Archive for the ‘Diagnoses’ Category

We’ve had multiple losses – what should we be asking about?

Wednesday, October 14th, 2009

“We seem to have no trouble getting pregnant, but we’ve had several first trimester losses.” Or, “We put back good-looking embryos every time, but they just don’t stick.” If this sounds like you, here are a few ideas you might want to discuss with your doctor.

Miscarriages can be caused by any one or more of the following factors:

  • structural
  • hormonal
  • immunological/autoimmune
  • environmental
  • genetic

Let’s start (as the drs often do) with the fairly basic hormonal tests. One of the first that’s included in a fertility workup is testing progesterone in the luteal phase. Most drs order this for CD21 (Day 21 of your cycle), but actually you should really have it done at 7dpo (7 days past ovulation). Of course, 7dpo=CD21 if you ovulate on Day 14 of your cycle, but if you usually ovulate late or early, or if it’s unpredictable, you might want to track your ovulation using BBTs (basal body temperatures) and go at 7dpo. If your progesterone (P4) levels aren’t high enough, you may need progesterone supplements (like utrogestan pessaries) after ovulation (O). Some specialists believe this is a VERY common problem with older women and that if you’re over 40 and ttc naturally you should take P4 after O every cycle.

Another important one to test early, especially if you have any family history or tend to feel tired a lot, is thyroid conditions. Hypothyroid (underactive thyroid) does pop up reasonably often as a cause for conception and sometimes miscarriage problems and is easy to test for. You can ask your GP for this if you’re not seeing a specialist.

If you’re ttc naturally you should also check whether you have a luteal phase defect, i.e. once you ovulate it takes fewer than 12 days for AF (your period) to arrive. You can usually figure this out by charting your basal body temperatures (BBTs) – and a really good site for learning how is Fertility Friend. Again, if your LP is too short, this can be easily fixed with progesterone support after O.

There’s a panel of blood tests you can ask for that are used to diagnose some of the possible causes of “recurrent pregnancy loss” (RPL) or “recurrent implantation failure” (when those embies just don’t stick). Broadly speaking, they cover three categories of issues – autoimmune issues (your body may be rejecting embryos as foreign bodies), clotting issues (not sure the exact mechanism for this, but if your blood clots too much, this makes pregnancy loss more likely – some clotting issues are caused by autoimmune problems) and some genetic issues. Here’s the list that we were sent for, and I think it’s a pretty typical list for New Zealand (some countries like the States seem to test for half a dozen kitchen sinks, several of which aren’t available in NZ):

  • Coagulation screen
  • Thrombophilia screen
  • Autoantibody screen incl.
  • antithyroid antibodies,
  • anti-gliaden antibodies
  • Factor V Leiden
  • Karotype
  • MTHFR mutation
  • Anticardiolipin antibodies
  • Lupus anticoagulant
  • … and a karotype for DH (who gets off easy, as usual).

Probably the next logical step is to get either a saline sono (ultrasound during which they squirt saline solution into your uterus to help them see better) or an HSG (similar, but it’s an X-ray procedure where they shoot iodine dye into your uterus and can also check whether you have blocked tubes). Either of these should tell you whether you have any structural issues in the uterus that might be preventing you from achieving or holding onto a pregnancy. Examples include uterine polyps, fibroids, scar tissue, and an unusual shaped uterus. The most likely issues can often be treated with some fairly minor surgery.

The main environmental causes of miscarriages are not usually tested for, but things you should look around you to check your exposure. Some to keep an eye out for include lead, mercury, organic solvents and ionising radiation. Other more common culprits like cigarettes, alcohol, coffee and other drugs should be cut right out (or, down as much as possible) while ttc. Some naturopaths will do things like send a sample of your hair for analysis for heavy metals, which can highlight things you are exposing yourself to without knowing it. They also advise avoiding those forms of radiation and related exposure that we are not often aware of. These include long-haul flights (which expose the body to as much radiation as a full-body X-ray, or so they say) and keeping a cell phone in your pocket right next to your ovaries – think about it!! Well, who knows which of these various things are real causes, but if you want to make sure you try everything you can to prevent another loss, you’ll probably do what I did and take the ideas pretty seriously.

But what if my specialist won’t run all these tests?

