It is estimated that over 1.4 million patients will be affected by cancer this year. Over 60 percent survive their disease (for patients with breast cancer, survival is approaching 90 percent).
This leaves over 948,000 survivors, many of who may not have yet started or completed their families. One side effect of cancer therapy is premature ovarian/testicular failure and/or infertility. This can create a significant amount of stress and anxiety for a patient and affect their quality of life after.
The Who, When, and How of Egg Freezing
It is estimated that over 1.4 million patients will be affected by cancer this year. Over 60 percent survive their disease (for patients with breast cancer, survival is approaching 90 percent). This leaves over 948,000 survivors, many of who may not have yet started or completed their families. One side effect of cancer therapy is premature ovarian/testicular failure and/or infertility. This can create a significant amount of stress and anxiety for a patient and affect their quality of life after.
At the Center for Reproductive Medicine, we understand the urgency of cancer therapy and other medical therapies that may compromise your fertility and we have a Fertility Preservation Center composed of a compassionate team of physicians, nurses and embryologists to help you make informed decisions about preserving your fertility. We provide expedited consultations for patients prior to and after cancer therapy, education and awareness about the effects of therapy, and support for patients as they begin the process.
The Center is also currently leading a large multidisciplinary research initiative evaluating markers predicting ovarian and sperm production failure, improved techniques for oocyte (egg) cryopreservation, in vitro maturation (IVM) and ovarian cortex cryopreservation, and medications to protect from loss of gonadal function prior to chemo/radiation therapy. Please contact us if you would like to participate in one of our ongoing studies.
Fertility Preservation For Women
All women are born with a limited number of eggs, approximately 400,000 at puberty. Prior to puberty, the gonads are relatively resistant to the effects of cancer therapy. Over time, there is a natural decline in the number of remaining eggs until a woman reaches menopause. Once a woman has depleted her ovarian reserve, at this time there is no therapy to replenish her reserve. It is well-known that cancer and other gonadotoxic medical therapies can quickly and dramatically reduce a woman's supply of eggs, leading to premature menopause in up to 80+ percent of patients. Risk factors include a women’s age, the type of chemotherapeutic agents used, or the dosage of radiation given and the cumulative dosage. Women who are older (particularly over 35) at the time of treatment, and those with Hodgkin's disease are particularly at risk.
Because it is difficult to predict whether a woman will be fertile after cancer therapy, it is important to consider fertility preservation options before starting treatment.
CRM is a proud member of LIVESTRONG’s Sharing Hope Program and as a participating center CRM works with LIVESTRONG to increase access to fertility preservation services for cancer patients.
Options Prior to Therapy
Options depend on whether a women is single, married, and how much time is available prior to cancer therapy.
In Vitro Fertilization and Embryo Freezing
*Requires between two to six weeks and a source of sperm
In vitro fertilization followed by cryopreservation (freezing) of the fertilized eggs can provide an opportunity to have a pregnancy after cancer treatment is completed. This procedure involves treatment with fertility drugs to cause development of multiple eggs. The eggs are retrieved transvaginally under light anesthesia and fertilized with the partner’s sperm. The fertilized egg is then frozen. The whole procedure requires two to four weeks and is, of course, most ideal for a patient with a partner (although donor sperm can be utilized).
IVF with cryopreservation of embryos has been used extensively for infertility treatment since the early 1980’s and is considered a safe and routine procedure. Pregnancy rates range between 30-50 percent. The embryos can be stored for a number of years until cancer treatment is completed. Even if the cancer treatment results in ovarian failure, the woman can be given hormones to mimic a normal ovulation cycle and the embryos transferred back to the uterus by a simple outpatient procedure. Sometimes this treatment option is not possible because of the need to start cancer treatment quickly.
Mature Oocyte (Egg) Cryopreservation
*Requires two to six weeks for therapy
For many years, sperm freezing prior to chemotherapy has provided a reliable method of fertility preservation. Because of the high water content in the human egg, the success of egg freezing is still considered investigational. Recent technological advances have resulted in dramatic improvements in egg survival and pregnancy rates and a few centers have reported pregnancy rates comparable to in vitro fertilization in their donor egg program.
These preliminary studies are encouraging and can be offered to patients at risk for losing their fertility as a result of gonadotoxic therapy. Like embryo freezing, this strategy typically requires a 10-14 day period of hormonal treatments to mature the eggs, thus making them suitable for freezing. It is a good option for patients who can safely delay their cancer therapy for two to six weeks.
CRM’s Fertility Preservation Center is the only program in Central Florida to offer egg freezing.
In Vitro Maturation
If cancer therapy cannot be delayed, patients can undergo a procedure where immature eggs can be retrieved. These immature eggs can be matured in the laboratory. Recent reports of pregnancies and healthy live born babies resulting from this technology holds promise for fertility preservation in female cancer patients. This is an option for those patients who cannot or do not wish to delay their cancer treatment. Similar to egg freezing, in vitro maturation is considered investigational and should be performed responsibly under ethics-board approved research protocols.
