Average number of blastocysts per IVF cycle

It’s a really simple question – what is the average number of blastocysts per IVF cycle?  After our failed IVF cycle I posted a status update in my local resolve support group’s facebook page, I explained what had happened with our cycle: 14 eggs retrieved, 11 mature, 11 fertilised, 2x 5 Day blastocysts transferred (5BB & 5CC) on Day 5, 9 still alive on day 5, but 0 were of sufficient quality for cryopreservation.   Some ladies commented how they had similar results with 0 embryos making it to the freezer, and one lady posed the very good question how common is it to have 0 make it to the freezer? Perhaps it is more common than we think?  So it got me thinking…at no point has my doctor said what a typical number of eggs, embryos or blastocysts she would expect out of a cycle for us – the only stats we were ever told was all about our likelihood of a successful pregnancy from 1 cycle of IVF, and ultimately, a live birth.  And of course, that is the only statistic we only really care about, right?  This holds true, until you get a Big Fat Negative (BFN), then the other statistics start to matter and grind at you.

So I looked into it, and asked google – what is the average number of blastocysts per IVF cycle?  But I couldn’t find an easy answer, or at least one that I held great confidence in.  I’m the kind of person who needs to see the supporting evidence, and not just some seemingly arbitrary numbers some random person has posted on a website.  But although I didn’t find any national statistics per se, what I did find, made me feel a whole lot better about our last cycle.

The statistics that the Pacific Fertility Center in Canada are claiming are [1]:

11 – Average number of eggs retrieved

9 – Average number of mature eggs

7 – Average number of eggs that fertilise (approximately 80%)

7 – Average number of fertilised eggs that will form embryos (98%)

7 – Average number of embryos on Day 3 of culture

3.5 – Average number of blastocycts on Day 5/6 (50% of good quality day 3 embryos make it to blastocyst)

It was not clear if this was their clinic’s statistics or where the source of this data came from.  So my confidence is not high in it, I don’t know over how many cycles or patients this average is calculated.  But at least it gives you a flavour of what numbers to expect.  Note, it does not mention average number of blastocysts making it to cryopreservation!

Another clinic, Advanced Fertility Center of Chicago, provides a nice pretty chart of their own statistics, broken down by age for the period of 2003-2005.  First of all my first alarm bell is that is over 10 years old now!  Has anything changed in Assisted Reproductive Technologies in the last 10 years? Hmmmmm.  Anyway, here it is….

ivf-eggs-embryos-babies

Advanced Fertility Center of Chicago’s average number of eggs, mature eggs, fertilised eggs, 8 cell embryos and Day 5 blasts [2]

Their numbers are slightly lower than the Canadian clinic’s…but there could be many reasons for this because, again, there is no clue as to how many cycles/patients this average is calculated over.  This clinic does publish their statistic of how many blastocysts make it to cryopreservation.  And here is the money shot statistic people!!!!

number-embryos-frozen-age

Advanced Fertility Center of Chicago’s average number of blastocysts frozen per cycle in 2010-2011 [3]

Just look at how low these numbers are! An average of 1.7 for women younger than 35 years old.  And this statistic is a little bit more up to date than the ones above – this was for cycles from 2010-2011.

So what is the point of this post?  The point is that we didn’t have any blastocysts that made it to cryopreservation, but we did have 2 blasts that were transferred and 1 that could have been frozen, but they decided it might not survive the thaw.  For our first cycle we had one blast make it to the freezer.  The point is, we had high expectations for more to make it to the freezer, when in actual fact the reality is, we were better than average to have so many good Day 3 embryos and we were typically average with transferring 2 on Day 5. Yes, IVF cycle 2 was a failure, but we were pretty average with our second cycle!!! This doesn’t mean we are less likely to succeed with cycle 3, rather the odds ARE in our favour.

Happy dance Dani!!!

stay the path

[1] Source: http://www.pacificfertility.ca/our-resources/guide-to-ivf-lab-results/

[2] Source: http://www.advancedfertility.com/ivf.htm

[3] Source: http://www.advancedfertility.com/cryo.htm

 

 

Good plan batman

First of all, let me say a big thank you to everyone who showed us support by commenting on my last update.  It has been a really difficult weekend.  Full of emotional roller coasters.  Chris and I have been brought to the edge with our sadness and confusion about our second failed IVF cycle.  I couldn’t reply to your comments without crying.  I am sure some of you who have been there have felt that overwhelmingness.  I read each and everyone one and they mean a lot, so thank you for your support.

Today we had our follow up appointment.  Chris and I prepared for the meeting the only way we know best….by making a list.  We wrote a list of all possible scenarios for ways ahead on this pudding club hunt.  And then we individually wrote down what we felt about each scenario and exchanged our thoughts.  We discussed where there were differences.  It was difficult and emotional to do as we realised that we agree in some situations, but not in others.  It’s OK at this stage that we don’t agree or have the same point of view, but it was bloody hard and we had some very raw and honest conversations.  We used up a few boxes of tissues 🙂  But what was good about this exercise is that we were ready to come to this follow up appointment prepared for whatever the doctor was going to suggest doing next.

