The Influence of Polycystic Ovairan Syndrome on Embryonic Developmental Timing
Condition: Polycystic Ovarian Disease
MeSH terms: Polycystic Ovary Syndrome; Ovarian Diseases
Study type: Observational

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.
    

Detailed 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.
    

Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        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 from February 2011 to May 2013.
      
Keywords: PCOS