Gonadotropin Type in Ovarian Stimulation

Sponsor

IVI Madrid (Other)

Overall Status

Completed

CT.gov ID

NCT02437032

Collaborator

(none)

100

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Infertility	Drug: recombinant FSH Drug: Urinary FSH Drug: hMG	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

100 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2009

Actual Primary Completion Date :

Sep 1, 2012

Actual Study Completion Date :

Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group 1: recombinant FSH 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 Controlled ovarian stimulation with 150-300 UI recombinant FSH Other Names: Gonal-F
Active Comparator: Group 2:urinary FSH 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 Controlled ovarian stimulation with 150-300 UI urinary FSH Other Names: Fostipur
Active Comparator: Group 3: with hMG 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 Controlled ovarian stimulation with 150-300 UI hMG Other Names: hMG-Lepori

Arm

Intervention/Treatment

Active Comparator: Group 1: recombinant FSH

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

Controlled ovarian stimulation with 150-300 UI recombinant FSH

Other Names:

Gonal-F

Active Comparator: Group 2:urinary FSH

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

Controlled ovarian stimulation with 150-300 UI urinary FSH

Other Names:

Fostipur

Active Comparator: Group 3: with hMG

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

Controlled ovarian stimulation with 150-300 UI hMG

Other Names:

hMG-Lepori

Outcome Measures

Primary Outcome Measures

GDF-9 and BMP-15 secretion [3 years]
To measure GDF-9 (ng/ml) and BMP-15 (micrograms/microliter)

Secondary Outcome Measures

Steroids levels in follicular fluid (estradiol, progesterone, testosterone, FSH) [3 years]
To measure estradiol (pg/ml), progesterone (ng/ml), FSH (mUI/ml) and testosterone (ng/ml)
Apoptotic rate in cumulus cells [3 years]
To measure early and late apoptotic rate (%)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 35 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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