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

Infertility Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01250821
• Other study ID #: 2010-021459-16
• Status: Completed
• Phase: Phase 4
• First received: November 30, 2010
• Last updated: April 18, 2013
• Start date: December 2010
• Est. completion date: April 2013

Study information

• Verified date: April 2013
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines Agency
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: April 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 39 Years

Eligibility

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.

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anovulation
• Infertility

Intervention

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.

Locations

Country	Name	City	State
Denmark	The Fertility Clinic, Section 4071, Rigshospitalet	Copenhagen

Sponsors (2)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Holbaek Sygehus

Country where clinical trial is conducted

Denmark, 

References & 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. — View Citation

Platteau P, Andersen AN, Balen A, Devroey P, Sørensen 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. Epub 2006 Mar 29. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The proportion of patients who reach the criteria for hCG-administration within 14 days of FSH stimulation.	The HCG-criteria is defined as: One follicle with a diameter of >17 mm or two or three follicles > 15 mm (verified by transvaginal ultrasound).; HCG should not be given if there is no response after 35 days or > 4 follicles > 15 mm (unless converted to IVF/ICSI).; 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	Yes
Secondary	Endocrinological characteristics and follicular dynamics of anovulatory infertility WHO Group II	Prediction of FSH response in anovulatory infertility WHO Group II based on endocrinology, sonography, FSH-receptor status and demography	35 days	No