This is quite a common comment from a lot of women/couples dealing with RPL (recurrent pregnancy loss). It may be frustrating, but there is another way to look at this. OK, you may not be able to test for the entire kitchen sink, but maybe you can ask your specialist to consider treating you as if you did have several of these issues going on but they just may well be undiagnosed. That may sound nuts, but there are actually quite a few low-tech options you can ask about that many doctors will agree fall into the “won’t hurt, might help” category. These include:

  • low-dose aspirin (usually 100mg/day) – addresses clotting issues
  • high-dose folic acid (4-5mg/day) – helps prevent neural tube defects
  • progesterone support (usually Utrogestan pessaries) after O on every cycle you are ttc
  • low-dose estrogen support after O too (2mg estradiol valerate, for example)

If you’re doing IVF, each cycle is a bit more high stakes, so you may be able to push for a bit more of a kitchen sink approach. Some other things that people are often allowed to try even if there hasn’t been a definitive diagnosis of a particular cause for repeated losses/failures include:

  • progesterone shots instead of (or as well as) the pessaries – for after egg collection
  • a low-dose steroid such as Dexamethasone – to address any undiagnosed immune issues
  • Heparin shots – Heparin is a blood thinner, so this also addresses clotting factors

Finally, don’t forget that there’s good evidence that acupuncture improves pregnancy and live birth rates for patients undergoing IVF – and good reason to believe this is also true for couples trying to conceive naturally or with IUI. Click on the category Acupuncture and Chinese Medicine in the left-hand column to see more posts on this topic.

IVF – the hurdles

Friday, October 2nd, 2009

So you’ve read the IVF manual and are all ready to start a cycle. What are some of the “wish I’d known that” snippets that veteran IVFers can share with you to help fill the knowledge gaps about what to expect? Well, one that comes up a lot is having a clear understanding of the not-so-straightforward hurdles involved in an IVF cycle. Here’s a typical comment from an IVFer …

When you start this journey you read the “ivf manual” and all sounds so easy – take some drugs, grow some eggs, have them collected, fertilised and put back in and voila! a baby. Ha!! They don’t tell you about the things that go wrong. Or the things that don’t work the way they should.

So, what are the main hurdles you face in an IVF cycle?

  1. Downregulation or precycle suppression might take longer – some gals do their downregulation blood tests after several days on Buserelin and find they need to keep downregulating for several more days before starting stims. If you’re on no precycle suppression or something very mild, you may find that you have a dominant follicle or a cyst at the beginning of your cycle and it may not be a good idea to proceed with stims.
  2. Assuming you get out of the starting blocks, your first hurdle is whether your ovaries will respond to the stims. This is assessed with blood tests (for estrogen, or E2) and an ultrasound. If you grow too few follicles or your E2 is too low or the follies don’t grow fast enough or your E2 doesn’t rise enough, the clinic is likely to cancel your cycle for poor response. The good news is that you may do better on another protocol – see an earlier post on IVF protocols for more information …
  3. Some women have the exact opposite problem to poor response – they overrespond. They grow too many follicles and their estrogen shoots dangerously high. In this case the clinic will either drop your dose of stims or stop stims altogether (this is called ‘coasting’). The blood tests continue, and if your E2 drops to a safe level they will let you trigger and go ahead with your egg collection; if the levels stay too high for too long, you may be cancelled for your own safety because you are at high risk of OHSS (ovarian hyperstimulation syndrome). Even if you make it to egg collection, you may be told it’ll be a freeze-all cycle – research shows that women at risk of OHSS are at higher risk if they do a fresh transfer and get pregnant.
  4. You make it as far as egg collection (a.k.a. ‘retrieval’) and have 10 follicles. That’ll be 10 eggs, right? Unfortunately not. Not all follicles yield an egg, and some women have major problems at this hurdle, getting only eggs from only 50% of their follicles, or sometimes fewer. [See Empty Follicle Syndrome] Others have a 100% strike rate just about every time. So, it’s just the luck of the draw. In any case, you shouldn’t expect to get an egg from any follicle that was smaller than about 15-16mm at trigger, and you shouldn’t expect all your mature (large) follicles to yield eggs.
  5. Yay, we got six eggs!! That’ll be six embryos, right? If you’re lucky, yes, but there are more hurdles here too. First, it’s possible not all of your eggs were mature. Only the mature ones can potentially fertilise. And not all of them do. Some couples get 100% fertilisation just about every time, and others get a very low %. Some also get abnormal fertilisation, such as when two sperm enter one egg. ICSI can improve fertilisation rates if there are sperm issues or if the eggs have hard ‘zona’ (eggshells).
  6. The day after egg collection, the embryologist will usually call you to let you know how many of your eggs were mature and how many have fertilised normally. From there, you are in a waiting game to find out how many of those embryos will make it to Day 3, and how well they divide. Some may ‘arrest’ (stop growing) along the way, some will divide more slowly (or quickly) than is optimal. The best possible result is to have 4-cell embryos on Day 2 and 8-cell embryos on Day 3. The survival rate from fertilisation to Day 3 is not usually too bad.
  7. If you’re taking your fresh or leftover embryos from Day 3 to blastocyst stage, there is a VERY high die-off rate at this point. Before deciding to do this, I strongly recommend you read the post on this issue (2-day, 3-day or blast transfer?), discuss it with your doctor, nurse and embryologist, and make your wishes crystal clear.
  8. Once the embryos are transferred back to the uterus, you are in the dreaded 2ww (2-week wait). Arrrghh! Enjoy the first week because you are going to drive yourself insane in the second week obsessing about every twinge. 🙂

