ORM Dictionary

Adenomyosis is a condition where glands from the uterine lining invade the muscle of the uterine wall. In some respects, adenomyosis resembles fibroids. On occasion, glandular tissue invades a fibroid, resulting in an adenomyoma. It may be suppressed by hormonal treatments and is likely to recur after discontinuation of suppressive treatment. A comparison of adenomyosis and fibroids is listed below:

Adenomyosis

• Poorly defined appearance on ultrasound (a diffuse infiltrative process)

• Asymmetric thickening of the front/back of the uterine wall

• Irregular, streaky shadowing on ultrasound

• Presence of myometrial cyst(s)

• Mainly in women who have given birth before

• Presents with localized uterine tenderness; excessive bleeding with clots is common

Fibroid

• Common in women who have not given birth

• Well defined appearance on ultrasound

• The fibroid causes “fall-out” shadows on ultrasound

• There are no cysts in the uterine wall –Abnormal bleeding is common, but fibroids rarely cause pain by themselves

Ultrasound appearance of the uterus with adenomyosis

The area circled in red indicates the thickened uterine wall affected
by adenomyosis.

In most cases, the actual process of insemination is a simple one, involving monitoring yourself for impending ovulation with a test kit, then undergoing the insemination the following day with an easy, quick, and painless office procedure. There are many potential reasons to pursue donor insemination. For couples, these would include:

• The male partner has a severely decreased or absent sperm count, and the couple wants to avoid performing an ICSI procedure Some men have undergone a vasectomy and therefore cannot father a pregnancy

• The male partner has a significant genetic disorder that he does not want to pass on to his offspring

Insemination provides an excellent opportunity of achieving pregnancy for women without a male partner.

Donors may be:

• Anonymous: Their sperm is carefully screened and stored frozen (“cryopreserved”) by a sperm bank. You select a donor based on physical and other characteristics (age, height, weight, ethnicity, hair color, eye color, complexion, etc.)

• Known: You provide a donor of your choice (perhaps a trusted friend or relative; in the latter case, a genetic link to the male partner may be preserved). The donor is then screened by the sperm bank to protect you.

An article published in the journal Human Reproduction describes the outcomes of over 6,000 artificial inseminations using donor sperm. The results described are not necessarily transferable to other infertility clinics, but they are likely to be similar.

The average pregnancy rate was 12.6% per cycle (month), but it varied greatly depending on the patient’s age.

Of all those who underwent as many as 12 treatment cycles (about one year), 75% conceived.

Of the 1001 women inseminated, 485 conceived at least once, and 442 delivered at least once.

The chance of conception is likely to be between 5 and 20% per cycle.

An article published in the journal Human Reproduction describes the outcomes of over 6,000 artificial inseminations using donor sperm. The results described are not necessarily transferable to other infertility clinics, but they are likely to be similar.

The average pregnancy rate was 12.6% per cycle (month), but it varied greatly depending on the patient’s age.

Of all those who underwent as many as 12 treatment cycles (about one year), 75% conceived.

Of the 1001 women inseminated, 485 conceived at least once, and 442 delivered at least once.

The chance of conception is likely to be between 5 and 20% per cycle.

Eggs obtained after gonadotropin stimulation and follicle aspiration from an anonymous or known individual. Typically used to address insufficient egg production or the lack of egg production in the intended mother.

Embryos are stored in a frozen state for future use. (Liquid nitrogen is used to freeze the embryos.) Excess embryos from IVF typically are frozen at the 2 pronuclear stages (sperm and egg nuclei are not yet joined) or the blastocyst stage (day 5 or 6 of development).

Two to four days after egg retrieval and insemination or sperm injection, embryo quality may be graded.

Embryos are assessed and selected as those most likely to implant in the womb and continue to develop.

This is done by applying a system of grading, using criteria for early-stage embryos, for example:

• The number of cells present

• How fast the cells are dividing

• Whether the division is even

• Whether there are any fragments of cells present

Grading systems vary slightly, but they all produce similar results.

Many believe that embryos with better grades (1 or 2) are more likely to implant than embryos of lower grades (4 or 5).

Endometriosis means the presence of tissue that normally lines the uterine cavity (the endometrium) outside the uterus. The endometrium is usually shed during the monthly menstrual bleeding. In most women, some of this tissue is also transported through the fallopian tubes into the pelvic cavity. In the majority of women, the endometrium then simply dissolves. In some women, however, the endometrium persists or grows in the pelvis, causing pain, scarring, and infertility. Endometriosis can be diagnosed and treated with (laser) laparoscopy. In general, the treatment options for endometriosis are surgical and medical. Surgical options include conservative surgery (preserving your fertility) and more “radical” approaches which are not recommended for women who have not completed their family.

