Friday, July 10, 2009

Bad eggs as a cause of unexplained infertility

For about 10% of infertile couples we cannot determine what the reason for their infertility is. The diagnostic label we use for them is unexplained infertility, which just means that we cannot provide an explanation as to why they are infertile. For many of these couples , we have now found that the reason for their infertility is poor quality eggs. This can often be a difficult diagnosis to make; and it is one which is often overlooked by many gynecologists , especially when the woman is young and has regular cycles.

Some women with poor quality eggs have poor eggs because they have impaired ovarian reserve. Every woman is born with all the eggs she is ever going to have in her life; and as she gets older, she keeps on depleting her ovarian reserve until she becomes menopausal. However , for at least 10 years before reaching the menopause , her egg quality declines, so that she has enough eggs to produce enough hormones to get regular menstrual cycles, but not enough to make a baby. This is called the oopause. Since her cycles are regular , this lulls her - and her gynecologist - into a false sense of security. The good news is that we now have accurate tests to check ovarian reserve. These include a high-resolution vaginal ultrasound scan to check the antral follicle count; and a blood test to check the levels of AMH , or anti-Mullerian hormone. A low antral follicle count and a low AMH level both suggest poor ovarian reserve. In these cases the problem is that we have to technology to make the diagnosis but the diagnosis is not made properly because of a lack of awareness.

There is an other group of women , who have apparently normal ovarian reserve, but poor quality eggs. The group is much more frustrating to deal with. It is only when we do IVF or ICSI for these women , that we find out that they have an egg problem. Let me explain.

Some of these women will grow eggs poorly in response to superovulation. Such a poor ovarian response is a marker for poor ovarian reserve. Unfortunately, they have a normal antral follicle count and normal AMH levels, which means this diagnosis is made only after the IVF superovulation has started.

The third group is perhaps the most difficult. These are women who grow a sufficient quantity of follicles in response to superovulation ; and have high estradiol levels as well. Egg collection is usually uneventful ; and the doctor often retrieves 8 to 16 eggs for them. If IVF is done, when the fertilization check is performed the following day, much to the embryologist’s surprise and the patient’s dismay , it is found that the fertilization is very poor even though the sperm are fine and actively motile. If ICSI is being done, the embryologist often finds that the eggs are morphologically normal ; or are very fragile. For example, these eggs have granular cytoplasm ; or vacuoles in their cytoplasm ; or dark areas within the cytoplasm. Since normal eggs are simple spherical formless blobs, these subtle cytoplasmic abnormalities are often missed or overlooked. The embryologist may also noticed that the eggs are fragile, and the cell membrane offers little resistance to the injection pipette. Many of these eggs may die during the ICSI process.
Unfortunately , because egg morphology has not been adequately studied , we still do not have good descriptive terms , when talking about these abnormalities. Since the eye only sees what the mind knows, often these abnormalities are not picked up. The patient is often subjected to repeated IVF or ICSI cycles , with the same poor results each time.

Why is abnormal egg cytoplasm such a difficult problem ? In order to understand this, let's first review the important role the egg cytoplasm plays in embryo development. The most dramatic events during fertilisation occur in the nucleus, when the male and the female pronuclei fuse. However, the energy to drive this fusion comes from the mitochondria in the egg - the energy powerhouses of the cell, which power cleavage and cell division. One major problem is that there is no way of testing egg cytoplasmic quality - either clinically, or in the research lab at present. While electron microscopy studies have confirmed these eggs have cytoplasmic abnormalities, this is still an area which has not been adequately studied.

Of course, part of the problem in some labs is that the failed fertilisation is not because of an intrinsic egg problem,but because of poor lab conditions. How can you as a patient find out if the problem is a lab problem ; or a biological problem with your eggs ? This is why, if there are fertilisation problems, it's very important to ask the lab to document egg morphology with photographs and videos, which can then be reviewed later. It's also a good idea to repeat the treatment cycle in a better clinic, to eliminate the possibility that the poor results maybe an artifact created as a result of suboptimal lab conditions ( such as infection; poor quality culture medium; or an unskilled or inexperienced embryologist).

