In this webinar, Dr Melvin H. Thornton, Reproductive Endocrinologist at Global Fertility & Genetics, has talked about fertility preservation for men, when should it be indicated, how it’s done and why.
Everyone in the world nowadays talks about the female biological clock and female fertility preservation. We all know that women have a biological clock that ticks, and their fertility rates decline once they’re over 30, particularly over 35. Because of the advent of new technology called vitrification of eggs, you hear about female egg freezing all the time. By doing that, we’re able to preserve a woman’s eggs so that when we go to thaw them out in the future, she would have the same chance of having a pregnancy that she would at the age that she froze the eggs. So that’s the latest technology for women. Because of this technology, they hear about it every day on the news.
However, it’s important to point out that men have an interest in preserving their fertility as well, just as women. It’s important because there’s a rumor out there that men can have children up until the day they die, which is true. However, you do lose sperm cells as they get older and have a decrease in fertility rates.
In men who are delaying their childbearing years, it’s important for them to understand this decline and to consider maybe preserving their fertility, particularly men in clinical situations where they have a genetic disorder, an autoimmune disease, or cancer treatment that can negatively affect the way sperm is produced.
Another important aspect about sperm is that for years now, sperm counts in the Western part of the world have been declining. What you’ll see is that I get about a 50% decline from 1973 to 2011, and this decline is anticipated to continue through until 2045. So, because men are naturally having a decline in their sperm counts, it’s a very important topic to talk about preserving fertility. Shown slide demonstrates that there are a lot of things in the environment that are affecting our sperm. This is looking at the mean sperm concentration and count associated with global plastic production since the 1970s. What you’ll see is that as plastic production goes up, sperm count has gone down. Talking about fertility preservation for men is a very important topic.
When we talk about fertility preservation in men, we’re talking about freezing sperm. Freezing sperm is the process of collecting it, analyzing it to make sure the sperm counts are healthy, and then storing that sperm for later use. That sperm can be used for fertility treatments such as inseminations or in vitro fertilization. It can be donated to other couples or individuals for their use, and it also can be stored indefinitely.
When we talk about sperm cryopreservation, the important thing is that sperm freezing has been around for many decades. Sperm can be stored indefinitely until it’s needed. There are reports of babies being born after using frozen sperm for more than 20 years. There are also a lot of new indications now for freezing sperm. One of the indications is advancing male age. Someone known to have a decreasing sperm count or very poor sperm count can freeze their sperm to bank it to increase the chances of having fertility success with IVF or insemination. We know that when men are diagnosed with certain cancers, there’s a risk that chemotherapy and radiation therapy will affect their sperm. Other situations, like certain lines of work, may be life-threatening and put fertility at risk. We also talk about preserving fertility in those men, such as men who are being deployed to a military or war zone, where there’s a high chance of injury that could threaten their fertility. Some men who have decided to have a vasectomy may change their minds afterwards and decide they want to have more children. So, it’s always important to consider banking your sperm before a vasectomy. For transgender patients, we always want to talk about preserving their sperm before transitioning.
Are there risks involved in sperm freezing? The answer is that sperm freezing has been around for decades, successfully used since 1953. It’s a very safe and standardized process and continues to improve as technology advances. There are no risks or side effects to producing sperm naturally because this is typically done by masturbation. If someone’s unable to masturbate or has a medical condition that prevents them from masturbation, then surgical procedures can be used. These are very small surgical procedures, but there are risks associated with that, such as bleeding and discomfort. The most important thing is that cryopreserved sperm has no time limits; you can leave it frozen indefinitely. Healthy babies have been born from sperm that has been frozen for more than 20 years.
Some clarification is needed about sperm and semen. Sperm are the male reproductive cells that contain the genetic material, while semen is the liquid that’s ejaculated, which may or may not contain sperm. So, when a male ejaculates, you can see sperm cells in the semen. However, many men produce semen without sperm cells, which is called azoospermia.
One of the biggest topics for male fertility preservation is cancer. In the U.S., 9% of cancer diagnoses are in individuals younger than 45, and 1% are in young men under the age of 20. The most important thing about cancer is that cancer survival has improved due to advances in cancer therapies. Now we talk about the concept of cancer survivorship, which means that most people diagnosed with cancer will have a good outcome with treatment and have a long survivorship. So, now we’re talking about being able to maintain their reproductive potential in the future after they’ve had treatment.
So, how does cancer treatment affect sperm and male fertility? Fertility problems in men from cancer treatment occur in two ways: direct damage to the endocrine glands, such as the testicles, and damage to the sperm, lower sperm production, lower semen production, and damage to the nerves or ducts that cause ejaculation. When you look at the effects of cancer treatment on men, there are greater effects on fertility when chemotherapy and radiation are used. The testes and testicles are very sensitive to chemotherapy and radiation therapy. When men are diagnosed with certain cancers, there’s a risk that chemotherapy and radiation therapy will affect their sperm. Surgery, such as testicular or prostate surgery, can damage nerves, leading to erectile dysfunction and ejaculatory dysfunction.