When my doctor spoke to me on the phone to tell me the bad news that our IVF cycle had failed she mentioned poor egg quality, I took away bad things from this when I needn’t have.  This was just my doctor’s first impressions report, she hadn’t really looked into my case in detail or reviewed my history.  But this is what she did at today’s appointment.

Our doctor was very positive and believes that our best chance is to try again.  We expected that, but she ruled out egg or embryo donation for us or the necessity for genetic testing.  Our chances are still high more than 50% success.  We will make a couple of minor adaptations to our next cycle with my medication protocol by switching from antagonist protocol to Lupron (Down regulation) protocol.  I am a good responder to stimulation so she believes this may help improve the egg quality.  We will also carefully review our Day 3 v Day 5 transfer options at the time.  I had some excellent Day 3 embryos this time around, similar to my first cycle when I got my positive.  May be my embryos don’t do as well in the culture afterwards.

But before we go into another round of IVF, I need to have a hysteroscopy.  This is a small surgical procedure where the doctor inserts a camera through my cervix to look at my uterus and fallopian tube opening closely to check for any potential damage from my suspected ectopic pregnancy, scarring or inflammation as well as checking for endometriosis and taking a small biopsy for further testing.  So I am scheduled for my procedure in two weeks time!

We have a plan we are both happy with.  I felt a huge relief off my shoulders because our doctor was genuinely positive for our next round of IVF – and we pushed her about it too (well Chris did!!) – there was no BS-ing!   So all things going well after the hysteroscopy, we are looking at an April IVF/ICSI Cycle:-)

Thank you all for sticking with us through this, it has been hard, but you make it all the better!!  XXX

butterfly

IVF Diary Vol II: 15th Jan 16

Medication(s) administered and dosage(s). Gonal-F 300 iu & Menopur 150 iu.  Chris really is great at this injection thing.  I prepared the Gonal-F whilst Chris prepared the menopur.  We both read the instructions to remind us how to mix everything up, but like riding a bike, it was easy this time around.  Chris was a little bit nervous, but he needn’t have been, he did a great job.  I even looked down at the needle as he was injecting it – I am still not good at watching the needle break the skin though :-s.  The menopur did burn a bit as it went in, but it wasn’t quite as bad as I remember it to be.

ivf2_day1Stims

Medical procedures undertaken. Nil.

What are my symptoms? Period started right on cue yesterday morning!  Hot flashes and a bit of dizziness a couple of hours after my 2 first injections of this cycle.

How do I feel today?  A little bit annoyed that my plans to have a more relaxing stim period and 2WW are falling to pieces. Some short turn around-high impact work may fall on my plate next week.  I would have to forgo some of my steadfast principles for quality work and accept that in this case a 40% solution can only be delivered in the time lines given.  I have stuck to my guns though to some extent – where I was going to be taking the whole week off work, I am now only taking Monday and Friday off.  Tuesday and Thursday I will be working from home, Wednesday I’ll be in the office.  As we talked about this potential work, I started to feel sick to my stomach.  I started thinking back to last time around when I was trying to get my project finished and how stressed I was feeling about balancing the IVF process and work.  I let down my quality levels then – no one noticed (of course I noticed), in fact I got lots of praise for that piece of work.  Last week when a senior boss praised this work in front of the whole division I sat there quietly proud, but felt a bit sad that I had accomplished that with little help during a shitty time of IVF, followed by the whole ectopic pregnancy thing and ultimately miscarriage.  My boss has been great by not dumping everything on me right now, he quite easily could have done, but he didn’t so I appreciate that, but I can’t quite help  thinking about how IVF is holding me back from doing my absolute best.  I don’t think my colleagues around me think like that (fortunately they are all smart, intelligent people who know me), it is just myself I am fighting with these thoughts.

All that being said, I’ll talk about something positive.  We decided to go out for dinner at our local restaurant to celebrate surviving and nailing those first two injections.  Chris deserved his beer!  As we were finishing our meal the power went out in some of the building.  There was a storm that evening so it must have knocked the power out.  I said don’t worry, we are on a different power grid to our neighbours over the road (the block our restaurant was on) and last time their power went out, ours stayed on.  As we walked back, we realised that our grid was out and our neighbours’ over the road was on! Typical.  Fortunately we are well prepared for such events (for hurricanes and other storms etc), and carried on with the power of candles 🙂  It was a little bit romantic…I snuggled up in bed preparing for the power to be out all night and the temperature to dip.

power_out

Power outage = Candle lit bedroom!! Fortunately we have quite a few candelabras left over from our wedding table decorations still 😉

But then came the hot flashes!  I needn’t have worried about keeping warm, it seemed the drugs were doing a great job of that for me!!

Any results?  Estradiol <20 (as it should be, the same as IVF 1).  Progesterone <.2 (as it should be, the same as IVF 1). FSH 3.21 miU/ml (IVF 1 was 9.29, in 2014 it was 6.8) LH 0.771 miU/ml (IVF 1 was 3.48, in 2014 it was 4.9).  My LH level came up as red in my results…this means it was out of the ‘normal’ range, it is very low.  But not by much.  So I looked into it.  Although lower FSH is good, low LH is not good…apparently calculating the FSH-LH ratio and knowing the LH levels are good predictors of IVF outcome.  Let’s just say that I read several scientific reports, plugged in my numbers and the stats aren’t good.  But, the good news is that I don’t care! Why?  Because women with this kind of level and ratio still got pregnant.  And I am going to be one of those women in 4 weeks time 🙂 In your face science!!! **

What’s next? The same injections Sat, Sun, then monitoring appointment on Monday morning.

