What Is the Role of Estradiol Patches in IVF?

By BSc, MSc (embryologist), MD (gynecologist), BSc, MSc (embryologist) and (invitra staff).
Last Update: 05/13/2020

The estrogen patches Evopad are mostly used in IVF treatments. They are self-adhesive transdermal patches that are applied directly to the skin and their active principle is estradiol, a female steroid hormone.

Besides being used in assisted reproduction treatments, estrogen patches are also used during menopause to alleviate its side effects.

What are the Evopad patches for?

The purpose of this drug is to supply estrogen exogenously. Below are the two situations in which estrogen patches can be applied:

Evopad for endometrial preparation

Endometrial preparation is part of many of the treatments carried out in assisted reproduction cycles. It is a process in which, through the administration of hormones, the endometrium reaches a receptive state that allows embryo implantation.

Naturally, estrogens are produced by the follicles that are growing in each ovary. As the woman's menstrual cycle advances, the levels of this hormone increase during the follicular phase and act on the endometrium modifying both its structure and its function, making it thicker and more receptive to the arrival of a possible embryo.

In the case of artificial insemination or fresh embryo transfers, endometrial preparation is not necessary, since the ovarian stimulation process itself has already increased estradiol levels and these naturally act on the endometrium.

However, progesterone is administered vaginally from the day of insemination or embryo transfer as a booster to increase the chances of implantation. This treatment is called luteal phase support.

However, there are certain situations in which it is necessary to resort to the use of hormonal medication for endometrial preparation. These are presented below:

  • Egg donation IVF: Since the eggs come from a donor and not from the future mother, the mother must be administered estrogen and progesterone patches before the transfer.
  • Frozen transfer: also called deferred transfer. When the embryos are frozen, either because they are leftover from previous treatment or because a fresh transfer could not be performed due to any contraindication, it is necessary to prepare the recipient's endometrium with this type of medication.

One of the reasons why a transfer can be canceled more frequently is when the woman is at risk of suffering an episode of ovarian hyperstimulation as a result of the stimulation treatment itself. In this situation, the transfer would be postponed until the woman has recovered, and, before this, the endometrium would be prepared.

Hormone replacement therapy

When menopause starts, the production and release of estrogens become irregular until it finally disappears. This occurs as a consequence of the exhaustion of the ovarian reserve because as the number of follicles decreases, the production of estradiol also decreases.

It is precisely the decrease in estrogen levels that is the main cause of the symptoms of menopause. Some of them are:

  • Hot flushes
  • Insomnia
  • Vaginal dryness
  • Risk of osteoporosis
  • Increased tendency to cardiovascular disease
  • Mood swings
  • Joint pain

In an attempt to alleviate many of the symptoms listed above, estrogen replacement therapy is used in menopause.

This medication can also be used in women who suffer from early menopause or surgical menopause, i.e. women who have had their ovaries removed and therefore do not produce estrogen.

Composition and presentation

Evopad patches contain estradiol hemihydrate, so they are natural estrogen patches but synthetically prepared in the laboratory.

Each box contains 8 square, transparent, adhesive transdermal patches, 0.1 mm thick, to be applied directly to the epidermis. It is supplied in a hermetically sealed protective envelope.

Evopad is marketed in 4 sizes corresponding to 4 different doses:

Evopad 25
its surface is 8 cm² and contains 1.6 micrograms of estradiol hemihydrate, which corresponds to a release of estradiol 25 micrograms every 24 hours. Its costs range from $37.00 to $51.28
Evopad 50
its surface is 16 cm² and contains 3.2 micrograms of estradiol hemihydrate, releasing 50 micrograms every 24 hours. One patch cost $45.00
Evopad 75
its surface area is 24 cm² and it contains 4.8 micrograms of estradiol hemihydrate, releasing 75 micrograms every 24 hours.
Evopad 100
its surface is 32 cm² and contains 6.4 micrograms of estradiol hemihydrate, releasing 100 micrograms every 24 hours Its price is at $172.44.

How Evopad is placed

The Evopad patches are placed directly on the clean and dry skin in an area below the waist, avoiding the chest area. It is recommended not to apply creams or lotions that may affect the adhesive properties of the patch, and to alternate the area of application.

Evopad must be used immediately after opening the package after carefully removing the protective film. Once opened, place it in the chosen zone, from the sides to the center, remove the second protective film and apply the part just uncovered. To avoid the appearance of wrinkles, it is advisable to press with the palm to ensure optimum adhesion. It is important to avoid contact between the fingers and the adhesive part of the patch during application.

