KatCarney

Geoffrey Sher, M.D.
Viagra and the Uterine Lining
March 28, 2000

INCIID Nancy Kay: Welcome, Dr. Sher! We're so excited to have you join us tonight.

Geoffrey Sher M.D.: Great to be with you.

INCIID Debbie: Ok, everyone's name has been added to the list and we will call on you in turn. We'll begin with a question from Moi.

moi: How does the Viagra make a thin lining thicker and what are the requirements to become a candidate?

Geoffrey Sher M.D.: Viagra improves blood flow to the uterine lining thus improving estrogen delivery. The indications include women who have thin linings that do not improve on fertility hormone therapy or with estrogen administration.

sinatra: Dr. Sher can you talk a little about nitro patches v. viagra -- also is the viagra given orally or is it in the form of an injection? And how is it toxic to the embryos? Also, how much monitoring is involved while being treated with viagra?

Geoffrey Sher M.D.: Nitroglycerine produces too many side effects and is poorly tolerated but it does exactly the same thing. Viagra administered vaginally is essentially without side effects. It is absorbed locally and reaches the uterus, presumably in high concentrations. Like the use of progesterone suppositories, the blood levels are likely to be much lower than with intramuscular or oral administration. The Viagra works to improve blood flow by causing local release of nitric oxide in smooth muscle such as in the uterus. The effect is gone within 12 hours or so thus no further NO release occurs thereafter. It is the NO that MAY have toxic effects on embryo development. Accordingly we discontinue NG with HCG administration and at the same time irrigate the vagina to remove all remnants of the suppository. Since blastocyst transfer occurs 7 -8 days later, there is no chance of there being any NO effect by the time the embryos are transferred and hence no real risk of teratogenesis.

Tracy1234: I've had three 1st tri m/c's after 1 successful pg. My lining was 3mm this cycle on cycle day 12 after 50mg of Clomid over stimulated so will do 25 mgs this next cycle if not pg. no answers with all 3 m/c's do you think thin lining is the problem? and if so what if I am pg this cycle will I most likely loss the pg?can the viagra suppositories be gotten at any pharmacy?

Geoffrey Sher M.D.: Clomid is an anti estrogen and consists of two isomers. The one is out of the system within a week of discontinuing clomid. The other hangs around for up to six weeks causing a lingering anti estrogen effect. Clomid notoriously causes diminished response of the lining to estrogen. Simply put, women with less than 3 follicles of greater than 15 mm and estrodiol level of below 400 pg/ml will likely not develop an adequate lining. That is why older women over 40 rarely if ever have a baby following Clomid. They are too resistant. Furthermore, given the buildup of the anti estrogen isomer, women who take Clomid for more than 3 months in a row , regardless of ovarian response will virtually always have a thin lining. Clomid acts in this way, as a relative contraceptive after 3 consecutive months of use, regardless of age or ovarian response.

Geoffrey Sher M.D.: This is mainly due to the lining thinning effect. After 6 consecutive months of use, Clomid is in effect a contraceptive. No-one will have a baby unless the Clomid is discontinued for 6 wks to get all anti estrogen isomers out of the system. Then the woman is back to ground floor zero with regard to her lining. Simply put, never take Clomid for longer than 3 consecutive months without at least a 6 wk break before restarting and women over 40 should NEVER take Clomid.

Tracy1234: Thank you Dr.

fourmaddox: I'm 26 yrs old and I have 3 kids already and I had my tubes tied 6 yrs ago. My doctor referred me to d.o.s.t. What are your thought for dost and what are my odds. Should I do dost because IVF is so expensive. My husbands sperm is fine also.

Geoffrey Sher M.D.: Dost has no advantages over IVF and to my knowledge success rates are far lower. In our program, women under 40 have a 50% pregnancy rate per egg retrieval if their FSH level is under 10 and they have a normal uterine cavity. Within three egg retrievals and as many embryo transfers (fresh and frozen) as the available blastocysts allow, 75-80% will achieve viable pregnancies. Moreover, in our program, for such women, we offer a risk sharing arrangement where if 3 such comprehensive attempts do not result in the birth of a baby, Most of the fee is refunded.

Geoffrey Sher M.D.: This would not be possible with dost, gift or IUI where the success rates do not come near this level. Hence, you should look at the cost of having a baby, not the cost of a procedure. After all the only indication of a successful procedure is the birth of a healthy baby.

JulieA1: So if I was on clomid for 8 months and now I am on pergonal injections do you think that my lining will get back to normal . and do our doctors up in my area of Wisconsin subscribe Viagra???

