Adalimumab is a TNF blocker, which is used for patients with elevated levels of TNF cytokines or Natural Killer (NK) cells, such as connective tissue disorders. It has been recommended and clinically beneficial in some patients with immune disorders associated with high TNF (tumor necrosis factor) levels.
The women at risk show alterations in CD56+ natural killer cells that secrete tumor necrosis factor. There have been no large studies done on patients with recurrent pregnancy loss or infertility, but several peer-reviewed publications have shown benefit in such conditions.
In cases of high TNF alpha: IL-10 and/or high INF-gamma: IL-10.
Two 40 mg subcutaneous injections: one at a time, 2 weeks apart. Occasionally, this course may be repeated if the TNF alpha: IL-10 or INF-gamma: IL-10 level is still high following the initial two injections.
Predisposition to infection.
Rash, nausea, vomiting, gastric disturbances, infections, headaches, rashes, and shingles.
Adalimumab has been shown not to cause fetal harm and is considered safe in pregnancy if used prior to 32 weeks’ gestation.
All patients, prior to the Adalimumab injections, will have a TB Gold Quantiferon test to ensure that this is negative.
If this is inconclusive, we will need to repeat the test. If TB is positive, then the patient may be referred to a chest physician for assessment and possible tuberculosis treatment prior to receiving the medication.
The TB test takes 5–7 working days to return, after which we will inform you of the result.
Granulocyte-Colony Stimulating Factor (G-CSF) is a cytokine (molecules that aid cell-to-cell communication in immune responses and stimulate the movement of cells towards sites of inflammation) that stimulates neutrophilic granulocyte proliferation.
Found to possibly reduce the risk of miscarriage. Based on research trials, G-CSF has been shown to be safe and well-tolerated for mothers throughout pregnancies and for newborns without signs of abnormality. No noticeable side effects were reported.
In certain studies, G-CSF was used in a series of women with unexplained recurrent miscarriage in whom previous treatment with other therapies had failed. It showed G-CSF to be effective in recurrent miscarriage. In one particular study, 29 out of 35 women delivered a healthy baby, whereas in the placebo group, this figure was 16 out of 33. However, further studies are needed to confirm the effectiveness of this treatment in women with unexplained recurrent miscarriage.
The 300 mcg injection is for subcutaneous use. Your doctor will provide instructions on the timing of the injections in line with your treatment plan.
You will need to have a blood test to check your full blood count every 2 weeks whilst on this medication.
Aspirin is one of a group of drugs called non-steroidal anti-inflammatory drugs (NSAIDs). It’s widely used to relieve mild to moderate pain and inflammation. It is also widely used in pregnancy for different indications such as reducing the risk of miscarriage, pre-eclampsia, and baby’s growth restriction in women at high risk of these disorders.
In our experience, Aspirin has been shown to reduce the risk of miscarriage, irrespective of outcome of the thrombophilia investigations. It is also used by fertility centres for women undergoing fertility treatment (IVF).
The low dose aspirin we recommend is 75 mg to be taken daily between 6-9 pm after food. Usually, the medication is taken until 20 weeks of pregnancy, but depending on the individual risk of preeclampsia (high blood pressure in pregnancy), the dose may be increased to 150 mg from 12 weeks gestation and continued until 36 weeks.
Not advisable to take if you suffer from asthma, stomach ulcers, known bleeding disorders,
or have mild to moderate renal/hepatic impairment.
Use of low-dose aspirin at any stage of pregnancy has not been associated with harmful effects.
Generally mild and infrequent, but in hypersensitive patients, side effects can include indigestion, heartburn, bloating, gastrointestinal upset with slight asymptomatic blood loss. In severe cases, it can cause an asthma attack and in rare cases, some skin reactions.
Prednisolone belongs to a group of medicines called steroids (corticosteroids). These steroids occur naturally in the body to maintain health and well-being. Boosting your body with extra steroids is an effective way in reducing inflammation. Steroids have widely been used in the treatment of recurrent miscarriage and fertility conditions with varying degrees of success in outcome.
