Did Childhood X-Ray's Affect My Fertility? Queries Australian Woman...

Question:

Hi,

I was born with Perthes Disease (a disease of the hip). From the ages 5 - 15 I would have had well over 100 X-rays, concentrated on that area - most taken from above my body looking directly down at my hips.

I have never been able to keep a pregnancy beyond weeks, and tests have come back saying the last one included the extra chromosome 15. I have been under fertility treatment for 2.5 years. Tests are going to be carried out on my latest "failed pregnancy" within the next 4 weeks. The X-rays took place from 1971 - 1986. I have been in 2 long term relationships since 16 years old. (The current one being 13yrs) and there is no history of infertility in my family - all 4 siblings successfully having multiple children. I believe my eggs may have been damaged as a result of these X-Rays.

Regards. K. from Australia

Answer:

Hello K. from Australia,

I have to agree that there could have been egg damage from the proximity of the X-rays that is now causing the embryos to have genetic abnormalities. There is no treatment that can be done to repair eggs, but one option you might want to consider is to do CGH in association with an IVF cycle. With CGH (Comparative Genomic Hybridization), polar body biopsies can be done on the eggs at the time of fertilization and thereby evaluate the genetic complement of the eggs. This will immediately allow you to eliminate the abnormal eggs and hope that there is a normal one that survives and can be transferred. There is always the chance that there are some good eggs left and that is the goal. It may take several IVF attempts before finding that good egg, but in the end it will be well worth it. There is no price you can put on a child.

If you don't want to go through this option, with the potential risks of failure, your alternative then would be to proceed with Donor eggs and IVF.

I was just at a National OB/GYN conference and one of the topics discuss was a new program in the U.S. called Oncofertility Consortium. This is a group of specialists in the field of infertility, oncology, therapists, etc. that are promoting fertility preservation in patients facing various cancers or treatments such as radiation, chemotherapy, etc. The reproductive outlook for women cancer patients is becoming as good as for men, who long have had the option of banking their sperm. It is our hope that patients, such as you, will undergo counseling for fertility preservation and be given the option of preserving your eggs or ovarian tissue prior to undergoing treatments. I know that this is not going to benefit you now, but we hope that it will benefit people like you in the future. For more information on this group from the American College of Ob/Gyn's website, go to: http://bit.ly/axAePh.

Thank you for your question. I will be keeping my fingers crossed for you!

Good Luck,

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

http://www.montereybayivf.com/

Monterey, California, U.S.A.

German Woman Suffers Multiple Miscarriages Over Two Year Period - Proceed To Clomid Superovulation?

Question:

I´m 31 years old and writing from Germany. I have no children and have suffered four miscarriages. My husband and I have been TTC for 2.5 years now. After using the implanon hormone implant for birth control, I had it removed in 09/07 to begin TTC. In 11/07 I fell pregnant only to miscarry at about 5w3d. My hormone levels showed an hcg level of less than six. I was told to wait three months and try again, that I would have better luck. In March of 08 I fell pregnant a second time. At my first appt. at 8w5d it was discovered that there was a large sac with no fetal pole. I began to miscarry at 11 weeks and had an emergency D&C because I was losing so much blood. I asked that the tissue be analysed, but was told it was not done for a second loss and that this was in all likelyhood caused by a chromosomal problem. I was told to wait three months before trying to conceive again. Exactly 28 days after the D&C I got my period. I fell pregnant the next cycle, but did not realize it until I started miscarrying. My doctor did not do a blood test, only looked at an ultra sound, shrugged her shoulders and said I wasn't pregnant anymore, if I had ever been. She suggested that I could go for genetic counseling if it would make me feel better.

My husband and I went for genetic counseling, had kareotypes done, both of which came back normal, were tested for various thrombophilic conditions and immune disorders plus thyroid. My results came back as normal for everything but Leiden Factor V. I carry one copy of the gene. I was told by the geneticist that it would be good to start heparin at 8weeks in my next pregnancy and sent on my way.

