Tuesday, 30 November 2010

Unbelievable

-1 dpo (days post ovulation)
I have my final Menopur injection, and a Pregnyl shot to trigger the release from a single 16.1 mm follicle. It is on my right ovary, the one with the partly blocked tube. My endometrium is a very thin 6.7 mm. It looks gloomy.

0 dpo
I have a romantic evening with my husband.

2 dpo
I get a call from the clinic telling me that our frozen embryo didn't make it, and our FET is cancelled. They tell me they can't book me in for a follow-up consultation for another seven weeks.

9 dpo
My husband leaves for a conference in a developing country with no phone contact and sporadic dial-up internet.

14 dpo
I am alone in the house. I figure there's no one there to laugh at me when I pee on a stick. This way it won't be such a shock when I get my period today. However, I look down, and I see the strangest thing:

A spectacular positive test. I had to blink several times, I was sure I was dreaming or hallucinating. No squinting, no colour correction (unlike all the other times). Two very strong lines. Then I remember the 5,000 U Pregnyl trigger 14 days ago. Is it just the trigger? No, it's too strong, and a 10,000 U Pregnyl shot was out of my system by 12 days during my last IVF. So then it must be real.

My husband doesn't respond to any of my text messages. I email a picture to him, but it is a long eight hours until I get his excited reply. He tells me that he secretly had his hopes up for this cycle.

I should make an appointment to get a blood test, but it feels too surreal. I tell myself I'll test again tomorrow and see how that looks.

15 dpo
Well, there's no mistaking this test for anything else:

It still doesn't seem real, and it takes me nine hours to psych myself up to call up the fertility clinic and tell them the news. I was sure that they were going to yell at me for being delusional and making up stories, but instead I hear a smile in her voice as she books me in for a blood test.

16 dpo
I go in for my blood test, so nervous as I watch my blood fill the tube. It looks like the same old blood that I've always had. I can't see any hCG antigens floating around. I make the poor nurse check three times that the tube has my name on it and that they are going to check for hCG, not just LH and FSH.

The clinic surprises me by calling at 11:13 AM. I didn't even have time to get nervous. She tells me that I have a beta of:

1,097

I am in shock. Last time I was pregnant we had a beta of 477 at 20 dpo. A beta of 1097 falls in the top 4% of singleton betas at 16 days post ovulation. My progestrone is great at 31.0. She books me in for another test in a week.

19 dpo
I am tired and sleepy, but then again I am always tired and sleepy. No spotting, no sore breasts, no nausea. Apart from the lack of a period, I do not feel any different. I suspect this is some sort of trickery. I take another pregnancy test at 2 weeks, 5 days post ovulation. I believe it for about 5 minutes.




23 dpo
I go in for my blood test, and again make the nurse triple-check that the label is correct on my tube is blood. I work from home because I can't imagine taking this call in an open office, plus I am too nervous to concentrate properly on anything else. By 12:30 they still haven't called. The later they call in the day, the worse the news, right? At 12:37 my phone rings. I pick it up with shaking hands.

Calmly the nurse tells me that everything looks good, and I am graduating from the clinic. I need to make an appointment with gynecology for an 8 week scan. I am in shock. I ask her for my beta number. "The gynecology number?", she asks. No, the hCG number. She tells me it is:

13,843

Which works out to a very respectable doubling time of 45.93 hours. My progesterone still looks good at 31.4. I beg her to let me pop in for a quick search for a heartbeat, but she says that their work is done.

After sharing the news with my husband, I sit and stare at the screen for about an hour. Then I pick up the phone and ring the gynecology department and book an 8 week scan like any other normal woman would.

28 dpo
Today. I still don't know what to think. I always thought that pregnancy was what happened to other women. I still don't quite understand how we got this fortunate. The embryo failed to thaw. The follicle was on the wrong side. My endometrium was too thin. This is just so unbelievable.

So how do I feel? Tremendously excited. Hopeful. Thankful. Lucky. Worried. Happy.

(If you somehow know me in real life, please keep this information to yourself).

Wednesday, 17 November 2010

To thecrazycatwoman

Dear Crazy Cat Woman,

I am so sorry that your sixth IVF failed, just days after you mourned an unfulfilled due date. You deleted your blog before I had time to leave a comment. Please know that I am so sorry for your loss, and still thinking of you and the babies you never met.

