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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) Dose

Mean 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

Page last updated: August 23, 2015

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