Fertility Preservation Options
Knowing that there are options for many women to protect or preserve their reproductive potential before cancer treatment begins can make it less challenging to discuss the possible reproductive side effects of treatment with your patients. There are two strategies that can be used: – (1) removing and freezing gametes (eggs) or (2) taking steps to reduce the reproductive impact of cancer treatment. For interested patients, consultation with a fertility specialist before treatment begins is highly recommended.
Cryopreservation of Gametes
Embryo freezing involves the freezing and storing of embryos obtained by ovarian stimulation, egg retrieval, and in vitro fertilization. Embryo freezing is performed by a reproductive endocrinologist. Prior to embryo freezing, the patient undergoes a cycle of in vitro fertilization. This process begins with ovarian stimulation using hormones that are self-injected daily by the patient for about 10 days, followed by a transvaginal retrieval of the eggs under anesthesia. The eggs are then fertilized with sperm from a partner or donor. The resulting embryos are frozen and stored for possible future use.
Note: Ovarian stimulation to cryopreserve eggs or embryos can be started at any time of the menstrual cycle avoiding long delays in treatment.
Who is Eligible?
Post-pubertal to pre-menopausal female (ages ~15-45) who are willing to use partner or donor sperm to create embryos and who are willing to store frozen embryos are appropriate candidates for this option.
What are the Potential Risks/Concerns?
There is a risk hormones administered for ovarian stimulation will elevate estrogen levels. Medications such as aromatase inhibitors can be given to lower estrogen levels in women with hormone-sensitive tumors or with a history of DVT/PE. This process takes 2 to 3 weeks.
Future Use and Success Rates
When ready to attempt pregnancy, the frozen embryos are thawed and transferred to the uterus of the patient or, in some cases, a gestational carrier. If the patient does not have adequate ovarian function at the time of the planned transfer, she can be given hormones for about three weeks before the transfer and three months after to support the pregnancy. Embryo freezing is a highly successful technique that has been in use for more than 25 years. Nationwide, pregnancy rates for frozen embryo cycles range from 42.4% for women under 35 and 17.8% for women over 42.1 1
References
1. SART National Data Summary 2012. https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?ClinicPKID=0
Egg freezing involves the freezing and storage of unfertilized eggs obtained by ovarian stimulation and egg retrieval. The procedure is performed by a reproductive endocrinologist. The patient undergoes a cycle similar to in vitro fertilization (IVF). The process begins with ovarian stimulation using hormones that are self-injected daily by the patient for about 10 days. Next, transvaginal (or, in some cases) trans-abdominal egg retrieval is performed under anesthesia. The unfertilized eggs are frozen and stored for possible future use.
Note: Ovarian stimulation can begin on any day of the menstrual cycle to minimize treatment delays.
Who is Eligible?
Post-pubertal to pre-menopausal females (ages ~15-45) can consider egg freezing for fertility preservation. Typically, single patients who do not have a spouse or male partner are most interested in egg freezing, because there is no sperm needed for fertilization (as is the case for embryo freezing).
What are the Potential Risks/Concerns?
There is a risk hormones administered for ovarian stimulation will elevate estrogen levels. Medications such as aromatase inhibitors can be given to lower estrogen levels in women with hormone-sensitive tumors or with a history of DVT/PE. This process takes two to three weeks.
Future Use and Success Rates
When ready to attempt pregnancy, the frozen eggs are thawed and fertilized. The resulting embryos are transferred to the uterus of the patient or a gestational carrier. If the patient does not have adequate ovarian function at the time of the planned embryo transfer, she can be given hormones for about three weeks before transfer and three months after to support the pregnancy. Egg freezing is no longer considered experimental according to the American Society for Reproductive Medicine.1 Success rates in young women are similar to those seen with embryo freezing and are directly related to the age of the patient when she froze her eggs.
What are the Costs?
The costs for egg freezing range from $8,000 – $12,000.
