Other Female Investigations

Before starting any treatment, we will assess your detailed family and medical history, perform a physical examination and vaginal ultrasound scan and blood tests measuring hormonal levels. Chromosome abnormalities and blood clotting disorders can be diagnosed with genetic testing and immunological testing may identify antibodies preventing implantation. Specific tests may include:

  • Ovulation examination: This test attempts to determine whether ovulation has taken place and also includes hormonal testing
  • Genetic testing for inheritable conditions
  • Screening for blood clotting disorder
  • Immunological testing including screening for antibodies against sperm, ovarian antibodies and trophoblast. If needed, patients may be referred to a reproductive immunologist or an endocrinologist
  • Hysterosalpingogram (HSG): A method to evaluate the fallopian tubes and uterus
  • Hysteroscopy to examine the uterus from within, as well as minor surgical procedures such as the removal of polyps, adhesions and smaller fibroids
  • Laparoscopy is additionally used to inspect the pelvic region enabling treatment of ovarian cysts and the evaluation of the fallopian tubes

Please find below more information on individual female investigations that are offered at City Fertility for both patients and out-patients. Please note that out-patients are required to provide us with a referral letter from their treating clinician or GP, alternatively they need to have a consultation with one of our Fertility Specialists first. 

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Cycle Monitoring (Ovulation Induction)

We can help diagnose fertility conditions using ultrasound scans and appropriate a blood tests. Investigations can look at ovulation and the way the dominant egg-containing follicle develops. Ovulation Induction uses oral and/or injected medications to boost the chances of fertilisation. 


3D Saline Infusion Sonohysterography (AquaScan)

A saline sonohysterogram, also known as an AquaScan, is a simple ultrasound procedure that looks at the endometrial cavity (the inside part of the uterus) and the endometrium (the lining of the uterus). It is usually performed in the ultrasound scan room and no sedation is needed but we are happy to offer a simple analgesia before the procedure upon request.

What does a saline sonogram involve? A speculum is inserted in the vagina to visualise the neck of the womb (like in a smear test). The neck of the womb (cervix) is cleaned and then a small soft catheter is passed gently through the neck of the womb into the cavity of the womb. An internal scan allows the lining of the womb to be seen clearly whilst some warm saline (salt water) is passed through the soft catheter. The endometrial cavity distends which enables the doctor to visualize the endometrial cavity. Any filing defect is noted and 3D images are taken. 

3D saline sonography can diagnose polyps and fibroids in the uterus, an abnormally shaped uterus, intrauterine adhesions and a uterine septum which may be associated with subfertility, recurrent IVF failure and recurrent miscarriages. 3D/4D imaging of the uterus during the sonohysterogram is particularly useful for the assessment of congenital uterine anomalies. 

  • Cost

    • Aquascan – Saline Infusion Sonography
      £300.00


3D HyCoSy (Tubal Patency Test)

A HyCoSy, also known as Hysterosalpingo-contrast sonography, is an ultrasound used to show the flow of fluid through the Fallopian tubes. It is very similar to the Saline Sonography (Aqua Scan) procedure but uses a contrast solution instead of saline to assess your fallopian tubes. This technique allows for identification of any blockage, which may be present in the Fallopian tubes.

What does a HyCoSy involve? The examination takes approximately 30 minutes and no anaesthetic is required. A catheter is passed into the vagina through the cervix into the uterus (womb). A small balloon is then inflated to keep the catheter in place. The contrast medium is then injected into the uterus through the catheter. The injection of the contract medium may cause some discomfort similar to the uterine cramps experienced during menstruation. A vaginal ultrasound scan is undertaken at the same time allowing your doctor to view the contract medium flowing through the Fallopian tubes.

The procedure should be performed after menstruation has ended in the first half of the cycle (usually from day 6 - day 12 of your cycle). It is recommended that you avoid intercourse from the first day of your last menstrual period up to the day of the procedure. Your treating clinician may suggest you have a high vaginal swab and chlamydia screen performed to exclude infection prior to the HyCoSy. An alternative is to cover the procedure with antibiotics. 

