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Conversa entre embrião e útero?

Na interessante revisão "Cross-talk between embryo and uterus" é explicado o conceito do priming endometrial, com o sobrenadante do meio de cultura, dos próprios embriões que serão inovulados, sendo injetado na cavidade uterina para uma prévia estimulação. Tal priming, dizem os pesquisadores, poderia melhorar a receptividade endometrial e a "conversa" entre o embrião e o endométrio, em preparação para a implantação. Essa conversa, entre embrião e útero, poderia ser mediada pelo VEGF-A e/ou IL-1, uma vez que o embrião precocemente secreta tais fatores tróficos. Os resultados da utilização desse priming, denominado de SEET (stimulation of endometrium embryo transfer), são promissores - com até 92% de taxa de implantação - mas dependem da inovulação de um blastocisto de boa qualidade.
Veja abaixo a revisão na íntegra (em inglês).


Cross-talk between embryo and uterus

Issue 03: 19 Feb 2009
Source: 1. Edwards RG, Beard HK. Is the success of human IVF a matter of developmental biology? In: Jansen R, Mortimer D (eds), Towards Reproductive Certainty. New York: Parthenon Publishing Group 1999: 414-418.
2. Goto S, Kadowaki T, Hashimoto H, et al. Stimulation of endometrium embryo transfer can improve implantation and pregnancy rates for patients undergoing assisted reproductive technology for the first time with a high-grade blastocyst. Fertility and Sterility 2008 Advance online publication
3. Goto S, Kadowaki T, Hashimoto H, et al. Stimulation of endometrium embryo transfer (SEET): injection of embryo culture supernatant into the uterine cavity before blastocyst transfer can improve implantation and pregnancy rates. Fertility and Sterility 2007 88: 1339-43.
4. Kapiteijn K, van der Weiden RM, Helmerhorst FM. Injection of embryo culture supernatant prior to blastocyst transfer—cofactor? Fertility and Sterility 2008 4: 1027-8.

Does any other species display such an immense loss of reproductive potential as the human, asked the IVF pioneer Robert Edwards in 1999.[1] Edwards was describing implantation rates of under 30 percent as “the most disappointing statistic of human IVF”, although the same low implantation rate is also evident in natural conception. Captive baboons, noted Edwards, have an implantation rate of 70 percent.[1]


In the late 1990s, studies from the Colorado group of Gardner and Schoolcraft caused a mini-sensation by reporting implantation rates of more than 50 percent for blastocysts transferred following a two-stage “sequential” culture. An explanation for the huge improvement, they argued, was that the sequential culture medium was physiologically closer to the progressive environment of the spontaneously conceived embryo (with the first stage being consistent with the environment of the Fallopian tube and the second stage being nearer the environment of the uterus).

Now, in a further milestone development, a randomized trial from Japan has demonstrated implantation rates of 92 percent following the transfer of good quality blastocysts in women who underwent endometrial priming before transfer.[2] The priming in the study group was performed by injecting (by catheter) the “supernatant” aspirated from the culture medium in which the patient’s own embryos were cultured into the uterus as an endometrial stimulant. Such priming, argued the investigators, would encourage endometrial receptivity and “cross-talk” between the embryo and endometrium in preparation for implantation.

Studies over 2 decades have indicated that the preimplantation embryo produces several factors, such as interleukin-1, human chorionic gonadotropin (hCG), and vascular endothelial growth factor during its development to signal its presence to the uterus and modulate endometrial receptivity.[2] Thus, the investigators suggest, these “cross-talking” embryonic factors might begin their conversation on the day of supernatant injection to prepare the endometrium for implantation in a way that appears closer to the physiology of natural conception and the embryo’s passage to the uterus. It was significant that the control group in the trial, which received conventional transfer of good quality blastocysts without supernatant injection, achieved an implantation rate of 64 percent. “We speculated that the lower implantation rate in [this blastocyst transfer] group with a high-grade blastocyst was due to the absence of cross-talk between the endometrium and the embryo during the period from the early embryo stage to the blastocyst stage,” the investigators reported.

Patients in a third arm of the trial, who were injected with the culture medium alone (not the supernatant) to assess the effect of the injection itself, had a slightly improved though statistically insignificant implantation rate (75.9 percent). Similarly, there was no improvement in implantation in the three groups with only low-grade blastocysts. The explanation here, they suggest, may not be absence of cross-talk but developmental arrest as seen with most poor-quality embryos.

This is not the first report of what has been dubbed by the investigators as “stimulation of endometrium embryo transfer,” or SEET. An earlier trial from the same Japanese group had tested the hypothesis in a trial of just 48 women, all with a poor IVF success record.[3] Again, the culture medium supernatant was injected into the uterus before blastocyst transfer to provide “an optimum environment for implantation”. And again, implantation rates, pregnancy rates, and hCG levels in the SEET group were statistically significantly higher than those in a non-SEET control group.

However, in subsequent correspondence there was concern that in this small original study there was no control group injected with a control medium alone to rule out any effect of the injection itself. This was rectified in the latest trial, with an additional control group. The same correspondence also suggested that the key embryonic mediator in the initiation of cross-talk between the blastocyst and the endometrium was vascular endothelial growth factor-A, because of its effect on endometrial angiogenesis.[4]

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