Prednisolone is prescribed to women with recurrent miscarriage or repeated failed assisted conception attempts in the presence of abnormal immune markers such as high NK cells.
The dose usually ranges between 15 and 25mg, and is taken after breakfast. When you have been taking this dose for 3 or more weeks, you will need to wean off the medication by dropping 5mg every 5 days.
Caution is necessary when prescribing prednisolone to patients with the following conditions: adrenal suppression and infection; hypertension, congestive heart failure, liver failure, renal impairment, diabetes mellitus, osteoporosis (post-menopausal women at special risk), glaucoma, psychiatric reactions, severe affective disorders, epilepsy, peptic ulcer, hypothyroidism, history of steroid myopathy.
Prednisolone is compatible with each trimester of pregnancy. Steroids vary in their ability to cross the placenta; 88% of prednisolone is broken down by the placenta and inactivated, therefore very little passes to the baby. There is no evidence that corticosteroids result in an increased incidence of congenital abnormalities, such as cleft palate/lip.
The most common complication is difficulty sleeping at night. Gastrointestinal discomfort, headaches, nausea, altered mood, skin reactions, fatigue, increased weight.
Other Uncommon Side Effects Include
Gastro-intestinal effects include dyspepsia, peptic ulceration, abdominal distension, acute pancreatitis, oesophageal ulceration and candidiasis.
Musculoskeletal effects include proximal myopathy, osteoporosis, vertebral and long bone fractures, avascular osteonecrosis, tendon rupture.
Endocrine effects include adrenal suppression, menstrual irregularities and amenorrhoea, Cushing’s syndrome, hirsutism, weight gain, negative nitrogen and calcium balance, increased appetite, increased susceptibility to and severity of infection.
Neuropsychiatric effects include euphoria, psychological dependence, depression, insomnia, increased intracranial pressure, psychosis and aggravation of schizophrenia, aggravation of epilepsy.
Eye effects include glaucoma, papilledema, posterior subcapsular cataracts, corneal or scleral thinning and exacerbation of ophthalmic viral or fungal disease.
Other side-effects include impaired healing, skin atrophy, bruising, striae, telangiectasia, acne, myocardial rupture following recent myocardial infarction, fluid and electrolyte disturbance, leucocytosis, hypersensitivity reactions, thromboembolism, nausea, malaise, shingles, hiccups.
Further Information: Please be aware that steroids can mask the common symptoms of pregnancy, such as pregnancy sickness.
Wellbeing blood tests are required at 3 monthly intervals.
Fragmin belongs to a group of medicines called low molecular weight heparins, which helps prevent the formation of blood clots by thinning the blood. It is widely used in pregnancy for reducing the risk of blood clots in the mother and in conditions associated with baby growth restriction.
Routinely prescribed in women undergoing treatment with IVF/ICSI and in cases of thrombophilia.
Dose is determined by weight, usually ranging between 5000 and 10 000 units, taken by subcutaneous injections once daily, taken between 6-9pm. Duration of medication is decided on a case-by-case basis.
Manufacturer advises caution in severe hepatic and renal impairment. Not known to be harmful in pregnancy; caution in patients with hypersensitivity to low molecular weight heparins.
Haemorrhage, skin necrosis, low platelets, high potassium, hypersensitivity reactions (including urticaria, angioedema and anaphylaxis); osteoporosis after prolonged use
(and rarely alopecia).
Blood clotting levels ad your full blood count will be checked at 3 monthly intervals.
This drug belongs to a group called ‘proton pump inhibitors’. They work by reducing the amount of acid that your stomach produces. Omeprazole is mainly used to help reduce the acidic effect of steroids in the stomach.
For patients started on steroids such as Prednisolone, omeprazole is advised to prevent ulcers from forming in the stomach or gut lining.
20mg tablet once a day before breakfast.
Omeprazole is widely used in pregnancy. It is not known to be harmful to an unborn baby.
Headache, effects on your stomach or gut such as diarrhoea, stomach pain or constipation. Nausea and or vomiting.
Intralipid infusion therapy is a sterile fat emulsion containing soya oil, chicken egg yolk, glycerine and water. The infusion is in liquid form and administered through the veins with an intravenous(IV) cannula*.