References
Ovarian tissue cryopreservation is a technique that involves the freezing and storage of tissue from the ovarian cortex. This tissue holds primordial follicles, each containing a single immature egg. Total or partial oophorectomy (the removal of the ovary) is, generally performed using a minimally invasive surgical procedure. After removal of the ovarian tissue, the cortex is dissected off the medulla, cut into thin strips, and frozen.
Who is Eligible?
Pre-menopausal females who do not have adequate time for egg or embryo freezing and pre-pubertal females who are not able to undergo ovarian stimulation and egg retrieval may want to consider this option. Women choosing ovarian tissue cryopreservation have a planned cancer treatment regimen that carries a high risk of infertility.
What are the Potential Risks/Concerns?
There is a risk of complications from anesthesia. To minimize this risk, ovarian tissue cryopreservation may be scheduled with another procedure requiring anesthesia. Invasive procedures also carry a risk of infection. To minimize this risk, a patient may be given prophylactic antibiotics. There is also a potential risk of reseeding cancer cells when ovarian tissues are re-implanted. Ovarian tissue cryopreservation is only available at selected reproductive endocrinology centers and some children’s hospitals.
Future Use and Success Rates
Ovarian tissue cryopreservation is no longer considered an experimental procedure by the American Society for Reproductive Medicine (ASRM). However, it remains a fairly uncommon procedure, and patients should enquire about the experience of the surgical center/clinic they are considering. About 130 babies have been born world-wide using re-implantated ovarian tissue; only one birth has been reported in a patient whose ovarian tissue was cryopreserved pre-pubertally. In addition, while methods of maturing the immature eggs in the stored tissue in the lab are being studied, there have been no births to date using this approach (known as in vitro maturation).
Additional Resources
1. OTC Considerations for prepubertal patients
2. ASRM Practice Committee Guidance recognizes OTC as no longer experimental
Minimizing Reproductive Damage
Ovarian transposition refers to a surgical repositioning of the ovaries outside the pelvic radiation treatment (RT) field to reduce ovarian exposure. Ovarian transposition is generally performed using a minimally invasive surgical procedure. The fallopian tubes may be transected from the uterus to ensure adequate mobilization of the ovaries. Metal staples are placed around the ovaries in their new locations in order to assist treatment providers visualizing the ovaries, to avoid including them in the RT fields. This procedure should be performed before RT simulation.
Who is Eligible?
Patients who will be receiving pelvic radiation treatment and whose ovaries are situated within the planned treatment field may want to consider this procedure. Ovarian transposition is an option for women with a planned cancer treatment that carries high risk of infertility due to radiation. It is an option for pre-menopausal females who do not have adequate time for egg or embryo freezing, and for pre-pubertal females who are not able to undergo ovarian stimulation and egg retrieval.
What are the Potential Risks/Concerns?
This procedure carries risks for complications from anesthesia and typical risks associated with any invasive procedure, including bleeding and infection.
Future Use and Success Rates
The retention of ovarian function using ovarian transposition is not guaranteed and patients should be offered egg or embryo freezing before treatment if there are no medical contraindications. If the fallopian tubes are resected, the patient will not be able to conceive naturally. Instead the patient would need to undergo ovarian stimulation and trans-abdominal egg retrieval. Alternatively, ovaries may be re-positioned after finishing RT in order to place them back into the pelvis for traditional IVF egg retrieval. If the uterus is exposed to a high dose of radiation during treatment, the patient may not be able to carry a pregnancy herself and may have to use a gestational carrier. Ovarian transposition will not protect the ovaries from the effects of systemic chemotherapy.
Ovarian suppression involves the use of GnRH agonists (e.g, leuprolide, goserelin) to suppress the recruitment of follicles to undergo maturation, to minimize blood flow to the ovaries, or to potentially directly protect eggs within the ovaries. While the exact protective mechanism is unclear, the aim is to potentially minimize the destruction of eggs from chemotherapy. GnRH agonist is administered by injections either monthly or every three months. It should be started two to four weeks before the first chemotherapy treatment and continued throughout the duration of treatment.
