Sperm’s ability to fertilize an egg is dependant on healthy DNA. But some sperm are fragmented.

Healthy DNA is arranged in a double-helix spiral bound by cross-bonds resembling a ladder. DNA damage means the bridges become unstable or broken causing instability in the DNA ladder.

That instability is referred to as fragmentation or damage of the DNA. If there is a high amount, you’ll likely see a reduction in male fertility, poor embryo development and lower rates of implantation.

Scientific literature shows that the extent of DNA fragmentation has little relevance to the basic semen quality parameters (concentration, motility, morphology, etc.) For example, a “good” sperm sample with high concentration, motility and morphology doesn’t guarantee you’ll get pregnant if there’s poor DNA Fragmentation Index (DFI).

Why is DNA Fragmentation important in the assessment of male fertility?

The test (flow-cytometry or TUNEL assays) is used to count the number of sperm cells per sample that contain suboptimal, damaged or fragmented DNA.

What are the values and what do they mean?

DNA Fragmentation Index (DFI) is used to quantify DNA damage in the sperm. DFI is inversely related to sperm’s ability to fertilize an egg and produce a viable embryo. DFI of less than 15% in sample is considered optimal. DFI between 16-29% is considered to be good or fair fertility potential. Sperm with DFI over 30% is considered to have poor fertility potential. Although exceptions do exist, these percent ranges have been established based on numerous scientific publications over many years of research.

What does testing mean for our ability to conceive?

• More accurate assessment of semen sample quality
• May explain previous failed attempts to conceive
• Determine suitability for IUI versus IVF/ISCI
• Assessment of efficacy of medical intervention or treatment of infectious diseases to improve
• Ultimately improve fertility potential of the male partner

What are the causes of DNA damage?

We don’t yet know all of the factors that lead to DNA damage. Most common ones we do know are chemical/toxin exposure, heat exposure, varicocele, age, infection, smoking, alcohol, radiation or testicular cancer.

The post What is DNA Fragmentation? appeared first on Fertility.ca.

However, there are some logistical challenges limiting choice. There is only one Canadian sperm bank: ReproMed, based in Toronto.

To allow for a greater variety of sperm available to Canadians, Health Canada has allowed for the importation of non-altruistically-donated sperm. Including ReproMed, there are three organizations that import sperm, the other two are Outreach Health Service and CanAmCryo. At our clinic we endorse Outreach and ReproMed.

When you choose sperm, Health Canada recommends that women who have never been exposed to Cytomegalovirus (i.e. “CMV negative”) should choose sperm that is also CMV negative. We test for CMV status for all women considering donor sperm.

When you make a purchase you’ll be offered washed and/or unwashed sperm samples. We re-wash the sperm regardless. From our perspective, there’s no functional difference which sample you’d choose to purchase. We see equal pregnancy rates from either approach.

When doing donor sperm inseminations, we ask that women trigger ovulation (usually with Ovidrel), to ensure that the timing of insemination is ideal. We use one sperm unit per cycle.

We’ll provide you with information on the count of the sperm being inseminated, and the average motility. Using fresh samples as a reference frame, we like to see at least 5 million sperm in the washed sample with 80% or greater motility. We won’t always see these numbers with frozen-thawed sperm: you may have a reduced success rate.

The success statistics that support the donor-sperm program are available from your clinical team and can be individualized to your specific situation by your doctor.

Next post, we’ll be covering guidelines for known donors.

The post We’re considering using an anonymous sperm donor. How does it work in Canada? appeared first on Fertility.ca.

1. Oocyte (egg) quality

Implantation is more likely to happen when a healthy embryo is present, and the best predictor for a healthy embryo is a healthy egg. Egg quality is based on a number of factors.

2. Sperm quality

We now know that paternally imprinted DNA is disproportionately expressed in developing placental tissue. In other words, sperm quality matters a lot when it comes to implantation. For a successful pregnancy, sperm should have stable, well balanced DNA.

