Gene-polymorphisms Relating to Human Subfertility

Analysis of Gene-polymorphisms Relating to Human Subfertility: Estradiol-receptor-polymorphism and Progesterone-receptor-polymorphism

Estradiol is synthesized by granulosa cells of ovaries under control of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). It is known that Estradiol plays a crucial role in maturation and fertilization of oocytes. Furthermore it is involved in development of secondary female sexual organs, fertility and maintenance of pregnancy.

Estradiol influences these processes by binding to estradiol receptors (ER). They are ligand-depending transcription-factors. In humans there are two subtypes: ERa and ERb, which are synthetized from gene ESR1 on chromosome 6 and ESR2 on chromosome 14. Both subtypes are expressed in the ovary. Both genes are polymorph. Especially for ERa subtype several polymorphisms and mutations are known which can be linked to breast cancer, spontaneous abortions, osteoporosis and the point in time of menarche. Furthermore some studies have shown a relationship between certain polymorphisms and the risk of infertility associated gynecological malfunctions and the result of IVF treatments.

Progesterone is a hormone which plays a crucial role in initiation and maintenance of pregnancy. It induces the transformation of the endometrium, which facilitates the implantation of the fertilized oocyte and supports the pregnancy. Progesterone acts by binding to its receptor. The gene for this receptor is polymorph within the population, whereas some variants seem to account for implantation failure of embryos.

In the investigators study the investigators will analyse the role of ERP and PRP polymorphisms in the context of IVF treatment. The analyzed genotypes are two polymorphisms of ESRI, called Pvu and Xba, as well as a variant of ESRII, ER2. In the progesterone receptor gene a single nucleotide exchange at position +331 (G->A) plays a role.

The parameters correlated with are concentrations of estradiol, progesterone and FSH, number of follicles, number of fertilized oocytes and pregnancy rate.

The investigators hope to optimize established treatment protocols and to improve the chances of success of IVF treatments depending on the genotype of the patient.

Study Overview

• Status: Completed
• Conditions: IVF; Subfertility; Estradiol Receptor Polymorphism; Progesterone Receptor Polymorphism

• Study Type: Observational
• Enrollment (Actual): 150

Contacts and Locations

Study Locations

• Germany
  • NRW
    • Dortmund, NRW, Germany, 44135
      • Infertility treatment center Dortmund

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Female patients at reproductive age seeking IVF treatment

Description

Inclusion Criteria:

• IVF/ ICSI treatment with hormonal stimulation
• reproductive age
• high response OR low response OR male subfertility

Exclusion Criteria:

• other fertility treatments like IUI or timed intercourse

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
high responder; females with >15 follicles or E2>3000 after treatment with gonadotropins
low responder; patients with <3 follicles or no response to treatment with gonadotropins
control; females with an indication for treatment because of male subfertility

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
genetic testing for two estrogene receptor genes, correlating to numbers of oocytes retrieved at oocyte punction after hormonal stimulation	30.06.2013

Collaborators and Investigators

• Sponsor: Infertility Treatment Center Dortmund
• Collaborators: Weill Medical College of Cornell University
• Investigators: Principal Investigator: Andreas Neuer, Infertility treatment center Dortmund

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: June 29, 2011
• First Submitted That Met QC Criteria: June 29, 2011
• First Posted (Estimate): June 30, 2011

Study Record Updates

• Last Update Posted (Estimate): March 25, 2015
• Last Update Submitted That Met QC Criteria: March 24, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: PRP-ERP2010