Natural killer cells, or NK cells, are part of our body’s immune system, helping us to fight infection and disease. Every organ has NK cells including the uterus where they are known as uNK cells.

uNK cells play a role in helping the body become pregnant by inflaming the lining of the uterus so the embryo can implant. It is thought that too few or too many uNK cells can cause infertility and miscarriage.

However, there is currently no clear evidence about the exact role that uNK cells play in miscarriage and what should be considered an ideal level or an imbalance.

The value of measuring natural killer cells either in blood or from the uterus, therefore, remains controversial and confusing. Here, reproductive medicine specialist Dr Amanda Tozer reviews Natural Killer Cell testing in Recurrent Pregnancy Loss (RPL) and Recurrent Implantation Failure (RIF).

The main reasons for this are:

1. Whilst there is an association between elevated NK cells and RPL and RIF, there is no established causal effect
2. There are no clearly established values for what constitutes elevated levels of NK cells
3. There are no clear guidelines on which NK cells should be measured and from where (blood or uterus)
4. Current evidence is not strong enough to support the use of either IVIG or intralipid with larger randomised controlled trials being needed

Below, Dr Tozer summarises what we do know at this stage:

CD 56 NK Cells

In peripheral blood, 90% of NK cells are CD56dim and 10% are CD56bright which is the opposite in the uterus. There are varying studies that suggest there is no correlation between the uterine NK cell levels and those in peripheral blood as well as studies that suggest there is a correlation.

Studies have shown an increase in the number of peripheral blood NK CD56 with high rates in recurrent implantation failure and recurrent pregnancy loss

A cut off level of >12% has been used for CD56 but levels of up to 29% have been seen in normal healthy individuals

CD 3 Cells (Pan T Cells)

High values may be found in women with RPL. Cut off values are set at 85%

CD19+/5+ (B-1 Cells)

When CD19 express cells known as CD5 they are classified as B-1 cells and are often involved in autoimmune disorders, Women with elevations of CD19+/5+ may be at risk of thyroiditis and premature menopause. Cut off values are >10%

CD19 (B cells)

Frequently found to be elevated in women with an immune cause for RIF or RPL. Cut off values are >12%

NK Cytotoxicity

This is the ability of agents to suppress the killing of target cells by the patients NK cells

Results are expressed as ratios of 12.5:1, 25:1 and 50:1. A reduction in cytotoxicity to <20% is desirable

Intralipid

The active ingredient in intralipid is purified soybean oil and purified egg phospholipids. A number of studies have assessed the use of intralipid in women with RPL and RIF who have elevated NK cells. Intralipid has been shown to be effective in decreasing NK cell activation and reducing production of proinflammatory cytokines with the aim of promoting healthy implantation and placentation. Studies have reported variable outcomes with clear evidence to support its use being limited. No studies have reported any serious adverse events.

Studies have shown intralipid to be comparable to using IVIG. IVIG is expensive, has an associated risk of anaphylaxis and, (albeit low) a risk of infection transmission. IVIG is not offered at ARIA.

To discuss this in more detail, book a consultation with Amanda or any of our fertility experts.

Currently rated as amber by the Human Fertilisation & Embryology Authority, the UK’s IVF regulator, the value of IVF add-on endometrial scratching has come under the spotlight in recent months.

Endometrial scratching is rated amber by the HFEA because there is conflicting evidence from randomised controlled trials (RCTs) in terms of its effectiveness in improving the chances of conception for those undergoing fertility treatment.

What is endometrial scratching?

Endometrial scratching is termed as a fertility treatment ‘add-on’ as it is performed in conjunction with in vitro fertilisation (IVF). It is used in preparation for a round of IVF with your fertility doctor ‘scratching’ the lining of the uterus known as the endometrium. During the first stage of conception, an embryo attaches to the endometrium in a process known as implantation.

By ‘damaging’ the endometrium, the body’s natural healing process is triggered and an inflammatory response is produced, releasing growth factors, hormones and proinflammatory cytokines.

It is a quick, simple, low-cost procedure performed without anaesthetic. It can cause some discomfort and bleeding, but more serious risks such as infection or uterine perforation are very rare.

Some studies have suggested that endometrial scratching makes the uterus more receptive to implantation. However, as indicated by the HFEA, other trials into endometrial scratching have found no evidence that it increases the chance of conceiving through IVF.

The latest research into endometrial scratching

Published in the journal Human Fertility in December 2021, were the results of a new survey of fertility doctors in the UK, Australia and New Zealand into their perception of endometrial scratching value.