When we look at different types of treatment and chemotherapy, alkylating agents are the most toxic to sperm. They can cause gonadal dysfunction by damaging the testicles, reduce or stop sperm production, and result in azoospermia. After chemotherapy and radiation therapy, sperm may or may not return, depending on the dosages. Even if sperm returns, it may not be the same as before treatment, and there can be long-term effects. Risk factors for increased fertility issues include higher doses of radiation or chemotherapy, existing fertility issues, and increased age.
Regarding paternal ageing, it causes slow, gradual changes in the reproductive system, a process called andropause. Erectile dysfunction is also common with ageing. Paternal aging leads to a decrease in fertility, and studies have shown that fertility rates peak at around age 32 for men. So, it’s important to consider the effects of age on male fertility.
Other things associated with paternal aging include a decrease in testosterone. Older men will experience a decrease in libido, sexual dysfunction, and sexual frequency, all of which lead to reduced opportunities for conception. When you look at the data, they control for the female age. In other words, when men’s age advances but the female age stays the same, studies comparing both show that the rates of pregnancy among men at 50 years of age were 23 to 30% lower compared to younger men at the age of 30. Similarly, when they conducted a larger study with about 90,000 to 93,000 patients, they found a statistically significant associated decline in semen volume, sperm motility (especially progressive motility), the shape of the sperm, and the presence of fragmented cells, as well as concentration, all leading to decreased fertility as men age.
Furthermore, as men get older, there’s an increased spontaneous miscarriage rate. In a retrospective study looking at 1,100 IVF cycles where they were sampling the embryos to check for normal chromosomes, they found that in men over the age of 40, there was a lower incidence of normal embryos (euploid embryos) compared to men aged 35 to 40. There’s also an increase in DNA fragmentation, which means that the DNA in the sperm cells is damaged, with about a 15% increase in highly damaged DNA and about a 20% increase in DNA breaks compared to younger men.
Additionally, as men get older, they are more prone to acquiring DNA mutations due to oxidative stress, which increases the risk of health issues or impacts on the health of their offspring. There is also a significant correlation between paternal age and neurocognitive disorders, supported by existing literature. Several hypotheses explain this increased risk, including the frequency of mutations, age-related epigenetic alterations in sperm, late fatherhood, secondary paternal psychiatric disorders or subclinical predisposition, and environmental factors, all contributing to an increased risk of neurocognitive disorders as a male’s age advances. The term ‘advanced paternal age’ typically applies to men over 40.
Another important category to focus on in terms of fertility preservation is transgender women. Before transgender women start hormonal therapy during their transition, it’s essential to consider fertility preservation. Hormonal therapy, particularly long-term estrogen treatment, may be associated with testicular damage. Spironolactone, also used during the transition phase, is also associated with testicular damage. The best practice is to encourage sperm banking before initiating any hormone therapy as part of the transition process.
How is fertility preservation or sperm collection performed? A collection room is typically used for this purpose. In the collection room, there are magazines and TVs to help men produce sperm samples. Nowadays, most men bring their own phones with videos to assist them. During the process, the male masturbates to orgasm, and the ejaculate is collected in a special container to ensure there is no toxicity associated with the container. If lubrication is needed, mineral oil is a suitable choice.
Once the sperm is collected, it is placed into a specimen cup and analyzed by the laboratory team. A semen sample should have a normal sperm count of at least 15 million sperm per ml, with at least 40% motility and a significant percentage of normally shaped sperm. Additionally, when banking for fertility preservation, infectious disease screening is usually required.
After the specimen is produced and analyzed, cryoprotectants are used to prevent damage during the freezing process. The sperm is then frozen using a slow freeze method, reaching temperatures as low as minus 196 degrees Celsius. In the future, it can be thawed for use in procedures like insemination or IVF. Depending on the quality of the sperm, one collection may yield 2 to 3 vials of frozen sperm, and multiple collections can improve the chances of successful fertility preservation.
In cases where a male can’t ejaculate or masturbate, such as some heterosexual couples needing intercourse to produce sperm, special condoms can be used to collect semen during intercourse. For individuals with specific conditions like spinal cord injuries or retrograde ejaculation, alternative methods like vibratory ejaculation, electroejaculation, or urine sample retrieval may be employed. Surgical extraction, such as testicular aspiration or testicular biopsy, can also be performed when necessary.
Once you have successfully preserved your sperm, you can consider your options for family building. The choice between intrauterine insemination (IUI) and in vitro fertilization (IVF) depends on the quality and quantity of the frozen sperm, as well as the female partner’s circumstances. IUI is a less invasive option and involves washing the sperm before placing it into the female partner’s uterus. IVF is a more complex procedure that requires the female partner to take injectable medication to stimulate egg production. Eggs are retrieved and fertilized, and embryos are created for transfer to the uterus.
