40 Year Old U.K. Woman With One Miscarriage Feels Time Is Running Out For Her: More IUI's, More IVF Or Donor Eggs?

This post concerns a woman in England who has written to me several times regarding her infertility journey. I would like to publish the entire correspondence for those of you who have a similar dilemma, that is, what to do if you have gone through multiple intra uterine inseminations, actually get pregnant naturally but miscarry, but because of your age, needed to consider IVF as the next step. Unfortunately, the first IVF cycle you do fails. What next? You can read my final response and advice at the very bottom. It is interesting to see how women in the U.K. receive infertility treatments through the National Health Service and the limitations of this government sponsored health care.

Question:

Hello Doctor Ramirez,

Hope you are well. It's L. from England again! I have added my previous questions below and your answers below as I didn't know how to add a link to my history. I have had my first round of IVF (NHS) and it did not go well. First I down regged with Buserelin Spray and this did not work after 3 weeks I was switched to the injection which then worked after another 2 weeks so all in all 5 weeks of down regging. I was then given Menopur 300 ui (Maximum dose at my clinic) after 12 days of stimming this has only produced 2 follies ( I have had 4 follies on puregon at a much smaller dose) at my scan today they have said the they will convert me to IUI as they need 3 min for IVF.

I am now so confused about what my next step should be if the IUI does not work. Unfortunately I am only really able to afford one more go at IVF, at a push with the help of family maybe 2 and wanted to ask what you thought my best option was. I have heard that mild/mini IVF may be better for me at my age however I am worried about my response, but then can't help thinking that my response was poor because I down regged for too long.

My niece has agreed to be a donor for me but im not sure she will be accepted by the clinic as her BMI is high and she is only 21 (she has a 1 year old daughter). My clinic said usually the lower age limit is 23. (I could possibly look at other European clinics with not as strict egg donation guidelines).

Or should I try again with my own old eggs? I have read about the benefits of taking DHEA to improve egg quality but feel that here in England I would need to self medicate this as I don’t think doctors here have taken this approach on board yet. What would you suggest I take if you indeed think it is appropriate. I am already taking the low dose aspirin and of course folic acid. Basically what I am trying to ask is if you were me what would you do in view of my low follie count on this IVF cycle. What regime would you put me on if I were at your clinic? or is it better to give up on my eggs and do down the donor route? Thank you in advance for your response. I always feel much better when I receive your advice. L. from the U.K.

PREVIOUS LETTERS:

Question: Hi, I am having IUI in England. My first attempt was cancelled as I ovulated myself before the follicle was large enough. My 2nd attempt I took 50 puregon every other day from day 5 and then had IUI on day 17 (I have a short cycle of 24 days), my period came on day 24 as usual. My 3rd attempt I again took 50 puregon every other day from day 5 and had IUI on day 14, again my period came on day 24. After reading many forums on the internet a lot of people seem to be having a larger dose every day from earlier in their cycle. Is it better to try and carry out IUI within my natural cycle or should the puregon be making my cycle longer? Should I be injecting earlier in order to have a follicle that is the correct size by my natural ovulation day of day 10? I have tried to contact my consultant but he never returns my calls and unfortunately I am starting to lose confidence in him. Thank you for your time. L. from the U.K.

Answer:

Hello L. from England,

First, if your doc does not return your calls, then find a new doc. He is not helping you. For example, my patients have access to me via by cell phone and via email, which I receive on my cell phone.

Second, I presume that your doc is monitoring you by ultrasound to determine the optimal day for trigger. Is he not? If not, then he is not the right person to see. If he is, you should be forming at least 3 follicles per cycle in order to optimize your IUI's. That's my goal and the number that studies have shown to increase pregnancy rates per cycle. In addition, you should be going on Progesterone the day following the IUI to supplement your luteal phase. The fact that your cycles are short, despite ovulating on CD#14-17, means that you have an inadequate luteal phase (luteal phase defect). Without adequate progesterone support, implantation will not occur or the pregnancy will not continue. With the additional progesterone, you will not have a period until the progesterone is stopped, which should be after a negative pregnancy test is done 12-14 days after the IUI. If it is positive, then the progesterone would be continued until you are 10 weeks gestational age.

