GONAL-f (Follitropin Alfa)
Recombinant Follicle-Stimulating Hormone for Fertility Treatment
Quick Facts About GONAL-f
Key Takeaways
- GONAL-f contains follitropin alfa, a recombinant human FSH used to stimulate follicle growth in fertility treatment
- In women, it is used for ovulation induction (when clomifene has failed), controlled ovarian stimulation for IVF, and in combination with lutropin alfa for severe gonadotropin deficiency
- In men, it stimulates sperm production when combined with hCG for hypogonadotropic hypogonadism
- The most serious risk is ovarian hyperstimulation syndrome (OHSS), which requires careful monitoring with ultrasound and blood tests
- Treatment increases the risk of multiple pregnancies; dosing and monitoring are managed by a fertility specialist
What Is GONAL-f and What Is It Used For?
GONAL-f contains the active substance follitropin alfa, which is a laboratory-produced (recombinant) version of human follicle-stimulating hormone (FSH). FSH belongs to the family of hormones known as gonadotropins, which play a central role in human reproduction and fertility. The medication is manufactured using recombinant DNA technology in Chinese hamster ovary (CHO) cells, ensuring a consistent and highly pure product that closely mimics the body's own FSH.
Follicle-stimulating hormone is naturally produced by the pituitary gland in the brain and is essential for reproductive function in both women and men. In women, FSH stimulates the growth and maturation of ovarian follicles, each of which contains an egg. In men, FSH acts on the Sertoli cells in the testes to support the process of sperm production (spermatogenesis). When the body does not produce sufficient FSH on its own, or when additional FSH is needed for fertility treatment, GONAL-f provides the necessary hormonal stimulation.
Uses in Women
GONAL-f is approved for several indications in adult women who are experiencing fertility difficulties:
- Anovulation (failure to ovulate): GONAL-f is used to stimulate ovulation in women who do not ovulate and have not responded to treatment with clomifene citrate, a first-line oral fertility medication. This is often the case in conditions such as polycystic ovary syndrome (PCOS).
- Severe gonadotropin deficiency: In combination with lutropin alfa (recombinant LH), GONAL-f is used to induce ovulation in women whose bodies produce very low levels of both FSH and LH. This condition, known as hypogonadotropic hypogonadism, means the pituitary gland does not release adequate gonadotropins to support natural follicle development.
- Controlled ovarian stimulation for assisted reproduction: GONAL-f is used to stimulate the development of multiple follicles in women undergoing assisted reproductive technology (ART) procedures such as in vitro fertilisation (IVF), gamete intrafallopian transfer (GIFT), or zygote intrafallopian transfer (ZIFT). The goal is to produce several mature eggs that can be retrieved for fertilisation.
Uses in Men
In adult men, GONAL-f is used in combination with human chorionic gonadotropin (hCG) to stimulate sperm production (spermatogenesis) in men who are infertile due to hypogonadotropic hypogonadism — a condition where the pituitary gland does not produce enough FSH and LH to support normal testicular function and sperm production. Treatment typically requires several months before sperm counts improve, as the full cycle of spermatogenesis takes approximately 74 days.
What Should You Know Before Taking GONAL-f?
Before starting treatment with GONAL-f, your fertility should be thoroughly evaluated by a physician experienced in assessing fertility disorders. This evaluation typically includes hormonal blood tests, ultrasound imaging, and a review of your medical history and that of your partner. Only a specialist in reproductive medicine should prescribe and monitor GONAL-f therapy.
Contraindications
- An allergy to follitropin alfa or any of the other ingredients
- A tumour of the hypothalamus or pituitary gland
Additional contraindications for women:
- Large ovaries or ovarian cysts of unknown origin (not caused by polycystic ovarian disease)
- Unexplained vaginal bleeding
- Cancer of the ovaries, uterus, or breast
- Conditions that make normal pregnancy impossible, such as premature ovarian failure or malformed reproductive organs
Additional contraindications for men:
- Permanent testicular damage or primary testicular failure
Warnings and Precautions
Several important warnings apply to GONAL-f treatment. You should discuss all of these with your healthcare provider before beginning therapy:
Porphyria: Inform your doctor before starting treatment if you or any family member has porphyria, a group of rare disorders caused by an inability to break down porphyrins. These conditions can be inherited and may be triggered or worsened by certain medications. If your skin becomes fragile and blisters easily, particularly in sun-exposed areas, or if you experience pain in the stomach, arms, or legs during treatment, contact your doctor immediately as they may recommend discontinuing GONAL-f.
