Study to Evaluate if the Addition of r-hLH (Luveris®) to FSH From Day 8 of Ovarian Stimulation is Able to Decrease Total FSH Dose and to Improve Cycle Outcome in Infertile Women Undergoing ART, Who Required High FSH Dose in a Previous Cycle
Information source: Merck KGaA
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Reproductive Techniques, Assisted
Intervention: Recombinant human Follicle Stimulating Hormone (r-hFSH) and Recombinant human Luteinizing Hormone (r-hLH) (Drug); r-hFSH (Drug)
Phase: Phase 3
Status: Terminated
Sponsored by: Merck KGaA Official(s) and/or principal investigator(s): Salvatore Longobardi, Study Director, Affiliation: Merck Serono S.P.A., Italy
Summary
The present study was designed to investigate, in hyporesponder subjects, that required in a
previous assisted reproductive technologies (ART) cycle follicle stimulating hormone (FSH)
>3500 International Unit (IU), the possibility to decrease through recombinant human
luteinizing hormone (r-hLH) supplementation, the FSH amount per oocytes retrieved and in the
mean time to improve the overall cycle outcome.
Clinical Details
Official title: A Phase III, Multicentric, Randomized, Open, Comparative Study to Evaluate if the Addition of Recombinant Human Luteinising Hormone [r-hLH (Luveris®)] to Follicle Stimulating Hormone (FSH) From Day 8 of Ovarian Stimulation is Able to Decrease Total FSH Dose and to Improve Cycle Outcome in Infertile Women Undergoing Assisted Reproduction Technology (ART), Who Required High FSH Dose in a Previous Cycle
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Total Dose of Follicular Stimulating Hormone (FSH) for Retrieved Oocytes
Secondary outcome: Mean Total Follicle Stimulating Hormone (FSH) and Recombinant Human Luteinizing Hormone (r-hLH) DoseMean Number of Ovarian Stimulation Days Change From Baseline in Oestradiol (E2) Levels at Human Choriogonadotropin (hCG) Day Mean Total Number of Retrieved Oocytes Mean Number of Mature Oocytes (Metaphase II) Fertilization Rate Number of Obtained Embryos Number of Transferred Embryos Percentage of Participants With Pregnancy Percentage of Participants With Clinical Pregnancy Percentage of Participants With Implantation Number of Participants With Ovarian Hyper Stimulation Syndrome (OHSS) Number of Cycles Cancelled Due to Risk of OHSS
Detailed description:
Recombinant human follicle stimulating hormone (r-hFSH), which totally lacks LH activity, is
widely used to induce multiple follicle development in women under pituitary
desensitization, in order to submit them to treatment with assisted reproduction techniques
(ART). Clinical experience from hypogonadotropic-hypogonadic women suggests that while FSH
alone is sufficient to induce follicle development, LH plays a significant part in final
follicle maturation, estrogen synthesis and optimal endometrium growth.
This was a phase III, multicentre, randomized, open-label comparative study to evaluate if
the addition of r-hLH (Luveris) in a 2: 1 ratio to FSH from day 8 of ovarian stimulation is
able to decrease the total FSH dose and to improve cycle outcome in 250 infertile women
undergoing ART, who required high FSH dose in a previous cycle (≥ 3500 IU). Subjects who
have met all the inclusion criteria, achieved pituitary desensitization and started
controlled ovarian hyperstimulation (COH) treatment with FSH, on stimulation day 8 (S8)
received an identification number and will be allocated to one of the two following arms:
Arm : FSH + r-hLH (2: 1 ratio of FSH: r-hLH), Arm : FSH alone. Treatment with Luveris was
commenced on day 8 (S8) and continued until injection of hCG or cancellation of the
treatment cycle.
Monitoring of stimulation, FSH dose escalation, criteria for injection of hCG, ovum pick up,
embryo transfer and pregnancy confirmation took place according to standard management
practice. The in-vitro fertilization (IVF) or intracytosolic sperm injection (ICSI)
procedure, including luteal phase support, was performed according to each centres' normal
procedures.
The subjects were followed up and the treatment outcome (menstruation or pregnancy) was
recorded. The delivery outcome for any pregnant subjects was recorded in the Case Report
Form (CRF).
Information on the delivery outcome for each pregnancy was collected. Information on adverse
events was collected during the study period.
OBJECTIVES
The primary objective of the study was:
To determine whether the addition of r-hLH (Luveris) from day 8 of ovarian stimulation
reduces the FSH dose needed to obtain/retrieve each oocyte.
The secondary objectives of the study were:
- To determine whether the addition of Luveris to FSH at day 8 of ovarian stimulation
improves cycle outcome based on secondary endpoints
- To determine the safety of Luveris in this indication
Eligibility
Minimum age: 18 Years.
Maximum age: 40 Years.
Gender(s): Female.
Criteria:
Inclusion Criteria:
- Pre-menopausal infertile woman, aged 18 to 40 years inclusive, who wishes to conceive
- Regular, spontaneous menstrual cycle of 25-35 days
- Body mass index (BMI) ≤ 28
- FSH ≤ 10 IU/L (follicular phase, days 2-5)
- Prolactin (PRL) within the normal ranges
- Evidence of both ovaries by ultrasound scan
- Women undergoing IVF-Embryo Transfer (ET) or ICSI, down regulated with Gonadotropin
releasing hormone analogues (GnRHa) (daily dose) under controlled ovarian
hyperstimulation (COH) with FSH
- Washout > 90 days from last dose of clomiphene or gonadotrophin, before ongoing COH
cycle
- Only one previous IVF-ET or ICSI cycle (in the last 9 months preceding the ongoing
COH cycle) resulted in a hypo-response properly documented (from 6 to 12 oocytes with
a total FSH dose ≥ 4000 IU)
- Negative pregnancy hCG test (urine or blood sample) before the ongoing COH cycles
- Willing and able to comply with the protocol for the duration of the study
- Written informed consent before applying any procedure related to the study protocol,
which is not part of routine medical care, with the understanding that consent may be
withdrawn by the subject at any time, without prejudice on their future medical care
Exclusion Criteria:
- Oligo/Anovulatory cycles (World Health Organization [WHO] I and II)
- Male partner azoospermia (assessed within the last 12 months)
- Follicular phase (day 2-5) FSH > 10 IU/L even if only once observed in the medical
history
- Abnormal cervical cytology (assessed within the last 12 months)
- History of unexplained gynecologic hemorrhage
- Any contraindication to pregnancy
- Known allergy to gonadotrophin
- Any clinically important systemic disease (e. g. insulin-dependent diabetes mellitus,
epilepsy, serious migraine, intermittent purpura, hepatic, renal or cardiovascular
disease, serious corticoid-dependent asthma) which constitutes a contraindication to
gonadotropin use
- Any medical condition which, according to the investigator's judgement, may affect
the absorption, distribution, metabolism or excretion of the drug. In case of doubt,
inclusion of the subject in question should be discussed with the Medical Responsible
of Serono
- Known Human Immunodeficiency Virus (HIV) positivity
- Any substance abuse or history of drugs or alcohol abuse within the past 5 years
- Prior inclusion in the present study or simultaneous inclusion in a clinical study of
another drug
- Refusal or inability to comply with the protocol
Locations and Contacts
Merck Serono S.p.A., Roma, Italy
Additional Information
Starting date: March 2005
Last updated: December 2, 2013
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