After Failing 3 IVF, Reader Has Pregnancy Success After Writing To Me

Dear Readers, Sometimes I get great news from one of the many couples I help on AllExperts.com and this is one I would like to share with you. Over a year ago I began corresponding with this woman regarding her failed IVF cycles. Her original questions appear right after the good news I received from her a few days ago. Makes it all worthwhile :)

October 7, 2013

Comment:   Dr. Ramirez helped me conceive from across the country thanks to his blog. We've never met and my husband and I credit him with the birth of our healthy baby boy. When my RE rejected our suggestions, Dr. Ramirez provided facts that played a major role in our "self" treatment which was to try naturally with baby aspirin. More doctors should provide online guidance and provide proven medical facts and suggestions to help those of us who are skeptical of patient forums. 

July 2012

Question:

Hello Dr. Ramirez,

I am writing from the United States.  I have been TTC for 2 years.  I began RE treatment 6 months after trying to conceive naturally at 34 yrs old. I am 36 now. I have failed 6 Intra Uterine Inseminations and Three IVF (in vitro fertilization) cycles. Below are the details: (for privacy purposes I have omitted the precise details of each cycle…except for the transfer details)

First IVF: 7 mature eggs, All ICSI 1 fertilized, transferred 4 cell Grade AB on day 3

Second IVF: 17 mature eggs, 9 fertilized, transferred 2 Grade AA on Day 3, one made it to blast and freeze (poor quality)

Third IVF - 18 mature eggs, 14 fertilized, 9 made it to blast, transferred 2 Grade AA, froze 6 good quality blasts ranging from Grades AA - BB

I never had a positive beta or urine test.  I've done all the preliminary testing, water sono, bloodwork, HSG, etc. everything is normal.  My husband’s tests and sperm are also normal.

I asked about immunology testing and Doctor said there is nothing to support that treating it helps.

I don't believe the early bleeding is normal. My luteal phase naturally is about 11 days long.  Dr said the PIO is plenty for me and would not recommend increasing it.

I asked about baby aspirin and heparin. They said baby aspirin is ok, but heparin can be dangerous.  I've read in your posts that you recommend that if there is one IVF failure.

Is there harm in taking heparin? I don't know what else to do to make them implant.  What are your thoughts considering my history?  I do not want to transfer any frozens unless the protocol is changed. I feel like continuing the same PIO / medrol protocol is setting me up for failure again.  I appreciate your advice. Thank you!

Answer:

Hello,

Since you have had decent embryos to transfer in at least two of your three IVF cycles, this would be regarded as implantation failure.  Thanks for reading my posts.  I also discuss these issues in my blog.

Your doctor is right in that the correct general opinion, kind of like being politically correct, is that the studies do not show any benefit to treating for immunologic problems in IVF.  However, it remains to be seen and depends which studies you prefer to believe.  There are certainly studies that show that immunology plays a role in miscarriages and some studies that show immunological treatments help with IVF.  I don't think it can be discounted completely but at the same time, don't believe in every treatment that is offered.

I certainly advocate low dose aspirin, low dose medrol and low dose heparin in my patients that fail two cycles of IVF for no clear reason.  I have had many be successful thereafter with that protocol, which I have been using for the past 18 years.  There is NO danger in using low dose heparin.  Full dose heparin is another matter.

I think that the dilemma you now face is whether to continue with this doctor or not.  If you want more, such as using the protocol mentioned, then you'll probably have to find a doctor that will provide that to you.  I certainly think your doctor needs to reevaluate and consider what else he/she can do since what is being done so far has failed.

You certainly can always fly out to California. :)  For an FET cycle, you would only need to be here for one day.

Good Luck,

Dr. Edward J. Ramirez, M.D., FACOG

Follow-Up Question:

Hello again,

We consulted with our RE again regarding the transfer and he suggested doing nothing differently and chalked it up to bad embryo genetics.  Again he reiterated no baby aspirin so we pleaded for him to do immunologic testing, cytogenetics (on us) and blood clotting work ups to which he agreed.

Everything came back normal, including cytogenetics on my husband, with the exception of my protein s free antigen level. It was 151 and regarded as "high" by the lab that ran it.  He referred me to a hematologist who ran protein s activity testing which thankfully came back normal. He said a high level protein s is not concerning and that only a low level would be.

So here we are again with his recommendation of transferring with the same protocol.  I asked again how about baby aspirin and he remained firm on "no".  I told him 3 doctors, including one at his practice, the hematologist and an online doctor i have emailed have said there is no harm in using it along with my friends who have used it with no pre-existing blood clotting disorders and went on to have successful IVFs.

He said taking baby aspirin with no blood clotting problem can cause more complications than help.  He said it can interfere with the growth of the placenta.  Is this true?  So far he is the only doctor that has said no to baby aspirin including the doctors of everybody I know who has gone through ivf unexplained.

Are there any facts you know of with baby aspirin and placental defects?

Again, I truly appreciate your knowledge and advice and thank you for your responses.  There should be more doctors like you who help others online with honest, professional opinions!

Follow –Up Answer:

Hello Again,

There are no studies that show any adverse affects of low dose aspirin on embryo or placental development.  In fact, and either you or he can look this up in any Infertility textbook, low dose aspirin is an approved and advocated treatment for recurrent pregnancy loss (now why would they endorse it if it caused placental problems?).  We have extrapolated its use in failed IVF with the same idea that it increases blood flow to the implantation site and reduces the formation of micro-clots in the tiny vessels supplying the implantation site.  There is no way to test for these. 

Since this doctor is not willing to work with you on this very simple and innocuous treatment, which may or may not help, I think you should seriously re-consider using him.

Good Luck,

Edward J. Ramirez, M.D.

Follow-Up Question:

QUESTION: Hello again

Have you noticed this email is more than nine months after your last reply?

Our RE did not budge again on the baby aspirin so we decided to wait on the next transfer and try naturally with baby aspirin.

That month I became pregnant for the first time. I went to my RE and he confirmed it with blood though the levels were low and I was bleeding and he did not offer progesterone cream. He said he doubted the pregnancy was due to the baby aspirin. At 5 weeks I miscarried, and although it was sad, I was elated at the fact that I did get pregnant. So we tried again naturally the following cycle with baby aspirin (2 weeks after miscarriage) and what do you know?

I got pregnant again.  I went back to RE and he confirmed with a blood test. I started bleeding again so he suggested progesterone cream.  I told him we did the baby aspirin thing again and if I should continue taking it and he said YES! 

He followed my progress until 2 months and referred me to my obgyn to monitor the pregnancy. I continued the progesterone cream until the end of the 3 months and continued taking baby aspirin until 37 weeks. Yes, 37 weeks.

Our healthy baby boy was born at 41 weeks, weighing 9lbs, 4oz and measuring 20.5 inches.

If I did not read your blog, he would not exist. My husband and I attribute his existence to your blog and cannot thank you enough.  Please continue your public advisement as it made our dreams come true.

Thank you!!!!!!
 

Follow-up Answer:

Hello,

I am absolutely delighted for you.  Congratulations :)  I'm saddened to see that you had to prescribe a therapy for yourself, but glad that it might have done the trick.  No one will ever know for sure if it helped or not and what the mechanism is, but it seems to help many people with your type of history.  I now put all my infertility patients on low dose aspirin from the beginning, IVF or not. Another possible factor is that you tried soon after your miscarriage--studies show that there is a higher chance of pregnancy after a miscarriage.

