REKOVELLE (Follitropin Delta)

What Is REKOVELLE and What Is It Used For?

REKOVELLE contains follitropin delta, which belongs to the family of hormones known as gonadotropins. Gonadotropins play a central role in human reproduction and fertility. Specifically, follicle-stimulating hormone (FSH) acts on the ovaries to promote the growth and maturation of ovarian follicles — the fluid-filled structures within the ovaries that each contain an egg (oocyte).

In a natural menstrual cycle, FSH produced by the pituitary gland typically stimulates the development of a single dominant follicle each month. However, in assisted reproductive technologies (ART) such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), the goal is to stimulate multiple follicles simultaneously so that several eggs can be collected. This process is called controlled ovarian stimulation (COS), and REKOVELLE is specifically designed for this purpose.

What distinguishes REKOVELLE from other FSH preparations is its unique origin. It is the first recombinant human FSH produced in a human cell line (PER.C6), rather than in Chinese hamster ovary (CHO) cells as used for follitropin alfa and follitropin beta. This human cell line production results in a glycosylation profile — the pattern of sugar molecules attached to the protein — that more closely resembles naturally occurring human FSH. The clinical significance of this different glycosylation pattern has been demonstrated in the ESTHER clinical trial program.

REKOVELLE is indicated for the treatment of female infertility and is used in women who are undergoing assisted reproductive procedures at a fertility clinic. It is used during the follicular stimulation phase that precedes egg retrieval, and its administration is always carried out under the supervision of a physician experienced in the treatment of infertility.

What Should You Know Before Taking REKOVELLE?

Before starting treatment with REKOVELLE, your doctor should conduct a thorough evaluation of the causes of infertility for both you and your partner. This assessment is important to rule out conditions that may make treatment inappropriate or require additional medical attention before proceeding with assisted reproduction.

Contraindications

Do not use REKOVELLE if any of the following apply to you:

• You are allergic to follicle-stimulating hormone or any of the other ingredients in the product
• You have a tumor of the uterus, ovaries, breast, pituitary gland, or hypothalamus
• You have enlarged ovaries or ovarian cysts that are not caused by polycystic ovary syndrome (PCOS)
• You have unexplained vaginal bleeding
• You have premature ovarian failure (early menopause)
• You have malformations of the reproductive organs that would make a normal pregnancy impossible
• You have uterine fibroids (myomas) that would make a normal pregnancy impossible

Warnings and Precautions

Blood clots (thromboembolic events): Blood clots in veins or arteries are more likely in pregnant women. Fertility treatment may further increase this risk, especially if you are overweight or have a personal or family history of thrombophilia (blood clotting disorders). Inform your doctor if this applies to you so appropriate preventive measures can be taken.

Ovarian torsion: There have been reports of ovarian torsion (twisting of the ovary) following assisted reproductive treatment. Torsion can compromise blood flow to the ovary and represents a medical emergency. Symptoms include sudden, severe lower abdominal pain.

Multiple pregnancy: Assisted reproduction increases the likelihood of multiple pregnancy (e.g., twins, triplets), which is related to the number and quality of embryos transferred and your age. Multiple pregnancy carries increased medical risks for both the mother and the babies, including premature delivery, low birth weight, and pregnancy complications. Your fertility specialist will discuss the optimal number of embryos to transfer to balance success rates against the risks of multiple pregnancy.

Miscarriage: The rate of miscarriage in women undergoing assisted reproductive treatment is somewhat higher than in natural conception. This is believed to be related in part to the underlying fertility factors that led to treatment.

Ectopic pregnancy: Women undergoing assisted reproduction have a slightly elevated risk of ectopic pregnancy (pregnancy outside the uterus) compared to natural conception. If you have a history of tubal disease, your risk may be further increased. Symptoms of ectopic pregnancy include one-sided abdominal pain, vaginal bleeding, and dizziness.

Ovarian and reproductive tumors: There have been reports of ovarian and other reproductive organ tumors in women who have undergone fertility treatment. It is not established whether fertility medications increase the risk of these tumors in women with infertility.

Pregnancy and Breastfeeding

Do not use REKOVELLE if you are already pregnant or breastfeeding. REKOVELLE is used specifically to achieve pregnancy through assisted reproduction, and its use is discontinued before embryo transfer. If you suspect you may already be pregnant, inform your doctor before starting treatment.

Other Medical Conditions

Before beginning treatment, inform your doctor if:

• Another doctor has told you that pregnancy would be dangerous for you
• You have kidney or liver disease
• You have uncontrolled thyroid or adrenal dysfunction

How Does REKOVELLE Interact with Other Drugs?

REKOVELLE is administered within a carefully managed fertility treatment protocol. While no dedicated drug interaction studies have been performed, the drug's mechanism of action and clinical use provide guidance on potential interactions. Your fertility specialist will coordinate all medications used during your treatment cycle.