Weight. Work stress = nom nom nom bads.  But I did do the mixed martial arts P90x3 routine and pushed myself hard, so I don’t feel so bad.

Waist.  NSTR

Boobs. NSTR

Hours of Sunshine 🙂 Still NONE.  Let’s see if the sun comes out this weekend!

Fun Activity to keep Dani from going insane. IT’S FRIIIIIIIIDAYYYYYYY!!  I need say no more.  Surprise date night.

*Notes.  I take First Response Reproductive Health multi vitamin gummies (pre-natal) and CoQ10 200mg gummies daily.  NSTR = Nothing Significant To Report.

** Reserve right to have science egg in my face later

Effects of flying and jet lag on fertility pt 2.

In my previous post I described some research that indicates fertility may be effected by the disruption to the body clock as a result of travelling across time zones (or any other job that requires shift work).  There is one hormone that may be taken as a supplement to help overcome and regulate the problems our bodies face as we fly in to different time zones – melatonin.

Melatonin is not new to me.  Some of my US colleagues have told me about the use of Melatonin to help them overcome their jet lag quickly when they are in Europe.

Last year I landed in Germany with a terrible headache that had lasted more than two days, pain killers just didn’t touch it, and I couldn’t sleep – which was probably perpetuating my headache.  So my US colleague suggested I took some melatonin to help me sleep and kick start my body into a natural rhythm.  He warned me that melatonin can have side effects, such as vivid dreams.  I already dream a lot normally, and I had problems in Afghanistan with Anti-Malerial drugs causing vivid dreams and hallucinations; so I was very cautious of taking melatonin.  But I was willing to give it a try as by my third night in Germany I was consistently unable to fall asleep until about 5AM, then working all day with this awful headache.  So I took two of the little melatonin pills, and they helped me to fall asleep before midnight.  Bliss.  I did have some vivid dreams, actually they were more like nightmares, but at least I got some shut eye!  My headache didn’t disappear though, so I decided not to take any more melatonin. I was more afraid of my dreams than my headache.

I didn’t know much about melatonin at that time; I didn’t really look into it.  But since suffering from infertility I have been educated more into melatonin and its purpose.  I came across it in the book “It starts with the Egg” by Rebecca Fett, but I didn’t pay it much attention.

So what is melatonin?  It is a hormone that helps regulate many other hormones in the body and helps to maintain our body clocks (or circadian rhythms).  During light hours of the day, our natural melatonin production drops and when it is dark, the body produces more melatonin.  If we are not exposed to enough light during the day or too bright artificial light in the evening this can disrupt the body’s natural melatonin cycle.

What does melatonin have to do with fertility?  Melatonin is produced by the pineal gland in the brain, but it is also produced by the follicles within an ovary, the mass of cells that surround the follicles, and in the immature follicle itself.  It is here where melatonin acts as an antioxidant which supports cellular health and protection of the immature egg from oxidative stress, especially at the time of ovulation.  Melatonin has beneficial effects not just on eggs but also on embryos.  Mouse embryos grown in a lab with melatonin showed an increased rate of forming bastocyst-stage embryos [1].  As a result of this success, clinical trials were undertaken.   A study of 115 women showed that melatonin may increase egg quality by reducing the level of one oxidising agent called 8-0HdG in the ovum, which is a natural product of DNA oxidation [2].  Women who were given melatonin had a fertilisation rate much higher than their previous cycle and nearly 20% of the melatonin treated women became pregnant.  Whereas only 10% of the non-melatonin group became pregnant.

Melatonin also helps to control body temperature, the timing and release of female reproductive hormones and possibly egg quality.

Finally, melatonin is known to act as an antioxidant during early pregnancy.  In addition, melatonin in the mother’s blood passes through the placenta to aid the creation of the fetal suprachiasmatic nucleus (SCN) where the central circadian regulatory system is located.

Melatonin levels decline with age, and as a result the ovaries lose their natural protector against oxidative stress; hence could be an additional contributor to age-related infertility.

If you are going to consider taking melatonin as a supplement when trying to conceive you need to be careful and should ask your doctor, because the melatonin supplement may disrupt the natural hormone balance and interfere with ovulation.  If you are going through a controlled hormone cycle with IVF this is less of a concern.  In addition, melatonin can cause side effects, such as daytime droziness, dizziness, and irritability and may worsen depression.  Melatonin can also interact with other drugs, so this is why it is important to check with your doctor before taking it.

If you are going to take melatonin as a supplement whilst travelling it is also important to know what time to take it.  You should take the supplement after dark the day you travel and after dark for a few days after arriving at your destination.  In addition, taking melatonin in the evening a few days before you fly if flying eastward.  Again, there is caution to be made here because the long term effects of taking the supplement are unknown.  Therefore this is not overly helpful for airline attendants or shift workers, and only for those who travel infrequently.

For me, personally, I am undecided as to whether or not I will take melatonin as a supplement for either my next IVF cycle or when I am on my next international trip.  But I will certainly be asking my doctor next time we speak.

