American Infertility Association
Live Chat Event, July 19, 2001

LisaRosenthal: Good evening. I am Lisa Rosenthal, Educational Coordinator for The American Infertility Association. Our speaker this evening is Dr. Carolyn Salafia, a reproductive pathologist. Dr. Salafia will be chatting on the topic of "Loss After ART." Dr. Salafia has a unique point of view, particularly about pregnancy loss.

LisaRosenthal: Good evening Dr. Salafia, thank you for joining The American Infertility Association tonight.

Dr. Salafia: Hi everyone. I'd like to start by just briefly describing what a reproductive pathologist happens to be. In hospitals where I've worked and been on staff, the clinicians came to be able to use the type of diagnoses that we can routinely give using pretty low-technology staining, standard microscopy, even after a first miscarriage to help them start thinking about their patients differently. A reproductive pathologist, in my case, is someone who is trained in pathology, that is the laboratory diagnosis, either with blood studies, urine studies, chemical analyses, or with a microscope and who uses that expertise only to understand problems related to pregnancy and the early newborn period.

I have to say that my goal would be to improve our ability to understand patterns of problems in women so that, using a combined approach of screening tissues cheaply and efficiently under a microscope and laboratory testing, even after a first pregnancy loss, you could get meaningful information as far as cause.

LisaRosenthal: Dr. Salafia, after how many miscarriages do you suggest your type of services?

Dr. Salafia: I think that it really depends on the individual. If you have to go outside of your insurance for specialty consultation that may only be incompletely reimbursed, that's not the same as being able to have this service provided at your own hometown pathology department. But there are things that are known about recurrence risks even after first miscarriage. For example, if you have a wrong chromosome number miscarriage (compared to a miscarriage of a pregnancy with normal chromosome number) your major risks for future problems are related to a second wrong chromosome number miscarriage, the type of problem that is mainly related to advanced maternal age. However if you have a miscarriage with correct chromosome number in the pregnancy, well that pregnancy was, to the best of our ability to assess it, "capable" as well as its genetic program of making a healthy baby.

Studies have shown that these types of pregnancy losses do carry risks of losing other pregnancies with, again, correct chromosome number. And the types of pregnancy losses of correct chromosome number of generally the types of things that we blamed on things like the uterine lining, blood flow, clotting, infection, uterine structural defects, etc. It's different from an extra chromosome in the egg or sperm, or two sperm getting in to fertilize one egg... that type of problem can not be fixed. If you have any troubles getting pregnant, waiting for the standard three miscarriages is going to cost you wait too much time.

LisaRosenthal: Can you describe what types of diagnoses you are referring to and how you identify them?

Dr. Salafia: I think I just started to get into that up ahead, with problems on blood vessel structure or function, evidence that the immune system is being called into the uterus in a nonstandard fashion, or other evidence that the uterus is not anything other than the perfectly receptive home that the pregnancy is seeking. Let's also a talk about preterm birth, premature rupture of membranes, later problems with growth and development of the baby, all of which can occur more commonly following assisted reproductive technology. A lot of the recurrent problems that I see are pregnancy loss. That's also a reason why some people end up in IVF (that's a reason I'm not sure I'm entirely comfortable with, but that's another story)

LisaRosenthal: Dr. Salafia, what is a red flag that your doctor is not handling your losses in an appropriate manner?

das: Hi Dr. Salafia. Thanks for offering your time tonight. I am 36 and had my first IVF/ICSI in February. I made 32 eggs (of which 25 were ICSI'd) and 19 of these fertilized. We transferred two 10 celled embryos. We found out on 2/18 that we were pregnant. Both embryos implanted but one stopped growing by the time we had our first ultrasound. The other one was growing but all they saw was the yolk sac but no fetal sac. We went back a week later and we saw the fetal pole and the heartbeat. It was the greatest sight of our life. It was like a dream come true.

