As demonstrated by the series of case discussions that follow, incorporating fertility preservation into cancer care requires flexibility on a case-by-case basis to consider a patient’s wishes as well as the optimal course of therapy needed to treat the disease.
Fertility preservation and breast cancer
A 34-year-old woman presented with an isolated 4-cm, firm left breast mass. After visualization by ultrasound and mammogram, core biopsy was performed, which demonstrated estrogen and progesterone receptor-negative and HER2-negative infiltrating ductal carcinoma. Treatment planning was discussed with the patient and included timing of chemotherapy, lumpectomy versus mastectomy, and the use of radiation therapy. The patient opted for primary surgery with lumpectomy followed by chemotherapy and radiation. Fertility preservation was also discussed, and the patient, who was single and had no children, stated that she would want to pursue as many options as possible to try and have a child after her treatment. After meeting with the surgical oncologist, the patient met with an oncofertility patient navigator, and her case was discussed with the multidisciplinary oncofertility team that included the patient’s oncologists, a reproductive endocrinology infertility specialist, and the patient navigator. The patient then met with the reproductive endocrinology infertility specialist who discussed fertility preservation options, including embryo cryopreservation, oocyte cryopreservation, and ovarian tissue cryopreservation. The patient opted for embryo and oocyte cryopreservation, and oral contraceptives were started immediately in preparation for oocyte retrieval following surgery. On final pathology, all lymph nodes and margins were noted to be free of tumor cells. During her four-week recovery from surgery, the patient underwent successful ovarian stimulation and oocyte harvest, which resulted in the cryopreservation of several oocytes and four embryos using an anonymous sperm donor. The patient subsequently began adjuvant chemotherapy to be followed by radiation, and she intends to pursue a pregnancy in the future with her preserved reproductive tissue.
Fertility preservation and testicular cancer
A 28-year-old single male presented to his internist for evaluation of a painless, firm, left testicular lump. A scrotal ultrasound revealed a 3-cm heterogeneous left testicular lesion, prompting a referral to a urologist. Repeat physical examination confirmed the presence of an indurated, nontender, left testicular mass. Serum tumor marker levels revealed normal alpha-fetoprotein, beta-hCG, and LDH levels. At that time, the patient was counseled regarding treatment options, and a recommendation was made for left radical orchiectomy. Additionally, he was encouraged to undergo sperm cryopreservation before surgery. He agreed to pursue each of these procedures. The patient noted upon questioning that he was engaged and that he and his fiancée had been trying to achieve a pregnancy for one year without success. He also reported that his fiancée had recently seen a reproductive endocrinologists for evaluation of her reproductive health. The oncofertility patient navigator was contacted, and she helped arrange semen analysis testing with concurrent sperm cryopreservation. The patient provided two separate semen samples for cryopreservation, each with an appropriate duration of 2–3 days of preceding abstinence. Both semen analyses revealed normal ejaculate volume, severely low sperm concentration (<100,000 sperm per mL), a moderately low percentage of sperm with motility, and a moderately low percentage of sperm with normal morphology. A total of six vials of sperm were cryopreserved, and a test thaw revealed that 25% of the sperm had progressive motility postthaw. The patient’s case was subsequently presented at the multidisciplinary oncofertility grand rounds, attended by his urologist, his wife’s reproductive endocrinologist, and the oncofertility patient navigator. A recommendation was made for the couple to undergo IVF with intracytoplasmic sperm injection (ICSI) given the severe male factor infertility present.
The patient underwent left radical orchiectomy, revealing a nonseminomatous mixed germ cell tumor. Postoperative imaging revealed a normal chest x-ray and no evidence of retroperitoneal lymphadenopathy, consistent with clinical stage I disease. After meeting with a medical oncologist and discussing treatment options, the patient opted for primary platinum-based chemotherapy consisting of two cycles of bleomycin, etoposide, and cisplatin. Upon completion of chemotherapy, he underwent serial semen testing every six months for two years. Each semen analysis showed normal ejaculate volume with azoospermia. Two years after completion of chemotherapy, the couple underwent IVF/ICSI using his cryopreserved sperm, and a singleton pregnancy resulted.
This case accentuates several important points. First, men affected by cancer may not initially volunteer their active efforts to achieve a pregnancy nor their desire for future paternity. It is imperative that the urologist or oncologist discuss the potential effects of cancer and cancer therapy with the patient, preferably before the initiation of treatment. Second, many males diagnosed with cancer present concurrently with impaired semen parameters. These changes may be due to a variety of factors, including fever, cytological immune response, hypogonadism, and congenital or acquired testicular abnormalities. Finally, surgical therapy and chemotherapy may result in persistent azoospermia, further highlighting the importance of offering sperm cryopreservation before the initiation of cancer therapy.
Fertility preservation and rectal cancer
A 38-year-old woman with a history of hemorrhoids noticed bright red blood in her stool for six months. When the bleeding did not stop and became associated with abdominal pain and some intermittent constipation, she underwent a colonoscopy which revealed a suspicious mass in the rectum. Biopsy results demonstrated high-grade adenocarcinoma, and a CT scan of the chest, abdomen, and pelvis indicated disease had spread to some local lymph nodes. No evidence of disease was seen in other organs. At the time of diagnosis, the patient had one 3-year-old daughter, and she and her husband had been trying to conceive their second child.
Treatment for stage III rectal cancer involves surgery as well as preoperative chemotherapy and radiation to the pelvis. In this case, pelvic radiation was the most significant threat to future fertility, and options, including pretreatment oophoropexy to move the ovaries away from the site of maximum radiation, were discussed with the patient and her husband. In addition, the decision was made to use a 5-FU-based chemotherapy regimen instead of the more gonadotoxic oxaloplatin. After meeting with her surgeon, the patient was referred to the oncofertility team, where additional options for oocyte or embryo cryopreservation were also discussed. The patient opted for oocyte retrieval and embryo cryopreservation prior to her scheduled oophoropexy and subsequent neoadjuvant chemotherapy and radiation. Dosimetry was specified to minimize exposure of the uterus and ovaries to radiation. At the time of surgery, eight weeks following chemoradiation, a 22-cm section of distal colon and rectum were removed, and margins were declared free of tumor. Thirteen mesorectal lymph nodes showed no evidence of residual cancer, and the patient recovered without complications. To date, 18 months after the completion of therapy, she has not yet become pregnant, although her periods have returned. The patient and her husband are now discussing the possibility of working with a reproductive endocrinologist to attempt a pregnancy using their cryopreserved embryos. If the patient’s uterus is determined to be too fibrotic postradiation to sustain a pregnancy, they have decided not to pursue the use of a surrogate and may instead investigate adoption possibilities.