Ovarian Hyperstimulation Syndrome (OHSS): This is the most significant medical risk associated with GONAL-f treatment in women. OHSS occurs when the ovaries over-respond to stimulation, leading to the development of large ovarian cysts, fluid shifts from the blood vessels into the abdominal and chest cavities, and potentially dangerous complications. Symptoms include lower abdominal pain, rapid weight gain, nausea, vomiting, and difficulty breathing. If you experience any of these symptoms, contact your doctor immediately. Severe OHSS can cause reduced urine output, blood clots, kidney failure, and in extremely rare cases may be life-threatening. The risk of OHSS is minimised by careful dose adjustment and monitoring, and by withholding the hCG trigger injection if an excessive ovarian response is detected.
Multiple Pregnancy: Treatment with GONAL-f significantly increases the likelihood of becoming pregnant with more than one baby (twins, triplets, or higher-order multiples). Multiple pregnancies carry elevated medical risks for both the mother and children, including premature birth, low birth weight, pre-eclampsia, and the need for caesarean delivery. The risk of multiple pregnancy can be reduced by using appropriate doses of GONAL-f and, during IVF, by limiting the number of embryos transferred to the uterus.
Miscarriage: Women undergoing ovarian stimulation or assisted reproduction have a somewhat higher risk of miscarriage compared to natural conception. This is partly related to underlying fertility factors and partly to the nature of assisted reproduction procedures.
Blood Clots (Thromboembolic Events): If you have a personal or family history of blood clots in the legs (deep vein thrombosis) or lungs (pulmonary embolism), heart attack, or stroke, the risk of these problems may increase during GONAL-f treatment. Thromboembolic events can occasionally occur independently of OHSS. Discuss your complete medical and family history with your doctor before starting treatment.
Special Considerations for Men
In men, elevated FSH levels in the blood may indicate primary testicular damage. GONAL-f is unlikely to be effective in such cases because the problem lies with the testes themselves rather than with insufficient hormonal stimulation. If your doctor decides to trial GONAL-f treatment, semen analysis will typically be performed 4 to 6 months after starting therapy to monitor whether the treatment is producing a response.
Pregnancy and Breastfeeding
GONAL-f must not be used during pregnancy or while breastfeeding. The medication is intended to help achieve pregnancy, and once pregnancy is confirmed, GONAL-f should be discontinued. If you discover you are pregnant during treatment, stop the injections and contact your healthcare provider immediately. There is no indication for continued FSH administration once conception has occurred.
Children and Adolescents
GONAL-f is not intended for use in children or adolescents under 18 years of age. Fertility treatment with gonadotropins is only appropriate for adults with diagnosed reproductive disorders.
How Does GONAL-f Interact with Other Drugs?
Drug interactions with GONAL-f are primarily related to other medications used within fertility treatment protocols. Since GONAL-f is typically prescribed and monitored by fertility specialists who carefully design the complete treatment regimen, interactions are usually anticipated and managed as part of the protocol. However, it is essential to inform your doctor about all medications you are currently taking, have recently taken, or may be planning to take.
| Interacting Drug | Type | Effect | Clinical Significance |
|---|---|---|---|
| Clomifene citrate | Synergistic | May enhance follicular response when used together | Dose adjustment may be needed; increased OHSS risk |
| Human chorionic gonadotropin (hCG) | Complementary | Used as trigger for final follicle maturation and ovulation | Essential part of protocol; OHSS may worsen if given with excessive ovarian response |
| GnRH agonists (e.g. leuprorelin, buserelin) | Protocol combination | Suppresses premature ovulation; may require higher GONAL-f dose | Standard IVF protocol; dose adjustment anticipated |
| GnRH antagonists (e.g. cetrorelix, ganirelix) | Protocol combination | Prevents premature LH surge; may require higher GONAL-f dose | Standard IVF protocol; dose adjustment anticipated |
| Lutropin alfa (recombinant LH) | Complementary | Provides LH activity needed for follicle development in LH-deficient women | Specifically indicated for hypogonadotropic hypogonadism |
No significant interactions have been reported between GONAL-f and commonly used non-fertility medications. However, certain medications may theoretically affect hormonal balance or fertility treatment outcomes. These include hormonal contraceptives (which should be discontinued before starting fertility treatment), corticosteroids (which may affect the hypothalamic-pituitary-gonadal axis), and some herbal preparations. Always provide your fertility specialist with a complete list of all medicines, supplements, and herbal products you use.
What Is the Correct Dosage of GONAL-f?
GONAL-f dosing is complex and must be individualised by your treating physician based on clinical response, ultrasound monitoring, and blood hormone levels. The doses described below are general guidelines — your actual dose may differ. Always follow your doctor's instructions precisely.