Have you taken melatonin as a supplement? What are your experiences with it?

flying

[1] The effect of melatonin on in vitro fertilization and embryo development in mice.  Available here: http://hera.ugr.es/doi/15015646.pdf

[2].  The role of melatonin as an antioxidant in the follicle.  Available here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296634/

Trying not to cry at work is HARD

On Tuesday, after my second beta test, I went home from work early so that I could receive the good or bad news in private.  But my results had not ‘come back in time’, so not knowing when I would receive my results, I went into work on Wednesday.  I was busy running around the office preparing for a one day workshop I was leading the next day when I received the phone call.  You may know already that the news was ‘not good’.  Receiving news like this whilst at work is difficult. My eyes were welling up when I dashed to the toilet quickly, passing one of my senior bosses and trying not to look him in the eye.   I called Chris and had a good old cry – lucky there are not many women at my work to gate crash my pity parade.  Chris said he would come to my work for a hug and he would be there in about 30 minutes.  So I collected myself, and headed back to my desk.  A colleague of mine who had promised to provide me some input to my project report for about 3 weeks decided to tell me he was not able to do it and he was going on leave the next day.  Let’s just say, this was the wrong time to be telling me this.  My attitude initially to him going on leave was….”and…..?????”.  I had waited some time for his input and my report was already late.  I said “No worries…..” in a very sarcastic and mean tone.  Then my friend walked past us happy and bubbly….realised she had just interrupted something and asked if she should go, to which I nodded.  Anyway, I was clearly in a grump.

After 40 minutes of being really pissy one minute, and on the verge of tears the next, Chris arrived at my work.  We had a big hug and cry together in my work car park (parking lot).  Chris stayed for a coffee, and we decided we would work from home for the rest of the day.  I went back to my desk to finish off my preparations for the next day when my colleague (who I had been grumpy to) asked if everything was OK?  So I told him about my phone call. I held back the tears as I said it, but said it was OK, I was going home for the afternoon, which he agreed I should do.  I felt a little bit bad for my pissyness, but I know he understood that it wasn’t personal against him.

Thursday….I kept myself super busy at my workshop all day, I hardly stopped to think about anything else other than work.  It was great!

Today, Friday, I had my third beta blood test.  It didn’t start out great as my appointment was already eating into some ‘compulsory training’ time at work…and of course, the clinic had a waiting room FULL of patients.  I was greeted by a nice enough nurse who I had never met before. I thought I had met them all!!!!  In fact, it was very bizarre, I noticed that the receptionist was someone I had never met before, and all the other nurses I saw wondering around were all new. I wondered briefly if they had done ‘swap staff with another clinic’ day.  V. weird.  Anyway, the nurse who took my blood was pretty distracted by another nurse who was ‘in training’ (who at my last beta test, I blamed for my late result 🙂 ).  They were gossiping, I did not appreciate a lack of attention when I was already upset with having to be there. Grrrr.

After I made into work this morning 40 minutes late, I sat in on about 1.5hrs of pointless training (I am actually already trained, and didn’t know they were going to be covering this same material).  You can tell it was going to be a good day for me….not.  The office was very quiet today, everyone was out on travel or on leave, which was probably a good thing, but I felt lonely.  So I took myself off to a quiet empty meeting room and typed up notes from Thursday’s workshop to keep me busy…but it was slow going, my mind kept wondering to my results.

At 2pm my phone rang, I was surprised because the results weren’t due back til 3pm.  It was the doctor who had done my egg retrieval and  transfer calling with the bad news.  He said my hCG levels were 395 (actually it turns out he was wrong, they were actually 345).  My first response was wow it went up again, OK – I wasn’t expecting that!  But he brought me back down to earth and said he did not believe this would be a normal pregnancy, he would expect an absolute minimum level of 800 by now, and I should stop taking my medications to prevent prolonging the pain (Emotional pain he meant), he did say that I could choose to stay on the meds if I wanted to be 110% sure, but he recommended to stop them. He also told me to arrange a follow up appointment with my doctor as soon as possible.  And that was it.  I actually did not cry, I was just confused.  Sad, but confused.  I stayed in my meeting room and focused on my task at hand, surprisingly I got a lot done in the next two hours.

It is so hard to not cry in front of work colleagues, but at the same time, being there has been a good thing when I needed to divert my mind’s wondering to sad things.

As I left work I received a phone call from my doctor, she started talking to me as if I did not know my results.  However, she was far more informative about my results and what she wanted to do next.  She told me that she agreed with the other doctor I should stop taking the medication, there is a very very small chance (about 1%) that this might be a viable pregnancy, but coming off the meds will not harm the developing foetus if in fact it is developing.  By stopping the medication my body will be allowed to do what it probably would ordinarily have done and let me bleed.  She wants to see me on Tuesday afternoon for an ultrasound and another beta test to be sure I do not have an ectopic pregnancy, although very unlikely, she wants to check.  It is normal if I don’t start bleeding for another 4-5 days, but in the mean time if I get any sharp sudden pains or difficulty breathing to call her immediately.  She also started talking about what we have in the freezer – we have just one blastocyst that was frozen on Day 5 stored away.  They won’t do a transfer with just one frozen, so we would have to do another round of IVF.  Can’t even think about that right now.

