Women who are not yet ready to start a family may choose to freeze their eggs to keep the option on the table for longer.

There has been significant promise, but also significant disappointment, with egg freezing to date. The disappointment stems from the relative lack of success rate data. Many more women are freezing eggs than thawing them. And until they are thawed, how do we know how successful the treatment really was?

At first, the data was generally only coming from egg donors, women pre-selected to have eggs that would be expected to succeed. Significantly less data was available for “social” egg freezing, that is, women who are choosing to delay their reproduction and hope to be able to freeze their eggs in time. The majority of our patients were waiting for the latter data sets to come through, as we tried to keep expectations firmly in check.

We are now finally seeing the numbers, and it appears that for most patients egg freezing works as well as embryo freezing, with success rates often in the range of 60% (see this article for more). This published data fit our internal data suggesting clinical pregnancy rates 55-60% per set of eggs for women under 38.

Egg freezing is promising when we have enough good eggs to freeze. If you are under 38 years old (age being a marker for egg quality) and have been told you should be able to freeze 12-20 mature eggs (ie. you have a good ovarian reserve), and are working with a good lab able to offer vitrification, you may anticipate having three or more fertilized egg develop to blastocysts and a reasonable expectation for pregnancy in the future. No, it isn’t perfect – all things being equal frozen eggs do not work as well as fresh eggs – but with good counselling egg freezing may provide some measure of reassurance that had been missing until now.

For a good video that walks you through the process check out this video, or a more detailed scientific review, see this article.

The post New data on non-donor egg freezing success rates! appeared first on Fertility.ca.

The process of assisted hatching refers to procedures done to the zona pellucida. The zona pellucida is the shell that surrounds the egg. Its clearest purpose in nature is to become suddenly hardened once one sperm has entered the egg. This prevents other sperm from entering the egg.

But this hardening of the egg shell can happen at other times too. For some women with egg quality concerns, perhaps women over thirty-seven years, the zona pellucida is hard from the beginning and this otherwise fertile egg will not be able to be fertilized naturally.

Under these circumstances, ICSI (intracytoplasmic sperm injection, the placement of sperm inside the egg) should help. But it still leaves a very hardened zona pellucida behind, and this can cause problems later in development.

By day five of embryo development, there are enough cells within the embryo that it is generally at the “blastocyst” stage, and the embryo attempts to hatch out of the zona pellucida. This generally goes without incident, but if the zona pellucida is too hard and too thick, the hatching may not occur and implantation will be compromised.

Assisted hatching is the process by which, generally on day three of embryo development, the integrity of the zona pellucida is compromised to weaken it to allow for the embryo to hatch more easily later on.

Historically, this was done chemically, but the problem with this approach was that the chemicals could sometimes leach further than the zona pellucida, damaging the embryo itself.

Modern technique is to use a laser, which can be so finely calibrated, that we routinely see no compromise at all. For that reason, assisted hatching can be offered with relative safety, for the downside risks appear to be small. There have been some worries that, even with a laser, there could be some residual damage. What if, for example, the sharpened edges associated with the laser would somehow damage an embryo that is hatching, perhaps severing the embryo in two? Were that to be the case, one would anticipate increased risk of monozygotic twinning (identical twins) associated with assisted hatching. People have looked to this in great detail with no definitive answers.

In our practice, we do see a heightened chance of monozygotic twinning compared to the background rate that might be expected in the general population, but have been unable to ascribe this to assisted hatching (or, in fact, to any particular event that occurs in the lab. It is possible that a subset of fertility patients is simply more at risk of monozygotic twinning than the background population).

It is not just women with egg-quality concerns that it may be beneficial for. For all embryos that are being cryopreserved, the zona pellucida is expected to come out harder than on a fresh embryo. Any couple with these circumstances may benefit from assisted hatching.

Furthermore, assisted hatching is helpful when doing pre-implantation genetic screening; it allows the biopsy catheter to access the cells to be assessed.

