Finally, an Explanation:

Why Fertility Outcome is Extremely Poor in Assisted Reproduction

IVF, IUI and Artificial Insemination procedures require hormonal preparation to establish receptivity

within the uterus so that a transferred embryo can implant and achieve pregnancy. These methods currently use intramuscular injection (IM) and perivaginal suppositories (PV) of progesterone whereby the hormone molecules travel throughout the bloodstream for 5 days and eventually reach the uterine lining (endometrium) where hopeful implantation of the embryo takes place.

These IM and PV methods are "systemic administrations" because they utilize the bloodstream as a means of molecular transport of progesterone to the uterus. While systemic administrations of progesterone do achieve pregnancy, they simply do not provide the proper bioavailability within the endometrium for most of the transferred embryos to implant. In fact, the majority of transferred embryos in IVF are introduced to a uterus that is past its receptive state

and actually in a contraceptive phase, whereby pregnancy is impossible.

In humans, Incintas' scientists demonstrated how progesterone concentration within the endometrium quickly rises to a contraceptive level soon after the uterus establishes receptivity

(within 24 hours, average), making pregnancy impossible after that point. The scientists demonstrated this discovery using endometrial genomics, a very reliable scientific method (ER-Map Study; Enciso, et.al., 2016 and 2018). For the first time in history, Incintas' scientific team identified the threshold concentration whereby progesterone becomes a contraceptive and further demonstrated that once this contraceptive phase is established within the endometrial tissue, it is impossible to re-establish receptivity for the duration of that IVF treatment. At this point, most of the genomic biomarkers have shut down and remain closed until the next ovulatory cycle.

We all know that embryonic implantation is an extremely complex phenomenon and takes a

significant amount of time in the establishment of pregnancy. With an average Implantation Window of only 24 hours in all IVF treatments, it should be no wonder why pregnancy rates have plateaued to a ~33% rate since the first successful IVF birth over four decades ago. With 2.5 million IVF cycles performed globally each year this means that about 1.5 million embryos are doomed for failure no matter their quality, since embryo quality is associated with fertilization (not implantation).

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Similarly, in ruminants (dairy, cattle breeding, etc.) systemically-administered progesterone involves the use of PRIDs and CIDR suppositories to prime the uterine lining for hopeful implantation of an embryo. These products also rely upon the cow's bloodstream and circulatory system to transport progesterone molecules to the uterine surface and establish receptivity. Similarly to humans, proper bioavailability within the cow's endometrium is not achieved for very long, establishing a very short estrus time period. This makes estrus determination very difficult for farmers who need to determine when their animals are in heat for successful reproduction. As a result, heat detection technologies have developed in an effort to identify precise timing for IUI, IVF and AI but still, these products are difficult to use and largely unsuccessful simply because the estrus time period established with these systemic administrations is so extremely short.

It is crucial to understand this point: 

The "Window of Implantation" in humans and "Estrus" in livestock are the ONLY periods of time when pregnancy can occur. A perfectly-formed embryo can enter the uterus any other time but cannot implant into the uterine lining and establish pregnancy because endometrial gene expression is not upregulated. This is true in both natural pregnancy and assisted means such as IVF.

These dramatically short time periods of receptivity in humans and livestock achieved by systemic progesterone administrations create the bottleneck in assisted reproduction.

And finally, a Solution to the Problem of Failed Implantation

Incintas Therapeutics eliminates the bottleneck with a novel targeted (and patented), intrauterine (IU) route of administration of progesterone. We also patented nano/time-release pharmaceutical capabilities to upregulate and sustain implantation biomarkers within the endometrium that are associated with the crucial "Window of Implantation" and "Estrus".

Incintas Therapeutics' IU technology enables direct modulation of the genes associated with implantation so that when an embryo is transferred, embryo-uterine dialog is augmented so that establishment of pregnancy can occur at a significantly higher rate than all other conventional means of hormonal preparation.

And, from the ER-Map Study findings: when the "receptive phase" of the endometrium is established,

implantation (pregnancy) occurs at an 81.5% Rate.

(This is the potential of Incintas' groundbreaking technology.)

Finally, after four long decades, there is a genomically-validated means of improving fertility outcome

in assisted reproduction.

Please contact us if you want to know more about Incintas' technology

or wish to become part of this novel paradigm in assisted reproduction.

Thank you, the Incintas Therapeutics Team