My IVF Journey Timeline !

1. IVF ( October 2008)
Antagonist protocol
AMH-3.5
One month of BCP
Started stimulation on day 2 with 112.5 iu of Gonal F
Increased upto 150 iu until day 12
Before triggering e2 was only at 626
Only 3 eggs retrieved
Only one fertilized (through IVF)
Transfer on day 3- 4 celled embryo ( After transfer 8% crinone once a day, Progynova 4mg/ day and HCG booster dose)
Negative pregnancy test


2. IVF- ICSI (December 2008)
Antagonist protocol 
NO BCP
Metformin 1500 mg
Started stimulation on day 2 with 175 iu of Gonal F
Continued with same stimulation dosage for 11 days
e2 after 4 days after stimulation 140
e2 after 7 days after stimulation 375
e2 after 10 days after stimulation 1120
9 eggs retrieved
7 mature eggs – 3 eggs used for fertilization by IVF and 4 eggs used for fertilization by ICSI
In IVFed eggs none fertilized.
In ICSIed 2 eggs fertilized
Endometrial lining > 8mm
Both fertilized eggs grade A with 4 cells on day 2
Transferred both on day 2 (After transfer 8% crinone once a day, Progynova 4mg/ day and HCG booster dose)
Positive pregnancy test- m/c at 8 weeks- no HB detected. But had scan only on 5w1d and again on 9w1d. On 5w1d scan a sac measuring 6mm with no yolk sac or foetal pole. On 9w1d there is yolk sac and foetal pole but no HB. D&C March.

3. IVF-ICSI (July 2009)
Antagonist protocol 
AMH-4.5
One month of BCP
Metformin 1500mg
Started stimulation on day 2 with 175 iu of Gonal F
First u/s 6 days after stimulation – Only one follicle on right measuring > 24mm ovary and on the left some follicles and two of them are more than 20mm.
Stimulated for 11 days (?)
Only 5 eggs retrieved and only 2 are mature and both fertilzed with ICSI
On day 2 one embryo had 2 cell and the other 6 cell- Both garde C embryos
Transferred on day 2 – Negative pregnancy test (After transfer 8% crinone once a day, Progynova 4mg/ day , no booster HCG)
Endometrial lining 12mm
Negative pregnancy test.


4. IVF-ICSI (September 2009)
Flare protocol
NO BCP
Metformin 1500 mg
Started with synarel on day 2- twice a day
Then from day 3 Pergoveris ( 150 iu Gonal F+75 iu LH)
After 3 days of stimulation e2 at 101
After 6 of stimulation e2 at 212 ( But still spotted because of synarel ???)
Due to slow growing follicles and slow rising e2 dosage of Gonal F increased to 225iu+75 LH
So after further 3 days of stimulation e2 at 828
Stimulation continued for another 3 days with 300iu of Gonal F + 75 LH
So after 12 days of stimulation at retrieval 8 eggs retrieved
7 mature 7 ICSIed and all 7 fertilized
Transferred 3 embryos with AH and with embryo glue. AH done on day 2.
On day 2 - I had one 2 celled, one 3 celled and one 4 celled embryo.
day 3 transfer- 3 embryos- 1 compacting morula, 2 at 6 celled stage. ( No grade for morula since it is much advanced for day 3 and other 2 embryos grade B)
(After transfer 8% crinone once a day, Progynova 4mg/ day , no booster HCG)
Endometrial lining at 10mm. Added Heparin.
Started bleeding after 9dp3dt. Lots of cramping and lower back pain.
Pregnancy test negative.

FET ( October 2009)
There were 4 frozen embryos (slow freezing)
3 embryos transferred
Negative pregnancy test

5. IVF- ICSI ( January 2011)
Antogonist Protocol
NO BCP
Metformin 1500mg
Baseline scan- no cysts
Started on 187,5 iu Gonal F
After 4 days e2 at 213
Gonal F increased to 225 iu
After 6 days of stimulation e2 at 375
Gonal F continued at 225 iu
After 8 days of stimulation e2 at 656
Total 11 days of stimulation
5 eggs retrieved- All 5 mature
3 eggs fertilized with ICSI
Day 4 transfer- 3 embryos ( 2 compacted morula and one 8 cell grade c)
Pregnancy test negative

All the above 5 IVF cycles are performed in Wetzlar, Germany.

