There are many services and approaches required for infertility treatments. This section offers definitions of those most commonly used by ARMS.
Andrology evaluation/semen analysis
Most men produce millions of sperm each day, however, many of these may be abnormal either in their shape, movement, or function. Many studies have shown that 50% of infertility is related to the sperm. An andrology evaluation of the male provides much of the data needed to assess the male’s fertility potential. Tests assess the number, appearance, movement, and functional capacity of the sperm present in the man’s specimen.
Anesthesia during egg harvesting/recovery
For each egg retrieval, patients undergo the egg harvesting procedure in our center under intravenous sedation. Not only is this environment more comforting and convenient, there is the added benefit of not incurring hospital fees. Our patients arrive at our IVF center approximately one hour before the scheduled time of retrieval. Recovery in our center is usually about an hour, after which our patients are sent home. Other than feeling a little sleepy from the anesthesia, most of our patients do very well and need little pain medication.
Assisted reproductive technology (ART)
Although various definitions have been used for ART, the definition includes all infertility treatments in which both eggs and sperm are handled. In general, ART procedures involve surgically removing eggs from a woman’s ovaries, combining them with sperm in the laboratory, and returning them to the woman’s body or donating them to another woman. They do NOT include treatments in which only sperm are handled (i.e., intrauterine—or artificial—insemination) or procedures in which a woman takes medicine only to stimulate egg production without the intention of having eggs retrieved.
Assisted hatching involves the use of mechanical or chemical thinning of the outer shell of the fertilized egg prior to transfer into the uterus. The technique of assisted hatching was introduced to enhance the embryo’s ability to hatch and implant after transfer. The outer shell becomes thicker and hardened with aging of the primitive egg cell, called an oocyte. As such, women of advanced age, or with an elevated follicle-stimulating hormone (FSH) level may have decreased chance for embryo implantation. The embryos of women with endometriosis and poor quality embryos also may have this problem. The technique of assisted hatching involves measuring the thickness of the outer shell in embryos that are candidates for the procedure. If an embryo has not initiated the thinning process naturally, a small “window” is created chemically in the wall of the protein coat using a dilute acidic solution pulsed onto the embryo surface through an extremely fine glass needle. The embryos are then implanted normally into the uterus.
Baseline follicle count
There are several ways that we try to predict “egg quantity and quality” as well as trying to estimate chances for conception with various forms of fertility treatment. Antral follicle counts performed at the beginning of a cycle (in conjunction with female age) are used for estimating the number of eggs in reserve and/or chances for pregnancy with in vitro fertilization (IVF). Antral follicles are small, fluid-filled sacs in the ovary that nurtures and finally releases the developing egg (or ococyte) during ovulation. These follicles can be counted via an ultrasound. The number of visible antral follicles is indicative of the relative number of microscopic developing egg-bearing follicles remaining in the ovary. Each primordial follicle contains an immature egg that can potentially develop in the future.
Blastocyst (embryo) culturing
Blastocyst culturing is a technique to grow embryos beyond the third day of culture. On the third day, embryos generally are between six to eight cells. In this process, embryos are kept two to three additional days in a culturing material before implantation in the uterus. During this additional culture period, the embryos continue to grow until the embryo reaches the “blastocyst” stage, when it is ready to implant. In certain patients, blastocyst culturing allows optimal selection of embryos for transfer, resulting in an increased implantation rate. It also allows fewer embryos to be transferred to eliminate the possibility of triplet and quadruplet pregnancies, while maintaining a high pregnancy rate.
Body mass index (BMI)
Body mass index (BMI) is a measure of body fat based on height and weight that applies to both adult men and women.
Challenge test (CCCT)
The number of eggs in the ovary naturally declines as a woman ages and approaches the menopause. However, diminished reserve can occur in younger women. Patients with this condition have a lower chance of conceiving in general and a shorter amount of time left to try to conceive.
In standard infertility treatments evaluation, levels of the hormones FSH, LH, and estradiol are measured on day 3. An elevated FSH level on day 3 is one indication of poor ovarian reserve or that the menopause is approaching.
