Gonadotrophin Dosage Using a Threshold Nomogram for Ovulation Induction in WHO Group II Anovulatory Infertility

This study has been completed.
Sponsor:
Collaborator:
Holbaek Sygehus
Information provided by (Responsible Party):
Mette Petri Lauritsen, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT01250821
First received: November 30, 2010
Last updated: April 18, 2013
Last verified: April 2013
  Purpose

Ovulation disorders are a common cause of infertility in women. Most of these women can be classified as World Health Organization (WHO) Group II anovulatory patients as they have irregular or absent menstrual cycles but normal serum concentrations of follicle stimulation hormone (FSH) and estradiol.

The purpose of this study is to optimize the low-dose-step-up protocol traditionally used for ovulation induction with follicle-stimulating hormone (FSH) in women with anovulatory infertility WHO Group II.

Previous studies have established that menstrual cycle history, mean ovarian volume and BMI are significant predictors of FSH threshold dose in women with anovulatory infertility WHO Group II undergoing ovulation induction (Nyboe Andersen et al., 2008). A FSH dosage nomogram has been constructed based on these variables.

The aim of this study is to evaluate the clinical use of the nomogram in order to test the use of the variables to determine whether an individualized starting dose of FSH can be used for ovulation induction in anovulatory patients.

It is the hypothesis that an individualized starting dose of gonadotrophin will minimize the disadvantages of the treatment and that the stimulation period of the individualized nomogram-based treatment will be 25% shorter than observed in the standard protocol.

The primary endpoint is the proportion of patients who reach the criteria for hCG-administration within 14 days of Menopur stimulation. The results of the study will be compared with the data obtained in the Menopur Ovulation Induction Trial (Platteau et al., 2006).


Condition Intervention Phase
Anovulation
Infertility
Drug: Menopur
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Gonadotrophin Dosage Using a Threshold Nomogram for Ovulation Induction in WHO Group II Anovulatory Infertility

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • The proportion of patients who reach the criteria for hCG-administration within 14 days of FSH stimulation. [ Time Frame: 14 days of FSH stimulation ] [ Designated as safety issue: Yes ]

    The HCG-criteria is defined as:

    1. One follicle with a diameter of >17 mm or two or three follicles > 15 mm (verified by transvaginal ultrasound).
    2. HCG should not be given if there is no response after 35 days or > 4 follicles > 15 mm (unless converted to IVF/ICSI).
    3. If a patient is seen with one to three follicles of 15 - 16 mms HCG can be administered on the same or on the next day due to a presumed growth of follicles of + 2 mm/day.


Secondary Outcome Measures:
  • Endocrinological characteristics and follicular dynamics of anovulatory infertility WHO Group II [ Time Frame: 35 days ] [ Designated as safety issue: No ]
    Prediction of FSH response in anovulatory infertility WHO Group II based on endocrinology, sonography, FSH-receptor status and demography


Enrollment: 75
Study Start Date: December 2010
Study Completion Date: April 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ovulation induction Drug: Menopur

The medication used in this study is the follicle-stimulating hormone "highly purified human menopausal gonadotrophin" (HP-HMG), Menopur, (Ferring a/s).

Stimulation with HP-hMG (Menopur) is started on day 2-5 of menstrual bleeding.The HP-hMG starting dose is calculated based on the nomogram predicting the threshold dose. The dose-range is from 75 IU/day to 187.5 IU/day.


  Eligibility

Ages Eligible for Study:   18 Years to 39 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Anovulatory infertility
  2. Age 18 - 39 years
  3. Anovulation with oligomenorrhoea (> 35 days of mean cycle length) or amenorrhoea
  4. Normal serum FSH (< 10 IU/l)
  5. Two ovaries
  6. BMI < 35
  7. First FSH/HMG cycle at the Fertility clinic.
  8. A sperm sample compatible with conception or semen from a donor.
  9. Tubal patency documented by either hysterosalpingography (HSG) or hysterosalpingography by ultrasound (HSU) in cases where the woman has had a pelvic infection or pelvic surgery.

Exclusion Criteria:

  1. A history of >12 ovulation induction cycles without achieving pregnancy.
  2. More than three earlier gonadotropin cycles at other clinics or earlier treatments with threshold doses below 75.
  3. Known hyperprolactinaemia or any other endocrine disturbance or systemic disease of the pituitary gland, thyroid gland, adrenal gland, pancreas, liver or kidney.
  4. Undiagnosed vaginal bleeding.
  5. Acute or chronic infection with HIV or hepatitis.
  6. Persistent ovarian cysts or endometriomas detected by ultrasound.
  7. Tumors of the hypothalamus, pituitary gland, breast, adrenal gland or ovary.
  8. Pregnancy or lactation.
  9. Current or past alcohol or drug abuse.
  10. A history of chemo- or radiotherapy.
  11. Malformations of reproductive organs incompatible with pregnancy.
  12. Hypersensitivity to any trial medication.
  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: NCT01250821

Locations
Denmark
The Fertility Clinic, Section 4071, Rigshospitalet
Copenhagen, Denmark, DK-2100
Sponsors and Collaborators
Rigshospitalet, Denmark
Holbaek Sygehus
Investigators
Principal Investigator: Mette P Lauritsen, MD Rigshospitalet, Denmark
Study Chair: Anders N Andersen, Prof. MD Rigshospitalet, Denmark
  More Information

Publications:
Responsible Party: Mette Petri Lauritsen, MD, PhD student, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT01250821     History of Changes
Other Study ID Numbers: 2010-021459-16
Study First Received: November 30, 2010
Last Updated: April 18, 2013
Health Authority: Denmark: Danish Medicines Agency

Keywords provided by Rigshospitalet, Denmark:
Infertility
Anovulation
Ovulation induction

Additional relevant MeSH terms:
Anovulation
Infertility
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Genital Diseases, Male
Menotropins
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on September 14, 2014