Lymphoma is cancer of lymphocytes, the cells that are part of the human immune system. The disease was first described in 1832 and can start anywhere lymphocytes are found (lymph nodes, spleen, bone marrow, or digestive tract). Two types are recognized; Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). The American Cancer Society estimates that approximately 3,800 women and 4,600 men will be diagnosed with HL in 2010. The majority of people diagnosed with HL are children and young adults (ages 15 to 40). Modern treatment carries high survival rates. (>80%). However, HD, by virtue of the disease itself or its treatment, poses a considerable risk to fertility in women and men, especially if it recurs after treatment.
When HD is usually suspected because of enlarged lymph nodes or other symptoms such as fever, weight loss, or night sweats, a lymph node biopsy is required for diagnosis. The biopsy requires special stains (CD15, CD 30) for proteins on the characteristic cell surface. Once certain imaging studies (especially PET) have been confirmed to detect the extent of the disease.
Chemotherapy for Hodgkin lymphoma; combination chemotherapy is used ABVD, BEACOPP or MOPP-ABV. Each of the letters represents a drug. The drug combination is used for several cycles, usually 3 to 6. This is the main treatment for HL.
Radiation external beam therapy is sometimes combined with chemotherapy. The radiation is usually localized to the area of the body that harbors enlarged lymph nodes.
Hematopoietic stem cell transplantation (HSCT). This treatment is used for resistant HL or HL that has come back after successful treatment in the past (relapse). This treatment requires 1. a very high dose of chemotherapy and possibly total body radiation and then 2. a transplant of the bone marrow stem cells that make our blood cells. The sources of these cells could be the person himself (autologous) or a donor person (allogeneic).
Effects of Hodgkin lymphoma and treatment on future fertility. It has been shown that men and women who tried to conceive after LH treatment were less likely to become pregnant than the general population (Aisner 1993).
Men: There is evidence to suggest that HL itself can affect sperm production in 50 to 70% of boys and men., probably due to impaired immune cells. Chemotherapy can also be harmful to sperm production. Alkylating agents, especially cyclophosphamide, can cause prolonged or permanent azospermia. (no sperm production). The other agents may have a reversible effect with some prospect of recovery after months or years. The final effect of chemotherapy is difficult to predict and is related to the type of regimen and the doses used. For example, the older MOPP regimen for 6 or more cycles results in a very high rate of azospermia, whereas the newer ABVD regimen often causes reversible azospermia.
HSCT involves the use of high doses of alkylating agents and sometimes radiation. It commonly results in prolonged azospermia. HL or its treatment can also affect sperm quality (shape and motility of spermatozoa) in addition to concentration. Suppression of sperm production has been suggested in trials using a group of medicines called gonadotropin-releasing hormone (GnRHa) agonists, but there is no evidence that they protect the gonads from the effects of treatment in men and women. Tests should be protected from the radiation field whenever possible.
Women: Chemotherapy for HL can result in reduced ovarian reserve and may reduce future fertility depending on the drug used, dose, frequency, intensity, age, and associated radiation treatment. Multiple studies have suggested that the risk of fertility loss is related to 1. Age > 30 years (or > 25 years with high-dose therapy) 2. Type of chemotherapy. MOPP was associated with loss of fertility than ABVD and BEACOPP. 3. Dose and frequency of chemotherapy. The increased dose of BEACOPP used in more advanced HL was more associated with ovarian failure. 4. Exposure of the ovaries to radiation. In one large study, about 20% of women experienced menopause. In another study, about 40% of women were able to conceive after treatment. In general, the published literature is not accurate in reporting fertility potential because they used menstruation as the end point. The resumption of menstruation after chemotherapy does not accurately reflect fertility potential. High-dose chemotherapy used before HSCT is associated with ovarian failure in the vast majority of women and girls.
Options for preserving fertility in men. 1. semen cryopreservation: This is a widely available and safe option in Adults. One or several sperm samples are obtained and frozen for later use. After remission, the sample is thawed and used for intrauterine insemination or in vitro fertilization. If IVF is used, a single sperm is injected directly into an associated oocyte (ICSI) and the rest of the sperm is cooled. ICSI is a very powerful tool that can compensate for the lower quality sperm found in men with LH. In preteen kids, sperm can be found in the ejaculate from the age of 12. Asking prepubescent boys to produce a sperm sample may carry some ethical consideration. Most cancer patients are interested in knowing their option about preserving genetic paternity in the future. Despite this, only about a quarter freeze their sperm, mainly due to a lack of information on sperm freezing (Schover et al 2002). A survey of more than 700 oncologists indicated that less than half offer this option to their patients diagnosed with cancer. 2. Surgical sperm retrieval (TESE). Testicular sperm extraction is a surgical procedure in which a small amount of tissue is removed directly from the tests to obtain sperm. It is used in men with azospermia before starting treatment. The sample is frozen for future use with IVF-ICSI. This is a common procedure in adults and has been reported in prepubertal children. 3. Testicular Stem Cell Freezing; either within the testicular biopsy or separate cells. This is an experimental method with no reported human pregnancy. It is considered for pre-pubescent children. Subsequently, the cells or tissue are transplanted again for sperm production.
Options for the preservation of fertility in women.
1. embryo freezing. This technology is widely available and suitable for women with a partner (or accepting sperm donors) and treatment can be delayed up to 3 weeks. It requires stimulation of the ovaries and egg retrieval (outpatient procedure under sedation). Embryos can be frozen for a long time and transferred after remission when fertility is desired.
2. egg freezing. It is used in women without a partner and declining the use of donor semen. It also requires ovarian stimulation and a 3-week delay in treatment. It is generally less successful than embryo freezing, although the use of the vitrification method can produce comparable results to embryo freezing.
3. Ovarian tissue freezing. This method is experimental. It is used in prepubescent girls or in women who need to start emergency treatment and do not have time to undergo ovarian stimulation. It is also considered in women or girls before undergoing HSCT as it is associated with a very high rate of ovarian failure. Usually, an ovary is removed by minimal access surgery (laparoscopy). The patient is discharged the same day and can start treatment immediately. The ovary is processed so that the outer part (2 mm thick) is insulated and frozen. The inner part of the ovary (does not produce eggs) is subjected to pathological examination. After remission, the ovary is transplanted back into the abdomen or under the skin.
Women and men diagnosed with Hodgkin lymphoma experience a high chance of cure. Counseling about fertility problems before treatment may allow them to keep their sperm, eggs, or embryos for future use after treatment.