I bled a little bit a week and a half later. The RE did not think it was a problem as it didn't last long and that it could have been due to the progesterone suppositories. I had my first OB appointment and they had me do an u/s due to the previous bleeding and because at the second ultrasound, the baby measured almost 2 weeks smaller than it should have. Well, when I went for this next u/s, the baby hadn't grown anymore and the heart had stopped beating. I was beyond devastated. How could it have happened? Why-after going through so much?

Our diagnosis was moderate to severe male factor. My husband had done a karyotype test that came back normal. I had a D&C since the baby didn't look like it was going to pass on its own. My RE did the blood clotting tests (not sure of the names-antilipids?). They came back normal. He did not due a karotype as the tissue sample from the baby came back normal. Do you have any ideas what could have gone wrong? What are my chances of having a successful pregnancy the next time around? I am currently doing a FET as we have 9 frozen embryos waiting for us. I want to be pregnant so much but am so afraid I will miscarry again. Sorry this is so long and thanks for any advice you can offer! Deb

Dr. Salafia: The earlier the embryo fails the statistically greater the likelihood of random wrong chromosome number accident. One of my colleagues who directs the chromosome lab at NYU tells me that five out of six early losses following IVF will be random wrong chromosome number accidents. So that would really be what I would be thinking about with the little one who never got past the stage of the yolk sac.

Dr. Salafia: This is a real tough one. I only failed IVF three times before my husband decided he'd had it and arranged to adopt our twins without telling me about it.

rdkvel: Hello Dr. Salafia, I have question. My husband has a low sperm count. Do they have to do surgery or is there anything else such as pills or vitamins?

AnnMarie: Dr.Salafia, do you feel that conception through IUI can increase/(cause) PROM?

Dr. Salafia: It's tough because I'd like to know whether the chromosome count on the pregnancy came back as normal or normal female. This is an important question and I can certainly understand that some people asked specifically not to know the sex of the child they had lost. It would be harder to bear the more they can understand what they had missed. But if the chromosome count was normal female, the very next question I would have to ask the doctor is what percent of the time due to get back in normal female chromosome count from that laboratory. You are normal female too.

Dr. Salafia: Just on odds, about 50 percent of first trimester losses are random wrong chromosome number accident. Half of those with CORRECT chromosome number on boys and how far gross, so if your hospitals laboratory is doing a good job of sorting out your tissues from the pregnancy tissues, your doctor should, over the course of a year, get back 25 percent normal female chromosome counts. If you get back never 25 percent, that laboratory is counting mothers tissues instead of pregnancies tissues. Therefore it's a little bit difficult for me because I can't, unless you tell me that this is a male chromosome count exclude that the laboratory counted your tissues in error

Dr. Salafia: However, I don't know how old you are and your message has aged off my screen. I don't know what else you may have as far as medical or family history, anybody in your family with high blood pressure or heart attack at age 60 or less? You said you were bleeding, and if I were embedded real-time working with the clinician I would have asked your doctor to do uterine artery resistance studies. It is any possibility that there is increased resistance of flow in the plumbing system that is your vascular bed, that could make it more likely for a pipe to burst and for you to have blood. My friends in cardiology tell me that they don't think we know half the ways half the causes on blood vessel injury in all folks, let alone in young reproductive age women's uteruses... so that your blood tests being "negative" only means to me that we can't put a label on you that way.

austin: I have not even made it to pregnancy yet. I had a failed natural FET yesterday.

LisaRosenthal: Austin, you have my sympathy. There is no worse news at the end of a cycle. I hope this chat will help in some way.

austin: I don't understand why it was failed because the RE said that I had perfect day 5 blastocyst embryos. She said that they were rated a 2bb and that they didn't even loose any color.

LisaRosenthal: Austin, it's a good question for Dr. Salafia, why do beautiful embryos not implant? Is this an early form of miscarriage?

Dr. Salafia: Austin just looking at the outside of the embryos isn't a very good way of counting the chromosomes. Beautiful embryos not implanting could be a reflection of our limited ability to know what beautiful really is at this very early age.