6. IVF-ICSI (at Malpani Infertility Clinic, Mumbai) (November 2011)
Long Lupron Protocol ( a modified version of long lupron)

AMH-1.8
DHEA 75mg (For 8 months)
No Metformin
Mdicines used : Lupron, Menogon, Cyclogest, Progynova
300 iu Menogon
24 eggs retrieved
20 fertilized
10 usable embryos 
7 embryos frozen (5 on day 3 and 2 on day 5)
3 Grade A embryos transferred
 Pregnancy test negative.

FET (June 2012) (at Malpani Infertility Clinic, Mumbai)
Problem with the growth of endometrial lining, after several days it grew to 7mm (took almost 3 weeks to grow to this thickness) Used G-CSF to improve lining.
Transferred 2 day 6 blastocysts
Pregnancy test negative

FET (June 2013) (at Malpani Infertility Clinic, Mumbai)
Thin lining, only 6.7mm at the time of embryo transfer.
Transferred 3 grade A day 3 embryos which are frozen in 2011. (at the age of 33)
Pregnancy test positive :)
First ultrasound showed twins :)
Completed 13 weeks successfully as of 11.9.2013, and so far so good !
Please keep me in your prayers !

Lost babies due to incompetent cervix at 20 weeks.

FET (March 2014) (at Malpani Infertility Clinic, Mumbai)
It was a surrogacy cycle.
Transferred two blastocysts to surrogate (these blastocysts were grown from day 3 embryos which are frozen and thawed during previous FET and frozen again on day 5)
Surrogate had a positive pregnancy test.
Week 6 ultrasound showed only a gestational sac measuring only 4 weeks old.
Surrogate miscarried !

7. IVF-ICSI (at Malpani Infertility Clinic, Mumbai) (May 2014)
Long Lupron Protocol ( a modified version of long lupron)

AMH-1.6
Vitamin D 12ng/ml
No Metformin
No DHEA
Mdicines used : Lupron, Menogon, Uterogest, Progynova
300 iu Menogon
21 eggs retrieved
19 fertilized
7 Blastocysts
One transferred to my uterus
6 frozen
Positive pregnancy test !

Our daughter Anisha arrived !

Anisha born on January 13th 2015

11 weeks and all is well :)

Today I had another ultrasound. Both the babies are measuring as they should (4.5 and 4.1 cms). They are very active: turning around, moving their hands and feet, covering their ear with hand and ........ everything which I saw today still appears unbelievable ! I was lying down looking at them; tears flowing down my cheeks; and I was overwhelmed with so many different thoughts. I was thinking of my dad; my IVF attempts and the miscarriage I underwent; Mumbai trips; suggestion from my RE in Germany to use heparin (I didn't even take baby aspirin this time around !); the HLA matching tests and the stupid therapy I underwent for that; the fear I had to endure; the determination I had; and now some beautiful ultrasounds ! Everything appears surreal.

 

I already have a small bump. Nausea and vomitting is still there and I feel very tired. Please excuse me for not updating my blog as I used to !

 

What more to say - thank you so much everyone for all the love and prayers !

The home pregnancy test showed two lines !

 

Yes, it is a positive. I saw a positive hpt almost 4 years back, in 2009 January. If that embie had managed to become my baby, my child would have been three and a half years by now. I need to remember that little embie which gave me the strength to hold on to hope and keep trying. I am feeling so calm and serene. No overt emotions are there. After expecting this for a long time, I feel surprisingly numb. I am grateful that I had a positive. I know from now on it is a long journey and I wish I get the strength to face whatever comes my way. Surprisingly, I am not afraid of the future.

I take this opportunity to thank my Dr. I am a very difficult patient to deal with - both scientifically and emotionally. He was always kind and compassionate. He never made me feel that I am stupid or irrational. His team is as wonderful as he is. If you are wondering about the photo above - the colourful Vinayaka is given by Dr. Sai, the embryologist. As soon as I got into the room, to get ready for embryo transfer, he sent this for me. He made me cry but from that time onwards I felt so happy and confident. Thank you Dr. Sai, your good luck charm worked ! The little Vinayaka is my DH's gift. My DH is happy and calm as usual. My mom is excited and I told her that she has to be calm and keep on praying. I believe that her prayers are answered. I want to thank Mr. Ali, Sister Mary and Mr.Vinayak who work in Dr.Malpani's clinic. They said after the transfer - there is a Muslim, Christian and Hindu praying for me (Isn't that sweet ?) . Dr said he will pray for me (Thank you Dr !). I thank Dr. Anjali for being so kind - thank you mam !

