound scan after ET divided by the number of embryos transferred per participant.

Biochemical pregnancy: Pregnancy proven by a biochemical pregnancy test using urine samples or serum samples collected at least 14 days after ET. Participants not having a positive biochemical pregnancy test result, but with an ultrasound scan showing at least one gestational sac were counted as having a biochemical pregnancy. Clinical pregnancy: Presence of at least one gestational sac as assessed by ultrasound scan. Vital pregnancy: Presence of at least one fetus with heart activity as assessed by ultrasound scan. Ongoing pregnancy: Presence of at least one fetus with heart activity as assessed by ultrasound scan at least 10 weeks after ET, or confirmed by live birth.

Singleton pregnancy is a pregnancy in which one fetus develops in the uterus. Multiple pregnancy is a pregnancy in which more than one fetus develops simultaneously in the uterus. Ongoing pregnancy: Presence of at least one fetus with heart activity as assessed by ultrasound scan at least 10 weeks after ET, or confirmed by live birth.

Miscarriage: Loss of the fetus without induction or instrumentation, also known as "spontaneous abortion." Clinical pregnancy: Presence of at least one gestational sac as assessed by ultrasound scan.

Miscarriage: Loss of the fetus without induction or instrumentation, also known as "spontaneous abortion." Vital pregnancy: Presence of at least one fetus with heart activity as assessed by ultrasound scan.

Ectopic pregnancy: A pregnancy in which the embryo attaches itself in a place other than inside the uterus. The most common site for an ectopic pregnancy is within one of the two fallopian tubes. Biochemical pregnancy: Pregnancy proven by a biochemical pregnancy test using urine samples or serum samples collected at least 14 days after ET. Participants not having a positive biochemical pregnancy test result, but with an ultrasound scan showing at least one gestational sac were counted as having a biochemical pregnancy.

After the first and after the second treatment cycle (i.e., a cycle in which corifollitropin alfa was administered for ovarian stimulation), participants could continue with a maximum of three FTET cycles before starting the following treatment cycle. This measure summarizes the number of participants with ongoing pregnancy following ET within an FTET cycle. Ongoing pregnancy: Presence of at least one fetus with heart activity as assessed by ultrasound scan at least 10 weeks after ET, or confirmed by live birth.

The ongoing pregnancy rate, cumulative over the entire study (in percent), is defined as 100 times the number of participants who had an ongoing pregnancy in Treatment Cycles 1, 2 or 3, or in any FTET cycle, or who had a spontaneous ongoing pregnancy, divided by the total number of participants who were administered corifollitropin alfa in the study. A participant could only be represented once in the count of ongoing pregnancies for determination of cumulative ongoing pregnancy rate. After the first and after the second treatment cycle (i.e., a cycle in which corifollitropin alfa was administered for ovarian stimulation), participants could continue with a maximum of three FTET cycles before starting the following treatment cycle. A spontaneous pregnancy is a pregnancy that was not considered to have resulted from ET in a treatment cycle or FTET cycle.

Blood samples for assessment of serum FSH were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

Blood samples for assessment of serum FSH were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

Blood samples for assessment of serum FSH were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

Blood samples for assessment of serum LH were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

Blood samples for assessment of serum LH were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

Blood samples for assessment of serum LH were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

Blood samples for assessment of serum estradiol were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

Blood samples for assessment of serum estradiol were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

Blood samples for assessment of serum estradiol were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

Blood samples for assessment of serum progesterone were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

Blood samples for assessment of serum progesterone were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

Blood samples for assessment of serum progesterone were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

Blood samples for assessment of serum inhibin-B were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

Blood samples for assessment of serum inhibin-B were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

Blood samples for assessment of serum inhibin-B were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.