Dr. Salafia: However chromosomally correct embryos, embryos with an apparently capable developmental program, not implanting, that would implicate some problem in the uterine environment or in the uterine interaction with the placenta that was keeping this capable being from executing its program, so to speak. That's why a number of the doctors that I work with use the tissues and tissue review in concert with chromosome studies of pregnancy losses. We don't count chromosomes, but we look at all of the non-chromosome reasons why pregnancies are complicated. Many of the problems with IVF that occur later in pregnancy, like membrane rupture or preterm labor, happened in chromosomally normal babies come up that the same types of placental problems that can damage a very early embryo, milder, less severe, just different version of the same problem can lead to a problem at 24 or 26 or 28 weeks...

Austin: Thank you Dr. Salafia

Jaws: Hi Doctor Salafia. If I recently lost one of my twins due to a "random" fatal birth defect, does this mean another pregnancy should be fine? My twin had no chromosome problems. I was told just random, but I'd like to use my 7 frozen embryos but am afraid it is a defect in them.

Jaws: my one twin was 20 weeks when we learned she had cystic admatoid malformation and would die..and did at 20 weeks inutero. I delivered her at 27 weeks and held on to twin b 9 more weeks..I want to know if since they said this was random and not chromosonal (via amnio) is it safe to use my frozens??

LisaRosenthal: jaws, was the other twin born and ok?

Jaws: Lisa yes, she was born at 36 wk and was healthy...I am having such grief over my lost twin, and want to use my frozens but I'm scared...

Austin: Dr. Salafia, My menstruation has been 32 - 34 days since fresh cycle when I was hospitalized for Hyperstimulation. After transfer for FET I went down to 27 days is this normal?

Dr. Salafia: Jaws, the lung problem you describe really is the bolt of lightning from the blue. Can you tell me if you had identical twins? It could have been part of the process of identical twinning which one doctor who was very famous than placentas says is really a "birth defect related" p[process... I would have to tell you that I could not give you any recurrence risk with that type of lung malformation. And I am a worry wart, who takes saying "no recurrence risk" very seriously.

wynn: Hi Doctor don't know if this has been asked BUT is a chemical pregnancy due to chromosomal defects?

LisaRosenthal: jaws, I'm sure the feeling of loss is enormous. Recovering from that type of grief is very difficult. Great book, "the grief recovery handbook". Check it out.

Diane: Dr. Salafia, do you have an opinion regarding the value of PGD? What are the risks/benefits?

Dr. Salafia: Diane, if you NEED to know the chromosome complements, if you other carrier of something that you cannot bear to take the chance of passing onto a child, PGD is extremely valuable. I would have a little bit of difficulty in justifying it for gender selection, and I also are not certain that it does what some people may be hoping it does, who want to avoid the pain of early miscarriage of wrong chromosome number embryo by guaranteeing themselves chromosomally correct number embryos

Jaws: Dr., I was told they were not identical....I am not sure why or how they no that...so your telling me basically I was the one in a million, and have a good shot with frozens?

Dr. Salafia: I think any technological intervention carries its own risks. IVF is certainly still less effective than normal human reproduction, and PGD is just another step in the pathway... that makes the intervention more complicated

Dr. Salafia: Austin, You don't carry diagnosis of PCO, do you?

Chuck: so is pgd simply counting chromosomes?

Austin: Dr. Salafia, Yes I do have PCO and blocked tubes

LisaRosenthal: Dr. Salafia, that was a fascinating answer to Diane. I'm not sure I follow it. Doesn't pgd basically give the same information as an amnio?

Austin: May I ask what pgd is?

Dr. Salafia: DAS, from my point of view I'm not aware of any recurrence for that type of lung problem. That is certainly the type of problem that could compromise a single pregnancy. When one pregnancy fails, especially if it's pretty far along, obviously, the changes going on in that tissue can irritate the uterus, and possibly make prematurity more likely...