Administration
GONAL-f is administered by subcutaneous (under the skin) injection, typically in the abdomen. The pre-filled injection pen allows for accurate dose selection in increments of 12.5 IU. The first injection should be performed under the supervision of a healthcare professional, who will teach you the correct injection technique. After appropriate training, you can self-administer subsequent injections at home. Injections should be given at approximately the same time each day, and a different injection site should be chosen each day to minimise local irritation.
| Indication | Starting Dose | Dose Adjustments | Maximum Dose | Duration |
|---|---|---|---|---|
| Anovulation (women) | Individualised (typically 75–150 IU/day) | Stepwise increases based on response | 225 IU/day | Until adequate follicular response, followed by hCG trigger |
| Severe FSH/LH deficiency (women) | 75–150 IU/day (with 75 IU lutropin alfa) | Increase by 37.5–75 IU every 7–14 days | As directed by specialist | Up to 5 weeks per cycle |
| Controlled ovarian stimulation (IVF) | Individualised (typically 150–225 IU/day) | Stepwise adjustments based on ultrasound and oestradiol | 450 IU/day | Approximately 10–14 days until follicles reach target size |
| Male infertility (with hCG) | 150 IU three times per week | As directed by specialist | As directed by specialist | Minimum 4 months; may continue up to 18 months |
Ovulation Induction in Anovulatory Women
For women who do not ovulate and have irregular or absent periods, GONAL-f is given daily. If menstrual periods are irregular, treatment should begin within the first 7 days of a cycle. If periods are absent, treatment can start on any convenient day. The starting dose is individualised and may be adjusted in a stepwise fashion. When monitoring shows an adequate response (typically a dominant follicle of 17–18 mm on ultrasound with appropriate oestradiol levels), a single injection of recombinant hCG (250 micrograms) or urinary hCG (5,000–10,000 IU) is administered 24–48 hours after the last GONAL-f injection to trigger final egg maturation and ovulation. Timed intercourse is recommended on the day of the hCG injection and the following day.
If the ovarian response is excessive, treatment is discontinued and hCG is withheld to reduce the risk of OHSS. The next cycle will use a lower starting dose. If no adequate response is seen, the treatment cycle may be cancelled and a higher starting dose used in the subsequent cycle.
Controlled Ovarian Stimulation for IVF
For women undergoing IVF or other assisted reproduction procedures, the goal is to develop multiple mature follicles for egg retrieval. The starting dose is individualised based on factors such as age, ovarian reserve (measured by AMH and antral follicle count), body weight, and response in previous treatment cycles. Doses are adjusted every 2–3 days based on ultrasound measurements of follicle size and number, and serum oestradiol levels. The daily dose must not exceed 450 IU. When follicles reach the target size (typically 17–20 mm), an hCG trigger injection is given, and egg retrieval is performed approximately 34–36 hours later.
Missed Dose
If you forget to take a dose of GONAL-f, do not take a double dose to make up for it. Contact your doctor as soon as you realise you have missed a dose for specific guidance. Consistency in daily dosing is important for optimal treatment outcomes, so try to administer your injection at the same time each day.
Overdose
The effects of an overdose of GONAL-f alone are not well characterised. However, ovarian hyperstimulation syndrome (OHSS) is expected to occur if an excessive dose is given in combination with hCG. OHSS is described in detail in the side effects section below. If you suspect you have taken too much GONAL-f, contact your healthcare provider or seek medical attention. Note that OHSS typically does not develop unless hCG is also administered.
What Are the Side Effects of GONAL-f?
Like all medicines, GONAL-f can cause side effects, although not everyone experiences them. The side effects differ between women and men and vary in severity. Careful monitoring by your fertility specialist helps detect and manage side effects early. Below is a comprehensive overview of reported side effects organised by frequency.
Serious Side Effects in Women
- Lower abdominal pain with nausea or vomiting — possible signs of OHSS
- Rapid weight gain or abdominal bloating
- Difficulty breathing or shortness of breath
- Reduced urine output
- Chest pain, sudden leg swelling, or sudden severe headache — possible signs of blood clots
- Skin rash, facial swelling, or difficulty breathing — possible allergic reaction
OHSS is the most clinically significant side effect. In its mild form (common, affecting up to 1 in 10 women), it causes lower abdominal discomfort and mild ovarian enlargement. Severe OHSS (uncommon, up to 1 in 100) involves markedly enlarged ovaries, ascites (fluid in the abdomen), pleural effusion (fluid around the lungs), reduced urine output, and haemoconcentration. Complications of OHSS such as ovarian torsion (twisting) or thromboembolic events occur rarely (up to 1 in 1,000). Very rarely (up to 1 in 10,000), serious blood clot complications can occur independently of OHSS.