Well, those are the main hurdles for an IVF cycle. The bad news is that if you DO get a BFP there’s a whole other set of even more hair-raising hurdles to clear! But we’ll save that for another post …

Our IVF/IUI/TI cycle just failed … What should we be asking at the review?

Thursday, September 24th, 2009

After all the waiting to GET on the waiting list and then all the waiting ON the waiting list, finally you got to try the “big guns.” You’ve somehow overcome your fear of needles, vaginal scans and then (for IVF) the dreaded egg collection procedure; you’ve survived the harrowing 2ww … and it’s a BFN. Or a chemical pregnancy. Or a pregnancy and then a miscarriage.

After all that anxiety, fear, hope and expectation, a failed cycle is just devastating. You’re booked for a review appointment with your specialist – but what should you be asking about now?

The most important question, of course, is WHY your cycle failed. There could be many possible explanations, some of which are just guesses and some of which are backed by concrete evidence or could be investigated further.

You don’t want to go through the expense and stress of another IVF cycle and only afterwards find out there was something else you should have addressed first. Here’s a quick list of other things you should be sure to have checked out if you haven’t already:

  • Male Factors. A full semen analysis is necessary – not just counts/motility/morphology but also tests for antisperm antibodies and SCSA (tests for DNA fragmentation).
  • Polyps and Fibroids. Uterine polyps and fibroids, even if they’re small, can influence the menstrual cycle and can interfere with implantation. They can typically be seen via ultrasound and can be removed through a relatively simple surgical procedure.
  • Thyroid Issues. Thyroid issues can impact fertility and need to be ruled out as a contributing factor. A thorough thyroid test needs to include TSH, free T3/T4 and anti-thyroid antibodies.
  • Ureaplasma. Ureaplasma is an infection for which you should be tested. “Ureaplasma may cause the formation of sperm antibodies and an inflammation of the uterine lining, either of which may interfere with implantation of the embryo” (Source)
  • Factor V Leiden. Testing for Factor V Leiden is also important. “Factor V Leiden is a relatively common hereditary blood coagualtion disorder and can lead to stillbirth or unexplained recurrent miscarriage” (Source)
  • Hysterosalpingogram (HSG). An HSG is a test to determine whether the fallopian tubes are open. Even if you’re doing IVF this is important because you could have a hydrosalpinx, which is a blocked tube that leaks toxic fluid into the uterus and can affect implantation. (More info)
  • Recurrent miscarriage/recurrent implantation failure testing panel. In New Zealand, the usual procedure is to run a set of blood tests (on the female partner) such as:
    • Coagulation screen
    • Thrombophilia screen
    • Autoantibody screen incl.
    • antithyroid antibodies,
    • anti-gliaden antibodies
    • Factor V Leiden
    • Karotype
    • MTHFR mutation
    • Anticardiolipin antibodies
    • Lupus anticoagulant
    • … and a karotype for the man

Follow this link for a very comprehensive list of possible causes of recurrent miscarriage that can be investigated systematically if you need to do some more serious digging.

  • Endometriosis. If you have period pain that requires more than a couple of Panadol (or any other of the possible symptoms of endometriosis), ask for a laparoscopy to investigate. Endometriosis is quite common and often missed or misdiagnosed, e.g. because women think their period pain is normal. For more information, check out Endometriosis New Zealand’s excellent website.

OK, nice laundry list, but what should I be asking my doctor?

Before your review appointment, if you did IVF, call the embryologist who worked with you during your cycle and ask him or her what they thought about the quality and maturity of your eggs, the fertilisation rates and the quality and development of your embryos. If you can, it’s best to do this soon after (or, the day you go in for) embryo transfer so that it’s fresh in the embryologist’s mind. Pump them for any information you can get.

When you see your doctor, start with an open-ended question about what he or she thought went well in your cycle and what didn’t. Summarise what the embryologist told you as well and ask the doctor to comment.

Your next question should be around the various other possible causes of cycle failure listed in the bullet points above. How many of these have we eliminated as a possible cause, how did we do so, and which of them should we investigate before leaping into another cycle? Make sure you study these beforehand and think whether you recognise any relevant symptoms.