I'm shocked and a little disappointed that your Ob doctor allowed you to go post-dates (41+ weeks) because that posed significant risk to the baby such as a fetal demise, fetal distress, etc.  I NEVER let my infertility or IVF patients go past 40 weeks.  The sooner the baby was out the safer it was at that point.

Thank you for reading my blog and using this service (AllExperts) as well.  I do it in tribute to the task and gifts that God has given me, which is a part of the love he has for us.  Your baby is also a gift from God for you to treasure and teach of his ways.  Devote your love to this son and shower him with Goodness so that when he grows up, he will shower others with goodness as well, and thereby contribute toward making this world a better place.  It is not often that I get feedback of successes attributed to my writings, but know that your feedback reinforces my dedication to this task.

Congratulations!

 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.

 

Similar IVF Protocol But Different Results: Why?

Question:

Hi Dr. Ramirez,

I'm back again with a question about my recent IVF (second one). This IVF (in vitro fertilization) cycle we did the same protocol as last time (antagonist) but started off at a higher dose of Gonal-f based on my response last cycle. This cycle we started off at 300iu gonal-f and 75iu menopur whereas last cycle we started with 225iu gonal f and 75 IU menopur but had to increase to 300 IU gonal f after day 4 showed an E2 of only 90. Both cycles I started out with similar AFCs of 10 and 12 at suppression check. My usual AFC is between 16-20. Last cycle it seemed that I recruited more follies along the way and ended up with an E2 of 3030 and 23 eggs retrieved (17 of which were mature based on icsi and conventional fert rates as we did 50/50 split fertilization). This cycle my E2 was 2100 at trigger and they retrieved 12 eggs (still waiting on fert report today but we are doing all conventional fertilization).

My question is why did I have such a different response this cycle given that we started off at a higher dose this cycle compared to last? Last cycle we went up from 225iu gonal to 300 IU gonal at day 4 and stayed there until trigger. this cycle we started at 300iu gonal and stayed there until we added ganirelex on day 7. At that point my E2 stalled and do they increased my gonal f to 375iu gonal f and kept me there until trigger.

As always thanks for your advice/insight. S. from the U.S.A.

Answer:

Hello S. from the U.S. (Virginia).

The human body is not a consistent nor predictable structure so I can't explain why your response is different.  I have always explained to patients that have low response to stims that the ovaries can react differently each cycle and your experience is a case in point.  That being said, I would not have increased your dosage since your stimulation was so good the previous time and you bordered on entering OHSS territory.  In any case, IVF is not a contest where the person with the highest number of follicles or eggs wins the prize.  The goal is to find 1 or 2 perfect eggs that will lead to perfect embryos and a successful pregnancy.  So despite the fact that you stimulated less, that might be a better thing.  Bottom line is you only need one good one.  Also, there have been some studies showing that when a patient stimulates hard with lots of follicles, sometimes the egg quality suffers and the pregnancy rate drops.  This is especially true in PCO patients.  In those patients, our preference is to stimulate less and get fewer follicles.

So, in any case, as the saying goes: "I don't think you should sweat the nitty gritty" i.e the fine details.  Hope for the one perfect one.  That is the goal.

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.

38 Year Old Has Five Failed Fresh IVF Cycles But Has Frozen Embies: Should She Try FET?

Question:

Hello - I have been reading you blogs for some time now and am so thankful that you take the time you do with such thoughtful answers.

I am 38 and husband is 41. My history is as follows: 2009 wasted time on clomid prescribed by my obstetrician, 2010 saw RE (reproductive endocrinologist) and began the real journey. Major issue is male factor morphology but I suspect with my age quality may be issue too.

In 2010 we had 2 Fresh IVF (in vitro fertilization) cycles, first was a failure 3 eggs collected, thankfully 3 fertilized and implanted 2 (1 frozen) but no pregnancy, cycle 2 doubled my stim meds to 300 gonal f and 150 repronex, collected 13 eggs but transferred 2 "decent" but beta was very low around 70 the pregnancy continued to around 11 weeks saw heartbeat but clearly there was issues as the size kept loosing ground until miscarriage and D&E. Cycle 3 same meds, 13 eggs, transferred 2 on day 5 and then arrived my beautiful baby girl delivered 12/29/2011.  Fast forward to 2013 where I have done two more fresh cycles same protocol, birth control, 10 lupron, to 5 lupron when stimming, retrievals after 9-10 days of stims. Cycle 4 resulted in collecting 20 eggs, 2 "decent" transferred on day 5 (blastocyst and morula) very low beta resulted in loss about a week later.  Cycle 5 same protocol except menopur instead of repronex, collected 18 eggs, 14 fertilized and transferred 2 blastocysts on day 5. This was a negative. BTW all cycles are ICSI and included medrol, baby aspirin, antibiotics, vivelle patches and  progesterone in oil injections. 

My question is what are your thoughts on FET (frozen embryo transfer).  I have 4 frozen embryos 1 from cycle 1, 1 from cycle 4 and 2 from cycle 5. RE and hubby think I should take a break and try for FET. I and concerned as I don't want to "waste" a cycle insurance will cover on the lower cost option but the meds did really affect me this time and see their point about giving my body a rest. I am at a very reputable clinic in Boston and doc said 4 frozen is a lot due to their strict freezing criteria so am optimistic although obviously embyro age has no advantage. Would FET also be something you would recommend at this point? Fresh cycles are a big logistical challenge as my husband travels 70% of the time.

Also if I go back to fresh cycle is there anything significantly different you would do (btw I am also doing acupuncture). Thank -you in advance for your time. I also want to say I am very grateful for my daughter and don't want to seem selfish but I would really like her to grow up with a sibling. 

J. from Boston

Answer:

Hello J. from the U.S. (Boston),

It sounds like you are in good hands.  Your clinic has accomplished several pregnancies, which is an IVF success.  Keep in mind that IVF can only give you the "opportunity" to become pregnant.  It can't make you pregnant because the last three steps (embryo hatching from its shell, attachment to the endometrial lining, and lining growing around the embryo are natural processes that are in God's hands.  That fact that you got a pregnancy (positive bHCG) shows that those steps occurred.  Continuation of the pregnancy is then based on pregnancy factors and not IVF factors.  Because of your age, your chances of a miscarriage are high due to abnormal embryos.  You've shown that you can get pregnant, and your ovaries stimulate very well.  Now it is just a matter of finding the perfect egg/embryo which will then lead to a successful pregnancy.  I wish all my 38 year olds responded as you do.  So hang in there!

I think I would advise proceeding with the FET cycle before another fresh cycle.  It is a much easier cycle on your body, and some newer studies are showing better pregnancy rates than fresh, probably because of the lack of overstimulation of the endometrial lining.  I don't completely agree that FET is "better" but it certainly gives a good chance.  If they fail, you can certainly try fresh cycles again.  I would advise two FET cycles consecutively.  In fact, I always advise my patients to do an FET cycle, if they have frozens, before trying a fresh cycle again.  You never know. . . the frozen might work.
In terms of additional protocol changes, you are doing everything that I have my patients do in terms of supplemental medications, but I also add low dose heparin (2000 U per day).  Not all RE's agree with this protocol, but it is an accepted protocol for recurrent pregnancy loss so you might want to ask your RE.

Thanks for following my Blog.

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.

Comment: Thank you much for the quick and thoughtful answer. I have several time contemplated seeking a more aggressive clinic despite my comfort level. Your response puts many of my worries at ease. You are truly a huge help to those of us in a constant state of limbo. Thanks again.

