Cyclogest^® (micronised progesterone)

Cyclogest^® is a natural progesterone pessary that has supported women across the world with their reproductive health since 1976.¹ Discover more about Cyclogest^® below, including its therapeutic indications, the evidence supporting its use in luteal phase support (LPS) in assisted reproductive technology (ART) treatments, and why it is demonstrated to be clinicians’ preferred treatment option in the UK.

What is Cyclogest^®?

A convenient twice-daily vaginal progesterone for Luteal Phase Support in ART.²

The preferred choice for Luteal Phase Support in 85% of IVF clinics surveyed in the UK.³

Supported across clinical trials with over 850 patients to have a demonstrated efficacy and safety profile.^4,5

Demonstrated to have similar efficacy via both rectal and vaginal routes.^6,7

Bioidentical to the progesterone produced by the patient’s body² and micronised for optimised absorption.^8,9

Cyclogest^® is suitable for vegan and vegetarians. This is certified with the Vegan Society.

Cyclogest^® 400mg UK Indications²:

Cyclogest^®can be an effective choice for Luteal Phase Support as part of ART treatment.¹⁰
The majority of patients undergoing ART cycles are affected by luteal phase defect, where the natural release of luteinising hormone (LH) and progesterone is inhibited following controlled ovarian hyperstimulation and oocyte aspiration. This negatively affects embryo implantation and development in the uterine lining and reduces the likelihood of a successful pregnancy.¹¹
Administering exogenous progesterone, such as Cyclogest^®, induces the secretory transformation of the endometrium to prepare the lining for embryo implantation through thickening of the endometrial lining and increasing vascularisation.¹²

Cyclogest^® 200mg UK Indications²:

Mechanism of action during Luteal Phase Support:

Hormonal actions:

Induces secretory transformation of the endometrium.
Stabilises the endometrium.
Stimulates the growth of the uterus.
Maintains uterine quiescence by stabilising lysosomal membranes.
Inhibits myometrial contractions.

Non-hormonal actions:

The clinical evidence for Cyclogest^®

Cyclogest^® supports successful embryo implantation

A 2018 randomised, observer-blind study involving 125 healthy individuals investigated the effects of various doses of Cyclogest^® progesterone vaginal pessaries. Part 1 of the study compared Cyclogest^® (200mg and 400mg) twice daily with progesterone vaginal gel (90mg) once daily. In Part 2, Cyclogest^® (100mg) twice daily was compared with Cyclogest^® (400mg) once daily. Placebo vaginal pessaries were also compared. Secretory transformation of the endometrium is  a surrogate marker for endometrial receptivity, thereby indicating an increased chance of implantation.⁵
The results demonstrated that Cyclogest^® 400mg achieved the required endometrial response in 90-94% of women. Additionally, similar transformation of the endometrium to early and late secretory states across Cyclogest^® 200mg administered twice daily, Cyclogest^® 400mg administered twice daily and 90mg vaginal gel administered once daily was indicated.⁵ This is relevant given the growing evidence indicating a direct correlation between serum progesterone levels and pregnancy in frozen embryo transfer (FET) cycles with artificial endometrial preparation.^17,18

A: Progesterone plasma concentrations after first dose application of different vaginal progesterone preparations on cycle Day 15 (A).

B: After repeated dose application on cycle days 24/25 (B).

bid, twice daily; od, once daily.
Adapted from: Duijkers et al., Hum Reprod 2018.⁵

Cyclogest^® 400mg BID demonstrated an adequate endometrial response in 94% of women in a trial.

*p<0.05 vs Cyclogest^® 400mg BID bid, twice daily; od, once daily. Adapted from: Duijkers et al., Hum Reprod 2018.⁵

Cyclogest^® supports the achievement of pregnancy
In a pivotal randomised phase III clinical trial involving 769 patients undergoing IVF, Cyclogest^® 400mg achieved a clinical pregnancy rate (CPR) of 38.3% (FAS dataset) and 38.1% (PP dataset) after 38 days administration, indicating that Cyclogest^® is an effective treatment for LPS in ART. Biochemical pregnancy and clinical implantation rates were comparable for both Cyclogest^® 400mg vaginal pessaries and 90mg vaginal gel.¹⁰

Pregnancy rates (biochemical and clinical), Days 18, 38 and 70 in the Full Analysis Set (N = 737).

