Young adults with a family history of familial Alzheimer's disease (FAD) face unique challenges when it comes to having kids. They may worry about passing a genetic mutation to their children. They may need to delay having kids in order to participate in a clinical trial. Whatever their reason, egg or sperm freezing is an option they may investigate. These forms of fertility preservation are also known as gamete cryopreservation.

In this interview, we discuss these topics with Dr. Laxmi Kondapalli, a fertility doctor at Colorado Center for Reproductive Medicine (CCRM) Fertility, and an Assistant Clinical Professor of Obstetrics and Gynecology/Director of the Fertility Preservation Program at the University of Colorado School of Medicine. Dr. Kondapalli is board certified in obstetrics and gynecology and the subspecialty reproductive endocrinology and infertility.

Dr. Kondapalli shares insights about assisted reproductive technologies for people who are at risk of or have a genetic mutation for FAD and weighing the difficult decision of joining a trial or starting a family. We discuss questions like:

What is gamete cryopreservation?
How long does it take?
What does it involve?
Is there a right age or time to do this?
Is it better to freeze eggs or embryos?
And more…

This conversation reflects Dr. Kondapalli’s unique perspectives and experiences as shared with us on January 26, 2021. Insights from experts like Dr. Kondapalli help us navigate the unique challenges we face as members of this community.

This transcript has been edited for clarity and readability. For the full interview, watch the video.

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LINDSAY: Today we're joined by Dr. Laxmi Kondapalli to talk about gamete cryopreservation, or in layman's terms, egg freezing and sperm freezing.

Dr. Kondapalli, thank you so much for joining us.

KONDAPALLI: Thank you, Lindsay, for inviting me to participate in this really important conversation. I'm thrilled to be here.

LINDSAY: A lot of your research has focused on fertility preservation for cancer patients, but our rare disease community has a lot to learn from your field. We're excited to learn from your expertise on these fertility related concerns our community faces.

KONDAPALLI: Absolutely. Well, I'm so excited to share the information that I have and hopefully, your audience will gain some insights and just be aware that these options are available.

Even though I focus on fertility preservation primarily in cancer patients, I also take care of patients that have a whole host of medical conditions outside of cancer, where their fertility may be impaired or their opportunity tostart a family may need to be postponed because of certain types of treatments. So I think that my experience is very applicable to the Youngtimers group.

LINDSAY: We have a lot of questions, so let's just get started. To set the groundwork, I was wondering if you could just define for us what is gamete cryopreservation or egg[/sperm] freezing.

KONDAPALLI: So [a] gamete is just the reproductive tissue that men and women have. For women, our oocytes (or eggs) are what we can preserve for future use. For men, the primary reproductive tissue is going to be the sperm.

When we think about fertility preservation, there's a couple of different options.

For men, it's freezing sperm.
For women, it’s freezing unfertilized eggs. A few years back this was considered experimental, but the techniques for freezing eggs have really evolved over the past 10 to 15 years, so it's no longer considered experimental or investigational. It's actually standard of care.
For some patients, they may go ahead and cryopreserve [or freeze] embryos. You can actually take the eggs fertilized with sperm, create an embryo, then that fertilized embryo can be frozen for future use.

LINDSAY: Thank you for clarifying. What are the reasons you see people pursue egg or sperm freezing?

KONDAPALLI: Well, I see a variety of different patients that want to come in for a consultation regarding fertility preservation:

People with medical conditions that impact fertility: Certainly, if a patient has a medical condition that may predispose them to issues in the future, they may want to think about preserving eggs or sperm before they go through their treatment. And if they face infertility, we have a backup option, because we've been able to freeze the sperm and the eggs, and they can continue and have a biological child in the future. A big group of patients that come to see me are patients either with cancer, medical conditions, or even patients with certain types of blood disorders. Sometimes those patients need treatment for their blood disorder, and that treatment predisposes them to long term infertility, so they would come to see me to preserve eggs or sperm.
People with hereditary diseases: We also see patients who specifically have a gene mutation that can be passed on in their family. So they know that something like in vitro fertilization (IVF) with genetic screening of embryos (PGT) may be on their horizon in the future, but they also recognize that age is catching up to them.