Who is Eligible?
Post-pubertal to pre-menopausal females who are planning for gonadotoxic chemotherapy (not protective with radiation exposure).
What are the Potential Risks/Concerns?
This procedure will cause menopausal like symptoms, which may be intolerable for some patients; add-back therapy may alleviate some of these symptoms. The use of GnRH agonist will decrease bone density but this is largely reversible if used for no longer than six months.
Future Use and Success Rates
Ovarian suppression is an experimental procedure. It has been studied primarily in women with breast cancer and lymphoma and results evaluating effectiveness in preserving fertility are conflicting. The retention of ovarian function is not guaranteed and patients should also be offered egg or embryo freezing before treatment if there are no medical contraindications.
What are the Costs?
The cost for ovarian suppression is $350/mo.
References
1. Turner NH, Partridge A, Sanna G, Di Leo A, Biganzoli L. Utility of gonadotropin-releasing hormone agonists for fertility preservation in young breast cancer patients: the benefit remains uncertain. Ann Oncol. 2013;24(9):2224–2235. [PubMed]
2. Bedoschi G, Turan V, Oktay K. Utility of GnRH-agonists for fertility preservation in women with operable breast cancer: is it protective? Curr Breast Cancer Rep. 2013;5(4):302–308. [PMC free article] [PubMed]
For appropriate cases of early-stage gynecologic cancers, certain conservative treatments to preserve fertility may be considered:
- Radical trachelectomy for cervical cancer
- Unilateral oophorectomy for ovarian cancer
- Progestin therapy for endometrial cancer
For women seeking fertility preservation under these circumstances, referral to a gynecologic oncology surgeon is recommended.
Knowing that there are options for many men to protect or preserve their reproductive potential before cancer treatment begins can make it less challenging to discuss the possible reproductive side effects of treatment with your patients. There are two strategies that can be used – (1) removing and freezing gametes (sperm) or (2) taking steps to reduce the reproductive impact of cancer treatment. For interested patients, fertility preservation must be completed before treatment begins.
Preserving Gametes (Sperm)
Sperm banking is the freezing and storage of semen at a sperm banking facility. Semen is obtained through masturbation. It is generally recommended that men collect three specimens prior to the start of chemotherapy, with 24-72 hours of abstinence before and between each collection. Patients who can collect only a single specimen, and those who have low sperm counts or sperm with poor motility, should also sperm bank as there are new reproductive techniques to fertilize eggs despite these limitations. Once the specimen is frozen, it can be stored for many years, until the patient is ready to use it.1,2
Who is Eligible?
Sperm banking is available for post-pubertal males. The patient has to be able to collect a specimen through masturbation. If he cannot, there are alternative, medical methods of collecting sperm.
Future Use and Success Rates
When ready to attempt pregnancy, the frozen semen specimens are thawed and a sperm analysis is done. The thawed specimen(s) is used with assisted reproductive technology procedures such as intrauterine insemination (IUI) or in vitro fertilization (IVF). Success rates vary based on age and fertility status of the female partner and on the quality of the pre-treatment specimen.
What are the Costs?
Costs vary, but generally average under $1000 for collection, testing and freezing. The number of samples will influence the cost, and storage fees are usually an additional $150-$300 per year. Some sperm banks offer discounts for cancer patients or reduced rates for long-term storage.
