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

The much awaited fertilization report

Blastocysts which were frozen on day 6

Growth arrested embryos

This post is going to be easy for me. I will just copy and paste Dr. Sai’s emails.

On day 1, I had 15 embryos. I guess one egg matured in the lab, so there were totally 15 mature eggs out of 19 retrieved, and all were in the 2 PN stage on day 1. This means all ICSIed eggs fertilized, a 100% fertilization rate! This is just awesome and clearly shows the technical expertise of Dr. Sai.

The Day 2 gradings of your embryos are as follows:

2x 5-cell grade A

4x 3-Cell Grade A

6x 2-Cell Grade A

3 Embryos got arrested at 2pn Stage.

There are total 8 Top Quality Embryos on day 3.

Day 3 Grading is as follows:

5 x 8-cell grade A

3x 7-Cell Grade A

1x 6-Cell Grade A

1x 5-cell Grade A

3x 4-Cell Grade A

Day 4 Grading of your Embryos as follows:

3x MORULA

6X 8-CELL Grade A (COMPACTION OF CELLS SEEN)
.

2X 6-CELL Grade A

1X 4-CELL Grade C

Day 5 Grading of your embryos as follows:

1x blastocyst grade 1AA

1X EARLY BLASTOCYST

6X MORULA

2X 8-CELL Grade A 

1X 6-CELL Grade A

1X 4-CELL Grade C

Day 6 (One must keep in mind that, on day 1, fertilization of eggs were done during late evening!)

We are Freezing Total 6 Blastocysts today on day 6.

All morulae Stage Embryos have Become Blastocysts.

Although Exp Blastocyst in image Cap1020 doesn't have great Trophectoderm (the last blastocyst in the above collage) we are freezing it becauze it has got a good Inner Cell Mass.

Altogether I got 7 blastocysts out of 12 cleaving embryos, this means 50% blastocyst formation rate. This is  a great result ! Normally women below 35 years old can expect a blastocyst formation rate of 40%

I am already getting queries regarding how it was possible to get so many eggs. I have no clue too. My AMH was infact low but my AFC count was high. Honestly, I didn’t expect such a good outcome. But, I had lots of faith in Dr. Malpani’s team. Dr. Malpani designed the protocol, Dr. Anjali monitored me very closely and decided when to give the trigger shot, ofcourse, as always, she did a great job during egg retrieval, Dr. Sai was excellent in doing his part of the job and my ovaries cooperated too well! I didn’t take any supplements. Two and a half years ago, when I had my first IVF cycle with Dr. Malpani’s clinic I took DHEA 75mg for 6-7 months and I thought might be DHEA helped me to get many eggs. But this time I took nothing and I do understand now that DHEA might  not have contributed to the improved outcome previous cycle. My first five cycles which I had in Germany were terrible (http://myselfishgenes.blogspot.in/2012/05/my-ivf-journey-timeline.html). I was much younger at that time, had great AMH value, yet, I had only very few eggs to work with.In short, I am very thankful to God and to everyone who helped me to get 7 blastocysts. In the beginning, prognosis of this cycle looked very bleak, but it ended up much pleasant and successful than expected.

There were 6 blasts frozen on day 6. What happened to the remaining one? :) Was it transferred to Rita and what happened thereafter? Keep reading ! :)

Dr. Sai was kind enough to provide the pictures of embryos which got arrested during its development. I have given the pictures of blastocysts frozen on day 6 and the ones which stopped growing in the above collage.

AMH, Vitamin D and my ovaries!

An AMH value of 0.6 ng /ml is bad, really bad. In the report I got in hand, it was written that, an AMH value of less than 1.6 ng/ml might indicate a poor response to ovarian stimulation. I was heartbroken and angry; my reproductive life is nearing its end! I expected it, but I didn’t expect such a drastic fall in my AMH. After I returned home with the results, I called Rajender. He was cool as a cucumber. He said, I read about women who produce eggs even with much lesser values. I was irritated by his positivity; I thought, why won’t he leave me in peace, take an alternate solution (donor eggs) and move on. I had no energy to argue with him or break his enthusiasm. Dr. Malpani gave me one more suggestion. He asked me, from which lab did you measure AMH. I told him that I got it measured from Thyrocare. He replied, Thyrocare is not so reliable, please measure your AMH again from SRL (Ranbaxy)! I was not hopeful, but I was badly in need of a miracle. I gave blood to SRL for AMH and Vitamin D measurement and waited for a couple more days.