I know that sometimes you have to step away from it all, to get some distance and try to heal. Please know that this community will be waiting for you if you choose to return.

Thank-you for all your support and comments during the year.

Dandle.

Wednesday, 10 November 2010

Happiness today, Hope tomorrow

No Baby Ruth was kind enough to nominate me for the "happiness today, hope tomorrow" award, created by Miss Ruby. Her instructions are to acknowledge something that's making you smile and a hope for one amazing thing to bring you even more happiness. Then pass this award on to anyone who would benefit from looking at their life now and finding happiness in it..



Previous recipients of this award include:
non geordie mum
The life and times of KitVonD
All In One Basket
one donor. one husband. one month at a time.
Adventures in Infertility-Land
My Cheap Version of Therapy
Blawnde's Blawg
The Elusive Embryo
Little Looman Log
My words fly up, my thoughts remain below
Our Fertility Journey
Mommy-in-waiting...
Half as Many Chances
The Road Less Travelled
And Baby WILL Make 3!
Going For It
Time Well Wasted
phoebe gone wilde
Serenity in Chaos
No Baby Ruth: Playing Baseball Without a Bat

I enjoyed reading through their entries and learning about their current joys and wishes for the future. Common themes included

Things that make us happy...
Job
Community
Beauty
Friends
Family
Food
Pets
Travel
Rest
Autumn
Vacation
Play
Sports
Body
Health
Home

Our hopes for the future...
Pregnancy
Birth
Adoption
Travel
Relationships
Friends
Family
Home
Relocation


As for me, I am so happy to be married to such a wonderful person. My husband is the best part of my life, and makes me smile with joy. I am hopefully that I never lose perspective, and that I remember that no matter where life takes us, as long as we have each other we will make a beautiful family.

I am passing this award along to anyone who wants a bit of hope and happiness in their life.

Friday, 5 November 2010

IVF#2: scheduled

Thank-you for all your advice yesterday.

I called the clinic today and spoke with a lovely midwife. She said The Professor had very recently put a big note on my file saying that he must meet with us before we proceed with our next cycle. My husband suspects that The Professor wants to talk to us about my thin endometrium and suggest some further tweaks to our protocol.

However, I managed to convince her to let me start BCPs before the consultation, and schedule me to put me into the system to start injections a few days after the consultation. So this is my tentative calendar:

November 16: Start BCPs
December 23: Consultation with The Professor
December 27: Start suppression with decapeptyl
January 6: Start Gonal-F stimulation
January 24: Tentative transfer
February 4: Tentative beta

I am so happy that I can ring in the New Year while in the midst of an IVF cycle, full of hope and excitement for the year ahead.

Thursday, 4 November 2010

FET#1: Cancelled

Oh yes, that word that is heard far too often in the Land of IF: "Cancelled".

Our poor little 6-celled embryo did not survive the thaw.

When the clinic rang this morning, I could tell by the tone of her voice that it wasn't good news. Then she confirmed this by saying "I am afraid that I don't have good news". I knew that we had a 40% chance of cancellation, as we only had one embryo to defrost. So this was not entirely unexpected.

But then she surprised me. She said that I had to have a meeting with The Professor before we started our next fresh cycle. I told her that, no, we just had a meeting with The Professor, and we had agreed on a new protocol for the fresh cycle. She told me, no, my file said that I had to have another meeting first. I told her that wasn't necessary. She told me it was. Fine, I said, and asked her when the next appointment was available.

December 23

That's seven weeks from now. I have to wait seven weeks to have a 10 minute conversation in which The Professor tells us what we already know. Look, I enjoy talking with The Professor as he is quite knowledgeable and can answer some of our questions. But I am not willing to wait seven weeks for the privilege. Last time we had the appointment, he had already reviewed our chart and determined a protocol. Nothing that we said changed this protocol. It was a reassuring meeting, but hardly medically necessary.

I am thinking of sending the clinic an email like this:

On September 23 we met with [The Professor] to discuss our treatment options. He told us that there was a 40% chance that our upcoming FET cycle would be cancelled due to the embryo failing to survive the thaw. We discussed our treatment options for the next fresh cycle if the FET cycle was unsuccessful. [The Professor] recommended an injectable GnRH-agonist instead of nasal buserelin, and the use of recombinant Gonal-F instead of urine-derived Menopur.

Today we learned that our FET cycle was cancelled because the embryo did not survive the thaw. However, I was told that we were required to wait another seven weeks for another meeting with [The Professor] before we can begin our next fresh cycle.

I understand that [Fertility Clinic] is a large and busy practise that deals with hundreds of patients every month. [The Professor] works many hours as an academic, a researcher, and a clinician. We appreciate the fact that he is very willing to take the time to meet with all of his patients one-on-one, and we understand that he meets with a large number of patients.

However, we do not feel that this appointment is strictly necessary, and we would love to be able to begin another fresh cycle as soon as possible. Is there any way that we could commence the next cycle earlier without having this appointment first? Or if a consultation appointment is essential, could we meet with another doctor in the clinic if they have an earlier slot available? We are also open to consultations via email or telephone.


What do you think? Am I over-reacting to a seven week wait? And how do I tell them that I don't want to wait for a consultation appointment, but I do want to ask them to add estrogen and sildenafil to my next cycle?

Wednesday, 3 November 2010

Endometrium thickness

For every single cycle, my final endometrium thickness has been 7 mm or below. For this last cycle it reached a maximum of 6.7 mm. I know this is bad, but how bad is it? I did some research for myself today, and wrote up my findings.

Endometrium Thickness
During the follicular stage of the cycle, estradiol released by the developing follicles to stimulate endometrial proliferation. In general, the greater the proliferation, the thicker the endometrium.

In both fresh and frozen IVF cycles, a thinner endometrium is associated with lower pregnancy rates. In one study of 1382 fresh IVF cycles, endometrial thickness of less than 10 mm on the day of transfer was significantly associated with lower pregnancy rates (Kovacs et al., 2003). One study of 768 FET cycles found that live birth rates were 1.9-fold lower in women with endometrial thickness of 7-8 mm compared to women with thickness of 9-14 mm, after adjusting for confounding variables. The lowest pregnancy rates were found in women with endometrial thickness less than 7 mm (El-Toukhy, et al., 2008). Biochemical pregnancies have been associated with a thinner endometrium (Dickey, et al., 1992).

Association or causation?
Of course these studies are not saying that a thin endometrium is causing implantation failure. It may be a proxy for another factor. However, in one study logistical regression found no association between endometrial thickness and embryo quality or age (Kovacs et al., 2003).

Multivariate analysis has concluded that endometrial development is one of the factors that play a significant role in IVF outcome. Other variables such as age, embryo quality, number of embryos transferred and stimulation protocol were also shown to have a significant impact on treatment outcome.

Does increasing endometrial thickness improve pregnancy outcome?
Numerous possible treatments for increasing endometrial thickness have been proposed. These include aspirin, tamoxifen, sildenafil, and estrogen.


Low-dose aspirin
Aspirin (acetylsalicylic acid) has anti-inflammatory, vasodilatory and platelet aggregation inhibition properties, and may promote uterine blood flow. Randomized clinical trials have produced conflicting results on the beneficial effects of aspirin in IVF.

One meta-analysis of 10 randomised clinical studies of fresh and frozen IVF cycles found that clinical pregnancies were 1.15-fold higher in low dose aspirin groups than placebo groups (Ruopp, et al, 2007). However, aspirin does not appear to improve endometrial thickness (Haapsamo, et al., 2009), and subsequent randomised placebo-controlled trials have failed to find a significant difference in pregnancy rates between aspirin-treated and non-aspirin treated groups (Dirckx, et al., 2009).

So if there is a positive effect of aspirin on the success of IVF cycles, it is very small, and not associated with changes in endometrial thickness.

Tamoxifen
I was only able to find a single study that examined tamoxifen and the endometrium. This study compared the use of supplemental Clomid or Tamoxifen in addition to injectable gonadotrophins in IUI cycles, and found that patients taking tamoxifen had increased endometrial thickness and improved ongoing pregnancy rates (Wang, et al., 2008). Tamoxifen is generally only used in IVF cycles in cancer patients.

Sildenafil
This magic blue pill has been found to improve blood flow by enhancing the release of nitric oxide and thus relaxing vascular smooth muscle. Does it also affect womens’ reproductive organs in a similar manner?

One randomised placebo-controlled study of 15 non-pregnant, nulliparous women found that sildenafil improved uterine volumetric flow during the luteal phase of their cycle (Hale, et al., 2010).

