Genetic Defect In Husband's Sperm Leading To IVF Failure: Screening With CGH Recommended

(If the blog radio program turns on, go to the Oct. 1st blog post and pause it...I will be keeping the show up for the month of October.)

Question:

Dear Dr. Ramirez,

My husband and I have been infertile for two years. The second year, we began IVF. We have completed 3 IVF rounds. The first was not successful. The second resulted in a chemical pregnancy / early miscarriage at 6 weeks. The third resulted in an ectopic pregnancy. My husband and I are both in good health, with no known infertility factors (endometriosis, etc.). We do not have antisperm antibodies. All our bloodwork was good. On our second IVF round, 1/2 of the eggs were fertilized by standard IVF and none of them merged. 1/2 of the eggs were fertilized by ICSI and did very well. On our third IVF round, all the eggs were fertilized with ICSI and did very well. We have 9 frozen embryos waiting.

After this ectopic pregnancy, we had genetic testing done. Mine were normal. My husband's were abnormal. The interpretation was:

"A male karyotype with a small supernumeray bisatellited marker chromosome was noted in all metaphases analyzed. The majority of bisattellited markers are derived from an inversion duplication of the pericentromeric area of chromosome 15. Apparently this market carries minimal with no phenotypic significance to the patient; however it may lead to decreased fertility, repeated pregnancy loss, or chromosomally abnormal offsrping. Parental follow up chormosome studies are recommended to determine if the marker is familiar or de novo in origin, and to further evaluete its clinical significance. De novo markers are associated with an increased risk for phenotypic abnormalities. Genetic counseling is recommended."

We are going to receive genetic counseling in the future, but what is your opinion about this chromosome 15 abnormality and its effect on conception and offspring? Thanks! A. from the U.S.

Answer:

Hello A. from the U.S.,

Unfortunately I am not a geneticist and will usually go by what the geneticists advise me in terms of the consequences of chromosomal abnormalities.

However, in general, this is what it means to me. Your husband is carrying a genetic abnormality that is "recessive" in nature, meaning that it does not necessarily present itself as an abnormality. Because his sperm can contain this trait, it is possible that this can result in abnormal embryos, which will lead to early embryo death (and lack of implantation) or an early miscarriage. The ectopic pregnancy you had was for a different reason and does not need to be considered in this discussion.

What I would recommend is that the embryos be tested by the relatively new CGH (Array Comparative Genomic Hybridisation) process or PGS (Preimplantation Genetic Screening) prior to transfer. Last year, in England, a 41 yr. old woman who had failed IVF 13 times had her embryos tested with CGH and in September delivered a healthy baby (see article here). If your embryos are D#3 embryos, they should be thawed, and biopsied for genetic testing done by CGH. They would then be cultured to blastocyst and transferred at that time. If they are already blastocysts, then they would need to be thawed, biopsied then frozen again for a later transfer. In any future IVF cycles, the embryos should be similarly tested to look for the normals so that the abnormal embryos are not transferred leading to a negative pregnancy, miscarriage and further disappointment.

Not knowing how the genetic transference of this abnormality is done i.e. does it occur every time with every embryo, or is there a chance that some embryos will not have the disorder? it is hard for me to give any more specific recommendations. Once you have your genetic counseling, they will be able to answer these questions for you, which will help to determine a more specific strategy.

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.

Comment: Thank you. You are an angel for helping with this guidance.

Husband & Wife With Different Blood Types: Did Rh Factor Lead To A Fetal Demise?

Question:

Hi,

I'm 33 years old my husband is 39. We are a healthy couple. Twice in one year we've gotten pregnant. First pregnancy, very early, I began to have spotting and eventually was diagnosed with an ectopic pregancy, I was given Methotrexate. This past May I was pregnant again, and during my first evaluation at 6 weeks everything was fine, except my progesterone level was low (12.17) and I began using shots and pills daily. After one week my levels reach 96.14.

At 8 weeks my evaluation showed no heartbeat, I was diagnosed with fetal demise. I'm concerned because my husband and I have different Rh and blood group (B- and O+) is this a problem? What should we do next? Infertility evaluation?