Does all of this mean that assisted hatching is right for you? That is a conversation for you and your physician, but assisted hatching is something that we are willing to consider for the majority of our patients at our clinic who are looking to IVF.

The post Assisted Hatching: When is it necessary? 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.

When we retrieve eggs, a lot of them may look good under the microscope, but in fact not be functional. Not every IVF patient is the same but on average it takes four to five eggs to generate one blastocyst.

Blastocysts are the best developed embryos we have in the laboratory and will take five to six days to generate.

Blastocysts are associated with the highest pregnancy rates. Not every blastocyst is genetically balanced.

A blastocyst with the correct number of chromosomes is called “euploid”. For women that are thirty-five, on average 70% of blastocysts will be euploid; for women thirty-six to thirty-eight, it is closer to 50%; and over thirty-eight years, it is closer to 30%. By the time women are over forty-two, it is likely an even lower fraction.

Even euploid embryos may have smaller genetic or other irregularities such that it will be an approximately 80% implantation rate.

Looking at all the numbers above, then, for the average thirty-seven year-old patient, mathematically at least, we can expect pregnancy if there are three blastocysts to be transferred over one to two cycles. To generate three blastocysts, we would like to have generated fifteen eggs.

That is why our goal for IVF is to generate twelve to twenty eggs.

I have seen cases where there were only two eggs, leading to two blastocysts and an ongoing twin pregnancy. If you have a very low ovarian reserve, but every reason to believe you have extraordinarily high-quality eggs, it is reasonable to hope that IVF could work for you.

But for most women, if there are fewer than twelve to twenty eggs being generated through IVF, then there is a lower chance for success based on the math described above.

So why not more than twenty eggs? The answer is that over twenty-two eggs, there may be enough hormonal imbalances that pregnancy rates may start to fall again. With such high numbers, the current community standard is shifting to freezing all embryos and not completing the transfer at all, instead waiting for a future cycle when your hormones are likely to be in better balance.

The post Why do you want 12 to 20 eggs for IVF? Isn’t that a lot? appeared first on Fertility.ca.

It holds great promise for maximizing pregnancy rates. Most IVF failures can be attributed back to embryo quality.

Is PGS right for you? Perhaps, but it’s a highly personal choice. It depends a lot on your circumstances and needs to be explored with your doctor.

PGS is expensive and complicated. Neither of these things are great to hear, of course, but the promise inherent in this level of testing is profound and, for some couples, it can be an extremely beneficial solution.

Why is it so difficult? To understand the science, I recommend starting with www.chromosome-screening.org. The short version is, the process is a part of IVF.

As you know, IVF is when your eggs are retrieved and inside a laboratory introduced to sperm. Some days later, the fertilized eggs are placed back into the womb. Before that happens, PGS can be done.

To do PGS, we remove one or more cells from the embryo. These cells are then analyzed in the laboratory or they’re shipped to an external lab.  We look at the number of chromosomes that those cells carry. The idea is, that the cells accurately represent the embryo about to be implanted.

There are two kinds of lab analysis done on the cells: The laboratory can look for specific and known genetic diseases or can count the number of chromosomes.

Most people choose to count chromosomes. Most people aren’t looking for any specific disease because both partners aren’t predisposed to any diseases that are inheritable. What they’re looking for is to find out if their embryo is going to be of sufficient quality to be consistent with an ongoing pregnancy.

The most common reason that embryos are not healthy is something called aneuploidy – that means the embryo has too many or too few chromosomes. PGS checks to make sure the embryo has the correct number of chromosomes or anything else that would be abnormal or not suitable for transfer.

PGS is not all that new but the techniques involved have been changing over time.

One aspect that has not changed – you will need to do ICSI and assisted hatching as part of the process. ICSI is the placement of the sperm into the eggs, and it is necessary rather than traditional fertilization (where many sperm are placed around the egg), as with traditional fertilization there are going to be extra sperm stuck to the edge of the zona pellucida (egg shell). That means when the biopsy is done, an extra sperm could accidentally come along with the cell and the test will appear to be abnormal when, in fact, the cells were just fine. Doing ICSI, where we place the sperm into the egg, negates that risk.

