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Glossary

Abortion is defined as a clinically recognized pregnancy loss before the 20th week of gestation. Spontaneous abortion, or miscarriage, is the loss of the infant naturally or accidentally, without the will of the mother. Most miscarriages are not preventable since chromosomal abnormalities account for approximately 50 percent of cases. Pre conceptual and prenatal counseling and care are the most important interventions for the prevention of spontaneous abortion in women with no prior history of miscarriage. The use of pharmacologic therapy (e.g., estrogen, vitamins, aspirin) has not been found to be effective.

A cap-shaped cellular structure located at the front of the sperm cell (spermatozoa) that contains a packet of
enzymes able to dissolve a hole in the specialized extracellular matrix surrounding the egg (oocyte). This enzymic
digestion then allows the spermatozoa to penetrate and fertilize the egg.

A disease of the uterus that is characterized by an enlarged uterus and painful, heavy periods.
Adenomyosis occurs when the tissue that normally lines the uterus (endometrial tissue) grows into the muscular wall of
the uterus. The displaced tissue continues to act normally — thickening, breaking down and bleeding — during each
menstrual cycle. The disease usually resolves after menopause. For women who have severe discomfort from
adenomyosis, hormonal treatments can help. Removal of the uterus (hysterectomy) cures adenomyosis.

A term used to describe clumping together of particles or substances. It can be used to describe the
changes that occur following sperm ejaculation or an immune response involving antibodies.

The absence of a menstrual period, it can be either primary (not yet had a period by 16 years of age) or
secondary (regular period that has now stopped for 3+ months).

AMH is a protein hormone produced by special cells inside the ovarian follicles. The level of AMH in the blood can help doctors estimate the number of follicles inside the ovaries, and therefore, the woman’s egg count, otherwise known as an ovarian reserve (i.e. the capacity of the ovary to provide egg cells that are capable of fertilization). However, AMH does not assess oocyte or embryo quality. This drawback precludes any good prediction of female fertility in the general population as well as in specific subgroups of patients. Still, the AMH assay can become an indirect marker of the remaining female fertile years in some cases such as in those women who are at risk for premature ovarian failure or in those suffering from polycystic ovary syndrome. A typical AMH level for a fertile woman is 1.0–4.0 ng/ml; under 1.0 ng/ml is considered low and indicative of a diminished ovarian reserve.

A diagnostic procedure done in the second trimester of pregnancy that can detect many fetal
abnormalities. It is performed by sampling a small quantity of the amniotic fluid that surrounds the fetus with a needle via a transabdominal approach under ultrasound guidance.

Laboratory tests to evaluate fetal health can be performed on amniotic fluid since this fluid is largely composed of fetal substances: urine, secretions, exfoliated cells, and transudate. The most common diagnostic indications for obtaining amniotic fluid are prenatal genetic studies. Other indications include, but are not limited to, evaluation of the fetus for infection, degree of hemolytic anemia, blood or platelet type, hemoglobinopathy, and neural tube defects. Assessment of fetal lung maturity, which used to be a common indication for amniocentesis, is now rarely performed.

Defined as the branches of science and medicine dealing with male reproductive functions under
physiological and pathological conditions.

A term in genetics used to describe an abnormal number of chromosomes in an individual, mainly (90%)
due to chromosome mal-segregation mechanisms during maternal meiosis (i.e. production of germ cells (eggs)). The
normal genome chromosomal set (n, 2n, 3n for each chromosome) for a species is referred to as euploidy, in humans
this is diploid (2n). If a specific chromosome has three copies, it will be referred to has being aneuploid.

The absence of ovulation, failure for an oocyte (egg) to be released from the ovary.

Semen can cause an immune system response in either the man's or woman's body, if there
are antibodies that target and bind to the semen. These antibodies can damage or kill sperm. An antisperm antibody

test looks for the antibodies that target a man's sperm in blood, vaginal fluids, or semen. The test uses a sample of
sperm and adds a substance that binds only to affected sperm.
If a high number of sperm antibodies come into contact with a man's sperm, it may be hard for the sperm to fertilize an
egg. A couple could have a hard time becoming pregnant. This is called immunologic infertility. A man can make sperm
antibodies when his sperm come into contact with his immune system. This can happen when the testicles are injured or
after surgeries (such as a biopsy or vasectomy) or after a prostate gland infection. The testicles normally keep the sperm
away from the rest of the body and the immune system. A woman can have an allergic reaction to her partner's semen
and make sperm antibodies. This kind of immune response is not fully understood but may affect fertility. This is a rare
cause of infertility.

A fertility treatment, involving placement of a sperm sample collected from a male inside
the female reproductive tract that can be carried out by a number of different techniques: intracervical insemination,
intrauterine insemination, intratubal insemination.

Removal of fluid and cells by suction through a needle. This technique applies to many
procedures in reproductive medicine, for example egg retrieval.

A procedure done by embryologists in the laboratory prior to embryo transfer in in
vitro fertilization (IVF) cycles. The procedure involves placing a small opening in the “shell” that surrounds every embryo. This assists the embryo in breaking out of this shell and extruding itself to implant in the endometrium after transfer.

A group of fertility therapies that employ manipulations of the egg (oocyte) and sperm in the laboratory in order to establish a pregnancy. These include In Vitro Fertilization
(IVF), Intracytoplasmic Sperm Injection (ICSI), donor egg cycles, assisted hatching, preimplantation genetic diagnosis (PGD) and others.

An infertility in males caused by both an abnormally low amount of sperm with good
motility (asthenozoospermia) and an abnormally low level of sperm of a healthy shape (teratozoospermia).

An infertility condition in men defined by the lack of sperm cells in repeated examination by qualified
professionals. Azoospermia is divided in two main types: Obstructive and non-obstructive. Obstructive azoospermia (OA)
is defined as the absence of spermatozoa in the ejaculate despite normal spermatogenesis (i.e. production of mature
sperm cells). OA is a common urologic condition and accounts for 6.1% to 13.6% of patients presenting for fertility
evaluation. Vasectomy is a frequent cause of OA; however, alternate etiologies such as infection, iatrogenic injury, and
genetic and congenital conditions are all possible causes of OA are frequently encountered. Non‐obstructive
azoospermia (NOA) is defined as no sperm in the ejaculate due to failure of spermatogenesis and is the most severe
form of male infertility. The etiology of NOA is either intrinsic testicular impairment, resulting from chromosomal or
genetic abnormalities, or inadequate gonadotropin production. The procedures for treating each type of azoospermia
are distinct. In cases of NOA, the reason for the condition will probably be unknown. The research into the condition is
still ongoing; many aspects are yet to be uncovered.

The temperature taken at its lowest point in the day, typically in the morning before
getting out of bed. Body temperature changes, primarily increases in temperature, are used to approximately establish
the time of ovulation.

Also known as the Human Chorionic Gonadotropin (hCG), is a hormone of early pregnancy. This hormone appears during the first trimester of pregnancy, a time characterized by rapid cell division and tissue differentiation in the developing embryo. The blastocyst implants itself about eight to ten days after ovulation, and begins to secrete hCG, whose concentration in the urine doubles every two to three days during early pregnancy. The hormone becomes detectable in the blood and urine within seven to nine days, reaching its highest concentration around the eighth week of pregnancy.
Due to its early secretion, hCG is quite useful for pregnancy detection. This hormone is also used as an injection to induce ovulation and maturation of the egg in ovarian stimulation protocols, as well as monitoring
the viability of the gestation.

Biochemical pregnancy, also known as a chemical pregnancy, is a very early pregnancy loss
taking place within five weeks after implantation. Many women who have a chemical pregnancy (do not even realize
they have conceived, since often the only sign is a late period). During a chemical pregnancy, the body produces enough
of the reproductive hormone, hCG (human chorionic gonadotropin), to initially result in a positive pregnancy test.
However, at this early stage, the pregnancy cannot be detected on an ultrasound scan, and ultimately implantation will
fail and serum hCG levels will decline. Since pregnancy hormone levels are present but low, women typically do not
experience any of the other signs of pregnancy, such as fatigue or nausea. Some women may experience more cramping
than normal or a heavier menstrual flow.

A fluid-filled cavity that forms in early development post-fertilization within the blastocyst. In humans, this
cavity is present during the end of the first week and into the second week of development. Initially the dividing cells
form a solid cellular mass (morula), continued cell division and compaction lead to the formation of this space or cavity.

A stage in the development of the placenta and fetus. Four days after fertilization, the morula. On the fifth day after fertilization, the morula (a solid mass of blastomere cells that enters the uterus from the fallopian tube on the fourth days after fertilization) becomes a blastocyst as fluid accumulates and polarization
of the cells occurs. The blastocyst has an outer layer of cells (trophoblast) that will form the placenta and fetal membranes, an inner cell mass at one pole that will form the embryo, and a fluid filled cavity. The inner and outer cell masses multiply and the fluid cavity enlarges until the expanded blastocyst hatches out of the zona shell. Within 24 hours of hatching (approximately day 6 after fertilization), the blastocyst implants in the uterine
lining, which provides access to substrates (glycogen filled stromal cells) necessary for continued growth.
Implantation involves movement of the blastocyst to an optimal location (typically the mid to upper anterior or posterior wall of the uterus), adhesion, and invasion. Is conceptus another term for Blastocyst?

A term used to describe the first cells formed by mitotic cell division of the zygote (the first cell formed by
the fertilized egg) during with 1 of post-fertilization development. This stage will be replaced by the morula and then the
blastocyst stages.