Thank you, M. writing from Puerto Rico

Answer:

Hello M. from Puerto Rico,

First of all, your difference in blood types does not lead to miscarriages. However, regarding your blood type differences, if you have a negative Rh factor (B-) and your husband is positive (O+) then you will need to receive an immunization called Rhogam (an Rh immune globulin injection), which should be given with this miscarriage, and should have been given already with the ectopic. This is because in a future pregnancy, the fetus can be affected by an immune response and develop a disorder called erythroblastosis fetalis. This is because your Rh antibodies may cross the placenta and attack the baby's red blood cells. The Rh positive baby then may develop Rh disease, a life-threatening condition that could cause anemia or other serious problems. For more on Rh factor, please visit the Mayo Clinic website: http://www.mayoclinic.com/health/rh-factor/MY01163

Secondly, you have to separate your two pregnancies because they are completely different. An ectopic is a pregnancy that implants in the tube. This is different from a miscarriage, which is in the uterus. They are not related. The only conclusion you could make is that because of a previous ectopic, you are at risk for another. However, you have already shown that you can get pregnant within the uterus despite this risk. Miscarriages are a natural occurrence. They occur in up to 40% of pregnancies, and the most common cause is a chromosomal abnormality in the developing fetus. The body (nature) realizes that the fetus is abnormal and stops the pregnancy or severe defects in the fetus causes it to die off. The good news is that most women that have miscarriages are eventually successful. You just need to keep trying and I don't think that you need to do anything different, necessarily.

Because of the progesterone issue, you might want to add supplemental progesterone after ovulation, just as a precaution. This can be given as injections or vaginal suppositories.

Despite the setbacks you have had, I am confident that you will be successful. Please follow up with your Ob/Gyn regarding your Rh factor!

Sincerely,

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.

Seventh IVF Cycle Brings Success But Patient Worried About Progesterone Levels

Question:

Hi Doctor!

I have recently become pregnant after my 7th IVF, and am currently 6 weeks. I had 2 very good quality blastocysts transferred and am awaiting my 7 weeks scan next week to see the heartbeat and hopefully tell if it's twins. I have been going in for blood tests to monitor my progesterone levels and initially I was taking 2 cyclogest (400mgs) a day, it then increased to 3 and now 4 a day. This was because my prog levels were fluctuating from 80 and 150 and my FS feels 150 is a good level. My last test showed it at 200. From doing my research, I realise that normal prog levels can be anything above 30 and less than 100. Are mine too high? IS there any danger of having prog at 150-200?

My Bhcg has also been monitored every 2-3 days and they have been climbing nicely, from 193,447,1863, 4990 and now 13900. Are those indicative of a viable pregnancy?Many thanks for your help and advice.

Regards, N. from the U.K.

Answer:

Hello N. from the U.K.,

Congratulations! I'm glad you persevered because most patients would not try IVF 7 times. All your levels are fine. Your progesterone is not too high and there is no danger with a level of 200. I'm surprised your doc is chasing the levels. Your bHCG levels are great. With a level of 13,900, the gestational sac should already be visible within the uterus, so your doc should go ahead and do a scan this week rather than wait until next week. At this point it is important to confirm the uterine pregnancy because there is a 2-5% risk of ectopic pregnancy with IVF (tubal pregnancy). If it were in the tube, this would be the time to treat it as medication can be used instead of surgery.

I don't mention this to scare you, but I normally do my first ultrasound at 6 weeks gestational age for this reason. You might want to ask your doctor to do so as well. More than likely everything will be fine. Again congratulations!

Follow-Up Question:

Hi Doctor,

Thanks so much for your advice, I really appreciate it. I took your advice and scheduled a scan for today, which confirmed a single uterine pregnancy and we saw the heartbeat. So it is a relief! I am currently 6 weeks and 4 days. Is there any chance of things going wrong after seeing a heartbeat? I haven't had any bleeding or haven't had any major cramping. I also haven't been experiencing nausea and morning sickness, but I have had lower back pain, fatigue, and strangely enough throbbing ankle or feet pain now and then. Thank you for your time and help. Regards, N.

Follow-Up Answer:

Hello N.,

Congratulations! At 6 weeks with the findings of a fetus of appropriate size and a good heartbeat, those are good signs for the pregnancy. There is still a risk of miscarriage that runs about 40% until 8 weeks gestational age. Your doctor should probably repeat the ultrasound in two weeks. If everything looks fine at the next ultrasound (8+weeks), then the risk of miscarriage drops to 5% until 12 weeks gestational age.