People interested in holding off on having a family: I also see a lot of professional people, men and women who are wishing to hold off on starting a family until they're older in life. We do know that the age of pregnancy and when women are starting a family is getting older and older. And because of that aging process, I do see professional women who will come to see me in their late 20s or early 30s to preserve eggs, so they can hold off on starting a family in the future. We will talk a little bit later about how age has an impact on the health of our eggs, and so they may decide to go ahead and freeze eggs when they're much younger, so that they can use it for assisted reproductive technologies in the future.

Those would be the primary reasons that a patient may want to have a consultation with me to talk about fertility preservation.

LINDSAY: For people in rare genetic disease groups, what important factors should they be thinking about when it comes to pursuing egg or sperm freezing?

KONDAPALLI:

Age: One of the biggest factors associated with the success of either freezing eggs or sperm is age. And that's particularly true for women. What's interesting about reproduction for males vs females is that women are born with a certain number of eggs, and that is finite. So all women are pretty much born with the same [number of] eggs. But we lose eggs over our lifetime. The rate at which women lose eggs is different from woman to woman. So even though we all start off with the same number, we might be losing eggs at a faster rate or a slower rate, and age is the biggest factor that's associated with that egg loss.

The other thing to keep in mind is that the older we get, the quality or the health of the eggs also declines, which means that the eggs that we have in our mid to late 30s may not be as healthy, meaning likely to result in healthy embryos or children, as when we were in our 20s.

So age is one of the biggest factors that's associated with a disease population .

For men, we also see that age has an impact on the quality of sperm. So men who are in their 40s and above, their sperm can be more prone to having genetic factors or chromosomal errors that can result in embryos that are not healthy. But certainly for women, it's much more of an impact. Boys [do not begin to make] sperm until they go through puberty, but men can make sperm well into their 70s or 80s, because there are stem cells within the testicle that can constantly reproduce sperm.

Unfortunately for women, there's no stem cells within the ovary, so we are born with all the eggs that will ever have, and then we lose them over our lifetime. So that time factor is going to be different from a male patient versus a female patient.

Safety: The other factor that I think about, for patients that have a medical condition in which they are considering fertility preservation, is the safety of the medications with their underlying medical condition. We want to make sure that the medications that we're using for women, to stimulate their ovaries, are considered safe with other medical conditions and other medications that they are on. And, some of the medications that they require for their underlying medical condition may not be safe to take in parallel with the fertility drugs that we use, so that's a second factor that we consider.

Timeline: And then third, what is the timeline? So a professional woman may not have a specific timeline outside of the ticking biological clock. But for a patient that has a medical condition, if there's some urgency on starting certain medications, and we have a certain opportunity or a window of time where patients are having to make very quick decisions - because they know that they need to embark on their medical therapy - they may not have months or weeks to think about pursuing fertility preservation.

A lot of times for patients with a medical condition, the process goes very, very rapidly. So we do consultations, we counsel patients, we do some basic fertility testing, they have a follow up appointment, and then we accelerate the process to get their eggs frozen in a timely fashion so that they can move on with their medical treatment. So, I agree with you, the considerations that I have for a medical population are very different from a patient who may just want to do this because she wishes to postpone pregnancy.

LINDSAY: Yeah, that's so relevant, especially in our population. Clinical trials use investigational drugs, and we don’t know their effects on reproduction. If a woman is in her 20s or 30s, and eligible for a clinical trial, but she is told she has to hold off on getting pregnant for 4 to 6 years, that could shift her reproductive window. So that could be a reason why they might want to have a fertility consultation.

KONDAPALLI: I agree with you.

When I have patients that are on these medications for an extended period of time, a lot of times, that medication is given in our prime reproductive years. And so that prevents women from that opportunity of starting a family. By going through a process like egg freezing, it may allow them to preserve eggs. Those eggs don't necessarily have to be used, because there are times that patients go through the process of egg freezing, and they’re able to conceive naturally. But if they want to expand their family, they're just getting a little bit older, that would be a great opportunity to use the frozen gametes when they're at a much younger age.

When I have women who are consulting with me for possible egg freezing, I tell them this does not preclude your ability for trying to have a natural conception, but this would be a great option if you're struggling with infertility or you are wanting to expand your family, and now you're in your late 30s or early 40s where natural pregnancy can be just be a little bit more difficult.

