Overview

The primary focus of this article is to raise awareness not only of general information about Fanconi anaemia, but also of its predominant impact on an individual's reproductive health. Looking at what can be done to support the individuals with this disease, although currently the knowledge of how this disease affects the reproductive system is limited (‘Endocrine Disorders in Patients with Fanconi Anaemia’). Could it reduce the hormones that regulate fertility due to the inherited mutations (as described later on)? Does the disease increase the risk of reproductive system abnormalities during development? And what does the future look like for patients with the disease? Can they have children?

What is fanconi anaemia?

Firstly, it is known that Fanconi anaemia is a rare genetic disorder that affects, on average, 1 in 136000 babies (Bhandari et al.). Early signs are often evident through physical abnormalities, such as low birth weight or skin pigmentation. These are just a couple to name, as often 60-75% of those with the disease have at least one physical abnormality (Fanconi Anaemia - Symptoms, Causes, Treatment | NORD; Fanconi Anaemia in Children | Boston Children’s Hospital). Fanconi Anaemia also displays other characteristics, such as a deterioration of bone marrow. This is due to the buildup of damaged DNA within the stem cells in the bone marrow, leading to a disruption in function for producing blood cells, and eventually, the bone marrow cells begin to die (Fanconi Anaemia in Children | Boston Children’s Hospital). There is also an increased risk of cancer due to mutations in the genes that repair DNA, which could lead to increased malignant cell growth (cancerous cells) (‘What Is FA?’; Fanconi Anaemia - Symptoms, Causes, Treatment | NORD). 

Symptoms

Other symptoms that can occur are as follows:

• Fatigue
• Bruising easily
• Low blood cell count (including white blood cells and platelet levels)
• Infections 
• Nosebleeds
• Pale skin
• Delayed growth
• Kidney problems
• Gastrointestinal issues

Not all symptoms may present themselves until adulthood, but it can be diagnosed in early childhood (‘What Is FA?’; ‘Fanconi Anaemia Treatment’). 

Genetics

As previously mentioned, this disease is classified as a genetic disease, which means it can be inherited from parents who carry the mutations, but they don’t necessarily have the disease themselves. This has a 25% chance of being inherited due to the disease being recessive, meaning that two mutated forms must be inherited for the disease to occur. The mutations occur in genes that repair DNA, causing reduced stability in the DNA and an increased risk of cell death (Bhandari et al.). It has been found that at least 23 different mutations can cause Fanconi anaemia (Fanconi Anaemia | Symptoms, Diagnosis & Treatment).

Reproductive system and fanconi anaemia throughout life

Birth

As previously mentioned, no matter the gender, most patients have physical abnormalities related to Fanconi anaemia, which can affect their reproductive system. This can present itself at birth, as often male patients can be born with smaller or a disruption to the male reproductive organs (Fanconi Anaemia - Symptoms, Causes, Treatment | NORD). An example of which could be undescended testicles. For female patients, there can be abnormalities with the uterus, such as its size, which can be smaller than expected. (‘Endocrine Disorders in Patients with Fanconi Anaemia’)

Puberty

During one of the most important stages in teenage development, patients can experience puberty at a normal age, have a delayed or premature onset of puberty. Therefore, patients are often monitored throughout this time to ensure they receive the right treatment. Female patients are often evaluated for hypothalamic dysfunction (‘Gynecologic Care for Female Patients with Fanconi Anaemia’), which means that there may be an issue with the hypothalamus, which is a part of the brain that controls another section of the brain called the pituitary gland. The pituitary gland controls hormone levels in the ovaries and testes (‘Hypothalamic Dysfunction Information | Mount Sinai - New York’). A simple blood or urine sample tests for this; if this is left untreated, it can lead to infertility. Therefore, patients would receive supplementary hormones to balance hormone levels, as in both male and female patients, certain hormones related to puberty may not be adequately regulated with Fanconi anaemia (‘Endocrine Disorders in Patients with Fanconi Anaemia’; ‘Gynecologic Care for Female Patients with Fanconi Anaemia’). 

