The number of reported new cancer cases is increasing every year. The probability of surviving cancer is high and is continually improving. The cancer treatment may induce ovarian or testicular failure by damaging ovarian follicles in females and spermatogonia in the males. Gonadal failure may affect all aspects of reproductive health, including pubertal development, hormone production, and sexual function in adult life. Therefore, the primary goal for cancer treatment is to ensure the highest possibility of cure and to maintain the reproductive health. The cancer patients should be provided with maximal chance to make an optimal decision without any significant impact and delay in cancer treatment. As a result of treatment innovations, the survival rates of young people have increased substantially; therefore, the need of fertility preservation has increased as well. The sperm cryopreservation and embryo cryopreservation have been standard methods of fertility preservation. Recently, the American Society for Reproductive Medicine has removed the experimental label from oocyte cryopreservation. However, other fertility preservation options including ovarian tissue and whole ovary cryopreservation and testicular tissue cryopreservation for pre-pubertal boys are still considered experimental. A coordinated approach by gynecologists, urologists, oncologists, pediatricians, surgeons, fertility specialists and counselors is required to make use of available fertility preservation options. Timely and complete information on the impact of cancer treatment on fertility and fertility preservation options should be presented to all patients when a cancer treatment is planned. The possibility of fertility preservation removes a huge concern and enables cancer patients to concentrate on their treatment and getting better. The purpose of this review is to present different options currently available to preserve fertility in men, women and adolescent children diagnosed with cancer and undergoing gonadotoxic therapy. All options are listed in two tables for quick reference. Most of the information is extracted from recent publications and presented in such a manner that it is valuable for cancer patients and professionals associated with fertility preservation.
Cancer spares no age group and loss of fertility is a major concern for patients after cancer treatment. Gonadal failure especially in young age may affect all aspects of reproductive health, including pubertal development, hormone production, and sexual function in adults. With advancement in cancer treatment, the probability of surviving cancer is high and is continually improving [
Currently sperm banking, regardless of the source (ejaculated, epididymal or testicular) and embryo banking are the standard methods to preserve fertility for cancer patients [
In many instances the cancer may not allow enough time to get results for communicable diseases before cryopreservation and the decision to cryopreserve sperm, oocytes, embryos or gonadal tissue have to be made immediately. It is, therefore, highly recommended that the specimens are stored in closed systems to avoid cross contamination in storage. Alternatively, dedicated dry shippers can be arranged for exclusive use of such high risk specimens. This article focuses on various options available to those females and males who are at risk of losing fertility due to surgery, chemotherapy, radiation or any other fertility threat.
Several studies indicate that fertility issues are very important to younger women with cancer. Studies from Canada, Sweden and US showed that 50% - 60% of women below 40 years with cancers expressed a wish to have one or more children in the future. An early referral to a fertility specialist who can provide clear advice can help the patients make an informed decision about fertility preservation [
American Society of Clinical Oncology recommends that as part of education and informed consent before cancer therapy, oncologists should address the possibility of infertility with patients and be prepared to discuss possible fertility preservation options or refer patients to reproductive specialists offering fertility preservation [
Most common and clinically applicable fertility preservation options for men and adolescent boys are summarised (
Sperm cryopreservation is one of the most well-established techniques in assisted reproductive technology laboratories worldwide. It is a useful tool for fertility preservation in adolescent and adult males. The sperm sample can be obtained by ejaculation (masturbation, vibratory ejaculation/electroejaculation), percutaneous epididymal sperm aspiration (PESA) or testicular sperm extraction (TESE).
After cancer treatment, up to 32% (n = 11/34) of the patients had significantly worse semen analysis findings, including four who suffered from azoospermia [
Option | Technique | Suitable Candidate |
---|---|---|
Semen cryoprservation | Ejaculation | Adult/adolescent males capable of ejaculateion |
Urine analysis post ejaculation | Retrograde ejaculation cases | |
Electroejaculation/penile vibratory stimulation | Adolescent or adult males unable to ejaculate | |
PESA | Obstructive azoospermia | |
Testicular tissue cryopreservation | TESE or micro-TESE | Failure to find sperm in the ejaculate or PESA or for prepubertal boys |
Testicular protection or transposition | Lead covers or surgery | If therapy is irradiation only |
suboptimal. With the advent and successful clinical use of ICSI, only one sperm per egg is required. No matter how poor the sperm concentration and motility are, it is possible in majority of cases to find enough sperm for ICSI for successful fertilization and embryo development. It is a simple and effective way of preserving fertility potential of adult males and pubertal boys undergoing gonadotoxic treatment. Successful sperm cryopreservation has been reported in adolescent patients from the age of 13 years [
Ejaculation is the most common way of obtaining sperm. In cases of failure to find sperm in the ejaculate, search for spermatozoa in post ejaculation urine sample to rule out retrograde ejaculation is recommended. Other methods described for retrieval of spermatozoa in adolescents include penile vibratory stimulation and electro-ejaculation [
The procedures of freezing and thawing of cryopreserved sperm samples have a negative impact on sperm quality and may impact successful assisted reproduction. Therefore, cryopreservation of at least three semen samples with an abstinence period of 48 hours in between samples is recommended [
Fertility preservation technique in males varies depending on the age and nature of the treatment. Post-pubertal boys undergoing chemotherapy can have semen cryopreservation like adults. However, fertility preservation for pre-pubertal boys undergoing chemotherapy implies testicular tissue cryopreservation [
Boys or adults undergoing irradiation can have testicular protection or surgical repositioning of the testicle. Shielding of the gonadal area is the standard procedure for reducing scatter radiation to the reproductive organs and to preserve fertility [
Fertility preservation options available to women and adolescent girls are graphically represented in
and listed in
Oocyte cryopreservation allows women to maintain reproductive autonomy and is recommended for unmarried women, women with no male partner, and for those who do not wish to preserve embryos because of religious or ethical concerns [
Oocyte cryopreservation is not possible in prepubertal girls. Further, it requires ovarian stimulation which causes delay in cancer treatment. It also generates a limited number of oocytes which restricts the number of attempts for pregnancy.
Cryopreservation of embryos is an established technology. Vitrification is predominantly used. Early cleavage stage embryos can be cryopreserved with equal success using slow cooling and vitrification. However, successful blastocyst cryopreservation may be more consistently achieved with vitrification. The post-thaw survival rates after vitrification are almost 100 per cent and the pregnancy rates are similar or better than those achieved after fresh embryo transfer.
Embryo cryopreservation requires the patient to undergo ovarian stimulation and in vitro fertilization. Since a sperm sample is required, it can only be used in married or patients with male partner or willing to use donor sperm. The other limitations are that it delays cancer treatment. It is not recommended for patients suffering
Option | Technique | Suitable Situation |
---|---|---|
Oocyte cryopreservation | Usually requires ovarian stimulation and oocyte collection | ・ When enough time is available before cancer treatment of unmarried women/adolescent girls for extraction of oocytes ・ Cancer is not aggravated by stimulation hormones |
Embryo cryopreservation | Ovarian stimulation and IVF | ・ Women with male partner or using donor sperm ・ When enough time is available before Cancer treatment ・ Cancer is not aggravated by stimulation hormones |
Ovarian tissue cryopreservation | Surgical removal of ovarian tissue | ・ Urgent cancer therapy is required ・ Prepubertal girls ・ Hormone sensitive cancers |
Whole ovary cryopreservation | Surgical removal of the whole ovary | ・ Same as mentioned for ovarian tissue cryopreservation |
Combination of ovarian tissue and oocyte/embryo cryopreservation | Surgery followed by ovarian stimulation and IVF/oocyte freezing | ・ Urgent cancer therapy is required ・ Cancer is not aggravated by stimulation hormones |
from estrogen-sensitive tumors and raises ethical, legal and religious implications for disposal of embryos in case patient dies. It can’t be used in pre-pubertal patients [