From now on, this post will turn a bit more scientific.  Many of you might wonder why I measured Vitamin D along with AMH. Is it necessary? What is the rationale behind that? There is a connection between Vitamin D and AMH. AMH gene (the sequence of our DNA which codes for AMH protein) has a Vitamin D-response element (a region which is responsive to the presence of Vitamin D in a positive manner). To put it in a more simple way, Vitamin D can bind to the AMH gene and increase its expression.  If this is so, can low Vitamin D level lead to low AMH levels in blood? When they initially found the presence of Vitamin D-response element in the AMH gene of prostate cancer cell line, frenzied researchers, as usual, hyped out of proportion the importance of Vitamin D in reproductive biology.  Their understanding was and still is, if high AMH levels in blood indicate good ovarian reserve, increasing AMH levels by increasing Vitamin D intake, especially when one is deficient,  (since Vitamin D could increase AMH level) will lead to good ovarian reserve too. What a simple way to solve the problem of poor ovarian reserve! Just pop in Vitamin D, and the problem will be solved! But, this kind of (il)logical reasoning without understanding the basics of the science of AMH is half-witted! To read more about the science of AMH please refer to:  http://myselfishgenes.blogspot.de/2012/08/amh-paradox.html

It is true that Vitamin D could increase AMH levels. But increasing the expression of AMH from the already existing follicles (antral follicles) cannot increase ovarian reserve. More antral follicles lead to more AMH production, but increasing your AMH levels artificially (either by taking substances which increase AMH production, like Vitamin D, or by injecting AMH into your body) cannot increase your ovarian reserve. Actually, increasing your AMH level artificially, could lead to opposite effect - high AMH can decrease the amount of antral follicles available for FSH stimulation. So, if you are having poor ovarian reserve, taking Vitamin D is unlikely to help and in worst cases it can bring down your antral follicle count (AFC) too.  In case, if your Vitamin D levels are low, or if you are Vitamin D deficient, your AMH levels might be artificially lowered even though your ovarian reserve is good (there is no solid proof for this statement!). And, this is the reason I measured my Vitamin D levels too when measuring AMH. 

After two days, I got my blood test reports from SRL. My AMH level was 1.6 ng/ml and my Vitamin D levels was 17ng/ml, while the minimum recommended Vitamin D level in blood is 20ng/ml. Need not to say that I was happy and hopeful again.  A value of 1.6 appeared very great when compared to 0.6.  My thoughts used to wander, and I would wonder, which lab result is correct! But, as per natural human tendency, my mind decided to stick with the more promising value.  I had only 12 more days for starting the stimulation. I was waiting for my periods so that I can measure my antral follicle count (AFC). I knew well that, AMH value could only be interpreted sensibly with antral follicle count (AFC). I was afraid, yet eager to know my AFC! I was wondering, what if there were only few antral follicles left!

You might ask whether I took Vitamin D to correct my deficiency. Again, I have a very different view of the whole Vitamin D story. I was in India, I was getting ample sunshine. I had no signs of Vitamin D deficiency. I read somewhere that 99% of Indian population is Vitamin D deficient. This kept me wondering! If 99% of Indians contain a particular range of Vitamin D in blood, then, which is the normal range for that population ( whether the value which occurs in 99% or the one in the remaining 1%) ?  There are not enough studies to show the normal range of Vitamin D for a healthy, Indian population. No one still knows how Vitamin D is processed by our body. People who live in places where sun light is meager, must have or must need mechanisms to store Vitamin D in body, so that they can utilize it during days where sunlight is not available. But, do people who live in tropical regions like India have such mechanism? If not, then what should be their normal blood levels? Nobody has the answer for these questions. After, all the initial hype about Vitamin D, and connecting its deficiency to almost all the diseases in the world, researchers have recently started to understand that, measuring Vitamin D or supplementing Vitamin D to a healthy person is not advisable. As more randomized clinical trials are performed, the results of such studies shows that there is no benefit of Vitamin D supplementation whatsoever, and some studies even showed a negative effect (17% increase in kidney stones!).  For further reading: To [Vitamin] D or Not to D? That Is the Question. After considering everything, I decided to not take Vitamin D. Since I had only 12 more days to start the stimulation, I was too chicken to change anything in my body drastically! Vitamin D has the ability to change the expression of 3000 different genes (not only AMH!) in our body and I didn’t want to take any invincible risks.

