Mild Versus Conventional Ovarian Stimulation Treatment for In Vitro Fertilization

Study Overview
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Brief Summary
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In vitro fertilization (IVF) is an assisted reproductive technique to achieve pregnancy in subfertile couples of which the average success rate is only 25%. Mild ovarian stimulation treatment yields less oocytes, has less adverse effects but has a comparable clinical outcome compared to conventional stimulation treatment. There is high inter- and intra person variability in ovarian response and fertility outcome parameters after stimulation treatment and little is known about explanatory variables herefore. Nutrition and in particular folate, or its synthetic derivative folic acid, is a B-vitamin which has been widely asssociated with reproductive outcome and subfertility. Therefore, in this study we aim to investigate the influence of preconception nutrition and folic acid use on ovarian response after mild/conventional stimulation treatment and to identify biomarkers in the follicular fluid which can indicate oocyte quality and other fertility outcomes.

Official Title
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Food Lifestyle and Fertility Outcome

Conditions
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Subfertility

Intervention / Treatment
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* Procedure: Mild Ovarian Stimulation Treatment
* Procedure: Conventional Ovarian Stimulation Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All couples with an indication for IVF/ICSI treatment in the Erasmus Medical Center Exclusion Criteria: Prior oocyte donation Endometriosis Hydrosalpinx MESA/PESA Age >37 BMI <18 or >29kg/m2 Menstrual cycle disruptions Indication for Intra Cytoplasmic Sperm Injection (ICSI) Prior IVF treatment without embryo transplant History of recurrent abortion Abnormal karyotype of male/female Uterine abnormalities

Ages Eligible for Study
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Maximum Age: 37 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Mild Ovarian Stimulation<br> | Procedure: Mild Ovarian Stimulation Treatment<br>* Administration of a fixed dose of 150 IU/day rFSH s.c. (Puregon® NV Organon, Oss, The Netherlands) from cycle day 5 onwards. As soon as the leading follicle reached a diameter of 14mm, a GnRH-antagonist (Orgalutran®, NV Organon, Oss, The Netherlands) was administered at 0.25 mg/day s.c.. To induce final oocyte maturation a single s.c. dose of 10.000 IE hCG (Pregnyl®, NV Organon. Oss, The Netherlands) was administered.<br>|
| Active Comparator: Conventional Ovarian Stimulation<br> | Procedure: Conventional Ovarian Stimulation Treatment<br>* Administration of GnRH agonist Triptorelin (Decapeptyl®, Ferring BV, Hoofddorp, The Netherlands) at 0.1 mg/day s.c., starting on cycle day 21 of the menstrual cycle preceding the actual stimulation cycle. After two weeks of the GnRH regimen, co-treatment with rFSH 225 IU/day s.c. (Puregon®, NV Organon, Oss, The Netherlands) was initiated. To induce final oocyte maturation a single s.c. dose of 10.000 IE hCG (Pregnyl®, NV Organon. Oss, The Netherlands) was administered<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endocrine, metabolic biomarkers and proteins and Fertility outcome parameters |  | At menstrual cycle day 2 before stimulation, on the day of hCG administration after stimulation treatment and after embryo transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Homocysteine-methionine cycle biomarker, endocrine and folate levels in serum |  | At menstrual cycle day 2 before stimulation and on the day of hCG administration after stimulation treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Folic Acid, Homocysteine, Ovarian response, In Vitro Fertilization