In December of 08 I fell pregnant a fourth time, was given 100mg of aspirin to take starting at 4w5d. At 5w1d I began to bleed, but the ob/gyn felt that my lining still looked good, gave me progesterone supplements to take and told me to come back in five days for another ultrasound. On my return visit she could not find a sac in the uterus, and was unsure if she wasn´t seeing a sac in müllerin duct. I was told to stop the progesterone immediately and go to the hospital immediately should I have any sharp pains. Otherwise I was to report to the hospital in another five days for a beta draw. After stopping the progesterone I miscarried the next day. Three days later my hcg levels were drawn at the hospital and found to be 144, so I was required to come back every 48 hours for another draw to be sure that they were indeed falling. My levels fell nicely and I was sent home to wait three months before ttc again.We have been trying for a year now, and have not been able to get pregnant.

I have charted, used the clear blue fertility monitor and opk's to no avail. After six months I went to see an RE hoping that he would be able to give me some answers about my miscarriages, but he offered no ideas as to why, only said that my miscarriages were not a result of the Leiden Factor V. He did some bloodwork at CD13 to check my hormone levels, which he said looked very good, did a SA for my husband and a penetration test and said he saw no reason for us not to be pregnant. He suggested a doing a lap but made no further recommendations.

My regular ob/gyn was not in favor of the lap and suggested that I try a bit longer, and that if I wanted to we could try clomid and progesterone to get a stronger ovulation.I am unsure and very confused as what my next course of action should be testing and treatment wise, and if I really have a chance at having a biological child. I would appreciate any thoughts you might have on this subject. Thank you very much for your time.

Answer:

Hello L. from Germany,

Recurrent miscarriages are a difficult problem. The most common reason is because of a spontaneous chromosomal abnormality. That means it occurred when the egg was dividing, and not because you are carrying something. Hematologic disorders, such as Factor V, have been shown to increase the risk of miscarriage. Since you underwent evaluation and that was the only abnormality found, that is good because most patients with recurrent miscarriage due to spontaneous abnormalities will eventually be successful.

You mentioned that you were 31 years old, which is a good thing. Age plays a significant role in the risks of spontaneous anomalies and increases the risk of miscarriage with increasing age, especially after 35 years old. I call this the "Age related egg factor." Most patients that have recurrent miscarriages are because of age related spontaneous genetic defects. In your case, although there may still be "abnormal" or "weakened" eggs within your ovary, your chances of spontaneous defects are low. That means that your chances for success are high.

It sounds like your RE was addressing the issue of your infertility and not the recurrent miscarriage problem. Laparoscopy would be indicated to evaluate for infertility only. I don't think it is indicated at this point as well, but I wonder why you have not gotten pregnant after 1 year of trying. Something has changed and an evaluation is definitely warranted. I would go back to doing a full basic infertility evaluation and not make any assumptions, despite having gotten pregnant in the past. A hysteroscopy would be warranted to evaluate the uterine cavity because of your history of D&C. Therefore, you might also want to consider laparoscopy to complete an infertility evaluation, but not for evaluation of recurrent miscarriages.

If you don't want to do an evaluation but want to proceed with trying for pregnancy, then it is a little shot in the dark. Certainly doing Clomid "superovulation" is an option. This is where the fertility drug Clomid is used to increase the number of eggs that you ovulate per month. This can be paired with either timed intercourse or IUI. I might suggest the latter, IUI (Intra Uterine Insemination) for a higher pregnancy rate between these two. You might want to use low dose aspirin (81mg)per day and heparin (2000 units/twice per day) and medrol 16 mg per day starting from the beginning of the cycle, as well as, supplemental progesterone (vaginal or injectable) and estrogen.

