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

Status

Terminated

Phase

Phase 2

Enrollment

93 participants (actual)

Sponsor

Merck KGaA, Darmstadt, Germany · Industry

Design

Randomized · Open label (no masking)

Countries

1 country

Spain

Start

Nov 2007

Primary completion

Oct 2010

Completion

Oct 2010

First posted

3 Mar 2010 (estimated)

Last update posted

27 Feb 2014 (estimated)

Conditions

Infertility · Ovulation Induction

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.

• Experimental

  r-hLH + r-hFSH

• Active comparator

  r-hFSH

1. Number of Oocytes Retrieved

   Time frame · Ovum pick-up (OPU) day (34-38 hours post r-hCG day [end of stimulation cycle {approximately 9 days}])

   Registry description

   Number of oocytes retrieved per reporting group on the day of ovum pick-up (OPU) (34-38 hours post r-hCG day) was calculated. Oocyte retrieval is a technique used in in-vitro fertilization (IVF) in order to remove oocytes from the ovary of the female participant, enabling fertilization outside the body.

2. Number of Mature Oocytes Retrieved

   Time frame · OPU day (34-38 hours post r-hCG day [end of stimulation cycle {approximately 9 days}])

   Registry description

   Number of mature oocytes retrieved per reporting group on the day of OPU (34-38 hours post r-hCG day) was calculated. Oocyte retrieval is a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body. The nuclear maturity is assessed based on the presence of a germinal vesicle (GV) or whether oocytes were in metaphase I (Meta-I) or II (Meta-II) stage or atretic.

3. Number of Participants With Ovarian Hyper Stimulation Syndrome (OHSS)

   Time frame · S1 to 1 month ± 1 week post r-hCG day (end of stimulation cycle [approximately 9 days])

   Registry description

   Ovarian Hyper Stimulation Syndrome (OHSS) is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting.

4. Number of Cycles Cancelled Due to Risk of Ovarian Hyper Stimulation Syndrome (OHSS)

   Time frame · S1 to 1 month ± 1 week post r-hCG day (end of stimulation cycle [approximately 9 days])

   Registry description

   Ovarian Hyper Stimulation Syndrome (OHSS) is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting.

5. Number of Participants With Adverse Events (AEs)

   Time frame · S1 to 1 month ± 1 week post r-hCG day (end of stimulation cycle [approximately 9 days])

   Registry description

   An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.

No study cites this trial.