I love all my blog readers and I will forever be grateful for all the love, support and prayers I received. Everyone are special in their own way. Ashu, is a medical student who reads my blog and leaves kind comments all the time. I am always very happy that I have a reader like him (he doesn't have anything to do with infertility yet took the pain to read my posts !) I am also thankful to everyone who shared their little one's pictures, conceived via IVF, which gave me so much happiness and hope. Pankaj thank you so much ! Caro, Kavitha, Anjani, Fawzia, Rita, Le, Mamtha, Sherin, Radhika, Ads, San, Nidhi, Mary, Jay, Nushi, Aakanksha.... and lot more of my friends who stood beside me; who shared their happiness and fears; who are kind enough to give me encouraging words when I needed the most eventhough I have never met 99.9 % of them. Many I knew only through my blog....

Another most important person I need to thank  is my boss. He is a very kind human being and made me understand how important is my job during my tough times. He was always pleasant when I asked for holidays for my treatment. I can't thank my friends enough for being so kind, understanding and supportive. Everyone did their best to make us feel good. When I came from India, my friend Priya held my hand and never left it until I wanted to leave. The warmth and compassion in it is so heart-warming. I know that touch helped my embies.This journey has just started, and I know the uncertainty inherent in it. I am holding on to hope and I am accepting today's blessing with utmost humility. My greatest joy is that it will give hope to so many and that is the sole intention for writing this blog.

Once again thank you so much Dr - without you this blog wouldn't have existed and I wouldn't have experienced so much goodness and satisfaction !


Last but not the least - thank you so much my little embies ! Make sure that you don't give up the fight; we have been waiting for you so long now. I need to  have you in my arms (if possible all of you !).

 “Never let go of hope. One day you will see that it all has finally come together. What you have always wished for has finally come to be. You will look back and laugh at what has passed and you will ask yourself... 'How did I get through all of that? ”

- author unknown

A quick update ! When going gets tough ...

I will be having a FET on June 29th, exactly one year after my previous FET. Until previous December, we didn't have holidays; and my attempts to grow my endometrial lining to decent thickness from the beginning of this year failed miserably. My lining would halt at 6.5 mm everytime ! I didn't try anythingelse other than progynova (different doses !). Went in for a hysteroscopy, a month ago, during a dummy FET cycle. Uterus is fine - no problems were detected ! My endometrial lining expressed estrogen and progesterone receptors as it should. There was no infection or malignancy ! During the dummy cycle, exactly one week after my hysteroscopy, my lining was only 4mm. I started progesterone and within 4 days it grew to 8mm. I didn't know lining grows after progesterone support ! Might be I am very unusual in all ways :) ! The speculation is, it is not the actual proliferation of endometrium but just an increase in thickenss of individual cells (change from proliferative to secretory endometrium) after progesterone support. But can it thicken 4 mm ! The happenings are very confusing, and there are no reasonable answers. This cycle I decided not to take more than 4 tabs of progynova (estrogen tablets), whatever may come ! My lining seems to be around 7mm ! Not the best. But we have decided to go for ET. This is the story from my side. I don't know when I will update my blog again. I have promised my DH that I will not sit in front of computer (he feels that I am stressed out because of writing !). I will definitely miss my blog, but I should respect my DH's view too, afterall he goes through a lot of struggle because of me. I will miss writing - it gives me so much solace ! When I start writing again, I would like to make a post about endometrium ! I learned a lot ofcourse ! Please do wish me good luck ! Thank you for all your love and support !

In the past , the standard was – Transfer the best, freeze the rest ! Is a freeze all policy better today ?

Vitrification

In a conventional IVF cycle , usually several embryos are generated and the best looking embryos (usually a couple of embryos ) are transferred to the uterus.  The remaining embryos are frozen and are used during subsequent embryo transfer attempts. 

How is an embryo frozen ? What happens to the embryo when it is frozen ? Freezing of embryo involves the use of cryogenic temperatures (below -150°C) and cryoprotectants
( substances which are used to protect the biological materials from damage due to freezing) .  Embryos which are frozen at such cold temperatures remain without any change in their functionality or in their genetic make-up for centuries. The embryos remain ‘frozen in time’ – metabolically inactive ! The length of time an embryo is frozen will not affect its quality in anyway.

What are the methods used for freezing embryos ?

There are two methods which are widely used for freezing embryos : slow freezing and vitrification.

The older slow-freezing techniques used a lower concentration of cryoprotectants. As the name suggests, freezing is achieved slowly, in a step-by-step manner and such programmed cooling requires costly instruments which could cool the embryos steadily by maintaining appropriate temperatures. It is also a time-consuming process and this technique doesn’t prevent the formation of ice crystals in embryos. These ice crystal can kill the embryo during freezing and thawing, as a result of which their survival rate was never optimal.

