The Effect of Polycystic Ovary Syndrome on the Embryo Morphokinetics ( PCOS )
Condition: PCOS
MeSH terms: Polycystic Ovary Syndrome
Study type: Observational

Summary: 
      Polycystic ovarian syndrome (PCOS) is a complex endocrine and metabolic syndrome which
      accounts for 75% of women with anovulatory infertility. The cause of infertility in PCOS is
      already unknown. Although efforts have been made, many PCOS patients turned out to have worse
      oocyte maturity and IVF outcomes. Time-lapse analysis of embryo development can detect the
      abnormal timeline and cleavage mode which may affect the embryo viability of PCOS. However,
      there are still some debates on the effect of PCOS on the early embryo development by
      time-lapse analysis.
    

Detailed description: 
      Method:

      A consecutive cohort of 153 infertile women attending In vitro fertilization (IVF) or
      Intra-cytoplasmic sperm injection (ICSI) treatment at Shanghai Ji Ai G-IVF institute was
      requited from March 2021 to December 2021. 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. Women aged < 38 years without endometriosis
      and with more than 6 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. Shanghai Ji Ai ethical Committees approved the
      study.

      Ovarian stimulation:

      Patients were treated with individual doses of gonadotropin, based on serum anti-mullerian
      hormone (AMH) and/or antral follicle count. Patients were stimulated by
      gonadotropin-releasing hormone (GnRH) antagonist protocol using rec-follicle stimulating
      hormone (FSH) or human menopausal gonadotropin (HMG) for stimulation according to clinical
      guidelines. A dose of 10,000 IU of human chorionic gonadotropin (hCG) was administered when
      at least 3 follicles measured ≥ 17 mm, and ultrasound 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 - third divisions and 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. 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, 768 embryos from 80 PCOS women, and 676
      embryos from 73 non-PCOS women were analyzed.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Infertility patients udergoing IVF/ICSI cycles at Shanghai JiAi G-IVF institute from March
        2021 to December 2021.
      
Keywords: PCOS; Time-lapse; Infertility; Morphokinetics