As soon as I got home I took off the estrogen patches from my stomach.  It feels good to not have anything stuck there, and we don’t need to think about doing an injection either.  I’m trying to think of the positives here!

I always say it’s never over ’til the fat lady sings….predicting a successful pregnancy outcome

fat_lady_singing

I always say it’s never over ’til the fat lady sings.  But that doesn’t mean I can’t see that fat lady getting ready to get on stage…I can also hear her warming up, running through a few scales too.

So, my suspicions were pretty much confirmed about why I didn’t get my results yesterday.  My results were not good.  And let me point out here that these are not my words, but the words of my nurse.

My hCG levels last Weds were 49 –  just a bit lower about where they should be, but were not overly worrisome…

My results from Tues this week, however, were 126.  They went up!!!! But those of you who are familiar with hCG levels and where they should be by now will know this is not a great number.  hCG levels should double every 2 to 3 days.  What does this mean?  Well my doctor wants me to keep taking my progesterone and estrogen, just in case – there is always a small chance this pregnancy is still viable!! But I have to go in for another beta test on Friday to double check that this pregnancy is, in fact, over.

I can safely say I am no longer feeling cautiously optimistic….I am feeling pessimistic as hell and sad.  If you would like to hold onto hope for us, I gratefully take your strength and thank you for helping to hold us up, but quite frankly when the nurse tells you it is not good, it’s not good.  I understand she is preparing us for the worst.

BUT!!!!! I decided to do a bit of research on what all this really means, what are MY chances?  You know I had to do it, as one of my colleagues told me today – GTS!  (Google That S#*% !!!).  OK, I’m going to get a bit technical here….hang in there if you have in interest in hCG levels (the beautiful pregnancy hormone!!)….


I found a very useful study* that looked at the predictive values of hCG levels for a viable pregnancy 13 days after a 3 day Embryo Transfer (I took my first beta test 14 days after my 3 day Embryo transfer).  My result of 49, according to their model, gives me the following chances of outcome: 45% successful singleton pregnancy, 31% miscarriage, 13% bio-chemical pregnancy, 9% ectopic pregnancy, 3% successful multiples pregnancy.  Well I am glad they didn’t tell me what my hCG levels were last week!

According to these researchers’ analysis, they decided that the cut-off level for predicting a viable pregnancy was an hCG level is 76 IU/I (80% sensitivity)….although this is considerably higher than some other researchers have reported (for example other studies have found the cut off at a similar sensitivity to be: 42 mIU/ml (Qasim et al., 1996); 55 IU/l (Bjercke et al., 1999); and 50 IU/l (Sugantha et al., 2000)).

Wow guys, 76 seems to be a whole lot higher than the others….so do they have credibility in their research?  Well from what I can ‘statistically understand’ and in understanding their research design, it looks solid; their sample size is excellent, some of the best I have seen in articles about artificial reproductive technologies….but I am not a medical professional, so I am totally relying on my knowledge of stats and may be there is something ‘medically awry’ that I cannot see.

If I use any of these models, and consider my hCG level of 49 from last week, these researchers would have told me my chances of a viable pregnancy were always going to be low.

However, there was one interesting point that came out from this study that caught my eye:

In subjects with unexplained infertility, ICSI may result in lower than expected HCG levels (Gold et al., 2000)….The explanation for this was not clear.  Although the early embryo cleavage is delayed in ICSI-derived embryos and the fragmentation of embryos is increased the implantation potential is comparable with IVF-derived embryos.

Even though my numbers have not multiplied nicely….in the back of my mind I am holding onto this slither of hope….holding on that we are the ones in that 5% extreme quantile who defy the norm, and it is because we are unexplained and our embryo was ‘ICSI-ed‘ that my hCG numbers are much lower.

Until Friday…………. :-s

*Pokkeus, P., Hiilesmaa, V. & Tiitinen, A. (2002) Serum HCG 12 days after embryo transfer in predicting pregnancy outcome. Human Reproduction 17(7):1901-1905. Available at: http://humrep.oxfordjournals.org/content/17/7/1901.full

Pregnancy chances increase among women who soak up sun before IVF treatment

Pregnancy chances increase among women who soak up sun one month before IVF treatment

I was researching my next blog post and accidentally came across this recent headline.  Basically, some Belgian researchers discovered that an increased exposure to sunshine one month before conception can increase chances of getting pregnant by IVF by more than a third.  WOAH.  An increase in chances of a positive outcome by a third?  Chris…quick book us a holiday to the Caribbean and let’s hit that beach! Stat!

Well, we do know that melatonin is important in cell development, as well as the importance of Vitamin D, so it does make some sense.  So I tried to hunt down the source of this claim.  It took me aaaages because the researcher they referenced was not the prime author.  Anyway.  It seems the researchers from Ghent University have not yet published their findings in a paper, but I did find their poster from the conference, so you can take a look at the results for yourself.  Now there are definitely some significant findings there, but as we all know, correlation doesn’t equal causation….but I’m happy to give the sun a go!  It’s pretty low risk, doesn’t require giving up anything and who doesn’t love a bit of sun?! Now, I wonder whether the factor of suncream makes a difference…hmmm….

So ladies – we all know about honey moons and baby moons…now we need to make pre-conception moons a thing #preconceptionmoon (I’m sure it will catch on).

