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

A Phase III, Uncontrolled Trial to Assess the Non-immunogenicity and Safety of Org 36286 in Patients Undergoing Repeated Controlled Ovarian Stimulation Cycles Using a Multiple Dose GnRH Antagonist Protocol

The objective of the trial is to assess the non-immunogenicity and safety of corifollitropin alfa (also known as Org 36286, SCH 900962 and MK-8962) in participants undergoing repeated COS cycles using a multiple dose GnRH antagonist protocol.

Study Overview

• Status: Completed
• Conditions: In Vitro Fertilization
• Intervention / Treatment: Drug: Corifollitropin alfa; Biological: FSH; Biological: GnRH antagonist; Biological: (rec)hCG; Drug: Progesterone

Detailed Description

This trial is designed as an open-label, uncontrolled, repeated cycle trial to assess the non-immunogenicity and safety of corifollitropin alfa in participants undergoing repeated COS cycles for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) using a multiple dose GnRH antagonist protocol. The trial period per participant will cover 1, 2 or 3 COS treatment cycles and no more than three (in-between two stimulation cycles) Frozen-Thawed Embryo Transfer (FTET) cycles following either or both of the first two treatment cycles. In each stimulation cycle, participants receive a single injection of corifollitropin alfa and one week later, treatment is continued with a daily dose of any FSH-containing preparation up to the day of (rec)hCG administration for final oocyte maturation. Assessment of anti-corifollitropin alfa antibodies and local tolerance after corifollitropin alfa injection are important safety endpoints in this trial.

• Study Type: Interventional
• Enrollment (Actual): 682
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 37 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Females of couples with an indication for COS and IVF or ICSI;
• >=18 and <=39 years of age at the time of signing informed consent;
• Body weight > 60 kg and body mass index (BMI) >=18 and <=29 kg/m^2;
• Normal menstrual cycle length: 24-35 days;
• Availability of ejaculatory sperm (use of donated and/or cryopreserved sperm is allowed);
• Willing and able to sign informed consent.

Exclusion Criteria:

• History of or any current (treated) endocrine abnormality;
• History of ovarian hyper-response or history of ovarian hyperstimulation syndrome (OHSS);
• History of or current polycystic ovary syndrome (PCOS);
• More than 20 basal antral follicles (size: <11 mm, both ovaries combined) as measured on USS in the early follicular phase (menstrual cycle day 2-5);
• Less than 2 ovaries or any other ovarian abnormality, including endometrioma >10 mm (visible on USS);
• Presence of unilateral or bilateral hydrosalpinx (visible on USS);
• More than three unsuccessful COS cycles since the last established ongoing pregnancy (if applicable);
• History of non- or low ovarian response to FSH/human menopausal gonadotrophin (hMG) treatment;
• FSH > 12 IU/L or luteinizing hormone (LH) > 12 IU/L as measured by the local laboratory (sample taken during the early follicular phase: menstrual cycle day 2-5);
• Any clinically relevant abnormal laboratory value based on a sample taken during the screening phase, including abnormal cervical smear (Papanicolaou [PAP]>=III, cervical intraepithelial neoplasia [CIN]>=1);
• Contraindications for the use of gonadotropins (e.g. tumors, pregnancy/lactation, undiagnosed vaginal bleeding, hypersensitivity, ovarian cysts) or GnRH antagonists (e.g. hypersensitivity, pregnancy/lactation);
• Recent history of or current epilepsy, human immunodeficiency virus (HIV) infection, thrombophilia, diabetes or cardiovascular, gastro-intestinal, hepatic, renal, or pulmonary disease;
• Abnormal karyotyping of the participant or her partner (if karyotyping is performed);
• History or presence of alcohol or drug abuse within 12 months prior to signing informed consent;
• Previous use of corifollitropin alfa;
• Use of hormonal preparations within 1 month prior to screening;
• Administration of investigational drugs within three months prior to signing informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Corifollitropin alfa 150 µg; Up to 3 COS cycles (also called treatment cycles) were performed, each including the following: A single injection of 150 µg corifollitropin alfa was administered on Day 2 or 3 of the menstrual cycle (Stimulation Day 1). Administration of GnRH antagonist (0.25 mg/day) started on Stimulation Day 5 or 6 and continued through day of administration of recombinant Human Chorion Gonadotropin ([rec]hCG) (5,000-10,000 IU/250 µg). Administration of (rec)hCG occurred when 3 follicles ≥17 mm were observed on ultrasound scan (USS). Daily dosing with Follicle Stimulating Hormone (FSH) (not to exceed 225 IU/day) began on Stimulation Day 8 and continued up to day of (rec)hCG administration. Progesterone for luteal phase support was administered starting on the day of oocyte pick-up (34-36 hours after [rec]hCG) and continued for approximately 6 weeks. After COS cycles 1 and 2, Frozen-Thawed Embryo Transfer cycles (up to 3 after each COS cycle) could occur.