Assisted hatching is where a laser penetrates the zona pellucida, at least partially in this case, so that the biopsy needle can be placed against the cells for removal.

Before PGS is even started, you are looking at the costs and complications implicit in IVF with ICSI and assisted hatching. But there are other expenses too. Most laboratories will charge a biopsy fee, the lab will also charge a diagnostic fee for the genetic testing and there can be some shipping charges when external labs are used.

Are the added expenses worth it? Well, in select circumstances, absolutely! If the technology can deliver on its promise, I’m willing to guess most of our patients would be more than happy. After all, many couples who have completed IVF without success can become frustrated by the apparent transfer of high-quality embryos into a healthy woman and still no pregnancy.

This happens because many so-called healthy-looking embryos, in fact, are aneuploid. Depending on the age group, only 30%-70% of apparently healthy, day-five embryos are, in fact, normal (and the ratio is even less for day-three embryos). Any technique that allows us to find the best embryo could be highly advantageous.

Historically, we have looked at cell number and the relative fragmentation of embryos to guess at an embryo most likely to be consistent with ongoing pregnancy. In more recent years, many labs strongly favour growing embryos to the blastocyst stage, which is five days of growth in the lab, to further differentiate the best-growing embryos. Finally, some laboratories are using “embryo scopes”, camera systems to allow constant visualization of the developing embryo. Huge amounts of data are being generated with such techniques, though it is difficult to say, of all this data, which of it is actually useful to predict who is going to have a baby.

And there’s the appeal of PGS: It gets right to the heart of the matter as we confirm whether or not there are the right number of chromosomes to be consistent with an ongoing pregnancy.

It is not that a euploid embryo is guaranteed to result in pregnancy, but some labs are reporting pregnancy rates in the range of 80% when euploid embryos are transferred. So, this is not a guarantee, but a far higher pregnancy rate than any other therapeutic approach to date.

But of note, I also mention the technical complications.

The chief amongst the complications are this: The biopsy and embryo manipulation.

Does the biopsy harm embryos? It may: There are some data suggesting embryos biopsied on day three do not fare as well as those biopsied on day five. Like any ongoing scientific processes, there remains debate on this point, but at this time, based on what information is available right now, I believe day-five biopsy makes the most sense. I may have to change my mind again in the future, the subject really is changing that quickly!

Though the day-five biopsy appears to be safe – cells are taken from the outer trophectoderm (cells that will eventually become the placenta) rather than from the inner cell mass (cells that will become the baby) – the challenge is deciding how best to handle the embryo from that point forward. There is going to be, after all, a waiting period while we look to the results of the PGS. This can be as short as twenty-four hours, or up to a week, depending on how the technique is done; but it necessitates for a day-five biopsy, either day six embryo transfer, or a freeze-all technique. Freeze-all meaning the embryos are frozen to be transferred in a future cycle (this will also add to the expense).

So, which is better? A day-six transfer or vitrification and transfer on a future cycle? I favour the latter, but again, this is lab dependent and you can get various opinions depending on which clinicians you speak to and the latest paper on the subject.

Lastly: The results that come from the laboratories regarding PGS are not always as reliable as we would like. There are some reports of embryos being retested and having completely different results than they did the first time around. Could this happen to you? Well, yes, it could and it is partly a limitation of the nature of the process: We are biopsying so few cells. This has to be contrasted with an amniocentesis, for example, done at sixteen weeks of pregnancy when literally hundreds of cells could be tested at a single time. It is much more accurate and you will find that even as PGS purportedly can rule out, for example Down’s Syndrome, you will be asked to have a definitive test later in pregnancy, regardless. PGS cannot be and is not definitive.

I like to write articles that discuss complicated subjects in transparent and easy-to-understand ways. PGS is a topic that is changing, at the information becomes more settled, I will continue to post information that I feel will be useful to a wider population.