Vitrification is a technique in which the cells are cooled ultrarapidly (at an extremely high cooling rate) . It needs a much higher concentration of cryoprotectants. The advantage of vitrification is that ice crystal formation within the cells is totally prevented. It transforms the cytoplasm within the cells into an amorphous glassy state. This technique doesn’t need expensive equipment; but does require experience and expertise.

Which embryo freezing technique is the best ?

Scientific studies have showed that vitrifying embryos resulted in better embryo survival after thawing. Vitrified embryos also had a much higher proportion of intact blastomeres (individual cells of cleavage stage embryos) when compared to embryos frozen using slow freezing technique. The post-warming morphology of the embryos is excellent and the pregnancy rate and implantation rate is found to be better with vitrified embryos. All these beneficial effects are attributed to the lack of ice crystal formation in vitrified embryos which in turn prevents injuries due to ice formation. Hence vitrification is the current preferred method of freezing embryos in most IVF clinics world-wide.

Why is embryo freezing important ?

Freezing embryos helps in utilizing the extra embryos produced during an IVF cycle in an efficient manner and hence the need for discarding supernumerary embryos is prevented.  When an embryo is discarded a life that might have the potential to develop into a full-fledged baby is lost. Since we still do not have accurate technology to pinpoint which embryo will develop into a baby, discarding human embryos becomes an ethical issue. Embryo freezing helps in addressing this ethical issue effectively. Freezing embryos also alleviates the need for further ovarian stimulation cycles when an embryo transfer attempt fails. Hence the financial and physical distress associated with a new IVF cycle is circumvented. The success rate of an IVF cycle naturally increases when there are many frozen embryos available since many more embryo transfer attempts could be made.

Is a fresh embryo transfer better than frozen embryo transfer ?

Before the introduction of vitrification for human embryo freezing, fresh embryo transfer had a higher success rate. With the introduction of vitrification , this scenario has changed dramatically.  When embryos are vitrified , the success rate of a frozen embryo transfer is equal to that of a fresh embryo transfer - or is even higher. Hence the statement ‘ Transfer the best, freeze the rest’ is no longer valid today !

Why is a frozen embryo transfer better than a fresh embryo transfer in terms of IVF success rates ?

1)  Vitrification for embryo freezing has led to a better survival rate of post-thawed embryos ; in good clinics, the survival is nearly 100% , and not a single blastomere is lost as a result of the freezing and   thawing.

2)  The endometrial receptivity is found to be excellent during a frozen embryo transfer cycle. During an IVF stimulation cycle (fresh cycle) the estrogen level in the body rises too high and such high estrogen levels are shown to be deleterious for optimal endometrial receptivity. A FET simulates a better and more natural endometrial environment when compared to a fresh IVF cycle. Embryo-endometrial synchrony can also be better achieved in a FET cycle.

If this is so, then is a freeze all policy better today ?

The data from randomised trials favour frozen embryo transfer as compared to a fresh embryo transfer (although larger trials are needed to confirm these results). Kato clinic in Japan , which does about 10000 cycles per year , performs only FET for all its patients and their reported success rate is very high ! It’s high time that all the IVF clinics and patients think of freezing all the embryos obtained during an IVF cycle and transfer them sequentially so that the chance of achieving a pregnancy increases. Apart from the positive aspects of FET described above , there is one more valid reason for opting to do a frozen embryo transfer. We still do not have a valid, fool-proof technique to determine which embryo has the potential to develop into a baby. Embryos which are selected to be transferred to the uterus using microscopic morphological criteria fail to achieve a viable pregnancy many a time. Many good looking embryos fail to implant  and many poor looking embryos do turn into a much desired baby. In such a situation, freezing all the embryos and transferring them sequentially might improve the odds of pregnancy when undergoing an IVF cycle.

Hence a freeze all policy is definitely a better option today and FET will soon replace fresh embryo transfer in the near future !

So if your fresh embryo transfer did not work, do not panic. A frozen embryo transfer is no less efficient than a fresh embryo transfer. Before starting an IVF cycle it is important for you to make sure that the IVF clinic you select has an embryo freezing facility - and , more importantly , that they use the vitrification technique for embryo freezing.

"This too will pass"

It's a negative again! At this moment so many different thoughts are running in my mind but "This too will pass". Thank you for each and every wonderful person who prayed for me and did their best to keep me happy. Only all your kindness, keeps me going. 