Geoffrey Sher M.D.: Yes your lining should return to normal within 2 cycles of your having stopped Clomid. As far as prescribing Viagra is concerned, I have gone on record as stating that Viagra should not be introduced clinically until our findings have been validated by controlled independent studies.

Geoffrey Sher M.D.: In the mean while, given our four year experience with nitroglycerine, to women with poor linings and the impressive results we have observed, followed by our more recent preliminary experience with Viagra (which is similar,) we now prescribe Viagra selectively to the select group of women who persistently have poor linings. In spite of best efforts to reverse this with gonadotropins and/or estrogen.

JulieA1: Thank you, doctor!

steff: I have had 4 failed ICSI cycles but my lining is always 9mm so viagra wouldn't help me, would it?

Geoffrey Sher M.D.: You don't need it. But remember, a thin lining is only part of the story. Most failed implantation is not due to a thin lining but rather due to immunologic problems such as increased local endometrial natural killer cell (NK cell) activity or NKa which in turn is seen in 1/3 of women who have thyroid antibodies (regardless of the absence or presence of clinical symptoms of hypothyroidism) and in about 20% of women undergoing IVF FOR FEMALE CAUSES, and who have antiphospholipid antibodies (APA).

Geoffrey Sher M.D.: We have just had a paper on this topic accepted for publication in a prestigious journal. This is the major cause of failed implantation. Women who have had good quality embryos transferred into what apparently seems to be a normal uterine lining and still don't conceive are most likely to be the ones who have such immunologic implantation problems.

steff: Thank you Dr. Sher, I will look into that.

Geoffrey Sher M.D.: Selective immunotherapy is the only treatment that helps in such cases. Since my practice comprises 70% patients who have repeatedly failed IVF, I would not be ale to achieve the kind of pregnancy rates cited above, nor could we offer risk sharing plans as described and still survive, let alone thrive if we did not pay as much attention to the soil (the endometrium) as to the seed quality (the embryo/blastocyst.)

matilda: Does Viagra come in different doses? Does it effect follicular development? I have had 2 IVF cycles with linings of 8mm and 7mm, no meds other than stims. How do I get my doctor to consider this tx?? Is this only for use with IVF or any type of tx? Can you use Viagra with 3 day transfers?

Geoffrey Sher M.D.: The dosage is standard but don't expect your MD to simply accept what we say to be true. This is a new and innovative as well as a much needed approach THAT WILL INEVITABLY FIND A PLACE in the ART therapeutic armamentarium ....... eventually.

krista2: Hi Dr. Sher, I've been to 2 of your seminars in St. Louis and was very impressed with you. We will be doing ICSI and MESA along with ZIFT. Is it necessary to have a cycle prior to taking the BCPs and then Lupron? Of course, I've missed this period and am concerned of a delay in my target date- any thoughts?

Geoffrey Sher M.D.: I hate to pop your bubble, but zift has no benefit over IVF. One of the only randomized controlled studies ever done in the clinical ART arena put that issue to rest. Simply trying ZIFT because IVF did not work is to ignore the fact that some other factor is playing a role. MESA or TESE are both procedures for in cases of men that have no sperm in the ejaculate, usually as a consequence of blockage (surgical, medical, comgenital or inflammatory)

krista2: ZIFT was suggested because of adhesions and it increases the chances. Are you saying we may not need ZIFT?

Geoffrey Sher M.D.: Lupron is necessary to suppress endogenous LH release while you are undergoing stimulation. This IS most likely to occur if your FSH or inhibin B levels indicate a degree of ovarian resistance. It is true that Lupron suppresses the action of FSH on follicle development. However, it is "a necessary evil" because without it, many women will have a premature LH surge and prejudice both their egg quality and their endometrial linings and they will not conceive, even with good looking embryos having been transferred.

Shadow: I was on Clomid for 4 mos, off 1 cycle and now on for 3 mos w/IUI. Prog post IUI was 39.6. I've never had estradiol levels or ultrasounds done to check uterine lining. Could this be my problem? I ovulate every month. Could the Clomid be working against me??

Geoffrey Sher M.D.: If you are off Clomid for 6 weeks, the anti estrogen effects disappear. I see no reason for anyone to go on more than one 3 month phase of Clomid. Furthermore, women who take Clomid with IUI will experience about a 30% lower pregnancy rate than those who use gonadotropins across the board and for all age groups. Clomid is a good drug if used in small doses (50-100mg daily) for five days and never for longer than 3 mths continuous. After that something else is needed. One important fact to note, women with endometriosis, no matter how mild, have a significantly reduced chance of having a baby per month of trying.

Shadow: So would the next step be injectables??

Geoffrey Sher M.D.: Neither fertility drugs (Clomid or gonadotropins, ) surgery or IUI will improve the chances of a normally ovulating woman with mild endometriosis (stage one and two) conceive, over NO TREATMENT AT ALL.

