It is imperative for the "Window of Implantation" to be open in order for pregnancy to be achieved both in healthy pregnancy and in ART, (including IVF, IUI, AI and timed intercourse treatment). When this window is closed, pregnancy is impossible because the embryo cannot implant into the uterine lining.
Did you know?
....that the current Implantation Window in ART
is only "open" for 24 hours on average, compared to 4-5 days in healthy pregnancy? This fact is validated genomically and more importantly, the rate-limiting factor in achieving
live birth rate in assisted reproduction.
Does this fact trouble anyone who understands embryology
and is passionate about ART,
other than Incintas Therapeutics?
(If not, it should.)
When exogenous progesterone is administered and reaches an ideal concentration range within uterine tissue, pregnancy occurs more than 80% of the time. These findings are clinically validated using genomics analysis of the endometrium
The problem with conventional P administrations is that this ideal concentration range is quickly exceeded because plasma values increase rapidly. The systemically-administered progesterone cannot modulate and maintain the ideal P concentration (like the corpus luteum does in healthy pregnancy), due to the manner in which it is administered, throughout the woman's bloodstream (perivaginally and/or intramuscularly).
Incintas administers progesterone where it is needed - inside the uterus (not the bloodstream),
which dramatically improves hormonal bioavailability and extends the Window of Implantation 3-4 times longer than all conventional methods. Incintas uses time-released nanoformulation capabilities that provide the precise amount of progesterone within the uterine lining.
For the first time in nearly a half century, Incintas takes direct control of receptivity within the uterus.
Incintas Therapeutics has patented this novel Route of Administration in assisted reproduction
to corner the market of this advanced means of uterine preparation and improved fertility outcome.
WHAT WE DO
"We intend to move the needle pretty far in assisted reproduction by focusing upon failed implantation."
Incintas Therapeutics is comprised of an accomplished team of scientists, physicians, geneticists and business professionals who are focused upon improving pregnancy outcome in reproductive medicine.
Our sole purpose is to resolve the problem of failed embryonic implantation (the main hurdle in achieving pregnancy in IVF) to ultimately encourage Single Embryo Transfer (SET) which is more likely to result in a healthy singleton pregnancy for the infertile couple.
On a mission to help millions of fertility challenged families
Kun Zoo Kim, MD
The Experts Behind Incintas Therapeutics' Breakthrough Technology
Carlo Bulletti, MD, CSO
Dr Carlo Bulletti is Associate Professor Adjunct at Yale University, New Haven (Ct) USA and Director of an IVF program at Extra Omnes Medical Center in Cattolica (Italy). He has authored 10 medical text books 130 medical book chapters and more than 200 scientific articles.
MD, PhD, CMO
Robert N. Taylor is
Professor in the Department of Obstetrics and Gynecology and Assistant Dean and Director of the MD-PhD Program at University of Buffalo.
Santiago Munné, PhD
PhD in Human Biology from the University of Pittsburgh and a degree in Biology from the Autonomous University of Barcelona. COO at Overture Life. Founder of: Reprogenetics, Recombine, Phosphorus, MedAnswers, Overture Life, G1 Sciences. Advisory Board (currently): Overture Life, Phosphorus, MedAnswers, PreVivo, G1 Sciences.
José Horcajadas, PhD
PhD in Molecular Biology and Biochemistry from the Autonomous University of Madrid. He has solid experience in the field of Human Reproduction Genetics, especially in the area of endometrial receptivity, genomics, transcriptomics, implantation and embryo viability.
David Cotán, PhD
Doctor in Biotechnology and Degree in Environmental Sciences from the University Pablo de Olavide (Seville). Entrepreneur, specialized in technical direction and project management in the field of rare diseases, reproduction and enzyme scaling in the Andalusian Centre for Developmental Biology.
CEO Programme by IESE, MBA by la Salle University, Bachelor of Arts Degree by UOC, Business studies degree and Tourism business studies by the University of Barcelona. More than 25 years of executive experience, half of them as Managing Director. Active business angel, writer, business consultant, and independent advisor.
Progesterone Concentration vs. Time
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 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.
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 as well as the histologic and biochemical processes associated with successful implantation. When an embryo is transferred, embryo-uterine dialog time is augmented so that establishment of pregnancy can occur at a significantly higher rate
than all other conventional means of uterine hormonal preparation.
And, from the ER-Map Study findings: when the "receptive phase" of the endometrium is established,
implantation and 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