What you can do:

There are many ways that sperm quality can be maximized. Antioxidant vitamins are a popular intervention. We have more on sperm here and here.

3. Embryo quality

Embryo quality is a reflection of both egg and sperm. If you are doing an IVF cycle, embryo quality can be determined by grading systems. The embryos most likely to continue to develop will have 6, 7, or 8 cells by day 3 of development in the lab.

If you are considering a frozen embryo transfer (FET), embryo quality is also a reflection of the laboratory’s freezing-and-thawing success rates. In some labs, FET cycles have a pregnancy rate of one-quarter to one-half that of fresh cycles, but the rates vary by clinic and many of us are now seeing the same (and even higher) success rates with FET. Embryos may be frozen with the traditional slow-freeze protocols, but with the flash-freeze vitrification methods we are seeing better success rates.

Here’s what you can do:

Maximize egg and sperm quality before you start treatments.

Consider a repeat fresh IVF cycle instead of multiple frozen cycles.

4. The number of embryos transferred

There are some suggestions that embryos help each other to implant. In other words, the more embryos that you transfer, the greater the chance that each one will stick.

Be very careful with this one. The movement in our field is away from multiple-embryo-transfer, not towards it, because the risks associated with multiple pregnancy are very real. Some clinics even advocate for elective single embryo transfer. But if there are other impediments to implantation–say, embryo quality is a known concern–then our standard of care is to transfer multiple embryos in the hope that one will take.

We also find we have more success with blastocyst embryos transferred at day 5 rather than morula embryos transferred at day 3.

5. The woman’s overall health

An overall health screen tests many things, and usually includes thyroid function and prolactin levels.

Depending on your situation and family history, you may also be screened for other systemic diseases that can affect implantation. For example, we might look to rule out diabetes, autoimmune conditions such as elevated Natural Killer cells, a pre-disposition to hypercoagulability, markers for celiac disease…and many more.

If you and your immediate family are otherwise healthy, many of these tests are not routinely offered.

Here’s what you can do:

Eat well, exercise moderately, don’t smoke, and continue seeing your family doctor for annual check ups even when under active fertility care. If you have or suspect a specific medical condition, ask your doctor if further testing is warranted.

6. Shape of the uterus and fallopian tubes

Some women have an anterverted uterus, some women have a retroverted uterus. Both are fine: the terms simply refer to which direction your uterus tips. Of more importance, we need to confirm that the uterine cavity is a normal size and shape for implantation to be successful.

To check the structure of your uterine cavity, the gold standard of imaging is a 3-dimensional sonohysterogram. Hysteroscopy (surgery) is used when necessary for things like fundal polyps, impinging or submucosal fibroids, and/or a uterine septum extends 10mm or more.

The shape of your fallopian tubes should be confirmed by ultrasound, a hysterosalpingram, or (less often) surgery. We also screen for chlamydial antibodies, because a history of this infection can affect tubes. We know that dilated tubes (”hydrosalpinges”) may compromise implantation, and sometimes suggest that they’re surgically removed before IVF.

Here’s what you can do:

Make sure that you have all the imaging tests available to you updated before starting your treatments. If your doctor suggests uterine surgery, you may want to get a second opinion. But don’t be too hesitant: the surgery is often a day procedure, and the benefits can be profound.

7. Lining of the uterus

We look at the uterine lining itself, to judge whether or not implantation may be expected. The endometrial lining can be assessed in the following ways:

Appearance on the transvaginal ultrasound

An ideal lining will be at least 7mm thick on day of ovulation trigger (the day your HCG spikes). Ideally, it will also have a “triple line” appearance (an ultrasound finding that shows a good response to estrogen).

After ovulation, the endometrium compresses somewhat, and the triple-line pattern will be less distinct. These are normal findings.

