Perifollicular Vascularity Assessment in in-Vitro Fertilization

This study has been completed.
Sponsor:
Information provided by:
University Magna Graecia
ClinicalTrials.gov Identifier:
NCT00458380
First received: April 6, 2007
Last updated: April 9, 2007
Last verified: April 2007

April 6, 2007
April 9, 2007
September 2004
Not Provided
Ongoing pregnancy rate
Same as current
Complete list of historical versions of study NCT00458380 on ClinicalTrials.gov Archive Site
Implantation rate
Same as current
Not Provided
Not Provided
 
Perifollicular Vascularity Assessment in in-Vitro Fertilization
Clinical Use of the Perifollicular Vascularity Assessment in in-Vitro Fertilization Cycles: a Pilot Study

On February 2004, a law (n. 40/2004) regulating assisted reproduction techniques (ARTs) was approved in Italy. This law aimed to regulate the treatment of infertility in Italy, contains several restrictions, such as the prohibition to fertilize more than three oocytes and the obligation to transfer simultaneously all embryos obtained. Several evidences showed that the outcome of the in-vitro fertilization (IVF) techniques is strongly correlated with quality of transferred embryos (choosing the right embryos). Furthermore, this prerequisite is actually illegal in Italy, and an optimal oocyte selection can be considered as the only one crucial factor in the determining the outcome of the IVF cycle (choosing the right oocytes). Experimental data have demonstrated that perifollicular blood flow assessment is a good marker of oocyte competence, embryo viability, implantation potential, and subsequent pregnancy rate.

The purpose of this study will be to evaluate in a clinical setting whether the assessment of the perifollicular vascularity is a feasible and useful procedure for the selection of oocytes with the best developmental potential in IVF programs when only a limited number of oocytes can be fertilized.

One hundred fourteen women with tubal factor or unexplained infertility undergoing IVF programs in our department will be enrolled in a wild protocol. Successively, the enrolled patients will be divided into two different sub-protocols evaluating the role of the perifollicular vascularity in good- and poor-prognosis patients. The diagnosis will be established by hysterosalpingography and/or laparoscopic dye test and with partner’s semen analysis.

All patients will be randomly allocated in two independent groups (experimental and control groups) using a computer-software, and the random allocation sequence will be concealed in closed and dark envelope until the interventions will be assigned.

In the experimental group alone, a power Doppler assessment of perifollicular vascularity will be performed the day of oocyte retrieval (36 h after hCG injection). The vascularity of each ovulatory follicle will be successively studied using an advanced image analysis software and its extension will be graded using a well validated grading system. The periovulatory follicles will be categorized in high-grade (grades 3-4) and low-grade (grades 1-2).

After patient’ sedation with IV propofol, oocytes will be retrieved using a 17 G double-lumen aspiration needle with a low pressure and individually cultured marking the test-tube and, successively, the culture plate with a code corresponding to perifollicular vascularity degree. The retrieved oocytes will be washed and the mature oocytes, determined by the presence of a first polar body (metaphase II; MII oocytes), will be classified by an experienced biologist initially blinded to previous perifollicular vascularization. In particular, MII oocytes will be graded into three groups according to the number of anomalies: grade I, oocytes without any anomaly; grade II, oocytes with one anomaly; and grade III, oocytes with at least two anomalies.

The three oocytes with the highest grade will be considered “the best” oocytes to fertilize in the control group, whereas in the experimental group they will be selected integrating morphological and ultrasonographic criteria. In particular, the embryologist will use the ultrasonographic criteria to choice within oocytes with similar morphologic degree.

In both groups, three MII oocytes will be inseminated at 4 h after recovery with 10000-20000 motile sperm and placed in the CO2 incubator at a temperature of 37°C in 5% CO2 in air, and the fertilization will be evaluated 18 h later and confirmed by the presence of two pronuclei and two polar bodies. The fertilized oocytes will be classified with a well standardized scoring system for zygotes and cultured for a total of 48 h from oocytes IVF. Before transfer, the cleavage embryos will be again graded according to the embryo morphology and the relative proportion of anucleate fragments present in the zona pellucida.

All embryos, with exclusion of those arrested (not cleaved after 24 h from IVF), will be replaced in each patient without ultrasonographic guidance using ultrasoft Frydman catheter. The luteal phase will be supported by 100 mg natural progesterone daily administrated. A serum β-hCG assessment will be performed on 15th day after embryos transfer.

For each cycle, the serum estradiol levels and the number of dominant follicles on the day of hCG administration, the duration of ovarian stimulation, and the units of r-FSH administered will be recorded. The concordance between the ultrasonographic grading score and the oocyte degree will be also evaluated in each case.

Cancelled cycles (cases of absence of follicular response after 35 days of treatment or a serum E2 value >2500 pg/ml), fertilization (percentage of fertilized oocytes / total oocytes), implantation (percentage of intra-uterine gestational sacs / total transferred embryos), clinical (percentage of rising β-hCG with sonographic evidence of intrauterine gestational sac and fetal cardiac activity at 7 weeks of pregnancy / total non-cancelled cycles) and ongoing (percentage of vital pregnancies confirmed by ultrasonography at 12 weeks of gestational age / total non-cancelled cycles) pregnancies rates will be evaluated in each patients. The number of multiple pregnancies and ovarian hyperstimulation syndromes (OHSS) will be also recorded in both groups.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Diagnostic
Infertility
Procedure: Controlled ovarian stimulation, perifollicular vascularity assessment, IVF, embryo transfer.
Not Provided
Palomba S, Russo T, Falbo A, Orio F Jr, Manguso F, Nelaj E, Tolino A, Colao A, Dale B, Zullo F. Clinical use of the perifollicular vascularity assessment in IVF cycles: a pilot study. Hum Reprod. 2006 Apr;21(4):1055-61. Epub 2005 Dec 22.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
116
February 2005
Not Provided

Inclusion Criteria:

  • Women with tubal factor or unexplained infertility undergoing IVF programs.

Exclusion Criteria:

  • Body mass index (BMI, Kg/m2) <18 and >30
  • Peritoneal factor infertility
  • Polycystic ovaries (PCO)
  • Other organic pelvic diseases
  • Abnormal partner’s semen
  • Neoplastic, metabolic, endocrinological, hepatic, and cardiovascular disorders or other concurrent medical illness
  • Abuse of alcohol
  • Current or previous use of hormonal drugs
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Italy
 
NCT00458380
09/2004
No
Not Provided
University Magna Graecia
Not Provided
Principal Investigator: Stefano Palomba, MD Department of Obstetrics and Gynecology, University "Magna Graecia" of Catanzaro
University Magna Graecia
April 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP