Saturday, March 20, 2010

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


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.

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
Monterey, California, U.S.A.

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