Learning Materials

Fertility Preservation Options

Fertility preservation was initially developed for young patients undergoing gonad toxic therapies. However, in recent years increasing delays in childbearing to later reproductive years have created demand for elective fertility preservation. Serial improvements in cell and tissue cryopreservation techniques have opened more options for patients.

Fertility Preservation for Women

Fertility preservation is offered to women in a variety of clinical situations; either “elective” usually pursued for social reasons or “non-elective” to avoid damage to the ovaries from medically induced causes.

Embryo cryopreservation is the most established fertility preservation technique. It has been successfully utilized for decades, - with hundreds of thousands of births. It requires that a woman of reproductive age undergo in vitro fertilization (IVF), which includes ovarian stimulation with fertility drugs and subsequent egg retrieval. Retrieved oocytes are then fertilized by sperm from either spouse or donor.

Embryo banking is, therefore, only an option if a woman is willing to commit to a given semen provider. Many single women considering elective fertility preservation are, therefore, not interested in embryo banking. It is an excellent method of fertility preservation for couples in stable relationships.

Since ovarian stimulation requires approximately two weeks, some newly diagnosed cancer patients may not have the option of undergoing an IVF cycle before treatment has to be initiated. Even if enough time for such a cycle is available, a single cycle may not yield enough embryos for cryopreservation. Studies have documented that only approximately 8 embryos are typically cryopreserved per treatment cycle in cancer patients, which may not be enough to achieve a later pregnancy. Therefore, additional IVF attempts or other fertility preservation techniques may be required to reach an adequate level of reasonable certainty that enough fertility potential has been preserved.

How many embryos should be cryopreserved will vary between patients, and will depend on the age of the patient, her ovarian reserve, and the degree of certainty of pregnancy the woman wants once she decides to attempt conception later in life. In most women, we recommend cryopreservation of at least 10 embryos at young ages, and of even more embryos in women in their late 30's and early 40's.

Oocyte Cryopreservation is, in comparison to embryo banking, a relatively newer technique of fertility preservation. Like embryo banking, this technique requires that a woman undergo ovarian stimulation which takes approximately two weeks followed by an egg retrieval. Retrieved eggs are, however, not fertilized with sperm, as in embryo banking, but immediately cryopreserved.

Though a much more recently developed technique of fertility preservation, oocyte banking in young cancer patients is no longer considered experimental because, even though we do not know yet enough about long-term outcomes, we know enough about the alternative in these patients (which is losing ovarian function and future fertility potential), from either chemo and/or radiotherapy to know that the risk-benefit ratio of the procedure favors oocyte cryopreservation.

Since oocytes are very large cells, it is still technically challenging to cryopreserve and thaw them efficiently compared to embryos, which consist of much smaller individual cells. Vitrification is probably the most effective technique to freeze eggs. Several thousand children have been born from thawed oocytes so far worldwide. Though still a relatively new procedure, elective egg freezing has become commonplace in many fertility centers in the US.

How many oocytes should be frozen to preserve fertility will also vary with female age at time of egg freezing and her ovarian reserve. Whether for medical or elective reasons, we recommend cryopreservation of at least 30 mature oocytes for young women and even more in women in their late 30's. Like with embryo banking, egg banking, therefore, in most women will require more than just one egg retrieval to secure a reasonable likelihood of pregnancy later in life.

Ovarian Tissue Cryopreservation is another established technique of fertility preservation. It can be coupled with in vitro maturation (IVM) of oocytes at time of tissue collection.

In this method of fertility preservation part of an ovary or a whole ovary is surgically removed. The ovary is then dissected in the laboratory, where its outer layer (the cortex) is peeled off. It contains all the primordial follicles, which are the most primitive and immature stage of follicles. This is the follicle stage at which follicles are when a female is born. From birth on until menopause women loose follicles. Most of this loss occurs because these resting follicles are after menarche steadily “recruited” on a 3 months-long journey of follicle and egg maturation until only one of these follicles reaches ultimate maturity and ovulates a mature egg.

Current medical knowledge does not yet allow for IVM of primordial follicles in the laboratory. However, it is reasonable to assume that the knowledge to culture primordial follicles to maturity will be obtained in the coming years. Once that is achieved, thousands of primordial follicles will be available for IVM after ovarian tissue preservation, potentially changing the whole concept of IVF.

Until IVM of primordial follicles will become available, ovarian tissue preservation can, , lead to pregnancies in a very different way: strips of ovarian cortex can be surgically reimplanted into the ovary or pelvis once the patient is cleared for pregnancy. These implants can become functional ovarian tissue, which again produces hormones and follicles with retrievable eggs for an IVF procedure.

Hundreds of births have so far been achieved worldwide with this approach. This technique, therefore, potentially offers a woman multiple attempts of achieving pregnancy if successful transplantation is accomplished.

Ovarian tissue cryopreservation can be done prior to or, sometimes, even after gonad toxic therapy. It can also be performed in still pre-pubertal girls. The method’s shortcomings include the need for laparoscopic surgery and the potential, and mostly hypothetical risk of transplanting cancer cells with the reimplanted ovarian cortex graft, when tissue is transplanted into cancer survivors.  