“We don’t have good evidence that endometrial scratching helps people to have a baby from IVF, and it’s a painful procedure associated with a cost for the patient too,” explains one of the study’s authors Sarah Lensen, postdoctoral research fellow at the University of Melbourne.

The study’s authors believe that earlier studies that found value in endometrial scratching lacked randomised controlled trials and were too small scale. Later larger, high-quality studies have cast doubt on these, meaning there’s no conclusive evidence that it boosts your chance of conception.

Yet, many fertility clinics continue to recommend this add-on. As identified in the study, many fertility specialists believe that it is valuable for patients who have unsuccessfully undergone more than one IVF cycle with good-quality embryos due to implantation failure.

“The idea of the scratch is that it might help these women who could theoretically have suboptimal endometrium, to achieve pregnancy,” Sarah says. “Secondly, people who have had multiple embryo transfers without success are often looking for something new to try that might help them to conceive.”

For more advice on endometrial scratching, call 0203 263 6025 to arrange an appointment with Dr Amanda Tozer at Aria Fertility Clinic.

A new study has identified new genetic risk factors in the development of polycystic ovary syndrome (PCOS). PCOS is the most common endocrine disorders affecting women and it can lead to difficulty getting pregnant.

Published in the journal Human Reproduction, genome-wide association studies were conducted by researchers at the Institute of Genomics of the University of Tartu to search for these variants in PCOS.

Polycystic ovary syndrome is often diagnosed through irregular periods, high levels of androgen hormones or enlarged ovaries known as polycystic ovaries, but the exact causes of PCOS remain unknown.

The study’s author analysed the genetic data of over 233,000 women from Estonia and Finland. Triin Laisk, Associate Professor at the Institute of Genomics, determined that PCOS “is a multifactorial condition, meaning both genetics and environmental or lifestyle factors increase the risk”.

The study found two new rare genetic variants that increase the risk for PCOS, which will probably affect the gene CHEK2. CHEK2 has been also linked to ovarian reserve and variation in age at menopause.

PCOS and fertility

One in five women in the UK suffer from PCOS and it can be a common cause of female infertility as it affects how the ovaries function. Although polycystic ovaries contain small antral follicles with eggs in them, the follicles often do not mature properly so there is no ovulation. Cysts can form instead.

Women will often experience irregular menstrual cycles and gradual worsening of excess facial and body hair growth as the result of high testosterone levels. Although the infertility rate can be high with PCOS, the good news is that the chance of getting pregnant using fertility treatments is good.

Women with PCOS usually require ovulation induction to conceive. Fertility treatment options include the use of medication such as Clomid or Letrozole. IVF is one of the most common fertility treatments for those suffering from PCOS and has a good success rate. The initial stage is taking medication to stimulate ovulation and then injections are given which will help the body to release an egg before they are harvested for fertilisation.

For more advice on PCOS and fertility treatment, call +44 (0) 203 263 6025 to arrange a consultation at Aria Fertility.

 

Globally, we are starting families later than ever. Although most couples do get pregnant within the first 12 months of trying, it is estimated that one in seven couples may have difficulty conceiving.

Though the latest data from the Human Fertilisation and Embryology Authority (HFEA) reveals that the rate of successful IVF treatments continues to rise, it also noted that the chance of having a baby after one treatment cycle for women under 35 years of age is 31.3%.

Fertility clinics are increasingly focusing on the biopsychosocial dimension of fertility and, using a unique and cutting-edge approach, Aria’s Laboratories are conducting an innovative study to investigate how non-invasive data could be used to tailor and maximise IVF treatments.

Mr Stuart Lavery, Consultant Gynaecologist and a Founding Director of Aria Fertility, explains: “Aria Fertility was born through the vision of leading clinicians and embryologists who have combined their experience and vision to deliver truly market-leading fertility care, whilst combining the latest technological advances and pioneering research in the field of embryology.

“Using a unique and cutting-edge approach, Aria’s Laboratories are conducting an innovative study to investigate how non-invasive data could be used to tailor and maximise IVF treatments.”

The Safe Assessment of Embryos (SAFE) study aims to integrate information on individual’s sleep quality, lifestyle habits, laboratory and clinical data, together with non-invasive genetic information and the most advanced algorithms for embryo selection using artificial intelligence (AI).

Embryo selection explained

Once embryos are created in in vitro, embryo selection is a decisive stage in IVF treatment. The healthier the embryo selected, the higher the chance of a successful pregnancy result.

