IVF and donor sperm
16 Replies
teri-chan - November 11

Dear Doctor Smith,

I've put my two questions at the end. But first, there's a lot of background.

Here's my reproductive history. I began trying to conceive in May 2005. Up until then I had had unprotected sex twice in my life and gotten pregnant twice. The first time in 1990 after taking the morning after pill. The second time in 2002 after having accidentally skipped two birth control pills. I had an abortion each time. The second pregnancy was with my husband (with whom I am now trying to conceive). In 2002 we were told by everyone we talked to (friends, the counselor at Planned Parenthood, and my primary care physician) that we would have no trouble getting pregnant in a few years, when the time was better.

I turned 41 the month we started trying to conceive, and I went to see my primary care physician for a check-up to make sure that I was in good shape to start trying. He said he thought we'd have no trouble at all. But then I started looking at the internet. And I soon learned that in spite of what everyone had told me, it might not be so easy to conceive at my age. (Yes, of course I'd previously heard all that stuff about fertility declining at 35, but with the exception of two, all my female friends have started trying only after they were 35, and not a single one of those failed to give birth to a healthy child (several at 37, several at 38, several at 39, a few at 40, and a few at 42). That made me tend to believe what Susan Faludi wrote in _Backlash_ about how these gloomy statistics are made the topic of much media hype in an effort to discourage women from having careers--that really there's nothing to worry about until the mid-40s.) We tried three natural cycles (the last with IUI), two IUIs with Follistim, and now we're at the tail end of an IVF cycle. 12 eggs were retrieved; ICSI was done on 8; 4 fertilized; 2 made it to day 5, but were only morulas and had some fragmentation (20% I was told). The transfer of those two went very smoothly this past Tuesday. Any guestimate as to my chances?

I know the chances are not so good, so I'm trying to think about what to do if the pregnancy test is negative. Donor eggs are out of the question for me, even though I know that the main issue is the age of my eggs. Donor sperm is not out of the question, so I wonder whether it would help chances at all if I try IVF one more time, but with donor sperm this time. Except for my age, everything with me--hormonally and mechanically--checks out fine. My husband's sperm counts have varied widely: 1.3 million total motile on a semen analysis done at our local hospital lab in early July; 24 million total motile on an IUI on two weeks later; 8 million total motile on an IUI in August; 35 million total motile on a semen analysis at the RE's office at the beginning of September; and less than 1 million total motile on an IUI two weeks later. On the semen analysis done at the RE's office, the sample had a morphology (strict) of 4% normal forms. The sample we sent for SCSA a month later had DNA fragmentation of 29% and high DNA stainability of 15.5%. He's been to a urologist, who found nothing wrong.

To sum up, I have two questions: (1) Would you give a guestimate as to my chances for the current IVF cycle? and (2) Do you think that we'd have any better chances using donor sperm on a future IVF cycle?

Thank you very much.

 

Dr Smith - November 11

It is unfortunate that you were lead to believe that pregnancy would be relatively easy in your 40's. Nothing could be further from the truth. This biological reality has nothing to do with discouraging women from careers - in spite of what Susan Faludi says. It is what it is - a rapidly decreasing probablity of success after 40. Unfortunately, there's no shortage of bad advice out there. If its any consolation, we see many, many women who have been told the same thing "As long as you're having regular periods, you won't have any trouble". Yeah, well, it just ain't so.

Your chances or pregnancy are around 20% considering the two morulas that were transferred. I know that doesn't sound great.

Althought the SCSA results were borderline (good/fair), IVF with ICSI can, for the most part, overcome the sperm problems you mentioned. I wouldn't rush to use donor sperm just yet. As you are now aware, the major rate limiting step here is the genetic potential of your eggs. You stimulate reasonably well for someone your age (12 eggs) and having two morulas on Day 5 (I am assuming it was Day 5) is not that bad. I think that as long as you are realistic about your chances, you should try IVF/ICSI again. Good luck.

 

teri-chan - November 11

Thanks for your answers. I want to echo all the people on this board who have commented on how good it is to have you as a resource.

You're certainly right that there's no shortage of bad information out there. And it's not just nutty feminist Pulitzer Prize-winning journalists! Here's a quote from the Reproductive Science Center of the San Francisco Bay Area web site: "Studies have demonstrated that over the age of 40 almost 50% of women will experience infertility." That, of course means that more than 50% of women over 40 (but presumably pre-menopausal) _won't_ experience infertility. And one would think that this would be the younger people over 40 but pre-menopausal--say those from 40-44.

