Fertility Preservation

Overview

Infertility is a condition of the reproductive organs of men and women that inhibits one of the body's most basic functions—the capacity to bear children. And, unlike lung cancer or HIV/AIDS, individuals are rarely told of the very direct linkages between their behavior, choices, and reproductive health in the United States, despite the fact that 6.1 million people are infertile.

 

What is fertility preservation?

Fertility preservation is the act of storing or protecting eggs, sperm, or reproductive tissue for future use in having biological children.

 

Basic Reproductive Biology

Understanding fundamental reproductive biology can help you make fertility decisions.

Your ovaries have 2 functions:

• They produce hormones (estrogen and progestin).
• They hold your eggs (oocytes). Each egg is contained in a sac called a follicle.

When you reach puberty, your pituitary gland (located in your brain) produces hormones that stimulate the growth of a set of follicles each month. Each expanding follicle's egg begins to mature. The ovary produces hormones that cause the lining of your uterus (endometrium) to thicken and prepare for pregnancy as the follicles expand.

Each month, one egg from the group of developing follicles develops completely. It is discharged into the fallopian tube from one of your ovaries. This is known as ovulation. The eggs are eliminated from the body when the other follicles maturing that month break down. Females lose numerous eggs over time as a result of this monthly process.

 

Pregnancy

If you don't use birth control and have vaginal intercourse with a male partner at the time you're ovulating, a single sperm may fertilize the egg. The fertilized egg begins to divide, resulting in the formation of an embryo. You get pregnant if the embryo implants in your endometrium. The embryo's cells continue to divide, eventually forming a fetus. During pregnancy, your uterus expands to accommodate the growing fetus.

 

Menstruation

If the egg produced during ovulation is not fertilized, or if the embryo does not implant in the endometrium, hormone levels decline, causing the uterine lining to shed. Your monthly menstrual cycle is formed by this crimson discharge. The cycle then restarts, with fresh eggs developing every month.

 

Ovarian reserve

Females are born with around one million eggs. Only 400 to 500 eggs are released during ovulation throughout a female's lifetime. Other eggs die naturally over time, reducing the amount of eggs in the ovaries (known as the ovarian reserve). It's more difficult to get pregnant when you have less eggs. There are eventually so few eggs that a female becomes infertile.

 

Menopause

When eggs are lost, the ovaries stop generating hormones. This results in the cessation of monthly menstrual cycles. Menopause occurs when a woman's menstrual cycles cease. Most women lose their fertility between 5 and 10 years before menopause. This is because they lose eggs and the quality of their eggs deteriorates over time.

 

What factors may lead to fertility preservation?

Fertility might be jeopardized for a variety of reasons. Age is obviously an issue, since many women are delaying children due to a profession or because they haven't met the perfect partner, and therefore they can save eggs for future use.

Each female contains around 1 million oocytes at birth. However, as she ages, the quantity of eggs she produces drops. The remaining egg number during puberty is around 400,000. Fertility begins to decline dramatically after the age of 37, and by the age of 40 or beyond, the odds of conception are considerably lowered since both the amount and quality of eggs are diminished.

However, the most prevalent reason people seek fertility preservation at Fertility Center is cancer, most commonly breast cancer, followed by lymphomas (Hodgkin and non-Hodgkin).

Cancer can impact reproductive organs, or the kind and amount of chemotherapy or radiation might cause harm to the ovaries and testes. Given adequate cancer treatment regimens, the majority of patients will survive their condition, making it critical to protect future reproductive choices from the potentially damaging effects of chemo or radiation.

Risk factors contributing to consider fertility preservation include:

• Chemotherapy: Reproductive organs, particularly the ovaries, are exceedingly vulnerable to chemotherapy. Certain medicines can harm the ovaries or testicles. These medications, in addition to destroying cancer cells, may also damage egg and sperm cells.
• Radiation therapy: This treatment damages the DNA of cancer cells by using high-energy X-rays, gamma rays, and/or charged particles. If the radiation location is close to reproductive organs, it may have an impact on fertility. Total body irradiation in preparation for bone marrow transplants has also been linked to decreased fertility.
• Surgery: Surgical removal of the reproductive organs may make it difficult or impossible for a woman to become pregnant unless she cryopreserves oocytes and embryos and then perhaps resorts to gestational surrogacy to carry a kid to term. To maintain his chances of fathering children in the future, a man undergoing testicular or prostate cancer excision should freeze his sperm prior to surgery and therapy.
• Late childbearing: American women are delaying having children for longer and longer. The average age of the first child increased from 21.4 in 1970 to 26 in 2013. It is becoming more frequent for first births to occur after the age of 35. As a woman's fertility declines with each passing year, many seek fertility preservation with the aim of starting kids in their late 30s or early 40s.
• Autoimmune diseases: Certain autoimmune diseases such as rheumatoid arthritis can harm a woman or man's fertility.

 

What kinds of treatments are used to preserve fertility?

