Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01953146 |
| Other study ID # |
PCOS_time-lapse |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
September 23, 2013 |
| Last updated |
September 25, 2013 |
| Start date |
September 2012 |
| Est. completion date |
September 2013 |
Study information
| Verified date |
September 2013 |
| Source |
University of Aarhus |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Denmark: Ethics CommitteeDenmark: Danish Dataprotection Agency |
| Study type |
Observational
|
Clinical Trial Summary
Polycystic ovary syndrome is one of the most common causes of female infertility. The cause
of infertility in PCOS is unknown. Factors other than anovulation, including inherited or
induced changes in the embryo quality have been suggested. Time-lapse analysis of embryo
development is a sensitive method of detecting reduced embryo viability. Yet, there are no
data regarding the embryo development in PCOS assessed by time-lapse analysis.
Description:
Method A consecutive cohort of 249 infertile women attending In vitro fertilization (IVF) or
Intra-cytoplasmic sperm injection (ICSI) treatment at the Fertility Clinic, Arhus University
Hospital was requited from February 2011 to May 2013. During the period, couples undergoing
IVF/ICSI treatment were offered blastocyst culture to day 6 and time-lapse imaging (TLI) as
part of a study evaluating parameters for embryo selection (Kirkegaard et al. 2013). Women
aged < 38 years without endometriosis and with more than > 8 oocytes retrieved were
eligible. Patients were categorized in two groups. Women with regular menstrual cycles and
no clinical signs of PCOS (non-PCOS) and women fulfilling the Rotterdam diagnostic criteria
for PCOS detected by the presence of anovulation and polycystic ovaries PCO, which was
diagnosed by luteal-phase progesterone testing and trans-vaginal ultrasound, respectively.
Biochemical parameters of androgen excess were included in the diagnosis when available, ,
whereas subjective symptoms of androgen excess (acne, hirsutism, alopecia) were not
included.
Ethical approval Written informed consent was obtained from all patients before inclusion.
The Central Denmark Region Committees on Biomedical Research Ethics and the Danish Data
Protection Agency approved the study.
Ovarian stimulation:
Patients were treated with individual doses of gonadotropin, based on serum AMH and/or
antral follicle count. Patients were stimulated by either a GnRH agonist- or antagonist
protocol using rec-FSH or HMG for stimulation according to clinical guidelines. A dose of
10,000 IU of hCG was administered when at least 3 follicles measured ≥ 17 mm, and UL guided
oocyte retrieval was conducted 36 h later.
Oocyte retrieval and ICSI/IVF Ovarian stimulation and oocyte retrieval were performed
according to standard procedures. After fertilization, ICSI embryos were immediately placed
in the time-lapse incubator (EmbryoScope™). IVF embryos were cultured for approximately 18 h
in a conventional incubator. Before IVF embryos were transferred to the EmbryoScope,
adhering cumulus cells were removed to ensure optimal image acquisition. In the EmbryoScope,
all embryos were cultured until arrest or removal at day 6.
Embryo assessment. All embryos with 2 pronuclei completing the first cleavage were annotated
manually.The following parameters were annotated with time-points: appearance and
disappearance of 1st nucleus and 2nd nucleus after 1st division, 1st - 7th divisions, final
divisions, compaction, morula, early and full expanded blastocyst, start of hatching and
fully hatched blastocyst. All time-points were normalized to first cleavage and treated as
durations for further analysis in order to overcome the limitation of inexact starting
points, and facilitate comparison between IVF and ICSI populations. For the same reason, no
parameters before first cleavage were investigated. Durations of cell cycles and cell stages
were subsequently calculated as the interval between two time-points. Two parameters
(multi-nucleation and direct cleavage to 3-cell stage) were assessed by binary values yes
and no. Embryos were selected for transfer according to conventional measures of
morphological quality on day 6 according to the Gardner criteria (Gardner et al. 2004) . No
time-lapse parameters were used in the selection process. The observer was blinded to the
patient's treatment data and medical history.
Statistics The influence of PCOS on embryo development was tested in regression models for
clustered data. A covariance regression model was used to account for potential confounding
variables: female age, BMI and fertility treatment. In total, 313 embryos from 43 PCOS
women, and 1080 embryos from 175 non-PCOS women were analyzed.