You're probably not one in one million to have a child with CAM, but it should not occur... and your shot with frozens ought to be as good as anyone else's, and if a problem happens in the pregnancy, it shouldn't have anything to do with the prior pregnancy's problem.

wynn: Doctor I had a chemical preg w/ 3 day all 8 celled embryos DX blocked tubes age 30 1st IVF was that due to chromosomal defects or something else. My RE said they were excellent quality.

laurel: Hi Dr., I miscarried at 7 weeks in March after IVF #2 with ICSI. Does ICSI increase the chances of miscarriage?

Dr. Salafia: PGD+preimplantation genetic diagnoses, where they take one cell out of the early embryo and count its chromosomes, to know which embryos have correct chromosome number, carry certain diseases, etc., etc.

LisaRosenthal: I want everyone to know that The American Infertility Association is lucky enough to have secured a monthly online chat with Dr. Salafia. Check out our chat schedule at americaninfertility.org Dr. Salafia will be here once a month. We are really grateful to Dr. Salafia for her time and really unique expertise.

Berni: Good evening! Quick Q b4 bed!!! Is m/c MORE likely with an IVF pg??

Diane: Thanks for answering my question. My question re: PGD came up largely b/c another "over-40" year-old woman said she participated in a study using PGD, and it helped to get a better idea of the percentage of "good" embryos she was producing. Then, voila, she got pregnant. (Lucky woman.) I'm curious whether there are correlational studies out there relating the superficially "pretty" embryos with the chromosonally good ones. What is the state of the art/science at this point in time?

Dr. Salafia: wynn, Again, my colleague at NYU is probably one of the most meticulous cytogenetics laboratory directors I know and she is very interested in miscarriage. She had her own children pretty late, and her laboratory is super at sorting out mothers from pregnancies tissues, even very, very early. She tells me that five out of six early losses following IVF are wrong chromosome number accidents I've recently seen one article of the literature that due to provide some evidence that ovarian stimulation increases your chances of wrong chromosome number accidents (I actually think that probably make some biological sense).

Chuck: ...so they are looking for specific chromosomal abnormalities, other than simply the number of chromosomes?

Dr. Salafia: wynn so So certainly I could tell you that if I had 100 women with your story, probably the single most common cause would be chromosome wrong number accident, but that unfortunately does not allow me to say anything at all about YOU. That's the problem with statistics... can't apply really to the individual...

LisaRosenthal: berni, it seems like Dr. Salafia touched on your question with her answer to Wynn. Feel free to repost if you want a more detailed answer.

wynn: Doctor that is kinda scary so IVF can cause problems that otherwise may not occur? Are my chances of having this happen again high my e2 at retrieval was 5500 fsh 4.2 age 30

Dr. Salafia: We have 2 questions that are related. Laurel asks if ICSI increases the chances of miscarriage. BERNI asks the miscarriage is more likely with an IVF pregnancy. Your body normally sets pretty strict criteria that limit the number of eggs that are allowed to be ovulated every month

Think of it as an escalator with narrow steps, and you have to be pretty alert and agile to jump onto the escalator and be able to ride all the way to the top

Austin: Dr., Salafia, On my retrieval I got 22 eggs. I understand that is why I had the Hyperstimulation. Should I have been watched closer. I feel that they should have given me less Gonal F. I was on 2 powders to 1 water.

rita: Dr. Salafia: I had a loss at 17 weeks. Could such a late loss be associated with IVF/ICSI. By the way, my slides are in your office.

laurel: So Dr., IF IVF increases the chances of chromosome problems and m/c does ICSi then make this even more likely? We have to do IVF with ICSI because of male factor problems.

Chuck: Austin: if that's the same size vials that we had, its not very much gonal-f....

Jaws: Dr. Being tubeless is my only problem due to 3 ectopics...are my chances higher for IVF and should I use less embryos to avoid multis

Dr. Salafia: One thing that can happen when you do if the protracted and high dose stimulation to the ovary is that you make the "window of opportunity" so wide, broaden the steps so that any foolish egg can step on...

