Progesterone use in women with previous pregnancy loss who are bleeding

You have received this information leaflet as you are currently experiencing some bleeding in your pregnancy and have previously experienced a pregnancy loss. Because of your history you may be suitable for progesterone treatment. This leaflet contains the information around progesterone use in women with previous pregnancy loss, who are bleeding.

We are sorry you are experiencing bleeding in the first weeks of your pregnancy. We are pleased that your scan is showing the pregnancy is developing normally. As you have had a previous pregnancy loss (miscarriage), we would like to provide you with information to make an informed decision about medication that may be offered to you.

The National Institute for Health and Care Excellence (NICE)¹ has recommended that Progesterone should be offered to women who experience bleeding in early pregnancy and have previously had a miscarriage. The new recommendation follows a review of available research data on progestogens to prevent a miscarriage. The committee found evidence of no benefit in women with early pregnancy bleeding but no previous miscarriage, nor in women with previous miscarriage but no early pregnancy bleeding in the current pregnancy. However, further research has been recommended in these two areas. It is clear that progesterone will not be able to prevent every miscarriage.

Benefits and concerns surrounding use of progesterone in a pregnancy with continuing bleeding with a normal scan

Benefits

A large study (The Prism trial³) found a slightly higher live birth rate (75% vs 72%) when progesterone was used compared to placebo (a non-active drug). A result that could be attributed to chance. No safety concerns were raised in studies on progesterone in the context of a miscarriage (the Promise² or Prism trials³) meaning the medication should be safe of use in this situation. There is also no evidence of harm from in-vitro fertilization (IVF) research where progesterone is used routinely (though in IVF the drug is replacing what would be there naturally). In women with a threatened miscarriage, additional hormone is added the long-term effects of which has so far not been studied in detail. Taking progesterone can stop your bleeding.

In women that have suffered recurrent miscarriages (three or more pregnancy losses), progesterone seems to be more effective in increasing your chances of having a live baby.

Concerns

There is a significant lack of study data to support the routine use of progesterone in women that have suffered one miscarriage. This includes data on how effective this treatment would be to prevent another pregnancy loss and how safe the treatment is for you and your baby.

The Promise trial² found that at most only 2% of miscarriages would be prevented in women with both a fetal heartbeat seen on scan and vaginal bleeding by using progesterone. The data is for women aged 16 to 39.

Currently, no long-term data on safety of high dose and prolonged use of progesterone in pregnancy is available. Some women, despite treatment with progesterone, will still have a miscarriage the cause of which may not be known. Taking progesterone may result in a delayed diagnosis of miscarriage, as you may not have any symptoms of a miscarriage.

Anecdotal data on progesterone use in pregnancy raises concerns regarding the normal development of female genitalia in girls born from mothers taking progesterone-type hormones. Similarly, there is some evidence that may link the use of progesterone-type hormones with development of autism. Authors of these studies do, however, highlight that more research is required to say if these links are true, or related to other factors and not the progesterone itself.

Treatment

Cyclogest© (the brand name for progesterone) is a pessary to be used vaginally or rectally.

Dose: 400mg twice a day.

There is no evidence that starting the progesterone after nine weeks has any benefit, so it should only be started at 6+0 to 8+6 weeks of pregnancy.

Please stop the medication only when advised by a medical professional or once you have had your dating scan.

Progesterone side effects

(Reference⁴.)

Stop using Cyclogest© and contact your doctor at once if you have an allergic reaction. Signs may include a skin rash, which may be itchy.

Common side effects (may affect up to one in 10 people)

Drowsiness, stomach discomfort or pain, breast pain.

Not known (frequency cannot be estimated from the available data)

Diarrhoea, soreness in your rectum (back passage), flatulence (wind), leakage after the pessary has dissolved (this is quite normal when using medicines that are inserted into the vagina or rectum).

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card scheme (opens in a new tab) or via the Yellow Card app, which can be downloaded from the Apple App Store or Google Play Store. By reporting side effects, you can help provide more information on the safety of this medicine.

How to store your medicines

Keep this medicine out of the sight and reach of children.
Do not store above 30°C.
Do not use this medicine after the expiry date which is stated on the label/carton/bottle. The expiry date refers to the last day of that month.
Do not throw away any medicines via wastewater or household waste.
Ask your pharmacist how to throw away medicines you no longer use.

We hope this leaflet has provided you with some more information regarding the medication offered to you in this difficult time. Please do not hesitate to contact your early pregnancy doctor or nurse specialist if you have any other questions or concerns regarding the management of your pregnancy. We aim to provide you with all the information currently available so that you can make an informed decision and be involved in your treatment.

Illustration of The Prism trial

In summary:

• 72% of women did not have progesterone and had a live birth (The Prism trial³).
• 25% of the women who did have the progesterone sadly still went on to have a pregnancy loss (The Prism trial³).

Contact details

Clinic 24 (Emergency Gynaecology Unit/Early Pregnancy Unit)
01223 217636
Monday to Friday 08.00 (8am) to 20.00 (8pm)
Weekends 08.30 (8:30am) to 14.00 (2pm)
Closed bank holidays

Daphne Ward (Inpatient Gynaecology Ward)
01223 257206
At all other times

References

1. NICE (2021) Ectopic pregnancy and miscarriage: diagnosis and initial management (opens in a new tab)
2. PROMISE Trial
   Coomarasamy A, Williams H, Truchanowicz E, Seed PT, Small R, Quenby S, Gupta P, Dawood F, Koot YE, Bender Atik R, Bloemenkamp KW. A randomized trial of progesterone in women with recurrent miscarriages. New England Journal of Medicine. 2015 Nov 26;373(22):2141-8.
3. PRISM Trial
   Coomarasamy A, Devall AJ, Cheed V, Harb H, Middleton LJ, Gallos ID, Williams H, Eapen AK, Roberts T, Ogwulu CC, Goranitis I. A randomized trial of progesterone in women with bleeding in early pregnancy. New England Journal of Medicine. 2019 May 9;380(19):1815-24.
4. Cyclogest© brand patient information leaflet (opens in a new tab) supplied by the drug company (March 2022).