It is hard, I did cry but I did feel peaceful within me after knowing for sure this is what it is. I haven't told my mom yet. I am gathering courage so that I can tell her without crying. Obviously she will tolerate the negative but not my sadness. I have let so many people down. I might have also shattered many of your dreams.  I have a friend who is also going through this. She told me 'Manju, if you get success it will give me lots of confidence to carry on'. Sorry! I know many people like her would have looked at my posts in search of some inspiration. Please remember-our baby making machinery is not so effective! Even couples without any problems need few months to a year to conceive. Do not take me as an example. I can show so many people who conceive with IVF/FET. There are so many people who conceive with a thin endometrium. Might be, I am just an exception who needs to fight a bit hard. I am not going to give up and every failure makes me stronger! I have 5 more frozen embryos. So hopefully when we are ready we will start the process all over again. My DH is calm and composed as always. I sometimes wish he breaks down as I do  - so that he will not accumulate the stress inside.

I still think my blasties looked so good and competent.  I failed to provide them the best : ( I just wish I accumulate enough patience, perseverance and persistence to go on with this process. As Winston Churcill said :

                  Success is going from failure to failure without loss of enthusiasm.  

Take care everyone! How much I wished I could put a picture of postive HPT in this post!!!! : ( 

Embryo Transfer

ET was scheduled to 4 PM today. It’s very hard to explain how I feel. My mom left to my native place yesterday. I feel heartbroken without her presence. DH had a hard time controlling my crying spells. I am in the grip of all sorts of blues now. I am excited and at the same time very scared. The result of all the toil will be out in two weeks. Why can’t someone make me to go into coma for two weeks? When I see my DH I feel very sorry for him. I am solely responsible for all the troubles he endures now. All this uncertainty, tension,travelling…….everything is because of me. I am very lucky to have him in my life. If he is not this understanding what would have happened to me? I feel I have a lot to vent. I am depressed probably because of progesterone. I wish I could go back to work so that I can distract myself. I am also dreading thinking about today and tomorrow. I do not believe in rest after ET but my DH will be very upset if I roam around. I have to lie down or sit all the time without doing anything and that is a big torture!

Inspite of all these thoughts, I feel very happy when I see my blasties. I hope they will wake up from their cold sleep happily without loosing any cells, snuggle within me tight and speak with my not so great endometrium for establishing connections. Let the cross-talk between my blasties and endometrium be successful! If someone reads this post send me some positive vibes. I will be very grateful. I am uploading my blastocyst pictures. Don’t they look beautiful? One day we saw a very cute little girl and I said to my DH ‘our child will look as beautiful as this littleone’. He said, ofcourse yes! Our blastocyts look very beautiful so definitely our child will look beautiful too :) These kind of small, sweet nothing talks, keeps us going!

Thin Endometrium and FET Outcome - Is there a correlation?

It is boring in hotel room and it is drizzling outside. So I am sitting in the room doing nothing. As usual, I have no mood to watch television programme. I did a short search in pubmed regarding thin endometrium and pregnancy outcome in  FET or IVF cycle. I feel so happy when I learn something new and also to update my blog with some decent information. Am I obsessed? I think I am not. When I watch TV or sit without doing anything a kind of depression sets in. My thoughts waver too much in the negative direction. I feel happy and relaxed when my mind is working, especially regarding my FET stuff and my blog. My DH is not happy about it. His accusation is that I am stressing myself too much. How will I make him understand how I feel? :(

So here we go: As always, there are two different views on whether thin endometrium affects the outcome of FET or IVF cycle. A paper in Clin Exp Obstet Gynecol.states that a 47 year old woman with an endometrial thickness of 4 mm conceived twins using donor embryos (PMID: 22268266). I do understand exceptions cannot become the norm.  But this information does give me lots of hope. My belief that embryo competency is important than endometrium thickness might be true. But my RE who has extensive experience in the field of IVF does not agree with me :) Might be my view is flawed, who knows? There is one more publication which makes me happy. You can view it here (PMID: 1513611). I could just get the abstract which states that, the largest study to date on the association of endometrial thickness and subsequent pregnancy rates following frozen embryo transfer, with the endometrium prepared by estrogen and progesterone found no improved or adverse outcome if the endometrium is too thick or thin :) I am now on progynova for a longer time. I started progynova on May 31^st and I added progesterone only on June 23^rd. So I am on estrogen supplement (increased from 6mgs to 64mgs as of now) for 24 days. I am bit uncomfortable with this long-time stimulation to grow my endometrium to decent thickness. 'Will this have an adverse effect on my endometrial receptivity? Will my endometrium quality be compromised?' These are the questions which haunt me sometimes. But my fear seems to be unnecessary. This (PMID: 16983519) paper states that long-term estrogen administration to bring the lining to a decent thickness is beneficial and does have a positive effect on pregnancy rate (infact the pregnancy rate was higher when compared to the control group!).