Luteal endometrial biopsy

An endometrial biopsy is not part of every cycle, but it may be done in the luteal phase of a cycle before IVF, in an effort to confirm that the implantation window exists. Various markers for this implantation window have been identified, including histologic appearance and grading, specific findings seen only by electron microscopy, and the staining for various markers that are thought to be associated with implantation.

There are several tests which analyze endometrial biopsy further looking for markers of implantation. This is controversial, as it does not work as well as we would like, but some tests include Harvey Kliman’s Endometrial Function Test, the “E-tegreity Assay” for beta-3 integrin, and sending a biopsy specimen off for culture (this is most useful when intrauterine fluid is collecting and worries about infection persist).

We offer the EFT through our office in partnership with Dr. Kliman.

Here’s what you can do:

When endometrial thickness is low (the lining is never more than 6mm thick), you should talk to your fertility doctor, for management is highly individualized. Many authorities recommend a BMI of >18.5; a healthy lifestyle that involves no smoking and limited caffeine; and ask that you consider red meat to be part of your diet. Supplemental estrogen is regularly used and acupuncture may also be suggested. But again: you should really speak with your doctor.

If you have irregular cycles and a tendency towards a thick lining (>12mm), you might benefit from an endometrial biopsy to rule out hyperplasia.

Even if the EFT is limited, the very act of getting an endometrial biopsy may help with implantation. The proper studies have not yet been done to support this statement, but many smaller ones suggest that implantation may be boosted by as much as 20% in some cases.

8. Embryo transfer technique during IVF

In an IVF cycle, embryo(s) selected for transfer will be collected into about 0.020cc of fluid and inserted into the womb. The process of insertion is highly physician dependent: this means that it matters who does your embryo transfer. The following issues will be considered by your doctor:

(a) Transfer medications like progesterone, antibiotics, and steroids.

(b) Cervical preparation

(c) Use of a tenaculum

(d) Catheter type

(e) Ultrasound guidance

(f) Post transfer instructions

Here’s what you can do:

Work with a doctor and clinic that you really trust. Embryo transfer is very important. Some physicians even suggest doing a mock transfer prior to the IVF cycle itself. It has been our experience that the uterus is lying in a slightly different position every time. In other words, the mock transfer did not help as much as we would have hoped for. We now judge the value of a mock transfer on a case-by-base basis.

9. Luteal Support

We support the luteal (post ovulatory) uterine lining with progesterone whenever we are worried about natural progesterone levels. Progesterone may be taken orally, intramuscularly, vaginally, or rectally. Other medications that you may read about for the luteal phase, and into early pregnancy, include estrogen, ASA, dexamethasone, Fragmin, Lovenox, IVIG, HCG, and others. We are very cautious here: some of these medications have side effects that, in some circumstances, could be of real concern to you or your baby.

Here’s what you can do:

Definitely talk to your doctor. The medications that you take in the luteal phase, and into pregnancy, must be compatible with bringing a healthy child into this world. That said, the ideal balance will keep your endometrial lining stable. If you find that you consistently have your period before the planned pregnancy test day, your luteal support may need to be re-examined.

10. Lifestyle

You need to minimize caffeine, quit smoking, and avoid alcohol. Intercourse during the “two week wait”? We think it’s fine, but I would ask your doctor, as everyone has a different opinion on this subject.

Conclusions

To be successful, your clinic must focus on implantation. Many protocols and techniques are well standardized across fertility clinics, but implantation standards are not. Because of this, there are great differences in implantation success rates across both clinics and doctors. We hope this article will help shed light on some of the complications and what you can do to help achieve a successful implantation.

The post How do I improve my chances for embryo implantation? appeared first on Fertility.ca.

Not everybody needs IVF. Many patients may benefit from intrauterine inseminations.