The other option would be to proceed with IVF (in vitro fertilization). In this case, embryonic genetic testing, called PGS (preimplantation genetic screening) can be done to determine which are the normal embryos so that only these would be transferred. If you decided to pursue this option, I would recommend that you choose a clinic that has experience doing this and can do testing at the blastocyst stage (trophectoderm testing), rather than an earlier stage where they take one of the cells, and test with CGH (comparative genomic hybridization) .

I hope this gives you some information to consider.

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

http://www.montereybayivf.com/

Monterey, California, U.S.A.

Young PCO Austrian Had 5 IVF Cycles Over 3 Years And Is Ready To Give Up - Short Protocol, CGH Advised & Keep Trying!

Dear Dr. Ramirez,

Thanks for taking the time to do this, I have read several of your previous answers on the website and I am looking forward to hear your thoughts on our case. I am writing from Austria. Both my husband and I are 30, we have been doing IVF/ICSI for the past 3 years (5 cycles) with no success. My husband has the CF gene and no vas deferens (0 count). Everything is fine with me (blood work, hormones, etc). I had a laparoscopy/hysteroscopy in 2006 (prior to the treatments) where an endometrial cyst was removed from one ovary, as well as one polyp from the uterus and some adhesions from the tubes. I have been getting continuously checked since then and my uterus, ovaries are clear from anything. My husband has had 3 TESE procedures, and good looking sperm was found each time and lots of it has been frozen.

We had 2 treatments in 2007, 1 in 2008, and 2 in 2009. In the first cycle (with fresh sperm) I had 14 eggs, 3 fertilized, and 2 grade A embryos were transferred. In my second and 3rd cycle I had 20 eggs (different protocols used in each of the treatments) and none fertilized. I hyperstimulated severely in cycle # 2 and ended up in the hospital. I was told we had an egg issue and to try with donor eggs. We took a year off to think about it and switched clinics. In 2009, cycle # 4, we had 15 eggs (frozen sperm), 3 fertilized and 2 grade A embryos were transferred on day 3. In cycle #5, we had 15 eggs again (frozen sperm), 7 fertilized, and we had 2 morulas transferred. We have a lot of trust in our doctor and clinic used for the past 2 treatments, and have a great relationship. The clinic is a stat of the art building with all new technology. This doctor does not think I have egg quality issues since I had good embryos (although very few of them) in the last two cycles, and thinks we should keep trying. However, we know it is not normal that within our age group we have not succeeded yet. It is hard to not think that there is something wrong with us. I stimulate very well in terms of numbers, and the protocol has been decreased (amount of drugs) with each treatment (always yielding a high number of eggs). We have tried acupuncture, yoga, bed rest, no bed rest, and all kinds of things. We do have a possibility to try one treatment in the US (due to the expenses), but are not sure of what we should do.

Any thoughts would be appreciated. What do you think of my egg quality issue? Would a US clinic suggest donor eggs? I would really like to try with mine...Best regards from Austria.

ANSWER:

Hello S. from Austria,

Based on the history you have given me, it sounds like you may be a PCO-type ovarian stimulator. That is why you have so many eggs, and had hyperstimulation syndrome. The good part of that is that you yield lots of eggs. There have been some studies that show a decrease pregnancy rate in PCO patients, however, and it is thought that it is because they stimulate too much. This leads to unequal maturation of the eggs within. Certainly, you seem to have had good quality (albeit external quality) embryos in the latter two cycles. At your age, I would have expected a pregnancy, easily. One concern is whether the sperm is contributing to poor embryos (again internal quality/genetically), because of your husband's CF gene. The embryo could still look good but be genetically abnormal. The only way to know this is to do preimplantation genetic screening, preferably by polar body biopsy and CGH, to verify that only normal embryos are transferred. CGH, or "comparitive genomic hybridization" is a genetic test that analyzes the chromosomal integrity of an egg or embryo. In IVF, it is ideally done in women under the age of 39 who have more than 6 healthy embryos after fertilization. They can be her own or donor eggs.

