A Phase II Study to Assess the Efficacy and Safety of Luveris® (Lutropin Alfa) in Mid Follicular Phase for Controlled Ovarian Stimulation (COS) in Advanced Reproductive Age

Summary

Ovarian reserve is related to chronological age; 35 years of age is the accepted threshold for significant decline in assisted reproductive technologies (ART) success with scarce follicular recruitment and poor oocyte retrieval. New therapeutic schemes are sought to improve follicular response in ovarian ageing because of the increasing number of infertile women aged older than 35 years who are trying to get pregnant. The advent of gonadotropin releasing hormone analogue antagonist (GnRHant) offers new perspectives to address the issues related to advanced reproductive age since it prevents premature luteinizing hormone (LH) surges while not causing suppression in the early follicular phase. Gonadotropin releasing hormone analogue antagonists are administered in the latter stage of the ovarian stimulation to prevent LH surge by competitive blockade of gonadotropin releasing hormone (GnRH) receptors, thus producing a marked decrease in LH levels just when the interplay between follicle stimulating hormone (FSH) and LH becomes important to complete follicular development and oocyte competence. Some studies in the past have shown the potential of recombinant human LH (r-hLH) supplementation in women of advanced reproductive age to improve oocyte quality, but these studies are of small size and did not provide data on the physiological mechanism behind the benefit obtained.

This randomized, comparative, parallel controlled Phase II study will be conducted in infertile female subjects aged 35-42 years undergoing in-vitro fertilization (IVF)/intra cytoplasmic sperm injection (ICSI), to investigate whether the addition of r-hLH (when the lead follicle is greater than \[\>\] 14 millimeter \[mm\] in size), to the standard protocol with recombinant human FSH (r-hFSH) under GnRHant, improves the number and quality of oocytes retrieved, implantation rate, and pregnancy rate, while assessing the hormonal milieu in the ovarian follicular fluid. Comparison will be performed against ovarian stimulation without addition of r-hLH, that is (i.e.) with r-hFSH under GnRHant alone.

Conditions

• Infertility
• Ovulation Induction

Interventions

DRUG

r-hLH + r-hFSH

Recombinant human follicle stimulating hormone (r-hFSH) injection will be administered subcutaneously once daily from stimulation Day 1(S1) at a starting dose of 300-450 International Unit (IU) and then dose adjusted depending on the ovarian response till recombinant human choriogonadotropin (r-hCG) administration day. Recombinant human luteinizing hormone (r-hLH, Luveris®, Lutropin alfa) injection will be administered subcutaneously once daily at a constant dose of 150 IU with flexible start, depending on the follicular growth (when the lead follicle is greater than 14 mm in size), along with r-hFSH treatment as a separate injection till r-hCG administration day.

DRUG

r-hFSH

Recombinant human follicle stimulating hormone (r-hFSH) injection will be administered subcutaneously once daily from S1 at a starting dose of 300-450 IU and then dose adjusted depending on the ovarian response till r-hCG administration day.

DRUG

Recombinant Human Choriogonadotropin (r-hCG)

The r-hCG will be administered as a single dose of 250-500 microgram (mcg) subcutaneously in the same day after the last dose of the GnRH antagonist.

DRUG

GnRH antagonist

The GnRH antagonist will be administered at a starting at a dose of 0.25 milligram (mg) subcutaneously daily in the morning when the ultrasound discovers a follicle of greater than or equal to (\>=) 14 mm, and maintained until at least one follicle of \>=18 mm and two additional follicles of \>=16 mm with appropriate plasma estradiol levels for the number and size of the existing follicles.

Sponsors & Collaborators

• Merck, S.L., Spain

  collaborator INDUSTRY

• Merck KGaA, Darmstadt, Germany

  lead INDUSTRY

Principal Investigators

• Medical Responsible · Merck, S.L., Spain

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

35 Years

Max Age

42 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-11-30

Primary Completion

2010-10-31

Completion

2010-10-31

Countries

• Spain

Study Locations