Side Effects in Women by Frequency
Very Common
- Ovarian cysts (fluid-filled sacs in the ovaries)
- Headache
- Injection site reactions (pain, redness, bruising, swelling, irritation)
Common
- Abdominal pain
- Nausea, vomiting
- Diarrhoea
- Abdominal cramps and bloating
- Ovarian hyperstimulation syndrome (mild to moderate)
Uncommon
- Severe ovarian hyperstimulation syndrome (OHSS)
- Significant ovarian enlargement
- Ascites (fluid accumulation in the abdomen)
Rare / Very Rare
- Ovarian torsion (twisting of the ovary)
- Thromboembolic events (blood clots in legs, lungs, or brain)
- Severe allergic reactions (rash, facial swelling, difficulty breathing)
- Worsening of asthma
Side Effects in Men by Frequency
Very Common
- Injection site reactions (pain, redness, bruising, swelling, irritation)
Common
- Varicocele (swollen veins above and behind the testes)
- Gynaecomastia (breast tissue development)
- Acne
- Weight gain
Very Rare
- Allergic reactions (rash, facial swelling, difficulty breathing)
- Worsening of asthma
Reporting Side Effects
If you experience any side effects, including those not listed above, inform your healthcare provider. Reporting suspected side effects after a medicine has been authorised is important because it allows continuous monitoring of the benefit-risk balance. You can also report side effects directly to your national medicines regulatory authority (for example, the EMA in Europe or the FDA in the United States).
How Should You Store GONAL-f?
Proper storage of GONAL-f is essential to maintain the medication's effectiveness and safety. Follitropin alfa is a protein-based medication that can be degraded by improper temperature exposure. Follow these storage guidelines carefully:
- Unopened pens: Store in a refrigerator at 2–8°C. Do not freeze at any time, as freezing will destroy the medication.
- Room temperature storage (before opening): Unopened pens may be stored at temperatures up to 25°C for a single continuous period of up to 3 months. If not used within this 3-month period at room temperature, the pen must be discarded.
- After first use: The opened pre-filled pen should be stored between 2–25°C and must be used within 28 days. Discard any remaining solution after 28 days.
- General precautions: Always keep the pen cap on to protect from light. Do not use the medication if it appears cloudy, discoloured, or contains visible particles — it should be a clear, colourless solution.
- Expiry date: Do not use GONAL-f after the expiry date printed on the label (EXP). The expiry date refers to the last day of that month.
- Disposal: Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to safely dispose of medicines you no longer need.
Keep GONAL-f out of the sight and reach of children at all times. Do not store the pen with a needle attached, as this may cause contamination or infection.
What Does GONAL-f Contain?
Understanding what GONAL-f contains helps you identify potential allergens and understand the formulation. The active substance is follitropin alfa, a recombinant human follicle-stimulating hormone produced using genetic engineering technology.
Active Substance
Each pre-filled injection pen contains follitropin alfa in the following strengths:
- GONAL-f 75 IU/0.125 mL: 75 IU (5.5 micrograms) of follitropin alfa per pen
- GONAL-f 150 IU/0.24 mL: 150 IU (11 micrograms) of follitropin alfa per pen
- GONAL-f 300 IU/0.5 mL: 300 IU (22 micrograms) of follitropin alfa per pen
Inactive Ingredients (Excipients)
The other ingredients in GONAL-f are:
- Poloxamer 188: A surfactant that helps stabilise the protein
- Sucrose: A sugar used as a stabiliser
- Methionine: An amino acid used as an antioxidant
- Sodium dihydrogen phosphate monohydrate: Buffer component
- Disodium phosphate dihydrate: Buffer component
- m-Cresol: A preservative that allows multi-dose use from a single pen
- Phosphoric acid and sodium hydroxide: For pH adjustment
- Water for injections: Solvent
Presentation
GONAL-f is supplied as a clear, colourless solution for injection in a pre-filled pen. Each pack contains 1 pre-filled injection pen and 4 disposable injection needles. The pen is designed for multiple injections, with the dose display window showing the selected dose in international units (IU). The minimum dose increment is 12.5 IU.
The marketing authorisation holder is Merck Europe B.V. (Amsterdam, Netherlands), and the manufacturer is Merck Serono S.p.A. (Modugno, Bari, Italy).
Frequently Asked Questions About GONAL-f
GONAL-f (follitropin alfa) is a fertility medication used in women to stimulate ovulation when clomifene has failed, to develop multiple follicles for IVF and other assisted reproduction techniques, and in combination with lutropin alfa for women with very low gonadotropin levels. In men, it is used together with hCG to stimulate sperm production when infertility is caused by low hormone levels (hypogonadotropic hypogonadism).