And I want to highlight how age has an impact on women, because I think that this will be really important for your audience. If we take women–let's say, for example, I had a woman who's 30 years old, and her possibility to get pregnant naturally at age 30 is about 15% per month. That same woman, if she waited until she was 35, that drops to 10%. If she waits until she's 40 years old, the probability of natural pregnancy per month at age 40 is less than 5%. So you can see, within that one decade that it really makes a difference. So if we have women who are on medications for 4 to 6 years, and they're in their 30s, that is going to take up most of their natural reproductive years. And it just becomes more challenging as they get older, when they stop the medications.

LINDSAY: Before we go into egg freezing, let's just talk about sperm freezing really quickly. Can you just explain what's involved in that?

KONDAPALLI: Absolutely. It's much, much simpler for men to go through gamete cryopreservation or fertility preservation. The mainstay of male fertility preservation is sperm cryopreservation, which just means [the process of sperm] freezing. This is appropriate for men; this would not be appropriate for adolescent boys that have not gone through puberty.

Collection: Men come in and essentially produce a sperm sample, and then that sperm is evaluated by our andrologist. Those are the specialists in our practice that specialize on the sperm side.
Separation: Basically when we freeze sperm, we eliminate all of the fluid. The ejaculate has two parts:

the sperm that's being produced in the testicle, and
the fluid is coming from the prostate gland.

So you can actually separate the fluid and get pure sperm.

Testing. Essentially when we freeze sperm, we only want the fastest swimming, healthiest sperm. So we can place the sperm [through something] almost like a collision course or cylinder. The fastest sperm [end up] at the bottom, [which will] then [be the] sperm [that is] frozen.
Freezing. The technique that we use for either freezing sperm or eggs is called vitrification. It's essentially flash freezing. The sperm can be placed into a little vial, and that vial can be frozen. The sperm can [remain] frozen for years to decades. There is no shelf life on frozen sperm.
Usually when we freeze sperm, we place the sperm into multiple small vials. So it is possible that you don't have to use all the frozen sperm for a single pregnancy. If we're able to separate it into multiple vials, it is possible that one vial of sperm may be appropriate for achieving a pregnancy.

Sperm banking usually only requires one appointment for a man to produce the sample. The sperm can be frozen. And then, there's opportunities for future pregnancy using that frozen sperm.

After sperm freezing:

There are two options for using cryopreserved sperm. It doesn't have to necessarily be in vitro fertilization (IVF). There is another option called intrauterine insemination (IUI), which is artificial insemination that does not necessarily require any fertility treatment.

IUI involves a male who has frozen his sperm. If the sperm meets certain criteria, it can be used for IUI. The female partner can use fertility medications, or check for ovulation. When the time in the month is correct, the sperm can be thawed and placed into a little straw. We place [the straw containing sperm] through the cervix into the uterus, and we can allow natural fertilization to happen in the fallopian tube.

So with frozen sperm, we don't always have to go straight to in-vitro fertilization (IVF). IUI might be a good option.

Alternatively, the other option would be IVF. That's fertilizing eggs outside the body. We then can thaw the sperm, fertilize the eggs, and then allow the embryo to grow essentially in a petri dish, which can then be transferred into the uterus for a pregnancy.

LINDSAY: Does freezing in any way harm the sperm or the egg in that process?

KONDAPALLI: It doesn't, no. We don't see the freezing technique altering the health or the quality of the sperm. One thing we do know is that not all sperm that freezes will be viable when we go to thaw them. The usual recovery rate is about 50%. So you will lose some of the sperm in the freezing and thawing process, but that's just natural. That would happen even if men collected a sperm sample and we allowed the sperm to sit in the lab. After a couple of hours, sperm are going to stop moving, and not be viable anyway. So that's just the way that the sperm acts. But in terms of harming the sperm in the freezing and thawing, we don't see that.

LINDSAY: Let's move on to egg freezing. There are a lot of different protocols among different fertility clinics, but can you just walk us through the basics of what someone can expect?

KONDAPALLI:

Priming and fertility medication: In the ovary for a woman at any given time, she has eggs that are essentially in the pipeline at different developmental stages. So, for example, today is January 26th. In a woman's ovary, she would have the eggs that were selected for January's menstrual cycle. But February, March and April are already in the pipeline. So when women take the first part of the treatment, which is called priming, the goal of that medication is meant to keep all the eggs in a particular month, all in this holding pattern or synchronized, so that when you start the treatment with the fertility drugs, all of a woman's eggs are growing at the right pace.

The fertility medications come in the form of injections. So these are subcutaneous shots that women take themselves. We do teach patients how to give themselves the injections. Subcutaneous injections means you just have to pinch your skin and put the needle right underneath. The needles are teeny tiny. It's always a little intimidating, maybe the first or second day. I always tell women, “Take a deep breath.” But you can do this.
The injections go into the skin of your abdomen, and women take the medications, usually for about 10 to 11 days. Once women start the injections, we do ultrasound monitoring and blood work to see how she's responding to the fertility medications.
Monitoring: The ultrasound is a vaginal ultrasound that allows us to see how the ovaries are responding. Eggs are microscopic, so we can actually see them with the eye. The eggs are in our ovaries and in little structures known as follicles, which essentially look like bubbles. So with the ultrasound, we can measure how big those follicles or bubbles are getting, and it's providing information about the microscopic egg inside.

We also do bloodwork on a frequent basis that allows us to see how a woman is responding. We can make adjustments to her dosing as we go along. So once women start the injections, we do have frequent appointments, for example, seeing us for bloodwork and ultrasound pretty much every other day.
Egg retrieval: Once the follicles are the appropriate size, women take one last medication. Colloquially, it's known as the trigger shot. It causes the eggs to mature and then, a certain amount of time later– usually in our practice, it's about 35 hours later–we can do a procedure called an egg retrieval.

The egg retrieval is surgery that does not require any incisions, so there's no stitches or scar tissue. Women will get anesthesia via IV sedation. It's like sleeping medicine. It's not considered general anesthesia where women have to have a breathing tube and be connected to a respirator. Women will be breathing on their own. They'll be comfortable. They won't feel the procedure. They won't remember the procedure.

The surgery usually only takes about 10 or 15 minutes. It's a pretty quick procedure. We use vaginal ultrasound in a small needle to go through the top of the vagina, where we then collect the eggs from the ovary. My embryologist will look through the fluid that we collect, identify the eggs. There's a characteristic appearance of a mature egg. Those are the eggs that we freeze.

Most women are able to go back to work the following day after the egg retrieval. It is an outpatient surgery, and it only takes at most 15 minutes.
Egg freezing: Once the embryologist looks at the eggs under a microscope, the eggs that are mature can be flash frozen, [which is] called vitrification. Basically, we place the eggs into a little straw, that straw is plunged into liquid nitrogen and then we can freeze the eggs for years to decades.
We don't see that the eggs degrade over time the longer they've been frozen in our facility.

CCRM was actually one of the first IVF clinics in the world to successfully freeze and thaw eggs. We've been doing it since 2007. Most other fertility clinics started in 2012. So that's one thing to keep in mind. If you're thinking about doing this, be mindful about where you select to do your treatment. It makes a big difference on your overall success. The viability of frozen eggs in our practice is about 95% and that would be true if we saw the eggs a year from now or ten years from now. Eggs don't decline as they are in the freezer.

That gives you a big overview of what the process would be for a woman. The protocol that you mentioned is actually the recipe, and we can tailor the recipe specific to a patient. That recipe includes the priming and the injections.

LINDSAY: How many rounds of fertility treatment does a woman need to get a good amount of eggs? Is there ever a good amount of eggs?

KONDAPALLI: The best way for me to counsel women is by doing some basic fertility assessment, or testing for ovarian reserve. Ovarian reserve is, what's the pool of eggs a woman has at any point in her lifetime? And the way that we can assess that is with bloodwork, which is hormone testing, and ultrasound. That basic testing, which is always timed with the menstrual cycle, is usually done on the second or third day of the period.

For your audience members, if they're thinking about going through this process, we do have patients, if they're on birth control pills or any type of hormones, we do have them stop it to get accurate information when we do the basic ovarian reserve testing. And then, we can do bloodwork and ultrasound that will give me an assessment of how many eggs I'm expecting to retrieve from a single cycle or a single surgery. That's important information, because that helps me counsel women.

Maybe I think we're going to get enough eggs from a single surgery, or maybe you should be prepared to do multiple retrievals.

Now, a lot of times women will ask me, how many eggs do I need to have frozen? And I go back and say, well, how many children ideally would you like to have in the future? What the data shows is that for women who are under the age of 35, having 8 to 10 mature eggs frozen is what we would recommend for one baby in the future. There is a lot of attrition that happens when women come back to use their frozen eggs. It’s different from men who freeze their sperm. Men can use that sperm for either IUI or IVF. When a woman wants to use her frozen eggs, the only option would be IVF. [In that case,] we would take the eggs out of the freezer. We would fertilize [them] with sperm. We [then would] let the embryo grow in the petri dish, and then that embryo can be transferred back into the uterus for pregnancy

So there wouldn't be other options there. So a woman under 35, 8 to 10 eggs for one baby. If she wants to have enough eggs for two children, I tell her she needs about 20 eggs. If a woman is 35 to 37, she needs about 12 eggs for one baby. So in order to have enough eggs for two children, she needs to have closer to 25. And the older a woman is, the more eggs she needs to have frozen for the family size that she requires or if she desires in the future.

LINDSAY: What is the ideal age to undergo egg freezing?

KONDAPALLI: Ideal candidates for egg freezing are women who are under the age of 35. Certainly, we will do egg freezing for women in their mid to late 30s, even their early or mid 40s. But again, what happens is that as women age, they will need to undergo more cycles of egg freezing to have healthy embryos in the future. So the ideal candidates are going to be women under the age of 35 or even under the age of 30.

LINDSAY: What is the typical success rate of using frozen eggs to make a baby? If people with familial Alzheimer's disease use their frozen eggs to create embryos, they might consider doing pre-implantation genetic testing (PGT) and only keep the embryos that don’t carry the mutation. So how would that affect their success rate?

KONDAPALLI: As women get older, their eggs and their embryos will be prone to more genetic issues. And so in general, in our practice, our viability of frozen eggs, eggs that we have frozen and thawed, is about 90 to 95% will be viable, [meaning they can be used for] fertilization.

Now, to get from the egg to an embryo, there's a tremendous amount of attrition. There's various factors that are associated with that. For example, a woman may go through the process of freezing her eggs when she is 28 or 30 years old. However, later in life, she has a partner that may have a male fertility issue. And so the sperm may not be as healthy. So we don't get as many embryos as we expect. Even though she went through the process when she was young and healthy at age 28.

So there's some other factors that are associated with success. If a patient is interested in genetic screening of the embryos, we always consider, is this an autosomal recessive illness or autosomal dominant illness? Because that will determine the proportion of embryos that would be affected versus unaffected.

In the case of an autosomal dominant genetic mutation, we would expect about 50% of the embryos to be affected. And so, if you think about losing half of the embryos on the genetic screening, then you can imagine you need to have a lot more eggs to start with to be able to overcome all of the speed to get to an embryo.

And then at the embryo stage, we have another obstacle to overcome, which would be the genetic testing. So it's all dependent on a specific patient's profile.

LINDSAY: If somebody does have a partner, would you then recommend freezing the embryo over freezing an egg?

KONDAPALLI: I think it depends on age. Because for women who are under the age of 35, what the data shows is that overall pregnancy rates in the future are very similar if that woman decided to freeze her eggs now, or went ahead and made embryos. So I think age would be a consideration that we would have. The other thing I advise patients is that once a woman decides to go through this process of fertility preservation, and we fertilize the eggs, and create embryos we cannot go back in time. We cannot un-fertilize those eggs.

And over time, there can be changes in relationship status. There can be different factors that can come up for a couple in the course of their relationship. And if we've already created embryos, and now she's a little bit older, we can't go back in case that relationship does not continue.

She might have a new partner, and she wants to start a family with a different partner. So freezing eggs is a great option because it gives women a lot of flexibility about selecting the sperm’s source for the future. And for women under the age of 35, their overall pregnancy rate is unchanged if they created embryos right away versus freezing eggs by themselves.

LINDSAY: Can you test an egg for a mutation, or do you have to wait until it's an embryo?

KONDAPALLI: You do have to wait until an egg is fertilized and we create an embryo to do genetic testing. So even if a female partner has the gene mutation, we can't just test the egg. When we do genetic testing of embryos, we actually biopsy or remove a couple of cells from the surface of the embryo, so we can extract the DNA, and then screen for a specific gene mutation. You can also do chromosome testing as well. So there's a variety of different types of genetic analysis that can be done.