Drug: Corifollitropin alfa; Corifollitropin alfa 150 µg administered as a single subcutaneous dose.; Other Names: Org 36286; SCH 900962; MK-8962; Biological: FSH; FSH administerd subcutaneously at a dose not to exceed 225 IU/day.; Biological: GnRH antagonist; GnRH antagonist administered subcutaneously at a dose of 0.25 mg/day.; Biological: (rec)hCG; (rec)hCG administered subcutaneously at a dose of 5,000-10,000 IU/250 µg.; Drug: Progesterone; Progesterone administered vaginally at a dose of at least 600 mg/day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Clinically Relevant Immunogenicity	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.	Pre-dose (Stimulation Day 1) and up to approximately 40 days post dose in each treatment cycle
Local Tolerance at Injection Site: Number of Participants With no Event of Itching and With Mild, Moderate and Severe Itching in Any of 3 Treatment Cycles	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.	30 minutes post dose in each treatment cycle
Local Tolerance at Injection Site: Number of Participants With no Event of Pain and With Mild, Moderate and Severe Pain in Any of 3 Treatment Cycles	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.	30 minutes post dose in each treatment cycle
Local Tolerance at Injection Site: Number of Participants With no Event of Redness and With Mild, Moderate and Severe Redness in Any of 3 Treatment Cycles	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.	30 minutes post dose in each treatment cycle
Local Tolerance at Injection Site: Number of Participants With no Event of Swelling and With Mild, Moderate and Severe Swelling in Any of 3 Treatment Cycles	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.	30 minutes post dose in each treatment cycle
Local Tolerance at Injection Site Overall Summary: Number of Participants With no Local Tolerance Event (Itching, Pain, Redness or Swelling) and With a Mild, Moderate and Severe Local Tolerance Event in Any of 3 Treatment Cycles	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.	30 minutes post dose in each treatment cycle
Number of Participants With AEs	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.	Up to approximately 26 months after first dose of corifollitropin alfa
Number of Participants With Serious AEs (SAEs)	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.	Up to approximately 26 months after first dose of corifollitropin alfa
Number of Participants With Moderate to Severe Ovarian Hyperstimulation Syndrome (OHSS)	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.	Up to approximately 1 month after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), within a treatment cycle

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of (Rec)FSH Needed From Stimulation Day 8 Onwards to Reach the Criterion for Administration of (Rec)hCG	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.	Stimulation Day 8 to day of (rec)hCG administration (approximately Stimulation Day 10), within a treatment cycle
Number of Follicles ≥11 mm, ≥15 mm and ≥17 mm Documented by Ultrasonography Performed in the Participant on Stimulation Day 1 During Treatment Cycle 1	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.	Stimulation Day 1 in Treatment Cycle 1
Number of Follicles ≥11 mm, ≥15 mm and ≥17 mm Documented by Ultrasonography Performed in the Participant on Stimulation Day 1 During Treatment Cycle 2	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.	Stimulation Day 1 in Treatment Cycle 2
Number of Follicles ≥11 mm, ≥15 mm and ≥17 mm Documented by Ultrasonography Performed in the Participant on Stimulation Day 1 During Treatment Cycle 3	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.	Stimulation Day 1 in Treatment Cycle 3
Number of Follicles ≥11 mm, ≥15 mm and ≥17 mm Documented by Ultrasonography Performed in the Participant on Stimulation Day 5 or 6 During Treatment Cycle 1	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.	Stimulation Day 5 or 6 in Treatment Cycle 1
Number of Follicles ≥11 mm, ≥15 mm and ≥17 mm Documented by Ultrasonography Performed in the Participant on Stimulation Day 5 or 6 During Treatment Cycle 2	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.	Stimulation Day 5 or 6 in Treatment Cycle 2
Number of Follicles ≥11 mm, ≥15 mm and ≥17 mm Documented by Ultrasonography Performed in the Participant on Stimulation Day 5 or 6 During Treatment Cycle 3	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.	Stimulation Day 5 or 6 in Treatment Cycle 3
Number of Follicles ≥11 mm, ≥15 mm and ≥17 mm Documented by Ultrasonography Performed in the Participant on Stimulation Day 8 During Treatment Cycle 1	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.	Stimulation Day 8 in Treatment Cycle 1
Number of Follicles ≥11 mm, ≥15 mm and ≥17 mm Documented by Ultrasonography Performed in the Participant on Stimulation Day 8 During Treatment Cycle 2	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.	Stimulation Day 8 in Treatment Cycle 2
Number of Follicles ≥11 mm, ≥15 mm and ≥17 mm Documented by Ultrasonography Performed in the Participant on Stimulation Day 8 During Treatment Cycle 3	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.	Stimulation Day 8 in Treatment Cycle 3
Number of Follicles ≥11 mm, ≥15 mm and ≥17 mm Documented by Ultrasonography Performed in the Participant on Day of (Rec)hCG Administration During Treatment Cycle 1	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.	Day of (rec)hCG administration (approximately Stimulation Day 10) in Treatment Cycle 1
Number of Follicles ≥11 mm, ≥15 mm and ≥17 mm Documented by Ultrasonography Performed in the Participant on Day of (Rec)hCG Administration During Treatment Cycle 2	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.	Day of (rec)hCG administration (approximately Stimulation Day 10) in Treatment Cycle 2
Number of Follicles ≥11 mm, ≥15 mm and ≥17 mm Documented by Ultrasonography Performed in the Participant on Day of (Rec)hCG Administration During Treatment Cycle 3	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.	Day of (rec)hCG administration (approximately Stimulation Day 10) in Treatment Cycle 3
Number of Oocytes Retrieved in a Participant Among Entire Study Population	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.	Day of oocyte pick-up, 34-36 hours after (rec)hCG administration (approximately Stimulation Day 10), within a treatment cycle
Quality of Oocytes Assessed Prior to Planned ICSI in Treatment Cycle 1	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.	Day of oocyte pick-up, 34-36 hours after (rec)hCG administration (approximately Stimulation Day 10), in Treatment Cycle 1
Quality of Oocytes Assessed Prior to Planned ICSI in Treatment Cycle 2	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.	Day of oocyte pick-up, 34-36 hours after (rec)hCG administration (approximately Stimulation Day 10), in Treatment Cycle 2
Quality of Oocytes Assessed Prior to Planned ICSI in Treatment Cycle 3	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.	Day of oocyte pick-up, 34-36 hours after (rec)hCG administration (approximately Stimulation Day 10), in Treatment Cycle 3
Number of Fertilized Oocytes Obtained in Treatment Cycle 1	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).	16-18 hours after start of IVF or ICSI, which occurs on day of oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 1
Number of Fertilized Oocytes Obtained in Treatment Cycle 2	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).	16-18 hours after start of IVF or ICSI, which occurs on day of oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 2
Number of Fertilized Oocytes Obtained in Treatment Cycle 3	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).	16-18 hours after start of IVF or ICSI, which occurs on day of oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 3
Number of Fertilized Oocytes Obtained That Were Frozen in Treatment Cycle 1	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).	16-18 hours after start of IVF or ICSI, which occurs on day of oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 1
Number of Fertilized Oocytes Obtained That Were Frozen in Treatment Cycle 2	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).	16-18 hours after start of IVF or ICSI, which occurs on day of oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 2
Number of Fertilized Oocytes Obtained That Were Frozen in Treatment Cycle 3	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).	16-18 hours after start of IVF or ICSI, which occurs on day of oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 3
Number of Fertilized Oocytes Obtained That Were Used for Embryo Development in Treatment Cycle 1	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).	16-18 hours after start of IVF or ICSI, which occurs on day of oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 1
Number of Fertilized Oocytes Obtained That Were Used for Embryo Development in Treatment Cycle 2	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).	16-18 hours after start of IVF or ICSI, which occurs on day of oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 2
Number of Fertilized Oocytes Obtained That Were Used for Embryo Development in Treatment Cycle 3	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).	16-18 hours after start of IVF or ICSI, which occurs on day of oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 3
