Study: Do BRCA mutations affect fertility?
|At a glance||Questions for your doctor|
This study is about:
Whether having a mutation affects ovarian reserve, which in general describes the capacity of ovaries to provide eggs that will ultimately result in a successful pregnancy.
Why is this study important?
"Ovarian reserve"—the amount of healthy eggs a woman has—is affected by her age. The older a woman gets the fewer healthy eggs she has to release from her ovariy each month. Because of this, age is often a factor in fertility and family planning. If faving a mutation also affects fertility, this would be more important information for women to take into account for family planning.
- mutation carriers had lower ovarian reserve, as measured by the concentration of the hormone AMH, than women who did not have mutations.
- There was no difference in ovarian reserve between women with mutations and women without mutations in .
What does this mean for me?
While the association between mutation carriers and lower ovarian reserve adds to previous data, more research will need to be done to prove this link. The actual difference in ovarian reserve found in this study was relatively small. Women with mutations may want to consult with both genetics experts and fertility experts to coordinate their family planning and their plans for cancer screening and preventive surgeries. mutation carriers who have been diagnosed with cancer should request a referral to a fertility expert if they are concerned about the affects of treatment on their ability to conceive.
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Human Embryology. Retrieved from: “Gametogenesis.”
Phillips K, Collins IM, Milne RL, et al. “Anti-Mullerian hormone serum concentrations of women with germline or mutations.” Human Reproduction. Published online first on April 19, 2016.
The Society of Obstetricians and Gynecologists of Canada. Retrieved from: “Age and Fertility.”
Whitman-Elia, GF. Retrieved from: “Low Ovarian Reserve- What does it really mean?”
This article is relevant for:
Women with a BRCA mutation who want to become pregnant
This article is also relevant for:
People with a genetic mutation linked to cancer risk
Breast cancer survivors
Women under 45
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IN DEPTH REVIEW OF RESEARCH
A woman is born with all of the eggs she will have throughout her life. Each month during her menstrual cycle, she releases one egg and in general, the healthier eggs are released when she is younger and the less healthy eggs are released later on. This is often referred to as lower ovarian reserve. Healthier eggs have a higher chance of resulting in a pregnancy, making it more difficult for women to get pregnant at older ages.
Some studies have suggested that genes are involved in reproductive aging, while others have not. Kelly-Anne Phillips and colleagues at the Peter MacCallum Cancer Centre in Australia and colleagues published findings in the journal Human Reproduction where they looked at how status affected ovarian reserve (as measured by concentration of the hormone called AMH (Anti-Müllerian hormone) in the blood.
Researchers of this study wanted to know:
- Does having a or mutation result in women having a lower ovarian reserve?
Population(s) looked at in the study:
The researchers used blood samples from 172 mutation carriers and 216 women from families with mutations who did not carry the mutation in their family, as well as 147 mutation carriers and 158 women from families with mutations who did not carry the mutation in their family. These women were between the ages of 25-45, had two intact ovaries and had no personal history of any cancer (except for non-melanoma skin cancer). Researchers measured AMH (Anti-Müllerian hormone) concentrations in the blood, which is a measurement of ovarian reserve as AMH is a hormone produced by eggs and represents a woman’s overall egg pool. AMH is a good measurement of ovarian reserve and is one of the most important tests that fertility specialists use when counseling patients.
- On average, mutation carriers had lower ovarian reserve as measured by AMH concentrations than women who did not carry mutations.
- The difference is comparable to a two-year increase, meaning a 35-year old woman who is a carrier and a 37-year old woman who is a non-carrier had similar ovarian reserves.
- There was no difference between the average ovarian reserve as measured by AMH concentrations between women with mutations and women without mutations.
The sample size used in this research study was relatively small. While the researchers saw that there was no difference in AMH concentrations between carriers and non-carriers, this may be because there were not enough patients in the study for the researchers to see a difference.
While this study suggests an association between mutation status and a lower ovarian reserve, more work needs to be done to confirm this finding, in addition to the finding, as it was a relatively small study. Additionally, because the difference in AMH concentrations between mutation carriers and non-carriers was not large, the authors write “…it is possible that the findings of our study might not translate to clinically relevant fertility implications for younger women, but may be important for the subgroup of mutation carriers who wish to conceive in their late 30s or 40s when fertility is reduced even in the general population.” Young mutation carriers do not need to rush to have children based on these findings alone. However, women in their late 30s and 40s do already have a reduced ovarian reserve due to age—may want to talk to a fertility expert, particularly if they are having trouble conceiving. These experts may suggest trying to conceive at an earlier age or freezing their eggs.
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The National Comprehensive Cancer Network (NCCN) provides guidelines for fertility in people diagnosed with cancer.