Now, I will also cite papers which say endometrial thickness is important and thin endometrium compromises pregnancy outcome. This paper (PMID: 22346080) states that mean endometrial thickness is significantly higher in pregnant women compared to non-pregnant.  But they concluded that ‘the mean difference between two groups was <1 mm which may not be clinically meaningful. Although there may be a relationship between endometrial thickness and pregnancy, implantation potential is probably more complex than a single ultrasound measurement can determine.’ So, they did not find a sure correlation between endometrial thickness and pregnancy rate. Another study states that in donor embryo cycles thin endometrium is one among several factors which  can compromises the cycle outcome (PMID: 15482759). This study (PMID: 17681313) says that in medicated FET an endometrial thickness of 9-14mm on the day of progesterone administration is positively associated with pregnancy outcome than an endometrial thickness of 7-8 mm :( One more interesting publication states that, in ICSI cycles (that is ART cycles performed due to male factor infertility) the endometrial thickness has no effect on pregnancy outcome while in IVF cycle endometrial thickness (where female fertility problems are involved) is a factor which determines pregnancy outcome (PMID: 8671501).

In short, studies fail to show a strong negative correlation between Pregnancy Rate (PR) in IVF/FET cycles and thin endometrium. There are several other factors which play a role in embryo implantation. The most important of it all is the age of the woman or the embryo quality.

Now after reading all this I just wish that my two little blasties have a competent genome. No matter how much I obsess nothing is going to change. Whatever happens will happen and let me face the reality with a strong heart and calm mind :)

Not a bad news afterall!

Yesterday, I had my ultrasound again, after taking 40 mg of progynova for 3 days. The uterine lining seemed to be good. It is trilaminar and Dr.Anjali said it is not at all bad. She continued saying 'ofcourse it is not super good'. So my endometrium looks average with a thickness of 6.8 and can go upto 7 when measured on a different angle. I am happy. I went expecting the worst (I read somewhere that the thickness can go down also!), so I am actually satisfied. Dr.Anjali spent some of her valuable time giving me some positive stories and some casual girly, girly (Ok, womany, womany! :) talks. I felt so relaxed and happy when I came out. When a doctor vibrates positive energy the patient becomes positive immediately. The power of doctor's words!

Now my progynova dosage has gone up even more. I am taking 64 mg! I am also eating heartily after a long time. I will again have an ultrasound on Friday. I sincerely wish my lining goes up a bit. Of course I am not expecting any dramatic improvement. I will be OK with a trilaminar lining at 7mm. The happiest happening is we are not cancelling the cycle. So, my little ones will come inside me soon. Yet we haven’t decided how many to transfer and whether to do a blast or day 3 ET.  Wish me good luck, I need a lot of it now :)

Thin Endometrium –a side-effect of calorie restriction and fat loss?

Vaginal ultrasound showing a thin endometrium

I always had great endometrial lining during all my IVF cycles (greater than 8mm, mostly between 10-12 mm). In FET cycle too there was no problem. So, what went wrong this time? Even though I can just speculate, I know deep within me that my speculation is right. I have lost lots of weight during the past 5 months. I was insulin resistant before. I had a HOMA IR (a measure of insulin resistance) of 4.1. There is no standard value for HOMA-IR. The current studies consider that HOMA-IR < 2 is normal, HOMA-IR ≥ 2 is pathological, with HOMA-IR > 4 reflecting the pre-diabetic stage. My fasting insulin was 17uUnits/ml (although a fasting insulin of 5-25uUnits/ml is considered normal, anything above 10uUnits/ml is not so good. People with fasting insulin of less than 5uUnits/ml are found to live longer). I have a family history of diabetes in my dad’s side. I was diagnosed with PCOD at the age of 25 and I am on metformin (1500mg) for a long time. I stopped metformin for the past year because of gastrointestinal problem. After stopping metformin my BMI was 26.2. I was overweight. Lack of implantation in my previous ART cycle made me to ponder what can be done to improve my chance of conceiving. The only sore point I had is my weight and perhaps insulin resistance because of it. My blood glucose was normal. I also became aware of the fact that calorie restriction has a positive impact on egg quality. This made me to think seriously about removing the excess weight. My boss is an endocrinologist. I used to discuss with him about the weight issue and ask him whether carbohydrate rich meals are the culprit. He used to say-eat anything, but eat less. I started a very strict calorie restriction diet and jogging. I limited my calories to 800-1000 for the first 2 weeks. I achieved this by intermittent fasting. To my surprise my fat deposits around my waist started to melt. After two weeks I upped my calories to 1200-1500 calories. I avoided sugar, sweets and carbohydrate rich foods. I avoided rice as much as I can. I took only 300 calories per meal. I started metformin 1000mg. I stopped non-vegetarian all together and I am not planning to eat it anymore during my lifetime :). Within 5 months my weight dropped from 68 kg to 61 kg. The best point is I lost all the excess fat. For the first time I had a flat stomach. My energy levels improved. I can skip a meal easily without any trouble. I attribute it to my lowered insulin levels. In short I felt great. Received mixed comments from friends. Some are worried. They said I have lost the charm. But my DH is happy. He said I looked better now. I am happy too :)