Of course there are lots of problems that can occur in pregnancy. Everyone has the same risks. But if you worried about every possible risk, you would go crazy and not enjoy your pregnancy. For now, I would recommend that you take things in stride and day to day. Don't worry about the future because you don't necessarily have control over it. Hope for the best because that is the most likely outcome. And as the sailors of olde used to say, pray for good winds!

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.

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U.K. Infertility Patient Had Four Fibroids Removed, Now Has Pain Upon Ovulation - Ovarian Adhesions?

Question:

Hi Dr. Ramirez,

I am a 28 year old lady who has been trying to conceive for 18 months. I had an ectopic pregnancy last June, but thank God both tubes are still intact as I was diagnosed early.

I decided to have a laparoscopy in February 2010 to find out what is wrong and my doc took out 4 fibroids and I also had mild adhesions to the right ovary but apart from that the tubes and the uterus looked healthy. But since the laparoscopy, I have been having this unbearable ovulation pain on the right side which I never experienced before. It lasts for 3-4 days. The pain is very uncomfortable and right hand side of the abdomen is very sore and tender. It feels exactly like the pain I had when I had the ectopic.

My question is could the adhesions be back on the right ovary already? If so, if they were mild before the lap, is it possible they got worse after the lap? Also, would the laparoscopy affect the functioning of the ovary as I have been having abnormal basal body temperature since the lap.Lastly, is it possible to ovulate from the same ovary every month, as I don't think I am ovulating from the left ovary at all?

Is my only chance of conceiving IVF?

Many thanks in advance for your suggestions. Regards, B. from the U.K.

Answer:

Hello B. from the U.K.,

Yes, adhesions can return and usually return within 24 hours. Also, any surgery, including laparoscopy, can result in adhesion formation. Normally, when you ovulate, your ovaries swell thereby "moving". Unfortunately, the adhesions may be fixing the ovary in place causing you to have uncomfortable pain. I would not expect the laparoscopy to affect your ovarian function if the ovary was not damaged in any way or its blood flow affected.

Yes, it is possible to ovulate from the same ovary every month.

My opinion is that you have tubal disease that was probably caused by some type of event, like an infection in the past. That usually leads to internal tubal damage and scar tissue formation. If significant enough, you can also get scar tissue within the pelvis and around the ovary and tubes. The main problem is that if there is damage within the tube, it cannot be fixed. These internal adhesions are probably what caused the embryo to get stuck in the tube, leading to the ectopic. Certainly patients that have had ectopics before do subsequently have normal pregnancies, but there is no way to know which category you will fall into. With the combination of problems, ectopic and peri-tubal adhesions, I would expect that your natural chances of pregnancy are low, in which case, IVF would be the treatment of choice. That is how I would advise you in my clinic. You could certainly continue trying with a more natural method such as ovulation induction with timed intercourse or ovulation induction with IUI. You need to be seen right away if you get pregnant because of your increased risk of recurrent ectopic.

If you don't get pregnant after a period of time, I would set it at 6 months or no more than 4 IUI attempts, then I would proceed directly to IVF.

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.

Patient Has Only One Tube, One Ovary & A History Of Ectopic Pregnancy: What Are Her Chances Of Conceiving?

Question:

Thank you for taking the time to answer my question. I am a 27 year old female with a history of endometriosis. I had my left ovary removed two years ago due to a cyst. My Dr found endometriosis that had pulled my bowels up to my uterus and did a laparotomy a few months later to correct this. I was then put on 10 months of Lupron injections to try and keep the endo from growing so fast and got pregnant two months after coming off of them. However, that resulted in an ectopic when I was only about 3 or 4 weeks along. My tube ruptured and he had to remove it. He also found more endo that he was able to remove. So I now I'm left with a right ovary and a left tube. It's been 5 months since my ectopic and I have yet to get pregnant again.