I would not recommend that you give up yet. If you give up, you certainly will fail. Since your ovary stimulates so well, and you are young, I think your chances of pregnancy are still high. The alternative to the above genetic testing on the embryos, would be to go to donor sperm, rather that donor eggs, in order to eliminate that paternal genetic factor. I know that you husband would probably prefer a genetic child, however, so in that case, you just have to keep trying.

If you came to me or any other clinic in the U.S., I don't think we would be ready to give up with your eggs. I think we would continue to encourage you to keep trying with your own eggs. I recently had a patient, similar to you that seemed to have poor embryo quality in another clinic. They did three IVF cycles there and then were recommended to use donor eggs. Fortunately, her husband got transferred to my locale and they came to me for consultation. I encouraged them to try at least one more time with her own eggs, again since her ovaries stimulated well. They decided to go with my recommendation and in their first attempt, became pregnant.

Follow-Up Question:

Thank you Dr. Ramirez for your answer.

In the meantime, I just had a hysteroscopy 3 days ago and a polyp removed from the uterine wall, this polyp was not showing up on ultrasounds. Could you please elaborate on why you think I have PCO? I do ovulate every month, no diabetes issues, no acne, no absence of menstruation, none of the signs I have read are present in me, but since it is the first time I hear that, please explain me how I could have it and how does it affect stimulation? How is it better to deal with it?

I forgot to mention that in the last two treatments (with 2 embryos/morulas transferred each time) we did polar biopsy of the eggs and only the 2 perfect/healthy ones were transferred each time, still no success. My doctor recommends that we continue to do this polar biopsy and we will. What kind of stimulation would you recommend for me? What could have caused this polyp I just had removed? Could it be the same stimulation drugs (estrogen), which is given to me as part of the treatments that made my uterine tissue grown into a polyp? (it was a long, flat polyp, not the regular ones that can be seen by ultrasound).

With regards to the couple you mention in the last paragraph, what did you do different from their 3 previous treatments that could have led to success? Is it just a matter of numbers/attempts, that we need to keep trying? The more one fails, the harder it is to believe it could happen....and I know mental power can do lots for either direction.

We might try one more treatment here (much more affordable) and then have a final treatment in the States. We are definitely not ready to give up! Thanks again!

Follow-Up Answer:

Hello Again,

There are many variations of PCO. Not all fit the classic descriptions. In your case, what makes me think that you have a PCO tendency is the fact that you overstimulated and developed hyperstimulation syndrome. I have had many patients that have surprised me in the same way. They are thin, have regular menstrual cycles, don't have any other PCO-type tendencies, yet they stimulate like a PCO patient. That is, their ovaries are very sensitive to the fertility medications. Since you don't have any of the other PCO findings, the only thing to keep in mind is that your ovaries are very sensitive to stimulation, so that the next time, a low dose protocol will be used and you don't develop hyperstimulation syndrome.

In terms of stimulation protocols, with my PCO patients I use a "step-up" protocol. Patients start at a low dose of Follistim 150IU for three days then the estradiol level is checked for response. If there is not a high response then I step up the dosage to Follistim 150IU + Menopur 75. We continue the same pattern of checking and adjusting the dosage as needed. I don't use Lupron agonist suppression (long protocol), but instead use the Antagonist Ganerelix. When the follicles are appropriate sized, I trigger with Lupron 0.5 mg instead of Ovidrel. This combination and protocol has been shown to be effective in preventing hyperstimulation syndrome.

Polyps are normal. It is very common and is due to an overgrowth of endometrial tissue. The finding is probably not significant in terms of pregnancy chances, but we prefer to remove them anyway so that they can't potentially interfere.

In terms of my couple, I used a completely different protocol than what she used previously, and some additional medications. Different clinics have different success rates because of differences in their protocols and techniques. "Failing" is when you stop trying. As long as you continue to try, you have a chance of success and that is what you have to focus on. Focus on the goal, not the pathway.

Good Luck,

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

http://www.montereybayivf.com/

Monterey, California, U.S.A.

***See continuing follow up to this question on May 16th, 2010...