My periods arrived after making me to panic a little! Have you ever noticed this - when you don’t need it, it comes on time and when you are waiting for it there will be no sign of it? I went to a nearby scan center to have my antral follicles counted on day 3 of my menstrual cycle.  I was too nervous. I entered the scanning room and there stood a lady doctor and her assistant. I told them that they must measure my antral follicle count, ovarian volume and make sure my uterine lining is thin and the cavity is free from any abnormality. She asked me where the doctor’s prescription was. I said, I don’t have one, I do my IVF in Mumbai and my Dr emailed me that I should measure all this. She looked at me uninterestingly and said, we do only follicle tracking studies. I had no energy to argue with her or teach her about IVF and the importance of measuring AFC! She was not ready to hear any of my lectures too; there were so many people waiting outside. She was still looking at me as an unwanted intrusion. The assistant was smirking. I felt so helpless and then I literally pleaded them, please do what I say. Since I have to do IVF, I need all these details. I must say that the scanning machine they had was excellent. The lady doctor counted my antral follicles. Unable to control my curiosity, I asked her, do I have antral follicles. She said 8 on one side and 10 on the other. I was so happy; I forgot how they behaved with me. With a broad smile I thanked them and came out, ignoring their strange looks. I waited for some time to get the results in hand. From the beautiful picture of my ovary they gave me, I counted my AFC once again. The result read: one of the ovaries is bulky – possible PCOD! I was too happy to have PCOD or anything that could give me more follicles and more eggs. I thanked my ovaries. Immediately after reaching home, I conveyed the results to my hubby and Dr. Malpani. I started to eagerly look forward to go to Mumbai- our happy vacation after staying away from each other for so long !

Beginning of our 7th fresh IVF cycle

Every IVF cycle is like a roller-coaster ride – they are scary as well as exciting! As you get used to it, you will learn to enjoy the fun and suspense. Beware, it can be addictive too! I wonder whether women (including me) who go through IVF get addicted to the thrill of it.  I find no other sane explanation for going through it again and again. Of course, the urge to reproduce, to propagate one’s own genes, does play a major role in going through this insane IVF journey. Few months ago, I was so sure that, I will never go through a fresh cycle again. I was in so much pain and everything appeared scary. But, spending some time in India, in the warmth of loved ones was enough to get back the Manju I lost. Thinking of crossing the bridge was fearful, but when I came near it, I got the courage to do my best.

I wondered and wondered why I wanted to use donor eggs in the first place. There were several reasons. This IVF journey is eating up our normal life. All we are doing for several years is to wage war against infertility. I think, we forgot, how a normal life would be! On the other hand, I would rate our life as very interesting when compared to most other people. It is painful at times, but extremely challenging too. We learn a lot about life because of our infertility struggle. I thought, we have learned too much already (which is not too good too :), and I just want this struggle to end as quickly as possible in a pleasant manner, so that we can move on to the next stage of life. I am already 36, and one of my biggest fears is, the possibility of high risk of miscarriage and begetting a child with genetic defect when using my own eggs (although still the possibility of such happening is not extremely high!) I thought, if using donor eggs could reduce miscarriage rate and give us a higher change of having a healthy baby, why not go for it? Afterall, I and Rajender want a baby to make our life more interesting, we badly want to nurture our parenting instinct before it vanishes with age. You might ask why not adopt then, we tried. We did go to an adoption agency in Madurai (Grace Kennet foundation) to collect details. When we asked about international adoption, the response was, it will take many years. For domestic adoption, we have to live in India for a year and then we are eligible to apply for adoption. If we apply, it might take another couple of years to actually finalize the entire process! Rajender went with so much expectation and when we came out of the adoption agency I could see his forlorn expression. After we lost our twins, the longing to have a little one in our life as early as possible is very high for Rajender too.  He was able to quench his paternal instinct by the company of little ones in our family and immediate neighborhood.  

I started preparing for another ovarian stimulation. Dr. Malpani asked me to measure my AMH and AFC. Two and a half years before my AMH was 1.8 ng/ml. I was wondering what will it be now! When I started my IVF journey it was in between 4.5-3.5 ng/ml. One fine morning, I went with my mom to a nearby lab (Thyrocare) to give my blood for measuring AMH. I also asked them to measure my Vit D and TSH. I waited for the results anxiously.