The clomiphene citrate challenge test (CCCT) provides an additional assessment of the “quality” of the eggs remaining within the ovaries. It is performed by measuring the day 3 FSH and estradiol levels, the patient takes 100 mg of Clomid on cycle days 5-9, and her FSH is measured again on day 10. The test is abnormal if either the day 3 or day 10 FSH values are elevated or if the day 3 estradiol is greater than 50 to 75 pg/ml.The normal test would show a low FSH on day 3, a low estradiol on day 3 and also a low FSH on day 10. Cut off values for the day 3 and the day 10 FSH values are very lab dependent and must be determined by experience with the laboratory being used. In other words, only your infertility specialist can interpret your results. This will confirm that your hormone levels are low and that your ovaries are ready to be stimulated.
In this procedure, eggs are obtained from the ovaries of another woman (donor), fertilized by sperm from the recipient’s partner, and the resulting embryos are placed in the recipient’s uterus. Older women and women who experience premature menopause are candidates for IVF using donor eggs.
In this procedure, sperm from another male one individual is donated to fertilize the harvested or retrieved eggs of the woman recipient. The resulting embryos are placed in the recipient’s uterus. The most common reasons for using donor sperm are that the recipient’s partner may be infertile or he may carry a genetic disease.
Embryo cryopreservation or freezing is a well-established form of assisted conception treatment. An increasing number of IVF clinics worldwide are now able to freeze spare embryos for later transfer. The first frozen embryo baby was born in 1984. Embryo cryopreservation allows multiple embryo transfers from a single egg collection and improves the chances of live birth.
Embryo Quality Assessment
The major components in assessing the “quality” or viability of embryos are cell number, cell size regularity and the amount of fragmentation. Other criteria include appearance, such as multinucleation, presence of vacuoles, granularity, thickness of the shell around the embryo among others. These observed characteristics do not, however, account for the true genetic potential of the embryo to continue development, the acceptance level of the uterine lining and the embryo transfer technique itself.
Embryo transfer for routine IVF is usually performed 3 or 5 days after the sperm and eggs have been mixed (insemination) and the embryos have grown to 6-8 cells (day 3) or the blastocyst stage (day 5 or 6). Typically, the selection process used to identify the most suitable embryos for transfer at this very early stage of their development relies on criteria relating to the appearance of the embryo. Culturing embryos to blastocyst allows the embryologist to better select the best embryo(s) for transfer.
A hormone released by developing follicles in the ovary. Blood plasma estradiol levels are used to help determine progressive follicular growth during ovulation induction. A high value for FSH or estradiol may predict a poor outcome of the IVF cycle.
In Vitro Fertilization (IVF) involves the harvesting of eggs right before ovulation occurs. After medication has been given to increase the number of eggs produced, the eggs are extracted. The eggs are combined with sperm so that fertilization might occur. Within a few days of fertilization the fertilized eggs are placed back into the uterus, so that implantation can take place.
Follicle-stimulating hormone (FSH)
Women are born with their lifetime supply of eggs within the ovaries. Each month follicles, each of which contains one egg, are recruited under the influence of follicle stimulating hormone (FSH). One follicle will become dominant, develop to maturity, and be ovulated. There are several ways to predict “egg quantity and quality” as well as trying to estimate chances for conception with various forms of fertility treatment. Female age and FSH levels are two very important variables. The response of the ovaries to ovarian stimulation with inject-able gonadotropins (a synthetic type of FSH) is another very important variable that affects the overall chance for conception when we attempt in vitro fertilization.
A hydrosalpinx is a blocked, dilated, fluid-filled fallopian tube usually caused by a previous tubal infection. The pelvic infections that lead to hydrosalpinx formation are usually caused by sexually transmitted diseases. Diagnosis of hydrosalpinx is usually made by a hysterosalpingogram (HSG), an x-ray procedure in which a special liquid is injected through the cervix into the uterine cavity to illustrate the inner shape of the uterus and degree of openness of the fallopian tubes. If the tubes are open, the liquid will spill out the ends of the tubes (Figure A). If the tubes are blocked, the liquid is trapped. Hydrosalpinx may also be diagnosed by laparoscopy, which is the insertion of a thin, telescope-like instrument called a laparoscope into the abdomen through an incision to visually inspect the tubes. They may also be visualized by ultrasound.
- FSH (follicle stimulating hormone)
- LH (luteinizing hormone)
- E2 (estradiol)
- TSH (thyroid stimulating hormone)
Infectious disease screening
Both the American Society for Reproductive Medicine (ASRM) and the Human Fertilization and Embryology Authority (HFEA) require full screening of the donors of both egg and sperm. Donors should be screened for infectious diseases such as HIV, Hepatitis B and C, Cytomegalovirus and syphilis. Donors may also be screened for genetic diseases such as cystic fibrosis carrier and the karyotype. Their blood group and Rhesus (Rh) status can also be determined. In addition, in appropriate ethnic groups, screening for sickle cell and thalassaemia is recommended. There is always the possibility that one or more of these tests may reveal a previously unsuspected condition or infection. All prospective donors should consider this carefully before giving permission to these tests.
An initial consultation includes meeting your ARMS IVF physician and other members of your care team and a review of fertility history, medical, surgical and family histories with and If necessary, determining which initial tests are needed for an accurate diagnosis. This session will also likely begin creation of an integrated treatment plan to address the infertility condition and will provide answers to any questions the patient has about the process. A meeting with our financial coordinator will also review costs, refund programs, insurance coverages and financing programs available. The initial consulation may be covered by insurance. (See Preliminary Testing / Pilot Cycle.)
Intracytoplasmic sperm injection (ICSI)
Intracytoplasmic sperm injection (ICSI) is a method of assisted reproduction that involves combining an egg with sperm in a laboratory dish. It utilizes the direct micro-injection of a single sperm into a single egg in order to assist fertilization. If the egg fertilizes and begins cell division, the resulting embryo is transferred into the woman’s uterus where it will hopefully implant in the uterine lining and further develop. IVF may be performed in conjunction with medications that stimulate the ovaries to produce multiple eggs in order to increase the chances of successful fertilization and implantation.
In vitro fertilization (IVF)
Typical steps or phases in IVF treatment include:
- Consultation with the doctor
- Consultation with the nurse or medical assistant
- Pre-cycle blood tests
- Pre-cycle sperm test
- Pre-cycle mock embryo transfer
- Pre-cycle assessment of a normal uterus (womb)
- The down regulation phase
- The ovarian stimulation phase
- The ocoyte (egg) retrieval
- The pre-embryo transfer consultation
- The embryo transfer
- The post embryo transfer phase
- The initial pregnancy test
- The post “in vitro” consultation
- The referral to the obstetrician/gynecologist
Mock embryo transfer
The mock or “practice” embryo transfer is a special examination during which a soft plastic catheter is passed through the cervix and into the womb in order to make a detailed map of the course of the cervix and the depth of the womb. This is done so that the actual transfer of the embryos can be performed without difficulty . Many patients describe the procedure as feeling like a routine “pap” smear or exam. It is best if the initial attempt at the mock embryo transfer is done with a moderately full bladder. The bladder is usually full enough when the patient senses that she could void, but can defer voiding without discomfort.
OB ultrasound monitoring
Ovulation induction is based on the administration of gonadotropins in order to enhance fertility. Daily administration of the drug causes an increase in serum FSH leading to the recruitment of an increased number of egg-producing follicles, which causes their growth and development, and finally, triggering ovulation of usually more than one follicle. The monitoring process is intended to enable the physician to choose the most suitable protocol, to obtain best possible outcome, and trying to avoid complications. Monitoring of stimulation can be done mainly by means of ultrasound, with some additional monitoring measures at various points of the treatment if necessary. Non-invasive ultrasound monitoring has been found to both increase both cost-effectiveness and patients’ convenience.
Gonadotropins are reproductive hormones. The two principal gonadotropins are luteinizing hormone (LH) and follicle stimulating hormone (FSH). Synthetic gonadotropins are fertility drugs given by injection to stimulate the to produce many egg-bearing follicles. They are similar in composition to the natural FSH and LH produced by the pituitary gland.
A hormone secreted by the pituitary gland in the brain that stimulates the growth and maturation of eggs in females and sperm in males. This pituitary hormone works in concert with FSH. FSH starts the development of the egg, and LH finishes the development and starts progesterone production. FSH is important to stimulate the cells of the follicle to produce Estrogen. LH is important to stimulate the cells of the follicle that produce Progesterone during the second half of the menstrual cycle. A certain ratio of FSH to LH tells the ovary when to release the egg (ovulation).
This treatment uses oral medications containing hormones to induce ovulation. Typical medications used for ovulation induction include:
- Clomiphene Citrate — Seraphene and Clomid
- Human Menopausal Gonadotropin (hMG) — LH/FSH (Pergonal, Humegon, Repronex)
- Follicle Stimulating Hormone (FSH)
- Human Chorionic Gonadotropin (hCG) — Profasi or Pregnyl
- Leuprolide (Lupron) and Synthetic Gonadotropin (FSH/LH) Inhibitor
As a woman ages, the eggs she developed before birth are being lost through menstrual cycles and general degeneration of the egg-bearing follicles, the ovaries become smaller. Using trans-vaginal ultrasound, the volume of each ovary can be calculated by measuring the length, width and depth. Determining the ovarian volume, ovarian reserve, ovary size, time to menopause, reproductive age can calculate a woman’s “reproductive age”. Her reproductive age may be older or younger than her actual age.
The sexual glands of the female which contain the eggs and which produce the reproductive hormones, estrogen and progesterone
Post pregnancy progesterone level monitoring
The human pregnancy hormone, human chorionic gonadotropin (HCG) is first found in a pregnant woman’s blood as early as 7 to 8 days after conception. As a pregnancy proceeds, the production of HCG increases. Measurements of HCG levels can be useful during the early weeks before the fetal heartbeat is seen on ultrasound, usually around 6-7 weeks after last menstrual period, or 4-5 weeks after conception.Pregnancies that will miscarry and ectopic (tubal) pregnancies are likely to show lower levels and slower rises, but often have normal levels initially. Since normal levels of HCG can vary tremendously, after 5-6 weeks of pregnancy, sonogram findings are much more predictive of pregnancy outcome than are HCG levels. Once fetal activity has been detected by ultrasound, the chance of miscarriage is usually less than 10%.
Pre-implantation genetic testing/diagnosis
The preimplantation genetic testing procedure can identify genetically defective human embryos before further development. This is usually requested by prospective parents who are concerned about passing an incurable genetically based disease or disorder to their child. Typically one or both partners have been genetically screened previously, and found to be a carrier. This technically demanding and complex procedure was developed only recently. Currently, ARMS is one of only a few clinics worldwide to offer the procedures screening for genetically determined diseases includes:
- adenosine deaminase deficiency
- alpha-1-antitrypsin deficiency
- Alzheimer disease (aap gene)
- beta thalassemia
- cystic fibrosis
- epidermolysis bullosa
- Fanconi anemia
- Gaucher disease
- hemophilia a and b
- Huntington disease
- muscular dystrophy (duchenne and becker)
- myotonic dystrophy
- neurofibromatosis type i
- OTC deficiency
- retinitis pigmentosa
- sickle cell disease
- spinal muscular atrophy
- Tay Sachs disease 11
- fragile x syndrome
- Lesch-nyhan syndrome – retinitis pigmentosa
- Charcot-marie-tooth disease
- Barth’s syndrome
- Turner syndrome
- Down’s syndrome
- Rett’s syndrome
Female ova can be also be checked for a gene that increases the propensity to develop breast cancer. Some genetic diseases are sex-linked. For example, some are known to only be passed on to male children. Even if a particular sex-linked disease cannot be detected directly, the PGD method can eliminate all of the male embryos and implant only female embryos, thus preventing the transmission of the disease.
Preliminary testing/pilot cycle
Upon starting infertility treatments, your ARMS physician may order some investigations before proceeding with treatment, often including:
- Semen analysis for men who have difficulty in producing semen samples on demand. The doctor may recommend that semen is produced at a convenient time and then frozen and stored prior to IVF treatment as a ‘back up’ just in case the male partner is unable to perform on the day of egg collection.
- Blood hormone tests to assess the female partners response to fertility drugs.
- Blood test to check for immunity to German measles.
- In some women, hysteroscopy or HSG may be ordered to inspect the uterine cavity.
- Screening for chlamydia infection is usually considered if the patient is at risk.
- Screening both partners for HIV, hepatitis B and Hepatitis C
It is necessary to take certain medications during the IVF cycle in order to prepare the body for the infertility treatments. The instructions for each medication vary from patient to patient. Your ARMS medical team will analyze your case closely to determine which medications to use, what dosage to take, when to administer the medications and how long to take them. Typical medications may include:
- GnRH Agonists – Lupron, taken as an injection just below the skin and Synarel, a nasal spray, allow the body to produce a greater number of high quality eggs during the treatment cycle. They also prevent the midcycle hormonal surge that can result in the cancellation of a cycle.
- Antagonists – Antagon and Cetrotide are antagonists of gonadotropin releasing hormone (GnRH) and are used to prevent premature ovulation. These medications are given by injection and the duration of treatment is usually three or four days.
- Gonadotropins – Gonadotropins are taken as subcutaneous injections that provide stimulation to the follicles that contain the eggs during the stimulation phase. Gonal F, Bravelle, Follistim, Pergonal and Repronex are the most commonly used gonadotropins.