The NCCN recommends doctors discuss the following with adolescents and adults with cancer before treatment begins:
- fertility plans and preferences
- fertility preservation options, including:
- whether therapy can be delayed long enough for a cycle of egg stimulation
- medications like GnRH agonist therapy during to preserve ovarian function in premenopausal women with breast cancer
- importance of follow-up with a gynecologist or fertility specialist to monitor ovarian function over time
- risks for infertility due to cancer and related treatment
- affects of treatment on breastfeeding
- the importance of avoiding pregnancy and options for safe and effective birth control while in treatment
- safe timing for considering pregnancy after treatment
- emotional impact of discussions about fertility preservation
- financial resources for fertility preservation
- effects of treatment on sexual function during and after treatment
Doctors should refer patients as indicated for the following services:
- All patients who are interested in preserving their fertility should be referred to a fertility preservation clinic before starting treatment.
- Patients who need assistance with complex medical decision-making should be referred to a mental health professional.
- Patients who are experiencing sexual disfunction should be referred to a sexual health specialist.
- I am a mutation carrier. What factors should I take into account when deciding when I should have children?
- I am having trouble conceiving. Are their options available to help?
- How do fertility treatments affect my cancer risk?
- How might cancer treatment affect my fertility?
The following research studies related to fertility preservation are enrolling patients.
Fertility preservation studies for women
- NCT01503190: The Immune System's Response to Young Women's Breast Cancer. This an observational trial looking at tissue samples from patients with Pregnancy-Associated Breast Cancer (PABC) versus non-PABC to understand how the immune system responds.
- NCT05443737: Evaluation of a Telehealth Oncofertility Care Intervention in Adolescent and Young Adult Cancer Patients. The purpose of this study is to evaluate the effectiveness of an intervention to improve young cancer survivors' oncofertility care.
- NCT0301168: Fertility Preservation Using Tamoxifen and Letrozole in Estrogen Sensitive Tumors Trial (TALES). Infertility as a result of cancer treatment effects long-term quality of life in survivors of reproductive-age cancers. This trial will study different options for fertility preservation in patients with estrogen-receptor-positive breast cancer.
- NCT00823654: Serum Biomarkers to Characterize the Effects of Therapy on Ovarian Reserve in Premenopausal Women With Breast Cancer or Mutations. This study will look at how cancer treatment affects the ovaries. Researchers will review blood samples before, during and after cancer treatment to look at levels of hormones that are produced by the ovaries and ask patients to fill out questionnaires about their menstrual cycles (periods), overall health and pregnancies.
- NCT01788839: Longitudinal Sexual and Reproductive Health Study of Women With Breast Cancer and . This study looks at how cancer treatment affects sexual and reproductive function. The patient will be asked to give a blood sample to see if and how cancer treatment affects the ovaries and the ability to have children (fertility). These blood draws are optional; patients can participate in the study questionnaire even if they choose not to have their blood drawn.
- NCT01558544: Cryopreservation of Ovarian Tissue. The study hopes to contribute to the development of technologies of ovarian tissue freezing-thawing the preserve fertility. The study is open to women who will undergo treatment or surgery for cancer or women with an inherited mutation who are considering undergoing risk-reducing surgery.
- NCT01788839: This study's goal is to see how cancer treatment affects sexual and reproductive function. Participants will also be asked to participate in optional blood tests to see if and how cancer treatment affects the ovaries and the ability to have children.
Fertility preservation for men
- NCT02972801: Testicular Tissue Cryopreservation for Fertility Preservation. Testicular tissue cryopreservation is an experimental procedure where testicular tissue is retrieved and frozen. This technique is reserved for young male patients, with the ultimate goal that their tissue may be used in the future to restore fertility when experimental techniques emerge from the research pipeline.
FORCE offers many peer support programs for people with inherited mutations.
- Our Message Boards allow people to connect with others who share their situation. Once registered, you can post on the Diagnosed With Cancer board to connect with other people who have been diagnosed.
- Our Peer Navigation Program will match you with a volunteer who shares your mutation and situation.
- Our moderated, private Facebook group allows you to connect with other community members 24/7.
- Check out our virtual and in-person support meeting calendar.
- Join one of our Zoom community group meetings.
If you are in your reproductive years and have been diagnosed with cancer, or you are considering steps to lower your cancer risk that will interfere with your fertility, you should request referral to a fertility expert.
- The Oncofertility Consortium maintains a national database of healthcare providers with expertise in fertility preservation and treatment of people who are diagnosed with cancer or at high risk for cancer due to an inherited mutation.
- Register for the FORCE Message Boards to get referrals from other members. Once you register, you can post on the Find a Specialist board to connect with other people who share your situation.
Who covered this study?
Medical News Today
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