If we were to extract the DNA out of an egg, there's no DNA that's available in that egg to fertilize and create an embryo. So that's one consideration.

The second thing is that when the egg and sperm meet at the time of fertilization, there's so much genetic shuffling that occurs. It's called recombination. And that always happens at the time of fertilization, [which is when] the embryo is inheriting certain types of genetic material. So you would only get half the information if you were only to screen the egg or the sperm.

And because of that genetic shuffling, the best opportunity, based on the technology as it is right now, is to screen the embryo. So unfortunately, you can't just do genetic screening on the egg. We do have to create the embryo and then do genetic testing on the embryo.

LINDSAY: One of the biggest burdens to egg freezing is costs. Although this can vary by state and clinic, what are the typical costs of egg freezing? And does health insurance cover it?

KONDAPALLI: This is one of the areas that's so variable from state to state, from insurance company to insurance company. So I wish I could give you an estimate of about a typical cost, but it is so widely variable. It could be a few thousand dollars to $15,000, depending on where a person seeks care.

A couple of things to keep in mind is that there are certain states across the country that have mandates for fertility treatments, and some states will also have insurance coverage for fertility preservation. So thinking about what state you live in, and seeing if it's one of the mandated states for insurance coverages, and then going a step further, and seeing if fertility preservation is also included in that state law.

In the state of Colorado, there was a bill that was sponsored last year, and I'm really pleased to say that it was approved and passed by the governor in Colorado. So Colorado proudly is the 18th state in the US that has a mandate for insurance coverage for fertility treatments, including fertility preservation. So checking with your state will be helpful.

Second is checking your insurance. There are certain types of insurance that you may have through your employer that has infertility or fertility coverage, and fertility preservation could be included in that. Also, checking with your human resources department to see if open enrollment is available. Are there certain opportunities to have additional insurance that would include fertility coverage? Some employers will actually have certain types of insurance, in addition to your health insurance, that's specific to fertility treatments. And egg freezing would be included in that. So those are the sort of opportunities or resources that a person may have. Now, I have had patients, where we have written a letter of medical necessity if they have a medical condition or something that predisposes them to infertility. So talking to a fertility specialist like myself, they can be your advocate, and sometimes they can approach the insurance company and make an argument as to why egg freezing or sperm freezing or fertility preservation would be indicated for a person.

[Editor’s note: Disclosing your risk of FAD to an insurance company can have unintended consequences.].

LINDSAY: What is the typical cost of a fertility consultation?

KONDAPALLI: I think that will depend on who you seek treatment from. It’s going to be specific to the practice that you go to. In our practice, a typical new patient consultation is around $300 or $350. And many times patients have coverage for it, so they may not even have an out-of-pocket cost for the actual consultation.

LINDSAY: I've heard that there are these physical and emotional burdens that women face when they go through egg freezing.

What do you think women should expect? And what might help them better overcome these barriers?

KONDAPALLI: Common side effects of fertility medications are going to be bloating. A third of women do feel bloated because their ovaries are getting enlarged and they feel pelvic fullness. Also because their hormone levels are going up, they may feel a little bit of extra water weight. It's very, very common for women to gain anywhere from 3 to 5 pounds during that two week period of time when they're on fertility medications. That could mean puffiness in their hands, puffiness in their ankles. Sometimes women can spill a little bit of fluid into their lungs and feel short of breath. All of this is self-resolving.

Oftentimes after we do the egg harvesting, a woman will get a normal menstrual cycle within 10 to 12 days, and by that time she will have [gotten rid of] all that extra water, and feel back to normal. So, bloating is the most common side effect.

Pain at the injection site because women are having to administer these medications in their abdomen. I do have women who say, “gosh, I start feeling like a pincushion because I'm giving myself these shots pretty frequently.”

I don't hear from a lot of women that [say] the hormones affect them [emotionally]. [Editor’s note: Some women have reported feeling more emotional during this time, emotions similar to when they’re on their period.] There are some other medications that we give women during the injections, and sometimes they [sometimes lead to] insomnia, or trouble sleeping. But I have more women who tell me that they were expecting the side effects to be much worse than they actually experienced.

