Female Infertility

Blood Tests

Blood tests are the first step in a woman's infertility work-up. They are an easy way for us to identify potential fertility-related problems. Here are some of the tests that your doctor may order:

Hormone-level tests

Follicle-Stimulating Hormone (FSH)

The measure of FSH is essential at the start of an infertility evaluation and prior to any treatment. The FSH level indirectly measures the store of follicles (ovarian reserve) and the eggs (oocytes) remaining in the ovary, and predicts the quality of the remaining oocytes. A high FSH level indicates a diminished quality and quantity of oocytes. To help predict your fertility, your doctor will measure your FSH levels by drawing blood on the second or third day of your menstrual cycle. The FSH test will fall into one of three ranges: normal (<10 microIU/L), borderline (10-12 microIU/L), or abnormal (>12 microIU/L). A borderline result suggests poor ovarian reserve and the need for prompt, aggressive treatment; an abnormal FSH level suggests a very poor ovarian reserve and a markedly low chance for a healthy pregnancy using your own eggs. Please note that FSH lab ranges may vary from institution to institution.

Estradiol (E2)

Estradiol is a type of estrogen. This hormone is produced by follicles in the ovaries. An elevated E2 level on the third day of your cycle could indicate a compromised ovarian reserve despite a normal FSH level.

Progesterone

Progesterone is a major hormone needed to prepare and sustain the uterus for pregnancy. It is produced by the corpus luteum and later, after an embryo develops, by the placenta. This blood test is performed to determine the proper functioning of the corpus luteum. Progesterone controls the development of the lining of the uterus and prepares it for embryo implantation. If progesterone production is inadequate, the endometrium may not be able to sustain the implantation of the embryo. Progesterone testing is usually performed about 7 to 9 days after suspected ovulation.

Prolactin

Prolactin is the hormone produced by the pituitary gland to stimulate the production of breast milk. Elevated prolactin levels (>25 ng/ml) may interfere with fertility.

Thyroid-Stimulating Hormone (TSH)

TSH levels are usually tested to check for thyroid disease, which is common among women. A suppressed level of TSH (<0.35 microIU/ml) is found in hyperthyroid patients, patients on suppressive thyroid medications, or possibly patients with hypothalamic pituitary disease. Conversely, a high TSH level (>5.0 microIU/ml) is consistent with hypothyroidism. Either condition may cause fertility problems by causing hormonal imbalances, leading to anovulation or other problems in a woman's menstrual cycle.

If your doctor suspects problems with ovulation, and especially if polycystic ovarian syndrome (PCOS) is suspected, additional hormone testing may be ordered.

Other blood tests

Additionally, the American College of Obstetricians and Gynecologists recommends that all women considering childbearing undergo testing for the following, so these tests would be routine in any preliminary blood work:

• Blood type
• HIV
• Hepatitis
• Rubella
• Cystic Fibrosis
• Bloodborne infections
• Other genetic screening based on specific risk factors

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Ultrasound

Ultrasound, or sonography, involves sending sound waves into the body. These sound waves are reflected off the internal organs, and the reflections are then recorded by special instruments that create an image of the organs. No ionizing radiation (X-ray) is involved in ultrasound imaging.

With transvaginal ultrasound, the ultrasound transducer (a hand-held probe) is inserted directly into the vagina. Transvaginal ultrasound is most commonly used to examine the uterus and ovaries and to monitor the health and development of the embryo during pregnancy. Ultrasound images can help to identify palpable masses such as ovarian cysts and fibroids, as well as ovarian or uterine cancers. IVF cycling patients are checked regularly with a transvaginal ultrasound to monitor the size and number of developing follicles.

Transvaginal ultrasound is performed very much like a gynecologic exam. The tip of the transducer is smaller than a gynecologic speculum. A protective cover lubricated with gel is placed over the transducer, which is then inserted into the vagina. Only two to three inches of the transducer end are inserted into the vagina. The images are obtained from different orientations to get the best views of the uterus and ovaries.

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Hysterosonogram

Hysterosonogram, also called a sonohysterogram, is a test to study the inner surface of the uterus. An ultrasound is performed using a vaginal probe, and at the same time saline solution is injected into the uterus through a thin catheter. This helps delineate the inner contents of the uterus. Lumps called submucosal fibroids or polyps cannot be seen well without the injection of saline solution. This test is used to find out the cause of heavy periods and to investigate infertility and repeated miscarriages.