The ethics of ICSI – Intra Cytoplasmic Sperm Injection

ICSI for unexplained infertility

I felt pretty well versed and comfortable in the ethical debate behind IVF, well, so I thought until we came across ICSI.  Intra-Cytoplasmic Sperm Injection (ICSI) was recommended by our doctor because we have been diagnosed with unexplained infertility.  She explained that this procedure is worth trying because in our case of unexplained infertility there could be a chance that there may be something in the fluid surrounding my eggs preventing fertilisation.  ICSI overcomes this potential problem by injecting a sperm directly into the egg, avoiding the fluid.  It is important to note that with unexplained infertility there could be many other reasons unknown to us why we have not been able to get pregnant yet; we just can’t pinpoint the exact cause at this moment.  By performing ICSI (for a few thousand dollars more) it slightly increases our chances of success.  I have been looking into the evidence behind unexplained infertility and ICSI and the jury is out on whether it is worth while or not.  Despite the mixed reports on the internet, I trust our doctor, and as our fertility clinic is attached to a medical school I like to think that they are up to date on these things.

I hadn’t thought much about ICSI previously because Chris’s sperm is pretty good, I didn’t think it was on the table.  So I hadn’t read much about the procedure.  As I began to read up on the procedure, I started to think more about the ethics and morality of it.  Selecting the ‘best looking sperm’…is it any different to selecting the ‘best looking egg or embryo’ as would be the case for normal IVF?  And so I decided to look into it a bit more to understand what ICSI really is, and the considerations for and against this artificial reproductive technology procedure.

This post is just me putting ideas out there and exploring the issues, I do not necessarily agree with everything written here.  I may have been unintentionally selective or biased in some of my arguments, there are probably many more arguments for and against ICSI, so please feel free to comment and add at the bottom of my post.

What is ICSI?

ICSI – Intra Cytoplasmic Sperm Injection is an in-vitro fertilisation procedure that has been in use since 1992.  Fertilisation is achived by the direct injection of a single sperm into the cytoplasm of the egg.  The sperm can be extracted from fresh or frozen ejaculate, as well as being extracted directly from the testes (yikes, sorry guys, doesn’t sound fun at all).  The egg is prepared to facilitate penetration of the sperm.  The preparation of the egg includes enzymatic treatment and micro dissection of the cells which surround the egg.  Injecting the sperm bypasses the normal interaction it would have with the egg upon first encounter.  The deliberate selection of sperm for the procedure involves an assessment of selection criteria including: size, form and mobility of the sperm.  Despite the selection criteria, there is no guarantee that the sperm is actually ‘normal’ and therefore, there is no guarantee that fertilisation will occur.  It is even possible to select X or Y sperm to select gender, but only few fertility clinics offer gender selection for when it is necessary to avoid a known genetic disorder being passed.  I have also read about some fertility clinics offering gender selection if the family has one child already, and they want to ‘complete the family’ by selecting the opposite gender of its sibling.  This totally blows my mind.  After the sperm is injected into the egg, the egg is placed in an incubator and checked the next day for fertilisation.  If fertilisation is successful, the embryo is left for 2 or 3 days and then a decision is made whether to transfer the embryos back into the woman’s uterus for the next stage implantation.

Statistically speaking, there is evidence that ICSI slightly increases the pregnancy rate (but not statistically significant) compared to normal IVF.  The spontaneous abortion rate with ICSI is slightly lower, but this maybe as a result of the younger age of the mothers and the absence of female-related infertility.  The frequency of multiples is about the same (probably because the policies for number of embryos transferred remains the same).  The statistics for randomised trials of normal IVF v ICSI show that there is no significant difference.  Some researchers suggest that ICSI should only be reserved for the use of severe male factor infertility.  However, the use of ICSI is on the rise and becoming the new normal as infertility clinics like to reduce the risk of failure for the patient.  I can understand why that little extra % chance all adds up.

Ethical and moral considerations of ICSI – the arguments pro and against.

All ethical debates relating to IVF still apply to ICSI.  But ICSI may be considered effectively as a further layer of ethical debate  because we are potentially further ‘messing with nature’ by selecting one single sperm.  Often Pre-Implantation Genetic Diagnosis (PGD) will be part of ICSI, where there is a screening of cells of pre-implantation embryos for the detection of chromosonal disorders before an embryo transfer.  We are not doing PGD.  This can also add a further level for debate.

I will start with what I have found regarding the pros of ICSI, and other Artificial Reproductive technologies, followed by the against arguments…

Pro ICSI: The right to procreate.  To want a child is probably the most legitimate need in the world.  The right to found a family is one of the most important human rights as declared in the Universal Declaration of Human Rights (948, Article 16.1)  ICSI enables and supports this right.

Pro ICSI : Genetically related offsping. Before ICSI was possible, couples with male infertility would likely have resorted to donor sperm, or due to religious or personal beliefs would have rejected the use of a donor and remain childless.  With ICSI, it is possible for couples to have a child that is genetically related to them that previously was not possible.

Pro ICSI: Reducing the risks to the couple. If natural IVF was chosen over ICSI the woman may be unnecessarily putting herself at increased risk, physically and mentally for both partners.  For instance, if natural IVF were to fail first time round, ICSI may have prevented failure.  There are no guarantees, but as a couple puts themselves through multiple rounds of IVF, the physical and mental stresses increase, including the financial burden.