At this time, the best I can say is that an educated conversation with your clinician is going to provide you the best sense for whether PGS is going to be helpful to you. That said, if you do not have confidence that you can generate a good number of blastocysts that PGS probably is not going to be helpful. After all, it is a sorting mechanism, and if you only have one or two embryos for transfer, sorting is not required. Careful transfer of your embryos may be all that is necessary.

The post Will pre-implantation genetic screening improve my IVF chances? appeared first on Fertility.ca.

Choosing the best embryo

The next day -day 1- each healthy embryo will still be a single cell, now at the two-Pro-Nucleii (2PN) stage. It is a black-or-white assessment, with little room for interpretation: either you have 2PN embryos, or you don’t. Most couples can expect 80-90% of the mature eggs to turn into 2PN embryos.

Embryos are rarely transferred at this point, because you really can’t tell which embryos of the group will be the most likely to continue to grow properly.

By day 2, the embryo should be 3-4 cells.

By day 3, the lab staff can finally grade the quality of the embryos by looking at them under a microscope. It is not a perfect science, but, it is our standard of care for the moment. The grading is done in two ways:

• We count cells. The ideal embryo has 8, 7, or 6 cells. More than this, and embryos may be growing too fast, using up the energy stored by the egg, and therefore more likely to burn out before they get the chance to implant. Slower than this, and the concern is that the embryos won’t continue to divide at all.
• As cells divide, they leave fragments behind…and too many fragments suggest that cells may not be dividing properly. We grade fragmentation on a 5 point scale, and ideally your embryos will be grade 1 or 2.

A perfect grading system would allow us to spot the ideal embryo every time. We’re working on that*, but in the meantime, to make up for our uncertainty, we usually encourage the transfer of more than one embryo.

For greater specificity in embryo selection , some doctors will encourage you to grow embryos along to day 5.

By day 5, listed in increasing order for pregnancy, we hope to see:

• morula
• cavitating morula
• blastocyst
• hatching blastocyst

A blastocyst will be about twice as likely to result in pregnancy as a morula.

Sometimes we will allow an embryo to grow to day 6 to become a blastocyst, but we won’t go further than that.

The pregnancy rate per blastocyst transferred is certainly higher than per day 3 embryo transferred, because the extra two days has allowed greater selection to occur. But in some ways, it isn’t a fair comparison. Perhaps pregnancy rates would have been just as good transferring 3 embryos on day 3 cf. 2 embryos on day 5.

In fact, doctors and laboratory staff will cite many factors when comparing day 3 to day 5, including patient age (some say >40y should always be day 3), optimization for freezing (historically better on day 3, but perhaps vitrification changes this equation), embryo health, the implantation window, uterine contractility…the debate goes on. Good people can disagree.

My advice would be to accept the day that your particular lab favours. In this way, you will be maximizing your chances as your work to the strengths of your particular group.

* Note that there are newer systems for embryo grading, include proteomics, metabolomics, and other variations in preimplantation genetic screening (PGS). I am happy to write to these topics, but they generally will not be offered in most laboratories in Canada or elsewhere.

The post IVF: choosing the best embryo, and the best day for embryo transfer appeared first on Fertility.ca.

But when you have a good ovarian reserve, you most likely will have some good quality eggs in there too.

You were born with millions of immature eggs.

Most of the immature eggs will be housed in microscopic follicles (small baskets of cells) that will lie quietly for months and years at a time. But every cycle during your fertile years, there will be some follicles that are primed to grow. These primed follicles are known as antral follicles.

Ideally, you will have a good-sized pool of these antral follicles each month.

Why is it so important to have a good-sized pool of antral follicles?

Actually, if you are trying to get pregnant naturally, ovarian reserve doesn’t matter too much. After all, up until menopause, your body will generally find 1 egg a month from the pool to mature and ovulate. I’m not saying ovarian reserve doesn’t matter with natural cycles, but we have all seen natural conceptions in women who have very low reserves.

