Written by Carly Hayes. Reviewed by Jenny Wordsworth.

When it comes to making decisions about our health and fertility, we all want to know that we’re choosing the best option. But how do we know which treatments or procedures are safe and have the best scientific evidence behind them?

Medical decisions are made based on clinical evidence that comes from observational studies, clinical trials and real life patient experiences. In this blog, we will explore the types of available scientific evidence and shed light on which types of evidence carry the most weight in the fertility sector. Clinical studies are often complex and bewildering, so we’ve worked with our scientific experts to simplify the jargon.

So, how do we handle clinical evidence at Ovum?

“When we were going through our own fertility journeys, the manipulation tactics and scientific unreliability we encountered made it almost impossible to make high-quality decisions, at a time when what we needed was reliable information and support.

No one wants to feel like their hopes and dreams for a family are one big sales opportunity – least of all us.” Jenny

Did you know that there’s a gender data gap when it comes to clinical evidence? Women have in the past been excluded from clinical studies due to the variation introduced by our hormonal cycles. What’s more, research into women’s health issues is underfunded in the U.K., leading to a health system that doesn’t properly meet our needs.

We know that, when it comes to your fertility, we can’t always wait for the perfect scientific evidence before we develop new products to support you. Randomised controlled trials (RCTs) can often take many years to give final results. But, as a woman, your fertility is continually declining. So, using the best and highest-quality evidence available at the time becomes even more important when decision making. For example, we now know that taking folic acid during the early stages of pregnancy reduces the risk of neural tube defects in your unborn child. But, if doctors had waited for the ‘perfect’ evidence before recommending that their patients take this nutrient, there would have been a substantial delay, which would have led to countless pregnancy losses and babies born with defects.

In a world where research into women’s health is already so underfunded, it would be absurd not to make use of the high-quality evidence that does exist. You can be confident the scientific reviews that go into our product development are a comprehensive analysis of relevant medical research with studies confirmed by multiple different groups involving real patients. We do not base our product development on isolated animal studies, nor do we focus on individual, animal or test-tube studies, as these can give only limited evidence. We’ve set a high bar for the evidence we consider and include in our product development.

What’s more, at OVUM, we constantly review the best-available and highest-quality scientific evidence in fertility and update our products, as needed. Globally, we’re the only company working in the fertility product space to do so. This is time-consuming and expensive, but it’s part of how we make sure our products are the best on the market.  

OVUM’s product development is led by expert embryologists, IVF consultants, nurses, and psychologists, working in both NHS and private clinics across the U.K. We will also fund fully independent research, to further ensure our products are as safe and effective as we can make them.

Why is clinical evidence important?

Understanding the different types of scientific evidence available is vital for making evidence-based decisions about whether to offer a treatment. 

Expert opinions are the published insights from experienced professionals, but are not backed by data. Observational studies tell us what is going on in the real world, while RCTs provide stronger evidence on the effect of a treatment on the disease or condition. Analyses where clinical studies are pooled together provide a broader picture by including a large number of people, while clinical guidelines give standardised recommendations from a team of healthcare professionals and represent the highest level of evidence.

When you’re navigating infertility, it’s natural that you’ll be paying close attention to studies reported in the news and that you’ll want to understand what that study might mean for you. Having an appreciation of the strengths and limitations of the different kinds of evidence you might come across will help you understand the importance of these studies.

No single study should be used on its own to guide healthcare decisions, if other evidence is available. Instead, your doctor will usually take into account multiple robust sources of evidence. By critically evaluating and understanding the weight of scientific evidence, we can make more informed choices to improve health for ourselves and our loved ones.

Read on for an explanation of different types of scientific evidence to help you understand the weighting that is given to each.

Types of Evidence:

In marketing materials, you’ll often see brands making claims based on the scientific study they are referencing being ‘peer-reviewed.’ But, all scientific work must be peer-reviewed before it is accepted and published. ‘Peer-reviewed’ means that other doctors or healthcare workers who are experts in the same field have reviewed the study results and are happy that the data have been reported and interpreted correctly. 