Ways to deal with some of the side effects:

Talk to a friend. If you have a friend or someone who's gone through the process, talking to them [will help] because having that personal experience or hearing from other folks and what they went through can be really, really helpful, to alleviate some of the myths or concerns about what the medications are like.
Leverage your clinical team. Your clinical team is a great resource. So for example, in our practice, when I have a woman who's already consulted with me, we've done the initial ovarian reserve testing, I have a follow up. We've made the decision that she wants to move forward, [so] she meets with one of my nurses, and my nurses do a very extensive consultation that gives them a much more detailed nuts and bolts, information about what the process looks like, what to expect, how to deal with some of the side effects, making sure they can take the medications themselves. We teach women how to do the shots, and that is a pretty extensive consultation with the nurse to go through all the specifics of the process.
Limit activities that aggravate side effects and complications. One other thing to keep in mind is once women start the medications, the injections part of the treatment process, we do have activity restrictions. So if a woman typically uses running or cycling or yoga or some other physical activity as a great way for stress relief, for managing symptoms, unfortunately, that would not be permitted once women start the shots.

We do limit activity to just walks, maybe even light hiking, but nothing more vigorous. The ovaries get bigger and bigger, and there is a rare complication known as torsion, where with any type of twisting motion of your torso, [can cause] the ovary [to] actually swing and twist on its blood supply. Torsion is an emergency situation that requires emergency surgery.

So we do have women, once they go start the injections until they get their period, limit exercise to just walking. So [although] exercise might be a great coping mechanism,unfortunately for this process, it's not one of the strategies, outside of extended long walks.

LINDSAY: I love the idea of creating a support network while you're going through this. At Youngtimers, we have a lot of support groups going on and it just makes that much of a difference when you're facing what feels like a very difficult thing.

Is there anything you would add, other than the bloating and torsion, about the risk of this procedure?

KONDAPALLI: Torsion is exceedingly rare. Bloating is pretty common.

There's a rare complication known as Ovarian Hyperstimulation Syndrome, or OHSS. That's where women's estrogen levels get very high. They become puffy all over. They can feel short of breath because they have fluid in their lungs. Even with that, it is self-resolving, and the treatment is actually drinking more liquids. Eventually the kidneys will kick in, and women will absorb all of that liquid and excrete [it out] in their urine. But that's a pretty rare complication that occurs.

The risks of the surgical procedure are rare. We use a needle through the top of the vagina, so there is a chance of bleeding. There is a chance of an infection developing from the procedure, but we give women prophylactic antibiotics to reduce that risk. There is a risk of injuring maybe the bowel or the bladder. But we do these procedures with ultrasound guidance, so we see exactly where the needle is going. And the likelihood of a complication is very minimal from these types of surgeries.

LINDSAY: We talked a little bit about the advantages and disadvantages of freezing eggs versus freezing embryos. Are there cases where you would recommend freezing embryos over freezing eggs?

KONDAPALLI: The biggest difference between freezing eggs and embryos is the viability of the thaw. So in our practice, about 95% of eggs will be viable in the future when we're ready to use them, versus about 98 to 99% of embryos will be viable. It's because an embryo is just a more robust structure. An egg has one single cell. So we're hoping that that one cell will survive that freezing and thawing process, versus an embryo which has close to 100 cells. It's a much more robust group of cells. And so that's why the survival rate is higher.

One of the advantages of creating embryos is that if we have a patient that is partnered, is committed to going ahead and fertilizing her eggs and is interested in genetic screening of the embryos, all of that can happen even before we freeze the embryo. So, for example, if there's a specific gene mutation that a couple is interested in screening their embryos for, we can go through the process. The process of the hormonal stimulation and the egg retrieval is exactly the same if a woman chooses to freeze her eggs or create embryos. So for the female partner, the process is the same. It's just what happens in the IVF lab [that is different]. If we're creating embryos, we'll go ahead and fertilize the embryos right at the time of the egg retrieval.

[To do this,] we will let the embryo grow in the IVF lab for 5 or 6 days. The embryo can be biopsied, which means we remove a couple of cells from the surface of the embryo, and then the embryo is frozen. [From that biopsy] we can then do the genetic testing.

The advantage of creating the embryos and going ahead and doing the genetic testing, is that a patient or a couple has a realistic idea of, “How many healthy embryos do I have when I'm ready to start a family?” And if that number of healthy embryos does not feel comfortable, they can choose to go through another retrieval, maybe make more embryos so they have them available for the future.

