From 3 eggs at the age of 29 to 24 eggs at the age of 33!

How many eggs will I lay, sorry : ) how many eggs will they retrieve from me is the most important question in my mind during all my IVF attempts.  I have thought about my eggs more than anything else after my marriage. When we started our journey to conceive; I would tell my DH, ‘I think today my egg will be released, I have all the signs of ovulation’. I will be saying it very seriously and with a determination to catch it and make a baby out of it : ) (poor DH!) He will respond with the most innocent face ‘Manju, why can’t you make an omelet out of that for me’ : ) I will break into laughter. These kinds of “eggie talks” have become a part of our life after starting TTC.

The most important question which lingers in the mind of many women who are undergoing IVF is - why didn’t I get more eggs during my IVF cycle? When I started my IVF journey I was young. I saw so many young women (even some 35+ women!) in infertility boards reporting that they got more than 20 eggs. I am so confident of my ovaries : ) I thought, I am only 29 and my problem is just fallopian tubes; I am a great candidate for IVF and for sure I will produce so many good quality eggs and will be successful very soon. I have read that young women with fallopian tube blockage are the best candidates for IVF and they get success very easily. With so much confidence in mind I started my first IVF cyle. My RE in Germany was too cautious. He started my ovarian stimulation regime with 112.5 iu of Gonal F! Each successive ultrasound for monitoring follicle development shrivelled up my hopes of getting large amount of eggs. After a week or so of stimulation my RE increased the dosage to 150 iu of Gonal F. There were only very few follicles developing and I was really worried. I was not prepared for such an outcome. When I asked my RE why am I responding so poorly to stimulation; he replied very coldly ‘it's your ovaries; how will I know?’(Great answer!).  When I didn’t get a proper reply from him I searched the internet for answers. I will always be grateful to the women in infertility boards who patiently answered all my questions and put my mind at ease.  I ended up with only 3 eggs during that cycle. Out of the three eggs only one fertilized via IVF and that lone embryo was only 4 cells on day 3 of fertilization. I felt so happy to see that single embryo – my first embryo sighting experience!

The next four cycles in Germany lead to the collection of 9, 5, 8 and 5 eggs respectively. I thought that the second IVF cycle was a bust too! Out of the 9 eggs retrieved 7 were mature. Since only one out of three eggs was fertilized during my 1^st IVF, my RE suggested that we should try ICSI. We agreed. But I could not accept the fact that my eggs and his sperms cannot even make love in a petridish without help :). I had a notion that IVF is more natural than ICSI. So I came up with an idea. I told the embryologist ‘please keep 3 eggs for normal fertilization (IVF) and do ICSI on the other 4 eggs’. He looked at me strangely and asked ‘do you think that will make a difference?’ I had no real answer but just nodded my head affirmatively. The day after egg retrieval I have to call the embryology lab to get the fertilization report. To call the embryologist and to take the fertilization report is the scariest part! The thought that there were only few eggs and the possibility of complete fertilization failure or any other unfortunate happening haunted me all the time. My heart used to race during those few minute conversations with the embryologist. The day after my egg collection I called the embryology lab for getting my fertilization report. The embryologist said ‘only two of your ICSIed eggs fertilized and there was no fertilization in the eggs which were kept for IVF’. I cried! I could not believe that I have only 2 embryos from 7 eggs. I kept on blaming myself for opting to use 3 eggs for normal fertilization. After the initial crying spell, I was happy that I had at least those two embryos. This is the first lesson my IVF journey taught me – always try to look at the positive side of the story and be happy! When I talked to my doctor he said, ‘come on Friday (which is actually day 2 of fertilization) we will transfer those two embryos’. I told my husband ‘anyhow they cannot select embryos after cleavage (in Germany, embryo selection after cleavage is prohibited by law!) that is why God has selected himself and gave us only two embryos.

I am so happy the day I saw those two perfect four celled embryos! They looked 100% perfect. The embryologist was beaming with pride. He said that my embies looked picture perfect. My hope was high again after the initial tragedy. After transfer I rested for 5 minutes and left the clinic. You know what? One of those 4 celled embryo was actually a fighter – it implanted in my uterus! I always think of that little one. Even though it didn’t become a full-fledged baby (I lost my precious baby at around 7- 8 weeks); that embryo is the one which keeps my hopes high even after undergoing 6 further futile embryo transfer attempts!

I think I have deviated a lot from the original topic. Now back to the topic - why some women get fewer eggs and some more?

As the women age their ovarian reserve gets depleted. Depletion of follicular reserve begins during foetal life and continues throughout a woman’s life.  At around 20 weeks of gestation a female foetus carries 7 million follicles and during menopause (approx. 51 years later) it is reduced to a few hundred. So younger women are expected to produce more eggs and older women tend to produce fewer eggs. PCOD otherwise called as Stein-Leventhal syndrome is a collection of metabolic derangements. Ovaries of women with PCOD produce excess androgen (male hormone) and they might also have more insulin circulating in their body. Women with PCOD have very high antral follicle count (AFC) and hence they produce lots of eggs when stimulated with gonadotrophins. Women, who undergo premature menopause at a younger age, will have very less AFC count, increased FSH and low AMH. They produce less number of eggs too!

