Gonadotropin Type in Ovarian Stimulation

Study Overview
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Brief Summary
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A key challenge facing reproductive biologists is the integration of the knowledge about oocyte-secreted factors into coherent physiological mechanisms of how oocytes govern folliculogenesis, cumulus cell function, and oocyte and embryo development. Although key oocyte-secreted factors have been identified, understanding their modes of action is complicated by multiple interactions between maternal and oocyte signaling molecules, as well as the constantly changing state of physical interactions between the oocyte and its companion somatic cells during folliculogenesis. Thus, the investigators study aimed to determine if there is any relationship between different gonadotropin preparations and oocyte-secreted factor secretion, the endocrine pattern in follicular fluid, and the apoptotic rate in cumulus cells during controlled ovarian stimulation.

Detailed Description
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The follicular environment is primarily influenced by the type of gonadotropin the follicle is exposed to during the follicular phase. The role of gonadotropins has been especially important in improving the efficiency of in vitro fertilization. Several studies comparing the use of human menopausal gonadotropin (hMG) with recombinant follicle-stimulating hormone (rFSH) have found significant differences in the endocrinological profile and the follicular dynamics. These differences have been related to the human chorionic gonadotropin (hCG)-driven luteinizing hormone (LH) activity added to hMG. Moreover, differences in the proportion of acid residues in FSH molecules should be considered. On the other hand, the main physiological regulatory hormones of follicular survival are the gonadotropins. Suppression of serum gonadotropins leads to massive apoptosis of granulosa cells in developing follicles resulting in atresia; whereas, gonadotropin treatment of early antral and pre-ovulatory follicles prevents this unplanned apoptosis. However, studies using cultured rat granulosa cells have shown that treatments with FSH or LH/hCG are ineffective in preventing spontaneous apoptosis, suggesting neighboring theca cells and local factors produced in the ovary are important for regulation of follicle growth and atresia.

Official Title
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Type of Gonadotropin During Controlled Ovarian Stimulation Affects the Endocrine Profile in Follicular Fluid and Apoptotic Rate in Granulose Cells

Conditions
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Infertility

Intervention / Treatment
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* Drug: recombinant FSH
* Drug: Urinary FSH
* Drug: hMG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-35 years old regular menstrual cycles no hereditary or chromosomal diseases normal karyotype negative for sexually transmitted diseases at least seven antral follicles per ovary Exclusion Criteria: PCO

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

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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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1: recombinant FSH<br>An oral contraceptive pill (Microgynon30®, Bayer Hispania, Spain) was taken for a maximum of 21 days, starting on day 1-2 of the menses of the previous cycle. After a wash-period of five days after the last pill, donors started to receive daily doses of 150-300 UI of rFSH (Gonal-F®, Merck-Serono, Spain; n=30) depending on their age, body mass index (BMI) and ovarian response in previous cycles. Daily doses of 0.25 mg gonadotropin- releasing hormone antagonist cetrorelix (Cetrotide®, Merck-Serono, Spain) were started on day six of stimulation in each group. When at least three or more leading follicles reached a mean diameter of ≥18 mm, hCG (Ovitrelle®, 250 µg; Merck-Serono, Spain) was administered subcutaneously | Drug: recombinant FSH<br>* Controlled ovarian stimulation with 150-300 UI recombinant FSH<br>* Other names: Gonal-F;|
| Active Comparator: Group 2:urinary FSH<br>An oral contraceptive pill (Microgynon30®, Bayer Hispania, Spain) was taken for a maximum of 21 days, starting on day 1-2 of the menses of the previous cycle. After a wash-period of five days after the last pill, donors started to receive daily doses of 150-300 UI of urinary FSH (uFSH) (Fostipur®, Angelini, Spain; n=30) depending on their age, body mass index (BMI) and ovarian response in previous cycles. Daily doses of 0.25 mg gonadotropin- releasing hormone antagonist cetrorelix (Cetrotide®, Merck-Serono, Spain) were started on day six of stimulation in each group. When at least three or more leading follicles reached a mean diameter of ≥18 mm, hCG (Ovitrelle®, 250 µg; Merck-Serono, Spain) was administered subcutaneously. | Drug: Urinary FSH<br>* Controlled ovarian stimulation with 150-300 UI urinary FSH<br>* Other names: Fostipur;|
| Active Comparator: Group 3: with hMG<br>An oral contraceptive pill (Microgynon30®, Bayer Hispania, Spain) was taken for a maximum of 21 days, starting on day 1-2 of the menses of the previous cycle. After a wash-period of five days after the last pill, donors started to receive daily doses of 150-300 UI of hMG (HMG-Lepori®, Angelini, Spain; n=30) depending on their age, body mass index (BMI) and ovarian response in previous cycles. Daily doses of 0.25 mg gonadotropin- releasing hormone antagonist cetrorelix (Cetrotide®, Merck-Serono, Spain) were started on day six of stimulation in each group. When at least three or more leading follicles reached a mean diameter of ≥18 mm, hCG (Ovitrelle®, 250 µg; Merck-Serono, Spain) was administered subcutaneously, and transvaginal oocyte retrieval was performed 36 h later. | Drug: hMG<br>* Controlled ovarian stimulation with 150-300 UI hMG<br>* Other names: hMG-Lepori;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GDF-9 and BMP-15 secretion | To measure GDF-9 (ng/ml) and BMP-15 (micrograms/microliter) | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Steroids levels in follicular fluid (estradiol, progesterone, testosterone, FSH) | To measure estradiol (pg/ml), progesterone (ng/ml), FSH (mUI/ml) and testosterone (ng/ml) | 3 years | 
| Apoptotic rate in cumulus cells | To measure early and late apoptotic rate (%) | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GDF-9, BMP-15, Steroids, Apoptosis rate, Endocrinology