 

36 Yr. Old Has Repeated Implantation Failure With Great Embryos...What's Wrong?

Question:

Dear Dr,

We have just had our 4th failed IVF (in vitro fertilization).

Our history.  I am 36, my husband is 39. 1st pregnancy was in 2009 after 3 IuI's (intra uterine insemination) and clomid, but had to terminate at 15 weeks due to large enphaloceale (was a random genetic mutation)and my 2nd pregnancy with IUI was a success with a full term healthy baby boy.

Started with IuI's for 2nd child in 2011! We had 10 IuI's and now 4 IVF's.  Each IVF has been with icsi (intracytoplasmic sperm injection) and this time we had Embryo hatching. Last 3 transfers were 3 top grade 8 cell embryos each time on day 3.  I am not a great responder and only ever have 5-7 eggs, of which usually 4 fertilise.

I have had all the immunity checks done, my husbands sperm dna damage is within normal, fertilisation rate is good.  My ovarian reserve was also checked and the level was 1.0- My specialist said that he wasn't overly worried about the reserve for my age.  I have had a hysteroscopy and all normal.  I have been on various drug protocols and this last one was the long Lupron cycle with menapur.

We are just not sure what to do next?  Do we keep going, as my doctors are very positive and we have the finances. Are my doctors missing something?  Is there anything else we can do to improve our chances.  I am on DHEA and Royal Jelly, and my hubby is also on supplements.

I am writing from CapeTown, South Africa.

Thank you for your consideration, R.

Answer:

Hello R. from South Africa,

The exact cause of your failure cannot be known as there are still four steps your embryo has to go through in order to produce a pregnancy: embryo has to develop to blastocyst, the blastocyst has to hatch our of its shell, it then has to attach to the uterine lining and the lining has to grow around it.  As of now, there is no technology that can make this happen.  "Assisted hatching" is just making a defect in the shell so that the embryo can exit (hatch) more easily.

Something I always worry about when I have patients tell me they have failed multiple cycles despite good embryos, is the quality of the final step of the IVF process, which is the transfer.  You can have the absolute best and perfect embryos but if the transfer technique is not done well, then it will fail.  This has been shown by numerous studies.  Since you have been going to the same clinic, I wonder if that is not the problem, in which case, I would recommend that you seek out a different clinic.

One thing that I do with my patients that is not universally accepted but done by many of us, is to use a recurrent miscarriage protocol to reduce the immune system, thinking that a heightened immune system might be at fault.  For this regimen I add low dose heparin or lovenox, medrol, low dose aspirin, extra estrogen and extra progesterone (both injectable and vaginal).  I don't think that DHEA does anything so I don't use it.

At 36 years old, I have a 66% pregnancy rate in my clinic.  By two to three attempts with good 8 cell embryos, you should already be pregnant.  Your rate should especially be increased over other 36 year olds since you have been pregnant before.  For these reasons, I think the fault may lie in your clinic and not in you or your husband. 

Good luck in your journey to have a second child,

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

 

Monterey, California, U.S.A.

Recurrent Pregnancy Loss: 5 Miscarriages Since 2009

Question:

Hello Dr. Ramirez,

My husband and I have been trying to conceive since 2007. I have PCOS (polycystic ovarian syndrome) and I have had 5 miscarriages, first one in April 2009 at 10 weeks and the others at 6 weeks. I've also lost a baby due to an incompetent cervix at 6 months. My most recent miscarriage was last month after an IFV cycle at 6 weeks. I was on baby aspirin, progesterone shot, metformin and Estrace. My fertility specialist was not able to say why I am having these recurrent miscarriages. My doctor has done blood work and all standard testing.

After numerous IUI cycles we went ahead with IVF which also led to a miscarriage. I still have four embryos left and don't want to pursue with another IVF cycle until I can get some answers as to what might have gone wrong or what I can do to change the outcome. Do you have any suggestions for me? Any feedback is greatly appreciated. N. from Canada

Answer:

Hello N. from Canada,

I am sorry for all your losses! The incompetent cervix is something that can easily be handled with your next  pregnancy by doing a cerclage (either a TVC or a TAC by the 16th week of gestation--a TAC can also be done pre-pregnancy). But you need to achieve and hold that next pregnancy. First, let me say that you should also read my website page where I have written extensively regarding evaluation of Recurrent Pregnancy Loss (RPL) and a possible protocol for treating this problem. Anyone who has miscarried three times or more needs to have this type of comprehensive evaluation. Some of the possible reasons you may be miscarrying include:

• Genetic/Chromosomal Causes (you don't state your age, but that could be factor)
• Polyps, Fibroids & Uterine Disorders
• Hematologic Disorders
• Hormonal (you have PCOS, so your cycle day 9 & 10 LH needs to be checked )
• Infectious, Genetic & Immune Factors

With a diagnosis of "Recurrent pregnancy loss", there is a protocol that is usually followed to evaluate for the possible causes. As stated above, this includes genetic testing (both you and your husband), immunological testing, infectious disease testing, anatomical testing, hematologic testing and hormonal testing. It is quite an extensive array of tests and can take up to two months.This is what should be done BEFORE you proceed with any more IVF cycles. The treatment will then depend on what is found. In some cases, for those with genetic causes, IVF with PGD (preimplantation genetic diagnosis) can be done to test the embryos for viability and chromosomal abherrations.

What is good is that you are able to ovulate, that your eggs fertilize and that you have been able to get pregnant. It is very difficult to go through as many miscarriages as you have and I hope that with proper evaluation you will be able to deliver a beautiful, healthy child in the near future.

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.

"Infertility Nightmare" After TTC For Seven Years & Two Failed IVFs

QUESTION:

Hi, I was very much hoping you could help me with my infertility nightmare!

Myself - 30 yrs old, AMH: 3 / FSH 9 / ttc 7 years / diagnosed this year with severe endometriosis mostly around my ovaries.

My partner - 39 yrs old - no issues

After trying unsuccessfully naturally for 4 years (tried using ov kits but no signs of ov) I consulted my gp and was referred to our local hospital for 'basic fertility tests'. No issues apparently found and I was diagnosed with 'unexplained infertility'!

I was then given 3 months of clomid and a follow up appointment for 6 months later! Clomid did nothing for me (no ovulation detected on ov kits). My periods were horrendous whilst on this and shortened to 24 days following it. They went back to 28-29 days after a few months.

I was then referred to another hospital for IVF. Again only the basic tests were carried out (blood, semen etc). This was when I was found to have an AMH of 3.

IVF 1 - 0.5 burselin / 4 vials of menopur / gonasi hcg trigger shot / 2x 200mg cyclogest.

Stimmed for 12 days in total - produced 10 eggs of which 5 fertilised. Transferred 1 hatching blast on day 5. Other 4 embryos did not make it to freeze.

Day 3 started to spot pink blood & by day 5 had period. I did have a very strong 'immune reaction' the day after transfer (flu like symptoms which lasted 12 hrs).

My consultant advised he thought the egg quality was to blame causing the early bleed after implantation.

I insisted on further tests and 3 months later has a Hysteroscopy and LAP (laparoscopy). I was then diagnosed with severe endometriosis. I was also given a cervical dilation due to a difficult transfer. I apparently have a small and narrow cervix and a forward tilting uterus.

IVF 2 - 0.5 buserelin / 6 vials of menopur / gonasi hcg shot / 3x 200mg of cyclogest (after my insisting).

Stimmed for 13 days and was very slow to respond this time. Six eggs collected of which 3 fertilised. Two blasts transferred on day 5 (1 more advanced than the other). Day 4 after transfer pink spotting again again developed into period. Felt slightly unwell the day after transfer (but not as intense as the first ivf).

Both IVF's resulted in negatives.

My questions are:

1. What is your opinion on the early bleeds? Do you think it's embryo quality (I don't know there officially grading by the lab). Or is it an immune issue possibly lined to the endo? Or both? My aim next is to have level 1 and 2 immune testing.

2. Do you think the progesterone support is enough? May I possibly also need estrogen support? My doctor does not believe in this!
My aim is to try with DE next time due to my poor response on IVF 2. Do you agree? My main concern is the amount of time I have been infertile plus the 2 failures. I have never achieved a pregnancy yet. Do I have hope in your opinion?

Thank you so much for taking the time to read this.

N. from Ireland

ANSWER: Hello N. from Ireland,

Please note that detailed and comprehensive recommendations cannot be given without review of your medical records. This venue only allows for short and succinct answers so I hope it suffices.

Embryo quality DOES NOT cause post-transfer bleeding. If bleeding occurred, there is probably no way to know exactly what the bleeding was from, however, the first question would be whether or not there was an adequate luteal phase i.e. whether the progesterone you took produced adequate levels. If you took the medication orally, it would not be adequate. The only way to take progesterone with IVF is either vaginally or by injection. Vaginal progesterone can, however, cause some cervical bleeding because of some eroding effects on the cervix. This is not an indication of an immune problem.

Estrogen is required for adequate endometrial formation as manifest by endometrial thickness and a trilaminar pattern on ultrasoud. Estrogen is also required in the implantation phase and is easy to use so many IVF programs do add this to the regimen.

I'm afraid I don't know what you mean by "DE", so cannot comment.

There is always hope. The key is to find the proper treatment, the proper doctor and the proper clinic to make that happen. I tell my patients, "we can get almost anyone pregnant. It is just a matter of what needs to be done to do so." The only sure way to fail is to stop trying.

Good Luck, Dr. Edward J. Ramirez, M.D., FACOG

FOLLOW-UP QUESTION:

Hi Dr Ramirez, many thanks for your reply and for taking the time.

Regarding the progesterone I was taking this rectally by Cyclogest pessarie 400mg x3 daily. The reason for taking it rectally is that i tend to suffer from thrush. I'm now wondering whether taking this rectally was not sufficient. I am also concerned I am not maybe absorbing the progesterone enough therefore and I'm now keen to try injections next time.

I do tend to suffer with a shorter luteal phase of 10 days before spotting / bleeding on natural cycles.

I will defiantly suggest using estrogen next time. I can not understand other than a hormone in-balance why i would twice suffer from such an early bleed. My lining on the last scan was found to be 10.9 and of a trilaminar pattern.

'DE' stands for donor eggs. I was advised after my first failure not to try more than 3 times with my own eggs. After my poor response to this cycle and the outcome again I am almost definitely considering trying with donor eggs on my third cycle. I just hope to try and determine any other causes for failure before doing this.

Other than the above and the immune testing the only other issue I'm concerned about was the fact both of my embryo transfers have not been straightforward. Although the second transfer was not as painful as the first, I could still feel the catheter going all the way up into my uterus which was incredibly uncomfortable.

Its such a pity your clinic is far, far away!

Thanks again for your time. If I am to reach a successful outcome in the future I will be to sure to come back and update this to hopefully give other women possible clues to their failures.

N. from Ireland

FOLLOW-UP ANSWER:

Hello Again,

I see no reason why you need to consider Donor eggs. Rather, I think you need to consider changing to a different clinic! Pregnancy rates vary highly from one clinic to another. For example, we have 14 clinics within 100 miles of my center and based on Nationally reported statistics (we are required to report to the Federal Government annually), our clinic has the third highest pregnancy rates within this area. The lowest clinics have rates that are 1/2 of our rate. So where you go makes a difference.

Upon reading your follow-up letter, I saw a significant problem that you have. The embryo transfer is one of the most critical steps, if not the most critical steps, in the IVF treatment process (see my Blog posting on "Step Seven: Embryo Transfer" ). You can have absolutely PERFECT embryos but if they are not transferred appropriately, the cycle will FAIL. The transfer should be a completely PAINLESS procedure and you should not feel a thing. If the catheter touches the back of the uterine cavity or there is bleeding, either of these will cause failure. Maybe that is the main problem? Technique is part of what makes one doctor different from another in terms of pregnancy rates.

I know that I am "far away" but I have had the pleasure of seeing patients from France, Italy, Serbia, Germany, South Korea thus far. Many of these patients tried in local clinics and failed. So, yes it is a 12 hour trip by air, and would definitely cost more for hotel, etc., but if the result is a positive one, would it not be worth it? I'm not trying to induce you to come to my center, but the point I am making is that patients don't have to suffer and endure multiple failures with their local clinic if it is not the best one.

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.

Comment: Thank you once again Dr Ramirez, I was very interested to read your answer & your article regarding embryo transfer & will be taking this up with the hospital on my follow up appointment in the new year. N.

32 Year Old With Two Failed IVF Cycles With Positive Beta's: Chemical Pregnancies?

Question:  Hi Doctor,
I live in Idaho where we only have 1 IVf (in vitro fertilization) clinic, so I don't have the option of a second opinion and can't decide if it's worth the six plus hour drive to find out if anyone else would do anything different so I really appreciate you reading this.

A quick medical run down is my infertility was both blocked tubes which 3 years ago I had opened, since they've been open I developed endometriosis which I had cleared last September. I am 32 years old with no medical issues. I have had 8 failed IUI's before finding the endo and then 4 failed IUI's since clearing it. I did have one pregnancy with the IUI but they thought it was ectopic and it aborted itself. I have just completed my second failed IVF. By the way DH has all "normal" counts and morphs for his samples. Both protocols for meds were the same I took Doxycycline and Medrol right after ER (embryo retrieval) and started Progesterone vaginal inserts day after ET (embryo transfer) and was on prenatals and baby asprin the whole time. Both transfer's were done with guided ultrasound with no complications.

1st IVF-September 2012. 10 eggs,10 matured, 4 embryo's fertilized (no ICSI) 1-six cell, 3-eight cell all grade 2's. Two embryo's transfered, last 2 died on day 6 before making it to blast. First beta was 9, second 32, then on day 11 I started spotting,cramping and clotting. Day 13 beta was 7.

2nd IVF-November 2012. 21 eggs, 18 matured, 13 fertilized with ICSI, 1-eight cell grade 1, 6-eight cell grade 2, 4-seven cell grade 2, 1-nine cell grade 2, 1-two cell grade 3. Transfered 2 embryo's back (one was hatching) and cryopreserved 6. Beta test 1 was only a 3 and then the second beta nothing improved. I started bleeding day 11 again.

I have not yet met with my RE but I am trying to gather all the info I can before meeting with her. This last fresh cycle will have been the last one that I think I will do just because the stress on my body of being on meds off and on for 3 years now I think is too much. So the 6 frozen are very important to me to use wisely. I read that you said a chemical pregnancy is not an implantation problem so does that mean that you think it would be a problem with the embyo's? My RE felt last time that there was no need for genetic testing and that my endo was not an issue. I'm just lost as to what my next step should be, what to test for or what I should do with my remaining embryo's (gestational carrier or gamble with them). Thank you again for your time, your blog's have been so much help for me while searching for answers. M. from Idaho, U.S.A.