Ultimately, the success of IUI or IVF depends on various factors, including the quality of the sperm, the female partner’s age, and her reproductive history. It’s important to discuss these options with a healthcare professional when ready to start the family-building journey.
In conclusion, fertility preservation is crucial for both males undergoing cancer treatment and those considering delaying parenthood. Sperm freezing is a safe and effective method to preserve fertility. Additionally, discussions about fertility preservation should be initiated early in cancer diagnosis, and all males should be counselled about the reproductive risks associated with cancer treatments. This ensures that individuals have the best chances of maintaining their reproductive potential in the future.- Questions and Answers
There is no time limit. Many case reports have shown that men have frozen sperm for over 20 years, and they’ve had healthy babies, so there’s no time limit for using the sperm if it’s frozen. It’s just a matter of choice whenever you’re ready to start your family building journey.
Medically, there’s no time limit, but what’s important I did not mention is that here in the U.S., freezing sperm may cost between 700- 800 US dollars, and then on an annual basis, the storage fees may be about 1000 dollars per year. Sometimes people look at those numbers, and they have to put a time limit on how long they’re going to store sperm just because of the cost, but medically it can be frozen indefinitely. There is a cost of storage fees, some sperm banks will give 3 to 5 years of storage for sometimes 2 or 3 thousand dollars, so it all depends upon the sperm bank.
Typically, it’s going to be oxidative stress. Oxidative stress comes from diet, the best way to treat that is with a good male multivitamin or antioxidants or a good diet. I always push my clients on fish oil, and fish oil has shown to decrease DNA fragmentation. Other things that can cause DNA fragmentation are environmental, such as smoking, poor diet, all those things can lead to DNA fragmentation, but it’s reversible by using antioxidants.
If one medication doesn’t work, then they will always go to a different medication. If you start with Clomiphene, then you try that for 3 months, if that doesn’t work, you’ll switch over to Letrozole, unless someone has side effects or has a contraindication where they can’t take it. We recommend either one, and it depends upon preference and what you’re looking to accomplish. They’re both equally effective as far as improving sperm in men.
Typically start with Clomiphene. Most people using Clomiphene are taking 25 milligrams every other day, and the dose of Letrozole is 5 milligrams every other day as well.
It’s not a value of FSH or LH, here in the U.S., we tend to start with the least invasive treatment, which is the oral medications Clomiphene and Letrozole and then move to the more invasive such as injections with gonadotrophins. The problem here in the U.S. is that gonadotrophin injection therapy may run about a thousand dollars per device with a pin, which tends to be very expensive. We try to start with the most cost-effective treatment, which is the oral medication, so we don’t use it directly, we use it mostly in couples or men who have not had success with the oral medication.
There’s no risk involved in freezing sperm.
In the first scenario, the fact that you had a much better response to the second egg donor means that it may have been an egg issue with the first egg donor. I would imagine the first one could have been an egg issue, particularly if you had the same sperm with a different egg donor and got much better quality embryos 5 out of 9.
Statistically, in nature, 50% of fertilized eggs will become a blastocyst, and that 25% will lead to a healthy blastocyst. It all depends upon how many eggs you’re starting with, how many are fertilized, then you’ll see how many develop. Looking at the individual age of the egg donor, someone who is 30 and below, you’d expect to have at least anywhere between 30 to 40% abnormality rates, that’s what the data shows. With your second donor, you had an excellent outcome.
That’s very minimal contraindications of using Letrozole. There are more contraindications with Clomiphene than you’ll see with Letrozole. If anyone has a history of migraines, anyone having a history of visual disturbances, you will stay away from Clomiphene, which affects those organs.
There’s no contraindication to using Letrozole unless, of course, they’ve had an allergic reaction to it the first time they took it or side effects that were unbearable the first time they took it, but there’s nothing as far as contraindications that stand out.
Typically, not because of the way the sperm is processed, you’re washing away the sperm that’s poor quality, so you’re left with a better quality sperm. There are new devices that are out there to separate the sperm a little better.
There’s something called a Zymote, which’s a new technology where only the sperm that have normal heads and tails can swim through, so you’re selecting up the sperm that are damaged with DNA fragmented DNA, but this routine handling of the sperm doing the IVF process does not cause DNA impairment.
I believe it’s a good option to use Letrozole or Clomiphene, I don’t have an issue with having everyone take Letrozole, I think it’s a good drug to improve sperm counts.
The results depend upon how responsive they are to the treatment, but in general, we’ve had good results with the Letrozole. When you talk about non-obstructive azoospermia, a good result doesn’t mean they go to a normal sperm count, a good result means that we can get them to the point where they have enough sperm to actually go through an IVF process or maybe have enough sperm for an IUI procedure.
I would say try to freeze another sample instead of waiting just because as you get older, the sperm quality and concentration will decline, so I would try to freeze as much as you can this year, and it all depends upon your goals in the future.
If you already have 7 or 8 samples of sperm frozen, that should be enough for any sort of treatment you desire inseminations or IVF, but if you’re going to produce more, I would do it sooner than later.