It is best to have the procedure during the second week (days 7 to 12) of your menstrual cycle. This timing reduces the chance that you may be pregnant during the procedure, and makes it easier to view the folds of the uterine cavity. Hysterosonograms are not usually uncomfortable, but if you are sensitive to pain or cramping you can ask your doctor about taking pain medication such as Tylenol or Ibuprofen. The test involves the following steps:

1. An ultrasound probe is placed in the vagina to inspect the uterus and ovaries.
2. A speculum is placed in the vagina and the doctor examines the cervix. The cervix is cleaned with antibacterial soap. A thin, soft tube of about 1-2 mm in diameter is placed in the cervix.
3. The vaginal probe is reinserted into the vagina.
4. Water is injected into the uterus through the soft tube. The fluid causes the uterus to stretch. This may cause uterine cramping.
5. The doctor spends about 3-5 minutes examining the uterine cavity and wall.
6. A small sample of tissue is sometimes obtained from the lining of the uterus at the end of the procedure, to rule out the presence of abnormal cells.

Your doctor will discuss the results of the hysterosonogram with you after the procedure. Based on the results, further tests may be needed. If a problem is detected, a treatment plan will be discussed with you.

A very few women have minor side effects after a hysterosonogram. These are not serious and usually go away after a day or two. Side effects may include cramps, slight vaginal bleeding, and sticky vaginal discharge as some of the gel and fluid drains out. A pad can be used for the vaginal discharge. Do not use a tampon.

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Hysterosalpingogram (HSG)

Hysterosalpingogram is a procedure in which radiographic contrast (dye) is injected into the uterine cavity through the vagina and cervix and X-ray pictures are taken as the dye is expelled from your reproductive system. The uterine cavity fills with dye, and if the fallopian tubes are open, the dye will then fill the tubes and spill out into the abdominal cavity. In this way we can determine whether the fallopian tubes are open or blocked and whether the blockage is located at the junction of the tube and the uterus (proximal) or whether it is at the end of the fallopian tube (distal). If a blockage is detected, we will discuss with you effective treatments for tubal factor infertility. Your HSG can also give us a better picture of the uterine cavity and detect the presence of polyps, fibroids, or scar tissue. The fallopian tubes can also be examined for defects within the tube or suggestion of a partial blockage.

The hysterosalpingogram takes only about 5 minutes to perform. During the procedure you are likely to experience some mild cramping, so you may wish to ask your doctor about taking pain medication such as Tylenol or Ibuprofen a half hour prior to the HSG . The test involves the following steps:

1. The doctor places a speculum in the vagina and examines the cervix. Your cervix is cleaned with an antibacterial soap.
2. A clamp may be attached onto your cervix to hold it steady. A small, bendable plastic tube is gently pushed through the opening of your cervix into your uterus, and a tiny balloon on the end of the tube is filled with air to hold it temporarily in place.
3. The speculum is removed but the thin tube will be left in place, with one end (about 6 inches of tubing) remaining outside of your vagina.
4. A small amount of contrast dye is injected through the tube into your uterus, and several X-ray pictures are taken. Your doctor may ask you to move your pelvis slightly or roll from side to side to provide the clearest view of your uterus. You may experience some uterine cramping as the contrast dye goes into the tube.
5. The procedure is now complete. The balloon will be emptied of air from the outside and the tube will be gently pulled out.

After the procedure, your doctor will review the X-ray pictures and discuss the results of the hysterosalpingogram with you.

You may experience slight vaginal bleeding and cramping after the procedure, and some sticky vaginal discharge as some of the gel and fluid drains out. A pad can be used for the vaginal discharge. Do not use a tampon.

Pregnancy rates in several studies have been reported to be slightly increased in the first months following a hysterosalpingogram. This may be due to the flushing of the tubes with the contrast, which could open a minor blockage or clean out some debris that may be hindering conception.

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Hysteroscopy

Hysteroscopy is a diagnostic and operative procedure performed with an instrument called a hysteroscope, which is a thin telescope that is inserted through the cervix into the uterus allowing better visualization of the uterine cavity. Hysteroscopy allows the doctor to clearly make out fibroids, polyps, and other problems that may be causing excessive menstrual bleeding and/or infertility.

Hysteroscopy is performed soon after menstruation because the uterine cavity is more easily evaluated early in the menstrual cycle and there is no risk of interrupting a pregnancy at this time.

During the procedure, an anesthesiologist administers light anesthesia (conscious sedation) to the patient, through an intravenous drip (IV). Hysteroscopes are so thin that they can often fit through the cervix with minimal or no dilation. The doctor will inject saline solution to expand the uterine cavity, clear blood and mucus away and view the internal structure of the uterus directly through the hysteroscope. If abnormalities such as fibroids, polyps, scar tissue, adhesions, or a congenital defect such as a Uterine Septum are detected, they may be corrected at this time through the hysteroscope.