Answer:

Hello M. from the U.S. (Idaho),

Once you get a positive bHCG, that means that implantation occurred. To be more specific, it means that after the embryo was transferred into the endometrial cavity (the limit of what IVF can do), the embryo progressed in its development, hatched out of its shell, attached to the endometrial lining and the lining grew and enclosed the embryo. These last steps are all natural steps that we do not have the technology to make happen. They have to happen on their own. The take away message from this is the knowledge that you can achieve a pregnancy with IVF. The ensuing problem, of miscarriage, is a pregnancy issue. Whether or not the embryo progresses to developing a successful pregnancy and ultimately a normal and healthy baby is based on the pregnancy alone.

Miscarriage is a more common occurrence than people think. We know that up to 50% of pregnancies can end in a miscarriage, many of which are chemical pregnancies like you had. In most cases of early miscarriage, the reason is because of an abnormal embryo, meaning the embryo had some sort of genetic abnormality. In most of these cases, it is a spontaneous abnormality that occurred at the time of embryo division and not something that you carry. But just to make sure, you and your husband might want to undergo genetic testing if you have not already done so.

One other thing I noticed is that your embryo quality, based on its external appearance because we don't have the technology to know the internal quality, was not optimal for someone your age. This could be related to an inherent problem with the eggs, sperm or lab conditions. In a woman under the age of 35, I would expect most of the embryos to be 8 cell, grade 1 embryos. Genetic testing in the embryos, PGS, is an option but I too would not have recommended it in your age group. In addition, PGS may do some harm to the embryo thereby reducing your pregnancy chances. You'll need to discuss this further with your doctor.

I don't think that any of this has to do with your endometriosis, which is not an issue with IVF.

Ultimately, because you have achieved chemical pregnancies, you have to keep in mind that the IVF can work. Now it is just a matter or time, or more specifically, a matter of getting the perfect embryo. That will take continuing to try and ultimately I am confident you will be successful. It is unfortunate that you only have one option for an IVF clinic in your area because pregnancy rates vary highly from clinic to clinic. That may be another option i.e. travelling to another clinic. We call that distance IVF where patients travel to another state to have the IVF done. It is easily coordinated and arranged so you don't have to limit yourself to one option only. There is more that can be said or advised, but a thorough review of your medical records would be required.

Good Luck,

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

Comment: I was amazed at the timely response and all the information given. I feel confident that the Dr. is giving a knowledgable response as well as very honest without pushing his own clinic which was comforting. Thank you again for your time.

High Responder Fails Two IVM and Two IVF Cycles: PCOD & Follicle Maturation Issues

QUESTION: Hello,

During the last year we did two IVM (in vitro maturation) and two IVF (in vitro fertilization) cycles at different clinics at Montreal, Canada. All failed. I'm 39 years old and my husband is 40. My FSH was 11.1 and AMH 2.2 two years ago. The first IVM was without stimulation, I was triggered when the lead follicle was 13mm, 11 eggs were collected, 7 managed to mature in the lab and 4 fertilized. By the day 3 we had transferred 2 embryos 6 and 8 cells (they did not give us their grade). Endometrium was 6.8mm by the day of collection. No pregnancy...

The second IVM I had 3 days light stimulation (about 150UI Puregon days 3-5 + Estrace from day 6). I was not aware of my hormone test that shown the E2 level fell on day 6. We had collected only 8 immature eggs from 17 follicles, the only egg fertilized and on the second day the weak embryo was transferred. Endometrium was 7.3mm. Of cause, no pregnancy.

We moved to another clinic and did there two IVFs. The first one I had stimulation from the second day: 225 Gonal-F + 75 Luveris. After 4 days dosage was increased up to 300 Gonal-F + 150 Luveris. On the day 13 I was triggered when I had one follicle about 22mm, 2 about 18mm, and many smaller ones. We collected 16 eggs, 12 were mature, 9 fertilized. My doctor decided to wait till day 5 for the transfer. We had one blast, the other embryos stopped developing. The lining was 8.2mm at the day of transfer. No pregnancy.

As the clinic doesn't work during weekends, the stimulation for our second IVF started on day 4 and lasted 9 days. It was more aggressive: 300 Gonal-F + 150 Luveris from the start and about 200 Gonal-F + 150 Luveris at the end as I had developed mild OHSS. I was triggered when my follicles were 1-19mm, 1-18mm, 3-16mm, and many 15mm and less. As I said the clinic doesn't work weekends. My collection was Friday. I asked to wait for follicle growing bigger and the answer was: no, they are big enough. We collected 25 eggs, only 13 were mature, and only 5 fertilized. They were stopping developing one after another. The last one stopped at day 6 on the morulae stage. The lining was perfect: 13.5mm. It was an epic failure: nothing to transfer... I was told that the issue is my egg quality (my husband has no issues with his sperm).

I see that I had the only follicle bigger 20mm at the collection and we had the only blast. So I really would like to understand whether it's not a coincidence? If there is a way to have more equal size of follicles by changing the protocol? If I'm a good responder and have many eggs and they usually fertilize good (if they are mature) but they stop developing - does it mean they are poor quality? Or they were not fully mature at the day of collection? As I'm getting older and we have no time to experiment with different protocols I would like to maximize our chances by using more effective protocol for our next attempt. It would be great to hear your opinion on it. Could the change in protocol give us better chance for success?

Thank you in advance! O. from Canada.

ANSWER: Hello O. from Canada,

I can't give you specific protocol recommendations because each doctor and each clinic do different things. There is no one way to do IVF as you have found out.

The latter stimulation cycles show that you are NOT a poor responder but a high responder with PCOD tendencies. That means your ovaries are very sensitive to stimulation and that is a good thing. Yes, your age and therefore your egg quality are issues. However, hope is not lost because there is a chance that you still have a few good eggs left. As long as your ovaries respond well to stimulation, your chances of finding the good eggs are high. However, it also means that you need to find the right clinic because pregnancy rates will vary highly depending on the skill of the clinic and factors such as when to retrieve. I think it is a mistake to go to a clinic that only does egg maturation, and a clinic that doesn't work weekends. Both clinics are short changing you. It's time to find a better clinic.

It is also known that when OHSS develops, the pregnancy rates also drops. Probably because the majority of the eggs are not adequately matured. So one goal would be to decrease the stimulation and try for fewer eggs and a longer stimulation to get higher quality eggs. That is my goal with patients that are high responders. One method I use to try to even out the stimulation is to use the "sandwich protocol" which is to use 2-3 days of antagonist prior to starting the stimulation (I don't use the long Lupron protocol)to suppress the ovaries so that the follicles all start at the same point. Not all doctors use this protcol.

One final note: I let my follicles reach 20 mms before trigger. In some cases, I'll go up to 24 mms on the lead follicles if there is some unevenness, the goal of which is to try to get as many mature eggs as possible. Again, these things/variations are what make clinics and doctors different. You need to find a clinic that has a respectable pregnancy rate for your age group (and that will stay open on the weekends) so that you don't waste any more IVF cycles.

FOLLOW-UP QUESTION:

Dr. Ramirez,

At first, thank you very much for your fast and detailed response.

I've forgot to mention that our infertility is unexplained and I always have a lot of follicles at any given cycle (the first time we asked medical help for infertility 4 years ago).

Today I've got some new details about my IVFs: first time the E2 was about 8000 at the day of trigger and progesterone was about 4. The second time E2 was more than 22000 and progesterone was 6.4 so that my doctor didn't wait anymore and triggered me when the lead follicle was still 19mm (and not because they do not work weekends, as he explained). Is it possible that the E2 level could compromise egg quality the second time?

My doctor told me that assisted hatching is not possible for a blast as it can be easily damaged. Do you agree with that? Is assisted hatching used for day 3 embryos only?

Also my doctor is tended to wait for a blast and do 5-day transfer as he believes it would give stronger embryo and higher chances of implantation. As I see we had many good-looking embryos on day 3 and 1 or no blast at day 5. Would it better to transfer at day 3 instead?

Thanks again for sharing your knowledge

Regards, O. from Canada.

FOLLOW-UP ANSWER:

Hello again,

You have to understand that my advice is my personal opinion and not necessarily the gold standard or generally accepted standard because there are many many variations in the stimulation portion of the IVF cycle. But let me give you my opinion.

Both cycles led to overstimulated cycles. If the peak E2's are correct, you went very very high and in the U.S., in general, we don't like the E2 to go above 4000. Yes, it has been shown that when hyperstimulation occurs, i.e. the E2 goes above 4000, there seems to be a decline in egg quality and pregnancy rates.

You don't necessarily have a diagnosis of "unknown" infertility. You have the "age factor" which means that your egg quality could be compromised based on your age. That is a diagnosis. My approach to transfer is to use D#3 transfers unless I have so many good D#3 embryos that it is harder to determine which ones to transfer. In that case I will proceed to D#5. I am not a big D#5 person because I don't think that it is an absolutely perfect technology and we probably lose some good embryos because of it (that has been shown by genetic testing of the embryos on D#3). Not all blastocysts are genetically good embryos. Because of your age, I don't think it makes any difference which day you transfer, but I would prefer to put back more and let nature decide that the lab. YES, assisted hatching can be done on blastocysts.

The only other option that might help you, is to consider preimplantation genetic screening so that only normal embryos are replaced. I would also recommend tranferring at least 4 embryos because of your age. PGS might decrease your pregnancy chances a little, depending on the expertise of the clinic, but can help you to distinguish the genetically normal from the abnormal. PGS can be done on D#3 or D#5.

Good Luck,

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

Comment: Dr. Ramirez gives detailed and clear answers. He is extremely helpful and very knowledgeable.

40 Year Old UK Woman Trying IVF After Implantation Failures: Assisted Hatching & PGD?

PGD

QUESTION:
dear doctor ramirez, i am so glad to find you on this website and would very much appreciate your help. I will try to give you some background.

i have had 3 failed iui, then found problems with my fallopian tubes which led to bilateral salpingectomy, myomectomy, adhesiolysis and cornual tubal occlusion, left ovarian cystectomy, i also have fitz hugh curtis syndrome.


so then after recovery from the above op i had

one fresh ivf cycle - 18 follicles, 14 eggs collected, 8 fertilised, 3 day transfer of 2 embryos(8 cell, grade 2)on 18/10, started bleeding 30/10

fet - 19/3. 2 embryos transferred (5 cell grade 2 & 7 cell

grade 1-) Negative test 4/4

fet - 9/8. 2 embryos transfered (6 cell grade 3/3 & 3 cell grade 4/4) Negative test 24/8

on each occassion as you can see i had 2 embryos put back (blastacysts on the last fet) and all failed at implantation stage. these were in 2006 & 2007.

now in june 2012 i have started my ivf journey again. so far:

low amh result (i am 40 in october)

2 new fibroids found on ultrasound, advised to proceed anyway

down regulation extended 1 week as lining not thin enough

stim injections all went to plan

15 follicles (2 v large suspected to be cysts)

10 eggs retreived

7 fertilised

7 made it to blast but one left to perish as structure wasnt great.

2 fantastic blasts put back after using embryoscope which i was told had started collapsing which was explained as a very good development.

4 frozen.

so, 2 put back in and progesterone pessaries used one morning & 1 night.

day 5 post transfer sign of period.

evening of day 6 post transfer period definately started with heavy bleeding & clots, continued until today (day 9pt) flow seems to be slowing down.

negative test today 9dpt

clinic advised me to continue with pessaries and re-test on saturday (day 11 pt)
theres the background for you, so here are my questions:

1. why am i failing at implantation stage every time?

doctor says it just nature but i cannot help feeling something else could be wrong and i am running out of time

2. is there any kind of contraception or other medication that i could use to stop producing eggs, thus preserving the small reserve i have left?

3. what tests can i have done to rule out ANY other problems? ie immunology, uterine probs, endometrium probs?

4. fibroids-what should i do have them removed or is there any medication available that may shrink them before my next fet

5. assisted hatching-could this help?

6. pgd (preimplatation genetic diagnosis)?

7. having read my history but you advise i do????

if need be i will pay for any tests that they wont complete at my clinic. i feel if i can rule all other possible problems out then i can admit that yes it is in gods hands and just a matter of keep trying but at the moment i feel what if there is something else that is being overlooked?

many thanks for your help in advance doctor.

as you can see i am getting pretty desperate now!

lisa, uk

ANSWER:

Hello Lisa from the U.K.,

The term "Implantation failure" means that the last two steps of the reproductive process did not occur. These last two steps are natural steps and we do not have the technology to make them happen. That is why IVF is not a perfect technology. Once the embryo is placed into the uterus, the embryo has to hatch out of its shell and attach to the endometrial ining. Then the endometrial has to engulf the embryo (implantation). So either of these two steps could have been the source of failure. In addition, it is well know that pregnancy rates will vary from doctor to doctor and clinic to clinic because the transfer technique can play a significant role.

In your previous cycles, your embryo quality was poor. I am not surprised that they failed. In this last cycle, despite having good blastocysts, there is still a potential deficiency that they have. This is because of your age, or what I refer to as the "age related egg factor." We know that as the eggs age, the internal structures of the egg become more debilitated and so less likely to thrive. One of these deficits is the chromosomal structures are more brittle and can lead to chromosomal abnormalities as the cell is dividing. Without doing genetic testing, these cannot be detected. Even chromosomally abnormal embryos can turn into good looking embryos but not necessarily into pregnancies. That is another possible source of failure. IVF helps to overcome this problem by increasing the number of eggs retrieved and therefore, statistically, increases the chances of finding the perfect egg. But that does not occur every time. You will have to keep trying in the hopes of finding the perfect egg eventually. The good thing is that your ovaries are still very responsive (you don't have decreased ovarian reserve and stimulate well), which gives you a good chance.

In terms of your other questions, I would not do anything with the fibroids, any birth control pill can stop your ovaries from going through the ovulatory cycles and hopefully preserve your eggs and I can't think of any other testing. Without thoroughly reviewing your medical record, however, it is difficult for me to give you specific advice.

I would recommend assisted hatching as this has been shown to increase pregnancy rates in older patients. I would also recommend that you scrutinize your clinic, because of all the failures. Pregnancy rates can be very clinic and doctor dependent. You should try to find one that has good pregnancy rates for your age group. I am getting a 57% pregnancy rate in 40 year olds and many of the clinics in the U.S. are getting similar results. I would also recommend that you consider transferring more than two embryos (we allow up to 4 in 40 year olds).

You faith in God will help you through this, and eventually it will happen. You may have to change course at some point and look at a different approach, but your faith will get you to that dream of having a child. When I complete my embryo transfers, I say a prayer with each of my patients and ask God to bless my couple with fruit of the womb and grant their wish for a child. I am confident that he will do so as He wills it.