The process that sperm must undergo in order to fertilize an egg.

Infertility due to a structural or hormonal abnormality of the cervix. This can be induced by previous surgery on the cervix (such as a LEEP or cone procedures) that leaves the cervical canal scarred or closed, termed stenosis. Also applied when there are factors associated with the cervix which inhibit sperm function such as thickened mucus which prevents the sperm from traveling through the cervix into the female reproductive tract. Cervical factor infertility can usually be overcome using inseminations of sperm past the cervix in to the uterus.

Normal secretions of the cervix which change in volume and consistency throughout the
menstrual cycle. Its quality is a reflection of hormonal stimulation.

The lower section of the uterus which protrudes into the vagina and serves as a reservoir for sperm. Its anatomical functions include being a natural barrier to the inner uterus, and also keeping pregnancies from delivering prematurely.

A positive pregnancy test, but with levels of pregnancy hormone (beta HCG) too low for
ultrasound documentation of a pregnancy (contrary to a clinical pregnancy). Typically this definition includes pregnancies that have low beta HCG levels that spontaneously decline without any further development.

Chimerism is a genetic phenomenon that occurs when a woman is pregnant with twins, one embryo dies,
and the other embryo absorbs the twin’s cells. This type of chimerism is called tetragametic because the baby was
derived from four gametes – one egg and one sperm for each embryo, but there are several other types of chimerism
that can develop. Most individuals with chimerism are not aware that they have a second genome. Consequently, most

remain undiagnosed throughout their lifetime, partly because the condition is not well known in the medical
community, and partly because there is no population-wide screening practice. Chimerism does not usually have many
signs or symptoms, but if people with the condition are not diagnosed an unexpected outcome may occur when they
have children. A baby born to an individual with chimerism can be more distantly related from a genetic perspective, as
if they were a niece/nephew. Most often a diagnosis does not occur unless someone fails a paternity or maternity DNA
test, and they seek out answers as to why.

Division of one cell into 2, 2 into 4, 4 into 8, etc. This is measured in the embryology laboratory
during in vitro fertilization (IVF) cycles.

A pregnancy in which the beating fetal heart has been identified by ultrasound.

An oral medication used to stimulate the ovaries and/or synchronize follicle development. The medication is sold under the commercial names: Clomid TM or Serophene TM.

In the development of the embryo, compaction (consolidation) is the process following the third cleavage
division of the zygote during which the blastomeres maximize their contact with each other by polarization and
adhesion, forming a compact ball that is held together by tight junctions; compaction segregates the inner cells of the
blastocyst that form the embryo from the outer cells that form the fetal part of the placenta.

A term that describes the developmental abnormalities that are detected before or are present
at birth. There are no internationally agreed definitions for congenital anomalies and there are a range of classifications
including the International Classification of Diseases (ICD), developed by the World Health Organization (WHO) to enable
comparability for mortality statistics.

An example of a congenital anomality is congenital dislocated hip (developmental dysplasia of the hip (DHH)). This term
refers to a spectrum of musculoskeletal disorders of hip instability due either to the femoral head being able to move
outside the acetabulum (luxation or dislocation), or abnormally within the acetabulum (subluxation or partial
dislocation).

Congenital bilateral absence of the vas deferens occurs in males when the tubes that carry sperm out of the testes (the vas deferens) fail to develop properly. Although the testes usually develop and function normally, sperm cannot be transported through the vas deferens to become part of semen, leading to the type of male infertility called obstructive azoospermia. As a result, men with this condition are unable to father children (infertile) unless they use assisted reproductive technologies. This condition has not been reported to affect sex drive or sexual performance. This condition can occur alone or as a sign of cystic fibrosis, an inherited disease of the mucus glands, and is responsible for 1 percent to 2 percent of all infertility in men.

The granulosa cells that directly surround the oocyte (egg), within the antral follicle region of the ovary. These cells are released along with the oocyte at ovulation and provide physical protection and the initial structural barrier that spermatozoa (sperm) must penetrate during fertilization.

A technique for freezing tissue or cells, including eggs, sperm, embryos, to preserve them for use at a later date.

Cryptorchidism is characterized by the absence of one or both testes from the scrotum, i.e. improper descent of one or both testicles into the scrotum, occurring in < 30% premature and 3-4% term males. Descent may complete postnatally in the first year. Depending on the class of cryptorchidism there are a number of different surgical repair techniques including: orthoplasty or penile straightening, urethroplasty, meatoplasty and glanuloplasty, scrotoplasty (oscheoplasty) and skin coverage.

The cloud-like collection of supportive follicle cells that surround the egg.

Fluid filled growths that can appear in the ovaries (and in many other organs). Ovarian cysts may be normal or abnormal depending on the circumstances. Often, they are just follicles that have not been fully reabsorbed from previous menstrual or treatment cycles. They are very common in both natural and stimulated cycles.

Oocyte cytoplasmic maturation includes those events that instill upon the oocyte a capacity to complete nuclear maturation, insemination, early embryogenesis and thus provide a foundation for implantation, initiation of pregnancy, and normal fetal development. Although we can define oocyte cytoplasmic maturation, we are only now beginning to understand the molecular steps that underlie this process. In general terms, oocyte cytoplasmic
maturation involves the accumulation of mRNA, proteins, substrates, and nutrients that are required to achieve the
oocyte developmental competence that fosters embryonic developmental competence.

Cytoplasmic transfer, also known as ooplasmic transfer, is an experimental fertility technique that involves injecting a small amount of ooplasm (cytoplasm) from eggs of fertile women into eggs of women whose fertility is compromised. The modified egg is then fertilized with sperm and implanted in the uterus of the woman attempting to achieve pregnancy. Children born from this procedure have been reported to possess cytoplasmic organelles called mitochondria from both their biological mother and the ooplasmic donor, a condition referred to as mitochondrial
heteroplasmy.

Clinical assisted reproductive technology term for a diagnosis that means that the ability
of the ovary to produce eggs is reduced due to congenital, medical, or surgical causes or advanced age.

The presence of two genomes or chromosome sets. Diploidy is a fundamental hallmark of eukaryotic evolution
and bisexual reproduction, because diploidy offers the basis for the bisexual life cycle, allowing for oscillation between
diploid and haploid phases. Meiosis (the cell division that occurs only in production of germ cells (oocyte, spermatozoa)
where there is a reduction in the number of chromosomes) produces haploid gametes (from diploid cells). At fertilization, male and female gametes fuse to restore diploidy in a zygote, which develops into a new life. At sex maturation, diploid cells enter into meiosis, culminating in the production of new haploid gametes.

Eggs that are harvested via an in vitro fertilization (IVF) cycle performed on the donor
(anonymous or known donor). The harvested eggs are inseminated with sperm in the lab to form embryos which are transferred into the womb of the intended parent.

The implantation of two IVF produced embryos into the uterus of the patient, instead of a single embryo, as a means of increasing the chance of the embryos (one or both) producing a successful pregnancy. This procedure could produce multiple pregnancies (i.e. twins). Multiple pregnancies result in adverse outcomes such as higher risks of prematurity, low or very low birth weight, intrauterine growth retardation, pregnancy-induced
hypertension, and caesarean section. Also, twin pregnancies have a six-fold increased risk of perinatal mortality and
morbidity and a fourfold increased risk of cerebral palsy compared to singleton pregnancies. Clinical trials have showed
that the likelihood of success with a single embryo transfer is equivalent to that of a double embryo transfer (60.7% vs
65.1%) and that the risk of having a multiple gestation following a double embryo transfer is significantly increased (53%
vs. 0%) compared to a single embryo transfer.

Also known as a tubal pregnancy, this is a pregnancy implanted outside the uterus; most
often in the fallopian tube. This can usually be diagnosed in its early stages by following the pregnancy hormone, beta HCG, very closely during the early part of pregnancy. Left undiagnosed and untreated, an ectopic pregnancy can have serious medical consequences.

The term used to describe the early stages of fetal growth. Strictly defined from the second to the ninth week of pregnancy but often used to designate any time after conception.

Happens when there is an uneven division of the cells of the embryo. Embryo fragmentation is
a fairly common occurance, and is typically due to an inherent defect in the egg. These fragments are of no use to the
embryo and are considered “junk” pieces of cytoplasm. The higher the degree of fragmentation, the lower the likelihood
of pregnancy. Embryo fragmentation can occur with both natural conception and in the IVF process. In the latter case, it
can lead to failed IVF, but not necessarily.

In embryos from IVF procedures, typically the laboratory denotes the degree of fragmentation by assigning it a grade along a four-point grading scale. One indicates an embryo with little fragmentation (<5%), and four indicates a high degree of fragmentation (>40%) and an embryo that is non-viable. Excessive embryo fragmentation (grade 3-4) is considered a marker for embryos with compromised developmental potential. These embryos rarely make it past the eight-cell stage, and it is unlikely that they will make it to the blastocyst stage. Embryos with >20% fragmentation may
continue to develop normally to the blastocyst stage, although pregnancy rates may be compromised. Also in IVF, since fragmentation can also be due to a poor ovarian stimulation, it can be improved as the protocol or management of the stimulation is changed on subsequent cycles.

The procedure of transferring embryos, created in-lab by inseminating an egg during an in
vitro fertilization (IVF) cycle, back into the womb of a patient. It occurs on the third or fifth day after an egg retrieval.