Again, it's really hard to set out, because many people who need IVF are like I was, something in their ovaries isn't working as perfectly as ought to be, and we really don't know how to make the ovary do its job, or pay attention more specifically than just "whacking it over the head" with FSH. So there may be some chance that you would have a miscarriage with an egg that your body would normally have "censored."

wynn: Doctor from what you're saying, doing natural IVF without drugs may have a place for some women? Correct or way off?

Austin: Chuck, When I read the instructions for the Gonal F it said that people with PCO should only take one powder to one water

Berni: I missed the exchange with Wynn - its gone off my screen - is it YES to "is m/c MORE likely with an IVF pg"??

Dr. Salafia: I was surprised to see literature coming out now that even in Singleton pregnancies in IVF, the increased risks for the later complications such as prematurity and low birthweight. That makes me think that the something more than chromosomes going on in the IVF technology issue. I've been trying to get some of the IVF groups interested in better understanding some of these problems. It's quite likely that the earlier we modify technique and methods, the better outcome will be. Waiting for a perinatologist to try to do something at 18 or 20 weeks isn't probably as good as, if we understood the process better, doing something around the time of conception, or very early in pregnancy

wynn: It seems to say that Bermie BUT I'm not sure.

Chuck: Austin: wasn't aware of that....highest we've done so far is 4, and they told us that was a "moderate" dose. New RE wants to start us w/ 4 in the am, and 3 more pm!! (DW is old..hee, hee). Also, no pcos....

Dr. Salafia: the answer is, I think it's biologically reasonable that you might have "extra" IVF pregnancies--- That you would NOT have had if you were not on IVF that are wrong chromosome numbers..

LisaRosenthal: wynn, in light of what Dr. Salafia is saying, that would make sense. Natural IVF, I mean.

Austin: Chuck, I am young at 30 and I know that in the long run I am lucky to have had 12 embryos make it to blastocyst stage.

Dr. Salafia: I myself am into trying to better understand your ovarian cycle (that is now down to 27 days) then beating your ovary over the head hoping to make that yield up a "good egg."

Chuck: Just my $.02: seems to me that natural IVG...the odds are just too long for a successful pg to justify surgery....know what I mean?

Christine: Dr. Salafia, I lost my identical twin sons in March of this year due to multiple birth defects that our geneticist and perinatologist attribute to their being identical. Something in the way the egg split that caused their cells not to form correctly. I've read a lot about increases in identicals due to IF tx...would you say there is any connection?

Berni: that is now down to 27 days???????

Dr. Salafia: But you have to understand that I was personally and unexplained infertility patient, ovulated normally and FSH made my ovary shutdown, and nobody has been ever able to explain that to me. We ended up in IVF before we were married three years (because of all the friends I have in this business) and it was the logical thing to do....
The FSH didn't work, it didn't make sense, but IVF was logical, so we continued to do it... this type of approach is what makes me have to tell you up front that I have some personal concerns about using technology to cure what is otherwise "unexplained

Austin: Dr. Salafia, Because my cycle did come down to 27 days does that mean that I might have had a miscarriage at a very early stage instead of the embryos just not taking.

LisaRosenthal: Dr. Salafia, you are very brave to share your own personal story with us. Did it work?

Chuck: I think that's really cool: an IF doctor that has been through it herself....how common do you suppose that is??

Dr. Salafia: Christine, I mentioned a "very famous doctor" who talked about identical twins a few posts ago... Dr. Benirshcke (his son was a place kicker with a football team a few years ago) talked about identical twining, splitting an early embryo as being an "teratogenic" process. That road in quotation marks means related to birth defects, that there is something happening to the baby to cause it to split the. Yes I would agree that identical twins can have very peculiar patterns are birth defects that can clearly be attributable to them having split early. And I also do know that not all multiple pregnancies in IVF are two-egg pregnancies. Many of my patients, and a lot of the doctors ideal with often lead to the conclusion that the through two embryos and, and two sacks are seen how to that they can't be identical. That isn't the case, as I know from looking at their placentas after delivery, and under the microscope...

Austin: I think that it is very cool as well Chuck. I know that it makes me feel better knowing that she understands how we feel.