Good Luck

FOLLOW-UP QUESTION:
hi doctor

thank you so very much for your speedy and detailed response, it has set my mind at rest on a lot of points. it is interesting to be told that the quality of the embryos on our cycle a few years ago were of poor quality. although that is sad, at least now i can accept that maybe that is why we failed on those 3 occassions. i had been under the impression that the embryos were good quality, particularly on the first fresh cycle after egg collection.

i have read lots on assisted hatching and am glad you agree this may be a way forward for us.

can i please just take a few more minutes of your time to clarify my point on pgd & other test (point 3&6)

When you mention checking the quality of the eggs/embryos were you suggesting asking our clinic to go ahead with pgd for our next fet?

also what is your opinion on other testing such as Natural Killer cells, immunology, uterine/endo probs? Which of these or any other tests would you suggest i rule out before going ahead with our fet?

also you mention my ovarian reserve being good but i was under the impression that the AMH test i had done suggested i was on the bottom level in terms of my remaining eggs? this has confused me slightly?

thank you in advance.

many many many thanks for you time again. Lisa

FOLLOW-UP ANSWER:

Hello Again,

There are pros and cons about using PGS. It can help to identify embryos that are chromosomally abnormal so that you can be more selective in the ones that you transfer. The downside is that there is a decrease in pregnancy rates, probably because of the impact of the biopsy on the embryo.

I check certain immunologic testing on my patients that fail two or more IVF cycles. The tests I choose do not include natural killer cells because I don't believe in that concept as a source of implantation failure. Despite this testing, I also automatically place my patients on low dose aspirin, low dose heparin and medrol, as well as, increase the progesterone supplementation. The latter is the treatment for patients that have endometrial biopsy for beta integrins and find that they are deficient. I figure, why waste money on doing the test and just cover any ways, since increasing the progesterone is the treatment.

Remember that AMH is an "indirect" test for ovarian reserve and does not necessarily predict how you will respond. Your have already shown good response so it is not an issue.

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.

Egyptian Fails One Fresh & One Frozen IVF Cycle: Advice On How To Improve Lining Thickness

Question:

Hi, I am 28 years old, married since 3 years, trying to get pregnant since 2 years. I had ectopic pregnancy since 15 months which ended by right laparoscopic salpingectomy. Then I tried clomid for 3 cycles, HMG induction for 2 cycles and I tried fresh IVF (in vitro fertilization) with long protocol.

I took 1 amp menogone , 1 amp fostimon 75 mg, 1 amp fostimon 150 mg/d. there was 36 mature follicles , all fertilized well, then 4 good embryos were transferred on 3rd day but ended badly on 5th week by blighted ovum.

Then I tried frozen embryo transfer by thawing the embryos and let them grow to the blastocyst stage. We got 14 good blastocyst from 19 embryos, then 2 hatched blastocysts were transferred. I took estrogen valereate 6 tab/d till endometrium thickness 8cm, then progesterone supp 800 mg/ d , aspirin 75 mg/d. but again a negative BHCG on due time.

Some history:

a) semen analysis is good with no abnormal forms or motlity
b) patent left tube by hysterosalpigogram
c) history of endometriosis discovered during laparoscopic salpingectomy.
d) good hormonal profile FSH, LH, TSH, prolactin, anti-phospholipid tests

Now I am planning to repeat but I still have 12 frozen blastocysts, but I need your advise because we thawed the 3rd day embryos from the first ivf , then let them grow till the blastocyst stage , then did the transfer the last time , then refreezed them again.

My question:

I am undergoing a new frozen cycle now. I take 6 tablets oral estrogen valereate/ day, 200mg sildenafil (viagra) vaginally/ day and vitamin e, aspirin, and after the endometrium reached 8.5 mm thickness on the 10th day stimulation, it decreased on the 13th day to 6 mm although I still take the same dose with no discontinuation, sure of the expiry date.

What is your explanation please, and what can I do to prevent cancellation of the cycle? If I continued the same dose is there any hope for restoration the thickness?

Please answer me because I am frustrated and breakhearted.

N. from Egypt

Answer:

 Hello N. from Egypt,

This is a protocol question, which I do not answer because protocols can vary widely and there is not only one way to do things. That being said, there is some general information that I can provide.

First, keep in mind that you have been pregnant with IVF and so can get pregnant again. IVF only gives you the opportunity to become pregnant, it cannot make you pregnant because there are still some natural steps that must occur on their own. Studies have shown that if you have gotten pregnant in the past, your chances of getting pregnant with IVF are higher. Also keep in mind that, just like trying to get pregnant on your own each month, it does not always work. Sometimes it can take several attempts before it is successful.

Second, it is well documented by studies that the best way to deliver hormones for IVF is either by injection, by patches or by vaginal delivery. Oral tablets can be used vaginally (you just push them to the very back). This helps with maximum absorption of the hormone and delivery to the uterus. Oral intake has been shown to be the worst way to give hormones for IVF because most of it is lost when it passes through the liver. I personally use patches, which most US doctors use, but tablets used vaginally is also a good option.

I would not necessarily cancel the cycle, because time can be taken to develop the endometrial lining further. It is only finalized once the progesterone is started. That is what determines the timing of the transfer, which for a blastocyst, should be on the 6th day after starting the progesterone. If you have not started the progesterone yet, you can keep using an increased amount of estrogen to get the lining to 9 mms.

Good Luck,

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

Young Canadian With Hydrosalpinx And Endometriosis Complicating IVF Cycle

Question:
Hello Dr. Ramirez,

I am 27 years old and last year stage 4 endometriosis was discovered and I had 2 large cysts removed from both my ovaries, one was 12cm and and the other was 5cm. My left ovary is almost completely gone and both my tubes are not functional. My hormones as far as I know it are normal and my antral follicle count is 8.

My first IVF with ICSI (my husband has blood in his semen due to unknown reasons) was last November with an antagonist estrogen priming protocol. I had 10 eggs retrieved, 5 mature, 3 fertilized, and ended up with 1 good quality day 3 embryo to put back. The cycle ended with a chemical pregnancy. I was on 400 puregon and 75 repronex.

I did my second IVF cycle with ICSI this month on the exact same protocol. They saw 11 follicles before my retrieval and 6 was retrieved, but none fertilized at all. My RE said that egg quality was very poor and may not suggest another cycle for me.

My questions are:
1. Is my endo the cause of bad eggs?

2. Will changing the protocol help better egg quality?

3. They noticed 2 small cysts on a recent ultrasound, and also a hydrosalphinx on the left. Would it help to have another surgery?

4. Do I have any hope in becoming pregnant with my own eggs?
Thank you so much for your information!

Thanks... A. from Canada

Answer:

Hello A. from Canada (Ontario),

I don't think that endometriosis is causing the egg problem, but that is certainly debatable. There are some studies showing better results if the IVF cycle is preceded by 3 months of Lupron depot in stage 3 and 4 endometriosis. There is definitely an effect if there are endometriomas that are penetrated at the time of egg retrieval. These endometriosis debris has been found to be detrimental to egg quality. Because of that, I am very careful to avoid the endometrioma at the time of retrieval, or if it is penetrated, I replace the needle and tubing before continuing.

In terms of protocol, you certainly seem to be stimulating well, which is the goal of the protocol and there are many variations that can be used. Each doctor has their own preferences. There is not one protocol that is better than another. However, I would probably use a stronger protocol if you were my patient (you are currently using a 475 combination protocol# such as a 600 IU combination protocol #450 FSH + 150 FSH/LH (Menopur)). Changing the protocol will not improve egg quality, but having more eggs may help with getting more embryos to work with.