References
1. Grayson Mathis, Charlotte E.;WebMD;”Baby Born From 21-Year Old Frozen Sperm”;(May 25, 2004); http://www.webmd.com/infertility-and-reproduction/news/20040525/baby-born-from-21-year-old-frozen-sperm
2. Guy, Sarah;Progress Educational Trust;”Sperm frozen for 22 years creates healthy baby girl”; 20, 2009); http://www.ivf.net/ivf/sperm-frozen-for-22-years-creates-healthy-baby-girl-o4125.html
This technique involves the collection of sperm by surgical removal from the testicular tissue. The patient is sedated. A reproductive urologist removes small pieces of testicular tissue by biopsy or aspiration. The tissue is examined for the presence of mature sperm. Any sperm that are found are extracted from the tissue, collected, and transferred to a sperm bank for freezing and storage.
Who is Eligible?
This technique can be used for post-pubertal males. It may be considered for patients who have no sperm found in the ejaculate (azoospermic).
What are the Potential Risks/Concerns?
These techniques involve the standard risks associated with anesthesia. To minimize risk, consider scheduling with other procedure(s) that the patient has to undergo requiring anesthesia. There are also the risks associated with an invasive procedure; to minimize risk, the patient may need prophylactic antibiotics.
Future Use and Success Rates
When ready to attempt pregnancy, the frozen specimens are thawed and used with in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI). Success rates vary based on age and fertility status of the female partner, and on the quality of the pre-treatment specimen.
Electroejaculation is a way of stimulating a patient through the use of a mild electrical current to obtain a semen sample. First, the patient is placed under anesthesia. Then a reproductive urologist positions a rectal probe over the prostate gland. The probe emits a mild electrical current to stimulate ejaculation. Any semen obtained is transferred to a sperm bank for freezing and storage.
Who is Eligible?
This technique can be used for post-pubertal males. It may be considered by those patients who would like to bank sperm but cannot produce a specimen through masturbation (because of illness, pain, anxiety, embarrassment, or religious or cultural prohibitions).
What are the Potential Risks/Concerns?
These techniques involve the standard risks associated with anesthesia. To minimize risk, consider scheduling with other procedure(s) that the patient has to undergo requiring anesthesia. There are also the risks associated with an invasive procedure; to minimize risk, patient may need prophylactic antibiotics.
Future Use and Success Rates
When ready to attempt pregnancy, the frozen semen specimens are thawed and used with in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI). Success rates vary based on age and fertility status of the female partner and on the quality of the pre-treatment specimen.
Minimizing Reproductive Damage
Testicular shielding involves the placement of shields over the scrotal sac to reduce testicular exposure. Clamshell-like shields are made during simulation and used each day of treatment with pelvic or inguinal radiation therapy. Intensity modulated radiation therapy (IMRT) may be used to minimize exposure in addition to or instead of shielding.
Who is Eligible?
This procedure can be used for patients receiving pelvic or inguinal field radiation.
What are the Potential Risks/Concerns?
Because patients may still receive some scatter radiation, they should also be offered sperm banking before treatment.
Future Use and Success Rates
Shielding reduces radiation dose to the testes by 3x – 10x. The farther the shielded testicle from the edge of the target area of radiation, the greater the reduction.1, 2
References
1. Fraass BA, Kinseela TJ, Harrington FS, et al. Peripheral dose to the testes: The design and clinical use of a practical and effective gonal shield. Int J Radiat Oncol Biol Phys. 1985;11:609–15. [http://www.ncbi.nlm.nih.gov/pubmed/3972670]
2. Yadav P, Kozak K, Tolakanahalli R, et al: Adaptive planning using megavoltage fan-beam CT for radiation therapy with testicular shielding. Med Dosim Summer;37(2):157-62. doi: 10.1016/j.meddos.2011.06.005. Epub 2011 Sep 16, 2012. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348436/]
Some cancer surgeries involve the removal of lymph nodes in the abdomen (retroperitoneal lymph node dissection [RPLND]), and these surgeries can damage the nerves involved in ejaculation. While this does not cause a man to be infertile, it does mean that, when ready to attempt pregnancy, sperm has to be retrieved in other ways. Nerve-sparing RPLND techniques should be discussed with appropriate patients, especially those interested in future fertility. Patients should also be offered sperm banking before treatment.