Several options are offered for women and men. These include:

• Embryo cryopreservation: This process involves the patient going through an in-vitro fertilization cycle that begins with stimulating the ovaries to grow many eggs, harvesting them, and then combining them with sperm cells to create embryos. Cryoprotectant chemicals are subsequently applied to the embryos to avoid ice crystal damage during cryopreservation.
• Oocyte cryopreservation (Egg freezing): In this technique, patients are given ovarian stimulation to produce numerous eggs, which are then cryopreserved. Although this treatment is new, pregnancy rates with frozen oocytes are currently comparable to those with frozen embryos. The American Society of Reproductive Medicine ruled in 2012 that this treatment was no longer experimental.
• Ovarian tissue cryopreservation: Some patients are pressed for time. They require prompt treatment for pelvic cancer or sarcoma. The sole alternative in these circumstances is to cryopreserve ovarian tissue. The physician uses a minimally invasive procedure to remove the ovarian cortical tissue, which contains the eggs. This tissue can then be stored in the freezer until the patient need it.
• Auto-transplantation of ovarian tissue: When the patient's cancer treatment is over and she wishes to conceive a family, she can thaw her own frozen ovarian tissue and have it returned to her body. It can be implanted in the pelvic side wall or on the surviving ovary. Ovarian function may resume four to six months after this procedure.
• Sperm cryopreservation:  The Fertility Center also assists males who are considering fertility preservation. Men may opt to donate sperm for cryopreservation. In certain situations, Yale doctors may use a testicular biopsy to extract sperm straight from the testis. The sperm can then be stored indefinitely until the patient is ready to become a parent.

Many of these therapies are now not commonly covered by health insurance providers. Many insurance policies in Connecticut include embryo freezing as part of in vitro fertilization. Furthermore, insurance firms must now cover fertility preservation treatment for male and female cancer patients aged 40 and younger. Unfortunately, cancer patients receiving chemotherapy or radiation treatment do not have the same level of protection, and egg freezing is not covered. 

 

Egg or embryo freezing

Egg and embryo freezing are procedures in which mature eggs are extracted from your ovary and frozen and kept for future use. They can be frozen as unfertilized eggs or as embryos after being fertilized with sperm. These treatments are carried out by reproductive endocrinologists (RE), who are specifically educated gynecologists. We don't have any REs at Memorial Sloan Kettering (MSK), but we can recommend you to someone who does.

The freezing of eggs or embryos takes around 2 weeks. Several stages are involved, including:

 

Evaluation 

A variety of tests will be performed by your RE to assist establish how successful egg or embryo freezing may be for you. They will also consult with your oncologist to ensure that egg or embryo freezing is safe for you. You may have the following tests:

• A transvaginal ultrasound is performed by inserting a tiny wand into your vagina. The wand's sound waves produce images of your ovaries and uterus. Your doctor can check your ovaries and count the number of big developing follicles in your ovaries with this test. This is referred to as the antral follicle count. If you've never had a gynecologic checkup or vaginal sex, your RE may be able to do the ultrasound on your abdomen rather than your vagina.
• Blood tests to determine the levels of reproductive hormones such as follicle stimulating hormone (FSH) and anti-mullerian hormone (AMH) 

 

Ovarian stimulation: 

If you decide to proceed, you will need to administer hormone injections (shots) to yourself every day for roughly 10 days. A nurse at the fertility facility will show you how. These hormones will accelerate the maturation of numerous eggs in your ovaries. You don't have to be in any certain stage of your menstrual cycle to start.

You will see the RE virtually every other day for blood tests and ultrasounds throughout this phase of stimulation. These tests reveal how your ovaries react to hormones. If necessary, your RE may adjust the hormone dosage. The egg retrieval will be scheduled after your eggs are fully developed.

 

Egg retrieval: 

This is an outpatient operation performed under anesthesia (medicine to put you to sleep), so you will not experience any discomfort. You do not require an incision (surgical cut).

• Once you're unconscious, your RE will insert an ultrasound wand into your vagina to view your ovaries. To retrieve mature eggs, a very tiny needle is pushed through the wall of your vagina up to your ovary.
• The entire treatment lasts around 20 minutes, and the majority of ladies are discharged within an hour.

Once the eggs have been recovered, they will be frozen for future use. The eggs can be frozen either unfertilized or fertilized with sperm to form embryos (in- vitro fertilization). Eggs and embryos can be kept for indefinite periods of time.

Before you begin egg or embryo freezing, consult with your oncologist to ensure you have the time and that the technique is safe for you. Most people only undergo one round of stimulation prior to cancer therapy. However, the more eggs you can freeze, the more likely it is that you will be able to have a kid with these eggs in the future.

Depending on how many mature eggs or embryos you can store, your RE may recommend a second cycle. If you are considering a second round, consult with your oncologist beforehand to ensure that you are not delaying your cancer treatment any longer than necessary.