- hCG – hCGs are taken as an intramuscular injection and are used to induce the final maturational changes in the eggs and prepare them for retrieval. The most commonly prescribed hCGs are Pregnyl, Profasi and Novarel.
- Medrol – Medrol is a steroid hormone given daily, typically for a period of four days during the cycle, to assist pre-embryo implantation.
- Doxycycline – Doxycycline, an antibiotic administered in pill form, is given to the male partner during the wife’s stimulation cycle to further reduce the low levels of bacteria that may be found in the semen and which may compromise the performance of the sperm during an IVF cycle. It is also given to the female partner to reduce the risk of infection following aspiration of the follicles at the time of egg retrieval.
- Progesterone – Natural Progesterone may be taken as a daily intramuscular injection beginning two days after egg retrieval and continuing until the placenta is making adequate amounts of Progesterone. Progesterone can also be given in the form of a vaginal gel or vaginal suppositories or pills (Prometrium).
Recurrent pregnancy loss
Recurrent miscarriage or recurrent pregnancy loss (RPL) is the occurrence of repeated pregnancies that end in miscarriage of the fetus, usually before 20 weeks of gestation. RPL affects about 0.34% of women who conceive. Recurrent pregnancy loss or recurrent miscarriage is the occurrence of 3 consecutive spontaneous miscarriages (spontaneous abortions). The majority (85%) of women who have had two miscarriages will conceive and carry normally afterwards, so statistically the occurrence of three abortions is regarded as “habitual.” There are various causes for RPL including uterine malformation conditions, propensity for blood clots, gene/chromosomal problems in one or both partners, endocrine disorders such as thyroid or diabetes, immune factors, ovarian age and infection among others.
Sperm chromatin structure assay (SCSA)
Sperm chromatin structure assay is a measurement of the proportion of sperm cells that have damaged DNA. Fewer than 15% is consistent with normal fertility; 15%-30% can result in sub-fertility; and more than 30% may cause sterility or recurrent miscarriage.
The sonohyseterosalpingogram/hysterosalpingogram (HSG) process involves the doctor inserting a small tube into the cervical canal. Dye or fluid is inserted through the tube and travels into the uterus and fallopian tubes. An x-ray or ultrasound screen is used to see the progression of the dye as it fills the uterus and moves through the tubes. If either or both tubes are blocked or scarred, this test will help to make that diagnosis.
Sperm quality/type of specimen
About 25% of all infertility is caused by a sperm defect and 40-50% of infertility cases have a sperm defect as the main cause, or a contributing cause. Sperm counts may or may not be indicative of a male fertility issue. Typically a semen analysis will be performed on the male which includes sperm count, motility (sperm’s ability to swim and move quickly), shape and maturity of the sperm cells, volume of semen, pH balance, clumping (potential autoimmunity issues), white/ red blood cell count (potential infections).
Correct controlled ovarian stimulation is of paramount importance in assisted reproductive technologies. Stimulation management consists of careful diagnosis and application of a one or more of a variety of different stimulation protocols to increase ovarian stimulation, for instance, the use of gonadotropin-releasing hormone antagonists in the late egg-bearing follicular phase. Careful recording and analysis of patient response history to these treatments is an important aspect of this task.
To help egg donors understand the egg donation/harvesting process, teaching visits are conducted by one of our trained nursing personnel to brief egg donors on:
- The general IVF process
- About the medications and their side effects.
- How to properly mix and administer the subcutaneous injections that you will be using. (It is recommended that you and the person administering the injections attend this class.)
- The stimulation and monitoring Process
- A review your calendar
- Review and signing of consent forms
- Open forum of questions
- Review of medical and genetic screening
- For married couples we ask that your spouse attends
A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs and make echoes. The echo patterns are shown on the screen of an ultrasound machine, forming a picture of body tissues called a sonogram. This is also called ultrasonography. A portion of the monitoring phase in IVF involves the use of intravaginal ultrasound to track follicular growth. The eggs develop inside fluid-filled cysts of the ovaries called follicles, which enlarge as the eggs mature. Ultrasound studies usually begin after an estrogen response has been measured and continue on a frequent basis until oocyte (egg) retrieval. The ultrasound studies are performed using a vaginal probe. Vaginal sonograms carry no appreciable risk but may cause slight discomfort, particularly as you near the point of ovulation. (See OB Ultrasound Monitoring)