Xpect: Predictive Factors for Ovarian Stimulation Using a Fixed Daily Dose of 200 IU Recombinant FSH (Study 142003)(P05696)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00778999
• Collaborator: (none)
• Enrollment: 442
• Arms: 2
• Actual Duration (Months): 21.7

Study Details

Study Description

Brief Summary

The success of assisted reproductive technologies (ART) is critically dependent on optimizing protocols for controlled ovarian stimulation to provide adequate numbers of good quality oocytes and embryos. This optimization is mainly valuable to a group of infertility patients (9%-24%) who respond poorly to Controlled Ovarian Stimulation(COS). It is also important for an additional 2.6% of the infertility patients who manifest a high response to gonadotropin and are at risk for hyperstimulation syndrome, a life-threatening situation. Extensive research was carried out and led to the introduction of GnRH antagonist, as an alternative to Gonadotropin Releasing Hormone (GnRH) agonist, for the prevention of premature Luteinizing Hormone (LH) surges. Further research to optimize the GnRH antagonist regimen concluded that a daily treatment with 200 IU of recombinant Follicle Stimulating Hormone (recFSH) in a GnRH antagonist regimen is safe, well tolerated and results in a good clinical outcome. This protocol is now frequently applied in the US and Europe.

Predicting a woman's response (based on the assessment of ovarian reserve) to COS is useful in determining individualized clinical management strategies for low and high responders and thus avoiding cancellation. Such prediction when based on reliable scientific evidence is valuable in consulting patients about their chances of success. A large number of studies have been performed, which used certain clinical, ultrasonographic and hormonal markers (called predictive factors), to try to optimize a COS protocol for patients who were down-regulated with a long GnRH agonist protocol. Prospective trials of predictive models have also been used to adjust the starting dose of FSH to prevent a too low or too high ovarian response. To date, however, none have been performed for women undergoing ovarian stimulation with a GnRH antagonist protocol.

The primary objective of this randomized, open-label, multicenter clinical trial was to identify one or more factors capable of predicting ovarian response in women treated with a daily dose of 200 IU recFSH in a GnRH antagonist protocol. Since many ART centers now use oral contraceptives as a means to schedule patients stimulated with recFSH and a GnRH antagonist for assisted reproduction, the trial evaluated also whether intervention with oral contraceptives affects the accuracy of predictive models for ovarian response.

Condition or Disease	Intervention/Treatment	Phase
Infertility	Drug: Marvelon	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 442 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-Label Clinical Trial to Identify Predictive Factors for Controlled Ovarian Stimulation Using a Fixed Daily Dose of 200 IU Recombinant FSH in GnRH Antagonist Regimen With or Without Oral Contraceptive Scheduling
• Actual Study Start Date: Oct 1, 2006
• Actual Primary Completion Date: Jul 24, 2008
• Actual Study Completion Date: Jul 24, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Oral Contraceptive Use of oral contraceptive pills prior to controlled ovarian stimulation	Drug: Marvelon; oral contraceptive 1 tablet daily for 14 to 21 days
No Intervention: Non-Oral Contraceptive No use of oral contraceptive pills prior to controlled ovarian stimulation

Outcome Measures

Primary Outcome Measures

1. Total Number of Oocytes [12 weeks]

   The total number of oocytes on the Day of oocyte pick-up is an indication of ovarian response

Secondary Outcome Measures

1. Number of Mature Oocytes [12 weeks]

   This is not a prespecified key secondary outcome; therefore, results will not be disclosed.

2. Number of Follicles on Stimulation Day 8 [12 weeks]

   This is not a prespecified key secondary outcome; therefore, results will not be disclosed.

3. Number of Follicles on Day of hCG [12 weeks]

   This is not a prespecified key secondary outcome; therefore, results will not be disclosed.

4. Number of Fertilized (2PN) Oocytes [12 weeks]

   This is not a prespecified key secondary outcome; therefore, results will not be disclosed.

5. Number of Good Quality Embryos [12 weeks]

   This is not a prespecified key secondary outcome; therefore, results will not be disclosed.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 39 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Females of couples with an indication for In Vitro Fertilization (IVF) and/or Intracytoplasmic Sperm Injection (ICSI) scheduled for their first COS treatment cycle

• Females >18 and <=39 years of age at the time of signing informed consent

• Body Mass Index (BMI) <= 32 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 endocrine abnormality

• Less than 2 ovaries or any other ovarian abnormality (inc.>10mm endometrioma)

• Presence of unilateral or bilateral hydrosalpinx

• Presence of any clinically relevant pathology affecting the uterine cavity or fibroids

= 5cm

• History of recurrent miscarriage (3 or more, even when unexplained)

• FSH or LH > 12 IU/L as measured by a local laboratory (sample taken during the early follicular phase: menstrual day 2-5)

• Any clinically relevant abnormal laboratory value (FSH, LH, estradiol (E2), Progesterone (P), total Testosterone (T), prolactin, Thyroid Stimulating Hormone (TSH), blood biochemistry, hematology and urinalysis) based on a sample during the screening phase.

