Clinical trial NCT03345030: The Role of DNA Damage of Granulosa Cell on Oocyte Quality and in Vitro Fertilization Outcome
Official title: The Role of DNA Damage of Granulosa Cell on Oocyte Quality and in Vitro Fertilization Outcome
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: in Vitro Fertilization
Keywords: comet assay
DNA damage
granulosa
IVF outcome
Lead sponsor: Suleyman Demirel University
Sponsor class: OTHER
First posted: 2017-11-17
Enrollment: 60
Sex: FEMALE
Minimum age (years): 19
Maximum age (years): 44
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Unexplained infertile (UI) group UI was diagnosed after normal standard infertility evaluation according to the guideline of The Practice Committee of the American Society for Reproductive Medicine which consist of the assesment of spermiogram, ovulation, hysterosalpingogram and if indicated ovarian reserve tests and laparoscopy. If the results of all this tests were normal, patients were accepted as UI. Control group The control group received IVF for male infertility (except azoospermia and severe oligoasthenospermia) or tubal factor included only those women who had salpingectomy for ectopic pregnancy.

Brief summary: Deoxyribonucleic acid (DNA) damage of granulosa cells obtained during oocyte retrieval will be evaluated by comet assay in unexplained infertile patients undergoing in vitro fertilization (IVF) treatment. The oocytes will be graded by particular criteria. Fertilization, embryo quality, transfer rate, implantation, clinical pregnancy, pregnancy outcomes (gestational age at delivery, route of delivery, and birthweight etc.) will be recorded as well as demographic data. DNA damage of granulosa cells will be compared between unexplained infertile and control groups. The effect of DNA damage of granulosa cells on fertilization, quality of oocyte and embryo, implantation, and clinical pregnancy will be also evaluated.

Detailed description: Granulosa cells surrounding the oocytes will be mechanically obtained during the oocyte pick-up procedure in women undergoing in vitro fertilization (IVF) treatment due to unexplained infertility. Deoxyribonucleic acid (DNA) damage in these cells will be evaluated by comet assay. The quality of oocytes retrieved during the oocyte pick-up procedure will be graded by particular criteria (zona pellucida thickness, granulation, vacuolization, etc). Fertilization rates, embryo quality by grading, and transfer rates will also be assessed. Implantation and clinical pregnancy rates, and pregnancy outcomes including gestational age at delivery, route of delivery, and birthweight will be recorded as well as demographic data such as age, body-mass index, smoking, alcohol use, employment, coexisting chronic disease, infertility duration, etiology of infertility, treatment protocol, and hormone levels on day 3. Implantation will be evaluated by determination of serum human chorionic gonadotropin (hCG) at day 12 following an embryo transfer. Clinical pregnancy will be diagnosed upon presence of gestational sac on ultrasound examination. DNA damage of granulosa cells will be compared between unexplained infertile group and control group. The effect of DNA damage of granulosa cells on fertilization, quality of oocyte and embryo, implantation, and clinical pregnancy will be also evaluated.

Eligibility criteria: Inclusion Criteria:

* Unexplained infertile patients undergoing in vitro fertilization (IVF) treatment

Exclusion Criteria:

1. Chronic systemic disease (rheumatoid arthritis, hypertension, diabetes..)
2. Endocrinopathy (Thyroid, prolactin... abnormalities)
3. Chemotherapy or radiotherapy history
4. Cigarette, alcohol, chronic medication use
5. Diminished ovarian reserve
6. Endometriosis
7. Having any medication use
8. History of any surgical procedure on ovaries and uterus
9. Smoking or alcohol consumption
10. Severe oligoasthenospermia
11. Tubal infertility associated with hydrosalpinx, severe pelvic adhesions, endometriosis or pelvic inflammatory disease

Primary outcomes:
measure: Clinical pregnancy defined as the presence of gestational sac in transvaginal ultrasonographic examination 5 weeks after embryo transfer
timeFrame: 5 weeks after embryo transfer
Secondary outcomes:
measure: Fertilization defined as the presence of two pronuclei under light microscope one day after intracytoplasmic sperm injection procedure
timeFrame: 1 day after intracytoplasmic sperm injection procedure
measure: Oocyte grade assessed by four parameters (cytoplasmic granulation, properties of the polar body, the perivitelline space and properties of the zona pellucida) under invert microscope 36 hours after human chorionic gonadotropin administration
timeFrame: 36 hours after human chorionic gonadotropin administration
measure: Embryo grade assessed under invert microscope 3 days after intracytoplasmic sperm injection procedure
timeFrame: 3 days after intracytoplasmic sperm injection procedure
measure: Implantation defined as positive serum human chorionic gonadotropin levels 12 days after embryo transfer
timeFrame: 12 days after embryo transfer
Other outcomes:
Locations:
city: Isparta
country: Turkey
facility: Esra Nur Tola
state: Cunur
city: Isparta
country: Turkey
facility: Suleyman Demirel University, Faculty of Medicine
state: Cunur
Study officials:
affiliation: Suleyman Demirel Univercity, Medicine Faculty, Department of Gyneacology and Obstetrics
name: ESRA NUR TOLA
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nersesyan A, Chobanyan N. Micronuclei and other nuclear anomalies levels in exfoliated buccal cells and DNA damage in leukocytes of patients with polycystic ovary syndrome. J BUON. 2010 Apr-Jun;15(2):337-9.
citation: Ramzan MH, Ramzan M, Khan MM, Ramzan F, Wahab F, Khan MA, Jillani M, Shah M. Human semen quality and sperm DNA damage assessed by comet assay in clinical groups. Turk J Med Sci. 2015;45(3):729-37. doi: 10.3906/sag-1407-50.
citation: Gunasekarana V, Raj GV, Chand P. A comprehensive review on clinical applications of comet assay. J Clin Diagn Res. 2015 Mar;9(3):GE01-5. doi: 10.7860/JCDR/2015/12062.5622. Epub 2015 Mar 1.