IUI, where sperm is washed and placed high within the womb, can address a variety of concerns including:

• concerns around cervical mucus or scarring after a LEEP procedure
• erection concerns
• difficulty timing intercourse (perhaps due to work, or irregularity of ovulation)
• unexplained infertility
• donor sperm
• financial: And understanding that IVF may be “better”, but it is also much more expensive and invasive, and a hoped for success through a trial of inseminations

As you can see, there’s a wide variety of reasons why people may choose IUI, so success rates vary greatly from less than 5% to over 20% per cycle. You would really need to speak with your clinical team to understand what the odds of inseminations may be like for you.

It can be difficult to make sense of these wide-ranging numbers. Specific questions of what approach will maximize pregnancy rate can be actually quite tricky to answer. Here are two:

1. Should we always trigger ovulation?

One of the advantages of inseminations is we should be able to get the timing exactly right.

But for the timing to be “exactly right” we want to be able to place the sperm before the egg is released. We say a released egg is viable for twenty-four hours but we know from watching eggs in the lab that they are really optimized in their first six hours upon release.

Sperm, while functional for up to five days, is almost always very functional for the first twenty-four hours. That means we want to place the sperm into the womb before the egg is released, ideally the day before, so that they will be available when the egg is available.

The challenge with placing it the day before, however, is that while we are organizing for the insemination, we don’t actually know if the egg is going to be released on time.

To ensure the egg is ready on time, we often encourage using a “trigger shot”. This is an HCG hormone. It is actually a pregnancy hormone – and after a trigger shot, if you did a home test, it would suggest that you were pregnant. We use HCG because it is almost exactly the same structure as LH, the natural hormone that releases eggs. By taking the HCG shot, you can ensure yourself and us that the timing of the insemination will be ideal.

Different clinics will have different approaches. And it’s important to make note, it hasn’t been proven that HCG shots improve pregnancy rates.

2. Should you do one or two intrauterine inseminations?

The worry is that the timing of the insemination may not have been perfect. For that reason, it may be helpful to do inseminations two days in a row. If one insemination is too early (or the other is too late), at least one of them will be ideally timed. So is it worth doing IUIs two days in a row?

You can discuss this with your clinic. Pregnancy rates that peak at 30% are frustrating: It means that 70% of patients at least won’t succeed with their insemination cycle.

At my clinic, we do the double IUIs as our standard of care, not because we know that it increases pregnancy rates – we can’t know that – but because we are certain that it helps to minimize the stress of all involved. Everybody needs to be able to look back on the IUI and know that it was done in the best possible way.

Having said that, when it comes to donor sperm, which is so much more expensive, we generally encourage a single insemination. Clearly, every clinic is going to have a different opinion on this approach.

As long as you find a clinic and solution that minimizes your stress and maximizes your comfort level, then you have the best approach that fits you.

The post Should I have one or two intrauterine inseminations? appeared first on Fertility.ca.

You can talk to your doctor to find out whether HCG, clomiphene, letrozole, and rFSH preparations will be helpful for you.

Vitamin therapy is one of the easiest steps to take. We suggest Vitamin E up to 400IU/d, Zinc up to 70mg/d, Selenium up to 250mcg/d, Folate (1-5mg/d), Vitamin C (500-1000mg/d), and Co-enzyme Q10 (200mg/d). If red meat isn’t a part of your diet, L’carnitine supplements may be helpful.

A recent analysis of 12 studies from around the world found that lycopene could contribute to greater sperm health. Either way, a diet rich in red fruit and vegetables such as tomatoes, strawberries, peppers and watermelon isn’t bad for your health.

The good news is that the majority of men will see a sperm quality increase through some basic lifestyle changes. Stay away from the sauna and hot tub for a few months, get plenty of exercise, rest up and reduce or quit smoking.

The post How long does it take to improve my sperm quality? appeared first on Fertility.ca.

IVF with Intracytoplasmic sperm injection (ICSI) should provide a success rate that is at least 3-4x better. Recent improvements in lab techniques have been shown to lower DNA fragmentation rates to ensure higher fertilization rates in eggs.

