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Infertility Cubby

Viagra Assisting With Blood Flow to the Uterus
by Geoffrey Sher, M.D.

Q. Can you share more regarding your opinion about Viagra assisting with blood flow to the uterus and lining thickness? Is it similar to baby aspirin or more effective? How can one introduce the idea to an RE who may be unaware of this treatment option?

A. It is far more effective. BUT alas "there are none so blind as those that will not see!"

In 1989, we were among the first to show that in normal and "stimulated" cycles, pre-ovulatory endometrial thickness and ultrasound appearance, is predictive of embryo implantation (pregnancy) potential following In Vitro Fertilization/Embryo Transfer (IVF/ET). With conventional IVF (where the woman receives fertility drugs and has her own fresh embryos transferred to her uterus), here needs to be a 9mm sagital thickness (Grade 2) and a triple line appearance (Grade A) accordingly, a Grade 2A lining is optimal in such cases. Anything less is associated with about a five- (5) fold reduction in live birth rate per ET. An exception to this rule seems to apply for third party embryo Recipients (Ovum donation, IVF-Surrogacy) and in cases of frozen embryo transfers (i.e., where the recipient receives supplementary estrogen/progesterone and not gonadotropins, to prepare the uterine lining. Here, a lining of 8mm thickness seems to be adequate.

A "poor" endometrial lining most commonly occurs in women with a history of unexplained recurrent IVF failures or early recurrent miscarriages and is usually attributable to: 1) inflammation of the uterine lining (endometrium), i.e., endometritis (occurring following a septic delivery, abortion or miscarriage), 2) adenomyosis (gross invasion of the uterine muscle by endometrial glandular tissue), 3) multiple fibroid tumors of the uterine wall, 4) prenatal exposure to the synthetic hormone, diethylstilbestrol (DES) and, 4) in women who have received clomiphene citrate (Clomid, Serophene) for at least 3 months in a row without a resting cycle (this effect is self-reversible within 4-6 weeks of discontinuing clomiphene).

Hitherto, attempts to augment endometrial growth in women with poor endometrial linings by bolstering circulating estrogen blood levels (through the administration of increased doses of fertility drugs, aspirin administration and by supplementary estrogen therapy) yielded disappointing results.

In 1995/96, we began to recognize that it was possible to improve endometrial development in women who had "poor uterine linings," by the daily application of nitroglycerine skin patches during ovarian stimulation with fertility drugs. We believed that the therapeutic effect was probably attributable to the local action of nitric oxide (NO) on the uterine vasculature, leading to improved endometrial blood flow and enhanced delivery of estrogen to the uterine lining. About 75% of our IVF patients with compromised uterine linings so treated with nitroglycerine skin patches, showed a marked improvement in estrogen-induced endometrial growth and many went on to achieve viable pregnancies. Unfortunately the lack of access to ultrasound color flow Doppler (UCFD) to measure uterine blood flow at the time precluded us from confirming that the observed enhancement in endometrial development was directly attributable to enhancement of uterine blood flow. Accordingly we did not publish these findings.

The high incidence of unpleasant side effects associated with nitroglycerine therapy (e.g. severe headaches, nausea, and light-headedness brought about by fluctuations in blood pressure) resulted in poor patient tolerance. Accordingly, when Sildenafil (Viagra) was shown to facilitate penile erection through increasing penile blood flow, without eliciting bothersome side effects, we decided to investigate whether this drug could replace nitroglycerine for the improvement of endometrial development. This time, with ready access to UCFD, we set out to examine for a cause and effect relationship between Viagra-induced enhancement of uterine blood flow and improved endometrial growth in women with poor endometrial development.

We elected to incorporate Viagra into vaginal suppositories in an attempt to improve local uterine absorption and minimize the incidence of systemic side effects. To this end, we enlisted the services of a compound pharmacist and began testing the effect of vaginally administered Viagra on uterine blood flow and on estrogen-induced endometrial development. Four women with chronic histories of poor endometrial development and failure to conceive following several advanced fertility treatments were evaluated for a period of 4-6 weeks and then underwent IVF with concomitant Viagra therapy. Viagra vaginal suppositories were administered four times daily for 8-11 days and were discontinued 5-7 days prior to embryo transfer in all cases.

We reported on our findings in a preliminary study, published in the prestigious journal, Human Reproduction (April 2000). The findings clearly demonstrated that vaginal Viagra produced a rapid and profound improvement in uterine blood flow and that this was followed by enhanced endometrial development in all four cases. While three of the four women subsequently conceived, the study is too small to prove that these pregnancies can be attributed to the Viagra therapy. Larger independent and controlled studies will be needed to demonstrate this.

In a manuscript which appeared in Fertility & Sterility (The official journal of The American Society of Reproductive Medicine) in October 2002, we reported on the administration of vaginal Viagra to 105 women with repeated IVF failure due to persistently thin endometrial linings. All of the women had experienced at least two (2) prior IVF failures attributed to intractably thin uterine linings. About 70% of these women responded to treatment with Viagra suppositories with a marked improvement in endometrial thickness and 45% of these achieved live IVF-births following a single cycle of treatment with Viagra. 9% miscarried. None of the women who had failed to achieve an improvement in endometrial thickness following Viagra subsequently and underwent embryo transfers in the same cycle during which Viagra was administered, achieved viable pregnancies.

Our very first patient to achieve a live birth following Viagra treatment subsequently again conceived following IVF where Viagra was administered and has since delivered a healthy baby (a girl this time), at full term.

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