If you are looking to to access fertility treatments, a good ovarian reserve is extremely helpful.

For example, in IVF, we find our best pregnancy rates occur when we generate 3-5 high quality embryos. The best predictor for this outcome is 10-15 eggs at retrieval. (It is possible to have 3 good embryos from 3 eggs, but less likely). And the best predictor for 10-15 eggs is a good ovarian reserve.

Tests of Ovarian Reserve

Antral Follicle Count (AFC)

The AFC is an ultrasound test. The u/s tech counts your antral follicles. The ideal AFC is 15-20 over the two ovaries. If your AFC is <10, your ovarian reserve may be low (assuming the tech is counting accurately).

As a test, AFC is very much technician-dependent: not every ultrasonographer can measure AFC well, and there tends to be a lot of inter- and intra-observer variability (i.e. everyone measures a different number). If you are a bit gassy (or a bit overweight), it can be difficult.

Our newest 3D ultrasound machines have the ability to record AFC’s automatically. However, the technology isn’t perfect, and we still prefer the accuracy of our clinical team to that of the computer.
Anti Mullerian Hormone (AMH)

AMH is a newer blood test, and in my opinion, the most accurate test of ovarian reserve. AMH is a hormone released by cells that are involved with the growth of antral follicles. AMH levels correlate with the number of active antral follicles present; the higher the antral follicle count, the higher the AMH levels. I trust it more than AFC, because it seems to correlate with the number of active follicles.

AMH can be tested through a regular blood test. It can be drawn during any day of the menstrual cycle whether or not you are on the birth control pill. In my opinion, AMH is the single most helpful test for women looking to understand their own fertility.

If you get an unusual number, it is reasonable to repeat the test. AMH can be difficult to process in the lab, so the occasional incorrect number will be generated. Ask to do it again if you are making important decisions based on AMH.

Follicle-stimulating Hormone (FSH)

FSH is a blood test, and is the traditional test of ovarian reserve, perhaps because it was more accurate than ultrasounds used to be. These days, ultrasounds are incredibly accurate, and AMH has taken over as the more accurate blood test.

FSH is the hormone that drives your antral follicles to grow.

If you have a good ovarian reserve, your body doesn’t need to make very much FSH to start the process of egg maturation. A number less than 10 IU/L is good; less than 8 is ideal. Greater than 12 is a worry. FSH levels change month-to-month, as the number of antral follicles change.

FSH levels are brought lower by the presence of estrogen, so your FSH level is only an accurate indicator of your ovarian reserve when Estradiol levels are <200pmol/l. Estrogen is lowest on day 3 of the cycle, which is why we usually measure FSH on day 3.

The main tests of ovarian reserve used to be day 3 FSH, but today we prefer antral follicle count studies and AMH to guide our care.Ovarian reserve is not the same thing as egg quality, but the two can be related. Women can achieve healthy pregnancies with a low ovarian reserve. Tests of ovarian reserve are important, but they are not your only measurement of future success. They are, however, a very helpful guide to optimizing and personalizing your fertility treatments.

The post What’s the difference between my ovarian reserve and egg quality? appeared first on Fertility.ca.

This is how it works: over the course of 10-14 days the egg will grow from immaturity within an antral follicle, and turn into a large, hopefully-soon-to-be-fertilized, mature egg in its dominant follicle. Both the egg and the follicle have to be functioning properly for the cycle to go well.

The dominant follicle makes estrogen, and once you ovulate, progesterone. Estrogen and progesterone together govern the activity of your uterus, which you experience as your menstrual cycle.

If you have a healthy egg, you have a healthy follicle and you expect a healthy menstrual cycle. This means the reverse is true too: when we think that your menstrual cycle is going well, we strongly suspect that you must be making healthy, high quality eggs.

