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

NCT01250821 | Completed Phase 4 DMC

• 1 other identifier: 2010-021459-16
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Anovulation; Infertility

Keywords

Infertility; Anovulation; Ovulation induction

Outcome Measures

Primary Outcomes (1)

• The proportion of patients who reach the criteria for hCG-administration within 14 days of FSH stimulation.

  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.

  14 days of FSH stimulation

Secondary Outcomes (1)

• Endocrinological characteristics and follicular dynamics of anovulatory infertility WHO Group II

  35 days

Study Arms (1)

Ovulation induction

EXPERIMENTAL

Drug: Menopur

Interventions

Menopur DRUG

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.

Ovulation induction

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Anovulatory infertility
• Age 18 - 39 years
• Anovulation with oligomenorrhoea (\> 35 days of mean cycle length) or amenorrhoea
• Normal serum FSH (\< 10 IU/l)
• Two ovaries
• BMI \< 35
• First FSH/HMG cycle at the Fertility clinic.
• A sperm sample compatible with conception or semen from a donor.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Holbaek Sygehus: collaborator

Study Sites (1)

The Fertility Clinic, Section 4071, Rigshospitalet

Copenhagen, DK-2100, Denmark

Location

Related Publications (2)

• Nyboe Andersen A, Balen A, Platteau P, Devroey P, Helmgaard L, Arce JC; Bravelle Ovulation Induction (BOI) Study Group. Predicting the FSH threshold dose in women with WHO Group II anovulatory infertility failing to ovulate or conceive on clomiphene citrate. Hum Reprod. 2008 Jun;23(6):1424-30. doi: 10.1093/humrep/den089. Epub 2008 Mar 26.

  PMID: 18372254 BACKGROUND

• Platteau P, Andersen AN, Balen A, Devroey P, Sorensen P, Helmgaard L, Arce JC; Menopur Ovulation Induction (MOI) Study Group. Similar ovulation rates, but different follicular development with highly purified menotrophin compared with recombinant FSH in WHO Group II anovulatory infertility: a randomized controlled study. Hum Reprod. 2006 Jul;21(7):1798-804. doi: 10.1093/humrep/del085. Epub 2006 Mar 29.

  PMID: 16571641 BACKGROUND

MeSH Terms

Conditions

Anovulation; Infertility

Interventions

Menotropins

Condition Hierarchy (Ancestors)

Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Gonadotropins, Pituitary; Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Peptides; Amino Acids, Peptides, and Proteins; Biological Products; Complex Mixtures

Study Officials

• Mette P Lauritsen, MD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

• Anders N Andersen, Prof. MD

  Rigshospitalet, Denmark

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD student

Study Record Dates

• First Submitted: November 30, 2010
• First Posted: December 1, 2010
• Study Start: December 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: April 1, 2013
• Last Updated: April 19, 2013

Record last verified: 2013-04

Locations

DK (1)