Fertilization Rate	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.	16-18 hours after start of IVF or ICSI, which occurs on day of oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), within a treatment cycle
Number and Quality of Embryos Obtained at Day 3 After Oocyte Pick-up in Treatment Cycle 1	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."	Day 3 after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 1
Number and Quality of Embryos Obtained at Day 3 After Oocyte Pick-up in Treatment Cycle 2	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."	Day 3 after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 2
Number and Quality of Embryos Obtained at Day 3 After Oocyte Pick-up in Treatment Cycle 3	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."	Day 3 after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 3
Number of Embryos Transferred	ET is the procedure in which one or more embryos are placed in the uterus. The number of embryos transferred, per participant, is summarized.	At ET, Day 3 or Day 5 after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), within a treatment cycle
Number of Participants by Category of Number of Good Quality Embryos Transferred in Treatment Cycle 1	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."	At ET, Day 3 or Day 5 after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 1
Number of Participants by Category of Number of Good Quality Embryos Transferred in Treatment Cycle 2	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."	At ET, Day 3 or Day 5 after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 2
Number of Participants by Category of Number of Good Quality Embryos Transferred in Treatment Cycle 3	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."	At ET, Day 3 or Day 5 after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 3
Number and Quality of Embryos Obtained That Were Frozen in Treatment Cycle 1	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."	Day 3 or Day 5 after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 1
Number and Quality of Embryos Obtained That Were Frozen in Treatment Cycle 2	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."	Day 3 or Day 5 after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 2
Number and Quality of Embryos Obtained That Were Frozen in Treatment Cycle 3	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."	Day 3 or Day 5 after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 3
Implantation Rate for Participants With ET	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.	Approximately 5-6 weeks after ET, within a treatment cycle
Number of Participants With Biochemical Pregnancy, Clinical Pregnancy, Vital Pregnancy and Ongoing Pregnancy in Any of Treatment Cycles 1, 2 or 3	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.	≥14 days (for biochemical pregnancy), 5-6 weeks (for clinical pregnancy), 5-6 weeks to 10 weeks (for vital pregnancy) and 10 weeks up to 9 months (for ongoing pregnancy) after ET, within a treatment cycle
Number of Participants With Singleton and Multiple Ongoing Pregnancy in Any of Treatment Cycles 1, 2 or 3	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.	10 weeks up to 9 months after ET, within a treatment cycle
Number of Participants With Miscarriage Among Participants With Clinical Pregnancy in Any of Treatment Cycles 1, 2 or 3	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.	5-6 weeks up to 9 months after ET, within a treatment cycle
Number of Participants With Miscarriage Among Participants With Vital Pregnancy in Any of Treatment Cycles 1, 2 or 3	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.	5-6 weeks up to 9 months after ET, within a treatment cycle
Number of Participants With Ectopic Pregnancy Among Participants With Biochemical Pregnancy in Any of Treatment Cycles 1, 2 or 3	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.	From 2 weeks up to approximately 5-6 weeks after ET, within a treatment cycle
Number of Participants With Ongoing Pregnancy in Any FTET Cycle	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.	10 weeks up to 9 months after ET within an FTET cycle
Cumulative Ongoing Pregnancy Rate: Percentage of Participants With Ongoing Pregnancy in Treatment Cycles 1, 2 or 3, or in Any FTET Cycle, or Who Had Ongoing Pregnancy That Was a Spontaneous Pregnancy	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.	Up to approximately 26 months after first dose of corifollitropin alfa
Serum Follicle Stimulating Hormone (FSH) Levels in Treatment Cycle 1	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.	Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 1
Serum FSH Levels in Treatment Cycle 2	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.	Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 2
Serum FSH Levels in Treatment Cycle 3	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.	Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 3
Serum Luteinizing Hormone (LH) Levels in Treatment Cycle 1	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.	Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 1
Serum LH Levels in Treatment Cycle 2	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.	Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 2
Serum LH Levels in Treatment Cycle 3	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.	Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 3
Serum Estradiol Levels in Treatment Cycle 1	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.	Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 1
Serum Estradiol Levels in Treatment Cycle 2	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.	Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 2
Serum Estradiol Levels in Treatment Cycle 3	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.	Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 3
Serum Progesterone Levels in Treatment Cycle 1	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.	Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 1
Serum Progesterone Levels in Treatment Cycle 2	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.	Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 2
Serum Progesterone Levels in Treatment Cycle 3	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.	Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 3
Serum Inhibin-B Levels in Treatment Cycle 1	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.	Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 1
Serum Inhibin-B Levels in Treatment Cycle 2	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.	Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 2
Serum Inhibin-B Levels in Treatment Cycle 3	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.	Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 3

