The Youngtimers Guide to Egg & Sperm Freezing
This guide was written to help individuals - who are at-risk of inheriting an autosomal dominant genetic disease, such as early onset familial Alzheimer's disease - understand fertility preservation or egg/sperm freezing. Individuals with a history of a genetic disease in their family may be interested in pursuing egg/sperm collection and/or freezing because:
They are interested in vitro fertilization (IVF) with preimplantation genetic testing (PGT) to avoid passing on the mutation to their children. Egg/sperm collection is the first step in the IVF process.
Clinical trial participation may occur during prime reproductive years leaving some participants with the difficult choice to join a trial or hold off on family planning. Egg/sperm freezing before clinical trial enrollment may provide an alternative option and peace of mind to those struggling with this decision.
This guide does not replace professional fertility counseling.
What options are available to someone interested in preserving their fertility or saving their reproductive cells for future use?
There are a couple of different options for individuals interested in preserving their fertility, which include freezing their eggs or sperm for future use (also known as gamete cryopreservation). For men and post-pubertal boys, sperm freezing is the main fertility preservation option. For women or couples, there are two options: egg (unfertilized egg alone) or embryo (fertilized egg) freezing.
Given that eggs are more fragile than embryos, frozen embryos give rise to high success rates in live births compared to frozen eggs. However, recent advances in reproductive medicine have made egg freezing a standard of care for many female patients seeking fertility preservation (Source: ASMR, 2013). In fact, egg freezing and thawing later has a higher pregnancy rate than using fresh embryos (Source: Cascante et al., 2022, Fertility and Sterility). For further information on deciding to freeze eggs or embryos, go to https://www.fertilityiq.com/topics/egg-freezing/freeze-eggs-or-embryos or https://extendfertility.com/freezing-eggs-vs-freezing-embryos/.
Note: Frozen eggs and sperm must eventually be used in other procedures, such as intrauterine insemination (IUI) and in vitro fertilization (IVF), to produce an embryo and pregnancy. We will discuss IVF and preimplantation genetic testing (PGT) in a future video and article.
What is the difference between freezing eggs and freezing embryos?
Individuals pursue egg or sperm freezing (or undergo the process of fertility preservation) to save or protect their eggs, sperm, or embryos so that they can use these cells in the future to have biological children. There are a variety of patients who pursue egg/sperm freezing:
Patients with medical conditions (such as endometriosis and uterine fibroids) that can cause future fertility issues. This could include individuals with low egg count or ovarian reserve.
Patients exposed to toxic chemicals or radiation during treatment for a disease (such as cancer or blood disorders); treatment that could lead to long-term infertility.
Patients with a history of a genetic disease in their family that are interested in pursuing in vitro fertilization (IVF) with preimplantation genetic testing (PGT) or other assisted reproductive technology. These individuals pursue IVF and PGT to avoid passing on the mutation to their children.
Patients concerned about aging out of their most fertile and reproductive years (such as working professionals who are holding off on having children until later in life).
What are typical reasons individuals pursue egg or sperm freezing?
Age: Age is an important consideration, particularly for women. Each woman is born with a certain number of eggs, and that number is finite (meaning it is limited). Over a woman's lifetime, she will lose eggs. Although it is hard to predict this loss, as the rate at which women lose their eggs varies from woman to woman, we know is that age is the most significant factor associated with egg loss. We also know that as women age, the quality or health of the eggs declines over time. For this reason, anyone interested in fertility preservation (or egg freezing) should see a fertility doctor sooner rather than later. The quality and number of a woman's eggs in her mid-to-late-30s may not be the same as in her late-20s, which could impact the success of giving birth to a healthy child.
Age also impacts men's fertility. Unlike women who have a set number of eggs to reproduce with over their lifetime, men harbor stem cells in their testicles that constantly generate sperm, allowing them to reproduce from their adolescent years (post-puberty) well into their 70s. Despite having this continual supply of sperm, as men age, the quality of their sperm declines over time. Studies have shown that men in their 40s or older are more prone to have sperm with genetic or chromosomal errors (ref). Thus, if a man is considering freezing his sperm, it is important to consider age at the time of collection.
Safety of medications: Another important consideration for people with an underlying medical condition is the safety of medications they are taking to treat their disease or medical condition. For example, we know that some cancer medications affect fertility; thus, preserving eggs or sperm before treatment is critical. For clinical trials that involve treatment with investigational drugs, it is not always well-known whether a given drug will impact the reproductive system. Thus, a patient needs to talk with their doctor about this to determine whether they should consider gamete cryopreservation before treatment and clinical trial enrollment.
It will also be necessary for the fertility specialist to establish whether fertility medications (e.g., the treatment women take to stimulate their ovaries) are safe to use with a person's medical condition or any current medications. Some medicines required for an individual's medical condition may not be safe to take in parallel with fertility treatments. A consultation with a fertility specialist will help answer these questions.
