I love the internet more than I love most things in life, but I'm also incredibly aware of its shortcomings – especially when it relates to conversations about fertility treatment.

One of the many problems with fertility-related message boards/forums is how IVF drugs and their side effects are discussed. For every medication, there'll be three trillion side effects noticed by the people who took it – even if those “side effects” are just coincidence or imagined.

So how can you know if your insane bloating (for example) was definitely caused by your IVF drugs, or if it was actually because you nervously chewed through a packet of gum while waiting for your first transvaginal ultrasound?

The leaflets inside your medication boxes are a good first step, but there are also lots of scientific studies that go into more detail and provide more comprehensive lists of side effects. This article aims to give you a summary of all the research and science I've read (rather than, say, a random forum anecdote from someone in Swindon who had itchy cuticles after taking Progynova back in 2009).

Skip ahead to your drug of choice:

Menopur / Repronex

Generic name: Human menopausal gonadotrophin (hMG), which consists of FSH and luteinising hormone (LH). hMG is also known as “menotropins”

Brand name(s): Menopur, Repronex

How is it taken? Usually subcutaneous injections (just under the skin)

When is it used? During the “stimulation” phase of IVF

What does it do? An uninterfered­-with female body produces FSH and LH naturally, and these hormones cause the egg-containing follicles in your ovaries to grow and develop. After a while, just one follicle (sometimes two) will emerge as the “dominant” follicle, and it will continue to grow until it's ready for ovulation. With IVF, you want lots of follicles to grow and develop to the “dominant” stage – so you’re given a more prolonged dose of FSH and LH. Some people take FSH on its own – also known as “follitropins” – rather than hMG. There's more on FSH-only drugs below.

Read about the IVF process from start to finish.

What are the side effects? Several clinical trials have been performed on people taking Menopur, Repronex, and other hMG drugs under different brands (usually prescribed in other countries). Other clinical trials have been conducted on hMG in general – with no brand names mentioned.

Regardless of the brand, the following side effects were reported in over 5% of cases (in the reports I looked at):

  • Abdominal cramps
  • Enlarged abdomen
  • Abdominal fullness
  • Abdominal pain
  • Headaches
  • Injection site pain + reaction
  • Injection site inflammation
  • Nausea
  • Vaginal spotting
  • Constipation
  • Respiratory disorder
  • Ovarian hyperstimulation syndrome (OHSS)

In less than 1% of cases, blood clots are reported – but this might be a consequence of OHSS rather than the medication itself.

Other studies have looked at side effects voluntarily reported by people after taking hMG. Of course, it's much harder to know how much to trust these because we know little else about the people taking the medication (such as other medical issues that may be the underlying cause). We also don't know how many people didn't report side effects (and therefore how widespread the side effects are) or those who had side effects but didn't report them.

With all that in mind, here are the reactions they reported:

  • Abdominal pain
  • Abdominal distension
  • Nausea
  • Vomiting
  • Abdominal discomfort
  • Injection site pain
  • Fatigue
  • Headaches
  • Dizziness
  • OHSS
  • Pelvic pain
  • Ovarian cysts
  • Breast pain, breast tenderness, breast discomfort and breast swelling
  • Acne
  • Rash
  • Hot flushes

Are there any differences between the brands? Yes. One (admittedly rather small) study compared the side effects experienced by women taking Menopur with the side effects experienced by women taking Repronex. The researchers found that the side effects were much of a muchness for each drug… except for one thing: “injection site reactions”.

While 34.4% in the Repronex “group” reported injection site reactions, only 4.9% of people in the Menopur “group” reported the same. What's more… “Among the three Menopur subjects with local injection site reactions, all were transient and mild to moderate in intensity, none developed welts/inflammation, and only one subject had localized swelling. These findings contrasted with the 22 subjects in the Repronex group with injection site reactions, among whom eight developed welts/inflammation… and four developed swelling.”

Papers, reports and studies used: 

  • https://www.ferringfertility.com/products/menopur (click on “Prescribing Information”)
  • https://reference.medscape.com/drug/menopur-repronex-menotropins-342877
  • https://www.emedicinehealth.com/drug-menotropins_injectable/article_em.htm#sideeffects
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1309620/
  • https://www.medicines.org.uk/emc/files/pil.1294.pdf
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1309620/pdf/1477-7827-3-62.pdf

Cyclogest, Lubion, and other forms of progesterone

Generic name: Progesterone

Brand name(s): Cyclogest (rectal/vaginal suppositories/pessaries), Utrogestan and Prometrium (oral tablets), Crinone (vaginal gel), Gestone, Prontogest, Agolutin (all intramuscular injections), Lubion (subcutaneous injection)

How is it taken? Subcutaneous injections (just under the skin)

When is it used? Most people start taking progesterone about a week before embryo transfer, and then continue taking it (in decreasing doses) until around the tenth week of pregnancy.

What does it do? Progesterone helps keep your uterus lining thick, to prepare for when the embryo is transferred. Your own body will have been producing progesterone during stimulation, but doctors often prescribe extra – just to be sure. You might be given more than one type of progesterone (e.g. you might be asked to take Cyclogest and Lubion).