A chance of pregnancy of 20% doesn't sound so bad when I consider the fact that my chances of pregnancy the first time were 5% (because the morning after pill is supposed to reduce one's chances by 75%, and at 26 years old, I was supposed to have had a 20% chance on a natural cycle) and the second time were 10% (because at 38.5 years old, I was supposed to have had a 10% chance on a natural cycle). But, of course, 20% is 20%. Still, I am a little surprised that you think my chances are that low, since according to the 2002 CDC statistics, 73% of 41 year olds who started ART cycles made it to transfer, and 18% of 41 year olds who started ART cycles got pregnant. That gives a pregnancy rate of about 25% for 41 year olds who made it to transfer in 2002. I thought that in 2002 most transfers happened on day-2 or day-3, and I would have thought that transferring two day-5 morulas would give better chances than transfering 3 or 4 (or however many they were transferring in 2002) day-2 or day-3 embryos. Can you explain to me what's wrong with my conjecturing here? (Is it that in 41 year olds, one would expect that more than half of the day-2 or day-3 embryos would make it to day 5? Or maybe that they transferred more than 3 or 4 day-2 or day-3 embryos in 2002?)

As for the donor sperm, you suggest not rushing into that just yet. But I guess I feel that given my age, nothing counts as "rushing". I don't know how much longer my FSH levels will be what they are (measured 3 or 4 times now and varying from about 4 to 5 (whatever the units are!)--I'm not sure what the lab methods were, so I can't give more meaning to those numbers--with E2s 60 or less (again, whatever the units are!)), and so I want to make the absolute most of the next IVF, if there is one, since it is likely to be my last. It's extremely important to me to have a child that is genetically related to me, while it isn't so important to my husband to have the genetic connection. (And if it does turn out later to be important to my husband to have a child that is his genetically, I would be happy to turn to a donor, as long as I have a child that is mine genetically.) Of course, all things being equal, I'd prefer to use my husband's sperm. Do you think that all things are _genuinely equal_ if we do ICSI with his sperm instead of IVF (with or without ICSI) with donor sperm?

Again, thank you.

 

teri-chan - November 11

Oops, in my just previous message, I was mistaken (but not by much) about the 2002 CDC stats per ART cycle. Here's what they were: age 41–42, Retrieval 80%, Transfer 73%, Pregnancy 17%, Live birth 11%. So that's a pregnancy rate of 23% per transfer for 41 and 42 year olds.

 

Dr Smith - November 15

The 20% percent chance is still realistic, even though they transferred two morulas on Day 5. Here's what I was thinking. I was taking into consideration that (according to information presented at a recent meeting I attended) there appears to be an increase in embryonic arrest at the morula stage when morphology is below 4% and DNA fragmentation index is above 30%. Since your husband has borderline values for these factors, I didn't give as much weight to the embryos reaching the morula stage as you did in your interpretation of the CDC stats (which, I might add, was a great analysis of the available data).

With regard to the sperm issue, I think there may be a [i]slight[/i] genetic advantage to using donor sperm (maybe a couple of precentage points on the success rate), but not enough to warrant using donor sperm if your husband was reluctant (as most husbands are). If he is as relaxed about it as you say, then you might want to tweak the next IVF cycle by using donor sperm to squeeze out a couple of precentage points.

 

teri-chan - November 16

Thanks for your response and for your compliment about my analysis of the available data.

It seems to me that there's a conflict though between your two paragraphs. But maybe I wasn't fully understanding the first. The first seems to say to me that I would have been right in assessing my odds as higher than the 23% that existed for 41-42 year olds who made it to transfer in 2002, EXCEPT THAT my husband's sperm issues would lead one to think that there was a more than usual chance of embryonic arrest at the morula stage. So instead of my assessing my odds at above 23%, you estimated them at 20%. Your second paragraph seems to say that by using donor sperm I'd gain maybe a couple of percentage points on success rate. But the difference between 23% and 20% is already three percentage points. I grant that that's not a significant difference from "a couple", so read on!

So here's my confusion. If donor sperm were used, then wouldn't my analysis of the CDC data hold? According to my analysis, all other things being equal, you should see a reasonably significantly higher pregnancy rate (more than a couple of percentage points) per transfer in day-5 transfers on 41 year olds in 2005 than you see in pregnancy rate per tranfer in who-knows-what-stage-transfers on 41-42 year olds in 2002. (I can think of one possible reason that the analysis might not hold if donor sperm were used. And that would be if donor sperm was less likely--even when using ICSI--to result in a pregnancy than average fresh sperm.)

Thanks again. It's really nice that you've been so genuinely responsive to my questions. Often, it seems, that it takes me a whole lot more effort than it's taken with you, for me to get my questions across. I know my questions aren't dumb ones, so I like to get them asked and answered. It's just that it's usually so much harder to get the person with the expertise in RE/embryology to understand my question. It's such a relief to communicate with you!