But you’re doing the right thing: getting yourself organized before taking this next, important step.

Thyroid control should happen quickly. But the effects of varicocele repair can take 3-9 months….and still not make a difference.

If you really aren’t certain what to do, get a second opinion if you can.

You’re about to embark on a new approach (surgery? IVF? both?). Before doing so, you want to be certain that you’re getting the best advice possible.

The post My husband has thyroid problems and a varicocele. We’ve tried IUI 6 times. What now? appeared first on Fertility.ca.

In the context of fertility, erectile concerns can often be interpreted as ambivalence about having children. Some men may refuse to have intercourse, or otherwise turn away. They may claim that they no longer want to have children, when really what they are saying is that the situation has created a deep sadness in them.

If your partner might be experiencing male subfertility, talk to him. Validate and listen to your partner’s feelings within the relationship and in the bedroom. I strongly recommend counseling to assist both of you in maintaining healthy communication and a supportive partnership.

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Many corners of the internet encourage people to continue lying on their back, perhaps with a pillow under their bum after intercourse. The speculation is that this allows more sperm access to the womb and increases the chances of pregnancy.

Does it work? I don’t know.

But, if it does, you would only need to lay in this position for about ten minutes. After that, all the “best” sperm will be gone. The vagina, after all, is a very acidic place and sperm do not last very long. After ten minutes, the remaining ejaculate will naturally come out when you stand up. But all the good sperm is gone.

Intrauterine insemination is different: The sperm have already been placed up into the womb. No amount of further lying on your back will change that.

Should you have a quiet day that day? You can! But only because you would like to have a quiet day.

After all, hopefully the sperm will be meeting the egg that same afternoon. But it takes a full five to seven days for the fertilized egg to float down and implant.

In other words, you are not going to achieve implantation that day, so there is no particular reason from a fertility perspective that you could not have as active a day as you had in the days leading up to that procedure.

Intrauterine inseminations do not have the highest success rates in a fertility clinic. IVF generally does.

IUI is much more straightforward and there are huge advantages. It’s a less expensive procedure. It’s less invasive, and it interrupts your life less. If having a quiet day the day of the insemination appeals to you, please take it! But it’s not a requirement for pregnancy.

The appropriate choice is to take on whatever level of activity emotionally fits the best choice for you.

The post Are there any activities I should do the day of my IUI? appeared first on Fertility.ca.

The use of donor eggs or sperm is permitted. It’s only the “sale” that is not allowed.

When this legislation first passed, I was living and practicing in the US. Clinics there were, and still are, able to pay sperm and egg donors for their time and effort. Many clinics, including the one at which I worked, actively recruited young women (usually around the age of 26-32) to act as egg donors for couples in which the eggs of the female partner were either not present or not deemed be likely to lead to a healthy pregnancy. I did have Canadian patients seeking egg donors in the US.

Most donor sperm in Canada comes from sperm banks in the US or other countries. The sperm is paid for in the jurisdiction where it is legal to purchase donor gametes, and is then imported into Canada. In an online article on the CBC website, I found the following statement:

“Health Canada told Enquête in a written statement that “in general, there may not be any violation of the law if the financial transaction takes place entirely abroad.””

This means if the transaction takes place in Canada, that charges could be filed. It remains untested in the courts if purchases over the internet with US-based agencies avoid triggering Canadian law.

With the advent of newer technologies, it has become possible to freeze and transport eggs just like sperm. Some fertility clinics in Canada have followed the donor sperm model and started the importation of frozen donor eggs. Others will ship patient sperm to the US to be fertilized with donor eggs, and then the embryos that are created are frozen and imported back into Canada.

But it’s hard to argue a difference between donor eggs and donor sperm.

Women who donate their eggs go through a time-consuming, potentially risky process and some compensation would seem reasonable. I think the legislation was intended to protect these donors from financial coercion. I think the legislation was also meant to protect the rights of children born through the process to know their genetic origin.