Always inform your fertility specialist about all medications you are taking, including over-the-counter drugs, supplements, and herbal products. Some herbal supplements (e.g., those affecting hormone levels) could theoretically influence the ovarian response to stimulation. Your doctor will advise you on which medications to continue, adjust, or discontinue during your treatment cycle.

What Is the Correct Dosage of REKOVELLE?

REKOVELLE uses a unique individualized dosing algorithm that differentiates it from other FSH products. Instead of starting with a standard dose and adjusting based on ovarian response, the initial dose is calculated before treatment begins using two patient-specific parameters: the serum anti-Müllerian hormone (AMH) concentration and body weight. This approach, validated in the ESTHER-1 and ESTHER-2 clinical trials, aims to optimize the number of oocytes retrieved while minimizing the risk of over- or under-stimulation.

How Dosing Is Determined

Before your first treatment cycle, you will need:

• A blood test for AMH taken within the last 12 months (AMH reflects your ovarian reserve and predicts how strongly your ovaries will respond to stimulation)
• Your body weight measured at the start of treatment

Your doctor will use these values to calculate your personal daily dose using the prescribing algorithm. The dose is expressed in micrograms and remains the same every day throughout the stimulation period — it is neither increased nor decreased during the cycle.

Note: The exact dose for each patient is calculated using a specific algorithm; the table above provides general guidance only. Your doctor will determine the precise dose for you.

Administration

REKOVELLE is administered as a subcutaneous injection (under the skin), usually in the abdomen. The pre-filled pen allows for precise dose setting in increments of 0.33 micrograms. Key points for administration:

• The first injection must be given under the supervision of a healthcare professional
• After receiving adequate training, you may self-administer subsequent injections at home
• Use a different injection site each day to minimize skin irritation
• Do not inject into areas that are tender, bruised, red, or scarred
• Hold the injection button for 5 seconds after injecting to ensure the full dose is delivered
• Always use a new needle for each injection

Subsequent Cycles

If your body's response to the first cycle was too weak or too strong, your doctor may decide to discontinue REKOVELLE during that cycle. For the next treatment cycle, the doctor will adjust the dose — either higher or lower than before — based on your previous response.

Missed Dose

If you forget to take a dose, do not take a double dose to make up for it. Contact your doctor as soon as you realize you have missed an injection. Missing a dose during ovarian stimulation can affect the quality of the follicular response, so timely communication with your fertility clinic is important.

Overdose

The effects of overdose with REKOVELLE are not fully known, but ovarian hyperstimulation syndrome (OHSS) may occur. If you suspect an overdose, contact your doctor or fertility clinic immediately. Symptoms to watch for include severe abdominal pain, bloating, nausea, vomiting, and difficulty breathing.

What Are the Side Effects of REKOVELLE?

Like all medicines, REKOVELLE can cause side effects, although not everyone experiences them. The side effects listed below have been observed in clinical trials and post-marketing surveillance. Because REKOVELLE is used during a complex fertility treatment cycle involving multiple medications, it can sometimes be difficult to attribute specific symptoms solely to follitropin delta.

Injection Site Reactions

As with any injectable medication, mild reactions at the injection site — such as redness, bruising, swelling, or mild pain — may occur. Rotating injection sites can help minimize these reactions. If a reaction persists or worsens, consult your healthcare provider.

Long-Term Considerations

The relationship between fertility treatment and long-term health outcomes, including ovarian cancer risk, has been extensively studied. Current evidence from large epidemiological studies and meta-analyses does not clearly demonstrate an increased risk of ovarian or breast cancer attributable to fertility medications. However, research in this area continues, and your doctor can discuss any specific concerns you may have.

How Should You Store REKOVELLE?

Proper storage of REKOVELLE is essential to maintain the effectiveness and safety of the medication. As a biological product containing a recombinant protein, follitropin delta is sensitive to temperature extremes and light exposure.

Before First Use

• Store in a refrigerator at 2–8°C (36–46°F)
• Do not freeze — freezing will damage the product and it must not be used
• Keep in the original packaging to protect from light
• Store out of the sight and reach of children

Room Temperature Storage

REKOVELLE may be removed from the refrigerator and stored at room temperature (not above 25°C / 77°F) for up to 3 months, including the period of use after the first injection. Once removed from refrigeration, do not return it to the refrigerator. If the pen has been stored at room temperature for more than 3 months without being used, it must be discarded.

After First Use

Once you have given the first injection from a pen, the pen can be used for up to 28 days when stored at room temperature (not above 25°C). After 28 days, any unused solution must be discarded, even if solution remains in the pen.

General Precautions

• Do not use after the expiry date (EXP) shown on the pen label and carton
• Do not use if the solution contains particles or appears cloudy
• Always remove the needle after each injection and replace the pen cap
• Do not store the pen with a needle attached
• Dispose of used needles in a sharps disposal container
• Do not dispose of medicines in wastewater or household waste — ask your pharmacist about proper disposal

What Does REKOVELLE Contain?