Here are the factors that we look at when deciding if a given menstrual cycle is going well:

Menstrual Cycle History

Day of ovulation

Ideally ovulation will occur on days 11 or 12. Delayed ovulation – day 13 or later – is not a sign of egg quality concerns; in fact, it is more commonly a sign of an excess ovarian reserve, which is generally a good thing. But early ovulation – days 8,9, or 10 of the cycle – implies lower quality eggs.

Premenstrual Spotting

Once the egg is released, the leftover follicle (now called a corpus luteal cyst) makes progesterone. Progesterone stabilizes the lining of the uterus. A low-quality follicle is less likely to be associated with enough progesterone, and therefore the woman may notice a shorter luteal phase and/or premenstrual spotting.

Cycle Length

Long cycles are ok, but short cycles are not. If previously-28-day-cycles are now 26 days, it suggests egg quality is failing. Cycles are shorter because of the early ovulation and shortened luteal phases described above.

Menstrual Cycle Lab Values

Peak Estrogen

When a woman is about to ovulate, estrogen will be at its maximum level. Estrogen effects may be noticed as spinnbarkeit. We can also measure estrogen levels through blood tests; peak estradiol is between 500 and 1000 pmol/litre per healthy follicle. When cycle monitoring, ask your clinical team what your peak estrogen was: bigger numbers are better. If the level is towards 500 (or lower) per mature follicle, then egg quality may be a concern.

Peak Progesterone

Progesterone is made by a healthy corpus luteal cyst. Peak progesterone values, traditionally measured on “day 21″ of your cycle (but more accurately recorded 7 days after ovulation) is usually 30 ng/ml or higher for a fertile cycle.

I can write to all this in greater detail if you are interested; the relationships between eggs, follicles, hormones, and the menstrual cycle is complicated but fascinating. (Well, fascinating if you are a Reproductive Endocrinologist…)

But the important part is, because of these inter-relationships, we can help you to maximize the likelihood of releasing a good egg in the next cycle by manipulating hormones in this cycle. It is called estrogen priming, and will be the subject of another post.

The post “How does my menstrual cycle reflect the quality of my eggs?” appeared first on Fertility.ca.

Lifestyle

When looking to egg quality, the first thing we suggest is that you consider lifestyle.

To some degree, maximizing egg quality is predicated on maximizing your overall health, and the quickest and surest route for most of us to improve our health is to improve our sleep hygiene. That might be as simple as going to bed on time. But, for others, it might be more complicated including minimizing screen time before we go to bed and other rituals that will maximize the likelihood of sufficient sleep. The evidence for cutting out caffeine as it relates to egg quality is poor. That said, most of the literature points to the safety of minor amounts of caffeine, but decreasing fertility with significantly higher doses. Certainly four cups per day of coffee would be too much. We do encourage people to consider limiting themselves to one per day, with decaffeinated drinks to follow.

Of all lifestyle changes, quitting smoking is, by far, the most helpful choice, well beyond any of the supplements that follow. The relationship of alcohol to egg quality is somewhat controversial. Certainly 4 drinks per day is too much. We are not certain if there is a minimum “safe” amount. Fertility can be stressful; if you find yourself tempted by drink too often, please ask for help. There is a controversial association between egg quality and elevated BMI. If your body mass index is over 30, try 5% weight loss, an achievable goal for many, with a potential upside for your eggs.

Acupuncture and Traditional Chinese Medicine

We are not able to differentiate the “best” practitioners of acupuncture. We do not know who has good quality control mechanisms in place, best practices for minimizing cross contamination, or who provides the most efficacious treatments. However, we have had the opportunity to meet with a number of practitioners in the field, all with a special interest in fertility. For those who are interested in trying, I am most supportive of a trial of acupuncture +/- TCM. I would suggest a minimum of 2 months. By six months you should see pregnancy if acupuncture is going to be successful.

Supplements

Supplements should be taken for a minimum of two months; you will find if they are going to work, pregnancy should happen quickly. Six months will be trial enough. Though we remain hopeful that in taking these supplements you will be maximizing egg quality, please be aware that none have been proven in scientific randomized controlled trials to be effective.