  • Cost

    • HyCoSy – Tubal Patency Test
      £450.00


Diagnostic and Operative Hysteroscopy

A hysteroscopy is a procedure during which the inside of the uterus (womb) is examined using a thin narrow tube called a hysteroscope. The hysteroscope (2-5mm diameter) is carefully passed through the vagina, the cervix (neck of the womb) and enables the doctor to see into the uterus via the hysteroscope telescope to assess the inside of the uterus and the opening of the Fallopian tubes. The procedure can diagnose polyps, adhesions and fibroids which can be removed at the same time (operative hysteroscopy).

The images may be viewed on a computer monitor as the hysteroscopy is being done. It can help to give a clear diagnosis of problems you are experiencing and help to decide the right treatment for you. These problems/symptoms you might be experiencing can include:

  • Repeated unsuccessful fertility treatments;
  • Previous uterine surgeries (e.g. caesarean, fibroids removal)
  • History of complicated or repeated miscarriages
  • Heavy or irregular vaginal bleeding
  • Post-menopausal vaginal bleeding
  • Unusual vaginal discharge
  • For the diagnosis of womb cancer.

If you have regular cycles, the procedure should be performed after menstruation has ended in the first half of the cycle (usually from day 6 - day 12 of your cycle). It is recommended that you avoid intercourse from the first day of your last menstrual period up to the day of the procedure. Your consultant may suggest you have a high vaginal swab and/or chlamydia screen performed to exclude infection prior to the hysteroscopy. An alternative is to cover the procedure with antibiotics. 

An operative hysteroscopy may involve removing:

  • Polyps (small lumps of tissue growing on the lining of the uterus)
  • Scar tissue and adhesions inside the uterus
  • Fibroids (non-cancerous growths)
  • Locate a 'lost' / stuck contraceptive device
  • Ablate endometrium
  • Divide a septum. 

If extensive treatment is expected, an operative hysteroscopy may require you to have a general anaesthetic (when you are asleep). You should not have a hysteroscopy if you are pregnant, have a vaginal or urinary tract infection or if you have cancer of the womb. 

  • Cost

    • Sedation Anaesthesia
      £250.00
    • Histology
      £250.00

      Sample sent for testing

    • Initial Consultation
      £200.00
    • Hysteroscopy
      £600.00 - £1,900.00

      Diagnostic hysteroscopy for City Fertility patients as part of the treatment is chargeable at £600.00. For out-patients, this is charged at £900.00. Operative hysteroscopy charged at £1,900.00 for everyone (sedation fee and histology fee chargeable extra). 


Endometrial Receptivity Assay ERA

A successful implantation is crucial for positive outcome, and there is only a small window when the endometrium is ready to accept the embryo for implantation. ERA is a novel diagnostic method that looks at the endometrial receptivity status of a woman, from a molecular point of view and determine the optimal implantation window. Normally the window of implantation is between 19 -21 days this is when the uterus is most receptive to the embryo. In some women this window can be displaced, and this constitutes a third of the women experiencing repeated implantation failure. The endometrium can be pre-receptive (not ready yet) or post-receptive (already past the implantation window).

Sample and Analysis

A biopsy of endometrial tissue is performed in a natural or a medicated mock cycle. Exact timings of biopsy are determined and discussed by your consultant. The sample is then analysed for 248 genes which are expressed during this time to detect any change in receptivity window.

Results

Results are expected in approximately 15 days. These results will help us tailor your upcoming frozen embryo transfer which may increase the chance of reproductive success.

Treatment add-on

ERA is outlined as an additional treatment option by the Human Fertilisation and Embryology Authority (HFEA) and has currently been deemed as red in the HFEA traffic light system for additional treatment options as there is no evidence from randomised controlled trials to show that it is effective at improving the changes of having a baby for most fertility patients. For more information on this HFEA add-on, please follow the link provided.

Risks

As per HFEA “As this procedure requires obtaining a biopsy of the endometrium patients can experience cramping and there is a small risk of infection and bleeding. There is also a very small chance of uterine perforation. The biopsy may need to be repeated in the rare event that either the results are inconclusive, or the biopsy fails to obtain a sufficient quantity or quality of tissue for testing.

ERA can only be performed in a frozen embryo replacement cycle, which carries a small risk that any frozen embryos would not survive the thawing process. ERA does not carry any additional known risks for the child born as a result of fertility treatment.
If you have any questions about the safety and risks, your clinic will be able to discuss whether a treatment add-on would be safe for you to use considering your specific medical history and circumstances.”

