Early pregnancy factor
Encyclopedia
Early pregnancy factor or early conception factor (ECF) is a protein
associated with mammal
ian embryo
s shortly after fertilization
. It may be composed of more than one molecule. It was first described in 1976.
) shortly after fertilization; EPF is also present in cervical mucus
and in amniotic fluid
.
EPF may be detected in sheep within 72 hours of mating, in mice within 24 hours of mating, and in samples from media surrounding human embryos fertilized in vitro
within 48 hours of fertilization (although another study failed to duplicate this finding for in vitro embryos). EPF has been detected as soon as within six hours of mating.
Because the rosette inhibition assay for EPF is indirect, substances that have similar effects may confound the test. Pig semen, like EPF, has been shown to inhibit rosette formation - the rosette inhibition test was positive for one day in sows mated with a vasectomized boar, but not in sows similarly stimulated without semen exposure. A number of studies in the years after the discovery of EPF were unable to reproduce the consistent detection of EPF in post-conception females, and the validity of the discovery experiments was questioned. However, progress in characterization of EPF has been made and its existence is well-accepted in the scientific community.
EPF is an immunosuppressant. Along with other substances associated with early embryos, EPF believed to play a role in preventing the immune system
of the pregnant female from attacking the embryo. Injecting anti-EPF antibodies into mice after mating significantly reduced the number of successful pregnancies and number of pups; no effect on growth was seen when mice embryos were cultured in media containing anti-EPF antibodies. While some actions of EPF are the same in all mammals (namely rosette inhibition), other immunosuppressant mechanism vary between species.
In mice, EPF levels are high in early pregnancy, but on day 15 decline to levels found in non-pregnant mice. In humans, EPF levels are high for about the first twenty weeks, then decline, becoming undetectable within eight weeks of delivery
.
Recent research has suggested that EPF may be associated with cell proliferation in a wide variety of biological situations, not just embryo development.
In humans, modern pregnancy test
s detect human chorionic gonadotropin
(hCG). hCG is not present until after implantation, which occurs six to twelve days after fertilization. In contrast, EPF is present within hours of fertilization. While several other pre-implantation signals have been identified, EPF is believed to be the earliest possible marker of pregnancy. The accuracy of EPF as a pregnancy test in humans has been found to be high by several studies.
methods act before or after fertilization. A 1982 study evaluating EPF levels in women with IUDs
concluded that post-fertilization mechanisms contribute significantly to the effectiveness of these devices. However, more recent evidence, such as tubal flushing studies indicates that IUDs work by inhibiting fertilization, acting earlier in the reproductive process than previously thought.
For groups that define pregnancy as beginning with fertilization
, birth control methods that have postfertilization mechanisms are regarded as abortifacient
. There is currently contention over whether hormonal contraception
methods have post-fertilization methods, specifically the most popular hormonal method - the combined oral contraceptive pill (COCP). The group Pharmicists for Life has called for a large-scale clinical trial to evaluate EPF in women taking COCPs; this would be the most conclusive evidence available to determine whether COCPs have postfertilization mechanisms.
(43% rate of early conceptus loss).
Use of EPF has been proposed to distinguish infertility caused by failure to conceive versus infertility caused by failure to implant. EPF has also been proposed as a marker of viable pregnancy, more useful in distinguishing ectopic or other nonviable pregnancies than other chemical markers such as hCG and progesterone
.
A study of EPF in women taking clomifene
to treat infertility found fertilization rates of about 40%-50% per cycle. In cycles where fertilization was detected, nearly 80% resulted in subclinical embryonic loss, a rate much higher than that found in healthy women.
A study of EPF in women undergoing in vitro fertilization (IVF) concluded that, while a significant number of embryos simply failed to implant, an equally significant number of embryos were likely damaged or killed by the transfer process itself. The researchers used these findings to call for more attention to the effective transfer of embryos during IVF procedures.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
associated with mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
ian embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
s shortly after fertilization
Fertilisation
Fertilisation is the fusion of gametes to produce a new organism. In animals, the process involves the fusion of an ovum with a sperm, which eventually leads to the development of an embryo...
. It may be composed of more than one molecule. It was first described in 1976.
Detection
Early pregnancy factor is tested for rosette inhibition assay. EPF is present in the maternal serum (blood plasmaBlood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
) shortly after fertilization; EPF is also present in cervical mucus
Cervix
The cervix is the lower, narrow portion of the uterus where it joins with the top end of the vagina. It is cylindrical or conical in shape and protrudes through the upper anterior vaginal wall...
and in amniotic fluid
Amniotic fluid
Amniotic fluid or liquor amnii is the nourishing and protecting liquid contained by the amniotic sac of a pregnant woman.- Development of amniotic fluid :...
.
EPF may be detected in sheep within 72 hours of mating, in mice within 24 hours of mating, and in samples from media surrounding human embryos fertilized in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
within 48 hours of fertilization (although another study failed to duplicate this finding for in vitro embryos). EPF has been detected as soon as within six hours of mating.
Because the rosette inhibition assay for EPF is indirect, substances that have similar effects may confound the test. Pig semen, like EPF, has been shown to inhibit rosette formation - the rosette inhibition test was positive for one day in sows mated with a vasectomized boar, but not in sows similarly stimulated without semen exposure. A number of studies in the years after the discovery of EPF were unable to reproduce the consistent detection of EPF in post-conception females, and the validity of the discovery experiments was questioned. However, progress in characterization of EPF has been made and its existence is well-accepted in the scientific community.