Cryopreservation Technique

The most established technique for ovarian tissue cryopreservation is slow freezing. Virtually all established pregnancies have used slow freezing of ovararian tissue. Vitrification is an alternative technique, which is often used to cryopreserve human oocytes and embryos. It involves a much faster freezing process but requires higher concentrations of cryoprotectants.

When used for oocytes and embryos, vitrification produces a solid glass-like cell, free of ice crystals. Vitrified cells have, likely, somewhat higher survival rates and better development compared to slow frozen cells and embryos.

Many embryology laboratories, therefore, have abandoned slow freezing, the needed equipment and lost the required expertise. Vitrification is, however, inferior to slow freezing in preserving ovarian tissue because currently available cryoprotectants do not penetrate whole tissues sufficiently. We, currently vitrify eggs and embryos but slow freeze ovarian tissue.

In Vitro Maturation of oocytes (IVM) is a relatively new technique in IVF, in which immature eggs are matured in the laboratory. It allows retrieval of immature oocytes without prior ovarian stimulation. Oocytes can then be matured in the laboratory and subsequently either fertilized with sperm and/or cryopreserved. We use IVM routinely in women with low ovarian reserve to maximize available egg and embryo numbers. Women with low ovarian reserve often produce disproportionally many immature eggs.

In women with polycystic ovary syndrome (PCOS), IVM technique can avoid the need for ovarian stimulation with fertility drugs. Also, in women who quickly must start gonadotoxic medical treatment and do not have time for an IVF cycle with ovarian stimulation, this technique sometimes is performed prior to initiation of therapy. IVM is also often done in combination with ovarian tissue cryopreservation.

Thousands of children have been born following IVM; however, pregnancy rates are significantly lower than with standard IVF.

Medical ovarian suppression with GnRH-agonists and -antagonists in conjunction with chemotherapy has been reported to help preserve ovarian reserve in young women. However, outcomes are highly variable, depending on patients age, ovarian reserve, and gonad toxicity of the selected treatment regimen.

Fertility-sparing surgical and medical treatments for women with gynecological cancers. These treatment options are disease specific, and are performed in conjunction with gynecologic oncologists.

Ovarian transposition prior to pelvic irradiation is performed laparoscopically, moving the ovaries surgically out of the pelvis prior to radiation therapy to the pelvis. This can help preserve both fertility and ovarian endocrine function.

Radical trachelectomy (removal of only the cervix and not the whole uterus) for early stage cervical cancer can be utilized to preserve the uterus and ovaries and allow future fertility in cases of cervical cancer. When surgical margins of the removed surgical specimen are clear of cancer, the procedure is curative. While the risk of preterm delivery is increased in subsequent pregnancies, most women are able to carry to term.

Ovarian cystectomy or unilateral oophorectomy, along with lymph node biopsy, can be utilized to spare the contralateral ovary and uterus in cases of borderline ovarian malignancy and early stage ovarian cancer, confined to one ovary. Recurrences are rare in properly staged patients with no residual disease.

Hormone therapy for early stage endometrial cancer can be successful with systemic or local high dose progestin treatment. Pregnancy should be established shortly after regression of the malignancy. After completion of pregnancy, a hysterectomy with comprehensive staging is typically performed.

Fertility Preservation in Men

Sperm cryopreservation is the most established technique, utilized for decades in post pubertal males prior to gonad toxic therapies. In recent years sperm cryopreservation has, however, also been utilized in other situations, including prior to military deployment and prior to elective sterilization via vasectomy.

Sperm cryopreservation can be done rapidly; it is relatively inexpensive and widely available in most areas. Multiple vials of washed sperm are cryopreserved for later use. In men with no sperm in the ejaculate, sperm can often be extracted from the testicle or from the urine in cases of retrograde ejaculation.

Shielding of the testes is an established technique in patients undergoing radiation therapy and should be utilized whenever feasible.

Fertility preservation in pre-pubertal children

Ovarian and testicular tissue cryopreservation techniques are considered experimental but are, due to the high probability of primary disease survival at a young age, frequently utilized. Since research is progressing rapidly in both young females and males, these options should be discussed with the family prior to initiation of gonad toxic therapies. Thawed tissue can be later utilized for either autologous transplantation or for potential in vitro maturation of gametes.

Important general considerations for fertility preservation

Fertility preservation techniques require a very detailed informed consent process. The patient’s and, where applicable, the family’s desires for later disposition of cryopreserved gametes and/or tissues must be carefully documented during this process. Specifically, the disposition of cryopreserved cells and/or tissues in cases of incapacity, death, and divorce should be addressed.

Ethical practice of medicine requires that patients be clearly informed about what treatment options are considered established and which are still considered experimental. Informed consents must reflect the status of each proposed treatment.

Further required are realistic assessments of later successful reproduction for each proposed treatment and/or fertility preservation method, assessment of likely required number of treatments and expected costs.

Direct communication between treating oncologist/oncologic surgeon and/or other medical specialists and the expected provider of fertility-preserving treatments are essential and will ensure that patients receive the best possible coordinated care in consideration of both treatment perspectives.