Timeline: A professional woman may not have a specific timeline outside of the ticking biological clock, whereas an individual with a medical condition may have some urgency in starting treatment. Under these circumstances, patients often have a limited opportunity and window of time to explore their family planning options. They may feel forced to make swift and critical decisions about their fertility. For patients that need to embark on their medical therapy immediately (with possibly only a few weeks or months to decide on family planning), pursuing fertility preservation can be a great option. In these cases, fertility specialists can schedule a consultation, counseling, basic fertility testing, and a follow-up appointment to accelerate the process of getting eggs frozen in a timely fashion so patients can move on to their medical treatment.
A note for young EOFAD at-risk individuals: Fortunately, current clinical trials are underway in the early-onset familial Alzheimer's disease community, offering drugs that target amyloid and tau in the hopes of delaying or preventing disease progression. Despite the eagerness to join these trials, some young patients may face a difficult decision: join a trial and hold off on family planning for an extended period (currently ranging from 4 – 6 years), or have a child and lose out on their chance to receive potential disease-modifying treatment.
Patients placed on medications for extended periods and given during treatments during prime reproductive years may face different circumstances in their ability to conceive naturally after treatment. For this reason, gamete cryopreservation may provide an excellent option for patients struggling with this decision. Egg or sperm preservation before clinical trial enrollment or treatment may provide individuals peace of mind in their ability to have a biological child or expand their family at a later time, despite their more mature age at the end of the treatment.
It's important to note that not all women who freeze their eggs will end up using these eggs, and freezing eggs does not preclude a woman's ability to have a natural conception. Many women can conceive naturally after egg freezing, but often return to frozen eggs or embryos if they struggle with infertility or wish to expand their family in their late 30s or early 40s when pregnancy can become more complicated.
It is important to highlight again how age impacts a woman's ability to become pregnant. A 30-year-old woman has a 15% chance per month of successfully getting pregnant, and that probability of having a natural pregnancy drops over time. That same woman at age 35 has a 10% chance per month ability to get pregnant and a less than 5% chance at age 40 (ref). Thus, during these critical reproductive years, requiring patients to withhold family planning for 4-6 years could impact (i.e., make it more challenging) a woman's ability to conceive naturally.
A fertility consultation before clinical trial enrollment may help young at-risk patients assess what options will work best for their situation, timeline, age, and bodies.
The reasons women pursue egg freezing in the general population (i.e., they have low fertility, low ovarian reserve) vs. in a rare genetic disease population (such as EOFAD, where there may be no diagnosed fertility issues) are different. What essential considerations would you recommend for individuals in the EOFAD community?
The process of gamete cryopreservation for fertility preservation is much more straightforward for men than for women. Sperm cryopreservation (sperm freezing) is how men preserve their fertility. This process is appropriate for males who have gone through puberty but not suitable for adolescent boys who have not. Here is a look at what this process entails:
Men come into the clinic and produce a sperm sample.
An Andrologist, a lab technician specializing in male fertility, evaluates the sperm sample for sperm number, movement (motility) and health.
Everything but pure sperm is removed from the sample. The ejaculate is composed of sperm from the testicle and fluid from the prostate gland, and for freezing purposes, fertility specialists prefer sperm alone.
A cylinder-like collision course helps isolate and test sperm. During this selection process, only the fastest and healthiest sperm travel to the bottom of the cylinder. The andrologist will collect the sperm at the bottom of the cylinder for freezing.
Sperm are distributed into multiple separate vials and then frozen through a technique called vitrification – also known as flash freezing. The process of freezing doesn’t harm or alter the health or quality of the sperm. (Sperm storage into multiple vials means not all frozen sperm needs to be used for one pregnancy. It is possible to use just one vial to achieve a single pregnancy, so one sperm sample could help achieve multiple pregnancies.)
Sperm can remain frozen and viable for years to decades. There is no shelf life on frozen sperm.
Image 2. The process of sperm freezing.
Once needed, the clinic will thaw the sperm. However, not all sperm that freezes will survive the thawing process; the recovery rate of sperm after freezing is 50%. (provide typical sperm numbers acceptable for freezing, if low how many samples provided?) This hampered survival is no cause for alarm - this also happens in the body; after a few hours, some sperm do not survive.
There are two options to achieve pregnancy with frozen sperm: 1) intrauterine insemination (IUI), commonly known as artificial insemination, and 2) in vitro fertilization (IVF). If the sperm meets specific criteria and there are no underlying female infertility issues, then no fertility/IVF treatment is required, and the couple can use IUI. In this procedure, the sperm is thawed, placed in a catheter, and inserted into the uterus, which usually takes just one appointment.
What are the steps involved in freezing sperm?
Paulsen JS, Nance M, Kim JI, Carlozzi NE, Panegyres PK, Erwin C, Goh A, McCusker E, Williams JK. (2013). A review of quality of life after predictive testing for and earlier identification of neurodegenerative diseases. Progress in neurobiology, 110, 2–28. doi:10.1016/j.pneurobio.2013.08.003.
