such as hereditary anemias or other metabolic disorders, often involve
similar treatment plans that result in gonadal failure. Therefore,
the term oncofertility is now more widely applied to any patient
facing potentially fertility threatening therapies.
The current standard of care for these patients is counseling at
the time of diagnosis and decision to treat. This is because most
fertility preservation options are only available prior to any gonadotoxic
therapy has started. Many cancers, especially in the pediatric
and AYA population, necessitate treatment very quickly after
diagnosis, so the window for counseling is easily missed.
Fertility preservation options are highly dependent on the
patient’s age plus the time frame of planned treatment start. In
post-pubertal females, oocyte and embryo cryopreservation has
been the gold standard treatment for several years. This option
does require that a patient has already started having periods. Patients
must also be able to safely wait about two weeks before starting
treatment for their condition, or the time it takes for one successful
cycle of ovarian stimulation and oocyte harvesting. These
options have a success rate of around 35% for live birth per cycle,
which is similar to rates achieved by infertile women pursuing in
vitro fertilization (IVF). 3 While oocyte and embryo cryopreservation
is widely available, the cost may be prohibitive for many
patients. There are some organizations, such as Livestrong and the
Alliance for Fertility Preservation, that will help defray some of
the cost, but these fertility preservation therapies often still cost
thousands of dollars.
For young girls who have not yet gone through puberty, or for
those that delaying the start of therapy would be dangerous, ovarian
tissue cryopreservation (OTC) was recently acknowledged as
standard of care by the American Society for Reproductive Medicine
(ASRM). 4 For this treatment, the patient undergoes surgical
removal of part or all of one ovary. The ovary is then processed,
and the ovarian cortex, which is the location of oocytes, is then
frozen for later use. Once a patient desires pregnancy, the frozen
ovarian tissue is thawed and surgically grafted back into the remaining
ovary or other pelvic structures, and endocrine function
and ovulation resumes after several months. This allows for both
spontaneous pregnancy and IVF if the patient desires. To date,
there have been over 160 live births reported from use of OTC, including
two in patients who had not yet started periods at the time
of surgery, for a success rate also about 35%. While this surgery
is often covered by insurance, ovarian processing and long-term
storage of tissue can still be expensive. There are some patients in
whom re-implantation of tissue is contraindicated due to risk of
re-introducing malignancy, such as those with blood cancers or
hereditary breast and ovarian cancer. An active area of research is
in vitro maturation (IVM). IVM aims to take immature oocytes
MOTHERS IN MEDICINE
from ovarian tissue and mature them in a scaffold so that the mature
oocytes can then be isolated and cryopreserved. This would
eliminate the need to re-implant tissue and allow patients to move
forward instead with IVF. At this time, pregnancy has only been
successful in mice and non-human primates, but research continues.
In males, the only option for fertility preservation currently is
sperm banking. This requires that the patient has completed or
nearly completed puberty. Processing and long-term storage of
sperm is typically much less expensive than options for females,
but still can be daunting for some. At this time, testicular tissue
cryopreservation (TTC) is an area of active research, and if successful,
would allow pre-pubertal boys the option for fertility preservation
as well. In this procedure, a wedge of testicular tissue is
removed and frozen for later use, with the hopes that spermatogenesis
would resume after thawing. To date, there have been no
successful pregnancies with this method, and the option is only
available at sites with an approved research protocol.
For our patients in Kentucky, Louisville has an active Oncofertility
Program that offers counseling and all options for standard
of care fertility preservation, including oocyte and embryo
cryopreservation, OTC and sperm banking. Research protocols
are also available for those who qualify. I would encourage every
provider who encounters a patient who may need gonadotoxic
therapy to make fertility preservation counseling a priority, giving
patients the opportunity to explore all their options and make a
decision for life during survivorship.
References:
1
Surveillance, Epidemiology, and End Results (SEER) Program. SEER*Stat
Database: Incidence. Available at http://www.seer.cancer.gov. Accessed August
6, 2020.
2
Chachamovich et al. Investigating quality of life and health-related quality
of life in infertility: a systematic review. J Psychosom Obstet Gynaecol. 2010;
31(2): 101-10
3
Cobo et al. Six years’ experience in ovum donation using vitrified oocytes:
report of cumulative outcomes, impact of storage time, and development of
a predictive model for oocyte survival rate. Fertil Steril 2015; 104: 1426-34.
4
Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy:
a committee opinion. Fertil Steril 2019; 112: 1022-33.
Dr. Dwiggins is a pediatric and adolescent gynecologist at Norton Children’s Medical
Group and is also Director of the Oncofertility Program at Norton Healthcare.
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