Endometrial Basis for Infertility in Women With Recurrent Implantation Failure and Pregnancy Loss

  • STATUS
    Recruiting
  • End date
    Sep 30, 2024
  • participants needed
    125
  • sponsor
    Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Updated on 17 September 2022
Accepts healthy volunteers

Summary

Background

Pregnancy loss is the most common complication of pregnancy. It occurs in roughly one-half

of natural conceptions. It most frequently occurs in the first 2 to 3 weeks of pregnancy. Researchers want to look at the lining of the uterus, called the endometrium, to see what role it plays in implantation and miscarriage.

Objective

To gain a better understanding of how normal and abnormal endometrium works.

Eligibility

Healthy, fertile women ages 18-42 who have had one prior child.

Design

Participants will have 3 study visits.

At visit 1, participants will have a medical history. They will have a radiologic/imaging review if needed. They will be taught how to monitor their urine luteinizing hormone (LH) at home with an ovulation predictor kit. They will have their second study visit 9 days after their LH surge.

At visit 2, participants will take a urine pregnancy test. They will have a physical exam and have blood drawn. They will have a uterine lavage and endometrial biopsy. For this, a speculum will be placed into the vagina. A soft catheter will be inserted through the cervical canal into the uterus. Saline will be added into the uterus and then recovered after 30 seconds. A tissue sample will be taken.

About 46 days later, participants will start another round of LH monitoring. They will have a third study visit 9 days after their LH surge. At visit 3, they will repeat the tests from visit 2.

Some samples will be used for genetic tests.

Participation will last for 3 menstrual cycles.

...

Description

Pregnancy loss is the most common complication of human gestation, occurring in roughly one-half of natural conceptions and most frequently in the first two to three weeks of gestation. In recent years it has become apparent that constitutive endometrial dysfunction represents an important contributor to infertility in women being treated with assisted reproductive technologies (ART). This application is specifically focused on the endometrial origins and basis of embryo implantation failure (EIF), early pregnancy failure (EPF), and recurrent pregnancy loss (RPL) in ART patients. The central hypothesis is that idiopathic infertility primarily stems from constitutive endometrial dysfunction, attributable to defects in progesterone responsiveness of the endometrial epithelium and stroma as well as immune cells. The goal of this research is to begin testing this hypothesis by focusing on infertile women experiencing the continuum of first trimester pregnancy loss. A team of exceptional extramural and intramural investigators with complementary and substantial expertise in basic reproductive biology and translational reproductive sciences will address that hypothesis by conducting a collaborative research project. At the NIH Clinical Center, the endometrium from cohorts of normal healthy fertile donors and infertile patients with carefully phenotyped and clinically-defined EIF, EPL or RPL will be biopsied in an outpatient setting (Aim 1). Advanced single cell technologies will be used to interrogate the endometrium (Aim 1). Organoids will be used to functionally study progesterone responses of the endometrial epithelium (Aim 2). In vitro decidualization will be used to functionally interrogate hormone responsiveness and decidualization capacity of the endometrial stroma and understand the influence of decidual immune cells (Aim 3). Cutting-edge genomic and transcriptomic technologies and advanced bioinformatics and data integration will be used to understand cell type heterogeneity, cell-specific differences in gene expression, and discern critical progesterone-driven biological pathways important for endometrial function that are disrupted in infertile women. The proposed aims are conceptually and technically innovative and together will have a broad impact on the field by filling a substantial gap in our fundamental knowledge of uterine biology and infertility. This application specifically targets NIH funding opportunity announcement PAR-18-951 entitled Opportunities for Collaborative Research at the NIH Clinical Center and focuses on major research priorities of the Fertility and Infertility Branch of the NICHD. These efforts will contribute to our understanding of the cellular basis of idiopathic infertility, enable the development of new tests enabling clinicians to diagnose and prescribe regimens directed at treating specific underlying endometrial dysfunction, and ultimately impact pregnancy outcomes in assisted and natural conceptions enabled by a personalized medicine approach.

Details
Condition Normal Endometrial Physiology
Clinical Study IdentifierNCT04939064
SponsorEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Last Modified on17 September 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

In order to be eligible to participate in this study, an individual must meet all of the
following criteria
Stated willingness to comply with all study procedures and availability for the
Female, aged 18-42, childbearing potential
duration of the study
In good general health as evidenced by medical history, previous fertility or
diagnosed with infertility with and without a previous pregnancy loss
Early Implantation Failure (EIF) - Infertility defined by a failure to conceive
Normal Fertile - Control- Women with proven parity based on spontaneous
after
conception without fertility treatment or prior diagnosis of infertility, normal
uncomplicated pregnancy, and birth of at least one healthy baby
ART Infertile - Control-Women that are part of a couple diagnosed with
unexplained infertility that conceived on the first embryo transfer (ET) attempt
a) three or more failed transfers of high-quality blastocyst(s) (grade 3BB or
higher); or b) two or more transfers of euploid blastocyst(s) (tested through
trophectoderm biopsy and preimplantation genetic testing for aneuploidy (PGT- A)
using next generation sequencing). These women will have a negative serum beta
human chorionic gonadotropin (hCG) 12 days after ET
Early Pregnancy Failure (EPF) - Infertility defined by two or more biochemical
pregnancies after transfer of a high-quality or euploid blastocyst with a
positive hCG 12 days after ET but without subsequent clinical signs of pregnancy
(detection of intrauterine or extrauterine gestational sac at 5-7 weeks of
gestation). While, by definition these are pregnancies of unknown location (PUL)
and will
include spontaneously resolving ectopic pregnancies, the vast majority of these will be
failed intrauterine pregnancies
-Recurrent Pregnancy Loss (RPL): Infertility defined by the loss of two or more
pregnancies after transfer of a high-quality or euploid blastocyst with a positive HCG 12
days after ET and subsequent clinical signs of pregnancy (detection of an intrauterine
gestational sac at 5-7 weeks gestation by ultrasound)

Exclusion Criteria

Women with prior hysterectomy as they do not have an endometrium
Postmenopausal women
Current smoker or tobacco use or tobacco use within 30 days
Current use of reproductive hormones and/or fertility medications
Women who are obese (BMI >30)
An individual who meets any of the following criteria will be excluded from participation
in this study
Women with a history of preterm delivery (<37-week gestation), preeclampsia and/or
stillbirth are excluded
Women with RPL must screen negative for the antiphospholipid syndrome (negative lupus
anticoagulant, negative IgG and IgM antiphospholipid antibodies and negative IgG and
IgM anti-2GP1 antibodies)
Women suffering from infertility with and without early pregnancy loss with prior
diagnosis of common known disease risk factors, including disorders such as uterine
anomalies, coagulopathy, balanced translocation, gynecological disease, other
reproductive disorders and/or autoimmune conditions, pathology confirmed or suspected
endometriosis, pathology confirmed or suspected adenomyosis, endometrial polyp(s) or
submucosal fibroids, pathology confirmed acute or chronic endometritis, hydrosalpinx
communicating with the endometrial cavity, history of Asherman syndrome, poorly
controlled endocrinopathies, HIV infection, ovarian insufficiency and irregular
menstrual cycles
Women who are currently Pregnant as we would not be able to obtain an endometrial
sample
History of gonadotoxic therapy, precancerous (endometrial hyperplasia) or cancerous
condition of the female reproductive tract
Current use of steroids or non-steroidal anti-inflammatory agents within the last 3
days
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note