The supplements we suggest include:

CoEnzyme Q10
Myo inositol (especially if PCOS)
Melatonin at bedtime unless you are taking thyroid medications
Omega 3 fatty acid
Vitamin C and E (antioxidants)
L’arginine
In our opinion, CoEnzyme Q10 is the most important of the supplements.
If you are only going to take one, take this one.
Dosing, and the “best” supplements for a patient, are individualized at the clinic.

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You can run a natural start cycle, which simply means that you come in at the beginning of your menstrual cycle, say on day 3, and if there are no cysts, you start taking stimulating medication.

This simple approach is appealing because it is, well, simple.  But there is a catch: it is quite likely that egg growth will be scattered across a variety of maturity levels.  ”Scattered” maturation makes the ideal timing of egg retrieval difficult, and the cycle might suffer as a result.

To keep some eggs from developing too quickly, we like to suppress the ovaries before stimulation. Suppression also makes scheduling treatments easier for our clinic and our patients.  Too many retrievals on the same day would compromise pregnancy rates for everyone.

The longest, deepest suppression is done with the long protocol.  It is, as the name suggests, the longest of the protocols: several weeks on the birth control pill in most cases, overlapping with a GnRH Agonist (Lupron, Suprefact, or Synarel) which is even more suppressive.  By the time you are done with this pre-treatment, your ovaries should be well-and-truly suppressed.

But there is the risk of going too far.  When your ovaries are over-suppressed, the stimulating medications simply will not work.  This means your estrogen starts off low – sometimes less than 50 pmol/l – and never climbs above 200 despite day after day of stimulation.  This happens only about 5% of the time.

So why use the long protocol?  Because when the long protocol works, we get the best pregnancy rates.

The long protocol isn’t the right choice for everyone.

If a woman has a low BMI (less than 21) or other reasons to suspect sensitivity to suppression, we usually opt for an OCP-antagonist protocol.  In this case, we use the birth control pill (aka oral contraceptive pill or OCP) for a bit of suppression, then once the cycle starts, use a GnRH Antagonist (like Orgalutran or Cetrotide) to prevent ovulation.  I like OCP-antagonist cycles, and have had a lot of success with them recently.  It is a more pleasant protocol for patients, with fewer injections and side effects.

The challenge with using a birth control pill, for some women, is that even a low dose pill (Alesse, Yasmin) for a short period (2 weeks) is too suppressive.  Natural start is one solution, but if the woman’s natural estrogen levels are not very high in the luteal phase, her FSH levels will drift up and…the ovaries will start to stimulate too early and egg growth scattering results.  In these select cases, we can use estrogen-priming, in which an estrogen patch (0.1 q2d) or Estrace tablets (8mg daily) are used starting about day 21 in the cycle before stimulation.  Estrogen priming is very successful in bringing down FSH levels, of real benefit to women of borderline ovarian reserve, and we have seen successful stimulations where none were possible before.

The catch (there is always a catch) is that estrogen primed cycles take a long time before we can see if they are going to work…..when we have to cancel them, it is usually quite late into a stimulation.

Estrogen priming is usually matched with an antagonist to prevent ovulation.  But there is one more protocol to consider: a flare cycle.  A flare cycle may involve OCP or estrogen-only pretreatment, but the key is that a GnRH agonist (Lupron, Suprefact, or Synarel) will be started at exactly the same time as the stimulating medication.  The result is invariably rapid egg development.  A flare protocol is the most “raw” of the protocols, sometime yielding difficult-to-interpret results.  But we do use it in select circumstances.

Yes, there can always be hope. But that hope should be balanced with the reality that donor egg cycles will provide much higher success rates, for many clinics in the 50 to 60 percent range, and in some clinics, even higher.

The choice then becomes highly personal for you, as you weigh the relative odds of success against personal desires for a biological child. Your final answer will be highly personal, and I strongly recommend counselling as you consider your options.

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