If you have a hydrosalpinx, you definitely need to have that surgically removed or excised from the uterus. Numerous studies have shown a reduction in pregnancy rates with IVF by 50% if a hydrosalpinx is present. In the U.S. it is now considered the standard of care. The cysts are not an issue.

I am always hopeful for my patients, in terms of your last question, even those that have a minimal chance because they are way too old. I see exceptions all the time and believe in miracles.You are only 27 years old. Your chances should be much much better and I am leery of the results you have had thus far. Frankly, it doesn't make sense to me, but I would have to review your medical records to see what might be going on. At your age, you should not have an egg quality issue and fertilization should be at least 60%. In my clinic, your age group has a 76% chance of pregnancy per attempt. That makes me worried about the quality of the clinic you are going to. You may want to seek a second opinion.

Good luck and don't hesitate to keep me updated,

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.

Fourth IVF Cycle Ends In A Chemical Pregnancy: What Can Be Done?

Question:

Hi Dr. Ramirez,

I have been on a rollercoaster ride for the past week and I am hoping that you can offer me your opinion.


I received a positive beta after my 4th IVF on Monday (11dp3dt). It was 14.3 and my RE said that it was quite low. I held out hope as I am convinced that I tend to implant a little later than others. In a previous cycle I had a negative beta 12dp3dt and found out that I was pregnant a couple of weeks later. I tested 3 days later and my beta was up to 52.8. I was so excited and felt so much better about things. I am scheduled to go back on Sunday morning for another beta.

I am currently taking Crinone 2xday. For the past week, I have had dark brown Crinone gunk(sorry for TMI). Last night and this morning there was some red blood on the applicator tip. At 1st I thought it was just irritation but for the past couple of hours, when I wipe there has been more red blood. I am also getting some minor cramping.

I am freaking out and I am so worried that things are moving in the wrong direction. I called my clinic and they said that they cant know anything until Sundays beta. They said it could be start of a miscarriage given the low beta #'s or it could be irritation from the Crinone or even pregnancy spotting.

I was hoping that you could offer some advice as I remember in the past that you prescribe Crinone to your patients.

Is RED spotting normal? How much spotting is normal? Was I foolish to be hopeful after my #'s doubled? Do you think its likely that this will end in miscarriage?

Any insight would be greatly appreciated. I dont know if i can hold out until Sunday's beta.

Thank you,

D. from Boston, Mass.

Answer:

Hello D. from the U.S.(Massachusetts),

The advice that your doctor gave you is completely correct. It could be from the Crinone, and I have seen an increased incidence of spotting in my patients using Crinone), it could be implantation spotting or pregnancy spotting or it could be indicating an abnormal pregnancy. There is no way to know which of these is the correct diagnosis. In general, I reassure my patients not to worry about spotting. I only worry if the bleeding is bright red flow like a period with accompanying cramping. The only way to determine the fate of this pregnancy at this point is to continue to follow the bHCG's every other day. This trend will then give you a better idea of how the pregnancy is doing. AS long as the bHCG is rising, then you can be reassured. If it plateaus or drops, then that is not a good sign.

Follow-Up Question #1:

 Dr. Ramirez,


Thank you for getting back to me. Unfortunately, my beta level dropped on Saturday so it looks like I will be having another chemical pregnancy. I am devastated of course. I was hoping that you might be able to provide me with some insight as to an explanation as to why this keeps happening.

A little history:

Me: 31 years old- normal FSH but AMH is .8

Husband: Very low morphology (less than 1%)

This was our 4th IVF cycle and 3rd chemical pregnancy. I have had tons of testing... RPL work-up, HSG, genetic testing, uterine biopsy and all came back normal.

I am a low responder and in previous cycles have had poor egg quality. I just switched REs and had a better response with an Estrogen Priming Antagonist protocol. He used a low dose HCG with Gonal F. Quality and ICSI fertilization rate was much better so I was hopeful that this was it.

My RE said that it was likely a chromosomal issue with the embryo and probably because of poor egg quality and we just need to keep trying and hopefully will get that “one” good egg. I don’t know if I am comfortable with that answer. We only have 2 insurance tries left and I want to make sure we are exploring all options before proceeding again. What would you recommend for your patients at this point? Do you think that it is worth doing a Sperm DNA fragmentation test?

What could be the reason for all of these chemical pregnancies?

Any insight is greatly appreciated.

Follow-Up Answer #1 :

Hello Again,

The exact reason cannot be known, of course but the most common reason for chemical pregnancies are a genetic abnormality in the embryo. With poor morphology in the semen analysis and your young age, definitely the genetic weakness could be from the sperm. I don't recommend the sperm DNA fragmentation test because it only gives the indication for the batch of sperm that it tests and not the sperm as a whole. In addition, the treatment recommendation is to use ICSI, which I presume you are doing already. So you won't gain anything from that test. If we suspect the sperm, other than ICSI you have the choice of either using donor sperm the next time or maybe try using a supplement for three months before doing IVF again. The supplements that your husband can try, which might help with sperm quality, are either Proxeed or Fertility Blend (vitamins) and CoQ10 600 mg per day. He will have to wait three months because sperm are on a 90 day cycle #the sperm made today won't be expressed for 90 days.

The only other options I could give are what I would do with my patients who have recurrent miscarriages (which is what you have even if it is a chemical pregnancy). Studies have shown the benefit of these meds and it is standard of practice to use these with recurrent miscarriages.

I would add: aspirin 81 mg per day, Medrol 15 mg per day until transfer then decrease to 8 mg per day, Heparin 2000 units twice per day and CoQ10 600 mg per day, all starting with the start of the cycle (CD#2). The Aspirin and Heparin are withheld from the day of HCG trigger until the day after the retrieval. The only other option you might want to consider is genetic testing of the embryos prior to transfer, called preimplantation genetic screening (PGS). That way you will know if the embryos are normal genetically or not. The downside of using PGS is I have observed and some studies have shown a drop in pregnancy rates after this. Some of my colleagues say that if it is done by a very experienced embryologist who does lots of these procedures, the pregnancy rate does not drop.

You'll have to discuss these options with your doc. I'm afraid there are no exact answers to your dilemma. But, studies on patients with recurrent pregnancies have shown that eventually these patients are successful. So, hang in there, even if your insurance coverage expires.

Follow-Up Question #2:

Thank you so much for your thorough response. I really appreciate it.

I am only 31 years old but I do have a low AMH (only .8) so along with that and the fact that I am a low responder, my RE suspects that I may have a diminished ovarian reserve. So, unfortunately, both my husband and I seem to have issues.

Do you think that the low AMH and dimished ovarian reserve contribute to the repeat miscarriages? Or do you think it is likely a sperm issue?

Is there any way to tell who is main contributor to this issue? We are not ready to talk about donors at this point and will continue to try with our own eggs/sperm for now but in the event that we need to explore other options, it would be helpful to know if we would be more likely to succeed using donor egg or donor sperm.

My RE has given us the impression that it is more a egg issue but hasn't given us any explanation of why.

Any help with this would be hugely appreciated.

Follow Up Answer #2:

Hello Agian,

There is no way to know what the exact cause of the recurrent miscarriages is. It could be egg or sperm derived since the genetics of the embryo come from both. Considering that you are ONLY 31 years old, I would suspect that it is NOT an egg issue but there is no way to be sure.

It is definitely not related to AMH or low ovarian reserve. The AMH is a measure of follicle availability and low ovarian reserve is a description of ovarian response to stimulation.

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/