Another thing to keep in mind here is that not all published studies are equal. For example, only the most high impact and well-designed studies will be published in the Journal of Reproductive Medicine,but some other journals may be less rigorous during the peer-review process. Each journal is given an impact factor and the higher the impact the more other scientists use (cite) that journal studies. 

Animal and Lab Studies

The lowest level of scientific evidence to consider when deciding whether you should be using a product or treatment is pre-clinical data (i.e. data from studies in animals or carried out on human cells artificially grown in a lab). The purpose of these studies is to decide whether the treatment is safe and shows enough signs of being effective that it’s worth considering testing in humans. It’s very difficult to compare humans to animals or cells grown artificially, so you should be wary about drawing any conclusions for your own health from these studies. For example, this article in The Times suggests that restriction diets could result in long-term fertility problems, but when you look into the details, the study only included a small number of zebrafish, so the results may not be relevant to humans at all. 

Expert Opinion

Healthcare professionals usually have a lot of experience in a particular field of medicine and can provide valuable insights when it comes to medical decisions. Published as expert opinions, these conclusions are made after years of clinical practice and take into account a wide range of cases. While expert opinions are a single, or collaboration, of doctors and scientists experiences and understanding of a careers worth of progrss they may not have the same scientific power as other types of evidence (discussed later). they should still be taken into account during the decision-making process, as these opinions will have been shaped by the patients they see in daily practice. 

Observational Studies

In observational studies, the people included are monitored only and the doctors running the study have no say in the treatments given. For example, one of these studies may be run to track those with a particular disease and how they are treated. Observational studies can monitor people over a period of time or can look back at past medical records.  Observational studies provide valuable information on how conditions progress or factors, such as passive smoking, that might increase the risk of infertility. However, these types of study can’t be used to work out what causes a disease because the investigator is only observing. Instead, these studies help generate hypotheses to be tested in clinical trials. One of the most famous observational studies was the first to link smoking with lung cancer by observing two groups in the 1950s, those who smoked and those who didn’t. The study found that those who did smoke had a significanty higher death rate than those who didn’t and this very much led the charge in changing public’s opinion of smoking.

Clinical Trials

Clinical trials are studies that include an experimental group (those getting the treatment being studied) and a control group (those given a dummy treatment or one already known to work). Clinical trials can be non-randomised or randomised.

Non-randomised controlled trials

In these studies, also simply referred to as ‘clinical trials’, those taking part are split between the two groups so that the researchers can test if the treatment works and is safe compared with the control. Non-randomised trials are not as powerful as randomised trials, as the researchers have chosen which group each person goes into and they may have introduced bias by putting people with certain characteristics together.

Randomised controlled trials (RCTs)

In these trials, people are assigned to a group at random at the start of the study. These trials are considered the gold standard in clinical research and, of all the individual studies, provide the best evidence for medical decision making.

So, why run RCTs? These studies allow doctors to work out just how well a treatment works in a range of different people. By carefully controlling anything that could affect the results, RCTs provide robust evidence that can be used to make accurate healthcare decisions.

But, it’s important to keep in mind that not all RCTs provide the same quality of evidence. Factors like the number of people included and the study design should be considered when evaluating the evidence. Large-scale randomised and double-blinded controlled trials with well-designed protocols generally provide the most trustworthy evidence.

Here’s an example of a great randomised controlled trial of CoQ10 - in women with lower ovarian reserve it found that after 60 days of supplementation prior to IVF, women who took CoQ10 had increased number of retrieved oocytes, higher fertilisation rate (67.49%) and more high-quality embryos. Significantly less women treated with CoQ10 had cancelled embryo transfer because of poor embryo development than controls (8.33% vs. 22.89%, p = 0.04).

What is trial blinding?