I also think it's time doctors coined new medical terms to describe these egg problems. We could borrow some of the terms we use at present to describe sperm problems ! Thus, if a patient has few eggs ( impaired ovarian reserve), this could be called oligo-ooctyosis ( = few eggs). If the eggs are abnormal, this would be terato-oocytosis ( = abnormal eggs) ; and if the eggs do not fertilise because of cytoplasmic problems, this would be astheno-oocytosis ( = weak eggs).

How do we tackle this problem in our clinic ? We trouble shoot, by checking if the problem is localised to just single patient; or if it's affect more than one ( which would suggest a lab problem rather than a patient problem). If we think the patient has abnormal eggs after egg retrieval, we take photographs of all these eggs , so the patient has adequate documentation. We prefer doing ICSI as compared to IVF for these patients. However it requires a skilled embryologist , because these eggs need to be handled with care and respect . If ICSI is done in the routine fashion , many of these eggs will die during the cytoplasmic aspiration.

If at the end of the ICSI cycle , we feel the patient has a problem with fragile eggs ; poor quality eggs; all eggs with cytoplasmic abnormalities, we explain this to the patient; and discuss their treatment options.

One possibility is that this was a one off phenomenon for unexplained reasons; and may not recur , if we try again. However , because we feel that the risk of recurrence is high , we change the superovulation protocol, with the hope that a change in medication may help to improve egg quality .

If this also fails , then the only realistic options are to consider either donor eggs or donor embryos. These can be very hard choices to make , especially for a young woman who felt she had normal eggs prior to starting the IVF treatment, because she had regular menstrual cycles , and a normal FSH and AMH level.
This is why we emphasize to patients that while the primary purpose of an IVF cycle is therapeutic , IVF cycles often reveal valuable diagnostic information , which can help us to pinpoint possible problems and create effective treatment solutions. These problems could never have been diagnosed unless IVF had been done !

9 comments:

  1. Anonymous3:50 PM

    I recently got Day 3 TVS. The Ultrasound doctor told me that my antral follicle count is as good as it gets for a 30 year old woman. Day 3 FSH level tests done last September also showed normal reports with Day 3 FSH of 6.09. I went in for a cycle of IUI(july 2) with injectible drugs. Must have taken a dozen shots last months. But still my home pregnancy test is negative. Will AMH test help me understand my problem?

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  2. I am an 34 y/o "unexplained infertility" patient who just completed my first IVF cycle. I was amazed when they retrieved 18 eggs, 15 fertilized, but only 2 were "normal" due to genetic problems in all the other eggs. It was so hard to hear that I have poor quality eggs, but yet at least I know feel like my infertility is explained. I couldn't agree more that IVF is as much a diagnostic tool as it is an infertility solution.

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  3. savvy_mummy4:03 PM

    I am not sure if my egg quality is good or okay. For my first ICSI, I have five eggs collected producing four grade 2 & 3 embryoes which did not give us a single pregnancy. Doc says it is embryo problem...but what does he mean by that? Egg or sperm specifically or both? Is there any way we can improve egg quality through herbs or diet? Looks like only God can grant me a pregnancy.

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  4. I want to thank you for this posting. I fall firmly into your third category (age 32) and have never seen it explained in such simple terms. I especially appreciate your attempt at naming the various discrete conditions. Lucky for me I had an extremely competent IVF doctor who diagnosed me after only two ICSI cycles. Please do keep writing and researching this topic! Thank you.

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  5. Dear Rachel,

    Thanks for your feedback.

    If expert patients and doctors collaborate, we'll all be able to do a much better job in diagnosing and treating this common and distressing condition !