I hope this helps, Good Luck. Edward J. Ramirez, M.D.,

Follow-Up Question:

Hi, I wonder if you could please give me your advice once again.

After your last reply I spoke to my fertility nurse and she indicated that I may have luteal phase defect but said that they did not use progesterone to help in IUI she basically said there was nothing I could do, I then managed to speak to the consultant who was very angry with the nurse as he did not think I have luteal phase defect. I argued with him about this but he was adamant. (I agree with you that I do have LPD) Just so you know my consultant has the best success rate in the country for IUI !My consultant was monitoring me with ultrasounds to check the size of the follicles and at my next scan I had 4 follicles he usually aims for 2 (The rules are different in England regarding multiple births, I had also been injecting a higher dose of puregon than the consultant recommended) He advised me to cancel the IUI as the risk of multiples was too high and told me to use contraception. Against his will I took my pregnyl trigger shot that night and had sex. I also purchased Pro-Gest progesterone cream (on the internet as it is not readily available in England without a prescription, is the cream as effective as pessaries?) and used it a couple of days after the trigger shot.Imagine my surprise and delight when I became pregnant!! Unfortunately at 9 weeks I had a missed miscarriage leaving myself and my partner devastated, I took pills at the hospital to expel the foetus rather than have a D&C.

I now have a dilemma as I can stay with the Consultant. I currently have another 4 cycles of IUI for free or I can go to a new clinic and receive 1 cycle of IVF free on the NHS. I realise that its great I can have this free treatment but there are drawbacks in that you cannot choose your doctor, you have to go to the clinic that your GP refers you to and each time you visit the clinic you may see a different doctor.

So in your opinion what is my best chance of getting pregnant? I am 40 in December 2010 and time is running out should I take the 4 rounds of IUI using higher doses and progesterone cream (as at least now I know I can get pregnant) or is the 1 round of IVF with a new consultant my best option?Which ever option I choose if it doesn’t work I will find the money to have at least 1 round of IVF at a private clinic even if I have to put it on my credit card then possibly look at donor eggs.Im sorry this is so long and hope it makes sense. Thanks very much in advance. L. from England

Follow-Up Answer:

Hello L.,

I presume that your consultant does not do IVF and therefore is not a fertility subspecialist? In any case, you have proven that you can get pregnant by natural means, so indeed you have a dilemma. Let me see if I can help you sort it out but ultimately, you will have to make the decision. Your age is a significant factor. Your natural chances of pregnancy is only about 10% per year of trying, or less than 1% per month. With IUI it is only slightly higher than that. This is mainly because (1) your body has to go through the entire natural process to become pregnant (there are 9 steps) and it does not do this perfectly every time, and (2) you have an age related quality of egg issue, I call "age related egg factor", that diminishes your chances as well. The probably cause of your miscarriage was an abnormal embryo. IUI will not help that.

IVF, on the other hand, has a much higher pregnancy rate than IUI because (1) it is not a natural process and does not necessarily rely on the body to do each of the steps except for the last two steps: embryo extrusion from the shell and implantation. For this reason, your chances of pregnancy with IVF runs about 40-65% per month in the U.S. (it is 68% in my program). This also reduces the chances of miscarriage because more eggs are recruited, giving a higher chance of finding a healthy normal embryo. There is still a miscarriage risk but as you can imagine, that risk is reduced. In addition, because you have gotten pregnant previously, you have shown that implantation can occur and all you need is a good healthy embryo. So, in my clinic I would advise you to do IVF, but with the caveat that it may take more than one attempt (remember the last two steps are still "natural" steps that we cannot control.

Certainly if you attempt the several IUI tries, for which your consultant has not been very cooperative mind you, you could get pregnant but I would be prepared for more miscarriages. In addition, at your age, I would try for 5 ovulatory sized eggs to increase your chances. The chances of a multiple are slim at your age. But I think IVF will give you a better chance, ultimately.In terms of donor eggs, I would not consider than unless you fail several IVF attempts (3-4), or you reach 43 years old, whichever comes first. You can do donor eggs at almost any age so time is not critical.

Most Recent Answer:

Hello L. from England,

Thank you so much for inserting your previous questions. As you probably can surmise, I get lots of questions and can't remember everyone.

I still think that you have a chance for pregnancy with your own eggs. I know that financial issues preclude that, but I am not convinced that you need donor eggs yet. That being said, if I were you I would find a different clinic. Go out of country if you have to. Your clinic is NOT giving you the best chances. 300IU of Menopur is an inadequate stimulation dose in your case. I am also concerned about your down regulation. I have not seen anyone need 5 weeks of down regulation. I would certainly do things differently.

First of all, my highest protocol is 450IU of Follistim and 150IU of Menopur, which is the highest protocol used in the U.S. Again the goal is to get the maximum stimulation so that we can retrieve the maximum number of eggs. That is the only way to overcome the "age factor."

Secondly, I NEVER cancel cycles even if I have only one follicle. That is because I have had many cycles with only one follicle, resulting in one egg retrieved and one embryo transferred, AND it may be the perfect egg that you just wasted.

Thirdly, we will allow directed donors (donors that you find and use) as long as they are over 18 years old (legal age).

Remember, as I mentioned before, you can do donor eggs at almost any age. So time is not an issue, whereas, it is an issue using your own eggs because of your age. What I mean by that is if you fail with an IVF cycle or two using your own eggs (in a good clinic), then you can save up your money for a year or two then do donor eggs. Of course if you don't want to wait and want the maximum chance of getting pregnant quickly, then donor eggs would be the way to go, and I would go elsewhere. I feel for you and hope that all goes well.

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.

Ovarian Follicle Size Is Key When Planning For Trigger Shot

Question:

Dear Doctor Ramirez,

I had 3 follicles when I received the trigger shot. 30mm 24mm and not sure what size the 3rd one was. Is the 30mm follicle a good size to have a mature egg to be released?

Thanks, G. from the U.S.

Answer:

Hello G. from the U.S.,

I'm sorry to say but those follicle sizes are way too big. The trigger should be given when the follicle is between 18-23 mms. Once larger than that, the egg becomes over mature and non-viable. In some cases the follicle will not ovulate and be retained as a retained physiologic cyst. This type of situation generally occurs when patients are seeing the wrong type of doctor. I would advise that you consider seeking out a specialist in infertility or at least an ob/gyn who knows how to monitor your cycle properly so that you trigger at the correct time.

Good Luck,

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

www.montereybayivf.com

Alternative Lifestyle Couple Trying To Conceive: Husband Is Transgender

Question:

I just want to know how to go about finding a sperm donor that doesn't cost hundreds of dollars. My wife and I are newlyweds who have settled into our lives together well and are wanting to have a child. Unfortunately I cannot get my wife pregnant (I am transgender and incapable of producing sperm). I would like to know if you know of any sperm banks (free ones maybe?) that are legitimate or of any other services that would work with us. The city of Louisville, KY doesn't have many open resources so I was hoping you could point us in the direction of something nearby or easily shipped. Thanks for your time. -R. from Kentucky

Answer:

Hello R. from the U.S.,

There are many sperm banks accross the U.S. and ordering from these can be done by phone or via the internet. However, I know of no "free" sperm donor banks. In general sperm costs $200-300 per specimen. This sperm usually needs to be delivered into the uterus by a treatment called intrauterine insemination (IUI). That will cost an additional $800-1000 per month of trying with a specialist. I know that some lesbian couples will try natural insemination with donor sperm, and that some sperm banks will sell sperm to them for that purpose. You'll have to check with each sperm bank. Most will require a doctor to do the procedure and obtain the sperm. With the "natural" method, done at home, the sperm is injected into the vagina with a syringe to deliver the sperm. Ovulation detector kits are used to time the injection. You would probably need two to three specimens done daily in order to hit ovulation exactly.

In order to do IUI (intra uterine insemination), you would need to see a fertility specialist. Most of us are aware of and have taken care of patients in your situation. I have helped lesbian couples and men who are incapable of producing sperm. These situations do not bother me or most fertility clinics. The fertility clinic will then help you to order the sperm. I use a clinic called the California Cryobank here in California. They have been in business for a long time (over 30 years!) and are very reputable. My patients have had excellent results with them & they will ship specimens worldwide.

Off the record, the only other option that I can think of, that could potentially be free, is to have your brother or friend, donate a sperm specimen for you, preserving the specimen in a cup. Keep in mind that the specimens should be collected and injected on the two to three days after the ovulation predictor kit is positive. This will, of course, depend on whether you have a brother or friend that would be willing to help you with that. (One of the most popular movies last year dealt with a lesbian couple who decided to go that route, "The Kids Are All Right".)

Hope this helps, 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.

45 Year Old Woman With FSH Of 13, Fails Four IUI Cycles: Go To IVF With Her Own Eggs Or With Donor Eggs?

Question:

Hello Dr. Ramirez,

I'm writing to you from Texas. I just turned 45 and in the past 4 months I have gone through 4 IUI cycles (3 w/Femara) and one natural. None worked, but my fertility specialist thought it was worth a try because there is no problem with me (other than my age) or my husband and our ability to conceive. He did mention that there was a small amount of endometriosis, but nothing to be concerned about. We had been trying for over 3 years before I finally went to a specialist. I know I should have gone much sooner.

My question is this: We have decided to try IVF . My big concern is the age of my eggs. My FSH was 13. Is there any greater chance of my becoming pregnant if I use my eggs and my husbands sperm to create an embryo, or if I use a donated embryo from a younger couple? I get somewhat different answers depending who I ask at my fertility clinic and it's quite frustrating. I don't want to change clinics if I can help it, because my doctor is top notch. His staff knows their stuff, but they seem to be too busy to give me any real in depth answers. I look forward to getting your opinion on this issue. I've found all kinds of websites that deal with donated embryos - are there any that you would recommend? Thank you! J. From Texas

Answer:

Hello J. from the U.S.,

I am very, very surprised that your "top notch" doctor recommended you to try IUI's (intra uterine inseminations) that many times based on your age and elevated FSH. Did he tell you that your chance of pregnancy was less than 0.5% per month? Did he tell you that your FSH was elevated and give you the diagnosis of decreased ovarian reserve, which essentially means time is critical for you. You may already be in a pre-menopausal state!

Unless my patient absolutely demands it, I do not recommend IUI in my 42+ year old patients or patients with FSH levels greater than 10. In my opinion, in order to have the best chances of pregnancy in the short time that you have left, IVF is the treatment of choice. At least there is a pregnancy rate at 45 years old that is about .5%, and for this reason I will let them try with their own eggs (many clinics do not), but it is with the understanding and plan that if it does not work then they will proceed with donor eggs. I have also had a few patients decide to mix their eggs with frozen donor eggs so that they don't know which resulted in the pregnancy (they preferred to not know that it was absolutely a donor). These eggs are purchased from an egg bank and are slightly less expensive than going the fresh donor egg route.

I think that based on your age of 45, and the elevated FSH of 13, I would strongly recommend that you proceed with donor eggs and IVF (in vitro fertilization). That will give you a pregnancy rate of 75% per attempt in my clinic and many other clinics.

In terms of finding a donor, there are three options: (1) finding your own donor that is either your family member, friend, acquaintance, which is the least expensive because you don't have to pay the donor but there could be some social issues, or (2) use a donor that is registered with that IVF center if the center has donors registered. This is usually the second least expensive way to go but there may be limited donor choices (3) Purchase frozen eggs from an egg bank or (4) go through an agency. There are many agencies across the country and you have to be very careful which agency to use. Some are reputable and some are not. This is the most expensive way to go and can double the cost of IVF because of the agency fee. We have worked with several agencies in the past, although most of my patients elect to use an egg donor in our registry.

Donor cycles are fairly easy to do from your side and will require a minimal amount of time at the IVF center. Because of this, many patients will travel to an outside clinic for a donor cycle due to price or the location of the donor. Many clinics, such as ours, can even arrange for preliminary and initial cycle visits to be done at a local clinic or IVF center so that the only travel required would be at the time of embryo transfer. So don't be limited by where you are. You have lots of options open to you. You just need to decide how you want to proceed from here.

I don't mean to be critical of your current clinic and I'm sure your doctor appreciates that you have a high opinion of their clinic. However, keep in mind that infertility clinics, doctors and treatments differ greatly. The fact that the staff at your center seem to be "too busy to give you any real in depth answers" should not be acceptable to you, considering the urgency of your situation. For example, our clinic is only one-on-one. Each patient is handled individually, and there is only one doctor that sees you, does your ultrasounds, does your procedures and makes recommendations. My patients have 24/7 email and phone access to me or my key staff. There are no mid level providers. We pride ourselves on being a boutique IVF center. It is what sets us apart from other, high volume, IVF centers that tend to make you feel more like a number. I hope this helps.

Follow-Up Question:

Hello again Dr. Ramirez, After reading your response I felt pretty emotionally bad, for lack of a better way of putting it. I was aware of the limitations with the IUI, the reason I did it is because my doctor felt there was nothing "wrong" with me or with my husband's sperm, and he assumed sluggish motility may have been part of the problem. I was planning on doing IVF next month, either using my own eggs (which I'm not entirely comfortable with) or a donor embryo rather than donor eggs, because of the price disparity. I don't live in CA where infertility treatments are covered under alot of insurance plans.

I said my doctor was top notch, in part because of the high ratings and recognition he has received in his field. That being said, I've never had a true one on one relationship with anyone at the clinic - although I tend to deal w/the same nurse and doctor. The clinic does offer an egg donor program, but based on your answer, I'm not so sure if I should continue on with them, since I don't believe their database is that comprehensive. In fact, I believe they go outside the clinic for donors, and the cost of the IVF with an egg donor is somewhere around 18,000. I asked you about FET (frozen embryo transfer), but you did not comment. I would like to get your opinion about this and if you have any recommended facilities that house frozen embryos. Unfortunately, the clinic I'm working with does not have any recommendations for embryo donors. After reading your answer, I'm not so sure about anything anymore. Thanks for answering, J. from Texas.

Follow-Up Answer:

Hello J.,

I apologize for causing you this strife. I don't want you to give up, rather, I am just here to give you advice and opinion. Certainly you can see that my opinion is greatly different from your doctor's.

California is not a mandated state in terms of infertility, so many of the insurances don't cover it here either. So I am very aware of the costs of treatments. It is a dilemma in my clinic as well where we lose 10-15 patients per cycle because of finances. Yes, I know that egg donor cycles can cost $18,000 or more per attempt.

Embryo donation is a fairly new option. I would recommend that you look at the web and you will find several organizations that assist with embryo donation. Keep in mind, however, that there are not a lot of embryos out there that are donated. Many parents do not want siblings all over the country. This certainly could be a lower cost than standar IVF because the transfer procedure is fairly simple. The medication cost is less and the procedure cost is less involved. Our clinic would charge $3500 for an FET (frozen embryo transfer). That is about what it costs in most of the clinics in our state. I don't know what the cost of these embryos would be, however, and most IVF clinics do not have embryos to donate. Most of the embryo banks are Christian organizations that either facilitate the process or have their own storage facility so that the embryos are not destroyed.

Another option is Frozen Egg Banks, which has now become a viable option. I recently had a 45 year old patient use that method. The costs were still higher than an IVF cycle, because the Frozen Egg cost was high, but it was less than using your own egg donor. Unlike embryos, these are unfertilized eggs that were frozen and can be fertilized with your husband's sperm. The protocol you would go through would be like an FET. It is more expensive than a simple FET because you have to purchase the eggs (I think then sell them in lots of two), ICSI would have to be done and the embryology process would have to be done like a regular IVF cycle. The only step that would not have to be done is the egg retrieval step, which is the most expensive part of the IVF cycle.

For both embryo transfer and frozen egg transfer, the pregnancy rates would be very high (75% per attempt in our clinic). It certainly is better than your own eggs.

Again, I apologize for the comments that I made because they deflated your hopes and made you feel emotionally deflated. I hope these new comments will help you more constructively.

P.S. Kelly Preston (John Travoltas wife) just delivered a healthy baby boy at the age of 48. Of course, she doesn't say whether she used any assisted reproductive technology (and I would bet she did), but if not, then there is always a chance. I never say NO to my patients that want to try, I only make sure they understand all their options and their chances up front.

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.

Norwegian Patient With Arcuate Uterus & PCOS Wants To Know: Is IUI A Good Option?

Question:

Hi, I wrote before. I have an arcuate uterus and polycystic ovaries. My hormonal results were fine as well as my test for cervical cancer. My husband and I have decided to go for artificial insemination since we have been trying to have a baby for 4 years. I have never gotten pregnant. My question will I qualify for that and what does the whole process involve? Is it less expensive than in-vitro? Thank you, N. from Norway

Answer:

Hello N. from Norway,

IUI (intrauterine insemination) is certainly an option for you, especially if you have been found to be completely normal except for ovulation, the polycystic ovarian syndrome. (As far as the "arcuate" configuration to your uterus, this is generally considered a normal variant and does NOT cause infertility, do not be concerned with that.) Because IUI is a "natural" treatment method, meaning your body has to go through all its natural steps to achieve pregnancy, each of these natural steps have to work properly to get pregnant. Therefore, it can take several IUI attempts to achieve pregnancy, just as it would take several months of trying normally for a regular couple. The pregnancy rates are age dependent and range from 3%-24%. The maximum pregnancy rate is 24% in a woman under the age of 30. It decreases from there due to age factors.

The basic problem with PCOS (polycystic ovarian syndrome) is that the ovary does not function correctly and therefore does not ovulate on a regular basis. Therefore, any infertility treatment that you do will require that you take fertility medications in order to induce the ovaries to ovulate. With IUI the goal is to get you to ovulate three eggs per month (that is what increases the pregnancy chances). Ultrasound is then used to gauge your progess and time when the insemination should be performed. Basically, when the ovulatory follicles reach appropriate ovulatory size (18-24 mms), then a trigger such as HCG is given to trigger ovulation. I do two IUI's at 24 and 48 hrs from trigger but some clinics will only do 1 IUI at 32-26 hrs. There are pros and cons of each and I believe that two IUI's are better despite the fact that studies have shown that they are equivalent (I'm not sure that the studies were good enought to show a difference). IUI cost tends to be much much less than IVF because there is less technology used. If you don't achieve pregnancy by four attempts, then the pregnancy rates decrease dramatically so it is recommended to proceed to IVF from there.

One of the difficulties with PCOS patients is that there ovaries are very difficult to stimulate, so that many (80-85%) end up proceeding to IVF. With the simple meds such as Clomiphene or Letrozole, many PCOS patients do not stimulate at all despite the highest dosages, whereas, with the injectables (gonal-f, Follistim, Bravelle, Menopur), they tend to stimulate too much and produce too many eggs necessitating cancellation of the cycle. With natural treatments like IUI we don't allow more than three ovulatory sized follicles because we cannot control how many get to the uterus, which would increase the risk of a super-multiple such as 5, 6 or 8 implanting. This is a situation you most certainly would want to avoid!

I hope this gives you the information that you desired. Thank you for writing me from Norway!

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.

39 Year Old IVF Patient, DH Severe Male Factor, Surprised By Treatment Protocol: May Also Have PCOS & Will Need Med Adjustment

Question:

Can you help figure out what the next step should be? I'm 39 but have day 3 tests of 6.4 FSH, 53 estradiol and 25 antral follicles. Also great uterine ultrasound. We're doing IVF due to severe male factor. Just finished our first cycle, during which I somewhat overstimmed (16 eggs, sky-high E2 levels) but we got 3 good embryos, froze 1 and implanted 2 (my lining was 10.2 if I recall correctly), but they didn't take. I feel like I got a bit of a "cookie cutter" treatment from current RE and am wondering what changes you might recommend.

What felt "cookie cutter" was that despite my great day 3 tests, RE put me on microdose Lupron flare protocol with 300 units of Follistim (150 twice a day). Isn't that kind of an aggressive protocol for someone with day 3 numbers like that? Couldn't that risk sacrificing egg quality to quantity? I just feel like all they saw was my birthday (almost 40), not the day 3 numbers, good health and family history (women in my family stay fertile pretty late).

Anyway, after 4 days of 300 units of Follistim I had tons of follicles and my E2 was too high--almost 900--so that day and the next they had me skip the PM dose of Follistim (in other words on days 4 and 5 I had 150 of Follistim once a day). The E2 kept climbing, to 1100+ on day 5 and 1900+ on day 6. So on day 6 they had me go back to two 150 unit doses of Follistim. The next day (day 7) my E2 shot up to 4300+ so they had me coast. By day 8 E2 had spiked to over 7300, but it fell to 5300+ on day 9.

In order not to lose the cycle they had me do HcG on day 9, even though apparently a lot of clinics won't do the HcG shot unless the E2 is under 4000 due to the OHSS risk. (To prevent OHSS they had me use a half-dose of HcG and also gave me albumin.) Out of 16 follicles we got 16 eggs, of which 14 were mature, and 7 fertilized. On day 3 after retrieval, we had 4 embryos. Two looked great--we transferred them, both 7 or 8-cell--and two didn't look so great. They let those continue growing; one made it to blastocyst and is frozen now.

My RE said, of my response to the protocol, that I "reacted WAAAY more than any of our testing led us to expect." I don't understand what part of my testing suggested that I would have any problem producing enough eggs. Do you see anything that suggests that? I am just trying to figure out if I can trust my RE... I don't know if they actually are less worthy of trust or if I'm just feeling that way because I'm upset at the failed cycle.

More importantly, do you think these estrogen spikes and/or the overly aggressive protocol damaged my egg quality? I've seen some things on the web saying that excess E2 can kind of "toast" the eggs. What would you do now, if I were your patient? My RE wants to switch me to a more standard Lupron downregulation cycle with 225 units of Follistim a day. She said it's up to me whether to precede the Lupron with birth control pills. I don't want to take the pills--it just seems like going from one extreme to another, IVF protocol-wise, and I don't want to risk being over-suppressed. What do you think? Also, is this a situation where you would lean towards antagonists instead of Lupron to avoid over-suppression?

Sorry for the long post. I just wanted you to know enough to comment. And thanks in advance for your help. M. from the United States.

Answer:

Hello M. from the U.S.,

Before I answer the specifics of your questions, let me precede with the disclaimer that (1) there are lots of variations of protocols and opinions in the world regarding stimulation and none are absolute (meaning apply to all people) and none are better than others, and (2) the opinions I give are my own opinions based on my knowledge and experience and (3) the first IVF cycle is hard to predict with everyone because there are too many unknowns as to how a person will respond until you do it the first time and (4) pregnancy does not occur every time a woman does IVF for many reasons.

In answer to your questions, the protocol you were on (300IU per day) is actually a low dose protocol. Medication can be given up to 600IU per day. However, based on your response, it seems that your ovaries have a tendancy toward PCO-type response even if you are not a classic PCO. That is to say, your ovaries were very sensitive to the stimulation and hyperstimulated. For that reason you had to coast. I don't use the microdose flare protocol, which is indicated for "poor responder" patients or patients with "decreased ovarian reserve", neither of which you fit. Your FSH level was fine and your antral follicle count was more like a PCO. If I see ovaries with PCO-type characteristics in the pre-IVF ultrasound, I will usually defer to a PCO protocol because I don't want to put the patient at risk for hyperstimulation syndrome.I think that the adjustment of the medications was appropriate.

One thing to keep in mind, which I think you already know and have read, is that PCO patients that hyperstimulate have a reduced pregnancy rate because many of the eggs within don't mature. In addition, there does seem to be a reduction in egg quality, and that is further enhanced when coasting is required. That is part of the reason why we try to avoid coasting, but the risk of hyperstimulation is much greater so we sacrifice the egg quality for preventing OHSS.

