Clinical trial NCT02437032: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Infertility
Keywords: GDF-9
BMP-15
Steroids
Apoptosis rate
Endocrinology
Lead sponsor: IVI Madrid
Sponsor class: OTHER
First posted: 2015-05-07
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: GDF-9 and BMP-15 secretion
timeFrame: 3 years
Secondary outcomes:
measure: Steroids levels in follicular fluid (estradiol, progesterone, testosterone, FSH)
timeFrame: 3 years
measure: Apoptotic rate in cumulus cells
timeFrame: 3 years
Other outcomes:
Locations:
Study officials:
affiliation: IVI Madrid
name: Antonio Requena, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.