The procedure usually takes about 30 minutes. It is performed on an out-patient basis and the recovery time is short, usually the same day.

** You should not eat or drink for at least 8 hours prior to a hysteroscopy.

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Laparoscopy

Laparoscopy is the final diagnostic procedure of an infertility evaluation. It is performed in a hospital, under general anesthesia. Gas (carbon dioxide or nitrous oxide) is used to inflate the abdomen via a tiny incision in the lower pelvis. This is done to push the abdominal wall away from the organs, allowing better visualization during surgery. A tiny telescope (laparoscope) connected to a camera, is then inserted through a small incision in the umbilicus, and the internal organs are examined. Laparoscopy is used to better diagnose pelvic disorders, adhesions and endometriosis. Surgical repair can often be accomplished at the time of a diagnostic laparoscopy by inserting tiny instruments through the scope.

The procedure usually takes about 1 hour. Based on the diagnosis and extent of surgical repair, a laparoscopy can be performed on an out-patient basis. Recovery time depends on the extent of repair, but is usually within a week. When the operation has been completed, the abdominal incisions are closed with a few stitches that will dissolve. There is little or no scarring. After the surgery you may experience pain in your shoulder which can be a side effect of the gas used to inflate the abdomen, dissipating from the body.

** You should not eat or drink for at least 8 hours prior to a laparoscopy.

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Ovulation Induction

Ovulation induction is used to treat female-factor infertility. Ovulation induction helps a woman to produce and release healthy, mature eggs (often more than one at a time) on a predictable schedule with the aid of fertility medication therapies. Initial therapy may include oral tablets taken for a few days (clomiphene citrate). However, not all women are considered good candidates for clomiphene citrate ovulation induction treatment.

Another ovulation induction therapy may require the use of injectable fertility drugs, which are similar to hormones found in the body, but administered in higher doses than are produced naturally. Again, the effect is to promote the release of mature eggs on a known schedule, increasing the chances of pregnancy.

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Intrauterine Insemination (IUI)

Intrauterine insemination uses injectable fertility drugs or oral medications (clomiphene citrate) to stimulate the release of mature eggs on a known schedule. At maturation, a semen specimen is obtained and placed into a catheter, which is positioned into the woman's uterus, where the semen is released. This places the sperm closer to the egg, allowing for easier fertilization.

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In Vitro Fertilization (IVF)

In vitro fertilization is an option for many people who cannot conceive naturally or who have failed to conceive after attempting ovulation induction therapy. IVF in its simplest terms is the process of stimulating the ovaries into producing multiple mature eggs, retrieving them from the ovaries, combining the eggs with sperm in the laboratory and once fertilization occurs, transferring the early embryos back into to the woman's uterus. Recently the American Society of Reproductive Medicine has recommended IVF as the first line of therapy for several types of infertility patients. The patient's diagnosis and history are the primary determining factors in choosing the appropriate course of treatment.

Various medications are given during an IVF cycle, and your own drug protocol will be highly individualized based on your unique medical history.

The IVF cycle consists of the following five stages:

1. suppression
2. stimulation
3. retrieval
4. transfer
5. post-transfer

During the suppression stage, you will be given medications that shut down or "quiet" the ovaries. This induced rest period allows the ovaries to respond better to hormonal stimulation. Also, suppressing the natural ovulatory cycle keeps the body from recruiting a single dominant follicle during the induced cycle, allowing for the maturation of multiple eggs. The suppression drugs you will be prescribed may include: oral contraceptives or Aygestin and Lupron or a GnRH Antagonist.

Next you will begin the stimulation phase of the IVF cycle, during which you will take injectable hormones (FSH and/or hMG) to stimulate egg maturation, along with suppression drugs (Lupron or GnRH Antagonist) to keep your natural ovulatory cycle from interfering with the recruitment of multiple eggs. During this stage, you will be monitored regularly with blood tests and ultrasounds, and when the eggs are on the verge of maturation, as determined by the size of the follicles, you will be given an exact time to administer a single dose of hCG, which completes the maturation of the eggs and readies them for retrieval.

Egg retrieval, also known as follicle aspiration, is scheduled to take place about 35 hours after the hCG is administered. By this time, the eggs have separated and are floating in their follicles. A needle is passed through the upper vaginal wall, and with the aid of vaginal ultrasound, fluid is removed from the follicles under gentle suction. The procedure generally lasts from 10 to 30 minutes. During the retrieval, an anesthesiologist will administer light anesthesia (conscious sedation) through an intravenous drip (IV). After the egg retrieval, you may experience light to moderately severe pain, although most patients tolerate the procedure very well.

