Clinical trial NCT01071200
Conditions: Reproductive Techniques, Assisted
Keywords: Reproductive Techniques, Assisted Recombinant human follicle stimulating hormone (r-hFSH) Recombinant leutinizing hormone (r-hLH)
Sponsor: Merck KGaA, Darmstadt, Germany
Start date: 2005-03-01; Completion date: 2009-04-01
Enrollment: 133 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

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

Arms: arm 1: Subjects treated with r-hFSH and r-hLH (2:1 ratio of r-hFSH:r-hLH) arm 2: Subjects treated with r-hFSH alone
Interventions: intervention 1: Recombinant human Follicle Stimulating Hormone (r-hFSH) and Recombinant human Luteinizing Hormone (r-hLH) intervention 2: r-hFSH
Intervention descriptions: intervention 1: One r-hFSH and one r-hLH injection subcutaneously (s.c.) once daily during the treatment phase from Day 8 of stimulation until injection of human chorionic gonadotropin (hCG) or cancellation of the treatment cycle. intervention 2: One r-hFSH injection s.c. once daily during the treatment phase from Day 8 of stimulation until injection of hCG or cancellation of the treatment cycle.

Protocol documents: