Is A Big IVF Clinic Better Than A Small One?

Question:

Hello,

I am writing from Japan and want to ask that can big, crowded clinics be good or are small ones always good? Which is a worst choice...I'm very confused actually....like the crowded one has all the plus points, it is experienced, and cost is little bit lower than other. The big one has the pioneer in begining the IVF (in vitro fertilization) in Japan, the other has good success rates but only opened 6 yrs back...I'm totally confused!

How many cycles should a clinic do per year and what can I use to make my decision?

Please help ! H. from Tokyo

Answer:

Hello H. from Tokyo,

I run a smaller, low volume clinic and have better pregnancy rates that they large ones in my area, including the ones at Stanford University and the University of California, San Francisco.  I feel that I give better more personalized care because I am caring for them personally and completely.  I don't have other people doing what I should be doing.  The biggest disadvantage of a very large clinic is that it is a factory and depersonalized.  IVF should be a personal and intimate procedure, NOT a mechanical one.  So, of course I have a bias.  I would not recommend a small clinic that has a poor pregnancy rate, but if it has a good pregnancy rate, I think that is the better place to go.  I don't care how big and famous the larger clinic is or how many cycles they do, if it were me and my wife doing this I would want a clinic where the doctor is going to give us personalized attention the entire way, including personally do the retrieval and transfer procedures. I know that at the larger clinic in Japan you will rarely if EVER get to see the "famous" doctor,  so what good is it to go there? The smaller clinic will probably give you a better experience even though it is at a slightly higher cost.

In the U.S., people prefer to go to clinics where they get one on one personalized care, not where they are treated as another number.

幸運 ... Good Luck!

Edward J. Ramirez, M.D.
Executive Medical Director
The Fertility And Gynecology Center
Monterey Bay IVF
www.montereybayivf.com

Monterey, California, U.S.A.

 

Canadian IVF Cycle Fails: Husband Asks, Try Again?

Question:

Hello Dr. Ramirez and thank you so much for answering these questions.

My wife and I just completed our first IVF (although there was no transfer).  A previous attempt was cancelled due to only a couple follicles (150 Gonal F/150 Menopur).  We had done 2 previous IUIs with Clomid (3 follicles).

My wife is 37 and has very low AMH (0.40), FSH that ranges from 7 to 14 and an AFC of 6 to 14.  My analysis has been normal but we were recommended ICSI as it was unlikely we would get many follicles.  The clinic said they generally like to aim for 2 good ones.

To bring down FSH, my wife used an estrogen patch before her period and had 3 Ganirelix injections.  She then started 300 Gonal F & 150 Menopur on Cycle Day 2.  From Day 9 to 15 she also used Ganirelix. She was told to change the patch every other day and on cycle day 4 stop changing the patch (but it would last 7 days so would still have medication until cycle day 10).

She was slow to respond, not developing any measurable follicles (greater than 1.0) until after 7 nights of stims, but in the end, used the same Gonal/Menopur dosages for 15 nights.  Her AFC had been 14 and when she triggered (with 10,000IU HCG) on night 15 she had 7 follicles (2.2, 3 at 2.0, 1.6, 1.4, 1.0).  On trigger night her e2 was just over 2,500 (I have converted this to the U.S. value - pg/nl). 
 
35 1/2 hours later was retrieval.  They got 4 eggs and had to skip a few on one ovary due to blood vessels. The next day the embryologist called and said they had been able to ICSI 3 of the 4 and as of that morning (day after retrieval) only 1 of the 3 remained.  The next morning (2 days after retrieval) they called to say that embryo failed to divide.  It was the same the next day so there was no transfer.  They didn't have a definite answer as to why but said one of the eggs was soft and they weren't all smooth so it is probably egg quality issues.

Also - up until day 11 of stims her lining had been building well daily (to 1.2 cm).  Over the next 3 consecutive days it got thinner each day (even though e2 was rising) and was 0.9 the day of trigger.  Her lining has never been a problem in any other cycle (natural or medicated - even on Clomid).

We are trying to decide if it is worth it to do another cycle.  Could this be a fluke?  Could the long stim period have compromised egg quality (in addition to her age/FSH/AMH?)  Could ICSI have damaged the eggs at all if they were soft?  Will the blood vessels mean some follicles have to be left in one ovary at every retrieval?

Did the thinning lining indicate anything - coincidentally - when the lining started thinning her own e2 was raising daily quite a bit, but this was the same time the medication from her final estrogen patch would have worn off.  She had a bit of bleeding a few hours before the trigger shot on night 15 and was put on 8 mg/day of estrace the day of retrieval in addition to progesterone because of that. 

I would appreciate your advice.  We would like to try again but I don't want my wife to have to go through another cycle of injections/monitoring/retrieval, etc. if our results would be the same.  She had 12 days of blood tests & ultrasounds between day 2 & 15 and the 12 blood tests made it really hard to find a vein for IV at retrieval which took a couple tries.

We would like to at least make it to transfer before considering other options, but if we can't develop embryos in a lab, we're not sure if we should try again.

Thank you,

T. from Ontario, Canada

Answer:

Hello T.  from Canada,

A lot of the answers you seek are due to technical quality issues and I cannot address that.  Without a thorough review and evaluation of your wife's medical records, I cannot evaluate if I would have done things the same or differently, and whether or not that will make a difference.  Suffice it to say that I am saddened by your results, but at the same time, I am a little leery about some of the embryology outcomes.

Let me just give some information that might help you in your review. 

1.  The dosage of 350/150 is NOT the highest stimulation protocol.  Your wife could go up to the max dosage of 450/150 which might make a difference in the number of follicles recruited. 

2.  Based on the number of follicles formed, she actually stimulated well so the AFC, AMH and FSH may not be valid in predicting her decreased ovarian reserve (which does not predict fertility).

3.  I have not heard of the failure to retrieve due to "veins" or "blood vessels".  There are techniques that can be used to move and manipulate the ovaries to avoid those problems.  I have, however, had patients where I could not retrieve completely because the ovaries moved too much and deep into the pelvis.

4.  I think that ICSI in a 37 year old woman is appropriate and would concur with doing that procedure.  Keep in mind that ICSI is a procedure and "technique and skill" are critical to preventing damage/injury to the embryo.  It has been shown that ICSI done by an embryologist without adequate experience and skill can reduce embryo survival.  That could possibly have been a problem, but certainly inherent egg quality can influence that as well.

5.  Embryo quality (based on external features) are certainly based on inherent egg quality and that decreases with age.  However, that does not mean that all the eggs are bad.  Studies have shown that at 37 years old, 2 of 10 embryos formed will be normal.  The trick is to find the two good ones.  That may take several attempts or you would have the option of moving to donor eggs.  Since you have never completed an IVF cycle, you certainly have not tested whether or not it will work.

6.  Finally, I don't think I have ever had a patient that needed 12 blood tests during an IVF cycle.  The maximum I've had was 7.  Keep in mind that IVF success rates are highly variable between clinics and doctors.  Even in the U.S., rates are highly variable as compiled by the CDC.  I'm sure they vary greatly in Canada as well.  Based on what you have told me in your review, I can't help but be a little skeptical of the level of care you are receiving, but again, I can't draw any conclusions without a careful review of your records.

Good Luck,

Dr. Edward J. Ramirez, M.D. F.A.C.O.G.
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Programwww.montereybayivf.com

Comment: Thank you very much for your quick and helpful response.

 

IVF Protocol For High FSH

Question:

Dear Dr. Ramirez,
I am 39 years old in 2 weeks and about to undergo my first ivf (in vitro fertilization). I have only one fallopian tube, which an hsg has shown to be blocked, probably by adhesions (my other tube was removed due to damage from extensive adhesions - a reaction to previous surgery to remove a dermoid cyst on my left ovary).


My FSH level was 14 in March. Two weeks ago my FSH dropped to 8 and my AMH level was 7.42. An ultrasound scan and follicle count showed 9 follicles on my right ovary and 3 on my left (the ovary which the cyst was removed from).

My consultant has suggested the long protocol, as he thinks I will respond ok. I have read much about the short protocol being better for my age group, and if fsh has been high. I am anxious to get the correct protocol from the outset. What do you think my response might be, based on my levels? Do you think a short protocol would be better in my case? Many thanks, R. from the U.K.

Answer:

Hello R. from the U.K.,

The worst thing you can do is try to second guess your doctor, especially with information that you read on the internet. You are not an expert and don't have sufficient knowledge to make a proper decision. However, it is good to be educated regarding what you will be going through, and certainly, I have the knowledge to answer questions, so you can trust my input. But, given that you are not my patient, I don't have all your medical information and am not doing the procedure, the answers I give you have to be generalities and cannot be specific.

I personally don't criticize "protocol" questions because there is not one way or best way to do IVF. There are many different protocols and usually the specific protocol is based on the training and experience of your doctor. They all have the possibility to work. Some doctors stimulate less, some more, some use only pure FSh, some use mixed protocols, some use the long Lupron protocol, some use the antagonist protocol and some use the micro-dose flare protocol. There is not way to predict how any one will respond to any given protocol. But studies have shown no benefit to the micro-dose flare protocol (short protocol) in comparison to any other protocol, just as there is no study that shows that the long protocol is better than the antagonist protocol. I prefer the antagonist protocol because there are less injections in comparison to the long protocol.

Because you have had an elevated FSh level, despite it being lower more recently, you would still be considered a poor responder (or at least have the potential of being a low responder). For that reason, my preference would be to NOT inhibit your ovaries with Lupron in the stimulation phase, and only begin ovarian suppression once the lead follicles are at least 16 mms. This is the technique used in the antagonist protocol. With the long protocol, your ovaries are suppressed by the lupron starting from the previous cycles and may not respond as well. Before the antagonist protocol was developed, the micro-dose protocol was developed to reduce that suppression phase. Without criticizing your doctor's choice of protocols, my personal choice would have been different. But that is what makes Infertility doctors and clinics different and gives them different pregnancy rates.

Good Luck,
Dr. Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
http://www.montereybayivf.com/

31 Year Old With DOR Advised To Keep Trying: Adjust Protocol To "Mixed" FSH & FSH/LH

QUESTION:

Hi Dr Ramirez

I am on my first round of IVF and my day 9 scan showed no follicles on left ovary and 3 tiny follicles on right. I am on 375 menopur which has now been upped to 450. Priot to starting treatment i was on the combined pill for irregular periods. I am 31 years old with FSH level of 6. My question is, can being on the pill interfere with follicles growing and am i on te right meds? When they scanned me prior to starting treatment i had more follicles than when doing IVF which doesn't make sense to me? I am having treatment in London, England.

Thanks, N. from England

ANSWER:

Hello,  N. from England,

With your age and FSH level, I would have expected a much better stimulation response. I think you are not being adequately stimulated. Menopur is not adequate. There needs to be more FSH in my opinion, but keep in mind that each doctor does things differently and one way is not necessarily better than another. If you were my patient, my preference is to use a "mixed" protocol using both FSH (Follistim or Gonal-f) and FSH/LH (Menopur or Repronex). I would have started at 300IU Follistim and 150IU Menopur (450IU total of FSH), then possibly decreased to the dosage you started at. But, that is my personal preference (and of course something that makes each clinic different with different results).

The pill should not and does not interfere with ovarian stimulation. I presume that you are also on a Long lupron protocol? Lupron will suppress the ovaries as well.

I have also been surprised by the lack of stimulation in a younger patient, such as your doctors were pretty surprised. Sometimes it is hard to predict what will happen. If the cycle fails, then I greatly increase the medications in the next cycle. Such a finding is called a "poor responder". But keep two facts in mind:

(1) each cycle is unique and the stimulation results can vary from cycle to cycle. One does not necessarily predict the next.

(2) it only takes one good embryo to be successful.

Good Luck!

Follow-Up Question:

Hi Dr Ramirez,

Thank you so much for your prompt reply. I carried on with the 450 Menopur until day 16 and they decided to cancel the cycle as the one follicle was not responding as they would have liked. The consultant at the IVF clinic told me that my chances of conceiving are zero per cent even with IVF. To say I was shocked was an understatement. I spoke to him about the possibility of a different protocol or different meds but he was adamant that I shouldn't try again. I don't quite know where to go from here. I have been under the care of a gynae at my local hospital for fertility investigations for 5 years and he kept telling me IVF was the answer. I got pregnant with Clomid two years ago but now I am at zero fertility, I mean not even 1% according to the IVF consultant.

My question to you would be, in America do you do things differently? I spoke to him about Gonal F and he said it wouldn't have made a difference. I also said about Synarel and he said it wouldn't have made a difference. I have low ovarian reserve and that is that. He is a highly regarded doctor here in England (Mr Tim Child) so I am sure he wouldn't have said zero if he didn't believe it. I know it's hard for you to give an opinion without knowing my full history, but have you seen seomeone with such a poor first reposne go on to do better second time around or should I just draw a line under it all?

Thank you so much for your guidance on this, as my husband and I are a bit shell-shocked. Over here in the UK we always consider the Americans to be further forward in medicine and cutting-edge treatments. We would be prepared to travel if we thought it was worth it. If only one follicle is growing very slowly under high stimulation, would you be inclined to say zero chance too? I appreciate your honesty.

Kind regards, N.

Follow-up Answer:

I am sorry for all the grief you have had to endure. I am afraid that I don't completely agree with your doctor. First of all 450IU is not the maximum dose of medication. You certainly have "decreased ovarian reserve", which means that your ovaries don't stimulate well, but given your age, I would expect you to have a good chance even with only ONE egg. So I would recommend trying with a higher protocol and even if there are only a few follicles, you should continue the cycle and give it a try. It stands to reason, if the cycle is cancelled you certainly won't get pregnant, so in my opinion if there is a follicle present the patient deserves to give it a chance.
In terms of decreased ovarian reserve, there have been several studies, including one that was just published, that showed that ovarian response will vary even in patients with decreased ovarian reserve. Therefore, it is still recommended to continue trying in a patient with decreased ovarian reserve. The next cycle may be completely different than this one, especially if a different protocol is applied.

In addition, I am a firm believer that there is a difference between a mixed protocol (using FSh + FSH/LH such as is found in Gonal-F or Follistim (pure FSh) and Menopur (FSH/LH). I know that there is no standard protocol and studies contradict each other, but FSH is the hormone that stimulates follicle growth (that is why it is called follicle stimulating hormone)and LH is not. In a normal natural cycle, the LH does not rise until just before ovulation whereas the FSh is rising all of the first half of the cycle.

I would encourage you not to give up.. . at least not yet anyway. It is possible that down the road you might have to resort to using donor eggs, for instance if your ovaries shut down completely (premature menopause/premature ovarian failure) or you have failed several attempts with your own eggs, but until then, hope is not lost, every cycle is a new and different cycle and every egg is a new and different egg; all with their own potential. I will never tell a patient that there is "zero" chance because there are always exceptions to the rule and I also believe in miracles. I've seen them happen many times. If you wish to come to California, I would be pleased to assist you in the best of my abilities.

Good Luck,

Dr. Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
http://www.montereybayivf.com/

Conceiving After The Age Of 40: What Are My Chances?

Question:

Hi. I am 43 and began my quest for motherhood about two years ago. I have been on Clomid and Femara and have tried IUI about 5 times. I most recently tried Follistem and IUI. Last month I was on oral contraceptives because of a cyst and returned this month to discover the cyst was still there AND I had another cyst on the other side. The doc gave the option of aspiration of cysts or to consult to discuss options such as donor eggs.

I have been pregnant once, with no fertility help, about 3 years ago (at 40 yo) which resulted in miscarriage at 8 weeks. We had a heart beat then lost the pregnancy. What are your thoughts about my fertility history and recommendations for an otherwise healthy 43 year old? The cysts are producing estrogen--level was checked. Thank you for your opinion. I am writing from Iowa....thanks! S.

Answer:

Hello S. from the U.S. (Iowa),

First you need to understand that you are trying to beat the odds and that statistics is only a reflection of real life, not an exact predictor of it. There are always exceptions. However, we try to make the best decision based on the information that we have.

It is well known and scientifically proven that a woman's fertility decreases with age beginning at 30 years old. This is due to the fact that a woman is born with all the eggs she has for her entire life and those eggs age with her. In addition, she is using up lots of eggs with each cycle so there is also a reduction in the number of eggs available.

We also know that by 40 years old, the remaining eggs will be of poor quality. This leads to a reduction in pregnancy rate or a significant increase in miscarriages, and was probably the reason you miscarried at 40 years old. Your statistical chances of pregnancy with IUI (intra uterine insemination) at 43 years old is less than 0.5% per cycle. This is due to the fact that IUI is still a "natural" treatment method and requires that your body go through the normal steps to achieve pregnancy. As you can see, your chances are not zero, but are pretty slim. (A 20 year old woman has instead a 20% chance of pregnancy per cycle.) At your age, with IVF (in vitro fertilization) using your own eggs, the chances of pregnancy rise to 33% per cycle. Unfortunately, because of pregnancy and miscarriage losses the delivery rate is 13%. It is still significantly better than IUI because most of the steps required are performed by the IVF and only two steps are left to natural processes. With donor eggs and IVF, the chances increase dramatically due to younger and healthier eggs, to 75% with 59% delivering.

Most fertility specialists would recommend donor IVF, but it is a personal choice that you have to make. Most of my older patients want to try at least once with their own eggs and I will give them the chance to try because as I said up above, there are always exceptions!

Good Luck,

Dr. Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
www.montereybayivf.com
Monterey, California, U.S.A.

How Can I Have A Year Of The Dragon Baby?

Question:
Dear Doctor,

We are a Chinese couple who would like to have a baby this year. We have been trying for many months in the natural way for timing the baby for the Dragon year but we are not successful so far. We are thinking that maybe we can make our chances better for a baby this year if we go see a baby specialist here in Hong Kong. My wife is 34 years old and I am 38 years old. We have been trying for six months now. If we try for test tube baby, can we choose for a boy or girl? What would you suggest would be the proper next step for us?

Thank you, you are very kind for your advice. L. from Hong Kong

Answer:

Dear L. from Hong Kong,

I appreciate the fact that many Chinese couples are looking forward to having a child in the Year of the Dragon. If you wish to time your wife's pregnancy for a delivery within this Chinese lunar year, you do not have much time to spare! In essence, since you have been trying to conceive already for six months, it may be time to look at alternatives. I will go over all your options, from least complicated to the most aggressive:

First option:

What I would suggest if you still choose to go the "natural way" for just this month, is that your wife begin taking prenatal vitamins that have at least 1 mg of Folic acid within it, and that you keep in mind that the actual fertile days are pretty narrow - 2-3 days. If your wife has regular and predictable cycles, you can predict ovulation by counting back 14 days from the period. That would show where ovulation probably occurred in the previous cycle and by counting from the first day of her period, gives you an idea of what cycle day ovulation occurred. Then with this information, you can use the calendar method by counting from the period the number of days where you can both expect ovulation to occur. You need to stop intercourse 5 days from that anticipated ovulatory day, then start intercourse two days prior and have intercourse daily, once per day, with having only one ejaculation per day for five days.

Second option:

I think that an IUI (intra uterine insemination or artificial insemination) is a better starting point and should be done right away, but you need to make sure that the appropriate treatment is being done to increase your chances. IUI's are better than trying naturally because the number of eggs ovulated are increased with fertility medications, timing is better known by ultrasound surveillance and the sperm is injected into the tubes to await the egg. Ideally, your wife should be ovulating 3 eggs per cycle, or have 3 eggs of ovulatory size (18-24 mms) so maximize the chances that an egg will find and get into a tube. You did not say if either one of you have been tested for infertility. In your age group (34yo), your chances of natural pregnancy are about 10% per month and with IUI, up to 24% per month.

At my center, typically, we do an hsg (hysterosalpingogram) to see if the woman's tubes are open and viable. We also do a semen analysis on her partner. A negative result in either of these tests would make it quite difficult for you to immediately succeed with either an IUI or naturally.

Third and probably best option:

Considering the fact that you do not have much time and that you are considering gender selection, then IVF (in vitro fertilization) or "test tube baby" may be the best choice if you wish to conceive within the next few months.

With IVF the woman can produce many follicles and as long as you get at least one good embryo, IVF has a better pregnancy chance than IUI because it is accomplishing 7 of the 9 steps your body goes through to achieve pregnancy (IUI only accomplishes one). The remainder have to be accomplished by your body. That is what gives IVF a pregnancy rate of 60-76% per cycle in your age group.

If you wish to do gender selection, then IVF with PGS (pre implantation genetic screening) is the only option you have. A microscopic biopsy of the trophectoderm (the outer cell layer of an embryo) is done by the embryologist and sent to a lab for analysis. Recently it has been shown that the pregnancy rates from a single PGS-selected euploid embryo were 58% and 60.7% compared to 42% and 40.7%, respectively, from a morphologically comparable but non-PGS-selected embryo. Interestingly, the miscarriage rates were seen to decrease to 6% and 6.3% from 12% and 12.5%, respectively. With transfer of one embryo, the risk of multiple gestation is essentially eliminated.

I know that in China, Korea and Japan, genetic screening for gender selection is not allowed. Here in California it is, though. We have had Asian patients come to us who have chosen to have PGS for gender selection and succeeded. Your chances would be reasonable if normal embryos were obtained and transferred. You can choose to freeze or vitrify some embryos and transfer one fresh (vitrification is a method of rapid cooling of embryos that minimizes ice crystal formation which has further improved success). If one is transferred and it takes (implants), I would expect that there would not be any abnormalities in the fetus or child.

I wish you luck in the Year of the Dragon and hope that you will find a good physician in Hong Kong or abroad that will be willing to work with you and help you succeed in your quest for a child this year.

I hope all this information is helpful.

Dr. 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.

A Little Miracle...Seven Years In The Making

I want to share a special story with you, my readers, about a couple who went through a recent IVF (in vitro fertilization) cycle with us. This couple had come to us back in 2004 for infertility treatment. After the normal trial of IUI's (intra uterine insemination) did not work, they opted to do IVF with us. The cycle went well, the retrieval went well and there were three embryos to transfer. While doing the transfer of all three embryos, one embryo "floated" (aspirated) back out of the catheter. This was an unusual event for me and my staff. The couple decided to freeze that one reluctant embryo. Unfortunately, the patient did not become pregnant with that cycle. As it so happens, she soon became pregnant naturally and in the ensuing years, as sometimes happens, they had no trouble conceiving again, having three children in all.

In the meantime, the frozen embryo remained in our cryobank storage facility. The couple elected to leave the embryo there for the last seven years until recently. Grappling with the options of either continuing to pay for storage, dispose of the embryo or put it up for adoption, the couple opted to go forward with a frozen embryo transfer. We transferred the one embryo successfully and crazy as it may seem, the patient is now pregnant! This child will be both the "oldest" and the "youngest" sibling by virtue of this unusual series of events.

I am a spiritual man, if you have not guessed already. For us, every child is special, but I have a feeling that this child will truly be a special one, for it is my belief that for some divine reason his or her birth was delayed. How often I feel defeated when a cycle does not succeed and yet when something like this happens, I know that we can only do what we can up until a certain point, at which time the final steps of creation are taken out of our hands. Which brings me to one of my favorite quotes from Deepak: "When you live your life with an appreciation of coincidences and their meanings, you connect with the underlying field of infinite possibilities."

After 11 IUI's, Canadian Fails 1st IVF cycle: Poor Embryos, Bleeding Or Implantation Failure?

Question:

Dear Dr. Ramirez,

I'm writing to you from Toronto, Canada. Thank you in advance for your answer!

My husband and I are both 37 years old. I was diagnosed with mild PCOS due to the shape of my ovary (pearl-like follicles) and irregular cycle (28-36 days), and as result was prescribed Metformin. My husband has low sperm count and motility. Last year I was pregnant after 5 attempts of IUI (intra uterine insemination), but unfortunately ended up in miscarriage due to chromosome abnormality. The protocols include Letrozole Femara on its own, Letrozole Femara in combination with Gonal-f and Hcg Ovidrel, and one unstimulated cycle. In all cycles, we only worked with 1 follicle. My husband's sperm ranged from 1-5 million after washed during those cycles. During our pregnant cycle, Letrozole Femara in combination with Gonal-f and Hcg Ovidrel were used, his sperm was 1.6 million after washed.

Three months after the miscarriage we tried again, with 6 rounds of IUI with similar protocols as before, but also include doubling Letrozole Femara with Gonal-f and Orgalutron, as well as Gonal-f injection only but none resulted in pregnancy. With the exception of 1 cycle where we worked with 2 follicles, the rest we only worked with 1 follicle. My husband's sperm ranged from 1-7 million after washed during those cycles.

Recently we went through an unsuccessful round of IVF-ICSI (in vitro fertilization with intra cytoplasmic sperm injection), with 5 days transfer. Protocols include Gonal-f, Repronex, Orgalutron, and Hcg Ovidrel. I was also put on a birth control pill the cycle prior to IVF cycle, and had an endometrium biopsy during the luteal phase of the birth control cycle. Post retrieval include antibiotics and vaginal natural progesterone 100mg in the morning and 200mg in the evening. Post transfer include vaginal natural progesterone 200mg in the morning and 200mg in the evening, and 81 mg aspirin daily.15 eggs were retrieved with 11 matured. 3 were IVF and 8 were ICSI. 1 out of the 3 IVF fertilized, and 4 out of the 8 ICSI fertilized. Since more than 3 eggs fertilized, the clinic's policy is to do 5 days transfer. By day 3 the quality of the 5 embryos were as follows: 10-12 cells grade 2 (good), 8 cells grade 1 (excellent), 8 cells grade 1 (excellent), 8 cells grade 2 (good), and 6 cells grade 2 (good).Unfortunately only 1 of the 8 cells (ICSI) turned into a blastocyst (with quality "not bad" according to my doctor).

The day 5 transfer include the only blastocyst we have and the 10-12 cells embryo. We ended up having no embryos to freeze. I started bleeding 7 days after the transfer.

Sorry for the long background story, my questions are as follows:

What should we do to ensure successful IVF next time? Failing the IVF, do I have an implantation problem?

What could have been done to prevent the early bleeding, could the progesterone injection prevent it? I didn't seem to have luteal phase defect in the past since my period normally come 14-16 days after ovulation.

What would have caused the poor embryo development after day 3? My doctor mentioned about possible sperm DNA fragmentation issue although this still need to be tested. Are there any other tests we should do?

What could have caused sperm DNA fragmentation, my husband doesn't smoke or drink, or exposed to any chemical environment in his day to day.

What protocol would you suggest for an IUI? Just want to mention that I didn't respond well to clomid and therefore my doctor prescribed letrozole. Why did IUI work for us last year and the last 6 attempts didn't? Also, I started taking Chinese herbs subsequent to miscarriage, therefore for the first 5 attempts out of the 6 IUI attempts I was also taking Chinese herbs at the same time, would that be why the IUI's failed?

I very much appreciate your time and help.Yours sincerely, E. from Canada

Answer:

Hello E. from Canada,

Thank you for all the information, it helps a great deal. Let me get to your questions directly.

1. Unfortunately, I don't comment on specific protocols because each doctor, clinic and country use different protocols. There is no right one or wrong one. These variations will often determine pregnancy success, however, and is the reason why some clinics are more successful than others. So, despite what I might advise you as to protocols, inevitably it will be your doctor's opinion, based on his training, knowledge and experience, that determines what protocols you use. Given that, it looks like you stimulated well, had a good number of eggs and embryos formed. The only changes I might suggest, which you have control over is (1) ICSI ALL eggs to allow for maximum fertilization and embryo number, (2) DO NOT PROGRESS TO BLASTOCYST CULTURE without at least 5 8-cell grade 1 or 2 embryos.There is an inherent attrition rate from day#3 embryos to blastocyst that may have nothing to do with inherent embryo quality. Based on preimplantation genetic testing data, sometimes even genetically normal and healthy embryos may not make it to blastocyst. Keep in mind that blastocyst culturing is still in its early development stages and not perfect. If you don't have enough embryos to lose, don't do it.

2. The bleeding after embryo transfer is very very common. I would refer you to my blog where that particular topic is the most often viewed. There is more information to this than I can give in this forum. Basically, however, it is not clear why or where this bleeding is from and how to prevent it. The good thing is that in many, if not most cases, it is of no consequence.

3. As mentioned above, the lack of embryo development does not necessarily have to be due to poor embryo quality. But, embryo quality can certainly affect the ability of an embryo to develop to blastocyst. The sperm fragmentation part . . . I'm not sure I would agree with that. Your age affects egg quality and therefore embryo quality more significantly.

4. Unknown what causes sperm fragmentation.

5. If you were going to return to IUI (which is an option but you have to consider that you will be lowering your chances of pregnancy) I would probably go to injectables only stimulation and not a combination protocol. The goal would be for you to have three to four ovulatory sized follicles (n0t one like you have been having), which will increase your chances of a successful pregnancy. The fact that you have gotten pregnant in the past is an indication that your reproductive system works but you have to overcome the sperm factors and the age factor. For these two, I would probably recommend IVF.

I would caution against adding herbal regimens. These are just un-purified pharmaceuticals. They could certainly have adverse affects.

Follow-Up Question:

Thank you so much for your reply.

In reading your blog on early bleeding, I mentioned to my doctor about using injectable progesterone. She wasn't on board and she still recommends vaginal progesterone. She explained that based on numerous researches, the vaginal progesterone is as effective as injectable, and the injectable create much discomfort. Instead for the next IVF, she will add estrogen patch. Should I insist on the injectable, I'm worried that I won't have enough progesterone support for implantation. Is it possible that's what might have caused the early period bleeding in my last IVF (7 days post 5 days transfer)?

Lastly, could the miscarriage that happened last year after IUI was also caused by lack of progesterone? That cycle I was only prescribed 100mg vaginal progesterone daily. However there was no bleeding whatsoever and after the fetal heartbeat stopped at 2.5 months pregnancy, I had a D&C done.

We will be doing another IVF 2 months later, in these 2 months, 1st month will be natural cycle and the 2nd month will be birth control cycle. Will doing the next IVF this early affect the eggs quality (the quality will be worse) and therefore reduce the pregnancy chance? Best regards, E.

Follow Up Answer:

Hello Again, Your doctor is correct in that studies have shown that vaginal progesterone is just as effective as injectable, and doesn't have the discomfort of the injection (Injectable progesterone has to be given intramuscularly). Injectable progesterone is still the gold standard, however, and if that is the form that you want, I don't see why your doctor can't change. But these kinds of things are what make each doctor different. Extra progesterone does not hurt, so why not? You could continue to argue with her but it sounds like she has her preferred way and will stand by it. The estrogen is a different hormone. I don't see any benefit to that for the bleeding but I certainly supplement with estrogen in my protocols.

Remember, I said that you cannot compare protocols because there is no one way, right way or wrong way. Protocols differ between doctors and clinics and that is okay.In the IUI pregnancy, which found a heart beat, progesterone was definitely not the cause. The lack of progesterone will result in very early pregnancy loss. Way before the placenta develops to produce its own progesterone. After that point, losses are usually due to abnormal pregnancies or fetal development.

The answer to your last question is NO. One can do an IVF cycle as quickly as every other month. Each cycle is different and unique and the eggs retrieved are unique. They can be good eggs or bad eggs, which is already predetermined prior to the IVF cycle depending on the state that the egg is in prior to stimulation.

Good Luck,

Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
www.montereybayivf.com
Monterey, California, U.S.A.

40 Year Old IVF Patient In Vietnam On Low Protocol Fails First Cycle: Has Many Questions, Concerns

Question:

Dear Dr. Ramirez,

My name is A. from Vietnam, 40 years old by end of March 2011. Just give you some information about me regarding Infertility/IVF. My menstruation cycles are different every month: 28 days in Feb, 26 days in March and 31 days in April. So, average: 26 days. Period in March was especially longer; maybe it was caused by hormone therapy in March. My FSH on March 6 (2.day of period) was 10.6mIU/mL and AMH on April 9 was 0.8ng/mL.

I started my first IVF cycle on March 6 2011 (2. day of period) and ended it with 2 embryos transferred on March 22. Unfortunately, it failed. On March 6, I got 1 Decapeptyl 0.1mg. However, I reacted allergic to this and the doctor stopped Decapetyl and gave me 2 days later on March 8: 1x Gonal F 300 i.u. each day and for 8 days until March 15. One day later on March 16, I got Pregnyl at 8.30pm. 2 day later on March 18 at 8.30am, I had my egg retrieval. 6 eggs were collected and 4 were fertilized. On Day 3 after retrieval at 8C stage I had 2xnormal embryos with grade 1, 1x embryo with grade 2 and 1 embryos with Monosomy 21. On day 4, 2 embryos were transferred. My husband semen test result shows 25% normal form (morphology) with total live count of 341 million sp/vol and has anti-sperm antibody. So, I used IVF, ICSI and PGD (for down’s syndrome) in March.

For the next IVF: One clinic suggested to give me on the 3.day of my menstruation 1x300 i.u. Gonal-F mornings and 1x 150IU Menopur nights for 4 days first. Based on the follicle count and size in the ovaries, they will decide on further dose. They are likely to follow a step-down protocol. They will not use any drugs like Decapeptyl this time.

Another clinic suggested to give me on the 2nd day of my menstruation 1x300 i.u. Gonal-F for 5 days and will see based on the ultrasound result.

Could you please kindly answer my following questions and tell me what would you do differently?

1. Do I need birth control pills? Why or why not? I think I need it, because my monthly cycles are different. So, with the birth control pills, the embryos will be implanted on time. What do you think?.

2. Which dosage and drugs would you use except for the 2 dosages of 2 clinics?. Which dosage of these 2 clinics does make more sense to you? Which one will give me more eggs with good quality? Last IVF, I just had 6 eggs, 4 fertilized and just 2 healthy embryos transferred at the end. As I know, I need 3 embryos for my age.. Do I need such kind of drugs like Decapeptyl? Why or why not?.

3. On which day would you start the IVF (2. or 3.Day of period)? Why?.

4. Will acupuncture and Chinese herbs support the success of IVF? Or will it be contra productive? If recommended: before or before and during the IVF? I am taking prenatal multi vitamin and 400mcg folic acid. Do the unfreezing eggs have the worse quality compared to fresh eggs?

5. Was the embryos’ transfer late (at the Murola stage) last time? Should it be transferred earlier this time at 8C stage? I will not use PGD this time. Did I have enough eggs (6 eggs last IVF) at my age? Do I need to increase them next time? Does one embryo have 9% success rate for women at 40?

Thank you very much for your time. Best wishes.

Answer:

Hello A. from Vietnam,

It is interesting for me to see that IVF is being done in Vietnam, proving that this is a procedure that spans the world. Keep in mind that protocols used are highly variable between clinics and doctors. No one protocol is better than another so the recommendations I give are based on my knowledge, experience and preferences.

I always use the birth control pill preceding an IVF cycle. I believe the studies that show better response to stimulation by using the BCP. In addition, it causes the ovaries to essential shut down so that they will be more responsive to the stimulation and so that the follicles will start out somewhat evenly when the stimulation is started.

One thing I noticed about the protocols you have been on is the fact that they are low dose protocols. My highest protocol is a total of 600IU of FSH and I prefer a "mixed" protocol using pure FSH and an FSH/LH mixed compound. The preferred medications I use are Follistim (pure FSH) and Menopur (FSH/LH) in an approximately 2:1 ratio. So, my highest protocol, which is what I would use with you, is Follistim 450IU and Menopur 150IU taken every evening. My highest protocol is a continuous protocol, meaning you stay at the same dose all the way through, but it will really depend on your stimulation. Sometimes, if the patient stimulates more strongly than expected, I will drop the dose but most patients with an elevated FSH like yours (decreased ovarian reserve) will stay at the same dose. I do think that you were understimulated and the number of eggs retrieved and resultant embryos was low. In your age group I would prefer to have 4-6 embryos to transfer.

I cannot comment on the two clinic's protocols specifically, as I mentioned earlier. I can only give you my opinion regarding the protocol that I use.

In my center, I start the IVF cycle on an arbitrary day called "cycle day #2" irregardless of when your period actually starts on that cycle. This is because having used the birth control pill, I am in total control of the cycle and don't have to rely on the natural cycle timing.

I do recommend acupuncture as some studies have shown it to be beneficial with IVF.

I do think that the transfer should have been on D#5 post retrieval if PGS was done (blastocyst) but if PGS is not going to be done, then D#3 is better because I believe the uterus to be a better culture environment that the lab. Frozen embryos tend to have a decreased pregnancy rate, mainly because the best embryos are used to do the fresh transfer and the second best left to freeze. Also, the freeze/thaw have a little effect on the embryos but if done right, this should not be significant.

Finally, pregnancy rates are highly variable between doctors, clinics and countries. I cannot compare them exactly. In my center, your chances of pregnancy per cycle is 70% with 60% continuing. The U.S. does tend to have higher pregnancy rates than most other countries. At 41 years old, this decreases to 47% pregnancy and 29% continuing. Since we batch pregnancy rates into a 38-40 yo category, the rate I gave for 40 years old might be a little higher than it should be.

"Chúc may mắn"....Good luck on your next cycle!

Dr. 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.

How To Interpret Positive BHCG Levels After IVF: When Will You Know For Sure?

Question:

My question is about beta levels, and how to interpret what they indicate.This is my first IVF / first pregnancy, so this is a constant learning process.

1st Beta at 14 dpo (11 days past 3 day transfer) was 158.
2nd Beta at 18 dpo was 704.
3rd Beta at 21 dpo was only 1537.

My beta levels started off doubling, but then slowed considerably.I have an ultrasound upcoming next week, but not sure what to expect at this point. I am feeling very concerned about this change, and not sure if it still falls into normal range or is a valid cause for concern. Should I request a 4th beta? Can an ultrasound at 5 1/2 weeks provide a definitive answer to the viability of a pregnancy?

Thank you so much for your answer! C. from New York

Answer:

Hello C. from the U.S.,

Absolute values of the bHCG cannot be interpreted (although many people try to). bHCG's are evaluated based on their trend i.e. up/down and double every other day (actually it only needs to increase by 80%). I would caution you on trying to interpret how things are going by your bHCG levels unless they drop precipitously. The ultrasound will give you a better idea of how things are proceeding.

Viability cannot be established at 5-1/2 weeks. It is too early. That ultrasound is mainly to rule out an ectopic (tubal) pregnancy. Viability is established at 7-8 weeks gestational age.

You have a positive pregnancy test, which is a good thing! Now all you can do is wait and see how it progresses.

Good Luck,

Dr. Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
www.montereybayivf.com
Monterey, California, U.S.A.

Tubal Reversal Vs. IVF: Which Would Be Better? Asks 38 Yr. Old Mom Who Wants One More Child

Question:

Dear Doctor, I've just turned 38 and I have three children. Right after the birth of my third, I had my tubes tied. Somehow it made sense at the time but now I regret it. My kids are between the ages of 6 and 9 all delivered by c-section, and we would like one more. My ObGyn highly recommends IVF instead of a tubal reversal. I have a consultation with an infertility doctor in a few weeks and I am a little nervous. I would like some information or advice for a woman in my situation. I had no problems conceiving at all, have never missed a period, except during pregnancy, and I ovulate every month without fail.

My husband and I would consider adoption as well. Either way, IVF or adoption, they both are expensive and carry a risk of not working out, so we really want to make the best decision for our family. We just know that we want to expand our family. Thanks so much. K. from Maine

Answer:

Hello K. from Maine,

Your question is a common one and one that I have to discuss often. Hopefully I will be able to give you the facts so that you can make your decision. I have to commend your Gyn doctor for his recommendations, as I think he/she is correct, and I am sure that your infertility doctor will concur. Here is what I tell my patients to consider.

Let's look at the pros and cons of each option:

First let's consider tubal reversal. What tubal reversal (called a tubal reanastamosis) does is it brings the previously damaged or separated tubes back together so that they are open again. There are two initial considerations when considering this procedure. One is what type of tubal ligation was done. Some tubal ligations, and the doctors that do them, are more permanent. Most doctors doing tubal ligations realize and fear that if the tubal ligation (or "BTL" bilateral tubal ligation) fails, they are at risk for a malpractice suit. For that reason, they make doubly sure that it doesn't fail by doing as much damage to the tube as possible i.e. either remove/burn a large portion of the tube or remove the end of the tube "fimbria". This is especially true when the BTL is done immediately after a delivery or during a c-section, called a postpartum tubal ligation. Because the tube is readily accessible, the Physician will usually cut, tie and burn a large segment. The more damage a tube undergoes, the less chances that it can be repaired or that the repair will work.

The second consideration is how much tube is left to repair. The Fallopian tube needs a minimal amount of length and structure for it to be a functional tube. If the fimbriated end is removed or a large portion of the tube removed or burned, there will not be sufficient tube to repair for a tube to be functional. The tube is after all, a functioning structure with muscle and cilia within. If the proper segments are not available it doesn't work. The fallopian tube is not just a tube. So based on the fact that your tubal ligation was done at the time of a c-section, I would make the assumption that there is not sufficient tube to repair.

Another disadvantage to consider, of course, is what if the surgery is not successful. Not because there is not enough tubal length, but because it does not come together properly or heal properly. Because a surgery is being done, you cannot control how it heals or repairs itself. We can only bring the tube together and hope for the best. What I mean is that the tube can become misaligned so that it is not patent. Or, you can develop scar tissue at the site of repair which can block the tube completely or partially. So even if we assume that there is sufficient length of tube, it may not work due to factors that you cannot control. If the tube heals partially so that there it is only partially open or has scar tissue, you would then be at risk for a tubal pregnancy or "ectopic", which is a surgical emergency and carries the risk of death from rupture and hemorrhage.

Next you have to consider what are your chances of pregnancy if the reversal were successful. If the repair is successful, that is that all the previous criteria is met, then it will restore your natural chances of pregnancy. However, because you have aged since your last child and are now 39 years old, your natural chance of pregnancy has decreased significantly. Your last pregnancy was at the age of 32 years old when you conceived. At that time you had a 50-60% chance of pregnancy per year or 15% per month of trying. Now you are 39 years old. Your natural fertility rate has declined due to age and is now 12% per year or approximately 1-3% per month.You will also need to consider that this is a surgery, done either by a small incision "minilaparotomy", large incision like your c-section "laparotomy" or by laparoscopy. It carries all the risks of surgery and requires general anesthesia. There is also the risk that you may have scar tissue formation around the tubes due to the prior c-sections and tubal ligation that would make the surgery difficult or not possible. It is not a simple surgery like the tubal ligation. (As someone who has done hundreds of cases and come up against mega scar tissue, believe me it is not a walk in the park.) It is actually a very difficult microsurgery that requires a Physician with the proper skills to complete properly.

Finally, there is the issue of cost. In my surgery center, it will cost $10,000 for a tubal reversal (Physician fee and Surgery center fee). That will vary according to your area so you will need to check to see what the price will be for you. I did have a patient go to North Carolina for a tubal repair, at 38 years old and it cost her about $8000. She is still not successfully pregnant. She did get pregnant but had a miscarriage (partly because of the decreased fertility rate due to age). In any case, is $8000-10,000 worth a 1-3% chance of pregnancy per month?

In your case, you also have to consider that since you want only one more child, after all this expense and surgery, will you then have another tubal ligation? Also, having had 3 c-sections, you know that you will need to have another c-section. Finally, you also need to consider that you have a genetic risk of Down's syndrome that is 1/100 births due to your age i.e. it is significantly increased and your risk of miscarriages is increased.

Now let's examine the alternative, which is IVF. In this procedure, the eggs are taken directly from the ovaries so the tubes are bypassed and not required to be repaired. First, it is not a surgery but a procedure where a needle is introduced through the vagina to retrieve the eggs, under ultrasound guidance. Sedation is used but general anesthesia is not required. There is some risk but nothing like a surgery. So, the benefit is that as long as your ovaries are still working well, so that they stimulate well and produce an adequate number of follicles that have eggs in them, you can be sure that the procedure can be completed in it's entirety. There is no risk that the treatment cannot be completed. Now, there is the risk that a pregnancy will not result, different from reversal in that there is both the risk that the surgery will fail and that a pregnancy will not result, because the last two steps your body has to go through to achieve the pregnancy are still natural steps and we don't have the technology to make it happen. But because IVF accomplishes 7 of the 9 steps required for a pregnancy to naturally occur, the chances of success are higher. Also, despite this, at 39 years old pregnancy rates are 50-60% per treatment cycle (i.e. per month of trying). As you can see, this treatment also helps to overcome the age factor as well because more eggs can be retrieved and so there is a higher chance that we will get a good egg. There is still the genetic and miscarriage risks due to age, but I think those are reduced because IVF is less of a "natural" procedure and the weaker eggs/embryos do not survive the process. But, those risks are still there.

In the 17 years that I have been doing IVF, I have only had two cases of Down's syndrome in my patients, both in patients over 40 years old.

Well I think I have written one of my longer answers :)... so I think I should stop here. As you can see, IVF is better because it has a better chance of success in consideration of your age and type of tubal ligation, and it is less risky. The cost is higher, approximately $15,000 in all, but it has a better chance of working. You should consult my blog where I have written on this subject as well.

Good Luck,

Dr. Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
www.montereybayivf.com

Monterey, California, U.S.A

Grading Of Embryos At Blastocyst: How Does It Reflect Implantation Rates?

Question:

My husband and I recently went through our first IVF. We have been trying for 2.5 years to get pregnant and have done 6 failed IUIs. We have stage 2 endometriosis that was cleared out by a laparoscopy last Fall. Aside from that we are unexplained infertility. We retrieved 10 eggs and 9 fertilized naturally. We transferred 2 blastocysts on Day 5 that were graded 2BB and 3BB at transfer. We had 5 others that made it to freeze on day 6.

I have been a little stressed out about the quality of the blastocysts. I know that 4AA is the highest. Will our blastocyst quality impact implantation rates? R. from the U.S.

Answer:

Hello R. from the U.S.,

The answer to your question is yes and no. It is ambiguous because grading does not necessarily predict whether implantation, pregnancy or a successful delivery will take place. I have often been surprised when I get a pregnancy from embryos that are "graded" as poor quality. I have also seen cases where when we do genetic testing called PGS (preimplantation genetic screening) the test results reveal that the good quality embryos are abnormal and the real bad one is normal! So I don't think you can say that the way your blastocyst are graded will necessarily have any impact on their ability to implant.

At this point in time, we do not have the technology to evaluate embryos fully to know which ones will implant and which ones won't. As far as I'm concerned, all embryos have the potential to implant and lead to a successful pregnancy. In my opinion, only God knows for sure. It is a good sign that you had embryos to transfer and freeze...Good luck with your transfer results!

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.

Doctor Cancels IVF Cycle Despite Follies Being Present: Can Patient Go On To Do A "Natural" IVF Cycle?

HI-
This is a pretty simple question - started IVF cycle with micro-dose lupron after 10 days on the pill (for the dr.s convenience) Follistem and menopur. I stimmed for 4 days then cancelled due to only having 3 follicles and low E2.

My question is, my period is due soon. Can I jump right in and re-start the process? This go around will be a "natural" cycle. I respond much better when it correlates to my body's natural timing. We have an issue with age and I hate to put it off another whole month.

Thank you! A. From Illinois

Answer:

Hello A. from the U.S.,

First let me say that using the birth control pill is NOT just for the doctor's convenience. After many many years of doing IVF worldwide, it has been shown to help increase the chances of success and helps to control the ovary better. Timing is critical with IVF so it especially helps with timing.

Yes, natural cycle IVF can be done and there are some (a minority) of specialists that think this works better in low responder or older patients. But if that were the thinking then why cancel a cycle? I am not one of those "believers" and I don't cancel cycles. Even if I have only one follicle, there is no way for me to know that that one follicle doesn't have the perfect egg that only comes up once every several months. Why should I waste the opportunity? I have had many pregnancies with only one follicle and one egg.

You certainly can go directly into another cycle using your natural period as the start point. You will need to check with your doctor about that, but physiologically there is not reason to not do that except if a persistent cyst is present. Sometimes, if ovulation has not occurred, you can have a persistent cyst that will cause dysfunctional bleeding and trick you into thinking that you are having a natural period. It just needs to be checked for at the beginning (CD#2) of the cycle.

Good Luck,

Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
www.montereybayivf.com

Monterey, California, U.S.A.

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.

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.