Understanding what is in your medication can help you identify potential allergens and understand the formulation. REKOVELLE is a clear, colorless solution for injection supplied in a pre-filled multi-dose pen.

Active Ingredient

Follitropin delta — a recombinant human follicle-stimulating hormone produced using recombinant DNA technology in a human cell line (PER.C6). The concentration is 33.3 micrograms per milliliter of solution.

Available Pen Strengths

• 12 micrograms in 0.36 mL solution (pre-filled pen)
• 36 micrograms in 1.08 mL solution (pre-filled pen)
• 72 micrograms in 2.16 mL solution (pre-filled pen)

Inactive Ingredients (Excipients)

• Phenol — acts as a preservative
• Polysorbate 20 — a surfactant that helps stabilize the protein
• L-methionine — an amino acid that acts as an antioxidant
• Sodium sulfate decahydrate — a tonicity agent
• Disodium phosphate dodecahydrate — a buffering agent
• Concentrated phosphoric acid — for pH adjustment
• Sodium hydroxide — for pH adjustment
• Water for injections — solvent

Packaging

Each pack contains one pre-filled pen and 3 disposable pen needles. The pen features a dose dial with a dose window for accurate dose setting, and can deliver doses from 0.33 to 20 micrograms per injection in fixed increments of 0.33 micrograms.

How Do You Use the REKOVELLE Pre-Filled Pen?

The REKOVELLE pre-filled pen is designed for ease of use, but proper technique is essential to ensure you receive the correct dose each time. Your healthcare provider should demonstrate the injection technique before you administer the first injection yourself. The pen is for single-patient use only and must not be shared with others.

Step 1: Prepare

• Wash your hands thoroughly
• Check the pen for any visible damage — do not use if damaged
• Inspect the solution in the pen cartridge: it should be clear and free of particles. Do not use if cloudy or containing particles
• Verify you have the correct pen strength
• Check the expiry date on the pen label

Step 2: Attach the Needle

• Remove the pen cap
• Peel off the protective seal from a new needle
• Click the needle onto the pen (you will hear or feel a click)
• Remove the outer needle cap (save it for disposal later)
• Remove and discard the inner needle cap

Step 3: Remove Air Bubbles (First Use Only)

This step is only necessary before the very first injection from a new pen:

• Turn the dose dial to the drop symbol
• Hold the pen with the needle pointing up and gently tap the cartridge to move air bubbles to the top
• Press the injection button fully until “0” appears in the dose window
• Confirm that a small drop of liquid appears at the needle tip
• If no drop appears after 5 attempts, try a new needle. If still no drop, use a new pen

Step 4: Set the Dose

• Turn the dose dial clockwise until your prescribed dose aligns with the dose indicator
• If you dial past your dose, you can turn back without losing medication
• Do not press the injection button while setting the dose

Step 5: Inject

• Clean the injection site on your abdomen with an alcohol swab
• Pinch the skin firmly and insert the needle straight in
• Press the injection button fully and hold for 5 seconds (count slowly)
• Release the button and slowly withdraw the needle straight out
• If bleeding occurs, apply gentle pressure with gauze

Step 6: Dispose and Store

• Carefully replace the outer needle cap
• Unscrew and discard the used needle in a sharps container
• Replace the pen cap for storage between injections

References

1. European Medicines Agency (EMA). REKOVELLE Summary of Product Characteristics. Last updated 2023. Available from: EMA — REKOVELLE EPAR.
2. Nyboe Andersen A, Nelson SM, Fauser BCJM, et al. Individualized versus conventional ovarian stimulation for IVF: a randomized controlled trial (ESTHER-1). Human Reproduction. 2017;32(12):2534–2543. doi:10.1093/humrep/dex330.
3. Olsson H, Sandström R, Bungum L. Pharmacology of follitropin delta. Frontiers in Endocrinology. 2020;11:581. doi:10.3389/fendo.2020.00581.
4. European Society of Human Reproduction and Embryology (ESHRE). Guidelines on Ovarian Stimulation for IVF/ICSI. 2023 update.
5. Practice Committee of the American Society for Reproductive Medicine (ASRM). Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline. Fertility and Sterility. 2024;121(2):230–245.
6. World Health Organization (WHO). Infertility: A Global Public Health Issue. Geneva: WHO; 2023.
7. Bosch E, Broer S, Griesinger G, et al. ESHRE guideline: ovarian stimulation for IVF/ICSI. Human Reproduction Open. 2020;2020(2):hoaa009. doi:10.1093/hropen/hoaa009.
8. La Marca A, Sunkara SK. Individualization of controlled ovarian stimulation in IVF using ovarian reserve markers: from theory to practice. Human Reproduction Update. 2014;20(1):124–140. doi:10.1093/humupd/dmt037.

Medical Editorial Team