The medical approaches are symptomatic (painkillers) and specific (aimed at reducing or halting endometriosis growth). The specific options are all hormonal, including:

• Birth control pills that may be taken continuously (i.e., skipping the “blanks” at the end of one pill pack and going directly to the next pack, without waiting for a period)

• Depo-Provera

• Danazol (Danocrine)

• Lupron or similar drugs

• Lupron with hormone “add-back”

Lupron is among the most powerful medications available, but it has certain risks and cannot be used for long-term treatment unless combined with hormone “add-back.”

Fibroids are common benign tumors of the uterine muscle. About one-third of all women have fibroids and are diagnosed by a pelvic exam, ultrasound, or HSG (hysterosalpingogram). They may be microscopic or approach the size of a basketball.

Symptoms depend on the size and location of the fibroid. Even small ones, if located inside or near the uterine cavity, may cause excessive bleeding, cramping, infertility, miscarriage, or premature delivery. Larger fibroids, if positioned on the outside of the uterus, may cause minimal or no discomfort. However, they may also cause pelvic pressure, urinary or bowel symptoms, pelvic pain, or low back pain.

Management options include:

• “Expectant” (wait and see approach)

• Surgical removal or myomectomy (by hysteroscopy or laparoscopy, both usually outpatient based

• Laparotomy, which often requires a brief hospital admission)

• Embolization (blocking the blood supply to the fibroid)

Hysteroscopy is surgery on the interior of the uterus. It involves the placement of a hysteroscope (a tube about 1/4 of an inch in diameter through which the interior of the uterus can be viewed) through the cervix into the uterine cavity. It is a minimally invasive outpatient surgery that does not entail the cutting of any normal tissues.

It is suitable for the diagnosis and treatment of many conditions including infertility, painful periods, recurring miscarriage, DES (diethylstilbestrol) exposure, and menstrual bleeding disorders (both excessive and decreased bleeding).

Problems That Can Be Corrected Include:

• Uterine septum (a dividing wall within the uterus that may provoke miscarriage)

• Endometrial polyps (usually benign growths of the uterine lining)

• Submucous fibroids (usually benign growths of the uterine muscle)

• Intrauterine scar tissue

IVF Assisted Reproductive Tech Description

IVF: The oldest of the ART procedures. Louise Brown, the world’s first IVF baby, was born in 1978. IVF involves ovulation induction with gonadotropins, office-based vaginal egg retrieval, fertilization with husband/partner/donor sperm in an incubator, and transfer of the resulting embryo(s) through the cervix into the uterus in a simple office procedure.

IVF was initially developed for couples with infertility due to tubal blockage, but other causes of infertility also respond to this treatment.

GIFT: Ovulation induction is as for IVF. The eggs are then retrieved during ambulatory (outpatient or “band-aid”) surgery, mixed with husband/partner/donor sperm, and returned to the fallopian tube during the same surgery. Due to the surgery, GIFT offers the opportunity of diagnosing and treating problems such as endometriosis and scar tissue.

GIFT requires at least one functioning fallopian tube.

ICSI: This procedure, first described in 1992, has revolutionized the approach to couples with male factor infertility. Even men who produce no sperm in their ejaculate can become biological fathers since very low sperm numbers that can be retrieved from the testicle can be used. This procedure is also useful in men who have undergone vasectomy reversal and who:

• Subsequently have sperm counts too low to allow for natural conception as well as men who discover that the vasectomy reversal has failed, but who cryopreserved (froze) sperm at the time of reversal for possible later use. Overall, the procedure is similar to IVF, except that rather than allowing sperm to burrow into the egg, it is injected into the egg under a microscope.

ZIFT: This is a combination of IVF and GIFT that is only rarely used. Embryos are generated for IVF and transferred to the fallopian tubes as for GIFT.

FET (Frozen Embryo Transfer): Any of the above procedures can yield surplus embryos which can be frozen and later transferred in a simple office procedure, as in IVF.

IVF-ICSI (in vitro fertilization through intracytoplasmic is an advanced form of IVF that allows men with extremely low sperm counts (5-10 sperm) to become biological fathers. Blastocysts are advanced pre-embryos. This is the latest stage (5-6 days from fertilization) at which pre-embryos can be grown in incubators before they have to implant in the uterus. Delaying transfer of pre-embryos to this stage enables us the maximum observation period to ascertain optimal development.

Frequently, a couple desiring fertility after female sterilization (tubal ligation or getting one’s “tubes tied”) is faced with the option of either undergoing a surgical procedure (sterilization reversal, or tubal anastomosis) or IVF (in vitro fertilization).

The following table may be a starting point for a discussion with your physician about the advantages and drawbacks of the two approaches.