ChrisP: Dr. Sher, thank you for being here. What kind of success rates have you seen w/ the viagra?

Geoffrey Sher M.D.: Women who develop a normal looking endometrial lining on Viagra or nitroglycerine patches, have in our experience the same pregnancy rate as do women with the same lining who did not receive Viagra. However, the data we published on Viagra precludes us claiming that the pregnancy rate is improved by this treatment. Our small preliminary study only showed that Viagra improves blood flow to the uterine lining and that this is followed by an improved lining in women with poor endometrial develop. All the rest is based on our prior and present rather anecdotal experience. I must stress this!!

Geoffrey Sher M.D.: By the way, any one who needs more information on our Viagra work or on any of the issues raised in my answers to your questions can access our website at "haveababy.com" or call us at 800 780-7437 and we will send you information.

Twinfish: I saw you in St. Louis on 02-24. You are the most compassionate, caring doctor I have met. I am on my 1st round of HRT to build my lining since my partial ovary failed 18 years ago. I am almost finished w/ my provera & still no period. Dr. Peter talked as though I will probably be on the Viagra when my time comes. Egg donor still has to be chosen,etc. Can I choose a friend as my egg donor? Or do I need to go through one of the recommended clinics? Also, am I on track? I am 41 & feel that my clock is ticking. Thank you!

Geoffrey Sher M.D.: If you have an endometrial lining problem and this can be confirmed, we would probably use Viagra (not to say that others do the same). Unfortunately, however, too many people believe that they have endometrial thickness problems when in reality it is due to other factors such as Clomid, severe over stimulation with fertility drugs, etc. Age is not a deterrent for OD. We have some patients who have had babies in their mid to late fifties. As physicians it is our responsibility to give people careful deliberation and consultation with more knowledgeable professionals who are competent to assess all of the factors that should be taken into consideration. Yes you can use a known donor if you choose.

Twinfish: Thank you!

juls1: I have a 5 year old son and got preg w/ him on 1 dose of clomid. Since than we have been trying for baby number 2 for 3 years w/ using clomid and hcg shots on /off. I just had my first IUI done on Saturday w/ 8 follicles in total w/o using clomid, and I haven't used clomid now for 6 months . We ran tests on my husband and his sperm is fine. What kind of workup's should I get from my doc since I can already have a baby ? I already had a lap done and everything was okay.

Geoffrey Sher M.D.: This is an excellent example of a major pitfall. Many women conceive once on a given therapy, sometimes in spite of treatment rather than due to it and thereupon erroneously believe that because they did so once before if will happen again on the same treatment. For example, a women with mild endometriosis who has a 4 x lower chance of having a baby in a given month, regardless of treatment (with the exception of ART) conceives on Clomid/IUI, in spite of treatment. Now she is 3-4 yrs older, approaching 40 with her oocytes declining in quality with the advancing biological clock and is persuaded to go back on Clomid since "it worked once before" This is dangerous since such a woman is usually wasting valuable time which waits for no-one. Over 35 with endometriosis she needs ART. Nothing else represents rational treatment.

loobyloo: Dr. Sher, I am 37 yrs old, never reached + pg test, unexplained IF, had 4 IVF's with Dr Zouves combined will full immune tx per Dr Beer (slightly elevated NK cells in blood test, negative for NK in uterus) great responder to all stims, great embryos and transfers etc. etc. My lining has never been more than 8mm and thats usually pushing it. Do you think this is the issue? Also, I called your office last week to set up a consult with you, someone was supposed to call me back but never did.

Geoffrey Sher M.D.: Please accept my apologies for our not returning your call. If you call tomorrow ask for Maureen and she WILL make sure that I get to talk with you. As you know, I brought Dr. Zouves to the US. He joined me at PFC in San Francisco when I was in charge of that organization. He is an outstanding physician and a good friend. However, all the work I did with Viagra was done after I took key members of my team and established SIRM at Las Vegas and more recently in Chicago and St. Louis. This we can discuss when I receive a copy of your records and we consult. As you are probably aware I do not charge for such phone consultations. Call me tomorrow.

loobyloo: OK thanks, I will call tomorrow. I just love Dr Zouves!

BDeeg: I am 35 and have 2yr old son, which took 18 months to conceive. I have been trying 18 months for 2nd child. I had a mc in May 99 at 9 weeks. I had an ovarian ectopic on Dec 99 cycle. I have been on clomid for 6 cycles, does this effect my chances for normal pg. I had to have my right ovary and tube removed. I have been benched since the surgery in Jan 11, 2000. My periods seem shorter and with less bleeding.