In a pilot study, 105 infertile women were recruited with prior IVF failures attributed to poor endometrial thickness

Estrogen
Estrogen supplementation during stimulation with Clomid during IUI cycles has been shown to improve endometrial development and to result in thicker endometria and improved morphology (Gerli et al., 2000; Elkind‐Hirsch et al., 2002).

Similarly, a placebo-controlled randomised trial of 81 women demonstrated that oral estrogen supplementation throughout a fresh IVF cycle was associated with increased pregnancy rates. The estrogren group had significantly thicker endometrial thickness and a 1.9-fold higher pregnancy rate (Jung and Roh, 1999). Supplementing progestrone with estrogen purely in the luteal phase has also been shown to increase pregnancy rates compared to progestrone-only supplementation during the luteal phase (Var, et al., 2010)

Conclusions
Supplemental sildenafil and estrogen may improve endometrial thickness and pregnancy rates in women with prior IVF failures due to thin endometriums. The evidence for estrogen is currently stronger than that for sildenafil.

Personal Implications
I am going to contact my clinic and ask them about the possibility of adding estrogen (and perhaps sildenafil) to my next fresh IVF cycle.

References

P. Kovacs, Sz. Matyas, K. Boda, and S.G. Kaali. The effect of endometrial thickness on IVF/ICSI outcome Hum. Reprod. (2003) 18(11): 2337-2341

Geoffrey Sher and Jeffrey D. Fisch. Vaginal sildenafil (Viagra): a preliminary report of a novel method to improve uterine artery blood flow and endometrial development in patients undergoing IVF Hum. Reprod. (2000) 15(4): 806-809.

Geoffrey Sher and Jeffrey D. Fisch. Effect of vaginal sildenafil on the outcome of in vitrofertilization (IVF) after multiple IVF failures attributed to poor endometrial development. Fertility and Sterility. Volume 78, Issue 5, November 2002, Pages 1073-1076.

Sarah A. Hale, Cresta W. Jones, George Osol, Adrienne Schonberg, Gary J. Badger, and Ira M. Bernstein. Sildenafil Increases Uterine Blood Flow in Nonpregnant Nulliparous Women. Reproductive Sciences April 2010 17:358-365

Marcus D. Ruopp, Tara C. Collins, Brian W. Whitcomb,and Enrique F. Schisterman. Evidence of Absence or Absence of Evidence? A Re-analysis of the Effects of Low-Dose Aspirin in IVF. Fertil Steril. 2008 July; 90(1): 71–76.

Mervi Haapsamo, Hannu Martikainen, and Juha Räsänen. Low-dose aspirin and uterine haemodynamics on the day of embryo transfer in women undergoing IVF/ICSI: a randomized, placebo-controlled, double-blind study. Hum. Reprod. (2009) 24(4): 861-866

K. Dirckx, P. Cabri, A. Merien, L. Galajdova, J. Gerris, M. Dhont, and P. De Sutter
Does low-dose aspirin improve pregnancy rate in IVF/ICSI? A randomized double-blind placebo controlled trialHum. Reprod. (2009) 24(4): 856-860


Tarek El-Toukhy, Arri Coomarasamy, Mohammed Khairy, Kamal Sunkara, Paul Seed, Yacoub Khalaf, Peter Braude, The relationship between endometrial thickness and outcome of medicated frozen embryo replacement cycles, Fertility and Sterility, Volume 89, Issue 4, April 2008, Pages 832-839

Hyuk Jung and Hyoung Kyun Roh. The Effects of E2 Supplementation from the Early Proliferative Phase to the Late Secretory Phase of the Endometrium in hMG-Stimulated IVF-ET. JOURNAL OF ASSISTED REPRODUCTION AND GENETICS. Volume 17, Number 1, 28-33

Turgut Var, Esra Aysin Tonguc, Melike Doganay, Cavidan Gulerman, Tayfun Gungor, Leyla Mollamahmutoglu, A comparison of the effects of three different luteal phase support protocols on in vitro fertilization outcomes: a randomized clinical trial, Fertility and Sterility, In Press, Corrected Proof, Available online 2 August 2010

Monday, 1 November 2010

FET#1: CD14

No more injections! We trigger tonight.

Right ovary: follicle 16.1 mm
Left ovary: nothing big here
Endometrium: disappointing 6.7 mm

Transfer is scheduled for Friday.