Is poor ovarian reserve an indicator of poor egg quality ? The answer is yes as well as a no! When women get older, their ovarian reserve decreases as well as their egg quality. But younger woman with less ovarian reserve can produce good quality eggs. AMH, FSH and AFC are all indicators of ovarian reserve. If a younger woman has higher FSH, low AMH and AFC her chance of producing good quality eggs and embryos is as high as her similar age counterparts. That is why young women with premature menopause are more successful in getting pregnant via IVF when compared to older woman who have low FSH and high AMH. The message here is age of the women is the best indicator of egg quality and not their AMH or FSH.

What helped me to get 24 eggs in my 6^th IVF cycle?

I made two important changes during my 6^th IVF cycle. I was advised to take DHEA (75 mg) by Dr.Malpani.  I started to take it regularly. I took it for 9 long months. The good thing is, I never had any bad side-effects. On taking DHEA I started to ovulate regularly. I had lots of fertile quality mucus during my ovulation time. I also had ovulation pain which is very prominent. People say DHEA can give them bad hair days. I never had problem with my hair. I should say my hair fall was reduced when taking DHEA.  Please visit CHR (Center for Human Reproduction) website for further details. DHEA was found to increase oocyte production (PMID: 16169414). The mechanism behind it is not so clear. DHEA is used in mice to induce PCOS phenotype in previously normal ovaries (PMID: 16514202). DHEA supplementation was also shown to decrease embryo aneuploidy (genetic defects) (PMID: 21067609)

The next change I made was to stop taking metformin (1500mg). I was on metformin from the age of 26 years. I was diagnosed as having PCOD using ultrasound pictures of my ovaries. My ovaries had a characteristic pearl-like structure. I also have insulin resistance. When I started taking metformin I started to ovulate regularly. I lost weight and felt a lot better. Metformin is found to have anti-cancer and anti-aging properties. It is also touted to prevent or postpone diabetes in PCOD women who are prone to it. So from the age of 26 I was on metformin. I never had a second thought about it. I never thought it can reduce my AFC count and can lead to less egg yield during my IVF cycles. Metformin can reduce your AFC count. A scientific study showed that one week of low-dose metformin therapy can bring down your AFC count (PMID: 17224152).  A recent publication which studied IVF cycles among PCOD patients with and without metformin administration showed that the stimulation length and gonadotropin doses were significantly higher in metformin group than in control group.  The number of dominant follicles on the day of ovarian maturation triggering and peak oestradiol levels was significantly lower in metformin group than in control group (PMID: 21770836).

I believe these two changes (taking 75 mg DHEA and stopping metformin) made a big difference in the egg yield during my 6^th IVF cycle. To be exact, I had suppressed my bodies PCOD tendency using metformin. So by stopping metformin and starting DHEA (which is a PCOD mimetic) I was successful to coax my ovaries to produce more follicles and hence more eggs. After 9 months of DHEA intake and stopping metformin my AFC count increased form 7-9 to 18-20!

Moral of this story is .......

If you are a woman who is having diminished ovarian reserve please try DHEA. It worked for many, might be it works for you too. Metformin is a wonderful drug. It really helps woman with PCOD and insulin resistance. If you are young, have excellent FSH and AMH value, have extremely high AFC count, if you are overweight – metformin is for you. It can reduce your insulin levels and thus can help with improving egg quality. It can prevent OHSS by reducing AFC count. If you have extremely high AFC you are prone to develop several follicles in response to gonadotrophin stimulation. More the number of growing follicles, higher will be your estrogen levels. A higher estrogen level is a risk factor for developing OHSS. But if your are a woman who has less AFC count, higher FSH, lower AMH and normal BMI metformin will not help you. I do not think it can improve egg quality in such woman and it can even lead to cycle cancellations by reducing your ovaries response to gonadotrophins! 

Update on endometrial ultrasound and G-CSF

I had a vaginal ultrasound yesterday to check for my uterus lining. Not so good news again! After 2 days of 16 mg estrogen (8 progynova tabs) my lining has grown from 6 mm to 6.7 mm. Dr. Malpani suggested that I should have neukine infused into my uterus. Neukine or Filgrastim is nothing but Recombinant Human Granulocyte Colony Stimulating Factor. It is sold under the brand name Neupogen in USA. It is a drug or a cytokine actually sold to prevent decrease in neutrophil count during chemotherapy which causes myelosupression. Decrease in neutrophil counts is called neutropenia and it is accompanied by fever. It causes the patient more prone to infections. Recombinant G-CSF causes a dose-dependent increase in circulating neutrophil counts thus preventing spurious infections in patients receiving myelosuppressive chemotherapy. What does G-CSF has to do with endometrial growth? Please visit this Center For Human Reproduction link for further information. Here is the blog post of Dr.Malpani regarding thin endometrium and the use of G-CSF to improve it.

So today I received an infusion of Neukine inside my uterus. Keeping my legs in that evil stirrup is uncomfortable. Dr.Malpani eased my tension by chatting with me. Still no signs of high estrogen in my body but I wish my endometrium responds well to Neukine giving me a nice, plump lining where my embies can snuggle in and start establishing contacts with me. Mumbai is great, I am very happy today. I will update about my Mumbai adventures soon.
Somemore interesting reads on G-CSF:
http://badplumbing.kurvy.com/2010/12/g-csf-the-last-frontier.html
http://clinicaltrials.gov/ct2/show/NCT01202656