In any case, the instructions mentioned here should never be replaced by the Evopad leaflet. In case of doubt about the application, it is advisable to consult only the specialist.

Contraindications

Evopad should not be administered in the following cases:

  • Pregnancy.
  • If you have, have had, or suspect the presence of breast cancer.
  • Allergy or hypersensitivity to the active ingredient or any of the excipients.
  • Estrogen-dependent tumors.
  • Vaginal bleeding of unknown cause.
  • Known thrombophilic disorders.
  • Acute renal or hepatic disorders.

It is advisable that if vaginal bleeding, chest discomfort, or pain, or any other symptoms occur during the use of this medicine, a specialist should be informed immediately.

Adverse reactions

The side effects that can appear more often during treatment with Evopad are those that occur in at least 10% of cases and are headaches, breast tension, and reactions in the area of application.

The less frequent reactions occur in between 10% and 1% of cases and the most prominent symptoms are insomnia, palpitations, nervousness, breast enlargement, irregular vaginal bleeding, uterine spasms and back pain.

The rare reactions (between 1% and 0.1% of the situations described) are vertigo, vomiting, abdominal pain, diarrhea, increased blood pressure, and migraine.

FAQs from users

When should I administer estrogens during the two-week wait?

By Dr. Esther Marbán Bermejo MD (gynecologist).

In the treatment of frozen embryos, oocyte or embryo donation, when carried out in a substituted cycle (with medication) the hormonal secretion of the ovary must be simulated. In this way, treatment is initiated with the patient's period and estrogens are added in tablets or patches to promote endometrial growth. Normally, a control ultrasound is performed after 10-12 days to check this growth. If the appearance is trilaminar and the thickness is above 7-8 mm, the endometrium is considered to be ready for the embryo transfer. For this, progesterone should be added as many days before the embryo to be transferred. Both hormones (estrogen and progesterone) must be maintained at least until the day of the pregnancy test and if it is positive, the first weeks of gestation will be maintained.
Read more

Do Evopad patches cause weight gain?

By Victoria Moliner BSc, MSc (embryologist).

As this is a hormonal treatment, there may be some fluid retention that makes us feel bloated for the duration of the treatment. However, the side effects of the treatment are very variable among women. In any case, the symptoms derived from this treatment are attenuated when it is abandoned.

Is Evopad always used in IVF?

By Victoria Moliner BSc, MSc (embryologist).

Evopad is not always used in endometrial preparation during IVF treatments. There are many other commercial brands as well as other types of medication for the exogenous supply of estrogens, such as oral administration.

Can Evopad patches be used during pregnancy?

By Victoria Moliner BSc, MSc (embryologist).

No, it is completely inadvisable to use Evopad if you are pregnant.

What are the costs of Evopad patches?

By Victoria Moliner BSc, MSc (embryologist).

The price of Evopad depends on the dose of estradiol supplied. For example, Evopad 25 costs between $37.00 and 51.28$ whereas Evopad 50 is $45.00. The price of Evopad 100 is at approximately $172.00.

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References

Authors and contributors

 Cristina Mestre Ferrer
Cristina Mestre Ferrer
BSc, MSc
Embryologist
Bachelor's Degree in Biological Sciences, Genetics & Human Reproduction from the University of Valencia (UV). Master's Degree in Biotechnology of Human Assisted Reproduction from the UV and the Valencian Infertility Institute (IVI). Embryologist at IVI Barcelona. More information about Cristina Mestre Ferrer
Dr. Esther Marbán Bermejo
Dr. Esther Marbán Bermejo
MD
Gynecologist
Bachelor's Degree in Medicine from the Alcalá University of Madrid. Specialist in Obstetrics & Gynecologist after being a resident doctor at Hospital General Universitario Gregorio Marañón of Madrid. Several years of experience as expert OB/GYN in the field of Reproductive Medicine. More information about Dr. Esther Marbán Bermejo
License: 282859737
 Victoria Moliner
Victoria Moliner
BSc, MSc
Embryologist
Degree in Biochemistry and Biomedical Sciences from the University of Valencia (UV). Master's Degree in Biotechnology of Human Assisted Reproduction from the UV and the Valencian Infertility Institute (IVI). Presently, she works as a Research Biologist. More information about Victoria Moliner
Adapted into english by:
 Romina Packan
Romina Packan
inviTRA Staff
Editor and translator for the English and German edition of inviTRA. More information about Romina Packan

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