A medical professional whose expertise is in reproductive medical procedures, or a researcher
who studies embryology. Embryology is the science of studying embryo development, usually applied to all development before birth (in humans, included both the embryonic and fetal period).

The study of hormones, their function, the organs that produce them and how they are produced.

The extraction of a small piece of tissue from the endometrium (lining of the uterus) for
microscopic examination.

The space inside the uterus that is created by the inner lining of the uterus that responds
to female hormones during the menstrual and treatment cycles. This lining, when properly prepared, forms the area of attachment and implantation of the embryo. Commonly referred to as the womb.

The presence of endometrial tissue (tissue that normally lines the uterus) in abnormal
locations such as the ovaries, fallopian tubes and abdominal cavity. These lesions lead to local irritation and inflammation that can cause scarring to occur which can bind-up pelvic organs to the point of dysfunction and pain.

The epithelium lining of the non-pregnant uterus. During pregnancy this epithelium undergoes
changes described as the decidual reaction and is renamed the “decidua”.

A section of the male genital tract located at the back of the testis where sperm maturation is partially accomplished. Receives sperm from the testis and continues as the vas deferens. Sperm reside in the epididymis for 12-16 days, and over this period of time their motility is developed.

An inflammation of the epididymis. Epididymitis is most often caused by a bacterial infection, including sexually transmitted infections (STIs), such as gonorrhea or chlamydia. Males of any age can get epididymitis. Signs and symptoms of epididymitis might include: 1) A swollen, red or warm scrotum; 2) Testicle pain and tenderness, usually on one side, that usually comes on gradually; 3) Painful urination or an urgent or frequent need to urinate; 4) Discharge from the penis; 5) Pain or discomfort in the lower abdomen or pelvic area; 6) Blood in the semen; 7) Less commonly, fever.

Epididymitis that lasts longer than six weeks or that recurs is considered chronic. Symptoms of chronic epididymitis might come on gradually. Sometimes the cause of chronic epididymitis is not identified.

 

The principal hormone produced by the growing ovarian follicle. It is frequently measured in the blood to assess the strength and development of the follicles during treatment cycles.

Genetic term used to describe the normal cell genome chromosomal set (n, 2n, 3n) or complement for a species, in humans this is diploid (2n). The terms used to describe the classes of numerical chromosomal abnormalities
include aneuploidy, polyploidy and mixoploidy.

The anatomic and physiologic connection between the uterus and the ovary which serves to
transport the egg and sperm. It is also the site of fertilization and supports and transports the conceptus in route to the uterus.

The ability to procreate and produce offspring. The degree of this ability is different between each male and
each female.

Fertility preservation is the process of saving or protecting eggs, sperm, or reproductive tissue so that a person can use them to have biological children in the future. People (male or female) with certain diseases, disorders, and life events that affect fertility may benefit from fertility preservation. These include people who: Have been exposed to toxic chemicals in the workplace or during military duty, have endometriosis, have uterine fibroids, are
about to be treated for cancer, are about to be treated for an autoimmune disease (such as lupus), have a genetic
disease that affects future fertility, delay having children.


A number of fertility-preserving options are available. Fertility-preserving options for males include: Sperm
cryopreservation and gonadal shielding. In cryopreservation, a male provides samples of his semen. The semen is then
frozen and stored for future use in a process called cryopreservation. In gonadal shielding, radiation treatment for cancer and other conditions can harm fertility, especially if it is used in the pelvic area. Some radiation treatments use modern techniques to aim the rays on a very small area. The testicles can also be protected with a lead shield.


Fertility-preserving options for females include: Embryo cryopreservation, oocyte cryopreservation, gonadal shielding, ovarian transposition. Embryo cryopreservation, also called embryo freezing, is the most common and successful option for preserving a female's fertility. First, a health care provider removes eggs from the ovaries. The eggs are then fertilized with sperm from her partner or a donor in a lab in a process called in vitro fertilization. The resulting embryos are frozen and stored for future use. Oocyte cryopreservation is similar to embryo cryopreservation, except that unfertilized eggs are frozen and stored. Gonadal shielding for women is similar to gonadal shielding for males. Steps are taken, such as aiming rays at a small area or covering the pelvic area with a lead shield, to protect the ovaries from
radiation. In ovarian transposition, a health care provider performs a minor surgery to move the ovaries and sometimes the fallopian tubes from the area that will receive radiation to an area that will not receive radiation. For example, they may be relocated to an area of the abdomen wall that will not receive radiation.


Some of these options, such as sperm, oocyte, and embryo cryopreservation, are available only to males and females
who have gone through puberty and have mature sperm and eggs. However, gonadal shielding and ovarian
transposition can be used to preserve fertility in children who have not gone through puberty.

Merger of a sperm with an egg to facilitate creation of a genetically unique embryo.

In humans, the development week 9 to 36 is the fetal stage (second and third trimester). This term is also used
non-scientifically to describe the human conceptus at both embryonic and fetal stages of development.

Benign overgrowth of the muscular tissue of the uterus that can distort the shape and function of the uterus. Fibroids are typically classified in to three categories, with each having class having different implications on fertility: Sub-mucosal fibroids are found in the uterine cavity and impair implantation. They need to be removed in order to conceive. Intramural fibroids are problematic when they become severely enlarged or impinge on the uterine cavity. Sub-serosal fibroids generally are left alone during fertility treatments.

The soft and supple finger-like extensions of the fallopian tube that aid in the gathering of the egg during ovulation.

Describes the period of human development following the embryonic period. The development between week 9 and 36 is the fetal stage (second and third trimester). This term is also used non-scientifically to describe the human conceptus at both embryonic and fetal stages of development.

A fluid-filled pocket in the ovary that houses the microscopic egg. Each ovary has many follicles within it and each follicle contains a single oocyte. Follicles are initially very small and then grow larger under the influence of hormones such as FSH (and the medications that mimic these hormones). Follicles are lined with granulosa cells which produce estrogen and nourish the egg.

A hormone produced by the pituitary gland in the brain that stimulates the ovarian follicles to grow and develop. FSH is measured in the blood at specialized times during the menstrual cycle to help measure ovarian reserve.

One of two phases that makeup the menstrual cycle, the other being the luteal phase. The follicular phase refers to the first half of the cycle, from onset of menses to ovulation, and lasts approximately 14 days. It is associated with developing follicles that produce estradiol.

The freeze-all strategy has emerged as an alternative to fresh embryo transfer (ET) during in vitro fertilization
(IVF) cycles. Women undergoing IVF who have high levels of the hormone progesterone when their egg cells are
retrieved benefit from having the resulting embryos frozen and transferred back to the uterus at a later date, the
researchers found. Studies have found that a delay in transferring embryos to the mother improves the success of in
vitro fertilization in certain cases.

Controlled ovarian stimulation (COS) is necessary for the development and maturation of many follicles and oocytes,
thus increasing the likelihood of positive outcomes and cumulative pregnancy rates during assisted reproductive
therapies (ART). However, there are many concerns about the possible adverse effects of COS over the endometrium.
The supra-physiological hormonal levels that occur during a conventional COS are associated with modifications in the
peri-implantation endometrium, that may be related to decreases in pregnancy rates, among other effects, when
comparing fresh to frozen-thawed embryo transfers.

An older method of assisted fertilization that involves surgically removing an egg from the ovary, combining it with sperm, and immediately surgically placing the egg and sperm into the fallopian tube, where fertilization takes place.

The period of time from conception to birth, which is more often referred to as a pregnancy. A pregnancy with multiple fetuses is referred to as a multiple gestation.

Also called a gestational surrogate, or simply a surrogate, is a woman who carries an embryo that
was formed from the egg of another woman; the gestational carrier is expected to return the infant to its genetic
parents.

Also called round-headed spermatozoa, is a human infertility syndrome caused by spermatogenesis
defects leading to a malformed or absent sprematozoa acrosome, a specialized section in the anterior of the sperm cell
that contains enzymes needed to penetrate the egg. The acrosomal reaction (release of the enzymes upon interaction
with the egg) being a key component of sperm fertilization of the egg.

Hormone produced by the hypothalamus in the brain that stimulates the pituitary gland to secrete gonadotropins.

A test where sperm are incubated with non-viable hamster eggs to determine the capacity of the sperm to fertilize.

Having a single set of chromosomes as in mature germ/sex cells (oocyte, spermatozoa) following reductive
cell division by meiosis. Normally cells are diploid, containing 2 sets of chromosomes. Ploidy refers to the number of sets
of chromosomes in the nucleus of a cell.

The emergence of the blastocyst (hatching), the early embryo, from the surrounding cells. Around the end of
the fifth day after fertilization the embryo frees itself from the enveloping pellucid zone. Through a series of expansion-
contraction cycles the embryo bursts the covering. This is supported by enzymes that dissolve the pellucid zone at the
abembryonic pole. The rhythmic expansions and contractions result in the embryo bulging out of and emerging from the
rigid envelope.

A purified extract of LH and FSH, the hormones secreted by the pituitary gland to stimulate the ovary. Humegon and Pergonal are commercial preparations of HMG used by injection to facilitate development of multiple follicles in treatment cycles.

Accumulation of interstitial fluid (edematous) in either one or both blocked uterine tubes or fallopian
tubes due to a previous tubal infection. Salpinx in the name of the condition refers to the trumpet shape of the uterine
tube. This blockage can impact maternal fertility and may require in vitro fertilization (IVF) techniques for reproduction.

A condition in which a man produces a larger than normal volume of semen. Semen is the fluid a man
ejaculates during orgasm. It contains sperm, along with fluid from the prostate gland. This condition is the opposite of
hypospermia, which is when a man produces less semen than usual, and is generally defined in humans when the
ejaculate is over 5.5 ml.

Hyperspermia can be caused by either excessive production of sperm in the testicles, or by overproduction of seminal
fluid by accessory sex glands. Hyperspermia can occur after long periods of sexual abstinence, which causes a build up of
fluids. In this case, the ejaculate may contain greater proportion of dead or dysfunctional sperm, that are not capable of
fertilizing the egg. If the volume of seminal fluid is significantly increased, it can lead to dilution of the sperm and lower
chances of fertilization. However, if the amount of sperm is proportional to the amount of semen, hyperpermia can
actually enhance fertility.

Hyperspermia is not a pathological condition of its own, and is often considered harmless by men experiencing it.
However, it should be investigated to prevent possible complications in the future and to rule out any associated
conditions affecting future fertility.

Male hypogonadism is a condition in which the body does not produce enough of the hormone that
plays a key role in masculine growth and development during puberty (testosterone) or enough sperm or both. Men can
be born with male hypogonadism (congenital), or it can develop later in life (acquired causes), often from injury or
infection. Defects, whether acquired or congenital, that interfere with interactions in the hypothalamic-pituitary-
testicular axis can cause male hypogonadism. It is essential to distinguish between primary hypogonadism (which
originates in the testes) and secondary hypogonadism (which originates in the hypothalamus or pituitary). The effects of
this condition — and what can be done about them — depend on the cause and at what point in life male
hypogonadism occurs. Some types of male hypogonadism can be treated with testosterone replacement therapy.
Symptoms highly suggestive of hypogonadism include decreased spontaneous erections, decreased nocturnal penile
tumescence, decreased libido, and reduced testicular volume. Ambiguous genitalia, micropenis, and bilateral
cryptorchidism are all signs of testosterone deficiency in pre-pubertal males. Karyotype testing is done in young adults
to rule out conditions such as Turner syndrome and Klinefelter syndrome which can result in testosterone deficiency.
Some causes of primary hypogonadism include Klinefelter’s syndrome, undescended testicles (Cryptorchidism), mumps
orchitis, hemochromatosis, cancer treatment, and normal aging. Causes of secondary hypogonadism include Kallman
syndrome, pituitary disorders, HIV, obesity, surgery, trauma, and stress-induced hypogonadism.
Hypogonadism is often under-reported. According to some studies approximately 40% of men over the age of 45 and
50% of men in their 80s are hypogonadal. Testosterone levels have been found to decrease by 100 ng/dL every ten
years. There appears to be no relationship between racial and ethnic groups with hypogonadism.

Defined as all stages of spermatogenesis (production of sperm cells) being present, but there is a
decline in the number of germ cells. This condition is the cause of infertility, specifically, non-obstructive azoospermia.
Treatment of hypospermatogenesis is testicular sperm extraction followed by extensive sperm searches.

A portion of the brain that stimulates the pituitary gland to secrete LH and FSH in order to stimulate ovarian follicle development. The hypothalamus acts as the “pacemaker” for many important hormone-driven processes, controlling the production and periodic release of hormones from the pituitary gland.

An x-ray procedure to examine whether the fallopian tubes are patent (open) or not. This test helps determine if the fallopian tubes are blocking sperm from reaching the ovulated eggs. Special x-ray dye is gently injected through the uterus and then x-ray pictures are taken to see where the dye travels.

A surgical device consisting of a small telescopic camera, much like a laparoscope, which is placed through the cervical canal into the uterine cavity. This allows direct visualization of the endometrium, the lining of the uterine cavity (the womb), making it possible to locate and remove any impediments to implantation, such as polyps or fibroids in the uterine cavity. Hysteroscopic surgery (or hysteroscopy) can be performed for both therapeutic or diagnostic indications. This surgical technique is minimally-invasive, well-tolerated and performed in a day-surgery center.

By the time of birth, the human ovary contains a pool of quiescent primordial follicles, each
consisting of a small inactive oocyte (egg), arrested in the germinal vesicle stage, and a single layer of granulosa cells;
the fate of each follicle is controlled by endocrine as well as paracrine factors secreted in the body during lifetime. Of the
millions of the primordial oocytes present at birth, only approximately 400 mature during a woman's lifetime. Oocyte
maturation is defined as the restart and completion of the first meiotic division from prophase I, through metaphase I
(MI stage), to metaphase II (MII stage), with accompanying cytoplasmic maturation, which includes the storage of
cytoplasmic enzymes, mRNAs, organelles, and metabolic substrates that are crucial for fertilization and early embryonic
development.
In contrast to the oocyte maturation that occurs as the result of the natural selection, in assisted reproduction cycles,
supra-physiologic gonadotropin doses induce multiple follicular growth and maturation, in order to ensure the
maximum number of obtained embryos, and thereafter the highest probability of a successful pregnancy. Even though
controlled ovarian stimulation (COS) has been developed and refined in attempt to obtain optimal oocytes number from
each cycle, different COS protocols may result in follicular asynchrony and variations in oocyte number, quality, viability,
and competence. Usually, 10 to 30% of oocytes are still immature at retrieval. Some of the immature oocytes may
extrude the first polar body and progress to maturity during in vitro culture, and might be considered for sperm
injection, while others, will not mature during the observation time.

The embedding of the embryo into the lining of the uterus to initiate a pregnancy.

A commonly used outcome parameter in in vitro fertilization (IVF) studies. The IR is calculated as [IR = ngestational sacs/ntransferred embryos, where ngestational sacs is the number of gestational sacs observed at vaginal ultrasound 3–5 weeks after transfer and ntransferred embryos is the number of transferred embryos]. This calculation can be performed per patient or aggregated per group of patients: very often the latter approach is chosen.

Refers to a commonly used procedure to help patients conceive pregnancies, in which the egg is fertilized by the sperm in the laboratory, rather than inside the female reproductive tract. IVF entails stimulating the ovaries to develop a large number of growing follicles multiple follicles. This is achieved with injectable medications (i.e. hormones). The eggs inside the follicles are then harvested through a short surgical procedure performed in the IVF unit. After extraction, the eggs are then inseminated with sperm in the laboratory, sometimes using Intracytoplasmic Sperm Injection (ICSI), in order to create embryos that can then be transferred back to the womb) of the patient.

A term used to describe a range of techniques for developing ovarian follicles and oocytes
(eggs) outside of the body. These oocytes are generally retrieved from the antral follicles of either unstimulated or
minimally stimulated (hormonally) ovaries. The technique has been suggested for polycystic ovary syndrome and other
ovarian pathologies for fertility preservation, as part of in vitro fertilization (IVF). This is a relatively new approach to
human fertility.

Reproductive term meaning not fertile, therefore unable to produce offspring. Infertility can be due to many
different causes (genetic, environmental, unknown) and also associated with many systems (germ cell formation,
endocrine abnormalities, abnormalities of the reproductive tract).

In an early mammalian embryo, at the blastocyst stage a small group of inner cells (also known as the
embryoblast) that will eventually grow into the embryo itself and subsequently into the adult. The remainder of cells
that form the wall are the trophoblast cells.

Insertion of sperm for the purpose of establishing a pregnancy. Inseminations are performed by placing a small, soft catheter through the cervix into the uterine cavity and depositing the concentrated and activated sperm.

Intracervical insemination is one of the oldest and most common artificial
insemination procedures. Similar to intrauterine insemination (IUI), it involves placing sperm directly into the woman's
reproductive tract to improve the chances of pregnancy. The main difference is that the ICI procedure places the sperm
sample near the cervix, rather than the uterus as in IUI. From the cervix, the sperm travels up the uterus and into the
fallopian tubes to fertilize the egg. Candidates for ICI procedures include couples that are dealing with male fertility
issues such as low sperm count or motility. The procedure is also recommended to women that have cervical mucus
problems. Depending on the reasons for infertility and the quality of the sperm sample used, success rates for ICI range
from 5 percent to 30 percent per cycle. To increase the chances of pregnancy, the insemination procedure is usually
performed two times during each cycle. Sperm washing may also increase the chances of pregnancy with ICI.

Uterine Insemination (IUI)- A technique for transferring sperm directly into the uterus that allows the sperm and egg to interact in close proximity. It bypasses the vaginal and cervical defense mechanisms of the female reproductive tract and allows better sperm delivery to the fallopian tubes. It is commonly employed when mild and moderate deficits are identified during semen analysis. IUI is typically used in conjunction with medications that increase the number of eggs per cycle and triggering of ovulation. This combination of treatments allows to have more targets for the sperm (i.e. eggs), perfect timing and better sperm delivery.

Placement of a single sperm into a single egg by penetrating the outer coatings of the egg. This technique is used in cases where there are very low sperm numbers, motility or morphology. ICSI is also used for patients who have had previous in vitro fertilization (IVF) cycles with failed fertilization.