I also will differ with your doc in that I prefer to use a "mixed protocol" (using both FSH + FSH/LH) because there have been some studies that show that LH is required for egg development and quality. In addition, I ALWAYS precede my patients with the birth control pill to help with quieting the ovaries (putting them at rest) prior to the IVF stimulation, to assist me with stimulation (studies have shown better stimulation) and to help with scheduling/controlling the cycle. Also, I strongly differ with your doc in the number of embryos I would have transferred. I would have transferred or recommended transferring all four of the embryos on day#3 just based on your age (that is totally based on whether or not you would be willing to take the risk of a twin pregnancy). We know that just based on your age, even with the family history of retained fertility at an older age, your chances of quality eggs are reduced, so the goal is to have a lot of eggs and embryos to work with in the hope of getting a good embryo in the end (keep in mind that "good looking embryos" does not necessarily mean that the embryo has good internal quality. We have no technology to access that at this time.) In my 39 year olds, I will transfer 4-6 embryos in order to get one implantation.

Finally, since we now know that you respond like a PCO patient, I would use a PCO protocol. In my practice, I exclusively use the antagonist protocol rather than the long protocol (Lupron), so that I can trigger with Lupron instead of HCG (which has been shown to reduce the chances of OHSS), and decreases the number of injections required. I call my PCO protocol the "low slow protocol", where I start with a low dose of medication and slowly increase it based on response.

Thank you for providing detailed information, it helps a great deal in formulating my response! I hope this answers your questions and that any subsequent cycles go better than the first.

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.

Donor Eggs and Surrogacy: The Possibility Of A Healthy Pregnancy & A Healthy Child

Emily Dickinson said: "Dwell In Possibility". I thought I would start the New Year with a blog post that centers on possibilities. I believe that everyone should leave themselves open to the wide array of options that are available to women and men who are struggling with their family building quest. An interesting example of one possible option was brought to my attention recently through an article on the American Fertility Association website, "The Amazing Story of the Birth of the Twiblings". Iris Waichler reviews an article that appeared recently in the New York Times and reflects on the courage it took for the author to reveal the complex journey she took using an egg donor and 2 different gestational carriers who end up giving birth to twins that are born 5 days apart.

In the December 29th NY Times article, Melanie Thernstrom writes an intensely personal account regarding her infertility journey ("Meet The Twiblings"). Recently married at 41, she and her husband underwent multiple IVF cycles without success. Her physician tells her after she begs to try for the fifth time that she should consider other ways of having a family. He asks, “Is your goal to have the experience of being pregnant or is your goal to have the best chance of having a healthy baby?” Ms. Thernstrom not only writes with feeling and fluency of what follows, but imparts a great deal of important information that would be helpful for any of you who are facing the decision to use donor eggs, surrogacy or a combination of both. What makes this couple's case unique is that they desired to have twins. This meant that in order to avoid the complication of a multiple gestation in one surrogate, they chose to have two surrogates, and each became pregnant with one successfully implanted embryo. The cost involved in doing this is discussed as well, which the author admits is a huge factor in being able to go this route. This is unfortunately always a big part of being able to do any kind of assisted reproduction treatment, as many of you well know.

Yet, all in all, this is an article about the possibility of doing something that would have been impossible a generation ago. Surrogacy and egg donation are still impossible in many states and parts of the world. We are lucky that here in California the laws allow for these types of treatment paths with protection for the intended parents, the donors and the surrogates. As the Times article points out, there are also a number of reputable agencies and counselors that can help with navigating the selection process, with all the legal aspects and with emotional support. Coincidentally, I was emailed recently by a woman in Italy who cannot carry a pregnancy because she has a heart condition and was wondering what her options were. She is 37 years old and wants to use her own eggs. Since surrogacy for financial gain is banned in Italy, I advised her on what was possible here and that her time for using "her own eggs" was growing short. I hope that she will find it possible to have the child she wishes for in 2011.

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.