Origin and function
Early embryos are not believed to directly produce EPF. Rather, embryos are believed to produce some other chemical that induces the maternal system to create EPF. After implantation, EPF may be produced by the conceptus directly.EPF is an immunosuppressant. Along with other substances associated with early embryos, EPF believed to play a role in preventing the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
of the pregnant female from attacking the embryo. Injecting anti-EPF antibodies into mice after mating significantly reduced the number of successful pregnancies and number of pups; no effect on growth was seen when mice embryos were cultured in media containing anti-EPF antibodies. While some actions of EPF are the same in all mammals (namely rosette inhibition), other immunosuppressant mechanism vary between species.
In mice, EPF levels are high in early pregnancy, but on day 15 decline to levels found in non-pregnant mice. In humans, EPF levels are high for about the first twenty weeks, then decline, becoming undetectable within eight weeks of delivery
Childbirth
Childbirth is the culmination of a human pregnancy or gestation period with the birth of one or more newborn infants from a woman's uterus...
.
Recent research has suggested that EPF may be associated with cell proliferation in a wide variety of biological situations, not just embryo development.
Pregnancy testing
In 1979, it was suggested that EPF could be used as a marker for a very early pregnancy test, and as a way to monitor the viability of ongoing pregnancies in livestock. Interest in EPF for this purpose has continued, although current test methods have not proved sufficiently accurate for the requirements of livestock management.In humans, modern pregnancy test
Pregnancy test
A pregnancy test attempts to determine whether or not a woman is pregnant.These markers are found in urine and blood, and pregnancy tests require sampling one of these substances. The first of these markers to be discovered, human chorionic gonadotropin , was discovered in 1930 to be produced by...
s detect human chorionic gonadotropin
Human chorionic gonadotropin
Human chorionic gonadotropin or human chorionic gonadotrophin is a glycoprotein hormone produced during pregnancy that is made by the developing embryo after conception and later by the syncytiotrophoblast .. Some tumors make this hormone; measured elevated levels when the patient is not...
(hCG). hCG is not present until after implantation, which occurs six to twelve days after fertilization. In contrast, EPF is present within hours of fertilization. While several other pre-implantation signals have been identified, EPF is believed to be the earliest possible marker of pregnancy. The accuracy of EPF as a pregnancy test in humans has been found to be high by several studies.
Birth control research
EPF may also be used to determine whether pregnancy prevention mechanism of birth controlBirth control
Birth control is an umbrella term for several techniques and methods used to prevent fertilization or to interrupt pregnancy at various stages. Birth control techniques and methods include contraception , contragestion and abortion...
methods act before or after fertilization. A 1982 study evaluating EPF levels in women with IUDs
Intrauterine device
A copper IUD is a type of intrauterine device. Most IUDs have a plastic T- or U-shaped frame which is wrapped in copper wire, with the exception of Gynefix, which is a plastic string with several copper beads, affixed to the fundus of the uterus...
concluded that post-fertilization mechanisms contribute significantly to the effectiveness of these devices. However, more recent evidence, such as tubal flushing studies indicates that IUDs work by inhibiting fertilization, acting earlier in the reproductive process than previously thought.
For groups that define pregnancy as beginning with fertilization
Beginning of pregnancy controversy
Controversy over the beginning of pregnancy usually occurs in the context of the abortion debate. Depending on where pregnancy is considered to begin, some methods of birth control or infertility treatment might be considered abortifacient...
, birth control methods that have postfertilization mechanisms are regarded as abortifacient
Abortifacient
An abortifacient is a substance that induces abortion. Abortifacients for animals that have mated undesirably are known as mismating shots....
. There is currently contention over whether hormonal contraception
Hormonal contraception
Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original hormonal method—the combined oral contraceptive...
methods have post-fertilization methods, specifically the most popular hormonal method - the combined oral contraceptive pill (COCP). The group Pharmicists for Life has called for a large-scale clinical trial to evaluate EPF in women taking COCPs; this would be the most conclusive evidence available to determine whether COCPs have postfertilization mechanisms.
Infertility and early pregnancy loss
EPF is useful when investigating embryo loss prior to implantation. One study in healthy human women seeking pregnancy detected fourteen pregnancies with EPF. Of these, six were lost within ten days of ovulationOvulation
Ovulation is the process in a female's menstrual cycle by which a mature ovarian follicle ruptures and discharges an ovum . Ovulation also occurs in the estrous cycle of other female mammals, which differs in many fundamental ways from the menstrual cycle...
(43% rate of early conceptus loss).
Use of EPF has been proposed to distinguish infertility caused by failure to conceive versus infertility caused by failure to implant. EPF has also been proposed as a marker of viable pregnancy, more useful in distinguishing ectopic or other nonviable pregnancies than other chemical markers such as hCG and progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
.
A study of EPF in women taking clomifene
Clomifene
Clomifene or clomiphene or Clomid or Clomifert is a selective estrogen receptor modulator that increases production of gonadotropins by inhibiting negative feedback on the hypothalamus...
to treat infertility found fertilization rates of about 40%-50% per cycle. In cycles where fertilization was detected, nearly 80% resulted in subclinical embryonic loss, a rate much higher than that found in healthy women.
A study of EPF in women undergoing in vitro fertilization (IVF) concluded that, while a significant number of embryos simply failed to implant, an equally significant number of embryos were likely damaged or killed by the transfer process itself. The researchers used these findings to call for more attention to the effective transfer of embryos during IVF procedures.