For women who require abdominal or pelvic radiation as part of their cancer therapy, it can be helpful to surgically move or suspend the ovaries (ovarian transposition) to minimize the amount of exposure to the radiation.
For women with cervical or ovarian cancer, fertility-sparing surgery may be an option depending on the stage and type of cancer. These surgical methods can be technically difficult and should only be performed by gynecologic oncologists with extensive experience with such procedures.
Medical Suppression of the Ovaries
Girls who have not yet gone through puberty are relatively protected from the effects of chemotherapy. However, even these girls can experience an early menopause years later after the treatment has been completed.
Because girls who have not yet entered puberty are relatively protected from the effects of chemotherapy, it may be useful to use a medication to inactivate or suppress the ovaries. This medication is called Depo-Lupron and is given as a monthly injection. It should be given at least 10 days before the start of chemotherapy to have maximum effect. This medication also has the effect of stopping menstrual periods. This can be useful because chemotherapy often lowers the platelet count, increasing the risk of heavy or prolonged bleeding during menstrual periods. The evidence is controversial whether this treatment is clearly able to protect a woman’s ovarian reserve, although an overall evaluation of the currently available studies does provide hope in regards to its efficacy.
Options after Therapy
For women seeking to build families post-cancer therapy, the first step should be an evaluation by a reproductive endocrinologist to assess their fertility potential.
Many women will resume regular menstrual periods after treatment. However, this does not necessarily indicate that they did not deplete their gametes or are fertile. Some women may resume fertility but undergo ovarian failure earlier than expected. Others may present with infertility from ovulation disorders or intermittent ovarian function. The most reliable way to assess fertility after cancer therapy is by measuring hormone levels in the blood. An ultrasound of the ovaries can also be useful to assess their antral follicle count.
What are the options?
Fertility Therapy And Assisted Reproductive Technologies
Once it has been determined that there is either ovulatory dysfunction or infertility, treatment options include in vitro fertilization, superovulation or ovulation induction with medications and intrauterine insemination. Their success rates vary approximately 10-12 percent for ovulation induction with oral medications and 15-20 percent for ovulation induction with gonadotropins.
Oocyte (Egg) Donation
For patients with no residual ovarian function after therapy, the use of donated oocyte with in vitro fertilization is very clearly the most successful fertility procedure that is available today. Women who are infertile or in menopause can still carry a pregnancy using eggs from an anonymous or known donor. The donor undergoes the in vitro fertilization process with retrieval of multiple oocytes transvaginally. The oocytes are fertilized with sperm. The fertilized oocytes are transferred back to the recipient’s uterus. In the meantime, the recipient’s uterus is primed with estrogen and progesterone. In women with male partners, donor eggs can be fertilized with the male partner's sperm to create embryos that are genetically related to the male partner. Costs approximate $20,000 with a pregnancy rate of 60-70 percent per cycle.
For women with compromise to the uterus after radiation therapy or surgery, a gestational surrogate can be a successful option for pregnancy. Gestational surrogacy refers to a treatment process in which a patient undergoes in vitro fertilization. After retrieval of multiple oocytes and fertilization with sperm, the embryos that result would be transferred to another woman (gestational surrogate) who carries the pregnancy to term. The intended parents are involved with the pregnancy, are typically present at the birth, and take over parenting responsibilities immediately thereafter.
Safety of Pregnancy after Cancer
Thus far, research on the safety of pregnancy after cancer is reassuring. Further research is necessary to confirm these findings.
Mothers And The Risk Of Gestation
In women with breast cancer or cancers responsive to hormones, there is a fear of recurrence with pregnancy. Although breast cancer is believed to be stimulated by estrogen and there are high levels of estrogen in pregnancy, there is currently no evidence that pregnancy after breast cancer increases the risk of recurrence or spread. This is still a controversial area and women with breast cancer should consider their options very carefully. Women with early uterine cancers may still be candidates for pregnancy if the cancer can be controlled without a hysterectomy. Uterine cancer is responsive to estrogen but also inhibited by progesterone and progesterone levels are extremely high in pregnancy.
Women who have had radiation to the pelvis or lower abdomen require special consideration with regard to pregnancy. If the uterus has been exposed to high doses of radiation, the endometrium or inner lining of the uterus may be destroyed. In this case periods will have stopped and it will not be possible for the uterus to support a pregnancy. In addition, women who have had radiation to the uterus do have a higher risk of miscarriage, early delivery, fetal growth restriction, etc, because the blood supply to the uterus is compromised. If the uterus has not been irreversibly affected, expectant management for one year may decrease these adverse events.
Another situation that requires special consideration is women who have received high doses of adriamycin, bleomycin and/or radiation to the chest. In pregnancy, the lungs and heart have to work considerably harder to pump an increased volume of blood to the baby. If the heart muscle or lungs have been damaged, it may not be apparent until an increased stress (like pregnancy) is placed on the heart and lungs and then heart failure can develop. Women who have had adriamycin, bleomycin treatment and/or radiation to the chest require careful evaluation by a cardiologist and careful follow-up in pregnancy to avoid serious complications.