Clinical Evidence

As per HFEA “One RCT has been performed to study the effectiveness of ERA at increasing a patient’s chances of having a baby. The outcomes of the study were promising but the results did not prove that ERA made a true difference to the patient’s chances of having a baby and we can’t be certain of their reliability.
 
At the October 2021 SCAAC meeting the Committee evaluated the evidence base for ERA. Minutes of this discussion and the evidence used to inform this discussion are available on the SCAAC webpage.”

  • Cost

    • Endometrial Receptivity Array (ERA) including the Minor procedure fee
      £950.00

      ERA is outlined as an additional treatment option by the Human Fertilisation and Embryology Authority (HFEA) and has currently been deemed as red in the HFEA traffic light system for additional treatment options as there is no evidence from randomised controlled trials to show that it is effective at improving the changes of having a baby for most fertility patients.

    • Monitoring ultrasound scan (each)
      £150.00 - £250.00

      In-house patient (£150) or out-patient (£250)

    • Blood test (each)
      £40.00
    • Medication
      approx. £60.00

      Confirmed once a plan has been confirmed


Recurrent Miscarriages

The majority of miscarriages happen due to randomly occurring chromosomal abnormalities in the embryo. These errors may originate in the egg, in the sperm or occur after fertilisation as the embryo develops. In the vast majority of recurrent miscarriages, no specific condition is found despite extensive investigations.

Conditions linked to recurrent miscarriage are:

  • Specific conditions with a clear link to recurrent miscarriages;
  • When either the male or female partner carries a balanced chromosomal translocation;
  • When the female partner has an antiphospholipid syndrome;
  • When the female partner has a significant level of anti-thyroid antibodies and thyroid dysfunction;
  • In the presence of uterine anomalies;

There are other conditions which may contribute to recurrent miscarriages, but the links have not been well established. These include problems in reproductive immunology, conditions other than antiphospholipid syndrome which cause clotting problems (thrombophilia) and high sperm DNA fragmentation.

The doctor who oversees your treatment will discuss the use of testing for any of the above conditions relevant to your medical history.


Recurrent implantation failure

The conditions contributing to recurrent implantation failure are very similar to those contributing to recurrent miscarriages.
The doctor who oversees your treatment will discuss the use of testing for any conditions relevant to your medical history. 


NACE, Non-invasive Prenatal Test

At GENNET City Fertility we feel that all pregnant women should have a worry-free pregnancy and in order to enjoy a peaceful and healthy progress we do offer NACE testing.

NACE® is a non-invasive prenatal screening test that analyses the most frequent chromosomal alternations without compromising the pregnancy. A simple peripheral blood extraction from the mother allows free DNA circulating in the maternal plasma to be detected via Next Generation Sequencing technology and advanced bioinformatic analysis.

NACE is a complete prenatal test to detect abnormalities in chromosomes 21, 18 and 13 (Down, Edwards, and Patau syndromes). It also detects the most common abnormalities in the sexual chromosomes X and Y (except for twin gestations). The NACE test detects foetoses with chromosomal abnormalities with very high precision.

The NACE test allows the testing in twin pregnancies (aneuploidies for sex chromosomes not analysed, presence or absence of Y chromosome informed), vanished twins and egg donation. It is especially recommended for women with:

  • An abnormal result in their first trimester screen
  • A previous Down syndrome pregnancy
  • A suspicious ultrasound finding

NACE® Extended 24 incorporates the detection of all 24 chromosomes and identifies five microdeletions associated with major genetic syndromes.

What happens in the case of a positive result?

In cases of positive results patients are recommended genetic counselling and comprehensive ultrasound examination, at the same time the results should be confirmed by genetic diagnostic testing.

Depending on the screening results, diagnostic testing approach should be karyotype and:

  • Rapid prenatal testing by qfPCR
  • Rapid prenatal testing by FISH
  • Microarrays for prenatal diagnosis

  • Cost

    • Non-invasive prenatal test NACE Basic (NIPT)
      £425.00

      A safe and highly accurate test for Down Syndrome with detection over 99%. Ultrasound scan subject to an additional fee as per valid price list. 