Klinefelter syndrome defines a group of chromosomal disorders in men in which there is at least one extra X chromosome. The extra X chromosome is due to improper maternal or paternal division of X chromosomes during gametogenesis (i.e. egg or sperm production). There is an equal chance of receiving the extra chromosome from the mother as there is from the father.  The extra copy of genes on the X chromosome interferes with male sexual development and can prevent the normal function of the testis testes, reducing the levels of testosterone. In fact, Klinefelter syndrome is the most common cause of primary hypogonadism, meaning a decrease in one or both of the two major functions of the testes: sperm production and testosterone production. The signs and symptoms vary among affected individuals. The prevalence of Klinefelter syndrome is approximately 1 to 2.5 per 1000 boys and men (0.1 to 0.25 percent). Only 25 to 50 percent of patients with Klinefelter syndrome are diagnosed during their lifetimes. Many of these missed diagnoses are likely due to the failure of clinicians to recognize the symptoms and signs of hypogonadism and the distinctive phenotype (e.g., small, very firm testes) of classic Klinefelter syndrome. Recognition and treatment of Klinefelter syndrome is important for prevention or treatment of its consequences, such as infertility.

Approximately 80 to 90 percent of men with Klinefelter syndrome have 47 chromosomes with an extra X chromosome. Approximately 10 percent of men with Klinefelter syndrome have mosaicism, with the additional X chromosome being present in some tissues and the normal set of chromosomes (46 chromosomes; only one X chromosome and one Y chromosome) in other tissues. Mosaic Klinefelter syndrome is due to post-fertilization mitotic nondisjunction during early fetal development. Men with mosaic Klinefelter syndrome have a milder phenotype. Very rarely, men may have more than two X chromosomes. Men with three or more X chromosomes have a more severe phenotype of Klinefelter syndrome than those with only one additional X chromosome.

A thin, lighted viewing instrument with a telescopic lens through which a surgeon views the exterior surfaces of a female’s reproductive organs and abdominal cavity, also known as laparoscopic surgery. In this minimally invasive procedure, the laparoscope is placed through the belly-button in order to view and operate on the abdominal cavity and reproductive organs. This surgical technique is minimally-invasive, well-tolerated and performed in a day-surgery center. It allows your physician to diagnose and remove endometriosis, as well as re-open a blocked fallopian tube, amongst many other indications.

A condition in which there is an unusually high number of white blood cells in the semen. According to
the World Health Organization, leukospermia is defined as more than 1 million white blood cells per milliliter of semen.
Leukospermia is an important condition in male fertility because white blood cells weaken the sperm and can damage its
genetic material. White blood cells release powerful substances called reactive oxygen species (ROS), which destroy
organisms that cause infections. Unfortunately, ROS can also affect healthy tissues, which includes sperm. ROS destroy
the sperm membrane, impair sperm movement, and damage sperm DNA.
Less than 5% of men with a fertility problem are diagnosed with leukospermia. Leukospermia can be caused by many
different things, including: Infection, inflammation (swelling), autoimmune conditions, urethra stricture (narrowing of
the tube through which urine passes), genital infections (such as herpes, gonorrhea, or chlamydia), varicocele (the veins
coming from the testicle are dilated, or widened), systemic illness (across the whole body), infrequent ejaculation, use of
tobacco, marijuana, and alcohol.

Male gonad (testis) cell which secrete the androgen testosterone, beginning in the fetus.

The delivery of one or more babies with any sign of life.

Lupron is a synthetic form of GnRH (gonadotropin releasing hormone) used to suppress ovarian function.

Refers to the second half of the menstrual cycle (after the follicular phase), which usually lasts fourteen days of an ovulatory. It begins at the time of ovulation and ends at the onset of menses, but is prolonged during pregnancy cycles. It is associated with progesterone production from the corpus luteum that facilitates implantation of embryos and supports early pregnancies.

In assisted reproduction techniques (ART), progesterone and/or human chorionic gonadotropin
(hCG) levels are low, so the luteal phase is supported with progesterone, hCG or gonadotropin‐releasing hormone
(GnRH) agonists to improve implantation and pregnancy rates. Progesterone prepares the endometrium for pregnancy
by stimulating proliferation in response to hCG produced by the corpus luteum in the luteal phase of the menstrual
cycle.

A hormone produced and released by the pituitary gland. In women it is responsible for ovulation and maintenance of the corpus luteum. In men it stimulates testosterone production and is important in the production of sperm cells.

The oocyte (eggs, ova, ovum) is arrested at an early stage of development (the first meiotic division)
within the ovary. Following puberty, during each menstrual cycle, pituitary gonadotrophin stimulates completion of
meiosis 1 the day before ovulation. This process is called oocyte maturation and these changes are essential since only
mature oocytes can be fertilized. In order for a sperm cell to fertilize an oocyte (egg), it needs to have gone through a
number of changes that favor so-called oocyte maturity.

In contrast to the natural in vivo process, where oocyte maturation occurs as the result of the natural selection, in
assisted reproduction cycles, supra-physiologic gonadotropin doses induce multiple follicular growth and maturation, in
order to ensure the maximum number of obtained embryos, and thereafter the highest probability of a successful
pregnancy. Even though controlled ovarian stimulation (COS) has been developed and refined in attempt to obtain
optimal oocytes number from each cycle, different COS protocols may result in follicular asynchrony and variations in
oocyte number, quality, viability, and competence. Usually, 10 to 30% of oocytes are still immature at retrieval.

Aqueous laboratory solutions containing nutritive growth substances that are used to allow cells (i.e. sperm) to survive in an artificial environment.

Commonly known as a “period”. Cyclic (monthly) flow of blood (menstruation) signifying ovulation, but failure to achieve pregnancy. Onset of bleeding is considered cycle day 1. The purpose of a natural menstrual cycle is to produce one follicle and ovulation per month.

Metrodin is Human Follicle Stimulating Hormone (FSH) prepared in an injectable form for ovarian stimulation.

A procedure performed on men who have a sperm
production problem and are azoospermic (non-obstructive azoospermia). MicroTESE is performed in the operating room
with general anesthesia under the operating microscope. MicroTESE is a more advanced procedure compared to other
sperm retrieval surgeries, has significantly improved sperm retrieval rates in azoospermic men, and is a safer procedure
since less testicular tissue is removed.
During a microTESE surgery, a transverse cut through the skin in the center of the testicle is used. Through this opening,
the inside of the testicle is ‘pulled out’, and with the help of a surgical microscope, the surgeon examines the
seminiferous tubules. He will use micro-surgical forceps to gently and thoroughly examine the testicle for evidence of
sperm cells, after which he will select for extraction the areas of the testicle that appear to be ‘filled’ with sperm cells
and are pink-colored, a characteristic which signifies that they are more likely to contain sperm cells. In total, during the
surgery, tissue samples are collected from a large number of epicenters (15-20 on average) across the entire testicle, but
from every spot only a very small and accurate tissue sample is removed.

A group of laboratory techniques that allow sperm, egg and embryo manipulation (examples) to be performed under the guidance of the microscope.

An IVF cycle without giving gonadotropin for stimulating oocyte maturation, but in which hCG is
used for triggering of ovulation for accurate scheduling of oocyte retrieval and thus increased oocyte yield. GnRH
antagonists are also used to prevent premature ovulations, albeit at the cost of adding some form of ovarian stimulation
to continue follicle development until ovulation triggering. These modified natural IVF cycles are associated with
decreased medication costs, they produce acceptable pregnancy rates, and they may be particularly appropriate for
patients at increased risk of ovarian hyperstimulation syndrome, poor responders, and those wishing to avoid
supernumerary embryo production.

Monosomy refers to the presence of only one chromosome from the normal pair in the embryo. A partial
monosomy is when there is only one copy of a segment of a chromosome present. A complete monosomy syndrome in
female humans is seen in Turner syndrome, associated with either a missing or altered second X chromosome. A partial
monosomy syndrome in humans is seen in Cri du Chat (cat's cry) syndrome, associated with a piece of chromosome 5
being missing (Deletions of the short arm of chromosome 5).

Refers to the shape of sperm cells which is one of the three criteria for examining the health and
fertilization potential of sperm together with sperm count and sperm motility. Abnormal sperm shape (small, large,
defects in the head, tail, and/or mid-piece) can be used for differential diagnosis of various infertility conditions such as
the OAT syndrome.

An early stage in post-fertilization development when cells divide rapidly (embryonic cell cycle) producing a
solid mass of cells (12-15 cells) with a "mulberry" appearance. In humans, morula stage of development occurs during
the first week following fertilization. Cell proliferation occurs still enclosed within the zone pellucida. This stage is
followed by formation of a cavity in this cellular mass (blastocyst stage).

Genetic term used to describe an abnormal genome chromosomal set, where there are two or more
genetically different cell lines in an individual. Each cell has 46 chromosomes grouped in 23 pairs. A person with
mosaicism may have some cells in his or her body with 46 chromosomes. But other cells have 47 chromosomes. This can
cause health problems in the body.
Mosaicism may be caused by an error in mitosis (the dividing of body cells). Mitosis causes the number of chromosomes
to double to 92, and then split in half back to 46. Mitosis continues throughout a lifetime. It replaces skin cells, blood
cells, and other types of cells that are damaged or naturally die. If there is an error in mitosis, a cell does not split evenly
into 2 cells. The result is that some cells have the normal number of 46 chromosomes, and other cells have more (47) or
fewer (45) chromosomes.

Sperm motility is the ability of the sperm cells to move rapidly. Motility is one of the three criteria for
examining the health and fertilization potential of sperm together with sperm count and sperm morphology. In order for
a male to be considered normal in terms of motility, 60% to 80% of the sperm seen in a sperm analsyis must be actively
moving.