Against ICSI: The risks to the child itself.  There is much debate about the use of ICSI in male infertility and associated genetic abnormalities.  Chris does not have male infertility, so the risk of genetic abnormality is supposedly lower.  But the case for natural selection is negated with ICSI, there is no competition as would be with natural fertilisation, the chosen sperm may be a factor in genetic malformation.  There is also a risk of choosing a sperm that is immature and may interfere with the process of genetic imprinting and could result in growth retardation and functional disorders.  However, there has been little evidence to support these concerns.  Having said there is little evidence, ICSI has been around only since 1992, so children born from ICSI have not reached far into their adulthood and so studies are limited on the long term health related issues of ICSI born children.  Not to say the least, that the long term generation effects of ICSI on the population overall are not well understood and are only theorised.  For example, will infertility be passed? In itself, will ICSI simply contribute to further medicalising in the future?

Against ICSI: Multiple Embryos.  With IVF, to give a couple the best chance for a pregnancy multiple embryos are produced, grown, and then implanted into the uterus.  Some embryos may be discarded if they aren’t of good enough quality to present a healthy chance of pregnancy.  ICSI increases the likelihood for the generation of surplus embryos.  For some people, each embryo represents a life and so the disposal of embyros is considered in the same light as abortion.

I found one eloquent and well articulated argument that explains why some people are against multiple embryos “Where doubt exists on the level of fact, the integrity of conscience requires that the presumption be in favour of the life.  There is a classic example, if a hunter hears a rustling noise in the bushes, and is unsure whether it is a deer or another human being, he must assume it is a human being until such time as he can establish that it is not.  Similarly we may accept the argument that there is scientific uncertainty as to the precise moment when an individual human life begins.  That uncertainty, however, does not remove the obligation of care and respect for what certainly has the potential to become, and may already be, a distinct human individual.”

Against ICSI: Human Error. I have read about people worried about sperm/eggs getting mixed up in the laboratories.  We learned that sperm is dyed a certain colour for each patient so there is no confusion – this was why Chris’s sperm was purple!!  But to err is human after all and so are we potentially increasing the risk for a morally complex problem?

Chris's purple sperm

Chris’s purple sperm

Partial ICSI – overcoming some of the issues at hand?  Partial ICSI is where some of the eggs are left to fertilise ‘naturally’ in the petri dish as with normal IVF, and the rest of the eggs are injected with individually selected sperm as ‘back up insurance’, just in case normal fertilisation does not occur naturally.

There are many different valid and understandable viewpoints about assisted reproductive technologies like IVF and ICSI.  I am the type of person who respects others’ viewpoints and tries to understand as much as possible all sides of an argument.  I am an analyst by profession so I like to think I am good at that.  We have decided to do IVF and ICSI knowing these issues.  I just hope that others can equally respect our decision for IVF and ICSI.  But I now feel suitably versed to think about some of the important ethical and moral issues surrounding these artificial reproductive technologies.


Other notes and interesting references

On a side note, I found an interesting statement as I was researching that I wanted to share with you, it is about IVF and women’s rights in general.  Mary Anne Warren, (a philosophy professor who wrote a lot about abortion and criteria for personhood) wrote:

“If women’s right to reproductive autonomy means anything, it must mean that we are entitled to take some risks with our physical and psychological health, in the attempt to either have or not have children.  Neither abortion nor many forms of contraception are entirely safe, but women sometimes reasonably judge that the alternatives are even less desirable.  Having a wanted child can be as important a goal as avoiding an unwanted birth.”

Other references which discuss some of the more interesting medical facts than I am not willing to describe in my blog as I am not a medical professional or just interesting…

Potential Health Risks Associated to ICSI: Insights from Animal Models and Strategies for a safe procedure, Front Public Health. 2014. 2: 241.  Accessible here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235077/

Ethics of Intracytoplasmic Sperm Injection: proceed with care, Wert, G.M., Human reproduction, 1998 vol 13 (1)  Accessible here: http://humrep.oxfordjournals.org/content/13/suppl_1/219.full.pdf

Dealing with uncertainties: ethics of prenatal diagnosis and preimplantation genetic diagnosis to prevent mitochondrial disorders, Human reproduction update,  2008, vol 14 (1), Accessible here: http://humupd.oxfordjournals.org/content/14/1/83.short

Ethical issues in Assisted Reproductive Technologies, a presentation by Effy Vayena: http://www.gfmer.ch/PGC_RH_2005/pdf/Ethics_IVF.pdf

Ethical issues arising from the use of Assisted Reproductive Technologies, Dickens, B.M., Accessible here: http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.195.8966&rep=rep1&type=pdf

Surprise surprise!!!! IVF!

Well my blog post title has given the game away, so in summary…our next step will be In-Vitro Fertilisation!