    • Non-invasive prenatal test NACE24
      £620.00

      Includes NACE + all other chromosomes. Ultrasound scan subject to an additional fee.

    • Non-invasive prenatal test NACE24 Extended
      £700.00

      Includes NACE24 + microdeletions. Ultrasound scan subject to an additional fee.


Reproductive Immunology

The use of reproductive immunology tests is controversial and is not routinely practiced at GENNET City Fertility. We do offer a series of tests for selected patients upon request. The consultant who oversees your case will discuss the option of performing such tests with you in detail and with full transparency. In the past decade, there has been considerable efforts and research trying to identify possible immunologic causes for poor fertility treatment outcome. Should you decide to carry out the tests and they highlight an immune issue, we will discuss the use of immune modulators such as steroids and intralipid treatments.

An overactive immune system may be the cause of implantation failures or recurrent miscarriages. This is because it is thought that the mother’s immune system may perceive that an embryo is a foreign cell owing to differences in their genetic codes and therefore fails to accept it. Advances in Fertility medicine have significantly improved the success rates of Assisted Reproductive Technologies (ART). Yet, some patients experience recurrent miscarriages (RM) or recurrent implantation failure (RIF)) after in-vitro fertilization (IVF). Robust scientific evidence highlights the role that the immune system has in the implantation process, development of the placenta and later on – in pregnancy and childbirth. As only half of the genes carried by the embryo are of maternal origin it is expected that the implantation process will provoke a maternal immune response. Indeed studies demonstrated an immune response at the site of implantation which is believed to be essential to the successful development of a healthy pregnancy.

There is also good evidence to suggest that the female immune system is subject to changes during the time of implantation and in pregnancy. It is therefore believed that a specific pattern of maternal immune response is required to allow a successful pregnancy while deviations from this pattern may lead to failed implantation, miscarriages or complications at a later stage of pregnancy such as pre-eclampsia, poor intrauterine growth, etc.

Albeit extensive research in the field of Reproductive Immunology the exact immune pathways leading to a successful pregnancy remain only partially understood and there is significant controversy as to the value of most Reproductive Immunology assays. Furthermore, the practice of offering immune therapy to patients with RIF or RM remains controversial as there is no sufficient evidence from double blinded randomised control studies to prove its effectiveness.

A host of immune factors were suggested to lead to failure in achieving healthy implantation. Studies were carried out to look at the count, profile and activity of peripheral (blood stream) and uterine NK- cells in an attempt to isolate findings which can predict the risk of RM or RIF. NK cells are immune cells that belong to a subcategory of white blood cells called ‘Lymphocytes’. NK (natural killer) cells is the name given to cells which have various roles in immune responses and in inflammation. While some of the cell lines in this group take part in ‘killing’; destroying elements which are a potential risk to the body, others (including the majority of NK-cells found in the lining of the womb) have no killing properties. These cell lines take part in the regulation of the immune system, in promoting construction of blood vessels, etc. NK cells account for more than 80% of the white blood cell population post ovulation and during pregnancy.

Studies based on small numbers of patients reported of increased natural killer cell activity in women with recurrent miscarriages and recurrent embryo implantation failure. Different medications (such as steroids and IV immune-globulins) have been found to suppress natural killer cell activity in vitro (in the laboratory) and in vivo (in the human body). Similarly, Intralipid was also shown to decrease natural killer cell activity.

This matter is controversial within the medical field. Results published in the medical literature have been contradictory; however, it is thought that recurrent miscarriages and recurrent implantation failures that cannot be explained by routine investigations might have an immune based cause.

You will have the chance to discuss carrying out those tests with your doctor during the consultation if you have a history of recurrent miscarriages, recurrent implantation failures or if you have a personal history of autoimmune disorders (such as lupus, rheumatoid arthritis, ulcerative colitis, auto-immune thyroid issues, Crohn’s disease). The clinic will only offer the tests when your consultant deems it appropriate for your treatment.

NK cells can be checked in the peripheral blood or in the womb lining (endometrium). Endometrial NK cells are checked by carrying out a minor procedure (a “scratch” of the lining of the womb) between days 15-25 of the period. Based on the results you might be offered immunomodulatory treatment like Oral steroid treatment (Prednisolone) and Intralipid infusion.