Everything sounds good, right? Then, where lays the problem? Calorie restriction is good. It was found to prevent aging in experimental animals. It also delayed egg cell aging and extended fertility in experimental mice. Metformin is a calorie restriction mimetic too. It can also improve egg quality (both by preventing egg cell aging and by decreasing insulin levels). I do not think short time calorie restriction will have any effect on egg quality in humans. If calorie restriction is started in 20s it might extend fertility into your 40s. The same is true with metformin usage. Long term metformin intake can preserve egg quality via preventing genetic defect accumulation, while short term intake can increase egg quality by decreasing insulin levels. It was found that exercise and weight loss is much effective than metformin in decreasing insulin levels. So bringing down your weight at any point of your lifetime will have positive effect on your overall health by decreasing insulin, glucose and harmful triglyceride levels. This will keep your hormones balanced which is necessary for optimal fertility. As a result egg quality (not genetic but physiological parameters) and  endometrial health improves. Consider calorie restriction if you are suffering with infertility due to overweight and PCOD (high insulin!).  Reduce your weight through calorie restriction and proper exercise. Continue exercise regimen and increase your calorie intake for maintaining the appropriate weight. BUT never do calorie restriction when you are on fertility medicines, if you are underwieght or when you are trying to conceive.  Never be on very restricted calories (less than 1500 calories) when you are trying to conceive. This is the mistake I did this cycle. Even after starting fertility medicines (progynova) I continued with fewer calories. Lesser calories actually signal your body to go into the survival mode (during which only minimal bodily functions are maintained). Reproduction is an extremely energy consuming process. Once your body senses that you do not have enough calorie supply (as in times of food scarcity) it switches on mechanisms which  prevents energy expenditure. It tries to switch off high energy demanding functions like reproduction. In short all the anabolic activities which require high energy are switched off and catabolic processes which produce energy are switched on. Since I took less calories my estrous cycle is severely affected leading to poor endometrial development. My body in short doesn’t want to get ready for performing reproductive function.

I got this information from a website:

Reproduction: Feeding the reproductive cycle

Energy metabolism is known to affect reproductive cycles, acting as an evolutionary oversight to ensure that reproduction occurs only in favorable nutritional conditions. A recent study characterizes a mechanism through which the liver integrates metabolic responses to control ovulation (Cell Metab. 13, 205–214).

Investigating the link between estrogen and food consumption in mice, Sara Della Torre and colleagues found that caloric restriction decreased hepatic estrogen receptor-α (ER-α) activation in the liver and arrested estrous cycle progression. Interestingly, amino acid supplementation was sufficient to rescue mice from this metabolic block of the estrous cycle.

The authors found that ER-α activation led to increased hepatic expression of insulin growth factor–like-1 (IGF-1) and increased the amount of circulating IGF-1. Increased IGF-1 expression was required for E2-induced proliferation of uterine lumen epithelial cells and for estrous cycle progression in vivo.

The findings highlight a crucial role of hepatic ER-α as an integrator of metabolic and reproductive functions. The exact mechanisms by which IGF-1 and E2 promote progression of the estrous cycle remain to be determined, but this study might provide insights into infertility conditions, especially those linked to metabolic dysfunction. 

On the other hand there must be a connection between fat reserve and estrogen function. It is known that estrogen is stored in fat reserves. I have read that people who are obese are prone to estrogen sensitive breast cancers. Overweight people are also more prone to endometrial cancer. You need healthy fat reserves for your estrogen to function properly. Dr.Malpani sent me the Frisch hypothesis paper which talks about the connection between body weight and onset of menarche.