The procedure is carried out in the Epsom clinic only as part of your treatment programme. Although not subjected to controlled trials, there are observed benefits in women with miscarriages and fertility conditions.
*Peripheral intravenous (IV) cannulation is an invasive procedure, and risks include phlebitis which may lead to pain or swelling at the infusion site.
Used as part of the treatment programme for high or complex NK cells.
If intralipids are to be included as part of your plan, these will need to be administered
within the CRP Clinic at Epsom where we follow strict clinical guidelines during preparation, administration and delivery of your intralipid therapy to maintain the highest levels of patient safety. Poor safety standards can lead to the introduction of micro-organisms, which may cause infection and other associated risks, including sepsis.
100ml bag of 20% intralipid given as an intravenous dose over 1 hour. The infusion may be required before ovulation, at positive pregnancy test and then repeated every 4 weeks until
20 weeks of pregnancy.
Allergies to Eggs or Soya. Liver disease.
Note: It is important to inform staff if you have had an illness such as a viral infection or diarrhoea and vomiting in the 48 hours prior to your infusion.
Headaches, dizziness, flushing, drowsiness, nausea, vomiting or sweating.
It is rare to have side effects in well patients.
Common side effects we have observed in our patients have included pain/swelling/redness at the infusion site and temperature fluctuations.
Serious side effects (more likely to occur in patients that require this medication on a regular basis for other health issues unlike fertility or miscarriage patients) include: signs of infection (fever, persistent sore throat), injection site reactions (pain, swelling, redness), pain/swelling/ redness of arms and legs, bluish skin, sudden weight gain, shortness of breath, back or chest pain, mental/mood changes, bone pain, muscles weakness, yellowing of skin and eyes, dark urine, bruising or bleeding, severe stomach or abdominal pain.
Hydroxychloroquine was originally an anti-malaria drug used in the 1940s but more recently has found a place in the treatment of conditions such as Rheumatoid arthritis and Lupus. This is because it has immune properties and seems to calm down inflammation. We have used it against Natural Killer Cells with possible help in women with miscarriages and fertility conditions. There are several publications which have shown its benefit in reducing risk of miscarriages and other immune related complications in pregnancy.
This drug could be considered in complex cases or if there are contraindications to use prednisolone.
300–400mg oral tablets. Usually started 4-6 weeks prior to pregnancy. A higher (loading dose) may be required for the first two days of use. The duration of the therapy will be based on individual circumstances.
Neurological disorders (especially in epilepsy), severe gastro-intestinal disorders and G6PD deficiency. Not to be used with azithromycin antibiotics.
Gastro-intestinal disturbances, headache and skin reactions, visual changes, hair loss and pigmentation of the skin, nails and mucous membranes.
You will be required to organise a pre-treatment eye examination and every 6 months whilst taking hydroxychloroquine at your local optometrist. Three monthly wellbeing bloods will be performed.
Most of our patients have tolerated this medication well and it has a good track record in pregnancy with no apparent fetal harm. If you are taking omeprazole, please ensure that you take the two medications at different times as it may inhibit absorption of the hydroxychloroquine.
Utrogestan contains progesterone, which is a natural female sex hormone, produced in the body. It works by adjusting the hormone balance within the body. It is used in different indications related to pregnancy such as IVF and pre-term birth. Recent findings have suggested that women who are at risk of a miscarriage because of current pregnancy bleeding and a history of a
previous miscarriage, could also benefit from progesterone treatment.
Given as routine to all women with history of recurrent pregnancy loss or preterm labour.
400mg, oral tablets, started around the time of ovulation until 16 weeks of pregnancy.
In some cases, Utrogestan may be used until 34 weeks.
Should be used with caution with diabetes, epilepsy, hypertension, migraine and cardiac dysfunction.
Bloating, fluid retention, breast tenderness, cramp-like pains due to gastric disturbances and skin irritation, possible menstrual cycle irregularities.
Fetal Medicine scan packages are available on request.
IVF packages are available on request.
IUI packages are available on request
