Gonadotropin Type in Ovarian Stimulation

Infertility Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02437032
• Other study ID #: MAD-GV-04-2009-01
• Status: Completed
• Phase: Phase 4
• First received: November 21, 2014
• Last updated: May 4, 2015
• Start date: April 2009
• Est. completion date: December 2012

Study information

• Verified date: May 2015
• Source: IVI Madrid
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: December 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 35 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infertility

Intervention

Drug:
• recombinant FSH
Controlled ovarian stimulation with 150-300 UI recombinant FSH
• Urinary FSH
Controlled ovarian stimulation with 150-300 UI urinary FSH
• hMG
Controlled ovarian stimulation with 150-300 UI hMG

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
IVI Madrid

References & Publications (3)

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. Review. — View 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. Epub 2006 Jun 1. — View 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. Epub 2006 Nov 16. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	GDF-9 and BMP-15 secretion	To measure GDF-9 (ng/ml) and BMP-15 (micrograms/microliter)	3 years	No
Secondary	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	No
Secondary	Apoptotic rate in cumulus cells	To measure early and late apoptotic rate (%)	3 years	No