Defined as the presence of more than one nucleus in at least one blastomere of the embryo. Embryo
quality has been shown to correlate with multinucleation, and 4-cell embryos on Day 2 and 8-cell embryos on Day 3
show reduced multinucleation compared with the other cell stages observed on these days. Multinucleation is
predictive of a decreased implantation potential and multinucleated embryos are associated with an increased level of
chromosome abnormalities as well as an increased risk of spontaneous abortion. Multinucleation evaluation should be
included in any embryo assessment protocol to select the highest quality embryo for transfer, and although these
embryos do give rise to live births, they should be excluded from selection for embryo transfer if an alternative embryo
is available.

When all the sperm is dead in a fresh semen sample. Incomplete Necrozoospermia is when many of
the sperm are dead. Some of the causes for necrozoospermia are infections in the reproductive tract, prolonged periods
of no ejaculation, or injuries. Treatment for necrozoospermia depends on the cause, such as prescribed antibodies for
infections or repeated ejaculation. The most common solution is to do a testicular sperm retrieval and IVF (ICSI). This
involves retrieving immature sperm cells from the testicles and injecting the sperm cell directly into the egg.

Azoospermia is divided in two main types: Obstructive and non-obstructive.
Non‐obstructive azoospermia (NOA) is defined as no sperm in the ejaculate due to failure of spermatogenesis (sperm
cells development) and is the most severe form of male infertility. The etiology of NOA is either intrinsic testicular
impairment, resulting from chromosomal or genetic abnormalities, or inadequate gonadotropin production. In cases of
NOA, the reason for the condition will probably be unknown. The research into the condition is still ongoing; many
aspects are yet to be uncovered.

Obstructive azoospermia (OA) is defined as the absence of spermatozoa (sperm cells) in the
ejaculate despite normal spermatogenesis (i.e. production of mature sperm cells). OA is a common urologic condition
and accounts for 6.1% to 13.6% of patients presenting for fertility evaluation. Vasectomy is a frequent cause of OA;
however, alternate etiologies such as infection, iatrogenic injury, and genetic and congenital conditions are all possible
causes of OA are frequently encountered.

A condition that includes low sperm number, low sperm motility and abnormal sperm morphology, is the commonest cause of male infertility. Disruptions of in the production of sperm cells (spermatogenesis) or conditions that cause the sperm to die during production (undergo apoptosis) results in low sperm concentration (oligozoospermia), which is major symptom of the male infertility. In contrast, defects in sperm production cause poor sperm motility (asthenozoospermia) and abnormal sperm morphology (teratozoospermia). These spermiogenic defects often induce sperm cell apoptosis, thus leading to a combination of the syndromes called oligoasthenoteratozoospermia (OAT syndrome). Although some cases of OAT syndrome can be clinically associated with varicocoele or other pathologies, approximately 60% of OAT individuals are diagnosed as idiopathic, which is assumed to include genetic abnormalities. However, the genetic factors underlying OAT are largely unknown.

A condition associated with the use of fertility drugs during in vitro fertilization (IVF) and treatment of other reproductive abnormalities. The drugs stimulate follicular development and egg maturation, there are no agreed standards for reporting this condition. Studies of the condition reported that it occurred in 0.8% of cycles that involved an oocyte (egg) retrieval with the incidence of OHSS increasing with the number of oocytes collected.

A low sperm count, meaning that the fluid (semen) ejaculated during an orgasm contains fewer sperm
than normal. A complete absence of sperm is called azoospermia. A sperm count is considered lower than normal if
there are fewer than 15 million sperm per milliliter of semen. Having a low sperm count decreases the odds that a
sperm cell will fertilize an egg, resulting in pregnancy. Nonetheless, many men who have a low sperm count are still able
to father a child.
The main sign of low sperm count is the inability to conceive a child. There might be no other obvious signs or
symptoms. In some men, an underlying problem such as an inherited chromosomal abnormality, a hormonal imbalance,
dilated testicular veins or a condition that blocks the passage of sperm may cause signs and symptoms. Low sperm count
symptoms might include: Problems with sexual function (for example, low sex drive or difficulty maintaining an erection
(erectile dysfunction)); pain, swelling or a lump in the testicle area; decreased facial or body hair or other signs of a
chromosome or hormone abnormality.
Treatments depend on the underlying cause (if identified). Surgery for correcting varicoceles, antibiotics for treating
infections, or hormone treatments in cases where infertility is caused by high or low levels of certain hormones, are all
potential treatments. Extensive sperm searches in semen samples can be done to identify and isolate vital and viable
sperm cells for IVF treatments. Surgical sperm extraction via TESE or MicroTESE surgeries can also be tried if other
options had failed.

Also referred to as an egg, is the female germ cell.

Egg freezing, also known as mature oocyte cryopreservation, is a method used to save
women's ability to get pregnant in the future. Eggs harvested from the ovaries are frozen unfertilized and stored for
later use. At a later stage, a frozen egg can be thawed, combined with sperm in a lab and implanted in the uterus (in
vitro fertilization). Unlike with fertilized egg freezing (embryo cryopreservation), egg freezing does not require sperm
because the eggs are not fertilized before they are frozen. Fertility medication (hormones) are needed to induce
ovulation of multiple eggs for retrieval. The risk of miscarriage after in vitro fertilization with cryopreserved eggs will be
primarily based on the age of the woman at the time the eggs were frozen. Older women have higher miscarriage rates,
mainly due to having older eggs.

Normal female fertility relies on proper development of the oocyte. This growth culminates just
prior to ovulation, when oocyte maturation occurs. Oocyte maturation is defined as a re-entry into meiosis that occurs
just prior to ovulation and subsequent fertilization. Oocytes within the ovary are arrested in prophase I of meiosis until
the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), stimulate follicular growth and
development, which then triggers the resumption of meiosis up to metaphase II. Oocytes are subsequently again held in
meiotic arrest until fertilization, when meiosis is completed.

An alternative term for the zona pellucida surrounding the oocyte (also called vitelline membrane and egg
coat). The oolemma is a specialized extracellular matrix that surrounds the developing oocyte (egg, ovum) within the
ovary and following ovulation.

The cytoplasm of the oocyte or egg. The ooplasm is the substance that surrounds the nucleus of the egg and
contain proteins and the many organelles of the cell.

A condition associated with fertility drugs used for in vitro fertilization and
other reproductive abnormalities (i.e. hormones associated with ovulation). The drugs stimulate follicular development
and oocyte maturation, there are no agreed standards for reporting this condition.
Normally, a woman produces one egg per month. Women who have trouble getting pregnant and are undergoing in
vitro fertilization (IVF) treatments are usually given medicines to help them produce and release eggs. If these medicines
stimulate the ovaries too much, the ovaries can become very swollen. Fluid can leak into the belly and chest area. This is
called OHSS. This occurs only after the eggs are released from the ovary (ovulation).
OHSS affects 3% to 6% of women who go through IVF. OHSS rarely occurs in women who only take fertility drugs by
mouth. Likelihood of OHSS is increased if the patient: Received a shot of human chorionic gonadotropin (hCG), received
more than one dose of hCG after ovulation, became pregnant during this cycle. Other risk factors for OHSS include:
Being younger than age 35, having a very high estrogen level during fertility treatments, having polycystic ovarian
syndrome.

Ovarian tissue freezing is a type of fertility preservation. It may be useful for women who want
to have children after having treatment that may cause infertility, such as certain cancer treatments. Also called ovarian
tissue banking and ovarian tissue cryopreservation. In this process, part or all of an ovary is removed, and the tissue that
contains the eggs is cut into thin slices and frozen. The tissue may later be thawed and placed back into the woman’s
body, usually on the remaining ovary.

The female sex gland with both a reproductive function (releasing oocytes) and a hormonal function (production of estrogen and progesterone).

The release of a mature egg from the surface of the ovary.

The total number of mature eggs produces during ovulation. A single egg can be called ova.

A screening test to determine the presence of cervical cancer. Done by gently touching the cervix with a swab to collect cells for examination by a pathologist.

Parthenogenesis is a form of reproduction in which an egg can develop into an embryo without being
fertilized by a sperm. Parthenogenesis is derived from the Greek words for “virgin birth,” and several insect species
including aphids, bees, and ants are known to reproduce by parthenogenesis. Recently, parthenogenesis has received
considerable attention as a tool for the production of stem cells. Human stem cells derived from embryos, fetal
primordial germ cells, umbilical cord blood, and adult tissues provide potential cell based therapies for repair of
degenerating or damaged tissues.

Pathology caused by an ascending infection of the upper female genital tract, usually a sexually transmitted disease (STD), mainly by Gram-negative bacteria. May also occur following childbirth, miscarriage, or a surgical procedure. PID can also be referred to as endometritis or salpingitis (an inflammation of the fallopian tube that can cause epithelial scarring leading to fertility problems and ectopic pregnancy).

PESA is a procedure performed for men who are having sperm
retrieved for IVF/ICSI who have obstructive azoospermia from either a prior vasectomy or infection. It is done with local
anesthesia in the operating room or office and is coordinated with their female partner’s egg retrieval. PESA is a blind
procedure. The surgical approach is dependent on physician preference and the clinical scenario. A fine needle is used to
puncture the epididymis, and the epididymal fluid is collected by fine-gauge needle aspiration. The epididymal fluid is
placed onto a petri dish and examined under the inverted microscope to confirm the presence of motile sperm.

Perivitelline space (PVS) is the space between the oocyte (egg) and the surrounding zona pellucida,
enlarged in the region where the polar body lies. In mice this has been shown to influence the site sperm entry

independent of any asymmetry of the oocyte membrane.