This includes minimally invasive outpatient surgical techniques (“band-aid surgery”) suitable for the diagnosis and correction of many problems, including infertility, pain, endometriosis, pelvic scar tissue, ectopic pregnancy (a pregnancy that is implanted in the fallopian tube or elsewhere other than the uterine cavity), as well as others.

Process

Typically, the patient arrives at the outpatient surgical center about one hour before the scheduled start of the procedure. She will be interviewed by the nursing and anesthesia staff and prepared for surgery. The patient is then taken to the operating room, and anesthesia is started. A small (1/2 inch) incision is made in or near the navel (belly button) and a laparoscope (or endoscope; a hollow tube with a small camera attached that is connected to a TV monitor) is introduced. The surgeon examines abdominal and pelvic organs, and one or more additional incisions may be made, typically 1/4 inch (but up to 1 inch) in size, in the lower abdomen.

The surgical procedure usually takes 1/2 to 2 hours. Anesthesia is then stopped and the patient is taken to the recovery room, usually for about one hour. She then returns home, where recovery is usually complete within 3-7 days.

The menstrual cycle begins with the first day of one period and ends with the first day of the next. It tends to be 25 to 35 days in length, with an average of about 28 days. Ovulation occurs on or around day 14. The time from the onset of the period to ovulation is known as the “follicular phase,” a time characterized by estrogen production and follicular growth (a follicle is an area in the ovary where an egg grows). Estrogen promotes the growth of the endometrium or the uterine lining.

The time from ovulation to the onset of the next period is known as the “luteal phase,” during which the “corpus luteum” (yellow body; the area where the egg was released) makes progesterone. Progesterone prepares the uterine lining for embryo implantation, which occurs about a week after ovulation (cycle day 21 to 22).

Some experts believe that luteal phase deficiency (a short luteal phase, insufficient progesterone production by the corpus luteum, or poor responsiveness of the endometrium to normal progesterone levels) may cause infertility; others believe that while LPD occurs occasionally, it is unlikely to be a persistent cause of infertility.

A commonly accepted treatment of LPD — clomiphene citrate — is so frequent a first choice in the treatment of infertility from a great variety of causes, that the diagnosis of LPD may become moot. Diagnosis requires the performance of endometrial biopsies in three consecutive months — an approach that is time-consuming, costly, and occasionally uncomfortable.

This term usually refers to the occurrence of an isolated (single) miscarriage. It is distinct from “habitual abortion” or “recurrent pregnancy loss” (RPL).

Most miscarriages appear to be due to genetic problems in the baby. The risk of miscarriage among previously infertile women who have conceived is similar to that among women without fertility problems and is generally quoted to be between 10 and 20% of recognized conceptions.

Because miscarriages are relatively common, and because a single miscarriage does not predict the occurrence of another, it is not usually appropriate to launch a diagnostic evaluation into the cause of an isolated miscarriage. The genetic causes that underlie many isolated miscarriages are usually genetic “accidents,” without pre-disposing parental or environmental factors.

Once a baby’s heartbeat has been documented by ultrasound (usually at 6-8 weeks of pregnancy), the risk of miscarriage is much reduced.

The cause of infertility does not appear to affect the risk of miscarriage. More than 80% of all miscarriages occurred before 12 weeks of gestation – in other words, once the first trimester of pregnancy is completed, the risk of miscarriage becomes very small.

The risk of miscarriage and chromosomal abnormality of an embryo or baby increases with parental age, especially that of the mother. However, paternal age also plays a role. Various studies have shown increased risks of pregnancy loss with fathers older than 35, 45, or 50 years.

Maternal age has a more profound effect on a baby’s genetics than paternal age, particularly with respect to Downs Syndrome.

PCOS probably is the most common cause of anovulation (lack of ovulation, or egg production), and is a common cause of infertility.

PCOS is characterized by some or all of the following:

• Lack of ovulation, leading to infertility

• Increased levels of male hormones (“androgens”)

• A tendency towards undesired facial hair growth and acne

• Insulin resistance and tendency towards diabetes

• Multiple small ovarian cysts

• Increased risk of miscarriage

• Increased weight

• An inversion of the normal LH/FSH ratio (LH is luteinizing hormone and causes ovulation and progesterone production; FSH is follicle stimulating hormone and causes egg development and estrogen production)

• Increased risk of endometrial cancer (the endometrium is the uterine lining)

Treatment:

If pregnancy is desired, there are the following options to cause ovulation (some of these may be used in combination):

• Anti-estrogens (clomiphene)

• Gonadotropins o metformin, rosiglitazone (Glucophage, Avandia; insulin-lowering agents.