Collaborators and Investigators

• Sponsor: Organon and Co

Publications and helpful links

General Publications

• Zandvliet AS, Prohn M, de Greef R, van Aarle F, McCrary Sisk C, Stegmann BJ. Impact of patient characteristics on the pharmacokinetics of corifollitropin alfa during controlled ovarian stimulation. Br J Clin Pharmacol. 2016 Jul;82(1):74-82. doi: 10.1111/bcp.12939. Epub 2016 May 31.
• Griesinger G, Verweij PJ, Gates D, Devroey P, Gordon K, Stegmann BJ, Tarlatzis BC. Prediction of Ovarian Hyperstimulation Syndrome in Patients Treated with Corifollitropin alfa or rFSH in a GnRH Antagonist Protocol. PLoS One. 2016 Mar 7;11(3):e0149615. doi: 10.1371/journal.pone.0149615. eCollection 2016.
• Rombauts L, Lambalk CB, Schultze-Mosgau A, van Kuijk J, Verweij P, Gates D, Gordon K, Griesinger G. Intercycle variability of the ovarian response in patients undergoing repeated stimulation with corifollitropin alfa in a gonadotropin-releasing hormone antagonist protocol. Fertil Steril. 2015 Oct;104(4):884-890.e2. doi: 10.1016/j.fertnstert.2015.06.027. Epub 2015 Jul 15.
• Norman RJ, Zegers-Hochschild F, Salle BS, Elbers J, Heijnen E, Marintcheva-Petrova M, Mannaerts B; Trust Investigators. Repeated ovarian stimulation with corifollitropin alfa in patients in a GnRH antagonist protocol: no concern for immunogenicity. Hum Reprod. 2011 Aug;26(8):2200-8. doi: 10.1093/humrep/der163. Epub 2011 May 27.

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2006
• Primary Completion (Actual): February 17, 2009
• Study Completion (Actual): May 15, 2009

Study Registration Dates

• First Submitted: June 11, 2008
• First Submitted That Met QC Criteria: June 11, 2008
• First Posted (Estimate): June 13, 2008

Study Record Updates

• Last Update Posted (Actual): February 3, 2022
• Last Update Submitted That Met QC Criteria: February 1, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Infertility; Multi-center; Pharmacological effects of drugs; Pharmacological Actions; Hormones, Hormone Substitutes and Hormone Antagonists
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: P05714; MK-8962-007 (Other Identifier: Merck Study Number); 38825 (Other Identifier: Merck Study Number); 2004-004966-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. Add data sharing links