This morning we met with our RE who reviewed our progress so far, or lack there of.  Our tests were all normal, the three IUIs all went according to plan (except of course for the pregnancy part), I responded well to the letrozole with 2-3 follicles, Chris had awesome sperm.  We remain unexplained, but she does still suspect endometriosis.  If my period pains were so bad that they affected my life and I wanted that to change then she would recommend a laparoscopy.  This surgical procedure comes with risk, side effects and can take several months to return to normal, so if my periods were so bad this would be the way forward, however, in my case the benefits are unlikely to outweigh the downsides.  So she recommends we move straight to IVF.  She explained the overall process:

Week 1 to 2 – after menstruation I start birth control pills for about 14 days, these help to control my hormones

Week 3 – start injectable medications to control ovulation and stimulate follicles to grow – many many more than the 2-3 that were stimulated with letrozole in order to get the best chance of retrieving some ‘good eggs’.

Week 4 – continue injectable medications…have ultrasounds every other day to monitor follicle growth, along with blood work to monitor hormone levels.  When the follicles are ready, we will inject the hCG Ovidrel trigger and 36 hours later I go for egg retrieval surgery.  Under sedation my eggs are extracted from my ovaries.  Chris provides his sperm and my eggs are fertilised in-vitro.  After the eggs have been fertilised, the embryos grow for a few days under close watch.  Then if they survive, one or two embryos are transferred directly into my uterus.

Week 5-6 – start injectable progesterone until the big pregnancy test either says – “woohoo you are preggers”! then I stay on progesterone, or…”booooo it’s a BFN my friend”, then we will…..well, let’s not go there right now.

This is everything I expected her to say, except for two things slightly different.

  1. First, I need to go for a hydrosonogram.  This procedure will produce a 3D ultrasound of my uterus.  I will have this last test because I have a severely retroverted uterus they could not see it very well on the HSG X-ray, they want to double check that there is nothing preventing the implantation stage.
    My HSG X-ray with my retroverted uterus (it's hard to see because it's hiding behind the catheter)

    My HSG X-ray with my retroverted uterus (it’s hard to see because it’s hiding behind the catheter)

    I have been promised this does not hurt quite as bad as the HSG.  THANKFULLY!!!!

  2. Secondly, she thinks it would be a good idea to do Intra-Cytoplasmic Sperm Injection (ICSI) because we are ‘unexplained’.  ART_logoThis is a procedure where a single sperm is selected and injected directly into the egg rather than normal IVF where the sperm is placed near the egg.  This procedure is an extra $2,420 so we need to check whether our insurance would cover this or not.

Talking of costs….it is going to cost $9,075 for the IVF which includes office visits, endocrine monitoring, ultrasounds, retrieval, transfer and first pregnancy test.  Plus, it is an additional $400 for the anaesthesia. Medication will be approximately $4,000 to $6,000.  Then the ICSI procedure is $2,420.  Cryopreservation is $1000 then $60 a month for any embryos frozen.  Yikes!!!!  But we roughly knew this anyway, it’s just a bit scary seeing it listed out like this.

So for now, we start the negotiating with our insurance and the diary planning. It’s looking like a late June start.

Ultimately, today I walked away with this one key figure she gave: for us – a 50% chance of success.  In my mind that is pretty amazing.  I’ll take that.  I’ve always been a glass half full kind of girl, lately it’s been half empty, today I think I’ve been topped back up 🙂

Thank you for all your support and kind thoughts so far, I’m feeling pretty encouraged this will work!

What is the probability of IUI success?

Our Doctor told us that we have a 20% chance of success with our IUI treatment (Letrozole Day 3-7, Ovidrel trigger 36 hours before IUI procedure and progesterone suppositories (50mg) for two weeks after IUI).  After three rounds, that would be a cumulative chance of success of 60%.  But this probability is a calculated estimate based on many factors that our doctor knows about us.  For example, if you were diagnosed with unexplained infertility the probabilities of success are lower than if you have been diagnosed with an ovulation related dysfunction.  Age, number of years trying to conceive and sperm quality are all examples of other factors that will influence your probability of success.

Success rates for IUI?

Success rates for IUI?

There are many predictive models out there to determine likelihood of success of IUI.  Each model seems to be slightly different, but in general they tend to range between 9-23% success for unexplained infertility, and the important factors that determine this success also seem to vary from model to model.  This is probably the real reason why that if you were to google ‘the probability of IUI success’, you won’t find much of a straight or clear answer.

Why do I care?  The difference between 10% (a one in ten chance) compared to 20% (a one in five chance), is psychologically different and I’d like to prepare myself for these seemingly different odds!  I trust my doctor, but I want to know more about why it’s 20%.

I spent several hours trying to find something useful that explained the most recent stats.  But the website with the most useful statistics explaining the different probabilities is www.advancedfertility.com.  However, the website is confusing, statistics are hidden away in text paragraphs that require reading several times, multiple hyperlinks to different pages that break up ease of understanding, how recent is this information and it is not always clear where their statistics have come from.

If you google ‘the probability of IVF success’ there is a plethora of useful information and supporting data (because the govt mandates the data is collected by clinics), also there is a really good resource, Society for Assisted Reproductive Technologies (http://www.sart.org/) who summaries the most recent data at the clinic level and the national level.  They even have a patient level ‘Predict my success’ interactive tool.

So, I herby call for greater transparency and clarity on IUI success rates, similar to what can be found online for IVF success rates.  I’m not looking for exactness, just more openness.

If you know of good resources to help understand success rates of IUI, please comment below and share!