I've switched to a high-risk OB/GYN. He did an HSG and my tube looked good. He also put me on 50mg of Clomid days 3-7. I had two ultrasounds to show that I had indeed ovulated and then he started me on progesterone suppositories (my progesterone in my first pregnancy was 7). It has been over a month since my last cycle, but all of my pregnancy tests have come back negative, so I believe the progesterone has delayed my period. My question is, do you think there is a chance of me conceiving again. My Dr told me to be saving for IVF (which my husband and I cannot afford right now). I would like to have 3 or 4 kids, but I don't know if that's possible now. I'm devastated over this and I would appreciate any advice you can give me.

Thank you. K. from the U.S.

Answer:

Hello Kasey from the U.S.,

Normally, it is possible to get pregnant when you only have one tube and one ovary that are opposite from each other. In fact, in nature, the egg ovulated from one ovary, say the right side, does not necessarily go into the right tube. This is a misunderstanding. The Fallopian tubes actually hang 2 cms (1 inch) down below the ovary and the egg can be ovulated from any part of the ovary. In reality, the egg is expelled from the ovary with all the fluid that surrounds it in the follicle. That fluid rushes out taking the egg with it. It then falls into a space called the culdesac located behind the uterus, where the ends of the fallopian tubes hang. Then by simple fluid motion (think of a spec of dust in a small puddle of water), the egg either contacts one tube or the other. It does not always find a tube. So in this way, it can contact either the right tube or the left tube and in your case, it can contact the opposite tube.

I think you might have another problems, however. Maybe two major problems. One is that you have endometriosis. That is a pelvic disease whereby the endometriotic implants cause an inflammation in the pelvis. This inflammation can attack and destroy the egg before it has a chance to be picked up by the tube. The second issue is that you have have multiple pelvic surgeries. Surgery tends to cause scar tissue in the pelvis and culdesac. Scar tissue (adhesions) are like spider webs in the pelvis and can block the egg and tube from getting together. There is a third problem as well, but not one that will prevent you from getting pregnant, but one that could be devastating, and that is that you have a history of ectopic pregnancy. Ectopics occur when the egg gets caught in tube, and is usually the result of scar tissue within the tube. This is most often from a previous infection that got into the tube and caused formation of the scar tissue from inflammation. It does not necessarily need to be bad enough to block the tube so the tubes would be open on HSG, as in your case. It could mean that there is scar tissue in the remaining tube, that could either prevent the egg and sperm from getting together i.e. damage the structure within the tube so that it is not functional, or lead to another ectopic.

With all of this going on, IVF is in fact the best treatment for you. Try to find a center that may help you with a financial plan (we have many) that fits your budget, even if it is far away. Your Ob/Gyn can monitor you for the IVF clinic if it is too far for you to visit.

I hope this helps,

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.

I Had An Ectopic, Can I Get Pregnant With Only One Fallopian Tube?

Question:

Hello, I am from India and I hope you would be able to help me.

I had an ectopic pregnancy 3 months back wherein I had to undergo laparoscopic surgery to remove my right fallopian tube where the fertilized egg had embedded.

Both my ovaries are intact.I didn't have any fertility issues before conceiving. My question is whether it is possible for left fallopian tube to collect the eggs released by right ovary? Also, I wanted to check with you whether the ovaries release eggs in alternate months. In your opinion, approximately how long it might take for me to conceive the next time?

Please help me with these questions!

Answer:

In answer to your questions, yes, it is possible for an egg that is ovulated from the right side to enter through the left tube.

That is because no matter what side the egg ovulates from, it falls into a space in the middle, called the culdesac, where the end of the tubes are usually hanging. Eggs are released randomly from the ovaries. They do not alternate. The problem that you have is that you had an ectopic pregnancy. This is usually caused by scar tissue within the fallopian tube. The egg/embryo gets stuck on this scar tissue and cannot advance, therefore, it implants there. If you have scar tissue on one side, you are at risk for having scar tissue on the opposite side because usually the inflammation that affects one tube, also affects the other tube (that is where the scar tissue came from). For that reason, you are at increased risk of another ectopic on the opposite side.

Your chances of getting pregnant are still the same, despite only having one tube, but you have a 30-50% chance of an ectopic. The treatment that I would recommend at this point would be to consider IVF so that the tubes can be bypassed.

I hope you succeed in your efforts to become pregnant and that you keep in mind the risk involved with trying to get pregnant naturally with your past medical history.

Sincerely,

Edward Ramirez, MD, FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF
Monterey, CA