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

Sponsor

Rigshospitalet, Denmark (Other)

Overall Status

Completed

CT.gov ID

NCT01250821

Collaborator

Holbaek Sygehus (Other)

Enrollment

Location

Arm

Duration (Months)

2.7

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Anovulation Infertility	Drug: Menopur	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

75 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2010

Actual Primary Completion Date :

Dec 1, 2012

Actual Study Completion Date :

Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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.

Arm

Intervention/Treatment

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Endocrinological characteristics and follicular dynamics of anovulatory infertility WHO Group II [35 days]
Prediction of FSH response in anovulatory infertility WHO Group II based on endocrinology, sonography, FSH-receptor status and demography

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 39 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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.