Key Dates

Related Announcements

PA-20-183 - NIH Research Project Grant (Parent R01 Clinical Trial Required)

PA-20-184- NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)

PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial not Allowed)

PA-20-194, NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required)

PA-20-195- NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

PA-20-196- NIH Exploratory/Developmental Research Grant Program (Parent R21 Basic Experimental Studies with Humans Required)

Issued by

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Research on Women's Health (ORWH)

Purpose

Early Pregnancy loss (EPL), defined as a pregnancy loss occurring up to 20 weeks gestation, is a very common pregnancy complication, occurring in 12-15% of clinically recognized pregnancies, with increased prevalence associated with increasing maternal age. The use of highly sensitive hCG assays allows the detection of pregnancy earlier in gestation than the time of clinical recognition, and gives an even higher estimated loss of 50-70% of conceptions prior to the second trimester. To achieve a successful pregnancy, a series of strict embryonic and maternal conditions must be met, that include high quality embryos, favorable conditions for embryo implantation, receptive maternal endometrium and optimal uterine environment to sustain the conceptus to term. In addition, maternal immune tolerance and hormonal factors play a critical role. While approximately half of all cases of EPL appear to be due to embryonic aneuploidy, very little is known about the physiologic and pathophysiologic processes that underlie non-aneuploid EPL. As a result, there is also a lack of understanding for the underlying causes of recurrent pregnancy loss (RPL). This NOSI seeks to address these critical knowledge gaps by encouraging basic, translational and clinical studies on biological processes that may uncover potential etiologies of EPL and RPL. This includes research to understand implantation mechanistically and identify a range of key factors, involved in implantation and placentation that are important for early pregnancy establishment, including abnormalities that contribute to sporadic EPL and recurrent pregnancy loss.

The major gaps that this NOSI targets include, but are not limited to the following

• Discovering novel contributing factors that disturb embryo implantation, placenta development, endometrial receptivity and decidualization that lead to EPL, as well as the mechanisms that govern these processes
• Investigation into maternal- and paternal-derived factors in gametes that may be responsible for EPL
• Errors in epigenetic reprogramming in gametes and preimplantation embryo and early pregnancy loss
• Studies of immunological disorders (e.g., inflammatory cytokines, NK cell dysfunction) that contribute to EPL

• Uncovering male factor contribution and underlying mechanisms that lead to EPL
• Development of new model systems that allow mechanistic investigation
• Studies of nutrition factor contribution to EPL (e.g., over- or under- nutrition and vitamin/protein factors)
• Studies of dynamic communication between endometrium and embryo

Of Special Interest:

Studies that explore immune system interactions between endometrium and placenta or embryo

Model systems that allow mechanistic investigation of multi-component interactions – e.g., organoids and organs on a chip

Studies focused on the following topics will be given low priority unless there is a clear demonstration that they provide special advantages (diagnostics, risk prediction) over current approaches.

• Genomic abnormalities, such as aneuploidy, and genetic determinants
• Maternal Infections
• Uterine structure anomalies, such as adenomyosis, intrauterine adhesions and fibroid

Prohibition on Research Iinvolving Human Embryos

As outlined in the NIH Grants Policy Statement 4.2.5:

NIH funds may not be used for (1) the creation of a human embryo or embryos for research purposes; or (2) for research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero under 45 CFR Part 46.204(b) and subsection 498(b) of the PHS Act (42 U.S.C. 289g(b)). The term "human embryo or embryos" includes any organism not protected as a human subject under 45 CFR Part 46, as of the date of enactment of the governing appropriations act, that is derived by fertilization, parthenogenesis, cloning, or any other means from one or more human gametes or human diploid cells. Furthermore, per the NIH Director's Statement of April 28, 2015, NIH will not fund any use of gene-editing technologies in human embryos.

In addition to the statutory restrictions on human fetal research under subsection 498((b) of the PHS Act, by Presidential memorandum of March 4, 1997, NIH is prohibited from using Federal funds for cloning of human beings.

Applicants with any questions about the acceptability of their proposed research studies should contact the persons listed below.

Application and Submission Information

This notice applies to due dates on or after September 8, 2022 and subsequent receipt dates through September 8, 2025. 

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice.

PA-20-183- NIH Research Project Grant (Parent R01 Clinical Trial Required)

PA-20-184- NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)

PA-20-185- NIH Research Project Grant (Parent R01 Clinical Trial not Allowed)

PA-20-194, NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required)

PA-20-195- NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

PA-20-196- NIH Exploratory/Developmental Research Grant Program (Parent R21 Basic Experimental Studies with Humans Required)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include “NOT-HD-22-026” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.

Inquiries

Please direct all inquiries to:

Clara Cheng, PhD

Fertility and Infertility Branch

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Telephone: 301-435-6992

Email: clara.cheng@nih.gov

Monica Longo, MD

Pregnancy and Perinatology Branch

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Telephone: 240-204-4605

Email: monica.longo@nih.gov

Elena Gorodetsky, M.D., Ph.D.
Office of Research on Women’s Health
Telephone: 301-594-9004

Email: egorod@mail.nih.gov