Efficacy and Safety of R-hLH (Luveris ®) Priming Prior to R-HFSH Treatment in Infertile Women Undergoing IVF-ET

This study has been completed.
Sponsor:
Information provided by:
NHS Greater Clyde and Glasgow
ClinicalTrials.gov Identifier:
NCT00441324
First received: February 27, 2007
Last updated: NA
Last verified: February 2007
History: No changes posted
  Purpose

In programmes of IVF, normal women undergo controlled ovarian stimulation using exogenous FSH injections to obtain multiple eggs. The process results in eggs of mixed quality with a broad range of developmental and implantation potential.

The aim of the study was to determine whether, treatment with recombinant human LH prior to the FSH injections can improve outcome for women undergoing IVF. High grade embryos implant with a higher frequency and baby delivery rate than poor quality embryos. The mature oocyte is the most important determinant of embryo quality. Early follicles, containing immature eggs, have LH receptors in the theca cells that surround the follicle, and LH stimulates these cells to produce factors essential for normal follicular development.

The intent of the study was to use recLH treatment prior to recFSH to treat a cohort of follicles, so that they can all mature together, thus increasing the proportion of high grade oocytes and their subsequent embryos


Condition Intervention Phase
Infertility
Procedure: recombinant human LH
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy and Safety of R-hLH (Luveris ®) Priming Prior to R-HFSH Treatment in Infertile Women Undergoing IVF-ET

Resource links provided by NLM:


Further study details as provided by NHS Greater Clyde and Glasgow:

Primary Outcome Measures:
  • Numbers of oocytes
  • Numbers of embryos
  • Numbers if high grade embryos

Secondary Outcome Measures:
  • Duration of FSH injections
  • Numbers of FSH injections

Estimated Enrollment: 160
Study Start Date: March 2003
Estimated Study Completion Date: February 2006
Detailed Description:

Normal women undergoing IVF (Total n = 146; GRI n = 43) were recruited in 4 centres in 3 countries, and all were started on treatment with a depo GnRH-agonist to suppress endogenous gonadotropin secretion. Block randomisation lead to a distribution 71 untreated cases and 75 cases treated with rec-hLH (Luveris,[Serono]; 300IU/d) for 7 days. On the following days recombinant follicle stimulating hormone (rec-hFSH) stimulation of the ovaries was initiated using Gonal-f (150IU/d) for approximately 12 days.

HCG (3500IU) was given when >2 mature follicles were seen by ovarian ultrasound, and oocytes (eggs) were fertilized in vitro after collection between 36 and 38h after the injection. Embryos were scored for quality, and a maximum of 2 embryos were transferred 2 or 3 days later.

Results During Luveris treatment the LH concentration was increased by approximately 3 IU/L, but there was no change in the hormone profiles of androgens or estrogens in blood samples measured in a central laboratory. Both groups of patients showed an increase in the circulating anti-mullerian hormone, although there was no difference between the groups.

The Luveris treated group showed a significant (p=0.007) increase in the number of small antral follicles, but to a degree that was not different from the control group.

During rec-hFSH stimulation, there was no difference in the duration of FSH injections required or the total dose, or the total number of follicles seen, or the hormone profiles observed.

The Luveris pre-treated group showed a slight (not significant) increase in oocyte yield. In this group there was a significant increase in the normally fertilized embryo yield (no treatment mean = 5.1; Luveris treatment mean = 7.0: p= 0.038).

Discussion The observations of negligible effects of LH upon the hormone profiles may be explained by the fact that the hormone concetrations were at the lower limit of sensitivity of the assay methods, and they do not preclude an effect within the follicles. We did observe effects upon follicular development in the ultrasound profiles. Effects upon hormone profiles may require both hormones (LH and FSH) to be present at the same time (instead of in sequence).

The small effect of the pre-treatment upon normal embryo yield may be an important observation.

Conclusion These results demonstrate that treating follicles with LH prior to FSH, may lead to the development of more viable follicles than with FSH treatment alone. This should lead to improved regimes of ovarian stimulation and improve the outcome potential for women undergoing IVF.

Future Research Exploration of this phenomenon will be required in order to maximise any potential benefit from the process. There are numerous sub-groups of patients who may possibly benefit, including poor responding patients, but further data are required.

  Eligibility

Ages Eligible for Study:   19 Years to 37 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • infertile undergoing IVF
  • normal menstrual rhythm

Exclusion Criteria:

  • polycystic ovaries
  • known resistance to FSH
  • other drug preparations
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00441324

Locations
Denmark
Fertility Clinic, Department of Obstetrics and Gynaecology, University Hospital of Odense, 5000
Odense, Denmark
France
Reproductive Medicine Unit, Department of Gynaecology and Obstetrics, Jean Verdier Hospital, University Paris XIII
Paris, France
United Kingdom
Assisted Conception Unit., Royal Infirmary of Edinburgh
Edinburgh, United Kingdom
Sponsors and Collaborators
NHS Greater Clyde and Glasgow
Investigators
Principal Investigator: Richard Fleming, PhD Greater Glasgow Health Board
  More Information

No publications provided by NHS Greater Clyde and Glasgow

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00441324     History of Changes
Other Study ID Numbers: RN03B001
Study First Received: February 27, 2007
Last Updated: February 27, 2007
Health Authority: Denmark: Danish Medicines Agency
France: Institutional Ethical Committee
United Kingdom: National Health Service

Keywords provided by NHS Greater Clyde and Glasgow:
Ovarian follicle
Thecal cells
Androgens
FSH sensitivity

Additional relevant MeSH terms:
Infertility
Genital Diseases, Male
Genital Diseases, Female

ClinicalTrials.gov processed this record on September 14, 2014