Overview

This trial is active, not recruiting.

Conditions infertility, subfertility
Treatments human chorionic gonadotropin (hcg), placebo comparator (for hcg)
Phase phase 4
Sponsor Michigan State University
Start date January 2013
End date January 2016
Trial size 30 participants
Trial identifier NCT01786252, Endo-hCG-755, IRB 12-755F

Summary

Worldwide, 1 in 12 couples experience difficulty in getting pregnant and seek the help of assisted reproductive technologies (ART) such as in vitro fertilization (IVF-egg is fertilized by sperm outside the body), ovarian stimulation (medications are used to stimulate egg development) and intra-cytoplasmic injection (ICSI-single sperm is injected directly into the egg).

Regardless of the ART procedure being performed, the newly fertilized embryo must still implant into the mothers endometrium (inner lining of uterus). This implantation process in humans is surprisingly inefficient and accounts for up to 50% of ART failures. Intrauterine infusion of hCG prior to embryo transfer has recently been shown to increase pregnancy rates but the cellular mechanism for this increase is unknown.

Successful implantation requires the newly fertilized embryo and the endometrium develop in a synchronized manner. This coordinated development is accomplished, in part, by proteins secreted by the embryo which circulate throughout the maternal bloodstream and alert the maternal body organs (i.e. ovary, endometrium, breast, ect) that fertilization has occurred.

One of the earliest of these secreted proteins is human chorionic gonadotropin (hCG), which is the molecule detected in over-the-counter pregnancy tests. From previous studies, we know that hCG production by the embryo alerts the ovary to continue producing progesterone, a hormone required for pregnancy. However, very little is known about the direct effect of hCG on the endometrium during early pregnancy in humans.

Using animal models, hCG has been shown to induce specific changes in the endometrium, suggesting that embryo-derived hCG may be "priming" the endometrium in anticipation of implantation. The goal of this research study is to examine the direct effect of hCG on the human endometrium and see if this "priming effect" is also present in humans. Findings from this research may reveal whether pre-treatment with hCG can enhance ART outcomes, especially pregnancy rates.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification pharmacokinetics/dynamics study
Intervention model parallel assignment
Masking open label
Primary purpose basic science
Arm
(Experimental)
Drug: human chorionic gonadotropin (hCG). A single intrauterine infusion of 500IU hCG dissolved in IVF media ("Global"-trademark) will be administered to participants in the experimental group three days after oocyte retrieval. Two days after this infusion, participant will return to clinic where a uterine lavage and an endometrial biopsy will be performed to obtain a sample of uterine secretory proteins and endometrial tissue, respectively, for research analysis.
human chorionic gonadotropin (hcg) Novarel, human chorionic gonadotropin
500IU of hCG diluted to a final volume of 50ul in IVF media ("Global"-trademark)
(Placebo Comparator)
Placebo Comparator for hCG. A single intrauterine infusion of IVF media without hCG will be administered to participants in the control group three days after oocyte retrieval. Two days after this infusion, participant will return to clinic and a sample of uterine secretory proteins and endometrial tissue, will be obtained via uterine lavage and endometrial biopsy, respectively, for research analysis.
placebo comparator (for hcg) IVF media
50ul of IVF medium ("Global"-trademark) to mimic hCG infusion

Primary Outcomes

Measure
Evaluate the effect of hCG on endometrial gene and protein expression levels
time frame: within three years of study completion

Secondary Outcomes

Measure
Evaluate the effect of hCG on endometrial secretory proteins.
time frame: within three years of study completion

Eligibility Criteria

Female participants from 18 years up to 34 years old.

Inclusion Criteria: 1. between the ages of 18-34 years old 2. successfully applied for oocyte donor status at the Investigators Infertility clinic (The Fertility Center, 3230 Eagle Park Drive NE, suite 100. Grand Rapids MI 49525) 3. meet the ASRM criteria for oocyte donation Exclusion Criteria: 1. younger than 18 years old or older than 34 years old 2. have not successfully applied for oocyte donor status at the Investigators Infertility clinic (The Fertility Center, 3230 Eagle Park Drive NE, suite 100. Grand Rapids MI 49525) 3. do not meet the ASRM criteria for oocyte donation

Additional Information

Official title The Effect of hCG on the Human Endometrium
Principal investigator Asgerally T. Fazleabas, PhD
Description Embryo implantation in humans is surprisingly inefficient and represents a major limiting factor for enhancement of ART success rates (ref 1-2). Successful implantation requires synchronized development between the newly fertilized embryo and the maternal endometrium within a specific window of time. In mammals, this coordinated development is accomplished, in part, by embryonic secretions which alert the body that fertilization has occurred. One of the earliest proteins produced by the embryo is human chorionic gonadotropin (hCG). Previous research has shown that hCG maintains progesterone production by the ovary, a hormone required for the maintenance of pregnancy. However, very little is known about the direct effect of hCG on the human endometrium. Our laboratory has previously shown that intrauterine infusion of hCG in the non-human primate can induce endometrial changes that mimic the initial stages of early pregnancy (i.e. altered cellular morphology, pre-decidual response and increased glandular activity; ref 3-4). These results suggest that embryo-derived hCG may also act directly upon the endometrium to "prime" it in anticipation of implantation. Research from other labs examining the effect of hCG on endometrial genes in vitro support this hypothesis (ref: 5-9). Additionally, a recent study of women undergoing ART revealed significantly increased implantation and pregnancy rates when the embryo transfer was preceded by intra-uterine infusion of 500IU hCG (ref 10). The purpose of this study is to determine whether the endometrial response to hCG seen previously in our non-human primate model is also present in women and to characterize this effect. Women who plan to undergo controlled ovarian stimulation for the purpose of egg donation will be eligible to participate in this research. Subjects in experimental group will receive a single intrauterine infusion of hCG (500IU) diluted in IVF media 3 days after oocyte retrieval. Control subjects will receive a single intrauterine infusion of IVF media only. Two days after infusion, both experimental group and control participants will return to the clinic where a sample of endometrial tissue will be obtained via pipelle biopsy and a sample of uterine secretory proteins will be obtained via uterine lavage. The uterine lavage samples will be examined using ELISA/proteomic analysis to determine the effect of hCG on uterine protein secretions. One portion of the endometrial biopsy will be formalin-fixed and paraffin-embedded for analysis of morphological and structural changes following hCG exposure. The second portion will be used for cellular and molecular analysis to determine the effect of hCG on genes and proteins of interest.
Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by Michigan State University.