I called Rajender and told him not to expect much out of this IVF cycle. I said, I am much older now and I have no idea how I will respond to stimulation. Perhaps, I might produce only a few eggs. Might be, we will not have enough embryos to grow to blastocyst stage. Who knows, I might not respond at all! I told him, be prepared for everything. He knows about me and how negative I could get. He thinks I am pessimistic, but I think I am cautiously optimistic and it helps me a lot to accept whatever comes my way.

Two days later my AMH results came. As I expected it was such a poor value. When I sent the results to Dr.Malpani, he sent me a sad smiley in return! My Vit D was 12 ng/ml and the normal range was 20 ng/ml (and this is after my skin enjoying lots of Indian sun!)

MY AMH WAS A MERE 0.6ng /ml :(

I have very low AMH and high FSH, should I use my own eggs or donor eggs?

I come across this question very frequently.  I would really wonder how to answer this because the person who asks this question is trying to make a very important, life-changing decision, which will determine their fate. I will not have any idea about their personal circumstances too (their financial strength, family and social pressures so on).  Recently I received one such query and I answered it in the following way. Hope it helps some of you to decide.

I have very low AMH and high FSH (poor ovarian reserve) should I use my own eggs or donor eggs?

Let me explain using an analogy. You have a basket (ovary) with balls (eggs) which are of two different colors, green and red. Assume that green balls are good eggs and red balls equate to genetically defective eggs. You are going to play a probability game (IVF cycle) in which you are going to blind-fold your eyes (no way of selecting only genetically normal eggs) and pick balls from the basket. You win if you pick more green balls. A young woman with a normal AMH and FSH will have more balls in her basket (more eggs in ovaries) and you will have less balls (number of eggs in your ovaries will be less because of poor ovarIan reserve). The probability of getting green balls from your basket becomes less if you have poor ovarian reserve as a result of advanced maternal age (older women will have more genetically abnormal eggs when compared to young women). If you are of young maternal age, suffering with poor ovarian reserve, the number of balls you can pick from the basket becomes limited as the total number of balls available for selection is less too.The game gets too complicated if you have to pick up green balls with your eyes closed (there is no fool-proof technology to select only genetically normal eggs) and transfer the balls safely into a narrow mouthed container situated nearby you (this equates to picking up good eggs, fertilize it, grow it safely into embryos in the lab and transferring it to your uterus). Even if you are successful in picking up the few green balls (very few good eggs available) there are so many other variables which determines IVF success like:  the sperm should fertilize the egg; there must not be any inadvertent lab errors;transfer to the uterus should be perfect; and your uterus must be receptive enough; hence your chance of IVF success decrease drastically. But a young woman with a normal AMH and FSH will have a high probability of picking up more green balls from her basket (presence of more eggs and more genetically normal eggs too) and hence her chance of success is high (in IVF).  If you are extremely lucky you might pick up the green ball (good egg) in your first IVF attempt and if all goes well the embryo created out of it might implant and may develop into a healthy baby. Such miracles do happen but very, very rarely (because the probability of getting a genetically normal embryo is less in your case !) If you have money, patience and determination you can play the IVF game for 'n' number of times with the hope that it will click one day. You might find success in the next attempt with your own eggs or after 10 attempts or never ! Now you have to decide whether you will go by luck or by scientific evidence and knowledge!

Good luck for whatever you decide. If I were you I will put my knowledge first and try to have a baby with donor eggs. Any baby you love will be yours and by doing this you give your husband a very good chance for propagating his genes. There is a technology available to select genetically normal embryos but again you need more eggs and eventually more embryos so that it will be easier to find couple of good embryos from the cohort.

NB: If the woman who ask this question is of younger reproductive age (less than 35 years), her chance of success is better (only slightly) than a woman of advanced maternal age (35 and above aged woman). Her chance of success is slightly better because her egg quality might equal to that of women of her age.  But her success rate cannot equal to that of women of her age since she is running out of eggs and the chance of success is better in IVF if there are more eggs to work with ! What if, if the woman is of advanced maternal age but with normal ovarian reserve (good AMH and FSH value)? Unfortunately her chance of success is not any better than a woman of her age. This is because eventhough she has good ovarian reserve, with age, her egg quality declines irrespective of the quantity. So her chance of success will not be equal to that of a younger woman with normal AM H and FSH value.