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Gonadotropin Type in Ovarian Stimulation

Primary Purpose

Infertility

Status

Completed

Phase

Phase 4

Locations

Study Type

Interventional

Intervention

recombinant FSH

Urinary FSH

hMG

About this trial

This is an interventional treatment trial for Infertility focused on measuring GDF-9, BMP-15, Steroids, Apoptosis rate, Endocrinology

Eligibility Criteria

18 Years - 35 Years (Adult)FemaleAccepts Healthy Volunteers

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:

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Arm Label

Group 1: recombinant FSH

Group 2:urinary FSH

Group 3: with hMG

Arm Description

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

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.

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.

Outcomes

Primary Outcome Measures

GDF-9 and BMP-15 secretion

To measure GDF-9 (ng/ml) and BMP-15 (micrograms/microliter)

Secondary Outcome Measures

Steroids levels in follicular fluid (estradiol, progesterone, testosterone, FSH)

To measure estradiol (pg/ml), progesterone (ng/ml), FSH (mUI/ml) and testosterone (ng/ml)

Apoptotic rate in cumulus cells

To measure early and late apoptotic rate (%)

Full Information

NCT ID

NCT02437032

First Posted

November 21, 2014

Last Updated

May 4, 2015

Sponsor

IVI Madrid

1. Study Identification

Unique Protocol Identification Number

NCT02437032

Brief Title

Gonadotropin Type in Ovarian Stimulation

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2015

Overall Recruitment Status

Completed

Study Start Date

April 2009 (undefined)

Primary Completion Date

September 2012 (Actual)

Study Completion Date

December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

IVI Madrid

4. Oversight

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Infertility

Keywords

GDF-9, BMP-15, Steroids, Apoptosis rate, Endocrinology

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

100 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1: recombinant FSH

Arm Type

Active Comparator

Arm Description

Arm Title

Group 2:urinary FSH

Arm Type

Active Comparator

Arm Description

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.

Arm Title

Group 3: with hMG

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

recombinant FSH

Other Intervention Name(s)

Gonal-F

Intervention Description

Controlled ovarian stimulation with 150-300 UI recombinant FSH

Intervention Type

Drug

Intervention Name(s)

Urinary FSH

Other Intervention Name(s)

Fostipur

Intervention Description

Controlled ovarian stimulation with 150-300 UI urinary FSH

Intervention Type

Drug

Intervention Name(s)

hMG

Other Intervention Name(s)

hMG-Lepori

Intervention Description

Controlled ovarian stimulation with 150-300 UI hMG

Primary Outcome Measure Information:

Title

GDF-9 and BMP-15 secretion

Description

To measure GDF-9 (ng/ml) and BMP-15 (micrograms/microliter)

Time Frame

3 years

Secondary Outcome Measure Information:

Title

Steroids levels in follicular fluid (estradiol, progesterone, testosterone, FSH)

Description

To measure estradiol (pg/ml), progesterone (ng/ml), FSH (mUI/ml) and testosterone (ng/ml)

Time Frame

3 years

Title

Apoptotic rate in cumulus cells

Description

To measure early and late apoptotic rate (%)

Time Frame

3 years

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

35 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Antonio Requena, PhD, MD

Organizational Affiliation

IVI Madrid

Official's Role

Principal Investigator

12. IPD Sharing Statement

Citations:

PubMed Identifier

18175787

Citation

Gilchrist RB, Lane M, Thompson JG. Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality. Hum Reprod Update. 2008 Mar-Apr;14(2):159-77. doi: 10.1093/humupd/dmm040. Epub 2008 Jan 5.

Results Reference

result

PubMed Identifier

17110397

Citation

Smitz J, Andersen AN, Devroey P, Arce JC; MERIT Group. Endocrine profile in serum and follicular fluid differs after ovarian stimulation with HP-hMG or recombinant FSH in IVF patients. Hum Reprod. 2007 Mar;22(3):676-87. doi: 10.1093/humrep/del445. Epub 2006 Nov 16.

Results Reference

result

PubMed Identifier

16740654

Citation

Orisaka M, Orisaka S, Jiang JY, Craig J, Wang Y, Kotsuji F, Tsang BK. Growth differentiation factor 9 is antiapoptotic during follicular development from preantral to early antral stage. Mol Endocrinol. 2006 Oct;20(10):2456-68. doi: 10.1210/me.2005-0357. Epub 2006 Jun 1.

Results Reference

result

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Gonadotropin Type in Ovarian Stimulation

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