Predicting Ovarian Response in Artificial Insemination With Low Stimulation

• Conditions: Subfertility
• Interventions: Drug: Follicle Stimulating Hormone

• Registration Number: NCT01662180
• Lead Sponsor: Isala

Brief Summary

This large prospective multi-center cohort study aims to identify patient's characteristics that significantly influence ovarian response to mild stimulation with a fixed dose of 75 IU recombinant FSH.

Detailed Description

A multi-center, open-label, prospective cohorts study. Patients with a regular indication for COH/IUI (controlled ovarian stimulation/ intra uterine insemination) will be asked to participate. Patient's characteristics will be documented including age, weight, BMI, smoking status, cycle day 2 3 or 4 FSH /Estradiol levels, antral follicle count, and AMH. AMH and FSH/Estradiol will be determined centrally after completion of inclusion of all patients in the study. All patients will receive a fixed 75 IU recFSH per day conform normal stimulation protocol starting from cycle day 3, 4 or 5 after exclusion of ovarian cysts by ultrasound. Ovarian response will be documented by ultrasound only. Once the dominant follicle(s) reach a mean diameter of 16-18 mm, hCG (5000IU or 250 mcg) will be applied and insemination will be scheduled 36-42 hours later. Cancellation criteria will be defined according to the national guidelines provided by the NVOG (7).

Study Timeline

• Study First Submitted: 2012-07-26
• Study First Submitted QC: 2012-08-07
• Study First Posted: 2012-08-10
• Status Verified: 2012-12
• Study Start: 2012-12
• Last Update Submitted: 2012-12-12
• Last Update Posted: 2012-12-13
• Primary Completion: 2014-09
• Study Completion: 2015-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 510

Inclusion Criteria

• couples with unexplained or mild male subfertility (1-3) and a spontaneous chance of conception below 40% (Hunault score).
• Unexplained subfertility including minimal to mild endometriosis (AFS grade 1 or 2) is defined as the failure to conceive after at least one year of unprotected intercourse whereas the standard fertility work-up was unable to detect any factors that might influence fertility negatively.
• semen analysis should be normal according to the WHO guidelines (8),
• ovulation should be documented (by BBT charts, ovulation detection by ultrasound or normal luteal progesterone values),
• tubal patency should be confirmed (HSG, laparoscopy or fertiloscopy) and when a postcoital test was performed a cervical factor should have been excluded.
• Mild male subfertility is defined as abnormal semen parameters according to the WHO (8) but an average total motile sperm account before processing of at least 10 million.

Exclusion Criteria

• Hunault score ≥ 40%
• Endometriosis AFS grade 3 or 4
• Contra-indications for the use of gonadotrophins (cysts larger than 2 cm, allergy for gonadotrophins)
• Total motile sperm count after sperm processing below 1 million
• Women aged younger than eighteen years or older than 45 years.
• Previous treatment with COH/IUI for treating current subfertility
• Unable to speak or read the Dutch language

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Subfertile couples	Follicle Stimulating Hormone	Subfertile couples presenting at fertility clinics with an indication for IUI in stimulated cycles All patients will receive a fixed 75 IU recombinant follicle stimulating hormone per day conform normal stimulation protocol starting from cycle day 3, 4 or 5. Once the dominant follicle(s) reach a mean diameter of 16-18 mm, hCG (5000IU or 250 mcg) will be applied and insemination will be scheduled 36-42 hours later. Patients will be followed for the time of one menstrual cycle.

Primary Outcome Measures

Name	Time	Method
To assess the relationship between AMH serum levels and ovarian response	one menstrual cycle, one month	(defined by the number of dominant follicles \>15mm) in IUI cycles stimulated with a fixed dose of 75 IU recFSH. All follicles \> 11 mm will be documented

Secondary Outcome Measures

Name	Time	Method
Pregnancy rate per started cycle.	three months	From start of the menstrual cycle until a positive heartbeat registered at 12 weeks of gestation.
Cancellation rate per stimulated cycle	one menstrual cycle, one month
To assess the relationship between age, weight, BMI, smoking, AFC, FSH/E2 on CD3 and ovarian response	one menstrual cycle, one month	(defined by the number of dominant follicles \>15mm) in IUI cycles stimulated with a fixed dose of 75 IU recFSH.
Multiple pregnancy rate per started cycle.	three months	From start of the menstrual cycle until positive heartbeats registered at 12 weeks of gestation.
Miscarriage rate per started cycle.	five months	miscarriage up to 16 weeks of gestation

Trial Locations

Locations (7)

OLVG; 🇳🇱 Amsterdam, Po 95500, Netherlands

Isala Klinieken; 🇳🇱 Zwolle, PO Box 10400, Netherlands

Catharina Ziekenhuis; 🇳🇱 Eindhoven, PO box 1350, Netherlands

AMC; 🇳🇱 Amsterdam, PO box 22660, Netherlands

VUMC; 🇳🇱 Amsterdam, PO box 7057, Netherlands

UMC Utrecht; 🇳🇱 Utrecht, PO box 85500, Netherlands

st Elizabeth Gasthuis; 🇳🇱 Tilburg, PO box 90151, Netherlands