Efficacy of Pergoveris in Aged IVF Patients

Study Overview
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Brief Summary
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To compare the efficacy between LH supplementation (Pergoveris) and non-LH supplementation (Follitropin alpha) in patients aged ≥ 35 years undergoing IVF treatment. Study hypothesis: Pergoveris (LH supplementation) is better than follitropin alpha (non-LH supplementation) for ovarian stimulation in aged IVF patients.

Detailed Description
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A randomized controlled single center study. Based on the difference of 19.1% in the clinical pregnancy rate between the two treatment groups, with and without LH supplementation, in a previous study, with 90% power and a 2-sided P-value of 0.05, the number of subjects required was 109 per group (total 218). The recruitment target was 120 subjects per group (total 240) to allow for dropouts. Eligible subjects were randomized in blocks of 4 via a computer generated random number list to either the Pergoveris arm or the follitropin alpha arm. Ovarian stimulation was performed by using GnRH antagonist protocol. Follitropin alfa (recombinant FSH) was administered on day 2 or day 3 of the menstrual cycle. The first FSH dose was determined according to each individual patient, based on the process as follows: AFC ≤ 6: 300 IU/day AFC 7-15: 225 IU/day AFC ≥ 16: 150 IU/day GnRH antagonist (Cetrotide, Merck-Serono) was administered on day 5 of FSH administration. Recombinant LH (in the form of Pergoveris) was supplemented from day 6 of FSH administration. Patients in the Pergoveris group would be administered a reduced dose of recombinant FSH (reduced by 150 IU/day) which was replaced with Pergoveris (150IU FSH + 75IU LH)/day. The Follitropin alpha group retained recombinant FSH. In both groups, if the number of developing follicles was inappropriate, the dose could be titrated depending on the physician's judgment. Monitoring the follicular development was performed by vaginal ultrasound probe, quantifying LH, estradiol and progesterone, starting from day 5 of FSH, based on the current processes of the hospital. OPU and embryo transfer: OPU was performed 36 hours after hCG administration. Embryos were transferred on day 2. Luteal phase support: daily vaginal progesterone Pregnancy testing and ultrasound: a pregnancy test was done 14 days after embryo transfer. Beta hCG > 5mIU/ml was considered positive. Fetal ultrasound was performed 3 weeks after a positive pregnancy test to verify clinical pregnancy.

Official Title
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A Randomized Controlled Trial to Compare the Efficacy Between Pergoveris and Follitropin Alfa in Ovarian Stimulation in Patients Aged ≥ 35 Years

Conditions
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Infertility

Intervention / Treatment
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* Drug: Pergoveris (FSH and LH)
* Drug: Follitropin alpha (FSH)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥ 35 years body mass index <28 kg/m2 had ≤ 3 previous IVF attempts receiving a GnRH-antagonist protocol agreement to participate in the study, and to disclose any medical events to the investigator. The subject must be willing and able to comply with the protocol requirements for the duration of the study. have given written informed consent with the understanding that the subject may withdraw consent at any time Exclusion Criteria: participating in another interventional clinical trial PCOS or WHO group 1 have uterine abnormalities have endocrine disorders such as hyperprolactinemia, thyroid disorders

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pergoveris (FSH and LH)<br>150 IU of recombinant FSH and 75 IU of recombinant LH (Pergoveris) daily subcutaneous injection | Drug: Pergoveris (FSH and LH)<br>* Drugs are injected subcutaneously everyday until ovarian follicles reach 17mm in diameter.<br>* Other names: Pergoveris;|
| Active Comparator: Follitropin alpha (FSH)<br>150 IU of recombinant FSH (follitropin alpha or Gonal-F) daily subcutaneous injection | Drug: Follitropin alpha (FSH)<br>* Drugs are injected subcutaneously everyday until ovarian follicles reach 17mm in diameter.<br>* Other names: Gonal-F;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical pregnancy | Clinical pregnancy is defined by the image gestational sac under ultrasonography. | 7 weeks after embryo transfer | 
| Live birth | Live birth is defined if a live newborn delivered. | at the time of delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total FSH international units (IU) used for stimulation | Calculate total number of IU of FSH used for stimulation at the last day of stimulation regime. | Measure at the time when stimulation finishes, eg. in average 10-11 days, maximum 20 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IVF, LH supplementation, ovarian stimulation, poor responder