Predicting Ovarian Response in Artificial Insemination With Low Stimulation

Study Overview
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Brief Summary
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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
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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).

Official Title
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Predicting Ovarian Response in Artificial Insemination With Low Stimulation

Conditions
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Subfertility

Intervention / Treatment
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* Drug: Follicle Stimulating Hormone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Subfertile couples<br>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. | Drug: Follicle Stimulating Hormone<br>* All patients will receive a fixed 75 IU rec follicle stimulating hormone per day subcutaneous injection stimulation protocol starting from cycle day 3, 4 or 5. The intervention done in this study is conform normal stimulation protocol and is not the target of this study.<br>* Other names: Gonal -F [Serono Benelux bv];|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the relationship between AMH serum levels and ovarian response | (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 | one menstrual cycle, one month | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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subfertility, IUI, rec FSH, FSH, E2, AMH