• Anti-androgens (agents that lower androgen levels)

• Gonadotropin releasing hormone agonists (GnRHa, for example, Lupron)

• Ovarian drilling ( “wiffle ball”)

If pregnancy is not desired, there are the following options (this is not necessarily an inclusive list):

To reduce the risk of endometrial cancer:

• Birth control pills

• Cyclical progesterone (for example, medroxyprogesterone acetate [MPA], e.g., Provera)

PGD allows for the diagnosis of genetic problems before the embryo implants into the uterus. Examples of disorders preventable by this process include:

• Breast cancer mediated by BRCA mutations

• Canavan Disease

• Chromosomal anomalies

• Cystic Fibrosis

• Down Syndrome (Down’s Syndrome)

• Fragile X Syndrome

• Hemophilia and other sex-linked conditions

• Huntington Chorea (Huntington Disease, Huntington’s Disease)

• Kennedy Disease

• Sickle Cell Disease

• Tay Sachs Disease

• Turner Syndrome

• Many other heritable diseases

PGD can also be used for sex selection, either to heighten the accuracy of sperm sorting or as a stand-alone technique.

Lastly, PGD has been used to help in the conception of HLA (human leukocyte antigen) compatible offspring to aid in the generation of stem cells for transplantation into a sibling with a fatal disease, such as leukemia.

The process of PGD requires the removal of a single cell from a preimplantation embryo (total size: 1/250th of an inch, or 1/10th of a millimeter).

Once it has been determined that an embryo is free of specific genetic defects, it can be transferred to the uterus, thereby greatly reducing the probability of conceiving a baby with those genetic problems for which screening was done.

This term refers to the loss of ovarian function, including ovulation, before age 40. Other expressions used to describe POF are “Ovarian Insufficiency” and “Hypergonadotropic Hypogonadism.”

POF is distinct from “diminished ovarian reserve,” which implies reduced ovarian function without loss of ovulation.

Ovarian failure leads to menopause (cessation of periods). Whereas the average age at menopause is around 51 years, POF affects about 1 out of 100 women.

Possible causes of POF

• heritable

• gene mutations

• chromosome abnormalities -including but not limited to fragile X syndrome

• autoimmune (the immune system attacks the ovaries and possibly also other organs)

Women with POF occasionally recover ovarian function, and 5-10% of affected women may even conceive, although miscarriage rates may be higher than average. There is no proven treatment to reverse POF. Women who do not desire pregnancy may benefit from hormone replacement or other therapies. Those who wish to conceive may succeed through the use of donated eggs.

Diagnostic criteria include the absence of menstruation for more than 4 months before age 40 and an FSH (follicle-stimulating hormone) level greater than 40 mIU/mL, obtained on at least 2 occasions at least one month apart.

This term usually refers to the occurrence of two or more consecutive pregnancy losses. It is sometimes also called “habitual abortion” (the medical term used for miscarriage is “spontaneous abortion”).

Causes for recurring pregnancy loss (RPL) may be:

• hormonal

• anatomic

–uterine problems, such as hysteroscopy

–tubal problems; in this case, a patient may have repeated tubal

pregnancies, although this circumstance is not always recognized by the

patient or her physician

• blood clotting problems (thrombophilia), including the antiphospholipid (APL)

syndrome

• genetic

–embryonic (common); some of these may be random.

Others may be related to parental age

–parental (rare)

• infectious

• environmental factors, such as smoking, caffeine, alcohol, medicines,

chemicals, radiation

• immune

–autoimmune (inappropriate immune responses to your own body’s

components)

–alloimmune (inappropriate immune responses to those components of the

baby that are derived from the father. See our News Page for an FDA

statement and articles on treatments using lymphocytes and intravenous

immunoglobulins).

• metabolic (uncontrolled diabetes)

• combinations of the above

• unknown

At times, it may be desirable to select the gender of a child before conception. Many methods have been proposed to attain this objective. These methods may be based on differences of timing, acidity, sperm motility or density, and sperm genetic composition. The latter is by far the most reliable method and allows purification of male sperm to approximately 70%, and female sperm to 80-85%.

Sperm are separated by fluorescence-activated cell sorting at an accredited laboratory facility. The sperm thus purified can be used for intrauterine insemination (IUI), in vitro fertilization (IVF), or intracytoplasmic sperm injection (ICSI). Because of the low sperm numbers usually obtained, most procedures use intracytoplasmic sperm injection.

Shettles’ Method

(This chart reproduced here is for reference purposes only. We believe that adherence to these methods may decrease your chances of conception, without improving the odds of having a child of the gender of your choice. Note that caffeine has been linked to miscarriage, and douching has been linked to tubal damage and infertility).

“Shettles’ Method”

We also refer you to an article, Timing of Sexual Intercourse in Relation to Ovulation — Effects on the Probability of Conception, Survival of the Pregnancy, and Sex of the Baby, in the New England Journal of Medicine, that has shown that “for practical purposes, the timing of sexual intercourse in relation to ovulation has no influence on the sex of the baby.”