 

Considerations for females with breast cancer

The hormone therapy required to accelerate the maturation of your eggs will raise your estrogen levels for 2 to 3 weeks. To reduce estrogen levels, we normally advise ladies with breast cancer to take letrozole during stimulation and for 1 to 2 weeks after the eggs are harvested. Your RE will talk with you about it and prescribe the medicine.

We don't know for sure if this brief exposure to estrogen is safe, but there have been no reports of females with breast cancer who undergo egg or embryo freezing being more likely to have the cancer return. Everyone's circumstance is unique, so we recommend speaking with your oncologist if you're thinking about it.

Furthermore, females with estrogen receptor positive breast cancer may require endocrine therapy for up to ten years after completing chemotherapy or radiation therapy. It is not safe to become pregnant while receiving this medication due to the possibility of birth abnormalities. Most women with estrogen receptor positive breast cancer are recommended to wait ten years before trying to conceive. If you're thinking about stopping endocrine medication to attempt to get pregnant before the 10-year mark, talk to your oncologist first.

 

How frozen eggs and embryos are used to attempt pregnancy

If you utilize your frozen eggs or embryos again, they will be thawed when you are ready to try for a pregnancy. Eggs that have been frozen will be fertilized with sperm to become embryos.

If you no longer have regular periods or are experiencing menopause as a result of your therapy, you will need to take hormones for several weeks to prepare your uterine lining for conception. The embryos will be implanted in your uterus. The embryos are collected in a tiny, soft tube that is inserted through your vagina and cervix into your uterus. The embryos are expelled, and the catheter is removed. The process is carried out in an examination room. Because it does not hurt, you will not require anaesthetic.

 

If you are unable to carry a pregnancy, the embryos can be transferred to another female's uterus to carry the pregnancy for you. Surrogacy with a gestational carrier is what this is termed.

A blood test is performed around 2 weeks following the embryo transfer to determine whether you or your gestational carrier have gotten pregnant. If the pregnancy test is positive, an ultrasound will be performed several weeks later to determine whether or not the embryo has implanted, confirming the pregnancy. You will next make an appointment with an obstetrician (a doctor who specializes in pregnancy and delivery) who will provide you with care throughout your pregnancy. To maintain the pregnancy, you may need to continue taking hormones for several months.

If the embryo does not implant and you have more embryos saved, your RE can conduct another embryo transfer when you are ready.

 

Success rates with frozen eggs and embryos

The likelihood of producing a kid with frozen eggs or embryos is determined by your age at the time of egg retrieval and the quantity of mature eggs recovered during the surgery. Not every egg gathered will result in a baby. Some eggs will not survive the freeze-thaw cycle, others may not fertilize and grow into embryos, and still others may fail to implant following the transfer. Females under the age of 35 have a better likelihood of success. After your initial examination, discuss your personal chances of success with your RE.

 

Ovarian tissue freezing

Due to the urgent necessity to begin treatment, some ladies will be unable to undertake egg or embryo freezing. They may be able to preserve fertility by freezing ovarian tissue. A complete ovary, or portions of an ovary, are removed during surgery in this experimental technique. The ovarian tissue is treated in a specialized laboratory. The ovary's outer layer, which contains the eggs, will be removed, split into little pieces, and frozen. A tiny portion of the tissue will be utilized for study to determine the optimum method of assisting females in having children utilizing ovarian tissue. The remainder of the tissue will be kept for your own use.

Currently, the only way to use this tissue in the future is to re-implant it into your body and hope that the eggs in the tissue develop and are released during ovulation. As of 2019, around 130 infants had been born globally following ovarian tissue re-implantation. Another way to use this tissue is to encourage egg maturation in the laboratory (in vitro maturation). The mature eggs might then be fertilized to develop embryos for transfer to your uterus. This method has yet to produce any children.

 

Other Options for Building a Family

Some females will be unable to maintain their fertility prior to treatment, while others may opt not to for personal reasons. This does not necessarily imply that you will be unable to start a family. Some women will be able to become pregnant on their own, without the assistance of a doctor. Some people may have a poor ovarian reserve but can still become pregnant with fertility therapy from a RE. If you are unable to have a biological kid in the future, you can still start a family following cancer treatment.

• Donor eggs or embryos can be used. Donor eggs are donated by young girls who have gone through an ovarian stimulation and egg retrieval cycle. These are fertilized with your partner's or a donor's sperm to produce embryos for transfer into your uterus. Donor embryos are typically offered by couples who have completed infertility treatment and do not wish to discard their leftover embryos. The expense of using donor embryos is significantly cheaper than that of using donor eggs.
• You are able to adopt. A cancer history does not preclude you from adopting as long as you are healthy and have been cancer-free for several years.

 

Conclusion 

Fertility preservation safeguards your reproductive tissues in the event that you want to have a child in the future. People select this treatment for cancer and other medical problems, as well as for aging and transgender care. Following fertility preservation therapy, many people have healthy infants.