BPR, biochemical pregnancy rate; CPR, clinical pregnancy rate; FAS, full analysis set; PP, per protocol set. Three patients were included in the FAS but did not have Day 38 pregnancy information.
Adapted from: Saunders et al., Hum Reprod 2020.¹⁰

It has also been demonstrated that 400mg of micronised vaginal progesterone administered twice daily may increase the number of live births in women with early pregnancy bleeding and a previous miscarriage.¹⁹ These findings have led to recommendations by NICE to offer vaginal micronised progesterone 400mg twice daily to women with an intrauterine pregnancy confirmed by a scan, if they have vaginal bleeding and have previously had a miscarriage.²⁰

Furthermore, data has shown that vaginal progesterone can help to reduce the risk of preterm birth before 34 weeks in women with a previous history of preterm birth, and in women with a short cervix (25mm or less). In these cases, progesterone treatment is recommended to start between 16+0 and 24+0 weeks of pregnancy and continue until at least 34 weeks. NICE therefore recommends that progesterone treatment should be offered as an equal option with cervical cerclage.²¹

Additional benefits of Cyclogest^®

Cyclogest^® contains a natural progesterone

Cyclogest^® is bioidentical to the progesterone produced by the mother-to-be’s body.²² Natural progesterone has no adverse effects on high-density lipoproteins, no teratogenic effects, and is more effective than synthetic derivatives in inducing secretory changes at the endometrium.²³

Progesterone

Progesterone
molecule

Progesterone in Cyclogest^®

Bio-identical progesterone
molecule in Cyclogest^®²²

Adapted from: National Center for Biotechnology Information. PubChem Compound Summary for CID 5994, Progesterone 2022.²⁴

Cyclogest^® has shown to be well-tolerated

In both the 2018 randomised, observer-blind study,⁵ and the 2020 pivotal randomised phase III clinical trial,¹⁰ Cyclogest^® was well tolerated. Adverse event (AE) rates were comparable among patients treated with Cyclogest^® and 90mg progesterone vaginal gel. The majority of AEs were mild or moderate in intensity and explained by the hormonal action of the administered drugs.^5,10 No differences in blood loss were found between Cyclogest^® and 90mg progesterone vaginal gel in pregnant patients throughout the 2020 study period.¹⁰

	Progesterone vaginal pessaries n=385	Progesterone vaginal gel n=383	Total n=768
Number of patients with any AE	168 (43.6%)	171 (44.6%)	339 (44.1%)
Number of patients with any SAE	6 (1.6%)	13 (3.4%)	19 (2.5%)

AE, adverse event; SAE, serious adverse event.
Adapted from: Saunders et al., Hum Reprod 2020.¹⁰

Cyclogest^® Benefits

There are a number of ways in which Cyclogest^® is a more convenient treatment option than other progesterone formulations:

Cyclogest^® is a self-lubricating pessary (Suppocire^® BS2 creates a smooth outer layer) that is small and discreet.
Cyclogest^® can be inserted easily by the patient without the need of an applicator.
Cyclogest^® requires only twice daily administration² to easily fit around a woman’s life.
Cyclogest^® can also be administered rectally, where vaginal administration is not possible.²
Cyclogest^® is suitable for vegan and vegetarians. This is certified with the Vegan Society.

Cyclogest^® provides a higher dosage treatment option

The option of a higher dose formulation with Cyclogest^® 400mg will improve ART success rates and decrease the need for adding progesterone injections to the IVF treatments. This is more convenient both for the clinicians and for the patients and will also reduce the total cost of the treatment.

Cyclogest^® was shown to be the clinician's preferred treatment option in the UK

In a study investigating real-world prescribing habits in 73 IVF centres (comprising 58,016 fresh IVF/ICSI treatments) across the UK, it was found that Cyclogest^® was the preferred first choice for luteal phase support.³

Reported first-choice preparation for luteal support.

Adapted from: Russell R et al., Hum Fertil 2015.³

Product information

View Cyclogest^® Summary of Product Characteristics (SmPCs):

Cyclogest^® 200 mg pessaries https://www.medicines.org.uk/emc/product/5568/smpc
Cyclogest^® 400 mg pessaries https://www.medicines.org.uk/emc/product/5569/smpc

Medicinal forms & pricing information for progesterone

https://bnf.nice.org.uk/drugs/progesterone/medicinal-forms/

HCP experiences with Cyclogest^®

Interview with Dr. Stuart Lavery, Consultant Gynaecologist, Medical Director in London and Divisional Director of Women’s Health at UCLH discussing the use and benefits of Cyclogest^®.

Learn about the importance of progesterone in luteal phase support for ART patients

Find out more

Discover answers to HCPs’ common questions about Cyclogest^®.

Find out more

References

Cyclogest^® (micronised progesterone)