What are the side effects? Most of the side effects are similar for all kinds of progesterone, and they're similar to PMS symptoms. The following reactions are believed affect up to 10% of people (but usually much less):

  • Headaches
  • Breast tenderness
  • Joint pain
  • Drowsiness
  • Depression
  • Dizziness
  • Fluid retention/bloating
  • Hot flushes
  • Abdominal pain/cramping
  • Diarrhoea
  • Vaginal discharge
  • Mood swings
  • Frequent urination
  • Night sweats
  • Itchy skin
  • Vaginal bleeding

There are no risks/side effects to the unborn baby.

Click here to download information about ALL the IVF drugs you'll be taking

Other side effects depend on the progesterone you're taking:

  • Intramuscular injections can be quite painful, and some women react to the oil in the injections and develop a rash.
  • Vaginal/rectal gels and suppositories/pessaries can be messy! And there's a risk they'll cause vaginal thrush.
  • Oral pills can cause nausea – especially in high doses.

Papers, reports and studies used: 

  • https://www.ivfbabble.com/2018/06/progesterone-the-facts/
  • http://www.mhra.gov.uk/home/groups/spcpil/documents/spcpil/con1526618757689.pdf
  • https://www.pharmasure.co.uk/uploads/lubion-patient-information-leaflet.pdf
  • https://www.nps.org.au/medicine-finder/prometrium-capsules

Progynova / Climaval / Evorel

Generic name: Oestradiol valerate

Brand name(s): Progynova (oral tablets, vaginal tablets), Climaval (oral tablets), Evorel (patch)

When is it used? Most people start taking it about a week before embryo transfer and then continue taking it (in decreasing doses) until around the tenth week of pregnancy. Some clinics only give oestradiol valerate to those doing frozen embryo transfers (more on this in a sec).

What does it do? Oestradiol valerate is a type of oestrogen, and – like progesterone – it's needed to create and maintain a thick uterus lining. Many fresh embryo transfers don't require oestradiol at this stage, as the uterus lining will already be thick (because oestradiol will have been produced from all the stimulation medication), but women undergoing frozen transfers need help to build the lining back up before the embryo is transferred over. You might be given more than one type of oestradiol valerate (e.g. you might be asked to take Progynova and Evorel).

What are the side effects? First, it's important to note that oestradiol valerate is also used as hormone replacement therapy (HRT) for women going through the menopause – and they take the medication for years rather than a few weeks. Many of the side effects listed by websites will only apply to women who take it long term.

For women who take it as part of the IVF process, there are far fewer potential side effects:

  • Spotting or light vaginal bleeding
  • Upset stomach, nausea, or vomiting
  • Vaginal discharge or itching
  • Weight gain
  • Bloating
  • Headaches
  • Breast tenderness or pain

Papers, reports and studies used: 

  • https://www.lifefertility.com.au/resources/factsheets/medications-used-fertility-treatment/ 
  • https://www.yourivfjourney.com/estrogen-why-do-fertility-patients-need-it/
  • http://www.homerton.nhs.uk/our-services/services-a-z/f/fertility-centre/common-medications-used/

Note: while there's lots of information about side effects of long-term usage, it's difficult to find much scientific literature about the side effects of taking oestradiol valerate for a short period (a few weeks/months). 

Fragmin / Clexane

Generic name: Heparin

Brand name(s): Fragmin, Clexane (and also Lovenox, which is a slightly different type of heparin)

When is it used? Most people start taking it about a week before embryo transfer and then continue taking it until around the tenth week of pregnancy.

What does it do? Heparin is a blood thinner (i.e. prevents clotting, like aspirin does), and it's been shown to increase the chance of a successful embryo transfer – possibly because it improves blood flow to the uterus. (I should mention that multiple studies conclude that heparin does nothing to improve a person's chance of IVF success, but enough doctors clearly think it's worth using anyway.)

What are the side effects? The side effects all relate to administering the injection:

  • Bruising and discolouration of the skin where the medicine was injected (disappears with time)
  • “Bumps” underneath the skin where the medicine was injected (disappears with time)
  • Pain when the medicine is injected

Papers, reports and studies used: 

  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4304855/
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500816/
  • https://obgyn.onlinelibrary.wiley.com/doi/full/10.1111/aogs.13359
  • https://www.ncbi.nlm.nih.gov/pubmed/24995856
  • https://www.rxlist.com/fragmin-side-effects-drug-center.htm#consumer
  • https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD009452.pub2/epdf/full

Remember: if you're worried, contact your doctor

As with all medication, get in touch with your doctor immediately (or go to A&E) if you notice any serious reactions. Including:

  • Yellowing of your skin or the whites of your eyes (jaundice)
  • Migraine-like headaches
  • Signs of a blood clot – such as painful swelling and redness in the legs or ankles, sudden chest pain, and difficulty breathing
  • Unusual vaginal bleeding/discharge
  • Breast lumps
  • Dark patches on the skin
  • Frequent or painful urination
  • Persistent nausea and vomiting
  • Chest pain
  • Signs of a stroke (sudden numbness or weakness, sudden severe headache, slurred speech, problems with vision or balance)
  • Chest pain, sudden cough, wheezing, rapid breathing and/or coughing up blood (which could be a sign of a blood clot in your lung)
  • Signs of ovarian hyperstimulation syndrome (OHSS): rapid weight gain, little/no urination, nausea/vomiting, stomach pain, stomach bloating

 

 

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