In some cases, female patients can experience heavy period flows, also known scientifically as menorrhagia. Although this is not unusual for menstruating females, those with Fanconi anaemia should be checked via ultrasound for polyps in the uterus lining (‘Gynecologic Care for Female Patients with Fanconi Anaemia’). For male patients, it is also common to experience a delayed onset of puberty(‘Brief Guide to Clinical Care for Patients with Fanconi Anaemia’); some patients may also not be able to produce any sperm in their ejaculate. This is known as Azoospermia, which limits their reproductivity.

Adulthood

The window for pregnancy is often a lot shorter for those with Fanconi anaemia, as menopause for female patients will start at around 30 years of age, instead of around 50 years of age (‘Gynecologic Care for Female Patients with Fanconi Anaemia’). This can often limit the opportunity for patients to have children, as, alongside this, patients can also experience infertility and have also been reported to have a high miscarriage rate (Untitled). Female patients are also more likely to develop tumours within the reproductive organs than the general public; this could show how these patients may experience infertility (‘Fanconi Anaemia Treatment’).

How to manage your fertility with fanconi anaemia

You may now be wondering what can be done? As shown by research, this disease is cruel and damaging to all patients who experience it. Firstly, let's focus on the possibility of pregnancy.

Due to the cancerous nature of the disease, patients who have undergone treatments such as chemotherapy will have further reductions to their fertility. Before any cancerous treatments, patients will be made aware of the preservation techniques such as embryo cryopreservation (‘Gynecologic Care for Female Patients with Fanconi Anemia’), this allows the production of an embryo outside of the human body within a lab with the patient's partner, the embryo is then frozen for future in vitro fertilization (Https; ‘IVF’). Patients can also receive treatments that can protect the reproductive organs from chemotherapy and radiotherapy, which are currently under experimentation but are not as regularly used. An example of this is the tissue cryopreservation of the ovary and testis tissue in young patients, similar to embryo cryopreservation, where the tissue is frozen to maintain the patient's fertility before any cancerous treatment. The tissue can then be used if they choose to have children in later life (‘Testicular Tissue Cryopreservation’).

Other options that can be considered for the patient are as follows (‘Gynecologic Care for Female Patients with Fanconi Anaemia’):

• Donor eggs or sperm
• Surrogacy 
• Adoption 

Due to the nature of the disease, patients will also need to consider the risk of blood loss, as the disease already limits the number of blood cells. This could put the patient's life at risk during pregnancy, and blood transfusions may be required; further complications may arise. Such as spontaneous abortions, requiring a caesarean section and failure to progress through labour (‘Gynecologic Care for Female Patients with Fanconi Anaemia’). 

Treatment to improve the quality of life for patients

To improve the likelihood of pregnancy, several treatments are available for patients, which can also enhance their overall quality of life. For example, hematopoietic stem cell transplantation involves the transfer of healthy stem cells into a patient's bone marrow from a matched blood donor. This will therefore increase the blood count in patients to reduce the depletion of bone marrow by the disease, as more healthy blood cells will be produced. However, this is not available for all patients (Bhandari et al.). 

Patients who cannot receive hematopoietic stem cell transplantation may be able to have androgen therapy. This stimulates more cell growth, increasing the number of red blood cells and potentially reducing the need for blood transfusions during pregnancy (Bhandari et al.).

Summary

With modern advancements in cryopreservation, the possibility for patients with Fanconi anaemia to remain fertile may become a reality. Although pregnancy may still be difficult for those with the disease. As a patient, there is much to consider with your healthcare provider to find the right option for you if you do want to have children. Learning that you may not be able to have children can be heartbreaking, so make sure you have the right support that may be available to you. Counselling would also be highly beneficial in a patient's position.