The risk of birth defects in children born to cancer survivors is reported to be similar to that of the general public: approximately 2-3 percent. Treatment of cancer during pregnancy would be expected to be a serious risk to the developing fetus. But for men and women who have completed their treatment some time before pregnancy, there does not seem to be an increased risk of birth defects, miscarriages or stillborns as a result of cancer treatment.
Children born to cancer survivors do not appear to be at increased risk for getting cancer themselves (except in true inheritable cancer syndromes).
Fertility Preservation For Men
In general, the gonads of boys are relatively resistant to the effects of chemotherapy before the onset of puberty. Boys may go through a normal puberty and have normal reproductive function for a while in spite of treatment in childhood or early adolescence. Radiation therapy to the pelvis or abdomen in boys may cause enough damage to the gonads so that puberty does not occur normally.
After puberty, age does not seem to affect the quality of the sperm produced until the age of 50. However, sperm production is very sensitive to chemotherapy and radiation. Radiation to the pelvis or directly to the testicles will stop sperm production. Radiation to the upper leg or upper abdomen may cause some damage to the testicles but sperm production may recover in these cases. Radiation therapy related to bone marrow transplantation usually causes infertility but this has been reversible in a few cases with recovery of sperm production up to seven years later. Risks as with women also depend on the age of the male, type and dose of the chemotherapeutic agent used, and the field and dose of radiation used.
Options Prior to Therapy
The best way for men to preserve their reproductive potential before cancer treatment is to cryopreserve (freeze) and store semen. In the past, this was not always a good option because many men with cancer had sperm counts that are less than normal. However, now with in vitro fertilization and ICSI (intracytoplasmic sperm injection) even very small numbers of sperm can be used to establish a pregnancy.
If possible and if time permits, several semen specimens should be cryopreserved at intervals of one to three days. Most men can delay treatment for several days or a week for this purpose.
If a patient cannot produce semen secondary to surgery or another medical condition a testicular biopsy can be performed. Under anesthesia, a small section of testicular tissue is obtained and then cryopreserved. Testicular sperm cannot naturally fertilize an egg and so intracytoplasmic sperm injection must be utilized with in vitro fertilization. In addition, sperm can also be obtained from the vas deferens or the epididymis as needed and then cyropreserved. These are performed as outpatient surgical procedures.
Shielding The Testicles From Radiation
If radiation to the pelvis is part of the treatment plan, discuss the possibility of shielding the testicles from the radiation. Cure of the cancer is, of course, the most important consideration so sometimes it will not be possible to shield the testicles and adequately treat the cancer.
Options after Therapy
After treatment is completed, an assessment needs to be made whether the man is producing any viable sperm. If a semen analysis shows any sperm at all, this is a favorable sign since sperm production will generally improve over time after treatment has stopped. If the semen analysis shows no sperm at all, the semen analysis should be repeated in a lab that has experience looking for very small numbers of sperm. Occasionally sperm production will return to normal over time. Return of fertility has been reported as late as seven years after bone marrow transplantation.
Assisted Reproductive Technologies
Sometimes, if the semen is centrifuged, a very small number of viable sperm can be detected. Even very small numbers can be used for in vitro fertilization with ICSI (intracytoplasmic sperm injection). In the ICSI procedure, once oocytes (eggs) have been retrieved transvaginally, individual sperm are injected directly into the oocytes. If numbers of sperm above five million are present, intrauterine insemination can also be performed.
For men who have no sperm in the ejaculate following treatment, there are fertility options available. Microdissection testicular sperm extraction is a surgical procedure to retrieve sperm directly from the testis for use with in vitro fertilization/intracytoplasmic sperm injection. This procedure is performed by select urologists who specialize in male infertility and is carefully coordinated with the female partner's egg retrieval.
For those men whose sperm production seems to be permanently damaged, artificial insemination of the female partner using donor sperm is an option to consider. There are several large sperm banks in the country. The donors are carefully screened with respect to their personal health and family histories. The semen is tested for sexually transmitted diseases, including HIV, and then quarantined for six months. The donor is then rechecked for HIV, hepatitis, etc. and the semen is released only if all the testing is negative. Using these large sperm banks, it is usually possible to match the physical characteristics of the male partner and often the hobbies or interests.
American Society For Reproductive Medicine (ASRM) – Www.Asrm.Org
Lance Armstrong Foundation – Www.Livestrong.Org
American Cancer Society – Www.Cancer.Org
Fertile Hope – Www.Fertilehope.Org
CRM Is A Proud Member Of LIVESTRONG’s Sharing Hope Program And As A Participating Center CRM Works With LIVESTRONG To Increase Access To Fertility Preservation Services For Cancer Patients.
Contact Our Winter Park, Flordia Egg Freezing and Fertility Preservation Specialists
Contact our practice in Orlando, Florida to learn more about egg freezing and fertility preservation.