The most common side effects include ovarian cysts, headache, and injection site reactions (pain, redness, bruising, swelling). In women, abdominal pain, nausea, vomiting, diarrhoea, and bloating are also common. In men, varicocele, gynaecomastia (breast development), acne, and weight gain may occur. The most serious risk is ovarian hyperstimulation syndrome (OHSS), which requires immediate medical attention.
GONAL-f is injected subcutaneously (under the skin), typically in the abdomen. Your healthcare provider will demonstrate the correct technique before you begin self-injecting at home. Key steps include: letting the pen reach room temperature for 30 minutes before use, attaching a new needle for each injection, selecting your dose using the dose dial, inserting the needle fully into a cleaned skin area, pressing the dose button completely, and holding for at least 5 seconds before withdrawing. Always use a new injection site each day and dispose of needles in a sharps container.
OHSS is a medical condition where the ovaries over-respond to stimulation medication, becoming swollen and painful. Mild OHSS is common (up to 1 in 10 women) and involves abdominal discomfort and mild ovarian enlargement. Severe OHSS (up to 1 in 100) can cause significant fluid accumulation in the abdomen and chest, reduced urine output, blood clots, and difficulty breathing. Severe OHSS requires hospitalisation and can occasionally be life-threatening. Your doctor monitors your response carefully with ultrasound and blood tests to minimise this risk, and will withhold the hCG trigger if your ovarian response is excessive.
Yes, GONAL-f stimulates the development of multiple follicles, which increases the chance of multiple pregnancies. The risk is higher during ovulation induction cycles (where multiple eggs may be released) and can also occur with IVF depending on how many embryos are transferred. Multiple pregnancies carry higher medical risks, including premature birth and complications for the mother. Your fertility specialist will monitor follicle development carefully and may recommend measures such as cancelling the cycle if too many follicles develop, or transferring a single embryo during IVF.
Treatment duration varies by indication. For ovulation induction, daily injections continue until adequate follicular response is achieved, typically over 1–3 weeks per cycle. For IVF, stimulation usually lasts 10–14 days. For women with severe gonadotropin deficiency, treatment may last up to 5 weeks per cycle. In men, treatment with GONAL-f and hCG continues for at least 4 months, and sometimes up to 18 months, to allow sufficient time for spermatogenesis to occur. Multiple treatment cycles may be needed to achieve pregnancy.
References
- European Medicines Agency (EMA). GONAL-f Summary of Product Characteristics (SmPC). Last updated January 2025. Available at: ema.europa.eu
- ESHRE Guidelines. Ovarian Stimulation for IVF/ICSI. European Society of Human Reproduction and Embryology, 2023.
- Practice Committee of the American Society for Reproductive Medicine. Use of exogenous gonadotropins in anovulatory women: a technical bulletin. Fertility and Sterility. 2020;113(4):728-740.
- World Health Organization (WHO). WHO Laboratory Manual for the Examination and Processing of Human Semen, 6th edition. Geneva: WHO; 2021.
- Bosch E, et al. ESHRE guideline: ovarian stimulation for IVF/ICSI. Human Reproduction Open. 2020;2020(2):hoaa009. DOI: 10.1093/hropen/hoaa009
- NICE Clinical Guideline CG156. Fertility problems: assessment and treatment. National Institute for Health and Care Excellence, updated 2023.
- Humaidan P, et al. Ovarian hyperstimulation syndrome: review and new classification criteria for early diagnosis. Human Reproduction Update. 2016;22(4):444-458.
- Balen AH, et al. The management of anovulatory infertility in women with polycystic ovary syndrome: an analysis of the evidence to support the development of global WHO guidance. Human Reproduction Update. 2016;22(6):687-708.
- Behre HM, et al. Efficacy and safety of recombinant human FSH (follitropin alfa) in men with hypogonadotropic hypogonadism. Fertility and Sterility. 2014;102(5):1323-1330.
- Cochrane Database of Systematic Reviews. Recombinant versus urinary gonadotrophin for ovarian stimulation in assisted reproductive technology cycles. 2021.
Medical Editorial Team
This article was written and reviewed by licensed medical professionals with expertise in reproductive medicine, endocrinology, and clinical pharmacology.
Editorial Standards: All content follows the iMedic Editorial Standards, based on GRADE evidence framework, international clinical guidelines (ESHRE, ASRM, NICE, WHO), and peer-reviewed research. No commercial funding or pharmaceutical sponsorship influences our content.