Sunday, January 20, 2013

What Kind Of Estrogen For Endometrin Priming & Luteal Phase Support?

Hi there, I'm in Ireland and having egg donation treatment in Spain. I've had several unsuccessful cycles and am now finding that my endometrium is not as thick as it used to be. When my period begins, I take 6mg of Meriestra orally. I was interested to read an earlier answer of yours to question "thin endometrium causing ivf failure" that said "Vaginal is better because the hormone goes directly to the endometrium without having to go through the liver first (first pass), where most of the estrogen is removed, when taken orally."

Should i go back to my clinic and question the oral administration of the drug? In earlier cycles I was applying patches to my body.

Thanks in advance for any guidance you can offer and I understand it would be general advice rather than a medical opinion.

Best Regards, A. from Ireland


Hello A. from Ireland,

Thank you for reading some of my previous answers. Multiple studies have shown that oral estrogen for endometrial priming and luteal phase support are the least effective method. For that reason, it has become the standard of care to use either injectables, patches, vaginal gels or vaginal tablets. I think this is something you should query your doctors about. If your lining is not developing adequately in an egg donor cycle, it may be because you are not getting adequate estrogen.

Your doctors should be evaluating this thickness prior to deciding whether or not to proceed with the transfer. If you were my patient, I would not do the transfer if your endometrial lining was inadequate. In that situation, I would freeze the embryos and plan a frozen embryo transfer at a later date, in a cycle where the lining is adequate.

Good Luck,

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

Saturday, January 12, 2013

Recurrent Pregnancy Loss: 5 Miscarriages Since 2009


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


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

Monterey, California, U.S.A.

Saturday, January 5, 2013

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


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


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


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 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.


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