You may find yourself in a situation where the doctor pronounces you have an egg quality problem. Now, this is a difficult one because, from a Western medicine perspective it’s seen as untreatable and just the hand you’ve been dealt. Further, this is really little more than an “eyeball” assessment, assuming you haven’t done a PGD (preimplantation genetic diagnosis) IVF cycle where the embryos are actually tested for chromosome abnormalities. Visual egg and embryo quality is correlated with chromosomal normality/abnormality and pregnancy rates, but it isn’t a direct assessment of these things. You can definitely have great looking eggs/embryos that are abnormal. And there are a few instances where very scrappy, sad-looking eggs and embryos turn into perfectly normal babies, but unfortunately not very often.

If you do get the “bad eggs” speech, there are a couple of questions you should raise. One is whether you can try a different protocol that might be better suited to your delicate eggs. For example, some specialists argue (and have evidence) that higher doses of stims can “fry” some women’s eggs, so that a lower dose may be more gentle and damage them less. [I personally had a dramatic improvement in embryo quality when I dropped my dose from 450IU to 150IU, and I know others who have experienced the same.]

The other thing to insist is that “bad eggs” isn’t just assumed to be the ONLY cause of your failure. Even if it’s true and you are looking at moving forward with donor eggs, you need to be sure you don’t have uterine or autoimmune issues or endometriosis (etc) that could jeopardise the success of that cycle.

Most fertility specialists in New Zealand don’t really buy into the idea of alternative medicines, but if you’ve been given the “bad eggs” or “old eggs” speech, I’d strongly recommend reading the following piece by Dr. Randine Lewis about the Chinese medicine perspectives on “poor egg quality” and whether there’s anything you can do to address it.

This website/blog also has several posts on acupuncture and Chinese medicine – see the menu at left to find items on that topic.

What are the main IVF protocols used in NZ?

Wednesday, September 23rd, 2009

Why is this important?

First, it’s good to know roughly what’s out there, and that there is more than one option, so that you can get your specialist to explain why this one and why not that.

Second – if you don’t do well on one protocol you may do fine on another.

Some women will need a few tries to find their “Goldilocks” (just right) protocol, but because most of us have only limited finances and stamina, it’s important to make sure you’re satisfied the first one is a good choice for you.

Basically there are three main protocols used by NZ clinics (plus a few variations, which I’ll try to add later):

1. The ‘long’ protocol (default for young women and those with normal FSH; not generally used on high FSHers unless they are quite young, and seldom on anyone over 40 because it can easily oversuppress those with diminished ovarian reserve).

Buserelin for about 10 days to downregulate (put you into temporary menopause), then the Buserelin dose is lowered and you start stims (Gonal F injections), stim for about 10 days with scans and blood tests every 2-3 days. When your follies are ready, you are instructed to take a trigger injection and turn up for egg collection about 36 hours later.

2. The microdose flare – usual starting protocol for high FSHers and women over 40. It’s less likely to oversuppress poor responders than the long protocol.

Usually but not always starts with a course of BCPs (birth control pills) for about three weeks, then you stop for a couple of days, then start your microdose course of Buserelin (this gives your ovaries a kickstart or ‘flare’), then a day or two later you start your stims (Gonal F injections). As with the long protocol, you stim for about 10 days with scans and blood tests every 2-3 days. When your follies are ready, you are instructed to take a trigger injection and turn up for egg collection about 36 hours later.

3. The antagonist protocol – another option for high FSHers, poor responders and older women. Often the first choice protocol for these women, but in NZ it’s typically tried only after the flare protocol has given a weak response because the drugs are cheaper for the flare.

Usually starts with a mild pre-cycle suppression course of estradiol valerate (E2V) from CD21 or 7dpo the previous cycle (you can ttc on your own the previous cycle; this won’t affect a pregnancy); when AF (your period) arrives this is counted as Day 1 and you may be asked to go in for a baseline scan to check that you have no cysts, your antral follicles are ready to go and no big dominant follicles; on CD2 you start stimming, having bloods and scans every 2-3 days. When your lead follicle reaches 14mm, you start Cetrotide (the antagonist that stops you ovulating too soon). When your follies are ready, you are instructed to take a trigger injection and turn up for egg collection about 36 hours later.

There’s another called the Colorado protocol, which is a variation on the antagonist. I don’t have all the details on this and how it’s done in New Zealand, but if someone would like to email me or post it as a comment, that would be a big help!

If you are a poor responder, have high FSH, low AMH, a low antral follicle count, or have been told you have diminished ovarian reserve (DOR), follow this link to check out protocols used for poor responders.

And here’s another link in case you want to know more about the various IVF, IUI and TI (timed intercourse) cycle medications and what they do.