Tag: stillborn

RPL: The effects of Age and Aneuploidy

RPL: The effects of Age and Aneuploidy

Just as the external physical body shows signs of aging, such as wrinkles and gray hair, the internal organs and cells also age. Thus, maternal age is one of the most determinant factors in regards to pregnancy success rates and live births. At the age of 40, it is estimated that as much as 30% of embryos are aneuploidy (a cell with an abnormal number of chromosomes), while at the age of 45, this increases to almost 100%. Thus the incidence of embryos with chromosomal abnormalities increase as maternal age increases. Most aneuploidies arise from errors in meiosis, typically due to nondisjunction (inability of a chromosome to properly separate) and account for approximately 50% of first trimester losses, 30% of second-trimester losses, and 3 % of stillborn births. Aneuploidy also accounts for unsuccessful IVF cycles when embryos are not screened.
Amongst the lethal aneuploidy category, 35% cause spontaneous abortions (such as 45X and trisomy 16, 21 and 22); while about 4% cause stillborn births (such as trisomy 13, 18 and 21). Of those aneuploidies that are somewhat compatible with life, trisomy 21, also known as Down syndrome, is the most common autosomal trisomy. Individuals with Down’s syndrome typically show signs of cognitive impairment, heart defects, and muscle weakness. The only other two autosomal trisomies that are detected in appreciable numbers are 13 and 18, however, affected individuals rarely survive the first few months of life.

trisomy21
Trisomy 21/Down’s Syndrome

On the other hand, Klinefelter’s syndrome (male 47, XXY) is an example of a sex chromosome trisomy. Affected individuals commonly show reduced sexual development and fertility, but they often have somewhat normal life spans. Monosomies are the opposite of trisomy, in that individuals affected have one chromosome less, 45 instead of 46. One uncommon monosomy is Turner syndrome (female 45, X0). Affected females have an array of symptoms, as there are a few variations of Turner’s syndrome (fully affected vs mosaicism), but typically include infertility, impaired sexual development, short stature, and heart defects.

Current Available Intervention

Couples who have conceived an embryo with an abnormal karyotype in the past, regardless of the pregnancy outcome, may be offered IVF with preimplantation genetic diagnosis (PGD) or comprehensive chromosomal screening (CCS). PGD encompasses both screening and diagnostic measures, which aims to analyze, select and transfer only embryos that have the appropriate number of chromosomes. PGD has been found to reduce the rate of miscarriage once pregnancy is achieved, but its ability to provide a better outcome for live birth compared to natural conception over time is controversial.

References:

Chromosomal Abnormalities: Aneuploidies | Learn Science at Scitable. (2017). Nature.com. Retrieved 11 August 2017, from https://www.nature.com/scitable/topicpage/chromosomal-abnormalities-aneuploidies-290

Bashiri, A., Harlev, A., & Agarwal, A. (2016). Recurrent Pregnancy Loss. Cham: Springer International Publishing.

The What, How, and Why of Recurrent Pregnancy Loss (RPL)

The What, How, and Why of Recurrent Pregnancy Loss (RPL)

Many of us, who have been in the journey of TTC for a while, might have unfortunately experienced one or several pregnancy losses. From biochemical pregnancy, early 1st trimester miscarriages, to a stillborn, each loss is emotionally tolling and frustrating. Many doctors would tell you that one loss is just an unfortunate fluke, very unlikely to happen again. But did you know that as many as 15% of all women under 35 years of age will experience an early loss (Bashiri, Harlev & Agarwal, 2016)? No woman likes hearing these statements or being a data entry in these statistics. So, like a good medical detective and curious “yenta” that I am, (and once my mourning and healing process allowed me to do so), I decided to investigate more about pregnancy loss. I hope that this information might help someone out there achieve closure, accept that you did nothing wrong to cause this, and believe that it is not your fault this happened.

But did you know that as many as 15% of all women under 35 years of age will experience an early loss (Bashiri, Harlev & Agarwal, 2016)? No woman likes hearing these statements or being a data entry in these statistics. So, like a good medical detective and curious “yenta” that I am, (and once my mourning and healing process allowed me to do so), I decided to investigate more about pregnancy loss. I hope that this information might help someone out there achieve closure, accept that you did nothing wrong to cause this and understand more about some of the causes and treatments.

What is RPL?

Recurrent pregnancy loss (RPL) is defined by ASRM as “two or more clinical pregnancies losses documented by either ultrasonography or proved in a histopathologic examination” before 20 weeks gestation. However, the “Royal College of Obstetricians and Gynaecologists (RCOG) and the European Society of Human Reproduction and Embryology (ESHRE) [defines it] as three or more consecutive losses before 24 weeks gestation”. This is a significant discrepancy, which might cause certain physicians to delay diagnosis and treatment in women with only two losses. (This is why is extremely important to understand and accept that you are your best advocate and to seek advice/treatment from an RE who is open minded and would proactively look for the patients’ input). As well, many physicians and medical societies do not count chemical pregnancies as part of the diagnosis of RPL, but after much controversy, it has been included in many studies as part of the RPL diagnosis (as implantation rate could be diminished due to poor uterine lining receptivity, uterine anomalies or blood clots).

Common causes of RPL:

RPL_Causes

  • Autoimmune disorders and other immunological anomalies
  • Parental chromosomal aberrations (genetic problems
  • Uterine anomalies
  • Endocrine/hormonal abnormalities
  • Thrombophilias/Blood clotting disorders.
  • Infections
  • Obesity/Undernutrition
  • RPL: The effects of Age and Aneuploidy

Over the next few articles, I will attempt to further examine each one of these causes and discuss potential treatments (if available).

References:

  • Bashiri, A., Harlev, A., & Agarwal, A. (2016). Recurrent Pregnancy Loss. Cham: Springer International Publishing.
  • Chromosomal Abnormalities: Aneuploidies | Learn Science at Scitable. (2017). Nature.com. Retrieved 11 August 2017, from https://www.nature.com/scitable/topicpage/chromosomal-abnormalities-aneuploidies-290
  • Schattman, G., Esteves, S., & Agarwal, A. (2015). Unexplained infertility. Pathophysiology, Evaluation and Treatment.. New York, NY: Springer.