The polar body is a small cytoplasmic structure formed from the excess DNA during the oocyte (egg)
meiosis and following spermatozoa (sperm cell) fertilization. There could be 2-3 polar bodies derived from the oocyte
present in the zygote, the number is dependent upon whether polar body 1 (the first polar body formed during meiosis
1) divides during meiosis 2. This exclusion body contains the excess DNA from the reductive division (the second and
third polar bodies are formed from meiosis 2 at fertilization). These polar bodies do not contribute to the genetic
complement of the zygote, embryo or fetus. Recent research in some species suggest that the space formed by the
peripheral polar body (between the oocyte and the zona pellucia) can influence site of spermatozoa fertilization.

A common endocrinologic condition that causes hormonal imbalances in women of reproductive age. It can lead to dysfunctional ovulation, infertility, weight gain, pre-diabetes and an increase in the male hormone, testosterone.

An overgrowth of the glandular surface of the endometrium. Polyps are often removed by hysteroscopic surgery to avoid any impediments to implantation procedures. What are the differences between a polyp and a fibroid?

Genetic term used to describe an abnormal number of chromosomes, includes triploidy, when there are
three copies of each chromosome, usually due to two spermatozoa fertilizing a single oocyte. The normal genome
chromosomal set (n, 2n, 3n) or complement for a species is referred to as euploidy, in humans this is diploid (2n). The
other classes of numerical chromosomal abnormalities include aneuploidy and mixoploidy.

An abnormal condition where the oocyte is fertilized by more than 1 sperm.

The microscopic analysis of a sample of vaginal and cervical secretions that has been collected after sexual intercourse. This test allows a physician to see if sperm survives in a women’s reproductive tract. It has largely been superseded by the semen analysis, but there are still some clinical indications that use PCT.

Also known as preimplantation genetic diagnosis (PGD) is a screening procedure
for embryos produced through in vitro fertilization (IVF) for genetic diseases that would generate developmental
abnormalities or serious postnatal diseases. Embryonic cells are removed and screened for chromosomal disorders or
genetic diseases before the embryo transfer in the womb.

Premature ejaculation occurs when a man ejaculates sooner during sexual intercourse than he
or his partner would like. The main symptom of premature ejaculation is the inability to delay ejaculation for more than
one minute after penetration. Premature ejaculation is a common sexual complaint. Estimates vary, but as many as 1
out of 3 men say they experience this problem at some time. The exact cause of premature ejaculation is not known.
While it was once thought to be only psychological, doctors now know premature ejaculation involves a complex
interaction of psychological and biological factors.

A clinical term describing an ovarian abnormality characterized by either an absent menarche (primary amenorrhea) or premature depletion of ovarian follicles before the age of 40 years (secondary amenorrhea). The rate increases with maternal age (1 in 10,000 women by age 20; 1 in 1,000 women by age 30; 1 in 100 women by age 40) and with endocrine low levels of gonadal hormones (estrogens) and high levels of gonadotropins (luteinizing hormone (LH) and follicle stimulating hormone (FSH)).

When a woman is unable to ever bear a child, either due to the inability to become pregnant or the
inability to carry a pregnancy to a live birth, she would be classified as having primary infertility. Thus, women whose
pregnancy spontaneously miscarries, or whose pregnancy results in a still born child, without ever having had a live birth
would present with primarily infertility.

A hormone produced by the ovary which prepares the uterus for implantation and supports the early pregnancy.

An Assisted Reproductive Technology term. The pro-nucleus is the nucleus of either a
spermatozoa or an oocyte during the process of fertilization after the sperm enters the egg, but before they fuse.
Transfer involves removing the pro-nuclei from a newly fertilized oocyte that has unhealthy mitochondria. The pro-
nuclei are then transferred into a donated embryo, with healthy mitochondria, that has had its own, original pro-nuclei
removed.

A specific and specialized step in the unification of the egg and sperm nucleus before they join to create a genetically unique embryo. After this union the conceptus is referred to as a zygote.

The clinical term for 3 or more consecutive miscarriages and is suggested to occur due to a range of maternal and embryonic causes. The definition of RPL varies, which makes studying the phenomenon, and determining which couples to counsel or treat, more challenging.

RPL is one of the most frustrating and difficult areas in reproductive medicine because the etiology is often unknown and there are few evidence-based diagnostic and treatment strategies. Studies on the etiology, evaluation, and management of RPL are often flawed. Common methodologic weaknesses include failure to adhere to generally accepted criteria for RPL, ascertainment bias, improper selection of controls, uneven monitoring of cohorts, no exclusion of aneuploid fetuses, lack of stratification for important factors such as number of previous losses, premature termination of study after interim analysis, and excessive postrandomization patient withdrawal

 

Secondary infertility is the inability to become pregnant or to carry a baby to term after previously giving birth to a baby. Secondary infertility shares many of the same causes of primary infertility. Secondary infertility might be caused by: 1) Impaired sperm production, function or delivery in men, 2) Fallopian tube damage, ovulation disorders, endometriosis and uterine conditions in women, 3) Complications related to prior pregnancy or surgery, 4) Age, weight and use of certain medications.

Secondary infertility is the most common form of female infertility around the globe, often due to reproductive tract infections. Generally, it is recommended that individuals see fertility specialists after trying unsuccessfully to conceive for 8-12 months. For people over age 35 or who have known medical conditions, it is generally recommended they see a specialist much sooner. Evaluating both partners ensures the most effective treatments can be recommended.

Examination of the male ejaculate under the microscope to determine the number (count), motility (ability to move) and morphology (shape) of the sperm. These parameters all provide important information about how the sperm will perform in treatment cycles. The semen analysis is a cornerstone of the evaluation of couples experiencing infertility.

Also known as Elective Single Embryos Transfer (eSET), is defined as only transferring a single embryo at the culmination of an in vitro fertilization cycle. SET is a strategy to decrease a patient’s chances of having even twins. The trade-off, however, is a lower pregnancy rate. This is different from the conventional practice of transferring more than one embryo, as many as is deemed safe for each age group. This ensures the highest pregnancy rates, but also exposes the recipient to the possibility of having more than one baby, such as twins or more. SET is popular for patients that have a good prognosis for pregnancy.

Eligibility for the procedure is decided based on these criteria: 1) A patient is in one of the younger age groups (<37 years of age), 2) A patients has very high-quality embryos on day 5 (i.e. blastocysts), or 3) The patient has a medical condition for which even twins poses a large medical compared to a singleton pregnancy.

In some couples, blood, semen and/or cervical mucus contain substances which hinder sperm action through an allergic or immune reaction.

A procedure used in sperm analysis. Observations on the semen of animals and of man have demonstrated that the distribution of sperm cells is not uniform throughout the entire ejaculatory process. This conclusion has been reached by the use of the split-ejaculate method, in which the total seminal specimen is partitioned or fractionated during the ejaculatory process and the various fractions are studied separately. The earliest ejaculated fluid contains the highest concentration of spermatozoa. Latter ejaculate contains relatively more seminal fluid.

A woman who gets artificially inseminated with the father’s sperm in order to produce a fertilized egg, the procedure is called surrogacy. Currently, there are two types of surrogacy — traditional surrogacy and gestational surrogacy. In traditional surrogacy, a surrogate mother is artificially inseminated, either by the intended father or an anonymous donor, and carries the baby to term. The child is thereby genetically related to both the surrogate mother, who provides the egg, and the intended father or anonymous donor. In gestational surrogacy, an egg is removed from the intended mother or an anonymous donor and fertilized with the sperm of the intended father or anonymous donor. The fertilized egg, or embryo, is then transferred to a surrogate who carries the baby to term. The child is thereby genetically related to the woman who donated the egg and the intended father or sperm donor, but not the surrogate.

The surgical removal of sperm directly from the testis or the epididymis using a needle for aspiration. This procedure is used for men who have no sperm in their ejaculates or have had vasectomies in the past. Sperm obtained through TESE requires Intracytoplasmic Sperm Injection (ICSI) to ensure fertilization of an egg.

The male gonad, i.e. where male germ cells (spermatozoa) are generated and also the source of testosterone (male hormone).

Also referred to as teratozoospermia, is the clinical term for a spermatozoa (sperm) with abnormal morphology (small, large, defects in the head, tail, and/or mid-piece) present in the semen or ejaculate. Any deviation from the normal size and shape of the sperm is referred to as teratozoospermia. A normal appearing sperm has an oval elongated head with the dark staining nucleus (contains the DNA) and 1 or 2 empty spaces (vacuoles). The head is connected to the tail by a mid-piece which has a neck. The sperm is examined carefully to look for the number of defects in each sperm. Teratozoospermia is diagnosed when more than 95% of the sperm in a man’s semen sample is of abnormal morphology. However, this is highly subjective as it depends on the person looking under the microscope. It may happen that a sperm has defects in only one part or that it has multiple defects. An index referred to as teratozoospermia index is employed to detect the most frequent type of defect in a semen sample. The teratozoospermia index may range from 1 to 3. A teratozoospermia index around 1 indicates a defect in one part is most frequently occurring, index around 2 means defects in two parts and an index of 3 means defects in three parts. The index is thus helpful in detecting the severity of sperm morphology defects.

The literature is limited to three forms of teratozoospermia. The first group consists of “polymorphic teratozoospermia”, where a majority of sperm display more than one type of abnormality. In this case, only a slight increase in aneuploidy frequency is observed, which cannot be differentiated from the results observed in oligo-astheno-teratozoospermia (OAT). The second group, named “globozoospermia”, is characterized by round spermatic heads, absence of acrosome and disorganization of mid-piece and tail. The third group consists of “enlarged head teratozoospermia”, where almost all sperm have an enlarged head, multiple tail and abnormal acrosome.