** You should not eat or drink for at least 8 hours prior to an egg retrieval.

The eggs are then examined microscopically by one of our embryologists. Next, the eggs are inseminated with sperm and then placed in an incubator. Often insemination involves ICSI (intracytoplasmic sperm injection), especially in cases of Male Factor Infertility. In ICSI, a single sperm is injected, using a tiny needle, directly into the egg to increase the odds of fertilization. The eggs are closely monitored during this time to see whether fertilization occurs. If an embryo develops, it is then closely monitored by the embryologist for cell division. A healthy embryo should divide to form 2 cells, then divide again to form 4 cells and again to form 8 cells. This division of the cells to an 8-celled embryo usually occurs on the 3rd day after egg retrieval, if the embryo is healthy.

The next stage of treatment is the transfer stage. Three to five days after the egg retrieval, the embryos are returned to the uterine cavity via a soft, thin catheter in a procedure known as embryo transfer. Healthy unused embryos can be frozen through a process known as cryopreservation and used for future attempts. Cryopreserved embryos can be stored for years and still remain viable.

The final stage of IVF is the post-transfer stage, during which the woman waits 11 days to find out whether the transfer has led to a pregnancy. Once the embryo transfer has taken place you should stay away from alcohol, greatly limit your caffeine consumption, and not smoke cigarettes or use recreational drugs. You should also avoid the following activities: heavy lifting; strenuous exercise and housework, including vacuuming; bouncing activities such as aerobics or horseback riding; hot tubs, saunas, and Jacuzzis; swimming and baths; and sexual intercourse. You will most likely be prescribed some form of progesterone to help maintain a rich endometrial lining during this time, and may be prescribed baby aspirin and/or Prednisone. If your first pregnancy test is positive, you will be scheduled to take a second blood test in two days; if that pregnancy test is also positive you will be scheduled for an ultrasound on the following week so that we can monitor your pregnancy.

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Assisted Hatching

A woman's egg is surrounded by a gel-like protective shell called the zona pellucida. When a fertilized embryo is about 5-6 days old, it must hatch out of the zona pellucida so that it can attach (implant) to the wall of the uterus and continue growing. As women get older, the zona pellucida may become harder or tougher, making it difficult for the embryos to hatch. As a result, implantation and pregnancy may not occur. Using micromanipulation, it is now possible to thin a patch in the zona pellucida by applying a weak acid solution to a very small area. Because this technique helps the embryo to hatch, it is referred to as assisted hatching.

Assisted Hatching is recommended for woman over 37 years old whose embryo quality is otherwise good. It is also routinely performed on thawed cryopreserved embryos because the freezing process tends to toughen the zona pellucida. It may also be performed if visual inspection reveals a potential problem with the zona pellucida. Assisted hatching, when indicated, is performed on good embryos, the same day that embryo transfer occurs.

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Embryo Transfer

Usually on the third day following follicular aspiration, your embryo(s) will be transferred to the uterus. The transfer takes only a few minutes, and the procedure involves placing a speculum into your vagina and transferring the embryo(s) via a small, soft plastic tube (catheter) placed through the cervix into the uterine cavity. No anesthesia is required and usually only minimal, if any, discomfort is felt. You will be asked to lie with your knees elevated for 15 minutes following the procedure to allow the embryos to settle. Most embryo transfers take place three days after the egg retrieval, when the embryos are in the 8-cell stage of development. In some cases, your physician may recommend transfer on day 5, when the embryos are in the blastocyst stage (see below). The number of embryos transferred will depend on a number of factors including maternal age and the number and quality of embryos produced.

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Blastocyst Cultures

With conventional IVF, embryos are usually transferred three days after retrieval, when they are at the 8-cell stage of development. The term blastocyst refers to the stage of embryo development just prior to implantation, when the embryo consists of some 100 cells which form an outer shell of cells protecting an attached inner group of cells surrounding a fluid core. The outer cells will develop into the placenta, which protects the fetus, which is created from the inner cells. The blastocyst stage is reached after approximately five days in the culture.

By extending the culture period, the best embryos can be selected, improving pregnancy rates for those embryos that are transferred. Also, only one or two embryos may be transferred at one time because the embryos are a better quality than 3-day embryos, lowering the possibility of high-risk multiple gestations. One possible downside to blastocyst cultures is that for some women, the uterus may still be a better incubator than the laboratory, causing some pregnancies to be lost by extending the culture time and delaying the transfer. Usually, blastocyst transfer is recommended for women who have a high number of embryos.

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