Ovarian tissue cryopreservation and re-implantation is an option to preserve fertility in patient who has to undergo chemotherapy and/or radiotherapy for aggressive malignancies and there is not enough time to allow ovulation induction, oocyte retrieval and cryopreservation of oocytes/embryos. It is the only option in pre-pubertal girls or women with hormone-sensitive cancers [
It is an efficient option to preserve fertility of children and young adults, however, alternative procedures such as oocyte or embryo cryopreservation should be considered as first options especially for older patients or if there is high risk of neoplastic cells within the ovaries [
Obtaining a small volume of cortical tissue that is rich in primordial follicles enables cryopreservation of a large number of oocytes. The ovarian tissue is transported to laboratory on ice and cut into 0.3 - 2 mm thick pieces and then cryopreserved. The tissue is transplanted after cancer therapy. The slow-freezing has been used more often; however, vitrification is now gaining popularity [
Ovarian tissue cryopreservation has many advantages. It does not delay cancer therapy, avoids risk of ovarian stimulation and does not require partner or donor sperm. It also preserves a larger number of follicles and allows for resumption of ovarian function which generally resumes between 60 and 240 days post-transplant [
The frozen cortical tissue can be thawed when the patient is declared cancer free and transplanted onto the patient’s ovary (orthotopic transplantation) or other sites (heterotopic transplantation), such as the forearm or the abdominal wall. Autologous orthotopic transplantation allows for the possibility of natural fertilization [
The whole ovary is removed with a large part of vascular pedicle attached [
Eleven women underwent fresh donor ovary transplantation, and 11 underwent cryopreserved ovary auto- transplantation in the same centre, with the same surgeon. Recovery of ovarian function and follicle recruitment was assessed and the potential for pregnancy was further investigated over 1-year follow-up. Seventeen babies were born to 11 fresh and eight cryopreserved ovary transplant recipients. The auto-transplantation of cryopreserved ovary tissue yielded results almost identical to fresh transplantation. These grafts can last for a long time despite reduced AMH levels if the donor’s ovarian reserve is high. In all cases of cryopreserved autotransplantation, just as in fresh transplants, a robust return of menstrual cycling and normal ovarian function were observed at almost precisely the same time after surgery (4.5 months) in all recipients [
The use of bilateral ovarian cortex cryopreservation followed by controlled ovarian stimulation and embryo freezing has been investigated [
Ovaries can be surgically moved outside the irradiation field. It consists of releasing the ovary from its pelvic attachments and placing it behind the uterus or any other suitable place. This strategy is useful in cervical cancer [
It is intended to be an alternative to ovarian tissue transplantation to avoid risk of reintroducing cancer. The end product of this in vitro culture system is mature oocytes from primordial and primary follicles. Much work still is required to make this approach clinically applicable [
It is of paramount importance that adequate quality control and quality assurance methods are applied for collection, transportation, processing and cryopreservation to consistently achieve desirable outcome from the cryopreserved material. For sperm samples, post-thaw motility assessment from a test vial of about 200 micro litres or even less is recommended. This also helps in deciding the number of samples to be cryopreserved before initiating cancer treatment. In some instances, advanced techniques of sperm viability assessment like hypo-osmotic swelling test [
For men and prepubertal boys, spermatogonial stem cell transfer holds promise if the risk of reintroduction of cancer can be eliminated by technologies such as purging the tissue and germ cell culture [
For women and girls, unravelling the complex mechanisms of activation and suppression of follicle growth will expand the care of women diagnosed with cancer. In addition, pharmacological protection against gonadotoxic agents, in-vitro follicle growth and follicle transplantation are likely to be optimised and established within the next decade [
There has been significant advancement in fertility preservation options available to cancer patients. It is essential that individuals under threat of fertility loss should be offered appropriate fertility preservation option. An integrated approach by oncologists, urologists, surgeons, gynecologists, pediatricians, fertility preservation specialists and counselors is needed to make use of these options to improve quality of life for cancer survivors.
MuridJaved,EssamMichael, (2015) Fertility Preservation Options for Cancer Patients. Advances in Reproductive Sciences,03,67-74. doi: 10.4236/arsci.2015.34008