One of the disadvantages of freezing eggs–and many times, I tell women this–is I don't know how good your eggs are or what the performance of your eggs are until the future, when you're ready to fertilize them. We create embryos, and then we know how many embryos we're having, even though I expect for a woman who is under 35 that she needs about 20 eggs for two kids in the future, it's possible that she has some underlying quality issue. Maybe her eggs are aging beyond her chronological age.

In the future when she comes back, we don't get that many embryos. And now she's much older and thinking about going through the process at age 40. We're not getting as healthy eggs as when we were 32 years old or so. So, those are some of the considerations that we have when we're talking to patients. Does it make sense to freeze eggs? Does it make sense to freeze embryos? Because for women who freeze eggs, we really don't have a good assessment about the performance or how many embryos will have until she's ready to fertilize them and create the embryos.

LINDSAY: Some people in the FAD community want to know their genetic status, and others don’t. Can you screen your embryos without actually ever learning your status?

KONDAPALLI: Yes, that is something known as non-disclosure. Sometimes we have patients that are interested in going through this process, but not actually knowing the genetic test results. We're pretty flexible in terms of disclosure to a patient in terms of how much information they will want, versus how much they don't want.

Now, one thing to keep in mind, if I have a patient that is interested in genetic screening of their embryos, let's say for a specific gene mutation, we do need to have a molecular report as to what that gene looks like. Because when we do that screening on an embryo, we essentially create a molecular tag, and that allows me to screen that embryo.

Now we're not doing routine screening of 25,000 genes, which is what the body is made of. So we're not doing global screening on embryos. But if I know that there's a specific mutation, then I can screen for that in an embryo.

If a patient doesn't want to know what their status is, they could potentially get that testing and have the results sent to my office. If it is positive, then we can go through that process of making the probe or molecular tag [to just screen the embryos, without disclosing that person is positive for the mutation].

LINDSAY: So if they had for example, their parent’s grandparent’s genetic testing report, that would also work for your lab?

KONDAPALLI: It would. And many times when we create these molecular tags, we do want to have other family members that have that genetic mutation. That helps us create that tag and increase the accuracy of that probe.

LINDSAY: If somebody is worried about losing their prime fertile years due to either treatment or study participation and is interested in egg freezing, what steps would you recommend they take to make an informed decision?

KONDAPALLI: I think getting the information and seeking a fertility consultation from a reproductive endocrinologist or infertility specialist would be a key first step. And if you can identify a specialist that also has expertise in fertility preservation, specifically in a medical population, that is what I would recommend.

That consultation, what that would look like is that we go through an extensive past medical history, get a sense of their gynecologic history, and their family history. And then, if a patient wishes to move forward with an evaluation, we would be scheduling hormone testing [and] the ultrasound.

For men, it's just a matter of coming in for a sperm collection and doing sperm freezing.

If I have patients that don't live in Colorado, and in fact, even if I have patients that live in Colorado, all of our appointments are virtual. So we just do a virtual visit. I review all of the medical history. We come up with a plan for what the testing would look like for a person who doesn't live in Colorado. They actually come to see me in Colorado for something known as a one day workup, where we can do almost all of the testing in a single visit. They meet with my nurses. It's a very efficient use of their time, because everything is done in one day. We can start to come up with the treatment plan.

They go back home, we have a follow up telehealth visit, and then they can move forward with treatment.

But step one is getting a fertility consultation. That way, you can have a tailored evaluation about your medical history. We can talk through a little bit more specifics about what the next steps are, and a little bit more information and counseling about if this is a good option for a particular person.

LINDSAY: A lot of people are concerned about genetic discrimination. They want to be cautious when they let medical professionals know about the risk of their inheritance of a disease. Is there a way to talk to a reproductive endocrinologist about those concerns without that necessarily going into their medical record?

KONDAPALLI: Absolutely. Sometimes, patients have those same kinds of concerns. So that could be something that is discussed at that initial consultation, so that we can maintain some privacy or to the level of comfort that a person has.

LINDSAY: Thank you again for all of your insight and expertise on gamete cryopreservation. We appreciate you taking the time away from your patients and to answer our questions.

KONDAPALLI: Lindsay, thank you so much for inviting me to participate today. I really enjoyed our discussion. I think that this is such an important topic, especially for young folks that are thinking about family planning for the future.