    ReplyDelete
  6. Anonymous8:00 AM

    As a physician reading this : Excellent explanation, wish all fertility Drs would keep and share a national database of all tried Ivf cycles and end results so we could learn more resolve more problems. I am myself in the third group with high amh, not pcos, afc 30-50, first Ivf retried 45, 26 mature, only 9 fertilized with Icsi, 3 made it to day 3 but arrested after!

    ReplyDelete
    Replies
    1. You seem to have occult PCOD.

      This is a common problem with PCO patients. Doctors are so scared of
      OHSS, that they end up mistiming the HCG injection, as a result of which they poor quality embryos.

      You can read more about how we treat PCOD at
      http://www.drmalpani.com/knowledge-center/the-infertile-woman/how-to-manage-your-pcod

      Taking treatment at a world-class clinic will maximise your chances of success and give you peace of mind you did your best !

      We look forward to helping you to have a baby !

      Dr Aniruddha Malpani, MD
      Malpani Infertility Clinic, Jamuna Sagar, SBS Road, Colaba
      Mumbai 400 005. India

      Clinic Mobile: 9867441589

      Tel: 91-22-22151065, 22151066, 2218 3270, 65527073

      Helping you to build your family !

      You can add a google review for us at https://plus.google.com/102706636605134081909/about

      My Facebook page is at https://www.facebook.com/aniruddha.malpani

      You can follow me on twitter at https://twitter.com/drmalpani

      Watch our infertility cartoon film at http://www.ivfindia.com

      Read our book, How to Have a Baby - A Guide for the Infertile Couple,
      online at www.DrMalpani.com !

      Read my blog about improving the doctor-patient
      relationship at http://blog.drmalpani.com

      Delete
  7. Anonymous6:53 PM

    My wife and I just completed our second IVF attempt. The first time the doctor retrieved 10 eggs all of which had vacuoles and the embryologist said they were unable to perform icsi. So we tried a second time under a different protocol which produced 17 eggs but all had the same poor quality. We are heartbroken and hope that physicians like yourself will be able to find a reason for this one day and a treatment as well. Thank you for your post.

    ReplyDelete
    Replies
    1. I agree this can be very frustrating.

      Can you send me more details about your IVF cycles ?
      DO YOU HAVE PHOTOS OF YOUR EGGS ?

      What were the meds used for
      superovulation ? What was the dose used ? How many follicles did you grow ? How many eggs were collected ? What was the E2 ( estradiol) level in the blood ? Can you please send me the printed treatment summary from your IVF clinic ?

      Repeating the ICSI cycle with better superovulation and careful monitoring would be your best treatment option
      as it would maximise your chances of conceiving. You can read more about our approach at www.drmalpani.com/knowledge-center/failed-ivf/failedivf

      Treatment takes about 20 days. Should I send you the treatment plan ?

      You can read about how we take care of our patients at http://www.drmalpani.com/knowledge-center/articles/pampered-ivf-patients

      Taking treatment at a world-class clinic will maximise your chances of success and give you peace of mind you did your best !

      You can talk to some of our patients by email at www.drmalpani.com/success-stories

      We look forward to helping you to have a baby !

      Dr Aniruddha Malpani, MD
      Malpani Infertility Clinic, Jamuna Sagar, SBS Road, Colaba
      Mumbai 400 005. India

      Clinic Mobile: 9867441589

      Tel: 91-22-22151065, 22151066, 2218 3270, 65527073

      Helping you to build your family !

      You can add a google review for us at https://plus.google.com/102706636605134081909/about

      My Facebook page is at https://www.facebook.com/aniruddha.malpani

      You can follow me on twitter at https://twitter.com/drmalpani

      Watch our infertility cartoon film at http://www.ivfindia.com

      Read our book, How to Have a Baby - A Guide for the Infertile Couple,
      online at www.DrMalpani.com !

      Read my blog about improving the doctor-patient
      relationship at http://blog.drmalpani.com




      Delete