There are several methods embryologists use to select for the best embryo. One method used in routine practice involves looking at the appearance of the cells which make up the embryo (morphological assessment). Another method involves tracking the growth of the embryo in a special incubator that records images over time (morpho-kinetic assessment).

One emerging method to score embryos involves AI, which can be used to rank the embryos most likely to become a baby. Even though all methods are valid, there are currently discrepancies between IVF laboratories when it comes to their criteria, use and implementation.

Currently, genetic data from the embryo is obtained through a biopsy of the embryo, where some cells are removed and sent for analysis. Although being invasive, preimplantation genetic testing of aneuploidies (PGT-A, formerly known as PGS) is considered the gold standard technique to check embryos for abnormalities in the number of chromosomes – key factor for successful pregnancy.

Chief Investigator and Laboratory Manager at Aria, Xavier Viñals Gonzalez explains why the SAFE study is unique. “The SAFE study proposes to use the culture medium, which is the nutrient fluid that embryos are placed in to grow, to gain genetic information in a non-invasive manner. Embryos gain their nutrients from the culture medium to grow, and they then secrete certain markers into the medium. Previous studies have connected these with embryo’s genetic makeup.

“In routine treatment, the culture medium is discarded after the embryos have been transferred or cryopreserved. Our laboratory will measure these markers in the medium to see whether they are predictive of a live birth.”

Sleep and fertility

Previous studies have shown that sleep quality and length to be associated with variations in fertility hormones, number of eggs collected during fertility treatment, egg maturation, and quality of semen.

Dr Sara McNeillis, Sleep Medicine and Anaesthesia Consultant, joins Aria’s study to investigate the vastly unexplored area of sleep disorders and infertility. With the aid of a smart watch, individuals sleep quality and patterns will be measured and further complemented with sleep questionnaires. Also, participants will be encouraged to record information on lifestyle habits while they are enrolled in the study.

Joining the fertility study

To be eligible to participate in this study, individuals must be between the ages of 18 and 44 and planning to have IVF with a single embryo transfer. Given its non-invasive nature, being part of the SAFE study will not impact individual’s treatment in any way. Results from this research could be the biggest game changer not only for how we analyse data to predict successful outcomes in IVF but also for patients to understand their options during their reproductive journey.

To find out more about our study and the work of the Aria embryologists, call us on +44 (0) 203 263 6025 to speak to one of the team.

Almost two years of living with COVID has resulted in ‘heartbreaking’ delays to fertility treatment, according to a survey of nearly 400 patients by the UK’s national fertility charity.

Last week was National Fertility Awareness Week, led by Fertility Network UK, to raise awareness of all aspects relating to fertility, from fair access to NHS-funded treatments, the emotional impact of male infertility, through to encouraging donor donation. The charity also reviewed the devastating impact the COVID pandemic has had on those waiting for fertility treatment.

Although clinics were officially given the green light to resume treating patients in May 2020, the backlog is still affecting many patients receiving fertility treatment through the NHS.

New research found that 58% of respondents had experienced delays being able to access treatment and a quarter had not been able to access counselling. Delays had affected both diagnostic testing, including semen analysis and blood tests, and surgical procedures with interruptions to treatment ranging from months to up to two years. Tests were often out of date and needed repeating.

Going it alone

Another upsetting aspect has been the impact on face-to-face services. In some instances, male partners were unable to attend fertility appointments and often patients had to receive devastating news over the phone.

The impact on mental health

Patients reported increased levels of stress, anxiety and depression as a result of delays. Counselling was also affected with many unable to access emotional support.

Gwenda Burns, chief executive of Fertility Network UK, said: “Our survey shows the devastating reality of delays to tests and treatment for fertility patients. It is clear the delays are ongoing and that many are concerned about how this will impact their chances of having a family. We are particularly concerned for those who haven’t been able to access counselling and would remind anyone affected by this that we are at hand to offer support.

“We are particularly concerned about the impact on fertility patients, where we know that age makes such a difference to outcomes. Time really is of the essence for fertility patients. Research from Aberdeen University earlier this year showed the impact that delays of six months or a year may have, and we know this is now a reality for many patients.”

One result of delays to NHS fertility provision has been more couples or individuals seeking treatment at private clinics.

Aria Fertility Clinic was developed during the height of the pandemic, receiving its license from HFEA in 2021. “We have managed to remain open throughout, providing consultations, investigations and the full range of treatment services, whilst always prioritising the safety of our patients,” Rob Smith, Clinic Director. Find out more about COVID and fertility treatment at Aria or call us on +44 (0) 203 263 6025 to speak to one of the team.