Toxins, infections and Varicoceles contribute to abnormal sperm morphology. The chances of a teratozoospermic man naturally impregnating a woman are highly unlikely. Assisted reproductive techniques have made it possible for teratozoospermic men to have their biological offspring. Assisted reproductive techniques rely on selecting the sperm with the best morphology for fertilization of an egg and then applying IVF and ICSI to produce a fertilized egg and implant it into a recipient to initiate a pregnancy. In the case of globozoospermia, ICSI can be proposed to these patients, but few successes occur. In males with enlarged head teratozoospermia, ICSI must be refuted, and patients have to be redirected to other possibilities, like sperm donation. 

High frequency sound waves that can be used painlessly, safely, and without radiation, to view the internal portions of the body. Ultrasound is especially useful for visualizing the female reproductive organs and pregnancies.

The literature is limited to three forms of teratozoospermia. The first group consists of “polymorphic teratozoospermia”, where a majority of sperm display more than one type of abnormality. In this case, only a slight increase in aneuploidy frequency is observed, which cannot be differentiated from the results observed in oligo-astheno-teratozoospermia (OAT). The second group, named “globozoospermia”, is characterized by round spermatic heads, absence of acrosome and disorganization of mid-piece and tail. The third group consists of “enlarged head teratozoospermia”, where almost all sperm have an enlarged head, multiple tail and abnormal acrosome.

Toxins, infections and Varicoceles contribute to abnormal sperm morphology. The chances of a teratozoospermic man naturally impregnating a woman are highly unlikely. Assisted reproductive techniques have made it possible for teratozoospermic men to have their biological offspring. Assisted reproductive techniques rely on selecting the sperm with the best morphology for fertilization of an egg and then applying IVF and ICSI to produce a fertilized egg and implant it into a recipient to initiate a pregnancy. In the case of globozoospermia, ICSI can be proposed to these patients, but few successes occur. In males with enlarged head teratozoospermia, ICSI must be refuted, and patients have to be redirected to other possibilities, like sperm donation. 

Inability to identify the cause of infertility despite a complete evaluation of semen, ovarian reserve, ovulation, endocrinologic disorders and pelvic anatomy.

Also referred to as the womb, the uterus is the reproductive organ that houses protects and nourishes the developing embryo and fetus. It consists of the cervix, the endometrium and the muscular layer that comprises the body of this reproductive organ.

A varicocele is an enlargement of the veins around the vas deferens and the testes. A varicocele is similar to a varicose vein in the leg.  With time, varicoceles might enlarge and become more noticeable. A varicocele has been described as looking like a “bag of worms.” The condition might cause a swollen testicle, almost always on the left side. Varicoceles can also cause testicles to fail to develop normally or shrink. Varicoceles are a common cause of low sperm production and decreased sperm quality (i.e. reduced motility and changes in morphology), which can cause infertility. However, not all varicoceles affect sperm production. Fortunately, most varicoceles are easy to diagnose and many do not need treatment. If a varicocele causes symptoms (e.g. infertility, pain or significant testicular atrophy), it often can be repaired surgically.

Surgical treatment of the varicocele usually involves tying off the affected vein to redirect the blood flow toward normal veins. Surgery can be open or laparoscopic, and is done on an outpatient basis. Pain after the surgery is mild, and often the patient can return to most normal activities within two days. Approximately half of men who have the surgery to correct infertility are able to father a child within the first year.

There are two approaches to microsurgical varicocelectomy, inguinal or subinguinal. If the procedure is being performed for pain, the inguinal approach is often used to allow access to the ilio-inguinal nerve which can be cut to provide permanent pain relief. Once the surgeon incises the skin, he or she dissects down to the spermatic cord where the abnormal veins are encountered. Each vein is meticulously dissected circumferentially and then tied off to disrupt flow and provide drainage of blood away from the testicle into the inner thigh and pelvis. Keys to a good operation are to interrupt every vein, leave every artery intact, leave the vas deferens intact and leave lymphatic drainage intact. If an artery is cut, damage to the testicle can occur. If the vas deferens is injured, sperm can be blocked. If lymphatics are cut, the scrotum can feel with fluid and require additional surgery to drain the fluid. The microsurgical approach has been statistically shown to reduce all of these risks.

One of the internal organs of the male reproductive system. The vas deferens is a long, muscular tube that travels from the epididymis into the pelvic cavity, to just behind the bladder. The vas deferens transports mature sperm to the urethra in preparation for ejaculation.

Also known as Y-chromosome microdeletion (YCM), this term refers to abnormalities in the genetic material that makes up the Y-chromosome in men. The human Y chromosome harbors genes that are responsible for testis development and also for initiation and maintenance of spermatogenesis in adulthood. The long arm of the Y chromosome (Yq) is susceptible to intra-chromosomal deletions, meaning the removal of gene sequences. Such deletions lead to changes in the number of copies for specific genes on the Y chromosome resulting in male infertility.

Males with Y chromosome infertility have azoospermia or severe, moderate, or mild oligozoospermia depending on the location and size of the Y chromosome deletion . Three common Yq deletions that recur in infertile males are termed as AZF (Azoospermia Factor) microdeletions: AZFa, AZFb and AZFc. Each AZF region contains several genes that play a role in different stages of spermatogenesis:

  • Interstitial or terminal deletions that include all of AZFa are rare and usually result in the severe phenotype of Sertoli cell-only (SCO) syndrome. One single-copy gene (USP9Y) located in AZFa has been directly implicated in the infertility phenotype. Complete deletion of USP9Y has been found in fertile individuals, albeit with hypospermatogenesis, suggesting that SCO syndrome usually associated with AZFa deletion is not caused by USP9Y deletion alone but must include deletion of at least one adjacent gene, DDX3Y, to result in azoospermia. Complete AZFa deletions thus involve loss of two genes, USP9Y and DDX3Y, and result in a much more severe phenotype than mutation of USP9Y alone.
  • Interstitial or terminal deletions that include AZFb and/or AZFb+c (hereafter designated AZFb/c) are uncommon and usually result in severe azoospermia due to mature arrest. Partial deletion of AZFb that removes the entire P4 palindrome decreases spermatocyte maturation but can be transmitted.
  • Interstitial or terminal deletions that include AZFc only result in a variable infertility phenotype, ranging from azoospermia and SCO syndrome to severe or mild oligozoospermia. This type of deletion is common. Eighty-seven percent of males with this deletion will have some sperm either in the ejaculate or at testicular sperm extraction that can lead to successful intracytoplasmic sperm injection.
  • Two partial deletions of AZFc, called b1/b3, b2/b3, are considered benign copy number variants (polymorphisms).
  • Another partial deletion of AZFc, gr/gr, may have some impact on fertility depending on ethnicity and geographic region. Males with gr/gr deletions can also have compensatory duplications of genes. The gr/gr deletion removes two of the four copies of DAZ in the AZFc region, and is a risk factor for oligospermia. The role of DAZ in spermatogenesis is quantitative. Usually the loss of all four copies of DAZ does not prevent some spermatogenesis from occurring because of the compensatory function of DAZL on chromosome 3.
  • AZFd

Most males with AZFa or AZFb/c deletions have a very poor prognosis for finding any sperm with testicular sperm extraction (TESE). Males with AZFc deletions (b2/b4 or gr/gr) have an extremely favorable prognosis (87%) for finding sperm sufficient for successful intracytoplasmic sperm injection (ICSI). he prevalence of Y chromosome deletions and microdeletions is estimated at 1:2,000 to 1:3,000 males. The frequency of Yq microdeletions in males with azoospermia or severe oligozoospermia is about 5%; however, the European infertile men are less susceptible to Yq microdeletions, the highest prevalence is in Americans and East Asian infertile men. In addition, partial deletions of the AZFc locus have been associated with infertility but the effect seems to be ethnicity dependent. Analysis of > 17,000 Y chromosomes from fertile and infertile men has revealed an association of gr/gr deletion with male infertility in Caucasians and Mongolian men, while the b2/b3 deletion is associated with male infertility in African and Dravidian men.

Males with Y chromosome infertility usually have no symptoms other than infertility. A physical examination may reveal small testes in those with Sertoli cell-only (SCO) syndrome. Physical examination is normal in approximately 30% of males with Y chromosome infertility. European and North American guidelines recommend screening in azoospermic and oligozoospermic men with sperm concentrations of <5 million sperm/ml; however, numerous studies have suggested that YCMs are rare when sperm concentrations are >1 million sperm/ml.

A specialized extracellular matrix that surrounds the developing egg (ovum) within the ovary and following ovulation. Following fertilization, the zona pellucida also surrounds the blastocyst during the first week of development, from which the blastocyst then “hatches”. The proteins from which the zona pellucida is assembled have different roles in fertilization. The zona pellucida itself has a role in fertilization, sperm binding, preventing polyspermy, blastocyst development and preventing premature implantation (ectopic pregnancy).

A specific stage in the development of the embryo. A conceptus in which the genetic material (pronuclei) of the egg and sperm have united.

Fallopian Tube Transfer (ZIFT)- A procedure in which eggs are aspirated, are fertilized in the laboratory and surgically transferred into the fallopian tubes before cell division. This procedure has largely been replaced by standard in vitro fertilization (IVF).

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