 

Dr Smith - November 16

Yes, your logic holds, BUT, not all Day 5 transfers are "equal". As you know, some Day 5 transfers are not at the blastocyst stage or the blastocysts are of poor quality. If they were to transfer two good quality blastocyst stage embryos on Day 5, then yes, the implantation rate (embryos implanting/embryos transferred) would be significantly higher than an equal number of Day 3 embryos. However, in most cases of Day 3 transfer in women over 40, they transfer all the embryos that are showing signs of continued development. In this case, the weeding out process occurs in the uterus instead of the dish, but the result is the same - the embryos that are going to make it to the blastocyst stage do and those that aren't going to make it don't. So, in practical terms, the pregnancy rate for Day 3 versus Day 5 is not markedly different in this age group. However, overall pregnancy rates have been steadily increasing for years, so 2005 will presumably be higher than 2002.

The other issue is pregnancy rate versus live birth rate. The miscarriage rate for women over 40 is significantly higher. So getting pregnant is one thing, staying pregnant is another. This is another place where donor sperm may give you a [i]slight[/i] advantage because of the borderline DFI value. The miscarriage is higher when the DFI is >30 (regardless of age group).



 

teri-chan - November 16

Ah, thanks so much! That's very useful information about the slight difference in miscarriage rates.

 

teri-chan - November 17

My pregnancy test yesterday was positive, but my hCG level wasn't as high as they'd like to see. Normally I'm an information hound, but I asked not to be told the actual number, since I figure that knowing it won't make a difference to any decision I might make and stands to make me even more worried than I am. Still, if you know what the (mere) chemical pregnancy rate for 41-year olds is, I suppose I'd like to know that to help me prepare to hear the results of tomorrow's hCG test. (I hope this still counts as an embrology question.) As always, thanks.

 

Dr Smith - November 17

I don't know the nationals stats on chemical pregnancy rates as they are not reported to the CDC. In our practice, the chemical pregnancy rate for 40-42 year olds is 18% (i.e. 18% of the positive pregnancy tests do not progress to a clinical pregnancy - defined as a gestational sac on ultrasound).

Hang in there. It ain't over 'till its over.

 

teri-chan - November 19

My hCG was up on Friday, but it hadn't doubled. And I took an HPT this morning with a sensitivity of 25 mIU/ml, and it showed negative, so it's over.

 

Dr Smith - November 21

Sorry to hear of your bad news. Chemical pregnancies are usually caused when the embryo develps to the blastocyst stage, attaches, initiates implantation, but has an inadequate number of stem cells to continue development. The sac cells (trophectoderm) of the blastocyst are responsible for attachment, implantation and secretion of the pregnancy hormone (hCG). They did their job, but with an inadequate number of stems cells, the embryo fizzles.

Chemical pregnancies can also occur when the maternal immune system mounts an inappropriate response and prevents the embryos from continued access to a blood supply. This inappropriate resonse is thought to be caused by an elevation in the number and activation of the natural killer cells (a type of white blood cell).

 

teri-chan - November 21

Well, it turns out that my hCG tripled from Friday. But my progesterone level is low. It's 8.9. Any thoughts? I go in again on Wednesday for another blood draw.

 

Dr Smith - November 22

Important lesson for the readers: Do Not Believe Urine Tests! Blood tests are the only accurate way to measure hCG.

Good news? I hope this will go the distance.

The progesterone level in the blood will be porportional to the method of administration. Suppositories deliver the progesterone directly to the uterus and the corresponding blood levels are lower than when the progesterone is taken by injection. 8.9 is on the low end for injection, but within the normal range for suppositories. In any case, its high enough to sustain the pregnancy (the natural progesterone level during early pregnancy is in this range), so you can relax about that, at least.

Good luck.

 

teri-chan - November 26

I just thought I'd let you know that on Wednesday (11/23) my hCG level was lower than on Monday, so now it is actually over. I'm thinking of trying another IVF in February/March 2006.

The nurse had told me on Monday (11/21) that with my low progesterone level, it was unlikely that the pregnancy would continue. She said that my low progesterone level was probably indicative of poor egg quality. What can you tell me about the link between progesterone level (especially in IVF) and egg quality? (Maybe this falls outside the realm of embryology, but it seems to me that you may have some informed comment.)

Thanks.

 

Dr Smith - November 28

The nurse has no clue. There is no link between progesterone levels and egg/embryo quality. The serum progesterone level during the two week wait is dictated by the amount you take either by suppository or injection.

 

Dr Smith - January 26

Don't know. Your question is outside of my field of expertise. Try posting your question on Dr Jacobs Infertility 101 Message Board. He's an M.D. and would know better than I about medications to be avoided during pregnancy.

 

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