Another term you might hear when reading about RCTs is ‘blinded.’ We’ve known for a long time that a patient’s perception of the treatment they’re given can affect the results. For example, if a patient is told they will be given a treatment that they have read has had huge success in earlier trials, they may report feeling better because they think they should get better and not because of the treatment. 

We know this because people given a dummy treatment (known as the placebo) and told it is a medicine can report getting better for two reasons:

• They think that the treatment is working when tests show that their symptoms aren’t actually improving; and/or 
• Their body mimics the expected effects of the treatment and they do improve, even though they are only taking the dummy treatment

This is known as the placebo effect and, to correct for it so that the results of the trial only take into account the effects of the treatment, doctors started to blind trials, or essentially keep the people in the trial blind to what group they were in. But, it’s not just those taking part that have a perception of how well the treatment works, the doctors do too. This is why the highest quality clinical trials are now ‘double-blinded’, which means that neither the doctor nor those in the trial know which group they are in.

Systematic Reviews And Meta-Analyses

Understandably, we’d like to have as much evidence as possible to hand when making decisions. Even though RCTs are the gold standard, doctors much prefer to recommend treatments based on a large number of RCTs rather than just one or two.  Confusingly RCTs can present opposing outcomes for interventions even in well designed trials due to differences in dosing or patient populations, for example.

Systematic reviews and meta-analyses are comprehensive analyses that pool together results from many studies on a particular topic. By combining data from various sources, these analyses often include large numbers of individuals and, as a result, offer the most reliable and accurate assessment of the evidence.

Systematic reviews include all relevant studies to ask a specific research question, while meta-analyses statistically analyse the data from these studies to generate a quantitative summary. These types of analysis carry a lot of weight, as they provide a broader perspective on the available research, reducing the bias and increasing the statistical power. By combining data from multiple studies, systematic reviews and meta-analyses help us come to more informed conclusions about how safe treatments are and how well they really work.

In this meta-analysis, the effect of Vitamin D on fertility was reviewed. In the 3711 women included in these studies they demonstrated that women with a sufficient vitamin D level (>50nmol/L) undergoing IVF had a significantly increased live birth rate, an odds ratio of 1.74.

Clinical Guidelines 

The best clinical evidence, even above pooled analyses, is clinical guidelines. These evidence-based recommendations are developed by many experts from professional medical organisations or who are on expert panels. Clinical guidelines provide practical recommendations for specific conditions, with a focus on providing standardised, high-quality care.

A great example of clinical guidelines are the NICE clinical guidelines. NICE are currently reviewing fertility guidelines and Ovum are part of this process as a regisitered stakeholder, sign up to our newsletter if you’d like to be kept up to date on the guidelines.

So what makes a good scientific study?

The hallmarks to look out for when assessing scientific evidence are:

• The number of people included (200 is better than 20)

• The characteristics of the people included (if you’re looking at the effect of vitamin D on time to pregnancy, the study will be more valuable if women actively trying to conceive are included rather than women who are not actively trying)

• How important the study has been in the development of that area of scientific research, most often judged by how many times the article has been cited.

Takeaways for Evidence-Based Medicine:

• Medical decisions are based on clinical evidence from observational studies, clinical trials and real-life patient experiences. RCTs are considered the gold standard in clinical research and provide solid evidence for medical decision making

• Clinical studies can be pooled together in systematic reviews or meta-analyses to provide more comprehensive evidence than any single clinical study. But the highest level of evidence is clinical practice guidelines, which are put together by many medical experts based on the evidence available and their own expert knowledge of the field

• When evaluating scientific evidence, it’s important to consider the number of people included, the characteristics they have and how old the study is

• Women’s health research is underfunded and there’s a gender data gap, so it isn’t always possible to wait for there to be enough evidence of the highest quality before making decisions that will affect your fertility

• At OVUM, we perform a comprehensive analysis of the available clinical research, including studies confirmed by multiple research groups. We also constantly review the best evidence in fertility medicine and update our offering to give you the best possible products to support your fertility journey.