Clinics are finding ways around the current law, but many in the field are left feeling very uncomfortable as patient needs and newer technologies have put them at the edge of the law. Anyone who violates the Assisted Human Reproduction Act could face a hefty fine of $500,000 or even jail term of 10 years. This scares many patients and physicians and drive practices underground, but doesn’t always stop them.

Importing donor eggs from the US puts the whole egg donation process, including the safety and rights of donors, outside of Canadian regulation. When donors come to Canada just to retrieve their eggs and then return to the US, and the donor is left in medical and legal limbo; who is looking after their health and any complications that arise from the process?

Instead of preventing a “business” around donor gametes, it has just pushed this “business” to the US.

Clearly, the law is confusing and unclear. Canadian couples do feel a need to use donor gametes and many families have been created or expanded through the use of donor eggs and sperm.

As it stands, neither donors, patients, nor the offspring that are created are being well served.

The post What does Canada’s Assisted Human Reproduction Act say about buying donor sperm and eggs? appeared first on Fertility.ca.

Sometimes, these are valid concerns. But there are things you can do about it.

1. Get a sperm test with DNA fragmentation. Women may not be able to confirm their egg quality until they complete an IVF cycle, but for men it’s much more straightforward.

2. If you have sperm quality worries, it may be appropriate to introduce lifestyle changes and vitamin therapy.

3. Get further testing done. Your testosterone levels can be checked with a simple blood test. Low testosterone levels can often be treated successfully with Clomid or Arimidex. You can also check for varicoceles, dilated veins that heat the testes. They can be found with a physical exam or scrotal ultrasound, and treated through minimally invasive surgery with faster recovery times than in the past.

4. Talk to your doctor to find out if Viagra or Cialis is right for you. You may not need these in other sexual encounters, but procreational intercourse can be quite stressful. If you worry that you can’t have an erection with timed intercourse, it’s okay.

Another option is intrauterine insemination. You might find it easier to just let your sex life be your sex life, and procreation can take the form of providing sperm samples in the morning for the clinic to inseminate later that day. In the event you’re unable to provide a sample one day, frozen sperm is available as a backup. This lessens some of the pressure to have procreational sex.

5. Take your overall health seriously. Some men worry that their ejaculate has less volume than it did when they were younger. In many cases, this can be addressed through better hydration. A volume drop may be related to other health concerns, such as retrograde ejaculation (ejaculate travels backward into the bladder rather than out the tip of the penis). Take care of your overall health by having frank discussions with your doctor.

Now and again, men are concerned they don’t “shoot” as far. Well, it does happen with age. Let me reassure you, there’s absolutely no proof that it makes any difference to anything whatsoever.

I don’t think the distance the ejaculate moves is as important as volume, which is necessary to protect the sperm with seminal fluids while they find their way out of the acidic vagina, into the cervical mucus, and ultimately up into the uterine cavity.

6. Do IVF with ICSI. Intracytoplasmic sperm injection (ICSI) will ensure eggs will be fertilized. Newer techniques in the lab have been shown to be associated with lower DNA fragmentation rates, rather than higher. That’s right! It’s possible the modern techniques are better able to sort out the “best sperm” than nature alone.

The only real problem with IVF is the expense. I don’t mean to minimize it – expense is a very real stress for most couples – but so can be the month-in/month-out lack of success for pregnancy and the strain of a sexual act that can make you feel further away from your partner, rather than bringing you closer.

In our clinic, we strongly recommend that couples consider IVF after all other reasonable options have been exhausted over a five month period. Fertility treatment can take an emotional toll on a couple, and we want to see you move past the hopeful phase and into the pregnant phase as quickly as possible.

The science behind paternal aging and how it may affect the health of children is interesting and changing all the time. (At least, it’s interesting to us.) If you want to know more, please let us know in the comments. I will be very happy to expand this section further.

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