No results from randomised clinical trials are available to show a clear benefit for patients receiving Immunomodulatory treatment versus those who have not. However, several studies suggest that there may be a benefit of immunological treatments compared to no treatment at all. It is important to note that the RCOG does not recommend testing or immunological treatment except in the realm of experimental medicine.

The Royal College also mentions that: “Steroid (Prednisolone) Treatment is a commonly used medication in the treatment of autoimmune diseases. It acts by suppressing the immune system. The role of immune mediators in the process of embryo implantation has not been confirmed. However, there is some evidence to suggest that steroid treatment may be beneficial in improving the implantation potential of your embryo.”

As the use of steroids is not evidence based with respect to improving live birth rates and is optional. Before commencing your medication it is important to ensure you have a blood test to check your liver function, and blood glucose level. Please let your consultant know if you have any medical problems, such as history of tuberculosis.

HFEA Treatment add-on

Immunological tests is outlined as an additional treatment option by the Human Fertilisation and Embryology Authority (HFEA) and has currently been deemed as red in the HFEA traffic light system for additional treatment options as there is no evidence from randomised controlled trials to show that it is effective at improving the changes of having a baby for most fertility patients. For more information on this HFEA add-on, please follow this link.

Costs

Cost for the Natural Killer test is £1,120.

Steroids

Risks

As per HFEA “Short courses of low-dose steroids generally do not cause significant side effects, but the likelihood and severity of side effects increase with higher doses used in IVF clinics. Side effects also become increasingly likely with longer courses of more than two months or many repeated short courses.

Common side effects include weight gain, restlessness, sleep disturbance, sweating, muscle pain/weakness and abdominal discomfort.

Steroids inhibit the immune system so put patients at increased risk of infections, from the minor to the very serious. These infections can cause considerable harm not just to the patient but also to the baby.

Other serious side effects are rarer but include fluid retention (swelling in your hands or ankles), breathlessness, high blood sugar, high blood pressure, mood/behaviour changes, visual disturbance, abnormal bruising/bleeding and risk of peptic ulcer. There is also the risk of allergic reactions which range from minor rashes to serious anaphylaxis with facial swelling and difficulty breathing.

While taking steroids, patients should carry a card on them to alert medical professionals in the event of serious complications. Patients taking steroids should not stop suddenly as they can suffer serious and life-threatening withdrawal symptoms.”

Clinical Evidence

As per HFEA “There is no scientific rationale for the use of steroids and no good quality evidence to support their use as an add-on in fertility treatments. At the October 2021 Scientific and Clinical Advances Advisory Committee (SCAAC) meeting the Committee evaluated the evidence base for immunological tests and treatments. Minutes of this discussion and the evidence used to inform this discussion are available on the SCAAC webpage.”

Costs

Costs confirmed once the course of steroid treatment has been agreed.

Intralipids

Risks

As per HFEA “Some common minor side effects include headache, nausea, vomiting, dizziness and flushing.

Intralipid is given by intravenous infusion (a drip) that always carries a risk of introducing infectious agents directly into the blood stream. More serious side effects are unlikely but may include signs of infection (e.g. fever, persistent sore throat), pain/swelling/redness at the injection site, pain/swelling/redness of arms/legs, bluish skin, sudden weight gain or back/chest pain.

Very rarely there may be emotional/mood changes, bone pain, muscle weakness, yellowing skin/eyes, dark urine, easy bruising/bleeding, severe stomach/abdominal pain and difficulty breathing.

Intralipids are not suitable for people with allergies to eggs, soya beans or peanut oil as they would be at risk of severe reaction. There is also a risk of reactions in patients without known allergies. Those range from minor rashes to serious anaphylaxis with facial swelling and difficulty breathing.”

Clinical Evidence

As per HFEA “There is little evidence that intralipid improves live birth rate.

At the October 2021 Scientific and Clinical Advances Advisory Committee (SCAAC) meeting the Committee evaluated the evidence base for immunological tests and treatments. Minutes of this discussion and the evidence used to inform this discussion are available on the SCAAC webpage.”

Costs

The cost for Intralipids is £250 per infusion.

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