Submitted by Dr R. Inchingolo on Tue, 25/07/2017 - 16:49
In this blog post Gavin Jarvis talks us through his work and inspiration behind looking into the evidence to answer the question, 'how do we know how many embryos die?'
Original article published on F1000Research Blog
Written by Gavin Jarvis
I started thinking about early human embryo mortality 10 years ago, when I sought a topic for a Masters dissertation in Bioethics. To be honest, I was looking for something that exploited my scientific background and this topic was in the news in relation to the ethics of human cloning and stem cell research. I was struck by the contrast between the confidence with which claims were made about the extent of embryo mortality and the diversity of the estimates offered. I also wondered at how we could possibly know what happens in the first week of the life of an embryo under natural circumstances.
Understanding the evidence
As a pharmacologist I try to discover how drugs work. Drugs are another topic of perennial public interest, yet most people have a limited understanding of how they work. I have always been fascinated by how we know what we claim to know – this is at the heart of science. Pharmacology is explicitly quantitative and I am particularly interested in how data analysis and statistics are used to make inferences in biology. It was therefore a natural progression to move from “how do we know how drugs work?” to “how do we know how many embryos die?” I simply wanted to understand the evidential basis for widespread quantitative claims regarding early embryonic death.
On the face of it, determining what happens to a newly fertilised egg in its first week of life under natural circumstances is not obvious. However, science enables us to know the unimaginable and achieve the extraordinary. Most people, including me, do not understand how planes fly, but I am confident that somebody does and more than happy to take advantage of the technology.
Examining the evidence
Detection of human chorionic gonadotrophin (hCG), a protein produced by early embryos, enables us to diagnose pregnancy with great accuracy. However, it only becomes detectable 6-7 days after fertilisation as the embryo implants into the mother’s womb. There have been many studies using hCG measurements to determine early pregnancy loss and my first article for F1000Research involved a re-analysis of three of these studies to obtain estimates of embryo loss in reproductively normal women. Nevertheless, despite the quality and usefulness of these data, hCG studies do not illuminate the first week of post-fertilization life.
Other sources are used to support claims about embryo mortality and these are described in my more recent F1000Research article. A short, speculative article published in The Lancet in 1975 has been surprisingly influential despite having limited value for quantifying embryo mortality. Observational studies of pregnancies are informative, although they cannot inform us about what happens prior to the initial pregnancy diagnosis.
Re-analysing the evidence
The principal source for claims relating to embryo loss in the first week after fertilisation is the work of Hertig and Rock in the 1940s. They examined wombs surgically removed from women to find days-old human embryos. There are however, serious flaws with these data and I decided to re-analyse them to quantify their limitations. My own view is that Hertig’s data give a misleading and imprecise impression of those early days of embryo life. Admittedly, it is the only direct data available; however, conclusions drawn from them must still be interpreted with great caution.
My re-analyses of the data had two objectives: firstly, to estimate a credible range for human embryo mortality from available data, and secondly, to critique other estimates and their sources.
- Using hCG data, I conclude that 10-40% of fertilised eggs perish in the first week, and 40-60% between fertilisation and birth. These wide estimates reflect uncertainty about what happens in the first week. Once implantation has begun, two thirds of embryos survive to birth, and after pregnancy is confirmed, losses are 10-20%, mostly in the early months.
- Some published estimates for embryo mortality are surprisingly high, up to 90%! One may speculate as to how such high values are derived but the purpose of my article was simply to draw attention to them and point out that the available evidence did not support such claims. Pregnancy loss is real but exaggerating the extent is unhelpful and unscientific.
Publishing new evidence
The open data and review platform of F1000Research was critical for these articles. After earlier versions submitted to regular journals received unenthusiastic and unhelpful responses, a colleague suggested F1000Research as an alternative. The unbiased editorial policy, open data and open refereeing have enabled the publication and improvement of the article. The reviews have been helpful and constructive and in one case, impressively long – I think it may be a record for an F1000Research peer review!
Claims about early embryonic mortality abound in the public domain. While some are consistent with available data, others are exaggerated. My hope is that readers of my article will gain a better appreciation of the sources and limitations of our knowledge and perhaps be a bit more cautious about claims they may hear and repeat.
Read more: Human reproduction likely to be more efficient than previously thought