Geoffrey Sher M.D.: One ovary is certainly sufficient and, no, provided you stop using Clomid for more than 6 wks and get on with something more effective, you will not be prejudiced by the inordinately long continuous period of time that you took Clomid for. However, it sounds like you may have a similar problem to the lady I answered a while ago. Don't be lulled into complacency because one viable pregnancy occurred. There is something else underlying which is reducing your chances of conceiving and this must typified and quantified before proceeding with treatment. I would not be surprised if you have mild endometriosis or subtle pelvic adhesions.

llsf: What can I do now for a 7mm lining? When will Viagra be readily available to us?

Geoffrey Sher M.D.: It depends on the reason for your thin lining. If it is due to an irreversible cause such as permanent damage to the uterine basal endometrium through prior endometitis (usually following an infected miscarriage or delivery) then no treatment would necessarily work. On the other hand, if the basal endometrium is not permanently damaged, improving the blood flow would deliver more estrogen and improve the lining.

alicatxxxx: Hi Dr. Sher are you saying that IVF will be successful for mild to moderate endometriosis, while IUI etc. will not? I am 35 had a lap, did 2 unsuccessful IUI with gonotropins (8 eggs) and will be starting IVF this month with St. Barnabus. By the way, your book has been a great inspiration to my husband and I. Thanks for your warmth and compassion!

Geoffrey Sher M.D.: There is no basis for treating early endometriosis with fertility drugs, IUI and/or surgery. No treatment is preferable provided the woman is ovulating normally on her own.

alicatxxxx: so IVF will not be better?

Geoffrey Sher M.D.: You should know that women under 35 who have mild endometriosis have a 40% chance of conceiving on their own within two to three years of timed intercourse. Isn't it interesting that the IUI success rate in the same women is no better.

alicatxxxx: what about IVF?

Geoffrey Sher M.D.: For women over 35, where declining egg quality reduces pregnancy rates and time may be running out, taking a "no treatment approach" is not rational. Proactivity demands that IVF be performed. However, please be aware that endometriosis has an immunologis component which translates into the fact that such women who have APA's should have heparin therapy and if they have NKa, they will need IVIG if they hope to have the same chance of an IVF pregnancy as the non-endometriosis counterparts.

chrissy 1: I am a 33 yr old mother of two. My first was conceived with clomid and my second was natural. In ttc#3 I went back on clomid and conceived first cycle but found no hb at 14w6d. My next pg was also conceived with clomid but found no hb at 9w. The only thing that came up abnormal was an equivocal ACA. I am currently pg again this time on third cycle clomid 50 mg. Do you think my losses were probably a cause of the ACA or could the clomid be a contributing factor to my losses? I am currently on crinone.

Geoffrey Sher M.D.: If Clomid renders the soil "endometrium" compromised after repeated use, why would it seem unusual that the roots of the seed (embryo) would not adequately provide a supply line to the developing "plant" (embryo) and if the embryo is being starved why would it be unusual to expect that it could succumb? Clomid in small doses, to young women, for less than 3 months in a row and for the appropriate indication is an excellent treatment but not under any other circumstances, in my opinion.

hope8: Hi Dr. Sher: Is there any age limit to use Viagra? Can it be used for women>40? Is it depend on FSH level? If FSH level is normal (but age>40), Viagra could be used?

Geoffrey Sher M.D.: Viagra usage is not age-dependent, but again, it should not be introduced clinically across the board until others validate its efficacy.

hope8: Thank you!

Geoffrey Sher M.D.: Unfortunately I will have to leave or have a divorce. I have really enjoyed this. For those who live in the Chicago area, please spread the word around that we are having three seminars in Chicago on the 11th, 12th and 13th of April. Many of these issues will be discussed in open forum there.

willow1: Have a nice evening Dr. Sher!

INCIID Debbie: Thank you so much, Dr. Sher and Maureen! This was a wonderful evening and we sure appreciate your time.

Geoffrey Sher M.D.: Also, Carolyn Coulam my partner in Chicago will be participating and she is an expert in reproductive immunology. For anyone else still around, feel free to call us at (800) 780-7437 for information about the seminars or on any other issue.

Geoffrey Sher M.D.: Thanks again.

INCIID Nancy Kay: Thank you from everyone at INCIID.


Geoffrey Sher, M.D.
Sher Institute for Reproductive Medicine
3121 S. Maryland Pkwy, Ste. 300
Las Vegas, NV 89109
Phone: (702) 892-6363 Fax: (702) 892-9666
email: ivfsher@earthlink.net

For more information, visit Dr. Sher's website at: http://www.haveababy.com and read his statement about Viagra research.




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