• Contraindications for the use of gonadotropins (tumors, pregnancy, lactation, undiagnosed vaginal bleeding, hypersensitivity, ovarian cysts)

• Contraindications for the use of oral contraceptive pills (history of (h/o) thromboembolism, breast cancer, undiagnosed vaginal bleeding)

• Recent history of/or current epilepsy, Human Immunodeficiency Virus (HIV) infection, diabetes, cardiovascular, gastrointestinal, hepatic, renal or pulmonary disease

• Abnormal karyotyping of the patient or her partner (if karyotyping is performed)

• History or presence of alcohol or drug abuse within 12 months of signing the consent

• Use of hormonal preparations within one month prior to randomization

• Hypersensitivity to any of the concomitant medication prescribed as part of the treatment regimen in this protocol

• Administration of investigational drugs within three months prior to signing the informed consent

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00778999
• Other Study ID Numbers: P05696; 142003; NCT00628641
• First Posted: Oct 24, 2008
• Last Update Posted: Feb 4, 2022
• Last Verified: Feb 1, 2022

• Additional relevant MeSH terms: Infertility; Desogestrel

Study Results

Participant Flow

Arm/Group Title	Oral Contraceptive	Non-Oral Contraceptive
Arm/Group Description	Use of oral contraceptive pills prior to controlled ovarian stimulation	No use of oral contraceptive pills prior to controlled ovarian stimulation
Period Title: Overall Study
STARTED	223	219
COMPLETED	195	185
NOT COMPLETED	28	34

Baseline Characteristics

Arm/Group Title	Oral Contraceptive	Non-Oral Contraceptive	Total
Arm/Group Description	Use of oral contraceptive pills prior to controlled ovarian stimulation	No use of oral contraceptive pills prior to controlled ovarian stimulation	Total of all reporting groups
Overall Participants	223	219	442
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	223 100%	219 100%	442 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	223 100%	219 100%	442 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Total Number of Oocytes
Description	The total number of oocytes on the Day of oocyte pick-up is an indication of ovarian response
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat, defined as all randomized subjects who received recombinant follicle stimulating hormone

Arm/Group Title	Oral Contraceptive	Non-Oral Contraceptive
Arm/Group Description	Use of oral contraceptive pills prior to controlled ovarian stimulation	No use of oral contraceptive pills prior to controlled ovarian stimulation
Measure Participants	209	199
Mean (Standard Deviation) [Number of oocytes]	12.4 (6.7)	12.1 (7.7)

2. Secondary Outcome

Title	Number of Mature Oocytes
Description	This is not a prespecified key secondary outcome; therefore, results will not be disclosed.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Number of Follicles on Stimulation Day 8
Description	This is not a prespecified key secondary outcome; therefore, results will not be disclosed.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Number of Follicles on Day of hCG
Description	This is not a prespecified key secondary outcome; therefore, results will not be disclosed.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Number of Fertilized (2PN) Oocytes
Description	This is not a prespecified key secondary outcome; therefore, results will not be disclosed.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Number of Good Quality Embryos
Description	This is not a prespecified key secondary outcome; therefore, results will not be disclosed.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Oral Contraceptive		Non-Oral Contraceptive
Arm/Group Description	Use of oral contraceptive pills prior to controlled ovarian stimulation		No use of oral contraceptive pills prior to controlled ovarian stimulation
All Cause Mortality
	Oral Contraceptive		Non-Oral Contraceptive
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Oral Contraceptive		Non-Oral Contraceptive
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/209 (4.8%)		9/199 (4.5%)
Gastrointestinal disorders
Colitis ulcerative	1/209 (0.5%)	1	0/199 (0%)	0
Pancreatitis	1/209 (0.5%)	1	0/199 (0%)	0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/209 (0%)	0	1/199 (0.5%)	1
Antepartum haemorrhage	1/209 (0.5%)	1	0/199 (0%)	0
Ectopic pregnancy	2/209 (1%)	2	2/199 (1%)	2
Retroplacental haematoma	1/209 (0.5%)	1	1/199 (0.5%)	1
Ruptured ectopic pregnancy	2/209 (1%)	2	1/199 (0.5%)	1
Reproductive system and breast disorders
Ovarian cyst	0/209 (0%)	0	1/199 (0.5%)	1
Ovarian cyst ruptured	1/209 (0.5%)	1	0/199 (0%)	0
Ovarian hyperstimulation syndrome	2/209 (1%)	2	3/199 (1.5%)	3
Surgical and medical procedures
Abortion induced	1/209 (0.5%)	1	0/199 (0%)	0
Other (Not Including Serious) Adverse Events
	Oral Contraceptive		Non-Oral Contraceptive
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	88/209 (42.1%)		81/199 (40.7%)
Gastrointestinal disorders
Nausea	8/209 (3.8%)	8	15/199 (7.5%)	18
Injury, poisoning and procedural complications
Procedural pain	53/209 (25.4%)	55	45/199 (22.6%)	45
Nervous system disorders
Headache	17/209 (8.1%)	23	12/199 (6%)	12
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	8/209 (3.8%)	8	12/199 (6%)	12
Antepartum haemorrhage	11/209 (5.3%)	14	9/199 (4.5%)	13
Reproductive system and breast disorders
Ovarian hyperstimulation syndrome	5/209 (2.4%)	5	11/199 (5.5%)	11
Pelvic discomfort	20/209 (9.6%)	21	14/199 (7%)	16
Pelvic pain	18/209 (8.6%)	20	14/199 (7%)	14

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor recognizes the right of the investigator(s) to publish, but all communication concerning the clinical trial must be based on data validated and released and will first be submitted to the Sponsor for written consent, which shall not be withheld unreasonably. Sponsor is free to use the data for publication. The investigator(s) may be invited to be co-author(s). In any communication concerning this clinical trial, the author(s) of this protocol will be included in the list of authors.