In short I learned a lesson which is invaluable. Do not change your diet or exercise regimen extremely during IVF or FET cycles.  Do not loose weight especially fat reserves when undergoing fertility treatment. Increase your intake of healthy fats. Do not restrict calories. The above said are very important for proper functioning of your reproductive harmones which intrun is important for your treatment success.

Another interesting information to ponder : In certain regions of south India, daughter-in-law who enters husband's home for the first time, after marriage, is given cow's colostrum. Perhaps a nice way of preparing her to carry their generation :) Milk is know to increase IGF-1 levels. When I say this I do not want to make IGF-1 master of all reproductive functions, just a note because I am talking about IGF-1 in this post. Our ancestors do have lots of wisdom :)

Stupid me ! Dr said –don’t beat yourself up! He asked me to read ‘Shoulda, Woulda, Coulda’ :). I will try not to regret. Hopefully G-CSF works and perhaps everything happened for my good :) Otherwise I will not have had a chance to use G-CSF which is supposed to increase pregnancy rates atleast in a couple of studies :)

In Bombay for FET

We came to Mumbai two days back. A heavy downpour welcomed us! Every time I enter India, for a day or two, a kind of depression sets in instead of happiness. I feel as if I am waking up from a pleasant dream. The reality slaps me hard. I live outside India for 7 years. The country where I live now is clean, sparsely populated, rich and comfortable. The first thing that makes me vexatious when I reach India is the dirty environment. Mumbai is the financial capital of India, and no need to say how densely populated it is. The dust, unruly traffic, dirt and poverty made me wonder why there is so much discrepancy between two countries. I saw a family of three; husband with torn clothes, wife with the dirtiest saree you can ever imagine and a newborn lying nearby them - all three are resting inside a shed of tarpaulin, on an elevated mound, which is found in between two parallel roads! I could clearly read the worry on their faces. They must have been living in platform and the heavy rain made them to panic. When I saw it, how much I wished I could just go back to Germany and imagine that life is hunky-dory everywhere! If you accuse me of being selfish – I AM. I am selfish to the core. I need the comfort which Germany gives me. I need the clean environment. I need the calm working atmosphere and I badly need the money for our baby-making journey. I am helpless, truly helpless. Every time I come to India my conscience kills me. I feel guilty for being comfortable, for being self-sufficient moneywise, for living in a clean environment, for attempting to create a costly baby when many road-side children are living in the footpath. Wait; do not judge India by what you read just now. This is just one half of the story. When I see such extreme poverty on one side, I also see supreme richness too. Costly cars, branded clothes, dining in five star hotels and lavish spending-this is also the way of life for many in India. Why is Indian society too unbalanced? Are these the result of evil caste system which we created long back?  

Do not form an opinion about me from what you read in the previous paragraph. I am not trying to project myself as a simple person with great social responsibility. I am a very normal and self-cantered woman. All the above said guilty feelings usually vanish from me in 24 hours. I get used to the way of life in India. I do walk past the hungry, homeless road-side children and enter into a mega shopping area to satisfy my shopping spree. My guilty feeling vanes away day by day until it becomes negligible. I indulge myself in all normal worldly pleasures ignoring the sufferings around me! Sometimes I wish I was non-existent or I wish I had the power to change every misery around me. But at the age of 34 I have learned that life is not fair. If I have to remain sane and serene I should surrender to the fact that life is unfair. As a human, I am trying my best to be compassionate and kind to my fellow beings. I try to lend a helping hand to the needy whenever I can. I also try to keep in mind the serenity prayer which Dr.Malpani taught me:

God, grant me the serenity

To accept the things I cannot change,

Courage to change the things I can,

And wisdom to know the difference.

This serenity prayer was written by the theologian Reinhold Niebuhr.

So coming back to the original story - we are doing a FET. We have 7 embryos left from my last ICSI cycle (5 day 3 embies and 2 blasties). I am happy to see Dr.Malpani and his team. Dr, understood that I am the anonymous person who leaves crazy comments (sometimes good ones too!) in his blog. All his staffs are very friendly as usual. Dr.Anajli Malpani is  cute and pleasant as always.

I took 6 mg progynova for 12 days and had a vaginal ultrasound on 11.6.2012 to check my lining. Dr.Malpani was not so happy about my endometrial thickness. My lining was only 6 mm. He increased my progynova dosage to 16 mg. I am going for an ultrasound today. I wish my lining has grown at least a mm by now. I have no EWCM even after taking such a massive dose of progynova. Does it mean anything? I do not know. I am worried and I started to write this blog post to calm my anxiety. I will update after today's scan what actually is the next course of action, and I would also like to speculate in my next post why I ended up with a thin lining!