LisaRosenthal: Chuck, I could give you 10 names off the top of my head!

Dr. Salafia: I started doing only reproductive pathology about eight years before I got married. Frankly I don't know that I could do what I do now if I had not "only" failed IVF. I think many of you folks are much braver then I am.

Dr. Salafia: I was speaking with a couple who had a stillborn child at 36 weeks, who were "surprised" that their IVF/ICSI pregnancy was not considered high risk. I am surprised too, given the investment in these pregnancies alone, and the data regarding increased preterm birth even if you only have one baby inside... the outlays that we must better understand only processes and pregnancy to make certain that we not only deliver a child, but the healthiest child that we can.

Christine: My twins were also monoamniotic, which I understand increased their chances for birth defects because of the late splitting of the egg. My biggest worry is having another baby with birth defects. I feel like I need to be reassured that nothing I did in my fertility treatment resulted in their defects and their subsequent deaths.


Dr. Salafia: Lisa, glad to know I am not alone!! Carolyn Coulam with her 11 kids always is the first face to leap to my mind. She is a reproductive immunologist in Chicago.

Jaws: This truly is helpful information for us all.

Dr. Salafia: Chuck, that is why I think the "why" is so important... parents need to know why, just for their own peace of mind, just to put to rest of the helpful comments that people tell them as far as things they could do better or could have done better, and to stop wondering in their own minds if they could have protected that child better.

And the doctors need to know, because these types of problems that compromise chromosomally correct babies throughout pregnancy are exactly the type of problems that have been recently recognized, over the past ten years, and have the potential to recur.

LisaRosenthal: I hope everyone here is aware that The American Infertility Association hangs our chat transcripts on our website at americaninfertility.org under "Facts and FAQ's". We have some unbelievable information available there. Also, our message board is monitored daily by doctors. A nice thing in the middle of a cycle. Terrific, supportive people hang out there as well. Great place to check out our chat schedule as well.

Jaws: Dr. can identical twins have 1 with fatal birth defect while the other is perfectly healthy????

Dr. Salafia: Jaws, the answer is yes to that.

Chuck: Oh, yes. I've thought the same thing, myself. If they told me we'd never have kids, that wouldn't be so bad....as long as they could say "why".

Dr. Salafia: Nothing upsets some of my patients more than having a loss at 24 weeks, for example after IVF, and going back to their IVF clinic and being told that they were counted the "success", so they are going to do exactly what they did the first time, and this time it's just not could have a problem to 24 weeks...??

Dr. Salafia: Many other later problems in pregnancy are not considered to be the area of the reproductive endocrinologist. One of the problems I think it really making improvements in this field is the lack of continuity between first trimester obstetricians (reproductive endocrinologist) and the high-risk perinatologist who worries about a baby who has the chance of being born alive

Austin: Dr. Salafia, Is it true that it usually take 3 IVF transfers for someone to get pregnant?

Dr. Salafia: You folks might want to check out my "Medical Student Lecture 2001" on my website. It's what I gave at Columbia this year... and the last section is on multiple gestation.

Christine: Dr. Salafia, I agree with you! My RE was incredible. She took all our information regarding the twins and even called the drug companies and they called me, etc. The follow up made me feel like she and everyone else involved in the process really cared...

Dr. Salafia: I think it takes three IVF transfers for you to start being somebody who is low odds to have IVF success... if a 15-20 percent of people get pregnant on each IVF cycle, by the time you are at three cycles, if the only issue is mechanical, you might reasonably expect to have been able to get pregnant at least once. It's a numbers/statistical probability game again.

wynn: Best of luck to everyone here tonight I hope all of our dreams are realized soon!

LisaRosenthal: Dr. Salafia, thank you so much for your time and expertise here this evening. You did a wonderful job answering questions, keeping everyone straight, and giving wonderful information. I am really looking forward to our next chat. Hope you enjoyed yourself.

Dr. Salafia: Thank you for having me. I hope I was clear... both about biology, and possibly my own bias. Good nite to all!

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