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PubMed This is a summary of 18 peer-reviewed journal articles Updated
Hematology · Sickle Cell Disease

Does Sickle Cell Gene Therapy Cause Infertility?

At a Glance

Yes, sickle cell gene therapy and stem cell transplants carry a high risk of permanent infertility. This is caused by the intense conditioning chemotherapy needed to prepare your body for the treatment. Patients should consult a fertility specialist early to freeze eggs, sperm, or tissue.

In this answer

4 sections

01

Why Does Treatment Cause Infertility?

02

Fertility Preservation for Females

03

Fertility Preservation for Males

04

Next Steps

Yes, both gene therapy (such as Casgevy and Lyfgenia) and stem cell transplants carry a very high risk of permanent infertility. The infertility is not caused by the new cells or the gene editing itself, but by the high-dose chemotherapy required to prepare your body for the treatment.

Because of this risk, it is critical to discuss fertility preservation (saving your eggs, sperm, or reproductive tissue) with your care team before you begin the treatment process.

Why Does Treatment Cause Infertility?

Before you can receive a stem cell transplant or gene therapy, your medical team must use chemotherapy to clear out your existing, diseased bone marrow to make room for the new, healthy cells [1][2]. This step is called conditioning.

The most common conditioning chemotherapy used for sickle cell disease is a drug called busulfan [3]. Busulfan is highly gonadotoxic, meaning it directly damages the reproductive organs—the ovaries in females and the testicles in males [4][5]. While lower-dose chemotherapy (reduced-intensity conditioning) carries a lower risk than high-dose treatments, the chance of infertility is still significant, so fertility preservation is recommended regardless of your conditioning type [6][7].

Fertility Preservation for Females

For females, the chemotherapy often causes premature ovarian failure, meaning the ovaries stop producing eggs and hormones [8][4]. This can also cause early menopause. You should ask your doctor if you will need hormone replacement therapy (HRT) after treatment to protect your bone and heart health, as well as manage menopause symptoms.

To preserve your ability to have biological children in the future, several options are available:

  • Egg or embryo freezing: This involves taking hormone medications to stimulate your ovaries to produce multiple eggs, which are then retrieved and frozen [9][10].
  • Ovarian tissue cryopreservation: If you cannot undergo hormonal stimulation, or if you have not yet gone through puberty, a surgeon can remove and freeze a small piece of ovarian tissue for future use [11][12].

Important safety note: The hormone medications used for egg freezing can increase the risk of blood clots and vaso-occlusive crises (VOCs) in people with sickle cell disease [13][14]. This process must be carefully monitored by both a fertility specialist (reproductive endocrinologist) and your hematologist.

If you freeze your eggs or embryos, you should also discuss with your medical team whether your body will be healthy enough to safely carry a pregnancy after surviving the transplant, or if you will need to consider a surrogate.

Fertility Preservation for Males

For males, the conditioning chemotherapy typically severely impairs or completely stops sperm production [5][4]. Options to preserve fertility include:

  • Sperm freezing (semen cryopreservation): This is the most common and straightforward method for adult and adolescent males who have gone through puberty [15].
  • Testicular tissue cryopreservation: For young boys who have not yet reached puberty and cannot produce sperm, removing and freezing a small piece of testicular tissue is an option [16][17].

Keep in mind that sickle cell disease itself, frequent priapism, and medications like hydroxyurea can lower sperm count and quality before you even begin the transplant or gene therapy process [15][16]. If you have been taking hydroxyurea, you may need to pause the medication for several months (under your doctor’s supervision) before freezing your sperm to ensure the best possible quality. Females should also ask their doctor if they need to pause any medications before egg freezing.

If pausing your disease-modifying medication makes you anxious about experiencing pain crises, talk to your hematologist about how your sickle cell will be managed during this time. They may switch you to regular blood transfusions to keep you safe and minimize crises while you prepare to preserve your fertility.

Next Steps

If you are considering a curative therapy for sickle cell disease, ask for a referral to a fertility specialist as early as possible. Do not wait until your treatment date is set, as fertility preservation can take weeks or months to complete safely [9][18]. Fertility preservation can also be expensive, so it is a good idea to ask your team or a social worker about financial navigators, fertility grants, or insurance advocacy to help with the costs.

Common questions in this guide

Why does sickle cell gene therapy cause infertility?
The infertility is not caused by the gene therapy or the new stem cells themselves. Instead, it is caused by the high-dose chemotherapy required beforehand to clear out your diseased bone marrow, which permanently damages the ovaries or testicles.
Can I preserve my fertility before a sickle cell stem cell transplant?
Yes, fertility preservation is strongly recommended before starting your treatment. Females can freeze eggs, embryos, or ovarian tissue, while males can freeze sperm or testicular tissue.
Is it safe to freeze my eggs if I have sickle cell disease?
Egg freezing requires hormone medications that can increase the risk of blood clots and pain crises in people with sickle cell disease. To keep you safe, this process must be carefully monitored by both a reproductive endocrinologist and your hematologist.
Do I need to stop taking hydroxyurea before freezing sperm?
Hydroxyurea can lower sperm count and quality, so your doctor may recommend pausing the medication for several months before freezing your sperm. During this time, your hematologist might switch you to blood transfusions to help prevent pain crises.
Will I need hormone replacement therapy after sickle cell gene therapy?
Females who undergo conditioning chemotherapy often experience premature ovarian failure or early menopause. You should ask your doctor if you will need hormone replacement therapy after treatment to protect your bone and heart health, and to manage menopause symptoms.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What specific conditioning chemotherapy will I receive, and what is its exact risk of causing permanent infertility?
  2. 2.How will you coordinate with a fertility specialist to ensure my sickle cell disease is managed safely while I undergo fertility preservation?
  3. 3.If I need to pause hydroxyurea or other medications before preserving my fertility, what is the plan (such as blood transfusions) to prevent pain crises during that time?
  4. 4.If I am female, will I need hormone replacement therapy (HRT) after treatment to protect my bone and heart health?
  5. 5.Based on my organ health, will I be able to safely carry a pregnancy in the future, or should I be prepared to use a surrogate?
  6. 6.Can you connect me with a social worker or financial navigator to help cover the costs of fertility preservation?

Questions For You

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References

References (18)
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    Exagamglogene Autotemcel for Severe Sickle Cell Disease.

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    Long-term event-free survival, chimerism and fertility outcomes in 234 patients with sickle-cell anemia younger than 30 years after myeloablative conditioning and matched-sibling transplantation in France.

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This page provides educational information about the fertility risks associated with sickle cell disease treatments. It does not replace professional medical advice; always consult your hematologist and a fertility specialist about your specific medical situation.

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