Can be found here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3833259/
Egg retrieval is a procedure done to collect the matured and stimulated eggs from the fertility treatment cycle. A fertility doctor collects the eggs by transvaginal ultrasound aspiration. They utilize an ultrasound probe and a needle connected to a suction device guided through the vagina to the follicles containing the eggs. Egg retrieval is a minor surgical procedure but does not involve any incisions, stitches, or scarring. Women will get anesthesia by intravenous (IV) sedation administered by an anesthesiologist – so they won’t feel or remember the procedure. However, this is not general anesthesia - so there is no need for a breathing tube or respirator.
Collecting the eggs usually takes less than 30 minutes (often around 10 – 15 minutes). Once harvested, an embryologist evaluates the fluid containing the eggs under a microscope. Only the mature eggs will be selected and frozen (via vitrification or flash freezing). The eggs can remain frozen for years to decades. While frozen, the eggs are not harmed and do not decline (or degrade over time). The success of thawing the eggs varies from clinic to clinic, but some clinics report a 90-95% recovery rate of viable eggs to use after thawing (ref). Egg retrieval is an out-patient surgery, and most women can go back to work the following day after the procedure. The ability to go back to work may be dependent on the number of eggs collected. Women with more eggs may require 1 –2 days to recover. Some women experience cramping the day of the retrieval, but this usually subsides by the next day. Some women report feeling full or pressure for several weeks following the surgery; again, this varies among women and could depend on the number of eggs collected or how enlarged the ovaries became during the treatment.
A gamete is a reproductive cell. Men’s reproductive cells are sperm and women’s reproductive cells are eggs (also referred to as oocytes). Each gamete typically contains 23 chromosomes, which is half the amount of a human’s DNA. Gametes can join together (i.e., sperm can fertilize an egg) to reproduce and ultimately create an embryo (fertilized egg) with 46 chromosomes, a complete set of chromosomes.
Image 1: Gametes
What are gametes?
The process for a woman wishing to freeze her eggs has two components: 1) priming* and 2) ovarian stimulation or the part where she takes fertility medication.
Priming: The goal of priming is to synchronize all the eggs in a particular month. At any given time, a woman has eggs at different developmental stages. For example, if we were to look at a woman’s ovary in January: she would not only have eggs for January’s menstrual cycle but also have eggs that were recruited for the next 2-3 cycles (many times they are too small to see by ultrasound). Priming aims to keep all the eggs of a particular month in a holding pattern. Thus, when a woman starts her fertility medications – all her eggs will be growing at the right pace. There are a number of different medications that can be used for priming, and a fertility specialist will select the right combination for each woman based on her clinical profile.
*For patients who need to speed up egg freezing, such as newly diagnosed cancer patients, priming can be skipped.
Ovarian stimulation: During the ovarian stimulation phase, patients inject fertility medications (or hormones) to stimulate the growth of multiple eggs in their ovaries. This phase typically lasts around 10 – 11 days for most women, but stimulation can vary from 8 –14 days. It is important to note that each patient is different, and a fertility doctor will tailor their protocol (or recipe of a specific combination of drugs and doses) for their unique set of needs.
Subcutaneous injections: The fertility drugs come in the form of subcutaneous (or under the skin) injections. Women can do these shots themselves, and fertility clinics will teach patients how to perform these injections independently or with a partner. These shots involve pinching the skin near the abdomen and inserting a tiny needle into that pulled area. It can be intimidating the first and second day of injections, but patients will quickly learn that they can do these injections with ease.
Ultrasound examinations: Once a woman starts the fertility medication injections, the fertility clinic will begin ultrasound monitoring and blood work to see how she responds to the medication. The ultrasound is a transvaginal ultrasound that allows the doctors to see how the ovaries are responding. Since eggs are microscopic, they are indiscernible to the human eye, so ultrasound is required. In the ovaries, tiny structures called follicles - that essentially look like bubbles - encase the eggs. By performing an ultrasound, doctors can measure how big these follicles or bubbles become over time, providing important information about the microscopic egg inside.
Blood testing: Blood work (usually checking for estradiol and progesterone levels) allows doctors to see how a woman responds to treatment, providing critical information to adjust her treatment. Typically, estrogen levels will increase as the follicles develop, and progesterone levels will stay low until after ovulation. Once the fertility medication begins, appointments for ultrasound and bloodwork become frequent, oftentimes occurring every other day.
Trigger shot: Once the follicles reach a specific size and are ready, women take one last medication, commonly known as the “trigger shot.” This shot causes the eggs to mature (and reach the final stage of maturation needed for fertilization). Women will then wait a certain amount of time after the trigger shot (usually 34-36 hours later) to undergo a surgical procedure to harvest the eggs, called a retrieval (see below).
Table 1. Commonly used fertility medications (gonadotrophins):